Comparative Proteomics Identified EXOSC1 as a Target Protein of Anticancer Peptide LVTX-8 in Nasopharyngeal Carcinoma Cells.

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy that usually occurs among the nose and throat. Due to mild initial symptoms, most patients are diagnosed in the late stage, and the recurrence rate of tumors is high, resulting in many deaths every year. Traditional radiotherapy and chemotherapy are prone to causing drug resistance and significant side effects. Therefore, searching for new bioactive drugs including anticancer peptides is necessary and urgent. LVTX-8 is a peptide toxin synthesized from the cDNA library of the spider Lycosa vittata, which is consisting of 25 amino acids. In this study, a series of in vitro cell experiments such as cell toxicity, colony formation, and cell migration assays were performed to exam the anticancer activity of LVTX-8 in NPC cells (5-8F and CNE-2). The results suggested that LVTX-8 significantly inhibited cell proliferation and migration of NPC cells. To find the potential molecular targets for the anticancer capability of LVTX-8, high-throughput proteomic and bioinformatics analysis were conducted on NPC cells. The results identified EXOSC1 as a potential target protein with significantly differential expression levels under LVTX-8+/LVTX-8- conditions. The results in this research indicate that spider peptide toxin LVTX-8 exhibits significant anticancer activity in NPC, and EXOSC1 may serve as a target protein for its anticancer activity. These findings provide a reference for the development of new therapeutic drugs for NPC and offer new ideas for the discovery of biomarkers related to NPC diagnosis. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (https://proteomecentral.proteomexchange.org) via the iProX partner repository with the data set identifier PXD050542.

Development and validation of YARN: A novel SE-400 MPS kit for East Asian paternal lineage analysis.

Y-chromosomal short tandem repeat polymorphisms (Y-STRs) and Y-chromosomal single nucleotide polymorphisms (Y-SNPs) are valuable genetic markers used in paternal lineage identification and population genetics. Currently, there is a lack of an effective panel that integrates Y-STRs and Y-SNPs for studying paternal lineages, particularly in East Asian populations. Hence, we developed a novel Y-chromosomal targeted panel called YARN (Y-chromosome Ancestry and Region Network) based on multiplex PCR and a single-end 400 massive parallel sequencing (MPS) strategy, consisting of 44 patrilineage Y-STRs and 260 evolutionary Y-SNPs. A total of 386 reactions were validated for the effectiveness and applicability of YARN according to SWGDAM validation guidelines, including sensitivity (with a minimum input gDNA of 0.125 ng), mixture identification (ranging from 1:1-1:10), PCR inhibitor testing (using substances such as 50 µM hematin, 100 µM hemoglobin, 100 µM humic acid, and 2.5 mM indigo dye), species specificity (successfully distinguishing humans from other animals), repeatability study (achieved 100% accuracy), and concordance study (with 99.91% accuracy for 1121 Y-STR alleles). Furthermore, we conducted a pilot study using YARN in a cohort of 484 Han Chinese males from Huaiji County, Zhaoqing City, Guangdong, China (GDZQHJ cohort). In this cohort, we identified 52 different Y-haplogroups and 73 different surnames. We found weak to moderate correlations between the Y-haplogroups, Chinese surnames, and geographical locations of the GDZQHJ cohort (with λ values ranging from 0.050 to 0.340). However, when we combined two different categories into a new independent variable, we observed stronger correlations (with λ values ranging from 0.617 to 0.754). Overall, the YARN panel, which combines Y-STR and Y-SNP genetic markers, meets forensic DNA quality assurance guidelines and holds potential for East Asian geographical origin inference and paternal lineage analysis.

PTEN deficiency induces an extrahepatic cholangitis-cholangiocarcinoma continuum via aurora kinase A in mice.

BACKGROUND & AIMS: The PTEN-AKT pathway is frequently altered in extrahepatic cholangiocarcinoma (eCCA). We aimed to evaluate the role of PTEN in the pathogenesis of eCCA and identify novel therapeutic targets for this disease. METHODS: The Pten gene was genetically deleted using the Cre-loxp system in biliary epithelial cells. The pathologies were evaluated both macroscopically and histologically. The characteristics were further analyzed by immunohistochemistry, reverse-transcription PCR, cell culture, and RNA sequencing. Some features were compared to those in human eCCA samples. Further mechanistic studies utilized the conditional knockout of Trp53 and Aurora kinase A (Aurka) genes. We also tested the effectiveness of an Aurka inhibitor. RESULTS: We observed that genetic deletion of the Pten gene in the extrahepatic biliary epithelium and peri-ductal glands initiated sclerosing cholangitis-like lesions in mice, resulting in enlarged and distorted extrahepatic bile ducts in mice as early as 1 month after birth. Histologically, these lesions exhibited increased epithelial proliferation, inflammatory cell infiltration, and fibrosis. With aging, the lesions progressed from low-grade dysplasia to invasive carcinoma. Trp53 inactivation further accelerated disease progression, potentially by downregulating senescence. Further mechanistic studies showed that both human and mouse eCCA showed high expression of AURKA. Notably, the genetic deletion of Aurka completely eliminated Pten deficiency-induced extrahepatic bile duct lesions. Furthermore, pharmacological inhibition of Aurka alleviated disease progression. CONCLUSIONS: Pten deficiency in extrahepatic cholangiocytes and peribiliary glands led to a cholangitis-to-cholangiocarcinoma continuum that was dependent on Aurka. These findings offer new insights into preventive and therapeutic interventions for extrahepatic CCA. IMPACT AND IMPLICATIONS: The aberrant PTEN-PI3K-AKT signaling pathway is commonly observed in human extrahepatic cholangiocarcinoma (eCCA), a disease with a poor prognosis. In our study, we developed a mouse model mimicking cholangitis to eCCA progression by conditionally deleting the Pten gene via Pdx1-Cre in epithelial cells and peribiliary glands of the extrahepatic biliary duct. The conditional Pten deletion in these cells led to cholangitis, which gradually advanced to dysplasia, ultimately resulting in eCCA. The loss of Pten heightened Akt signaling, cell proliferation, inflammation, fibrosis, DNA damage, epigenetic signaling, epithelial-mesenchymal transition, cell dysplasia, and cellular senescence. Genetic deletion or pharmacological inhibition of Aurka successfully halted disease progression. This model will be valuable for testing novel therapies and unraveling the mechanisms of eCCA tumorigenesis.

Discovering ferroptosis-associated tumor antigens and ferroptosis subtypes in pancreatic adenocarcinoma to facilitate mRNA vaccine development.

Pancreatic adenocarcinoma (PAAD) is an aggressive, heterogeneous malignancy. We studied the potential of ferroptosis-related tumor vaccines for PAAD treatment. Ferroptosis-related genes, gene expression profiles, and clinical information were extracted from the FerrDB, UCSC Xena, and International Cancer Genome Consortium databases. Differential expression levels and prognostic indices were calculated, genetic alterations and correlations with immune-infiltrating cells were explored, and consensus clustering analysis was performed to identify ferroptosis subtypes and gene modules. Immune enrichment scores were calculated using gene set enrichment analysis, and gene modules were screened using weighted gene co-expression network analysis. The ferroptosis subtype distribution was visualized using graph learning-based dimensionality reduction analysis of the Monocle package with a Gaussian distribution. We identified four ferroptosis-related tumor antigens, AGPS, KDM5A, NRAS, and OSBPL9, which were associated with pancreatic cancer prognosis and antigen-presenting cell infiltration. We determined three minor ferroptosis subtypes, with different clinical prognosis and tumor immune status. Of the subtypes, FS3 may be more suitable for mRNA therapy. We constructed a PAAD ferroptosis landscape to identify the ferroptosis status of patients and predict their prognosis. Finally, we found that the eigengene of the green module was an independent prognostic factor, with a significantly better prognosis in the high-score group than in the low-score group. In conclusion, we identified four ferroptosis-related genes as targets for mRNA vaccines and three ferroptosis subtypes, providing a theoretical basis for the anti-PAAD mRNA vaccine and defining suitable patients for vaccination.

A simple and effective genotyping workflow for rapid detection of CRISPR genome editing.

Genetically engineered mouse models play a pivotal role in the modeling of diseases, exploration of gene functions, and the development of novel therapies. In recent years, clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated genome editing technology has revolutionized the process of developing such models by enabling precise genome modifications of the multiple interested genes simultaneously. Following genome editing, an efficient genotyping methodology is crucial for subsequent characterization. However, current genotyping methods are laborious, time-consuming, and costly. Here, using targeting the mouse trypsinogen genes as an example, we introduced common applications of CRISPR-Cas9 editing and a streamlined cost-effective genotyping workflow for CRISPR-edited mouse models, in which Sanger sequencing is required only at the initial steps. In the F0 mice, we focused on identifying the presence of positive editing by PCR followed by Sanger sequencing without the need to know the exact sequences, simplifying the initial screening. In the F1 mice, Sanger sequencing and algorithms decoding were used to identify the precise editing. Once the edited sequence was established, a simple and effective genotyping strategy was established to distinguish homozygous and heterozygous status by PCR from tail DNA. The genotyping workflow applies to deletions as small as one nucleotide, multiple-gene knockout, and knockin studies. This simplified, efficient, and cost-effective genotyping shall be instructive to new investigators who are unfamiliar with characterizing CRISPR-Cas9-edited mouse strains.NEW & NOTEWORTHY This study presents a streamlined, cost-effective genotyping workflow for clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) edited mouse models, focusing on trypsinogen genes. It simplifies initial F0 mouse screening using PCR and Sanger sequencing without needing exact sequences. For F1 mice, precise editing is identified through Sanger sequencing and algorithm decoding. The workflow includes a novel PCR strategy for distinguishing homozygous and heterozygous statuses in subsequent generations, effective for small deletions, multiple-gene knockouts, and knockins.

cdh23 affects congenital hearing loss through regulating purine metabolism.

Introduction: The pathogenic gene CDH23 plays a pivotal role in tip links, which is indispensable for mechanoelectrical transduction in the hair cells. However, the underlying molecular mechanism and signal regulatory networks that influence deafness is still largely unknown. Methods: In this study, a congenital deafness family, whole exome sequencing revealed a new mutation in the pathogenic gene CDH23, subsequently; the mutation has been validated using Sanger sequencing method. Then CRISPR/Cas9 technology was employed to knockout zebrafish cdh23 gene. Startle response experiment was used to compare with wide-type, the response to sound stimulation between wide-type and cdh23-/-. To further illustrate the molecular mechanisms underlying congenital deafness, comparative transcriptomic profiling and multiple bioinformatics analyses were performed. Results: The YO-PRO-1 assay result showed that in cdh23 deficient embryos, the YO-PRO-1 signal in inner ear and lateral line neuromast hair cells were completely lost. Startle response experiment showed that compared with wide-type, the response to sound stimulation decreased significantly in cdh23 mutant larvae. Comparative transcriptomic showed that the candidate genes such as atp1b2b and myof could affect hearing by regulating ATP production and purine metabolism in a synergetic way with cdh23. RT-qPCR results further confirmed the transcriptomics results. Further compensatory experiment showed that ATP treated cdh23-/- embryos can partially recover the mutant phenotype. Conclusion: In conclusion, our study may shed light on deciphering the principal mechanism and provide a potential therapeutic method for congenital hearing loss under the condition of CDH23 mutation.

Expression of circ-PHC3 enhances ovarian cancer progression via regulation of the miR-497-5p/SOX9 pathway.

BACKGROUND: Accumulating studies have reported indispensable functions of circular RNAs (circRNA) in tumor progression through regulation of gene expression. However, circRNA expression profiles and functions in human ovarian carcinoma (OC) are yet to be fully established. METHODS: In this research, deep sequencing of circRNAs from OC samples and paired adjacent normal tissues was performed to establish expression profiles and circ-PHC3 levels between the groups further compared using RT-qPCR. The effects of ectopic overexpression of miR-497-5p and SOX9 and siRNA-mediated knockdown of circ-PHC3 and an miR-497-5p inhibitor were explored to clarify the regulatory mechanisms underlying circ-PHC3 activity in OC proliferation and metastasis. Information from public databases and the luciferase reporter assay were further utilized to examine the potential correlations among circ-PHC3, miR-497-5p and SOX9. RESULTS: Our results showed significant upregulation of circ-PHC3 in both OC cell lines and tissues. In the luciferase reporter assay, downregulation of circ-PHC3 led to suppression of metastasis and proliferation, potentially through targeted effects on the miR-497-5p/SOX9 axis in OC. SOX9 overexpression or miR-497-5p suppression rescued OC cell proliferation and invasion following silencing of circ-PHC3. Moreover, SOX9 inhibition induced restoration of OC cell invasion and proliferation under conditions of overexpression of miR-497-5p. Thus, circ-PHC3 appears to exert effects on cancer stem cell differentiation through regulation of the miR-497-5p/SOX9 axis. CONCLUSION: Taken together, our findings suggest that circ-PHC3 enhances OC progression through functioning as an miR-497-5p sponge to promote SOX9 expression, supporting its potential as a promising candidate target for OC therapy.

A mouse model for high-efficient Flp-recombinase-mediated genetic manipulation in the pancreas.

BACKGROUND: Tissue and cell-specific gene targeting has been widely employed in biomedical research. In the pancreas, the commonly used Cre recombinase recognizes and recombines loxP sites. However, to selectively target different genes in distinct cells, a dual recombinase system is required. METHOD: We developed an alternative recombination system mediated by FLPo, which recognizes frt DNA sequences for pancreatic dual recombinase-mediated genetic manipulation. An IRES-FLPo cassette was targeted between the translation stop code and 3-UTR of the mouse pdx1 gene in a Bacterial Artificial Chromosome using recombineering technology. Transgenic BAC-Pdx1-FLPo mice were developed by pronuclear injection. RESULTS: Highly efficient recombination activity was observed in the pancreas by crossing the founder mice with Flp reporter mice. When the BAC-Pdx1-FLPo mice were bred with conditional FSF-KRasG12D and p53 F/F mice, pancreatic cancer developed in the compound mice. The characteristics of pancreatic cancer resembled those derived from conditional LSL-KRasG12D and p53 L/L mice controlled by pdx1-Cre. CONCLUSIONS: We have generated a new transgenic mouse line expressing FLPo, which enables highly efficient pancreatic-specific gene recombination. When combined with other available Cre lines, this system can be utilized to target different genes in distinct cells for pancreatic research.

Physical regulation of copper catalyst with a hydrophobic promoter for enhancing CO2 hydrogenation to methanol.

The hydrogenation of CO2 to methanol, which is restricted by water products, requires a selective removal of water from the reaction system. Here, we show that physically combining hydrophobic polydivinylbenzene with a copper catalyst supported by silica can increase methanol production and CO2 conversion. Mechanistic investigation reveals that the hydrophobic promoter could hinder the oxidation of copper surface by water, maintaining a small fraction of metallic copper species on the copper surface with abundant Cuδ+, resulting in high activity for the hydrogenation. Such a physically mixed catalyst survives the continuous test for 100 h owing to the thermal stability of the polydivinylbenzene promoter.

Transcriptomics Based Network Analyses and Molecular Docking Highlighted Potentially Therapeutic Biomarkers for Colon Cancer.

In this study, machine learning-based multiple bioinformatics analysis was carried out for the purpose of the deep and efficient mining of high-throughput transcriptomics data from the TCGA database. Compared with normal colon tissue, 2469 genes were significantly differentially expressed in colon cancer tissue. Gene functional annotation and pathway analysis suggested that most DEGs were functionally related to the cell cycle and metabolism. Weighted gene co-expression network analysis revealed a significant module and the enriched genes that were closely related to fatty acid degradation and metabolism. Based on colon cancer progression, the trend analysis highlighted that several gene sets were significantly correlated with disease development. At the same time, the most specific genes were functionally related to cancer cell features such as the high performance of DNA replication and cell division. Moreover, survival analysis and target drug prediction were performed to prioritize reliable biomarkers and potential drugs. In consideration of a combination of different evidence, four genes (ACOX1, CPT2, CDC25C and PKMYT1) were suggested as novel biomarkers in colon cancer. The potential biomarkers and target drugs identified in our study may provide new ideas for colonic-related prevention, diagnosis, and treatment; therefore, our results have high clinical value for colon cancer.

Proteomics-based molecular and functional characteristic profiling of muscle tissue in Triploid crucian carp.

Triploid crucian carp (TCC) is a kind of artificially bred fish with huge economic value to China. It has several excellent characteristics, such as fast growth, strong disease resistance and delicious taste. However, as a regionally specific fish, the underlying molecular mechanisms of these characteristics are largely unknown. In this study, we performed quantitative proteomics on the muscle tissues of TCC and its parents, allotetraploid (♂), red crucian carp (♀) and common carp. Combined with multiple bioinformatic analysis, we found that the taste of TCC can be mainly attributed to umami amino acid-enriched proteins such as PURBA, PVALBI and ATP5F1B, and that its rapid growth can be mainly ascribed to the high expression and regulation of metabolism-related proteins such as NDUFS1, ENO1A and CS. These play significant roles in substrate and energy metabolism, as well as in bias transformation. Subsequently, we identified several proteins, including MDH1AA, GOT1 and DLAT, that may serve as potential regulators of innate immunity by regulating the biosynthesis and transformation of significant antibiotics and antimicrobial peptides. In conclusion, this study can serve as a significant reference for similar investigations and shed light on the molecular and biological functions of individual proteins in TCC muscle tissue.

Identifying Human Remains from 20th Century Warfare: A State of the Field Essay.

As we continually reflect on the wars of the 20th century, identification of the remains of victims takes an increasingly prominent position in ongoing research. Existing work on the identification of human remains from 20th century wars primarily covers the determination of phenotypic characteristics, kinship and geographic origins, supporting the establishment of genetic information databases. Compared with standard forensic methods, DNA analyses have revealed greater effectiveness. The process of DNA analysis includes DNA extraction, genetic marker testing and data analysis. Protocols from ancient DNA research can be applied to degraded remains, and next-generation sequencing (NGS) techniques can compensate for shortcomings in the most commonly-used PCR-capillary electrophoresis typing. As it stands, wide-ranging inter-governmental and inter-institutional collaboration is necessary in order to set up NGS-based public databases, and thereby promote the identification of human remains and archaeological forensics.

A trefoil knot self-templated through imination in water.

The preparation of topologically nontrivial molecules is often assisted by covalent, supramolecular or coordinative templates that provide spatial pre-organization for all components. Herein, we report a trefoil knot that can be self-assembled efficiently in water without involving additional templates. The direct condensation of three equivalents of a tetraformyl precursor and six equivalents of a chiral diamine produces successfully a [3 + 6] trefoil knot whose intrinsic handedness is dictated by the stereochemical configuration of the diamine linkers. Contrary to the conventional wisdom that imine condensation is not amenable to use in water, the multivalent cooperativity between all the imine bonds within the framework makes this trefoil knot robust in the aqueous environment. Furthermore, the presence of water is proven to be essential for the trefoil knot formation. A topologically trivial macrocycle composed of two tetraformyl and four diamino building blocks is obtained when a similar reaction is performed in organic media, indicating that hydrophobic effect is a major driving force behind the scene.

Microhaplotype and Y-SNP/STR (MY): A novel MPS-based system for genotype pattern recognition in two-person DNA mixtures.

BACKGROUNDS: Y-chromosomal haplotypes based on Y-short tandem repeats (STRs) and Y-single nucleotide polymorphisms/insertion and deletion polymorphisms (SNPs/InDels) are used to characterize paternal lineages of unknown male trace donors. However, Y-chromosomal genetic markers are not currently sufficient for precise individual identification. Microhaplotype (MH), generally < 200 bp on autosomes and consisting of two or more SNPs, was recently introduced in forensic genetics with the development of massive parallel sequencing technology and may facilitate identification and DNA mixture deconvolution. Therefore, combining the two kinds of genetic markers may be beneficial in many forensic scenarios, especially crime scenes with male suspects, such as sexual assault cases. METHODS: In the present study, we developed a novel MPS-based panel, Microhaplotype and Y-SNP/STR (MY), by multiplex PCR and 150-bp paired-end sequencing, including 114 Y-SNPs (twelve dominant Y-DNA haplogroups), 45 Y-STRs (N-1 stutter < 0.09; estimated mutation rate < 5 × 10-3), and 22 MHs (allele coverage ratio > 0.91; pairwise distance > 10 Mb). Additionally, MY system-based genotype pattern recognition (GPR), a regression-based method to identify the genotype pattern for each MH locus, is proposed for two-person DNA mixture deconvolution. We integrated 26 two-person genotype combinations into nine genotype patterns and validated the application range of GPR based on DNA profiles of ten sets of simulated male-male DNA mixtures (1:10-1:2). RESULTS: The effective number of alleles (Ae) ranged from 3.62 to 14.72, with an average of 7.17, in 100 Chinese Guangdong Han individuals. The cumulative discrimination power was 1-5.00 × 10-31, and the cumulative power of exclusion was 1-5.00 × 10-8 and 1-4.85 × 10-12 for duo and trio paternity testing, respectively. Furthermore, the actual mixing ratio-depth of coverage (DoC) ratio (RDoC) regression relationships were established for different genetic markers and genotype patterns. In five overlapping areas, genotype differentiation of the major and minor contributors required likelihood ratio methods. In nonoverlapping areas, the genotype pattern could be recognized by comparing the observed RDoC and RDoC ranges. CONCLUSION: The GPR can be used to deconvolute two-person DNA mixtures (application range: 1:10-1:2) for individual identification.

Cross-continental admixture in the Kho population from northwest Pakistan.

Northern Pakistan is home to many diverse ethnicities and languages. The region acted as a prime corridor for ancient invasions and population migrations between Western Eurasia and South Asia. Kho, one of the major ethnic groups living in this region, resides in the remote and isolated mountainous region in the Chitral Valley of the Hindu Kush Mountain range. They are culturally and linguistically distinct from the rest of the Pakistani population groups and their genetic ancestry is still unknown. In this study, we generated genome-wide genotype data of ~1 M loci (Illumina WeGene array) for 116 unrelated Kho individuals and carried out comprehensive analyses in the context of worldwide extant and ancient anatomically modern human populations across Eurasia. The results inferred that the Kho can trace a large proportion of their ancestry to the population who migrated south from the Southern Siberian steppes during the second millennium BCE ~110 generations ago. An additional wave of gene flow from a population carrying East Asian ancestry was also identified in the Kho that occurred ~60 generations ago and may possibly be linked to the expansion of the Tibetan Empire during 7th to 9th centuries CE (current era) in the northwestern regions of the Indian sub-continent. We identified several candidate regions suggestive of positive selection in the Kho, that included genes mainly involved in pigmentation, immune responses, muscular development, DNA repair, and tumor suppression.

Forensic application of a novel MPS-based panel (90 STRs and 100 SNPs) in a non-exclusion parentage case with three autosomal STRs incompatibilities.

In kinship tests, the investigating of the forensic STRs usually provides decisive information to resolve relationship cases. We describe a parentage case with 3 genetic incompatibilities (D6S1043, D18S51 and D2S1338) between the child and alleged parent. With 90 STR loci and 100 SNP loci, the massively parallel sequencing (MPS)-based genotyping results support the certainty of parentage, and the mismatched alleles were considered to be mutations. MPS can provide additional allele sequence structures that can be used to infer the origins of the mutations. SNPs as supplementary markers can provide effective information to give an unequivocal statement of the parentage.

Development and validation of a novel 133-plex forensic STR panel (52 STRs and 81 Y-STRs) using single-end 400 bp massive parallel sequencing.

Short tandem repeats (STRs) are the preferred genetic markers in forensic DNA analysis, routinely measured by capillary electrophoresis (CE) method based on the fragment length features. While, the massive parallel sequencing (MPS) technology could simultaneously target a large number of intriguing forensic STRs, bypassing the intrinsic limitations of amplicon size separation and accessible fluorophores in CE, which is efficient and promising for enabling the identification of forensic biological evidence. Here, we developed a novel MPS-based Forensic Analysis System Multiplecues SetB Kit of 133-plex forensic STR markers (52 STRs and 81 Y-STRs) and one Y-InDel (M175) based on multiplex PCR and single-end 400 bp sequencing strategy. This panel was subjected to developmental validation studies according to the SWGDAM Validation Guidelines. Approximately 2185 MPS-based reactions using 6 human DNA standards and 8 male donors were conducted for substrate studies (filter paper, gauze, cotton swab, four different types of FTA cards, peripheral venous blood, saliva, and exfoliated cells), sensitivity studies (from 2 ng down to 0.0625 ng), mixture studies (two-person DNA mixtures), PCR inhibitor studies (seven commonly encountered PCR inhibitors), species specificity studies (11 non-human species), and repeatability studies. Results of concordance studies (413 Han males and 6 human DNA standards) generated by STRait Razor and in-house Python scripts indicated 99.98% concordance rate in STR calling relative to CE for STRs between 41,900 genotypes at 100 STR markers. Moreover, the limitations of present studies, the nomenclature rules and forensic MPS applications were also described. In conclusion, the validation studies based on ~ 2200 MPS-based and ~ 2500 CE-based DNA profiles demonstrated that the novel MPS-based panel meets forensic DNA quality assurance guidelines with robust, reliable, and reproducible performance on samples of various quantities and qualities, and the STR nomenclature rules should be further regulated to integrate the inconformity between MPS-based and CE-based methods.

Tuning product selectivity in CO2 hydrogenation over metal-based catalysts.

Conversion of CO2 into chemicals is a promising strategy for CO2 utilization, but its intricate transformation pathways and insufficient product selectivity still pose challenges. Exploiting new catalysts for tuning product selectivity in CO2 hydrogenation is important to improve the viability of this technology, where reverse water-gas shift (RWGS) and methanation as competitive reactions play key roles in controlling product selectivity in CO2 hydrogenation. So far, a series of metal-based catalysts with adjustable strong metal-support interactions, metal surface structure, and local environment of active sites have been developed, significantly tuning the product selectivity in CO2 hydrogenation. Herein, we describe the recent advances in the fundamental understanding of the two reactions in CO2 hydrogenation, in terms of emerging new catalysts which regulate the catalytic structure and switch reaction pathways, where the strong metal-support interactions, metal surface structure, and local environment of the active sites are particularly discussed. They are expected to enable efficient catalyst design for minimizing the deep hydrogenation and controlling the reaction towards the RWGS reaction. Finally, the potential utilization of these strategies for improving the performance of industrial catalysts is examined.

Insights Into Forensic Features and Genetic Structures of Guangdong Maoming Han Based on 27 Y-STRs.

Maoming is located in the southwest region of Guangdong Province and is the cradle of Gaoliang culture, which is the representative branch of Lingnan cultures. Historical records showed that the amalgamations between Gaoliang aborigines and distinct ethnic minorities had some influences on the shaping of Gaoliang culture, especially for the local Tai-kadai language-speaking Baiyue and Han Chinese from Central China. However, there is still no exact genetic evidence for the influences on the genetic pool of Maoming Han, and the genetic relationships between Maoming Han and other Chinese populations are still unclear. Hence, in order to get a better understanding of the paternal genetic structures and characterize the forensic features of 27 Y-chromosomal short tandem repeats (Y-STRs) in Han Chinese from Guangdong Maoming, we firstly applied the AmpFLSTR® Yfiler® Plus PCR Amplification Kit (Thermo Fisher Scientific, Waltham, MA, United States) to genotype the haplotypes in 431 Han males residing in Maoming. A total of 263 different alleles were determined across all 27 Y-STRs with the corresponding allelic frequencies from 0.0004 to 0.7401, and the range of genetic diversity (GD) was 0.4027 (DYS391) to 0.9596 (DYS385a/b). In the first batch of 27 Yfiler data in Maoming Han, 417 distinct haplotypes were discovered, and nine off-ladder alleles were identified at six Y-STRs; in addition, no copy number variant or null allele was detected. The overall haplotype diversity (HD) and discrimination capacity (DC) of 27 Yfiler were 0.9997 and 0.9675, respectively, which demonstrated that the 6-dye and 27-plex system has sufficient system effectiveness for forensic applications in Maoming Han. What is more, the phylogenetic analyses indicated that Maoming Han, which is a Southern Han Chinese population, has a close relationship with Meizhou Kejia, which uncovered that the role of the gene flows from surrounding Han populations in shaping the genetic pool of Maoming Han cannot be ignored. From the perspectives of genetics, linguistics, and geographies, the genetic structures of Han populations correspond to the patterns of the geographical-scale spatial distributions and the relationships of language families. Nevertheless, no exact genetic evidence supports the intimate relationships between Maoming Han and Tai-Kadai language-speaking populations and Han populations of Central Plains in the present study.