Construction of a 5-Gene super-enhancer-related signature for osteosarcoma prognosis and the regulatory role of TNFRSF11B in osteosarcoma.

Osteosarcoma, one of the most common primary malignancies in children and adolescents, has the primary characteristics of a poor prognosis and high rate of metastasis. This study used super-enhancer-related genes derived from two different cell lines to construct five novel super-enhancer-related gene prognostic models for patients with osteosarcoma. The training and testing datasets were used to confirm the prognostic models of the five super-enhancer-related genes, which resulted in an impartial predictive element for osteosarcoma. The immunotherapy and prediction of the response to anticancer drugs have shown that the risk signature of the five super-enhancer-related genes positively correlate with chemosensitivity. Furthermore, functional analysis of the risk signature genes revealed a significant relationship between gene groups and the malignant characteristics of tumours. TNF Receptor Superfamily Member 11b (TNFRSF11B) was selected for functional verification. Silencing of TNFRSF11B suppressed the proliferation, migration, and invasion of osteosarcoma cells in vitro and suppressed osteosarcoma growth in vivo. Moreover, transcriptome sequencing was performed on MG-63 cells to study the regulatory mechanism of TNFRSF11B in osteosarcoma cells, and it was discovered that TNFRSF11B is involved in the development of osteosarcoma via the phosphoinositide 3-kinase signalling pathway. Following the identification of TNFRSF11B as a key gene, we selected an inhibitor that specifically targeted this gene and performed molecular docking simulations. In addition, risedronic acid inhibited osteosarcoma growth at both cellular and molecular levels. In conclusion, the super-enhancer-related gene signature is a viable therapeutic tool for osteosarcoma prognosis and treatment.

Unintended dural tears during unilateral biportal endoscopic lumbar surgery: incidence and risk factors.

BACKGROUND: An unintended dural tear (DT) is the most common intraoperative complication of lumbar spine surgery. The unilateral biportal endoscopic technique (UBE) has become increasingly popular for treating various degenerative diseases of the lumbar spine; however, the DT incidence and risk factors specific to UBE remain undetermined. Therefore, this study aimed to evaluate the incidence and risk factors of DTs in UBE. METHOD: Data from all patients who underwent UBE for degenerative lumbar spinal diseases from November 2018 to December 2021 at our institution were used to assess the effects of demographics, diagnosis, and type of surgery on unintended DT risk. RESULTS: Overall, 24/608 patients (3.95%) experienced DTs and were treated with primary suture repair or bed rest. Although several patients experienced mild symptoms of cerebrospinal fluid (CSF) leaks, no serious postoperative sequelae such as nerve root entrapment, meningitis, or intracranial hemorrhage occurred. Additionally, no significant correlations were identified between DT and sex (P = 0.882), body mass index (BMI) (P = 0.758), smoking status (P = 0.506), diabetes (P = 0.672), hypertension (P = 0.187), or surgeon experience (P = 0.442). However, older patients were more likely to experience DT than younger patients (P = 0.034), and patients with lumbar spinal stenosis (LSS) were more likely to experience DT than patients with lumbar disc herniation (LDH) (P = 0.035). Additionally, DT was more common in revision versus primary surgery (P < 0.0001) and in unilateral laminotomy with bilateral decompression (ULBD) versus unilateral decompression (P = 0.031). Univariate logistic regression analysis revealed that age, LSS, ULBD, and revision surgery were significant risk factors for DT. CONCLUSIONS: In this UBE cohort, we found that the incidence of DT was 3.95%. Additionally, older age, LSS, ULBD, and revision surgery significantly increased the risk of DT in UBE surgery.

A Novel Defined Necroptosis-Related Genes Prognostic Signature for Predicting Prognosis and Treatment of Osteosarcoma.

Osteosarcoma (OS) is a frequent primary malignant bone tumor, with a poor prognosis. Necroptosis is strongly correlated with OS and may be an influential target for treating OS. This study's objective was to establish a necroptosis-related gene (NRG) prognostic signature that could predict OS prognosis and guide OS treatment. First, we identified 20 NRGs associated with OS survival based on the TARGET database. We then derived a 7 NRG prognostic signature. Our findings revealed that the 7 NRG prognostic signature performed well in predicting the survival of OS patients. We next analyzed differences in immunological status and immune cell infiltration. In addition, we examined the relationship between chemo/immunotherapeutic response and the 7-NRG prognostic signature. In addition, to probe the mechanisms underlying the NRG prognostic signature, we performed functional enrichment assays including GO and KEGG. Finally, CHMP4C was selected for functional experiments. Silencing CHMP4C prevented OS cells from proliferating, migrating, and invading. This 7-NRG prognostic signature seems to be an excellent predictor that can provide a fresh direction for OS treatment.

Single-Cell RNA Sequencing Pro-angiogenic Macrophage Profiles Reveal Novel Prognostic Biomarkers and Therapeutic Targets for Osteosarcoma.

Osteosarcoma (OS) is a malignant bone tumor that most commonly occurs in children and adolescents. OS patients have a poor prognosis, and 5-year survival rates have rarely improved significantly over the past few decades. OS prognosis may be related to the infiltration of tumor-associated macrophages (TAMs). However, the role of proangiogenic macrophages, a subtype of TAMs, in OS prognosis has not been reported. In this study, seven subtypes of TAMs were identified from single-cell RNA sequencing (scRNA-seq) data that we propose defining as proangiogenic TAMs (Angio-TAMs), interferon-primed TAMs (IFN-TAMs), inflammatory cytokine-enriched TAMs (Inflam-TAMs), immune regulatory TAMs (Reg-TAMs), lipid-associated TAMs (LA-TAMs), and resident-tissue macrophages like TAMs (RTM-TAMs) (containing two subcellular types). In the survival analysis of each macrophage subtype, it was found that patients with Angio-TAMs had the most significant difference in survival. Eight genes associated with Angio-TAMs were obtained by differential expression analysis, and these genes were built into a prognostic model using the LASSO algorithm. Clinical OS case samples were categorized into high-risk and low-risk subgroups using median risk scores. In comparison to the low-risk subgroup, the survival time of the high-risk subgroup was much shorter. Additional studies on immune cell infiltration and immune checkpoint molecule expression in the two risk subgroups were carried out. In immunotherapy response prediction, the Angio-TAM-associated gene risk signature was found to be negatively correlated with immune checkpoint responses. In addition, the associated enriched GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were mainly involved in the malignant progression of tumors. As suggested by these findings, the Angio-TAM gene risk signature may be an underlying prognostic biomarker and novel therapeutic target for OS patients.Kindly check and confirm whether the ESM file is correctly identifiedWe have checked this file and confirmed that it can be correctly identified.

Identification of a novel MYC target gene set signature for predicting the prognosis of osteosarcoma patients.

Osteosarcoma is a primary malignant tumor found mainly in teenagers and young adults. Patients have very little long-term survival. MYC controls tumor initiation and progression by regulating the expression of its target genes; thus, constructing a risk signature of osteosarcoma MYC target gene set will benefit the evaluation of both treatment and prognosis. In this paper, we used GEO data to download the ChIP-seq data of MYC to obtain the MYC target gene. Then, a risk signature consisting of 10 MYC target genes was developed using Cox regression analysis. The signature indicates that patients in the high-risk group performed poorly. After that, we verified it in the GSE21257 dataset. In addition, the difference in tumor immune function among the low- and high-risk populations was compared by single sample gene enrichment analysis. Immunotherapy and prediction of response to the anticancer drug have shown that the risk signature of the MYC target gene set was positively correlated with immune checkpoint response and drug sensitivity. Functional analysis has demonstrated that these genes are enriched in malignant tumors. Finally, STX10 was selected for functional experimentation. STX10 silence has limited osteosarcoma cell migration, invasion, and proliferation. Therefore, these findings indicated that the MYC target gene set risk signature could be used as a potential therapeutic target and prognostic indicator in patients with osteosarcoma.

Genetic footprint of population fragmentation and contemporary collapse in a freshwater cetacean.

Understanding demographic trends and patterns of gene flow in an endangered species is crucial for devising conservation strategies. Here, we examined the extent of population structure and recent evolution of the critically endangered Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis). By analysing genetic variation at the mitochondrial and nuclear microsatellite loci for 148 individuals, we identified three populations along the Yangtze River, each one connected to a group of admixed ancestry. Each population displayed extremely low genetic diversity, consistent with extremely small effective size (≤92 individuals). Habitat degradation and distribution gaps correlated with highly asymmetric gene-flow that was inefficient in maintaining connectivity between populations. Genetic inferences of historical demography revealed that the populations in the Yangtze descended from a small number of founders colonizing the river from the sea during the last Ice Age. The colonization was followed by a rapid population split during the last millennium predating the Chinese Modern Economy Development. However, genetic diversity showed a clear footprint of population contraction over the last 50 years leaving only ~2% of the pre-collapsed size, consistent with the population collapses reported from field studies. This genetic perspective provides background information for devising mitigation strategies to prevent this species from extinction.

Parentage-Based Group Composition and Dispersal Pattern Studies of the Yangtze Finless Porpoise Population in Poyang Lake.

Social behaviors are poorly known for the critically endangered Yangtze finless porpoise (YFP, Neophocaena asiaeorientalis asiaeorientalis). Here, group composition and dispersal patterns of the YFP population living in the Poyang Lake were studied by parentage-based pedigree analyses using 21 microsatellite loci and a 597 bp segment of the mitochondrial DNA control region. In this study, 21 potential mother-offspring pairs and six potential father-offspring pairs (including two potential parents-offspring pairs) were determined, among which 12 natural mother-offspring groups and a maternal group of three generations were found. No genetically-determined fathers were found associated with their offspring. This study also found that maternally related porpoises at the reproductive state tend to group together. This suggest maternal relationship and reproductive state may be factors for grouping in the YFP population. In natural mother-offspring groups, male offspring were all younger than two years old, which suggest male offspring may leave their mothers at approximately two years of age, or at least they were not in tight association with their mothers as they may have been under two years old. However, female offspring can stay longer with their mothers and can reproduce in the natal group.

Genetic diversity and population structure of the critically endangered Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis) as revealed by mitochondrial and microsatellite DNA.

Ecological surveys have indicated that the population of the critically endangered Yangtze finless porpoise (YFP, Neophocaena asiaeorientalis asiaeorientalis) is becoming increasingly small and fragmented, and will be at high risk of extinction in the near future. Genetic conservation of this population will be an important component of the long-term conservation effort. We used a 597 base pair mitochondrial DNA (mtDNA) control region and 11 microsatellite loci to analyze the genetic diversity and population structure of the YFP. The analysis of both mtDNA and microsatellite loci suggested that the genetic diversity of the YFP will possibly decrease in the future if the population keeps declining at a rapid rate, even though these two types of markers revealed different levels of genetic diversity. In addition, mtDNA revealed strong genetic differentiation between one local population, Xingchang-Shishou (XCSS), and the other five downstream local populations; furthermore, microsatellite DNA unveiled fine but significant genetic differentiation between three of the local populations (not only XCSS but also Poyang Lake (PY) and Tongling (TL)) and the other local populations. With an increasing number of distribution gaps appearing in the Yangtze main steam, the genetic differentiation of local populations will likely intensify in the future. The YFP is becoming a genetically fragmented population. Therefore, we recommend attention should be paid to the genetic conservation of the YFP.

Isolation of Robinsoniella peoriensis from the fecal material of the endangered Yangtze finless porpoise, Neophocaena asiaeorientalis asiaeorientalis.

The aim of this study was to determine the causative agent of diarrhea in an endangered Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis). From the fecal material collected from this porpoise Robinsoniella peoriensis was isolated.

Herpes-like virus infection in Yangtze finless porpoise (Neophocaena phocaenoides): pathology, ultrastructure and molecular analysis.

A moribund juvenile Yangtze finless porpoise (Neophocaena phocaenoides) with skin lesions and ulceration was found in Dongting Lake, China. Pathologic examination, electron microscopy, and polymerase chain reaction of liver tissue revealed widely distributed necrotic lesions, sinusoidal dilatation, congestion and herpes-like virus particles.

Analysis of the bacterial diversity in the fecal material of the endangered Yangtze finless porpoise, Neophocaena phocaenoides asiaeorientalis.

The aim of this study was to determine the bacteria present in the fecal material of the endangered Yangtze finless porpoise, Neophocaena phocaenoides asiaeorientalis. Fecal samples were collected from 12 Yangtze finless porpoises living in the wild at Poyang Lake, located in Jiangxi Province, China. To determine the bacterial diversity, a 16S rRNA gene clone library using the bacterial PCR primers fD1 and rP2, was prepared. A total of 138 near-full-length sequences were analyzed and 39 operational taxonomic units (OTUs) were identified. Sequences showing ≥97% similarity were grouped together as an OTU. Six different phyla were identified in which 38 OTUs were classified. Most of the OTUs contained sequences belonged to the phylum Firmicutes (51.3%), followed by Tenericutes (17.9%), Proteobacteria (15.4%), Actinobacteria (7.7%), Deinococcus-Thermus (2.6%) and Cyanobacteria (2.6%). A phylum could not be assigned for one clone within one OTU (2.6%). It appears that the Yangtze finless porpoise has a more diverse range of bacteria compared to other aquatic mammals, such as seals.

Variation in sexual behaviors in a group of captive male Yangtze finless porpoises (Neophocaena phocaenoides asiaeorientalis): motivated by physiological changes?

Most male mammals in temperate regions demonstrate seasonal sexual behaviors that coincide with seasonal variations in gonadal activities and androgen hormones. The Yangtze finless porpoise is a temperate freshwater cetacean species and an obvious seasonal breeder. To investigate the relationship between sexual behavior and gonadal activity in this animal, testicular size (volume) and structure (ultrasonogram pixel intensity) of two adult male porpoises (AF, AB) and one sub-adult male (TT) were longitudinally monitored from November 2008 to November 2009. Serum testosterone concentration was also monitored during the same period. Variations in the frequency of sexual behavior in AF and AB had similar, but seasonal trends. Their testicular size and pixel intensity also varied seasonally. Testicular size increased in March, peaked from April through June, and decreased gradually from August through September, whereas testicular pixel intensity started to increase in early February. The frequency of sexual behavior was positively correlated with testicular volume and pixel intensity (P = 0.000018 and P = 0.00012, respectively) in AF. Serum testosterone concentrations also varied. The sub-adult male porpoise, TT, was undergoing puberty, as evidenced by its marked increase in testicular volume, testicular pixel intensity, and serum testosterone concentrations from the beginning of 2009. Interestingly, TT exhibited the highest frequency of sexual behavior, most of which was same-sex pairing. However, its oversexed behavior neither quantitatively correlated with its smaller testicular volume (P = 0.61) nor with its testicular pixel intensity (P = 0.69).

High MHC DQB variation and asymmetric allelic distribution in the endangered Yangtze finless porpoise, Neophocaena phocaenoides asiaeorientalis.

The endangered Yangtze finless porpoise is found in the middle and lower reaches of the Yangtze River and its adjoining big lakes. To explore the major histocompatibility complex (MHC) genetic diversity and allelic distribution patterns across its range, we investigated variation at DQB exon 2. From 76 porpoises, we identified 18 DQB sequences. The freshwater Yangtze populations had much higher allelic diversity than marine populations. Among these freshwater populations, the middle-reach population had higher allelic diversity than the lower-reach population. The high DQB diversity level, relative to that of a neutral mtDNA locus, suggests that balancing selection is acting at the DQB gene and that rapid evolution and local positive selection play critical roles in generating and retaining high MHC diversity in the freshwater population. As the balancing selection might be driven by environmental pathogens, we suggest that maintaining MHC variation should be a high priority in the conservation and management of this endangered population, especially as an ex situ conservation strategy.

Shape dependence of band-edge exciton fine structure in CdSe nanocrystals.

The band-edge exciton fine structure of wurtzite CdSe nanocrystals is investigated by a plane-wave pseudopotential method that includes spin-orbit coupling, screened electron-hole Coulomb interactions, and exchange interactions. Large-scale, systematic simulations have been carried out on quantum dots, nanorods, nanowires, and nanodisks. The size and shape dependence of the exciton fine structure is explored over the whole diameter-length configuration space and is explained by the interplay of quantum confinement, intrinsic crystal-field splitting, and electron-hole exchange interactions. Our results show that the band-edge exciton fine structure of CdSe nanocrystals is determined by the origin of their valence-band single-particle wave functions. Nanocrystals where the valence-band maximum originates from the bulk A band have a "dark" ground-state exciton. Nanocrystals where the valence-band maximum is derived from the bulk B band have a "quasi-bright" ground-state exciton. Thus, the diameter-length configuration map can be divided into two regions, corresponding to dark and quasi-bright ground-state excitons. We find that the dark/quasi-bright ground-state exciton crossover is not only diameter-dependent but also length-dependent, and it is characterized by a curve in the two-parameter space of diameter and length.

Aquatic Resource Conservation. The first Yangtze finless porpoise successfully born in captivity.

BACKGROUND: As the sole freshwater subspecies of finless porpoise (Neophocaena phocaenoides), the Yangtze finless porpoise (N. p. asiaeorientalis) lives only in the middle and lower reaches of the Yangtze River and its appended Poyang and Dongting Lakes. As a result of human activity on the river, including over and illegal fishing, pollution, transportation and dam construction, the population of Yangtze finless porpoises has been steadily and rapidly decreasing during the past several decades, which leads the animal to be endangered. METHODS: For saving this unique animal from extinction, three corresponding measures, in situ conservation, ex situ conservation, and intensifying breeding research in captivity, were proposed and have been implemented since the 1980s. RESULTS: After successfully rearing the animals in captivity for almost nine years, the first Yangtze finless porpoise was successfully born in captivity on July 5, 2005. The calf is male, with a body length of 69 cm. This is the first freshwater cetacean ever born in captivity. CONCLUSION: The successful birth of this calf confirms that it is possible to breed the Yangtze finless porpoise in captivity. Furthermore, this will greatly benefit the conservation efforts, and also greatly bolster our on-going efforts to study the reproductive biology of these animals. RECOMMENDATION: More studies and efforts are expected to establish a sustainable, captive colony of the Yangtze finless porpoise, which will not only greatly expand our knowledge about the reproduction biology of this animal, but also help to redeem the wild population through a careful yearly 'soft releasing' process.