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Abstract Background High-quality genomic datasets from under-representative populations are essential for population genetic analysis and medical relevance. Although the Tujia are the most populous ethnic minority in southwestern China, previous genetic studies have been fragmented and only partially reveal their genetic diversity landscape. The understanding of their fine-scale genetic structure and potentially differentiated biological adaptive features remains nascent. Objectives This study aims to explore the demographic history and genetic architecture related to the natural selection of the Tujia people, focusing on a meta-Tujia population from the central regions of the Yangtze River Basin. Results Population genetic analyses conducted on the meta-Tujia people indicate that they occupy an intermediate position in the East Asian North-South genetic cline. A close genetic affinity was identified between the Tujia people and neighboring Sinitic-speaking populations. Admixture models suggest that the Tujia can be modeled as a mixture of northern and southern ancestries. Estimates of f 3 /f 4 statistics confirmed the presence of ancestral links to ancient Yellow River Basin millet farmers and the BaBanQinCen-related groups. Furthermore, population-specific natural selection signatures were explored, revealing highly differentiated functional variants between the Tujia and southern indigenous populations, including genes associated with hair morphology (e.g., EDAR) and skin pigmentation (e.g., SLC24A5). Additionally, both shared and unique selection signatures were identified among ethnically diverse but geographically adjacent populations, highlighting their extensive admixture and the biological adaptations introduced by this admixture. Conclusions The study unveils significant population movements and genetic admixture among the Tujia and other ethno-linguistically diverse East Asian groups, elucidating the differentiated adaptation processes across geographically diverse populations from the current genetic landscape.

Abstract Background Ancient northern East Asians (ANEA) from the Yellow River region, who pioneered millet cultivation, play a crucial role in understanding the origins of ethnolinguistically diverse populations in modern China and the entire landscape of deep genetic structure and variation discovery in modern East Asians. However, the direct links between ANEA and geographically proximate modern populations, as well as the biological adaptive processes involved, remain poorly understood. Results Here, we generated genome-wide SNP data for 264 individuals from geographically different Han populations in Shandong. An integrated genomic resource encompassing both modern and ancient East Asians was compiled to examine fine-scale population admixture scenarios and adaptive traits. The reconstruction of demographic history and hierarchical clustering patterns revealed that individuals from the Shandong Peninsula share a close genetic affinity with ANEA, indicating long-term genetic continuity and mobility in the lower Yellow River basin since the early Neolithic period. Biological adaptive signatures, including those related to immune and metabolic pathways, were identified through analyses of haplotype homozygosity and allele frequency spectra. These signatures are linked to complex traits such as height and body mass index, which may be associated with adaptations to cold environments, dietary practices, and pathogen exposure. Additionally, allele frequency trajectories over time and a haplotype network of two highly differentiated genes, ABCC11 and SLC10A1, were delineated. These genes, which are associated with axillary odor and bilirubin metabolism, respectively, illustrate how local adaptations can influence the diversification of traits in East Asians. Conclusions Our findings provide a comprehensive genomic dataset that elucidates the fine-scale genetic history and evolutionary trajectory of natural selection signals and disease susceptibility in Han Chinese populations. This study serves as a paradigm for integrating spatiotemporally diverse ancient genomes in the era of population genomic medicine.

Abstract Background The underrepresentation of human genomic resources from Southern Chinese populations limited their health equality in the precision medicine era and complete understanding of their genetic formation, admixture, and adaptive features. Besides, linguistical and genetic evidence supported the controversial hypothesis of their origin processes. One hotspot case was from the Chinese Guangxi Pinghua Han people (GPH), whose language was significantly similar to Southern Chinese dialects but whose uniparental gene pool was phylogenetically associated with the indigenous Tai-Kadai (TK) people. Here, we analyzed genome-wide SNP data in 619 people from four language families and 56 geographically different populations, in which 261 people from 21 geographically distinct populations were first reported here. Results We identified significant population stratification among ethnolinguistically diverse Guangxi populations, suggesting their differentiated genetic origin and admixture processes. GPH shared more alleles related to Zhuang than Southern Han Chinese but received more northern ancestry relative to Zhuang. Admixture models and estimates of genetic distances showed that GPH had a close genetic relationship with geographically close TK compared to Northern Han Chinese, supporting their admixture origin hypothesis. Further admixture time and demographic history reconstruction supported GPH was formed via admixture between Northern Han Chinese and Southern TK people. We identified robust signatures associated with lipid metabolisms, such as fatty acid desaturases (FADS) and medically relevant loci associated with Mendelian disorder (GJB2) and complex diseases. We also explored the shared and unique selection signatures of ethnically different but linguistically related Guangxi lineages and found some shared signals related to immune and malaria resistance. Conclusions Our genetic analysis illuminated the language-related fine-scale genetic structure and provided robust genetic evidence to support the admixture hypothesis that can explain the pattern of observed genetic diversity and formation of GPH. This work presented one comprehensive analysis focused on the population history and demographical adaptative process, which provided genetic evidence for personal health management and disease risk prediction models from Guangxi people. Further large-scale whole-genome sequencing projects would provide the entire landscape of southern Chinese genomic diversity and their contributions to human health and disease traits.

Abstract Background The underrepresentation of Hmong-Mien (HM) people in Asian genomic studies has hindered our comprehensive understanding of the full landscape of their evolutionary history and complex trait architecture. South China is a multi-ethnic region and indigenously settled by ethnolinguistically diverse HM, Austroasiatic (AA), Tai-Kadai (TK), Austronesian (AN), and Sino-Tibetan (ST) people, which is regarded as East Asia’s initial cradle of biodiversity. However, previous fragmented genetic studies have only presented a fraction of the landscape of genetic diversity in this region, especially the lack of haplotype-based genomic resources. The deep characterization of demographic history and natural-selection-relevant genetic architecture of HM people was necessary. Results We reported one HM-specific genomic resource and comprehensively explored the fine-scale genetic structure and adaptative features inferred from the genome-wide SNP data of 440 HM individuals from 33 ethnolinguistic populations, including previously unreported She. We identified solid genetic differentiation between HM people and Han Chinese at 7.64‒15.86 years ago (kya) and split events between southern Chinese inland (Miao/Yao) and coastal (She) HM people in the middle Bronze Age period and the latter obtained more gene flow from Ancient Northern East Asians. Multiple admixture models further confirmed that extensive gene flow from surrounding ST, TK, and AN people entangled in forming the gene pool of Chinese coastal HM people. Genetic findings of isolated shared unique ancestral components based on the sharing alleles and haplotypes deconstructed that HM people from the Yungui Plateau carried the breadth of previously unknown genomic diversity. We identified a direct and recent genetic connection between Chinese inland and Southeast Asian HM people as they shared the most extended identity-by-descent fragments, supporting the long-distance migration hypothesis. Uniparental phylogenetic topology and network-based phylogenetic relationship reconstruction found ancient uniparental founding lineages in southwestern HM people. Finally, the population-specific biological adaptation study identified the shared and differentiated natural selection signatures among inland and coastal HM people associated with physical features and immune functions. The allele frequency spectrum of cancer susceptibility alleles and pharmacogenomic genes showed significant differences between HM and northern Chinese people. Conclusions Our extensive genetic evidence combined with the historical documents supported the view that ancient HM people originated from the Yungui regions associated with ancient “Three-Miao tribes” descended from the ancient Daxi-Qujialing-Shijiahe people. Then, some have recently migrated rapidly to Southeast Asia, and some have migrated eastward and mixed respectively with Southeast Asian indigenes, Liangzhu-related coastal ancient populations, and incoming southward ST people. Generally, complex population migration, admixture, and adaptation history contributed to the complicated patterns of population structure of geographically diverse HM people.

Pathogen‒host adaptative interactions and complex population demographical processes, including admixture, drift, and Darwen selection, have considerably shaped the Neolithic-to-Modern Western Eurasian population structure and genetic susceptibility to modern human diseases. However, the genetic footprints of evolutionary events in East Asia remain unknown due to the underrepresentation of genomic diversity and the design of large-scale population studies. We reported one aggregated database of genome-wide SNP variations from 796 Tai-Kadai (TK) genomes, including that of Bouyei first reported here, to explore the genetic history, population structure, and biological adaptative features of TK people from southern China and Southeast Asia. We found geography-related population substructure among TK people using the state-of-the-art population genetic structure reconstruction techniques based on the allele frequency spectrum and haplotype-resolved phased fragments. We found that the northern TK people from Guizhou harbored one TK-dominant ancestry maximized in the Bouyei people, and the southern TK people from Thailand were more influenced by Southeast Asians and indigenous people. We reconstructed fitted admixture models and demographic graphs, which showed that TK people received gene flow from ancient southern rice farmer-related lineages related to the Hmong-Mien and Austroasiatic people and from northern millet farmers associated with the Sino-Tibetan people. Biological adaptation focused on our identified unique TK lineages related to Bouyei, which showed many adaptive signatures conferring Malaria resistance and low-rate lipid metabolism. Further gene enrichment, the allele frequency distribution of derived alleles, and their correlation with the incidence of Malaria further confirmed that CR1 played an essential role in the resistance of Malaria in the ancient ''Baiyue'' tribes.

Abstract Photoreceptor apoptosis is an important pathogenesis of retinal degeneration and a primary cause of vision loss with limited treatment methods. Mesenchymal stem/stromal cells-derived small extracellular vesicles (MSC-sEVs) have shown therapeutic value in various ocular disorders. Recent studies have revealed that hypoxic preconditioning can improve the effectiveness of MSC-sEVs in tissue regeneration. However, whether hypoxic preconditioned MSC-sEVs (Hyp-sEVs) exert superior effects on photoreceptor protection relative to normoxic conditioned MSC-sEVs (Nor-sEVs) remains unclear. Here, we reported that Hyp-sEVs further improved retinal structure, recovered retinal function, and suppressed photoreceptor apoptosis in N-methyl-N-nitrosourea (MNU)-induced mouse model compared with Nor-sEVs. Hyp-sEVs also exhibited enhanced anti-apoptotic roles in MNU-provoked 661 W cell injury in vitro. We then analyzed the protein profiles of Nor-sEVs and Hyp-sEVs by LC-MS/MS and found that growth-associated protein 43 (GAP43) was enriched in Hyp-sEVs. The knockdown of GAP43 abolished the retinal therapeutic effects of Hyp-sEVs. Mechanistically, hypoxic stimulation-induced hypoxia-inducible factor-1α (HIF-1α) activation was responsible for preventing tripartite motif-containing protein 25 (TRIM25)-mediated GAP43 ubiquitination and degradation, leading to the upregulation of GAP43 in Hyp-sEVs. Together, our findings uncover the efficacy and mechanism of Hyp-sEVs-based photoreceptor protection and highlight the potential of Hyp-sEVs as optimized therapeutics for retinal degeneration. Graphical abstract

Abstract Background Non-recombining regions of the Y-chromosome recorded the evolutionary traces of male human populations and are inherited haplotype-dependently and male-specifically. Recent whole Y-chromosome sequencing studies have identified previously unrecognized population divergence, expansion and admixture processes, which promotes a better understanding and application of the observed patterns of Y-chromosome genetic diversity. Results Here, we developed one highest-resolution Y-chromosome single nucleotide polymorphism (Y-SNP) panel targeted for uniparental genealogy reconstruction and paternal biogeographical ancestry inference, which included 639 phylogenetically informative SNPs. We genotyped these loci in 1033 Chinese male individuals from 33 ethnolinguistically diverse populations and identified 256 terminal Y-chromosomal lineages with frequency ranging from 0.0010 (singleton) to 0.0687. We identified six dominant common founding lineages associated with different ethnolinguistic backgrounds, which included O2a2b1a1a1a1a1a1a1-M6539, O2a1b1a1a1a1a1a1-F17, O2a2b1a1a1a1a1b1a1b-MF15397, O2a2b2a1b1-A16609, O1b1a1a1a1b2a1a1-F2517, and O2a2b1a1a1a1a1a1-F155. The AMOVA and nucleotide diversity estimates revealed considerable differences and high genetic diversity among ethnolinguistically different populations. We constructed one representative phylogenetic tree among 33 studied populations based on the haplogroup frequency spectrum and sequence variations. Clustering patterns in principal component analysis and multidimensional scaling results showed a genetic differentiation between Tai-Kadai-speaking Li, Mongolic-speaking Mongolian, and other Sinitic-speaking Han Chinese populations. Phylogenetic topology inferred from the BEAST and Network relationships reconstructed from the popART further showed the founding lineages from culturally/linguistically diverse populations, such as C2a/C2b was dominant in Mongolian people and O1a/O1b was dominant in island Li people. We also identified many lineages shared by more than two ethnolinguistically different populations with a high proportion, suggesting their extensive admixture and migration history. Conclusions Our findings indicated that our developed high-resolution Y-SNP panel included major dominant Y-lineages of Chinese populations from different ethnic groups and geographical regions, which can be used as the primary and powerful tool for forensic practice. We should emphasize the necessity and importance of whole sequencing of more ethnolinguistically different populations, which can help identify more unrecognized population-specific variations for the promotion of Y-chromosome-based forensic applications.

Designing a novel photocatalytic composite for the efficient degradation of organic dyes remains a serious challenge. Herein, the multi-layered Co3O4@NP-CuO photocatalyst with unique features, i.e., the self-supporting, hierarchical porous network as well as the construction of heterojunction between Co3O4 and CuO, are synthesized by dealloying-electrodeposition and subsequent thermal treatment techniques. It is found that the interwoven ultrathin Co3O4 nanopetals evenly grow on the nanoporous CuO network (Co3O4@NP-CuO). The three-dimensional (3D) hierarchical porous structure for the catalyst provides more surface area to act as active sites and facilitates the absorption of visible light in the photodegradation reaction. Compared with the commercial CuO and Co3O4 powders, the newly designed Co3O4@NP-CuO composite exhibits superior photodegradation performance for RhB. The enhanced performance is mainly due to the construction of heterojunction of Co3O4/CuO, greatly promoting the efficient carrier separation for photocatalysis. Furthermore, the possible photocatalytic mechanism is analyzed in detail. This work provides a promising strategy for the fabrication of a new controllable heterojunction to improve photocatalytic activity.

To obtain qualified logging while drilling (LWD) data, a new acoustic LWD tool was designed. Its overall design is introduced here, including the physical construction, electronic structure, and operation flowchart. Thereafter, core technologies adopted in this tool are presented, such as dominant exciting wave bands of dipole source, a sine wave pulse excitation circuit, broadband impedance matching, and an intellectualized active reception transducer. Lastly, we tested this tool in the azimuthal anisotropy module well, calibration well, and normal well, working in the model of the cable, sliding eye, and logging while drilling. Experiments showed that the core technologies achieved ideal results and that the LWD tool obtained qualified data.

Non-contact ultrasonic motors (USM) show potential for future use, especially in the industrial fields because of its simple structure and quick response. It is therefore important to comprehensively understand their theoretical background so as to push this research forward. In this study, we shall fully explain and deduce the driving mechanism of a linear ultrasonic levitation transporting system. Oscillation equations from the initial exciting Langevin transducer and flexural traveling wave propagation on the linear guide were first established. Then the squeezing fluid movement between the linear guide and the levitating slider was analyzed. Next, after being excited by the progressing wave under corresponding boundary conditions, the related tangential velocity of the middle flow field was obtained. Finally, the validated experiment was set up to test slider velocity. [ABSTRACT FROM AUTHOR]

Residual stress is a key factor that directly affects fatigue, stress corrosion, fretting wear and other performance of engineering materials and components. However, it is difficult to accurately obtain the distribution of the deep residual stress field of the components using theoretical analysis and traditional non-destructive testing methods, which greatly hinders the development of advanced components. Due to the high penetration ability of thermal neutrons, neutron diffraction is an excellent engineering tool for providing mapping of residual stresses nondestructively in bulk components. Therefore, neutron diffraction was the most suitable non-destructive technique to characterize the deep residual stresses distribution. Therefore, National Important Project on Scientific Instrument and Equipment “the Neutron Diffractometer for Residual Stress and Defect in Materials and Components” was funded to built Engineering and Scientific Stress Diffractometer at China Advanced Research Reactor (CARR), which will serve the development of national important equipments, provide testing technique for manufacturing process of large-scale component and accumulate technical data for new material design. In order to fully play the role of Engineering and Scientific Stress Diffractometer in residual stress characterization of the engineering components, the mostly used crystal planes and the required wavelength for diffraction angle of about 90° of steel, nickel, copper, aluminum and titanium were analyzed. Thus, the optimal wavelength of the diffractometer was chosen to be around 0.164 nm, which satisfies the residual stress measurement for most commonly used metal materials. With this wavelength, the error of Fe(211) diffraction peak position was used as figure of Merit for the optics optimization. Optimized optics was obtained by tuning the horizontal and vertical focusing parameters. The neutron flux at the sample position that measured at the optimized optics with wavelength of 0.164 nm is a key parameter for the intensity performance of diffractometer. The activation method is the most commonly used technique to measure the distribution of neutron flux, which has the advantages of flexibility, adaptability, wide sensitivity and small disturbance to neutron field. In this work, the neutron flux at the sample is 3.0×107 cm−2·s−1 (±4.5%) at full reactor power of 60 MW. The resolution at the diffraction angle of about 90° is 0.42% by analyzing Fe(211) diffraction peak. The position resolution of the area detector was tested using a cadmium plate with three slit with known size. The horizontal position resolution is (1.44±0.03) mm. In this work, the optical optimization and performance calibration of Engineering and Scientific Stress Diffractometer at CARR were completed, which provides an experimental foundation for the instrument operation.

The in-situ experimental study of the microstructure of materials under thermodynamic coupling under near-working conditions is very important for in-depth understanding of the evolution mechanism of material service performance. The microscopic distribution of nanostructures on the sample can be given. Based on the advantages of small-angle neutron scattering method with good statistics and large sampling volume, in-situ experiments can be carried out, based on the small-angle neutron scattering spectrometer of China Advanced Research Reactor, an in-situ experimental device with simultaneous loading of high temperature and tensile force was designed and developed, and the morphological changes of materials at the nanoscale were measured online at high temperature and high pressure. The test results of the inspection and calibration experiment show that the maximum load of the device can reach 20 kN, the maximum temperature is 800℃, and the temperature control accuracy is better than ±1℃. The device was used to carry out in-situ small-angle neutron scattering experiments on nickel-based single crystal superalloy samples, and the obvious changes in the internal nanostructure of the samples under temperature tension conditions were obtained, indicating that the device could carry out the experimental research ability of in-situ thermodynamic coupling loading small-angle neutron scattering. The device and its corresponding experimental methods can also be used for in-situ experimental research of various high-temperature structural materials such as nuclear power stainless steel to provide microstructure evolution data.