Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Zebrafish mutants in egln1 display a hypoxic response and develop polycythemia.

AIMS: Prolyl hydroxylase domain 2 (PHD2), encoded by the Egln1 gene, serves as a pivotal regulator of the hypoxia-inducible factor (HIF) pathway and acts as a cellular oxygen sensor. Somatic inactivation of Phd2 in mice results in polycythemia and congestive heart failure. However, due to the embryonic lethality of Phd2 deficiency, its role in development remains elusive. Here, we investigated the function of two egln1 paralogous genes, egln1a and egln1b, in zebrafish. MAIN METHODS: The egln1 null zebrafish were generated using the CRISPR/Cas9 system. Quantitative real-time PCR assays and Western blot analysis were employed to detect the effect of egln1 deficiency on the hypoxia signaling pathway. The hypoxia response of egln1 mutant zebrafish were assessed by analyzing heart rate, gill agitation frequency, and blood flow velocity. Subsequently, o-dianisidine staining and in situ hybridization were used to investigate the role of egln1 in zebrafish hematopoietic function. KEY FINDINGS: Our data show that the loss of egln1a or egln1b individually has no visible effects on growth rate. However, the egln1a; egln1b double mutant displayed significant growth retardation and elevated mortality at around 2.5 months old. Both egln1a-null and egln1b-null zebrafish embryo exhibited enhanced tolerance to hypoxia, systemic hypoxic response that include hif pathway activation, increased cardiac activity, and polycythemia. SIGNIFICANCE: Our research introduces zebrafish egln1 mutants as the first congenital embryonic viable systemic vertebrate animal model for PHD2, providing novel insights into hypoxic signaling and the progression of PHD2- associated disease.

Tri-frequency simultaneous ultrasound pickling for the acceleration of the NaCl content and quality improvement of pork (longissimus dorsi).

BACKGROUND: The pickling process with NaCl is an essential step for pork preservation. This study aimed to investigate the effect of different ultrasonic intensities of tri-frequency simultaneous ultrasound (TSIU) pickling on the NaCl content and quality of pork (longissimus dorsi). After 30 min pickling, the NaCl content, moisture content, pickling yield, cooking loss, textural properties, color, pH, moisture migration and distribution as well as microstructure of pork were assessed. RESULTS: Results showed that among all the ultrasonic treatment intensities (85-150 W L-1 ), the NaCl content of the sample pickled by an intensity of 101.3 W L-1 was higher than that of other intensities. TSIU 101.3 W L-1 showed 59.95% higher NaCl content than the control sample. In addition, the sample treated with TSIU of 101.3 W L-1 had higher pickling yield and moisture content, better textural properties of pork (including hardness and chewiness), and less cooking loss. The results of the low-field nuclear magnetic resonance showed that, compared with the control group, the relaxation time T21 of the ultrasound-assisted pickling samples increased, while the proportion of T22 (A22 ) reduction ranged from 175.0% to 379.9%. The microstructure designated that the ultrasonic treatment could facilitate changes in meat texture. CONCLUSION: Ultrasound marination of different intensities promoted the diffusion of NaCl and affected the quality of pork tenderloins. The TSIU at 101.3 W L-1 could better accelerate NaCl transport and homogeneous distribution on meat, thereby improving the sample quality. © 2024 Society of Chemical Industry.

Streptomyces cathayae sp. nov., an endophytic actinobacterium from the root tissue of Cathaya argyrophylla.

An endophytic actinobacterium, designated strain HUAS 5T, was isolated from the root tissue of Cathaya argyrophylla collected in Chenzhou city of Hunan Province, PR China. This strain produced grey aerial mycelium that differentiated into spiral spore chains with spiny-surfaced ellipsoidal spores on Gause's synthetic No. 1 medium. Strain HUAS 5T grew well on Gause's synthetic No. 1, Reasoner'2 and ISP serial media. This strain grew at 15-40 °C (optimum, 28 °C), pH 6.0-9.0 (optimum, pH 7.0) and in presence of 0-5.0% (w/v) NaCl. The predominant cellular fatty acids of strain HUAS 5T (> 5.0%) were iso-C16:0, iso-C14:0, anteiso-C15:0, iso-C15:0, C16:0, iso-C16:1 H and Sum in Feature 3 (C16:1 ω7c/C16:1 ω6c). Sequence analysis of the 16S rRNA gene indicated that this strain belonged to the genus Streptomyces and exhibited highest sequence similarity to Streptomyces hirsutus NRRL B-2713T (97.3%), which is much less than 98.7% cut-off point of species definitions for bacteria and archaea. Phylogenetic analysis of 16S rRNA gene sequence and whole genome indicated that strain HUAS 5T formed an independent lineage, which suggested that it belonged to a potential novel species. Based on the morphological, cultural, physio-biochemical properties and chemotaxonomy, strain HUAS 5T (= MCCC 1K08552T = JCM 36055T) is deemed to represent a novel Streptomyces species, for which we put forward the name Streptomyces cathayae sp. nov.

Comparison of prediction models for soy protein isolate hydrolysates bitterness built using sensory, spectrofluorometric and chromatographic data from varying enzymes and degree of hydrolysis.

The bitterness of soy protein isolate hydrolysates prepared using five proteases at varying degree of hydrolysis (DH) and its relation to physicochemical properties, i.e., surface hydrophobicity (H0), relative hydrophobicity (RH), and molecular weight (MW), were studied and developed for predictive modelling using machine learning. Bitter scores were collected from sensory analysis and assigned as the target, while the physicochemical properties were assigned as the features. The modelling involved data pre-processing with local outlier factor; model development with support vector machine, linear regression, adaptive boosting, and K-nearest neighbors algorithms; and performance evaluation by 10-fold stratified cross-validation. The results indicated that alcalase hydrolysates were the most bitter, followed by protamex, flavorzyme, papain, and bromelain. Distinctive correlation results were found among the physicochemical properties, influenced by the disparity of each protease. Among the features, the combination of RH-MW fitted various classification models and resulted in the best prediction performance.

Data-adaptive and pathway-based tests for association studies between somatic mutations and germline variations in human cancers.

Cancer is a disease driven by a combination of inherited genetic variants and somatic mutations. Recently available large-scale sequencing data of cancer genomes have provided an unprecedented opportunity to study the interactions between them. However, previous studies on this topic have been limited by simple, low statistical power tests such as Fisher's exact test. In this paper, we design data-adaptive and pathway-based tests based on the score statistic for association studies between somatic mutations and germline variations. Previous research has shown that two single-nucleotide polymorphism (SNP)-set-based association tests, adaptive sum of powered score (aSPU) and data-adaptive pathway-based (aSPUpath) tests, increase the power in genome-wide association studies (GWASs) with a single disease trait in a case-control study. We extend aSPU and aSPUpath to multi-traits, that is, somatic mutations of multiple genes in a cohort study, allowing extensive information aggregation at both SNP and gene levels. p $p$ -values from different parameters assuming varying genetic architecture are combined to yield data-adaptive tests for somatic mutations and germline variations. Extensive simulations show that, in comparison with some commonly used methods, our data-adaptive somatic mutations/germline variations tests can be applied to multiple germline SNPs/genes/pathways, and generally have much higher statistical powers while maintaining the appropriate type I error. The proposed tests are applied to a large-scale real-world International Cancer Genome Consortium whole genome sequencing data set of 2583 subjects, detecting more significant and biologically relevant associations compared with the other existing methods on both gene and pathway levels. Our study has systematically identified the associations between various germline variations and somatic mutations across different cancer types, which potentially provides valuable utility for cancer risk prediction, prognosis, and therapeutics.

Pan-cancer Analysis Reveals SRC May Link Lipid Metabolism and Macrophages.

Background: SRC is a member of the membrane-associated non-receptor protein tyrosine kinase superfamily. It has been reported to mediate inflammation and cancer. However, the exact molecular mechanism involved is still not clear. Objectives: The current study was designed to explore the prognostic landscape of SRC and further investigate the relationship between SRC and immune infiltration in pan-cancer. Materials and Methods: Kaplan-Meier Plotter was used to detect the prognostic value of SRC in pan-cancer. Then using TIMER2.0 and CIBERSORT, the relationship between SRC and immune infiltration in pan-cancer was evaluated. Furthermore, the LinkedOmics database was used to screen SRC co-expressed genes, followed by functional enrichment of SRC co-expressed genes by Metascape online tool. STRING database and Cytoscape software were applied to construct and visualise the protein-protein interaction network of SRC co-expressed genes. MCODE plug-in was used to screen hub modules in the PPI network. The SRC co-expressed genes in hub modules were extracted, and the correlation analysis between interested SRC co-expressed genes and immune infiltration was conducted via TIMER2.0 and CIBERSORT. Results: Our study demonstrated that SRC expression was significantly associated with overall survival and relapse-free survival in multiple cancer types. In addition, SRC expression was significantly correlated with the immune infiltration of B cells, dendritic cells, CD4+ T cells, macrophages, and neutrophils in pan-cancer. The expression of SRC had shown to have close correlations with M1 macrophage polarisation in LIHC, TGCT, THCA, and THYM. Moreover, the genes that co-expressed with SRC in LIHC, TGCT, THCA, and THYM were mainly enriched in lipid metabolism. Besides, correlation analysis showed that SRC co-expressed genes associated with lipid metabolism were also significantly correlated with the infiltration and polarisation of macrophages. Conclusion: These results indicate that SRC can serve as a prognostic biomarker in pan-cancer and is related to macrophages infiltration and interacts with genes involved in lipid metabolism.

Accurate prognostic prediction for patients with clear cell renal cell carcinoma using a ferroptosis-related long non-coding RNA risk model.

INTRODUCTION: Ferroptosis is a recently discovered type of programmed cell death that plays a crucial role in tumor occurrence and progression. However, no prognostic model has been established yet for clear cell renal cell carcinoma (ccRCC) using ferroptosis-related long non-coding RNAs (lncRNAs). METHODS: In the present study, lncRNA expression profiles, sex, age, TMN stage, and other clinical data of ccRCC samples were extracted from The Cancer Genome Atlas database. In addition, ferroptosis-related lncRNAs were identified using co-expression analysis, and the risk model was established using Cox regression and least absolute shrinkage and selection operator regression analyses. Log-rank test and Kaplan-Meier analysis were performed to evaluate the predictive accuracy of the risk model for the overall survival (OS) of patients with ccRCC. Moreover, the functional enrichment of ferroptosis-related lncRNAs was performed and visualized using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. RESULTS: Eight prognostic ferroptosis-related lncRNAs were identified, such as LINC01615, AC026401.3, LINC00944, AL590094.1, DLGAP1-AS2, AC016773.1, AC147651.1, and AP000439.2, making up the ferroptosis-related lncRNA risk model. The risk model effectively divided patients with ccRCC into high- and low-risk groups, and their survival time was calculated. The high-risk group showed significantly shorter OS compared to the low-risk group. The nomogram to predict the survival rate of the patients revealed that the risk score was the most critical factor affecting OS in patients with ccRCC. The ferroptosis-related lncRNA risk model was an independent predictor of prognostic risk assessment in patients with ccRCC. CONCLUSION: The ferroptosis-related lncRNAs risk model and genomic clinicopathological nomogram have the potential to accurately predict the prognosis of patients with ccRCC and could serve as potential therapeutic targets in the future.

Screening and Identification of a Prognostic Model of Ovarian Cancer by Combination of Transcriptomic and Proteomic Data.

The integration of transcriptome and proteome analysis can lead to the discovery of a myriad of biological insights into ovarian cancer. Proteome, clinical, and transcriptome data about ovarian cancer were downloaded from TCGA's database. A LASSO-Cox regression was used to uncover prognostic-related proteins and develop a new protein prognostic signature for patients with ovarian cancer to predict their prognosis. Patients were brought together in subgroups using a consensus clustering analysis of prognostic-related proteins. To further investigate the role of proteins and protein-coding genes in ovarian cancer, additional analyses were performed using multiple online databases (HPA, Sangerbox, TIMER, cBioPortal, TISCH, and CancerSEA). The final resulting prognosis factors consisted of seven protective factors (P38MAPK, RAB11, FOXO3A, AR, BETACATENIN, Sox2, and IGFRb) and two risk factors (AKT_pS473 and ERCC5), which can be used to construct a prognosis-related protein model. A significant difference in overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS), and progression-free interval (PFI) curves were found in the training, testing, and whole sets when analyzing the protein-based risk score (p < 0.05). We also illustrated a wide range of functions, immune checkpoints, and tumor-infiltrating immune cells in prognosis-related protein signatures. Additionally, the protein-coding genes were significantly correlated with each other. EMTAB8107 and GSE154600 single-cell data revealed that the genes were highly expressed. Furthermore, the genes were related to tumor functional states (angiogenesis, invasion, and quiescence). We reported and validated a survivability prediction model for ovarian cancer based on prognostic-related protein signatures. A strong correlation was found between the signatures, tumor-infiltrating immune cells, and immune checkpoints. The protein-coding genes were highly expressed in single-cell RNA and bulk RNA sequencing, correlating with both each other and tumor functional states.

Proposal of Streptomyces sporoverrucosus Gause et al. 1983 as a later heterotypic synonym of Streptomyces goshikiensis Niida et al. 1966 and an emended description of Streptomyces goshikiensis.

The taxonomic relationship of Streptomyces goshikiensis and Streptomyces sporoverrucosus was re-evaluated using comparative genome analysis. The 16S rRNA gene sequence analysis indicated that S. goshikiensis JCM 4640T and S. sporoverrucosus CGMCC 4.1796T shared 100% sequence similarity. Phylogenetic analysis based on 16S rRNA gene and genomic sequences exhibited that they were closely related to each other. However, the values of average nucleotide identity (ANIb/ANIm) and digital DNA-DNA hybridization (dDDH) between the genomes of two type strains were 98.33%/98.69% and 87.2%, respectively, greater than the two recognized thresholds values of 96.7% ANI and 70% dDDH for species delineation. These results suggested that S. goshikiensis and S. sporoverrucosus should share the same taxonomic position. In addition, this conclusion was further supported by highly similar morphological, cultural, physiological, biochemical and chemotaxonomic characteristics between them. Consequently, it is proposed that S. sporoverrucosus is a later heterotypic synonym of S. goshikiensis.

Associations of circulation levels of cytokines with birthweight, preterm birth, spontaneous miscarriages, and stillbirth: A Mendelian randomization analysis.

Background: The association between immune imbalances and adverse pregnancy outcomes has been extensive investigated by observational studies, but remain unclear. Thus, this study aimed to establish the causality of the circulation levels of cytokines on adverse pregnancy outcomes, such as offspring's birthweight (BW), preterm birth (PTB), spontaneous miscarriage (SM), and stillbirth (SB). Methods: Two-sample Mendelian randomization (MR) analysis was employed to investigate potential causal relations between 41 cytokines and pregnancy outcomes on the basis of previously published GWAS datasets. Multivariable MR (MVMR) analysis was implemented to investigate the effect of the composition of cytokine networks on the pregnancy outcomes. Potential risk factors were further estimated to explore the potential mediators. Results: Genetic correlation analysis based on large GWAS data sources revealed that genetically predicted MIP1b (ß = -0.027, S.E. = 0.010, p = 0.009) and MCSF (ß = -0.024, S.E. = 0.011, p = 0.029) were associated with reduced offspring's BW, MCP1 (OR: 0.90, 95% CI: 0.83-0.97, p = 0.007) was associated with reduced SM risk, SCF (ß = -0.014, S.E. = 0.005, p = 0.012) associated with decreased number of SB in MVMR. The univariable MR showed that GROa (OR: 0.92, 95% CI: 0.87-0.97, p = 0.004) was associated with decreased PTB risk. Except for the MCSF-BW association, all above associations surpassed the Bonferroni corrected threshold. The MVMR results revealed that MIF, SDF1a, MIP1b, MCSF and IP10 composed cytokine networks, associated with offspring's BW. Risk factors analysis indicated that the above causal associations might be mediated by smoking behaviors. Conclusion: These findings suggest the causal associations of several cytokines with adverse pregnancy outcomes, which were potentially mediated by smoking and obesity. Some of the results did not been corrected through multiple tests and larger samples verification is required in further studies.

Jirovecia branchilis n. sp. (Microsporidia) from glands of Branchiura sowerbyi (Oligochaeta: Tubificidae) in China.

Jirovecia species primarily infect oligochaetes and are typically characterized by large rod-shaped spores with a tail-like posterior prolongation. Presently, seven Jirovecia spp. are reported worldwide with only one described in China. Here, a new species, Jirovecia branchilis n. sp. was discovered in glands of oligochaetes Branchiura sowerybi Beddard, 1892 in China. Jirovecia branchilis n. sp. elicited the formation of numerous opaque xenomas of 0.12 to 0.20 mm (n = 30) in diameter. Electron microscopic observations demonstrated that the earliest developmental stages observed were uninucleate meronts residing directly with the host cytoplasm. Mature spores were rod-shaped with blunt ends and possessed a collar-like anchoring disk, a manubrium-type polar filament, a bipartite polarplast, and a three-layered spore wall. A tail-like prolongation was distinctly observed in the posterior of spores and measured 13.2-28.6 µm long (n = 30). Jirovecia branchilis n. sp. showed 98.54% sequence similarity with Janacekia tainunus isolated from the fat body of chironomidae larvae Kiefferulus tainanus based on obtained partial SSU rDNA gene sequence, but was significantly different in morphology, host, and infection sites. SSU rDNA-based phylogenetic analysis indicated Jirovecia branchilis n. sp. clustered with Janacekia tainanus within the Jirovecia-Bacillidium-Janacekia clade. In conclusion, a new species within Jirovecia, Jirovecia branchilis n. sp. is erected herein based mainly on its morphological, ecological, and to a lesser degree on its molecular characteristics. The whole relationship between Jirovecia spp., Janacekia spp., and Bacillidium spp. is in need of revision and could potentially be elucidated by using additional makers and sequencing a broader diversity of the already described species.

Application of simultaneous ultrasonic curing on pork (Longissimus dorsi): Mass transport of NaCl, physical characteristics, and microstructure.

This study aimed to investigate the effect of ultrasound curing with various working modes and frequency combinations, including mono-, dual- and tri-frequency, on the content of NaCl and tenderness of pork loins (Longissimus dorsi). The physical qualities, myoglobin, moisture migration, distribution, and microstructure of pork were also evaluated. The results displayed that the NaCl content of samples cured by simultaneous ultrasound (100 W/L) working mode with a frequency combination of 20, 40, and 60 kHz was higher than that of other ultrasound working modes. The effect of ultrasonic brining was significantly better than the static curing when the saline solution was >35 mL. In addition, the samples cured by simultaneous ultrasound had better physical qualities, including more pickling absorptivity, less cooking loss, and lower hardness, tenderness, and chewiness value. The intensity of lightness was reduced, although redness and yellowness remained unaltered compared to static curing. The myoglobin content decreased drastically without changing the oxygenation level, and the relaxation time of T2b and T21 was delayed. The microstructure indicated that the ultrasonic treatment could promote changes in meat texture. Overall, the simultaneous ultrasound at various frequencies could efficiently accelerate NaCl penetration and improve pork quality.

ChrII-Encoded DNA Helicase: A Preliminary Study.

BACKGROUND: DNA helicases are unwinding enzymes that are essential for many cellular processes. Research has suggested that both the model microorganisms of a single chromosome and the model microorganisms of multiple chromosomes adopt DNA helicases encoded by chromosome I. Therefore, studying DNA helicases encoded by chromosome II may lay some foundation for understanding nucleic acid metabolism processes. OBJECTIVE: To prove the existence of DNA helicase encoded by chromosome II and to reveal its difference compared to DNA helicase encoded by chromosome I. METHODS: The DNA helicases of Pseudoalteromonas spongiae JCM 12884T and Pseudoalteromonas tunicata DSM 14096T were analyzed by sequence alignment and phylogenetic relationships with other known DNA helicases. Then, proteins of P. spongiae JCM 12884T and P. tunicata DSM 14096T were obtained by heterologous expression. N-terminal sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were performed to confirm the form of proteins. A fluorescence resonance energy transfer (FRET) assay was used to measure the activity of helicases. RESULTS: DnaB-pspo and DnaB-ptun belong to the same family, the PRK08840 superfamily, and form a branch with helicases encoded by chromosome I. YwqA-pspo and YwqA-ptun have similar domains and form another branch with helicases encoded by chromosome II. All four helicases have DNA unwinding activity. YwqA is more efficient than DnaB for DNA unwinding, especially YwqA-pspo, which is encoded by bidirectional replication chromosome II. CONCLUSION: This is the first study to show that the existence of a DNA helicase encoded by chromosome II, and DNA helicase encoded by chromosome II is more efficient than chromosome I for DNA unwinding.

A spatiotemporal steroidogenic regulatory network in human fetal adrenal glands and gonads.

Human fetal adrenal glands produce substantial amounts of dehydroepiandrosterone (DHEA), which is one of the most important precursors of sex hormones. However, the underlying biological mechanism remains largely unknown. Herein, we sequenced human fetal adrenal glands and gonads from 7 to 14 gestational weeks (GW) via 10× Genomics single-cell transcriptome techniques, reconstructed their location information by spatial transcriptomics. Relative to gonads, adrenal glands begin to synthesize steroids early. The coordination among steroidogenic cells and multiple non-steroidogenic cells promotes adrenal cortex construction and steroid synthesis. Notably, during the window of sexual differentiation (8-12 GW), key enzyme gene expression shifts to accelerate DHEA synthesis in males and cortisol synthesis in females. Our research highlights the robustness of the action of fetal adrenal glands on gonads to modify the process of sexual differentiation.

Correction: Chemo-photodynamic combined gene therapy and dual-modal cancer imaging achieved by pH-responsive alginate/chitosan multilayer-modified magnetic mesoporous silica nanocomposites.

Correction for 'Chemo-photodynamic combined gene therapy and dual-modal cancer imaging achieved by pH-responsive alginate/chitosan multilayer-modified magnetic mesoporous silica nanocomposites' by Hong Yang et al., Biomater. Sci., 2017, 5, 1001-1013, https://doi.org/10.1039/c7bm00043j.

Changes of Neolithic subsistence in south Hangzhou Bay coast, eastern China: An adaptive strategy to landscape processes.

The transition from hunting and gathering to agricultural subsistence is a striking feature of the Neolithic revolution worldwide. Known as the cradle of a series of representative Neolithic cultures, south Hangzhou Bay (SHB) witnessed substantial changes in both landscape and human subsistence during the Holocene, yet the relationship between them was not well established. Here, we combined archaeobotanical results from sediment cores with archaeological findings to illustrate the subsistence changes during the Neolithic regime in the context of the landscape process in SHB. Our result showed that SHB was inundated by marine transgression 8,200 years ago without significant human imprints. At 8,200-7,600 cal yr. BP, the initial coastal wetland formation at locations with the semi-enclosed landscape would have facilitated the activities of hunting-gathering, incipient rice cultivation, and collecting seafood if accessible. Pollen and phytoliths evidence from multiple sediment cores in the Yaojiang Valley (YJV) suggested a desalinization process of wetland in the following hundreds of years. This amelioration of the environment had favored the intermittent rice cultivation at various locations in the YJV, where archaeological evidence was absent. Since 7,000-6,600 cal yr. BP, as freshwater wetland expanded with coastal progradation, a wide variety of food resources became available. Meanwhile, rice domestication began to serve as a crucial food supplement as evidenced by both microfossil results and archaeological findings. With the expansion of the coastal plain after 5,500 cal yr. BP, rice farming became widespread and rice consumption was increasingly important in the diet, as supported by discoveries of upgraded farming tools, abundant rice remains, and ancient rice paddies. Above all, the change of subsistence from hunting-gathering to rice farming exhibited an adaptive strategy in response to landscape evolution from an initial marine-influenced setting to a later coastal plain.

Mitochondrial phylogenomics of Acanthocephala: nucleotide alignments produce long-branch attraction artefacts.

BACKGROUND: Classification of the Acanthocephala, a clade of obligate endoparasites, remains unresolved because of insufficiently strong resolution of morphological characters and scarcity of molecular data with a sufficient resolution. Mitochondrial genomes may be a suitable candidate, but they are available for a small number of species and their suitability for the task has not been tested thoroughly. METHODS: Herein, we sequenced the first mitogenome for the large family Rhadinorhynchidae: Micracanthorhynchina dakusuiensis. These are also the first molecular data generated for this entire genus. We conducted a series of phylogenetic analyses using concatenated nucleotides (NUC) and amino acids (AAs) of all 12 protein-coding genes, three different algorithms, and the entire available acanthocephalan mitogenomic dataset. RESULTS: We found evidence for strong compositional heterogeneity in the dataset, and Micracanthorhynchina dakusuiensis exhibited a disproportionately long branch in all analyses. This caused a long-branch attraction artefact (LBA) of M. dakusuiensis resolved at the base of the Echinorhynchida clade when the NUC dataset was used in combination with standard phylogenetic algorithms, maximum likelihood (ML) and Bayesian inference (BI). Both the use of the AA dataset (BI-AAs and ML-AAs) and the CAT-GTR model designed for suppression of LBA (CAT-GTR-AAs and CAT-GTR-NUC) at least partially attenuated this LBA artefact. The results support Illiosentidae as the basal radiation of Echinorhynchida and Rhadinorhynchidae forming a clade with Echinorhynchidae and Pomporhynchidae. The questions of the monophyly of Rhadinorhynchidae and its sister lineage remain unresolved. The order Echinorhynchida was paraphyletic in all of our analyses. CONCLUSIONS: Future studies should take care to attenuate compositional heterogeneity-driven LBA artefacts when applying mitogenomic data to resolve the phylogeny of Acanthocephala.

Integrative Analysis of Bulk RNA-Seq and Single-Cell RNA-Seq Unveils the Characteristics of the Immune Microenvironment and Prognosis Signature in Prostate Cancer.

The immune microenvironment is a culmination of the collaborative effort of immune cells and is important in cancer development. The underlying mechanisms of the tumor immune microenvironment in regulating prostate cancer (PRAD) are unclear. In the current study, 144 natural killer cell-related genes were identified using differential expression, single-sample gene set enrichment analysis, and weighted gene coexpression network analysis. Furthermore, VCL, ACTA2, MYL9, MYLK, MYH11, TPM1, ACTG2, TAGLN, and FLNC were selected as hub genes via the protein-protein interaction network. Based on the expression patterns of the hub genes, endothelial, epithelial, and tissue stem cells were identified as key cell subpopulations, which could regulate PRAD via immune response, extracellular signaling, and protein formation. Moreover, 27 genes were identified as prognostic signatures and used to construct the risk score model. Receiver operating characteristic curves revealed the good performance of the risk score model in both the training and testing datasets. Different chemotherapeutic responses were observed between the low- and high-risk groups. Additionally, a nomogram based on the risk score and other clinical features was established to predict the 1-, 3-, and 5-year progression-free interval of patients with PRAD. This study provides novel insights into the molecular mechanisms of the immune microenvironment and its role in the pathogenesis of PARD. The identification of key cell subpopulations has a potential therapeutic and prognostic use in PRAD.

Nile waterscapes facilitated the construction of the Giza pyramids during the 3rd millennium BCE.

The pyramids of Giza originally overlooked a now defunct arm of the Nile. This fluvial channel, the Khufu branch, enabled navigation to the Pyramid Harbor complex but its precise environmental history is unclear. To fill this knowledge gap, we use pollen-derived vegetation patterns to reconstruct 8,000 y of fluvial variations on the Giza floodplain. After a high-stand level concomitant with the African Humid Period, our results show that Giza's waterscapes responded to a gradual insolation-driven aridification of East Africa, with the lowest Nile levels recorded at the end of the Dynastic Period. The Khufu branch remained at a high-water level (∼40% of its Holocene maximum) during the reigns of Khufu, Khafre, and Menkaure, facilitating the transportation of construction materials to the Giza Pyramid Complex.