Acid-assisted self-assembly of pyrene-capped tyrosine ruptures lysosomes to induce cancer cell apoptosis.

Induced lysosomal membrane permeabilization (LMP) by peptide self-assembly has emerged as an effective platform for lysosome-targeted cancer therapy. In this study, we shift this strategical paradigm and present an innovative approach to LMP induction through amino acid-based self-assembly. Pyrene-capped tyrosine (Py-Tyr), as a proof-of-concept molecule, is designed with acidity-responsive self-assembly. Under acidic conditions (pH 4), Py-Tyr is protonated with reduced charge repulsion, and self-assembles into micrometer-scaled aggregates, which exceed the biological size of lysosomes. Cell experiments showed that Py-Tyr specifically accumulates in lysosomes and induces lysosome rupture, leading to the release of cathepsin B into the cytoplasm for subsequent apoptosis activation in cancer cells. This study capitalizes on the concept of amino acid assembly for efficient LMP induction, providing a simple and versatile platform for precise and effective therapeutic interventions in cancer therapy.

An ALP-responsive, anionic iridium complex for specific recognition of osteosarcoma cells.

Poor cellular permeability greatly hampers the utilization of anionic Ir(III) complexes, though efficiently emissive and remarkably stable, in cell-based diagnosis. To overcome this barrier, we present the development of an alkaline phosphatase (ALP)-responsive, anionic, and aggregation-induced emission (AIE)-active Ir(III) complex (Ir1) for specific recognition of osteosarcoma cells. Containing phosphate moieties, Ir1 exhibits a net -1 charge, enabling charge repulsion from the cell membrane and resulting in low cellular uptake and good biocompatibility in normal osteoblast cells. Upon ALP-mediated hydrolysis of phosphate groups, the resulting dephosphorylated product, Ir2, demonstrates a positive charge and increased lipophilicity, promoting cellular uptake and activating its AIE properties for specific recognition of osteosarcoma cells that express elevated levels of ALP. This study elucidates the role of ALP as an ideal trigger for enhancing the cellular permeability of phosphate ester-containing Ir(III) complexes, thus expanding the potential of anionic Ir(III) complexes for biomedical applications.

Health risk assessment for soil radioactivity around Shidaowan nuclear power plant in Shandong, China.

Monitoring radioactivity levels in the environment around nuclear power plants is of great significance to assessing environmental safety and impact. Shidaowan nuclear power plant is currently undergoing commissioning; however, the baseline soil radioactivity is unknown. The naturally occurring radionuclides 238U, 232Th, 226Ra and 40K, and artificial radionuclide (AR) 137Cs in soil samples around the Shidaowan nuclear power plant were measured to establish the baseline levels. Human health hazard indices such as external hazard indices (Hex), Radium equivalent (Raeq), outdoor absorbed dose rate (Dout), annual effective dose (AED) and excess lifetime cancer risk (ELCR) were estimated. The average concentration of 232Th, 40K, 137Cs, 238U and 226Ra were 42.6 ± 15, 581 ± 131, 0.68 ± 0.38, 40.13 ± 9.07 and 40.8 ± 12.8 Bq per kg, respectively. The average Hex, Raeq, Dout, AED and ELCR were 0.40, 146 Bq per kg, 68.8 nGy per h, 0.09 mSv per y and 3.29E-04, respectively. These data showed an acceptable level of risk to residents near the nuclear power plant and that the current radioactivity in the soil may not pose immediate harm to residents living close to the nuclear power plant. The observed lower AED and 40 K and 137Cs concentrations were comparable to other studies, whilst ELCR was higher than the world average of 2.9E-04. The commissioning of the Shidaowan nuclear power plant is potentially safe for the surrounding residents; further continuous monitoring is recommended.

G-quadruplex in the TMV Genome Regulates Viral Proliferation and Acts as Antiviral Target of Photodynamic Therapy.

Plant viruses seriously disrupt crop growth and development, and classic protein-targeted antiviral drugs could not provide complete protection against them. It is urgent to develop antiviral compounds with novel targets. Photodynamic therapy shows potential in controlling agricultural pests, but nonselective damage from reactive oxygen species (ROS) unexpectedly affects healthy tissues. A G-quadruplex (G4)-forming sequence in the tobacco mosaic virus (TMV) genome was identified to interfere the RNA replication in vitro, and affect the proliferation of TMV in tobacco. N-methyl mesoporphyrin IX stabilizing the G4 structure exhibited inhibition against viral proliferation, which was comparable to the inhibition effect of ribavirin. This indicated that G4 could work as an antiviral target. The large conjugate planes shared by G4 ligands and photosensitizers (PSs) remind us that the PSs could work as antiviral agents by targeting G4 in the genome of TMV. Chlorin e6 (Ce6) was identified to stabilize the G4 structure in the dark and selectively cleave the G4 sequence by producing ROS upon LED-light irradiation, leading to 92.2% inhibition against TMV in vivo, which is higher than that of commercial ningnanmycin. The inhibition of Ce6 was lost against the mutant variants lacking the G4-forming sequence. These findings indicated that the G-quadruplex in the TMV genome worked as an important structural element regulating viral proliferation, and could act as the antiviral target of photodynamic therapy.

Whole mitochondrial genome analysis in highland Tibetans: further matrilineal genetic structure exploration.

Introduction: The Qinghai-Tibet Plateau is one of the last terrestrial environments conquered by modern humans. Tibetans are among the few high-altitude settlers in the world, and understanding the genetic profile of Tibetans plays a pivotal role in studies of anthropology, genetics, and archaeology. Methods: In this study, we investigated the maternal genetic landscape of Tibetans based on the whole mitochondrial genome collected from 145 unrelated native Lhasa Tibetans. Molecular diversity indices, haplotype diversity (HD), Tajima's D and Fu's Fs were calculated and the Bayesian Skyline Plot was obtained to determining the genetic profile and population fluctuation of Lhasa Tibetans. To further explore the genetic structure of Lhasa Tibetans, we collected 107 East Asian reference populations to perform principal component analysis (PCA), multidimensional scaling (MDS), calculated Fst values and constructed phylogenetic tree. Results: The maternal genetic landscape of Tibetans showed obvious East Asian characteristics, M9a (28.28%), R (11.03%), F1 (12.41%), D4 (9.66%), N (6.21%), and M62 (4.14%) were the dominant haplogroups. The results of PCA, MDS, Fst and phylogenetic tree were consistent: Lhasa Tibetans clustered with other highland Tibeto-Burman speakers, there was obvious genetic homogeneity of Tibetans in Xizang, and genetic similarity between Tibetans and northern Han people and geographically adjacent populations was found. In addition, specific maternal lineages of Tibetans also be determined in this study. Discussion: In general, this study further shed light on long-time matrilineal continuity on the Tibetan Plateau and the genetic connection between Tibetans and millet famers in the Yellow River Basin, and further revealed that multiple waves of population interaction and admixture during different historical periods between lowland and highland populations shaped the maternal genetic profile of Tibetans.

Large and tunable magnetoresistance in van der Waals ferromagnet/semiconductor junctions.

Magnetic tunnel junctions (MTJs) with conventional bulk ferromagnets separated by a nonmagnetic insulating layer are key building blocks in spintronics for magnetic sensors and memory. A radically different approach of using atomically-thin van der Waals (vdW) materials in MTJs is expected to boost their figure of merit, the tunneling magnetoresistance (TMR), while relaxing the lattice-matching requirements from the epitaxial growth and supporting high-quality integration of dissimilar materials with atomically-sharp interfaces. We report TMR up to 192% at 10 K in all-vdW Fe3GeTe2/GaSe/Fe3GeTe2 MTJs. Remarkably, instead of the usual insulating spacer, this large TMR is realized with a vdW semiconductor GaSe. Integration of semiconductors into the MTJs offers energy-band-tunability, bias dependence, magnetic proximity effects, and spin-dependent optical-selection rules. We demonstrate that not only the magnitude of the TMR is tuned by the semiconductor thickness but also the TMR sign can be reversed by varying the bias voltages, enabling modulation of highly spin-polarized carriers in vdW semiconductors.

Unveiling 2,000 years of differentiation among Tungusic-speaking populations: a revised phylogeny of the paternal founder lineage C2a-M48-SK1061.

Previous studies demonstrated Y chromosome haplogroup C2a-M48-SK1061 is the only founding paternal lineage of all Tungusic-speaking populations. To infer the differentiation history of these populations, we studied more sequences and constructed downstream structure of haplogroup C2a-M48-SK1061 with better resolution. In this study, we generated 100 new sequences and co-analyzed 140 sequences of C2a-M48-SK1061 to reconstruct a highly revised phylogenetic tree with age estimates. We also performed the analysis of the geographical distribution and spatial autocorrelation of sub-branches. Dozens of new sub-branches were discovered, many sub-branches were nearly unique for Ewenki, Evens, Oroqen, Xibe, Manchu, Daur, and Mongolian. The topology of these unique sub-branches is the key evidence for understanding the complex evolutionary relationship between different Tungusic-speaking populations. The revised phylogeny provided a clear pattern for the differentiation history of haplogroup C2a-M48-SK1061 in the past 2,000 years. This study showed that the divergence pattern of founder lineage is essential to understanding the differentiation history of populations.

The formation of proto-austronesians: insights from a revised phylogeography of the paternal founder lineage.

OBJECTIVES: Previous studies suggested that the Y-chromosome haplogroups O2-N6-B451-AM01756 and O1a-M119 are two founder lineages of proto-Austronesians at about five thousand years ago. The objective of this study was to investigate the formation of proto-Austronesians from the perspective of the paternal gene pool. MATERIALS AND METHODS: In this study, we developed a highly evised phylogenetic tree with age estimates for haplogroup O2-N6 and early branches of O1a-M119 (M110, F1036, and F819). In addition, we also explored the geographical distribution of eight sub-branches of O2-N6 and O1a-M119, and spatial autocorrelation analysis was conducted for each sub-branch. RESULTS: The paternal lineage combination of proto-Austronesians is a small subset of a diverse gene pool of populations from the mainland of East Asia. The distribution map and results of the spatial autocorrelation analysis suggested that the eastern coastal region of northern China is likely the source of lineage O2-N6 while the coastal region of southeastern China is likely the diffusion center of early branches of O1a-M119. We developed an evolutionary diagram for Austronesians and their ancestors in the past 18,000 years. DISCUSSION: We proposed that the millet farming community in North China is the common ancestor group of the Austronesians and the Han people, while the diverse ancient people in the southeast coastal areas of East Asia form the common ancestor group of the Austronesians and the East Asian mainland population. The demographic history of multiple ancestral groups of the most recent common ancestor group itself in the more ancient period is helpful to understand the deep roots of the genetic components and cultural traditions of Austronesians.

Engineering self-healing adhesive hydrogels with antioxidant properties for intrauterine adhesion prevention.

Intrauterine adhesion (IUA) is the fibrosis within the uterine cavity. It is the second most common cause of female infertility, significantly affecting women's physical and mental health. Current treatment strategies fail to provide a satisfactory therapeutic outcome for IUA patients, leaving an enormous challenge for reproductive science. A self-healing adhesive hydrogel with antioxidant properties will be highly helpful in IUA prevention. In this work, we prepare a series of self-healing hydrogels (P10G15, P10G20, and P10G25) with antioxidant and adhesive properties. Those hydrogels exhibit good self-healing properties and can adapt themselves to different structures. They possess good injectability and fit the shape of the human uterus. Moreover, the hydrogels exhibit good tissue adhesiveness, which is desirable for stable retention and therapeutic efficacy. The in vitro experiments using P10G20 show that the adhesive effectively scavenges ABTS+, DPPH, and hydroxyl radicals, rescuing cells from oxidative stress. In addition, P10G20 offers good hemocompatibility and in vitro and in vivo biocompatibility. Furthermore, P10G20 lowers down the in vivo oxidative stress and prevents IUA with less fibrotic tissue and better endometrial regeneration in the animal model. It can effectively downregulate fibrosis-related transforming growth factor beta 1 (TGF-ß1) and vascular endothelial growth factor (VEGF). Altogether, these adhesives may be a good alternative for the clinical treatment of intrauterine adhesion.

The impacts of bronze age in the gene pool of Chinese: Insights from phylogeographics of Y-chromosomal haplogroup N1a2a-F1101.

Objectives: Previous studies of archaeology and history suggested that the rise and prosperity of Bronze Age culture in East Asia had made essential contribution to the formation of early state and civilization in this region. However, the impacts in perspective of genetics remain ambiguous. Previous genetic researches indicated the Y-chromosome Q1a1a-M120 and N1a2a-F1101 may be the two most important paternal lineages among the Bronze Age people in ancient northwest China. Here, we investigated the 9,000-years history of haplogroup N1a2a-F1101 with revised phylogenetic tree and spatial autocorrelation analysis. Materials and Methods: In this study, 229 sequences of N1a2a-F1101 were analyzed. We developed a highly-revised phylogenetic tree with age estimates for N1a2a-F1101. In addition, we also explored the geographical distribution of sub-lineages of N1a2a-F1101, and spatial autocorrelation analysis was conducted for each sub-branch. Results: The initial differentiation location of N1a2a-F1101 and its most closely related branch, N1a2b-P43, a major lineage of Uralic-speaking populations in northern Eurasia, is likely the west part of northeast China. After ~4 thousand years of bottleneck effect period, haplgroup N1a2a-F1101 experienced continuous expansion during the Chalcolithic age (~ 4.5 kya to 4 kya) and Bronze age (~ 4 kya to 2.5 kya) in northern China. Ancient DNA evidence supported that this haplogroup is the lineage of ruling family of Zhou Dynasty (~ 3 kya-2.2 kya) of ancient China. Discussion: In general, we proposed that the Bronze Age people in the border area between the eastern Eurasian steppe and northern China not only played a key role in promoting the early state and civilization of China, but also left significant traces in the gene pool of Chinese people.

Specific discrimination and efficient elimination of gram-positive bacteria by an aggregation-induced emission-active ruthenium (II) photosensitizer.

The infections caused by Gram-positive bacteria (G+) have seriously endangered public heath due to their high morbidity and mortality. Therefore, it is urgent to develop a multifunctional system for selective recognition, imaging and efficient eradication of G+. Aggregation-induced emission materials have shown great promise for microbial detection and antimicrobial therapy. In this paper, a multifunctional ruthenium (II) polypyridine complex Ru2 with aggregation-induced emission (AIE) characteristic, was developed and used for selective discrimination and efficient extermination of G+ from other bacteria with unique selectivity. The selective G+ recognition benefited from the interaction between lipoteichoic acids (LTA) and Ru2. Accumulation of Ru2 on the G+ membrane turned on its AIE luminescence and allowed specific G+ staining. Meanwhile, Ru2 under light irradiation also possessed robust antibacterial activity for G+in vitro and in vivo antibacterial experiments. To the best of our knowledge, Ru2 is the first Ru-based AIEgen photosensitizer for simultaneous dual applications of G+ detection and treatment, and inspires the development of promising antibacterial agents in the future.

Succinic Ester-Based Shape Memory Gelatin Sponge for Noncompressible Hemorrhage without Hindering Tissue Regeneration.

Shape memory sponges are very promising in stopping the bleeding from noncompressible and narrow entrance wounds. However, few shape memory sponges have fast degradable properties in order to not hinder tissue healing. In this work, based on cryopolymerization, a succinic ester-based sponge (Ssponge) is fabricated using gelatin and bi-polyethylene glycol-succinimidyl succinate (Bi-PEG-SS). Compared with the commercially available gelatin sponge (Csponge), Ssponge possesses better water/blood absorption ability and higher mechanical pressure over the surrounding tissues. Moreover, in the models of massive liver hemorrhage after transection and noncompressive liver wounds by penetration, Ssponge exhibits a better hemostasis performance than Csponge. Furthermore, in a liver regeneration model, Ssponge-treated livers shows higher regeneration speed compared with Csponge, including a lower injury score, more cavity-like tissues, less fibrosis and enhanced tissue regeneration. Overall, it is shown that Ssponge, with a fast degradation behavior, is not only highly efficient in stopping bleeding but also not detrimental for tissue healing, possessing promising clinical translational potential.

Hydroxyapatite-Tethered Peptide Hydrogel Promotes Osteogenesis.

Hydroxyapatite (HAp) as natural bone composition is highly osteoinductive. To harvest its osteoinductivity in bone regenerative engineering, the HAp-supporting hydrogel is urgently needed to minimize inhomogeneous aggregation of HAp. Here, we developed a HAp-stabilizing hydrogel based on peptide self-assembly. FmocFFRR was efficient for HAp-capping due to arginine-phosphate interaction. Tethering FmocFFRR on the HAp surface facilitated self-assembly to form FmocFFRR/HAp hybrid hydrogel, enabling stable dispersion of HAp in it. The molecular interactions between FmocFFRR and HAp particles were studied using microscopic and spectral characterizations. FmocFFRR/HAp hydrogel exhibited more enhanced mechanical properties than FmocFFRR. The biocompatibility of FmocFFRR/HAp hydrogel was verified using an ATP assay and live-dead staining assay. More importantly, FmocFFRR/HAp hydrogel not only enabled cell attachment on its surface, but also supported 3D cell culturing inside the hydrogel. Further, 3D culturing of MC3T3-E1 preosteoblasts inside FmocFFRR/HAp hydrogel significantly enhanced the expressions of osteogenesis markers, including alkaline phosphate (ALP), type-I collagen (COL1), and osteocalcin (OCN), demonstrating the promoting effect of osteoblast differentiation. These findings inspire its potential application in bone regenerative engineering.

Genomic insights into the genetic structure and population history of Mongolians in Liaoning Province.

The Mongolian population exceeds six million and is the largest population among the Mongolic speakers in China. However, the genetic structure and admixture history of the Mongolians are still unclear due to the limited number of samples and lower coverage of single-nucleotide polymorphism (SNP). In this study, we genotyped genome-wide data of over 700,000 SNPs in 38 Mongolian individuals from Fuxin in Liaoning Province to explore the genetic structure and population history based on typical and advanced population genetic analysis methods [principal component analysis (PCA), admixture, FST, f 3 -statistics, f 4 -statistics, qpAdm/qpWave, qpGraph, ALDER, and TreeMix]. We found that Fuxin Mongolians had a close genetic relationship with Han people, northern Mongolians, other Mongolic speakers, and Tungusic speakers in East Asia. Also, we found that Neolithic millet farmers in the Yellow River Basin and West Liao River Basin and Neolithic hunter-gatherers in the Mongolian Plateau and Amur River Basin were the dominant ancestral sources, and there were additional gene flows related to Eurasian Steppe pastoralists and Neolithic Iranian farmers in the gene pool of Fuxin Mongolians. These results shed light on dynamic demographic history, complex population admixture, and multiple sources of genetic diversity in Fuxin Mongolians.

Highly Luminescent Nucleoside-Based N, P-Doped Carbon Dots for Sensitive Detection of Ions and Bioimaging.

The efficient detection of Fe3+ and MnO4 - in a water environment is very important and challenging due to their harmful effects on the health of humanity and environmental systems. Good biocompatibility, sensitivity, selectivity, and superior photophysical properties were important attributes of carbon dot-based CDs sensors for sensing applications. In this work, we synthesized N, P-co-doped carbon dots (N/P CDs) with guanosine 5'-monophosphate (GMP) as a green carbon source, with high fluorescence quantum yield in water (QY, 53.72%). First, the luminescent N/P CDs showed a three-state "on-off-on" fluorescence response upon the sequential addition of Fe3+ and F-, with a low detection limit of 12 nM for Fe3+ and 8.5 nM for F-, respectively. Second, the N/P CDs also exhibited desirable selectivity and sensitivity for toxic MnO4 - detection with the limit of detection of 18.2 nM, through a turn-off mechanism. Moreover, the luminescent N/P CDs successfully monitored the aforementioned ions in environmental water samples and in Escherichia coli.

Assessment of Occupational Exposure to Eye Lens Dosimetry for Interventional Radiology Workers in China during 2017-2019.

ABSTRACT: The eye lens is a sensitive tissue to ionizing radiation and recently has been recognized as more radiosensitive than previously considered. The International Commission on Radiological Protection (ICRP) has recommended a considerable reduction in the equivalent dose limit of eye lens from 150 mSv y -1 to 20 mSv y -1 , averaged over a defined period of 5 y. In this paper, the eye lens dose of interventional radiology workers in China during 2017-2019 is analyzed to understand the current status of eye lens occupational exposure and to provide decision-making suggestions for health supervision departments using data obtained from the National Radiological Health Information Platform in China. A total of 3,026 eye lens dose records of interventional radiology workers were collected. The average annual eye lens dose (AAELD) for interventional radiology workers ranged from 1.07 to 1.51 mSv during 2017-2019 and was 1.44 mSv for all monitored interventional radiology workers, with 2,973 records (98.2%) lower than the public limit of 15 mSv and 33 records (1.1%) exceeding the newly revised occupational eye lens dose limit of 20 mSv y -1 . During the period of 2017-2019, the AAELDs of interventional radiologists (1.61 mSv) and of interventional cardiologists (1.59 mSv) were significantly higher than that of other interventional workers (0.62 mSv); the AAELD of doctors (1.50 mSv) was significantly higher than that of nurses (1.01 mSv); the AAELD of western China (2.00 mSv) was significantly higher than that of eastern (1.11 mSv) and central China (1.27 mSv); and the AAELD of males (1.59 mSv) was significantly higher than that of females (0.84 mSv). The eye lens dose of interventional radiology workers meets the Chinese standard limit of 150 mSv y -1 , while some cases exceed the one recommended by ICRP. The study shows that the interventional radiology workers' eye lens dosimetry data complied with the existing Chinese eye lens dose limits. However, education, training, and supervision of radiation protection also should be strengthened continuously for interventional radiology workers, especially for the interventional radiologists and interventional cardiologists. Significant attention should be paid to the radiation protection of underdeveloped regions in China in future works.

Genomic history and forensic characteristics of Sherpa highlanders on the Tibetan Plateau inferred from high-resolution InDel panel and genome-wide SNPs.

Sherpa people, one of the high-altitude hypoxic adaptive populations, mainly reside in Nepal and the southern Tibet Autonomous Region. The genetic origin and detailed evolutionary profiles of Sherpas remain to be further explored and comprehensively characterized. Here we analyzed the newly-generated InDel genotype data from 628 Dingjie Sherpas by merging with 4222 worldwide InDel profiles and collected genome-wide SNP data (approximately 600K SNPs) from 1612 individuals in 191 modern and ancient populations to explore and reconstruct the fine-scale genetic structure of Sherpas and their relationships with nearby modern and ancient East Asians based on the shared alleles and haplotypes. The forensic parameters of 57 autosomal InDels (A-InDels) included in our used new-generation InDel amplification system showed that this focused InDel panel is informative and polymorphic in Dingjie Sherpas, suggesting that it can be used as the supplementary tool for forensic personal identification and parentage testing in Dingjie Sherpas. Descriptive findings from the PCA, ADMIXTURE, and TreeMix-based phylogenies suggested that studied Nepal Sherpas showed excess allele sharing with neighboring Tibeto-Burman Tibetans. Furthermore, patterns of allele sharing in f-statistics demonstrated that Nepal Sherpas had a different evolutionary history compared with their neighbors from Nepal (Newar and Gurung) but showed genetic similarity with 2700-year-old Chokhopani and modern Tibet Tibetans. QpAdm/qpGraph-based admixture sources and models further showed that Sherpas, core Tibetans, and Chokhopani formed one clade, which could be fitted as having the main ancestry from late Neolithic Qijia millet farmers and other deep ancestries from early Asians. Chromosome painting profiles and shared IBD fragments inferred from fineSTRUCTURE and ChromoPainter not only confirmed the abovementioned genomic affinity patterns but also revealed the fine-scale genetic microstructures among Sino-Tibetan speakers. Finally, natural-selection signals revealed via iHS, nSL and iHH12 showed natural selection signatures associated with disease susceptibility in Sherpas. Generally, we provided the comprehensive landscape of admixture and evolutionary history of Sherpa people based on the shared alleles and haplotypes from the InDel-based genotype data and high-density genome-wide SNP data. The more detailed genetic landscape of Sherpa people should be further confirmed and characterized via ancient genomes or single-molecule real-time sequencing technology.

Genomic Insights Into the Genetic Structure and Natural Selection of Mongolians.

Mongolians dwell at the Eastern Eurasian Steppe, where is the agriculture and pasture interlaced area, practice pastoral subsistence strategies for generations, and have their own complex genetic formation history. There is evidence that the eastward expansion of Western Steppe herders transformed the lifestyle of post-Bronze Age Mongolia Plateau populations and brought gene flow into the gene pool of Eastern Eurasians. Here, we reported genome-wide data for 42 individuals from the Inner Mongolia Autonomous Region of North China. We observed that our studied Mongolians were structured into three distinct genetic clusters possessing different genetic affinity with previous studied Inner Mongolians and Mongols and various Eastern and Western Eurasian ancestries: two subgroups harbored dominant Eastern Eurasian ancestry from Neolithic millet farmers of Yellow River Basin; another subgroup derived Eastern Eurasian ancestry primarily from Neolithic hunter-gatherers of North Asia. Besides, three-way/four-way qpAdm admixture models revealed that both north and southern Western Eurasian ancestry related to the Western Steppe herders and Iranian farmers contributed to the genetic materials into modern Mongolians. ALDER-based admixture coefficient and haplotype-based GLOBETROTTER demonstrated that the former western ancestry detected in modern Mongolian could be recently traced back to a historic period in accordance with the historical record about the westward expansion of the Mongol empire. Furthermore, the natural selection analysis of Mongolians showed that the Major Histocompatibility Complex (MHC) region underwent significantly positive selective sweeps. The functional genes, alcohol dehydrogenase (ADH) and lactase persistence (LCT), were not identified, while the higher/lower frequencies of derived mutations were strongly correlated with the genetic affinity to East Asian/Western Eurasian populations. Our attested complex population movement and admixture in the agriculture and pasture interlaced area played an important role in the formation of modern Mongolians.

Genomic Insight Into the Population Admixture History of Tungusic-Speaking Manchu People in Northeast China.

Manchu is the third-largest ethnic minority in China and has the largest population size among the Tungusic-speaking groups. However, the genetic origin and admixture history of the Manchu people are far from clear due to the sparse sampling and a limited number of markers genotyped. Here, we provided the first batch of genome-wide data of genotyping approximate 700,000 single-nucleotide polymorphisms (SNPs) in 93 Manchu individuals collected from northeast China. We merged the newly generated data with data of publicly available modern and ancient East Asians to comprehensively characterize the genetic diversity and fine-scale population structure, as well as explore the genetic origin and admixture history of northern Chinese Manchus. We applied both descriptive methods of ADMIXTURE, fineSTRUCTURE, F ST , TreeMix, identity by decedent (IBD), principal component analysis (PCA), and qualitative f-statistics (f 3, f 4, qpAdm, and qpWave). We found that Liaoning Manchus have a close genetic relationship and significant admixture signal with northern Han Chinese, which is in line with the cluster patterns in the haplotype-based results. Additionally, the qpAdm-based admixture models showed that modern Manchu people were formed as major ancestry related to Yellow River farmers and minor ancestry linked to ancient populations from Amur River Bain, or others. In summary, the northeastern Chinese Manchu people in Liaoning were an exception to the coherent genetic structure of Tungusic-speaking populations, probably due to the large-scale population migrations and genetic admixtures in the past few hundred years.

Genomic Insight Into the Population Structure and Admixture History of Tai-Kadai-Speaking Sui People in Southwest China.

Sui people, which belong to the Tai-Kadai-speaking family, remain poorly characterized due to a lack of genome-wide data. To infer the fine-scale population genetic structure and putative genetic sources of the Sui people, we genotyped 498,655 genome-wide single-nucleotide polymorphisms (SNPs) using SNP arrays in 68 Sui individuals from seven indigenous populations in Guizhou province and Guangxi Zhuang Autonomous Region in Southwest China and co-analyzed with available East Asians via a series of population genetic methods including principal component analysis (PCA), ADMIXTURE, pairwise Fst genetic distance, f-statistics, qpWave, and qpAdm. Our results revealed that Guangxi and Guizhou Sui people showed a strong genetic affinity with populations from southern China and Southeast Asia, especially Tai-Kadai- and Hmong-Mien-speaking populations as well as ancient Iron Age Taiwan Hanben, Gongguan individuals supporting the hypothesis that Sui people came from southern China originally. The indigenous Tai-Kadai-related ancestry (represented by Li), Northern East Asian-related ancestry, and Hmong-Mien-related lineage contributed to the formation processes of the Sui people. We identified the genetic substructure within Sui groups: Guizhou Sui people were relatively homogeneous and possessed similar genetic profiles with neighboring Tai-Kadai-related populations, such as Maonan. While Sui people in Yizhou and Huanjiang of Guangxi might receive unique, additional gene flow from Hmong-Mien-speaking populations and Northern East Asians, respectively, after the divergence within other Sui populations. Sui people could be modeled as the admixture of ancient Yellow River Basin farmer-related ancestry (36.2-54.7%) and ancient coastal Southeast Asian-related ancestry (45.3-63.8%). We also identified the potential positive selection signals related to the disease susceptibility in Sui people via integrated haplotype score (iHS) and number of segregating sites by length (nSL) scores. These genomic findings provided new insights into the demographic history of Tai-Kadai-speaking Sui people and their interaction with neighboring populations in Southern China.