Multiple Human Population Movements and Cultural Dispersal Events Shaped the Landscape of Chinese Paternal Heritage.

Large-scale genomic projects and ancient DNA innovations have ushered in a new paradigm for exploring human evolutionary history. However, the genetic legacy of spatiotemporally diverse ancient Eurasians within Chinese paternal lineages remains unresolved. Here, we report an integrated Y-chromosome genomic database encompassing 15,563 individuals from both modern and ancient Eurasians, including 919 newly reported individuals, to investigate the Chinese paternal genomic diversity. The high-resolution, time-stamped phylogeny reveals multiple diversification events and extensive expansions in the early and middle Neolithic. We identify four major ancient population movements, each associated with technological innovations that have shaped the Chinese paternal landscape. First, the expansion of early East Asians and millet farmers from the Yellow River Basin predominantly carrying O2/D subclades significantly influenced the formation of the Sino-Tibetan people and facilitated the permanent settlement of the Tibetan Plateau. Second, the dispersal of rice farmers from the Yangtze River Valley carrying O1 and certain O2 sublineages reshapes the genetic makeup of southern Han Chinese, as well as the Tai-Kadai, Austronesian, Hmong-Mien, and Austroasiatic people. Third, the Neolithic Siberian Q/C paternal lineages originated and proliferated among hunter-gatherers on the Mongolian Plateau and the Amur River Basin, leaving a significant imprint on the gene pools of northern China. Fourth, the J/G/R paternal lineages derived from western Eurasia, which were initially spread by Yamnaya-related steppe pastoralists, maintain their presence primarily in northwestern China. Overall, our research provides comprehensive genetic evidence elucidating the significant impact of interactions with culturally distinct ancient Eurasians on the patterns of paternal diversity in modern Chinese populations.

Oral microbiome sequencing revealed the enrichment of Fusobacterium sp., Porphyromonas sp., Campylobacter sp., and Neisseria sp. on the oral malignant fibroma surface of giant panda.

Introduction: Microbial community composition is closely associated with host disease onset and progression, underscoring the importance of understanding host-microbiota dynamics in various health contexts. Methods: In this study, we utilized full-length 16S rRNA gene sequencing to conduct species-level identification of the microorganisms in the oral cavity of a giant panda (Ailuropoda melanoleuca) with oral malignant fibroma. Results: We observed a significant difference between the microbial community of the tumor side and non-tumor side of the oral cavity of the giant panda, with the latter exhibiting higher microbial diversity. The tumor side was dominated by specific microorganisms, such as Fusobacterium simiae, Porphyromonas sp. feline oral taxon 110, Campylobacter sp. feline oral taxon 100, and Neisseria sp. feline oral taxon 078, that have been reported to be associated with tumorigenic processes and periodontal diseases in other organisms. According to the linear discriminant analysis effect size analysis, more than 9 distinct biomarkers were obtained between the tumor side and non-tumor side samples. Furthermore, the Kyoto Encyclopedia of Genes and Genomes analysis revealed that the oral microbiota of the giant panda was significantly associated with genetic information processing and metabolism, particularly cofactor and vitamin, amino acid, and carbohydrate metabolism. Furthermore, a significant bacterial invasion of epithelial cells was predicted in the tumor side. Discussion: This study provides crucial insights into the association between oral microbiota and oral tumors in giant pandas and offers potential biomarkers that may guide future health assessments and preventive strategies for captive and aging giant pandas.

Malaria resistance-related biological adaptation and complex evolutionary footprints inferred from one integrative Tai-Kadai-related genomic resource.

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.

Differentiated adaptative genetic architecture and language-related demographical history in South China inferred from 619 genomes from 56 populations.

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.

Differentiated genomic footprints suggest isolation and long-distance migration of Hmong-Mien populations.

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.

A comparative assessment of time-consuming and laborious diatom analysis：Brief experimentation with suggestion of automatic identification.

Diatom testing is considered a useful method for providing supportive evidence for the diagnosis of drowning in forensic pathology. However, various factors remain controversial for recognizing diatoms, such as being time-consuming and laborious and influencing the consistency of the results. Given the absence of precise and well-defined studies on this subject, this study aimed to determine the relationship between the ability to identify diatoms and researchers with different technical backgrounds. A total of 55 samples from 18 cases, including water, lungs, liver, and kidneys, were treated using the microwave digestion-vacuum filtration-automated scanning electron microscopy (MD-VF-Auto SEM), which was used to compare diatom analyses among three groups of well-trained forensic pathologists (FPs), trained junior employees (JEs), and new trainees (TEs). In addition to achieving similar accuracy of positive findings from drowning cases, counting efficiency was evaluated based on taxonomy records and counting time after viewing more than 5500 diatom images. In contrast to the higher counting efficiency of the JE group than that of the TE group, we observed a statistically significant difference (p < 0.05) in the diatom classification between these two groups. Based on our experiments, an efficient analysis for automatically identifying and classifying diatoms is urgently required.

First report on female monozygotic twins discordant for congenital nephrogenic diabetes insipidus.

Ninety percent of congenital nephrogenic diabetes insipidus (NDI) are X-linked inherited and are caused by mutations in the vasopressin type 2 receptor gene (AVPR2). Most affected individuals are males. Only sporadic female cases have been reported. Here, we first reported a female monozygotic twin with discordant phenotypes for NDI carrying a missense variant c.845T>C (p.Leu282Pro) in exon 4 of AVPR2. Intracellular cAMP concentrations in COS7 cells transfected with AVPR2-L282P were significantly decreased by about 60% compared with those in wild-type AVPR2 plasmid transfected cells, suggesting this variation was pathogenic. The X-inactivation pattern was investigated in peripheral leukocytes and urine sediments in both the unaffected and affected pair. Results showed that the affected pair had a skewed X chromosome inactivation (XCI) pattern in urine sediments and a random XCI pattern in leukocytes, while the unaffected pair showed a random XCI pattern both in leukocytes and urine sediments. This was the first report of monozygotic twins who developed different phenotypes of NDI. Our study suggested that the development of NDI symptoms is more closely associated with the XCI pattern in urine sediments compared with the XCI pattern in peripheral leukocytes. Analysis of XCI in peripheral leukocytes may not be enough to explore possible mechanisms.

Distinguished biological adaptation architecture aggravated population differentiation of Tibeto-Burman-speaking people.

Tibeto-Burman (TB) people have endeavored to adapt to the hypoxic, cold, and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period. However, the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people, as well as their interaction mechanism, remain unknown. Here, we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity, admixture history, and differentiated adaptative features of geographically different TB-speaking people. We identify genetic differentiation related to geography and language among TB-speaking people, consistent with their differentiated admixture process with incoming or indigenous ancestral source populations. A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin hypothesis. We finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish speakers. Adaptative signatures associated with the physical pigmentation (EDAR and SLC24A5) and metabolism (ALDH9A1) are identified in Loloish people, which differed from the high-altitude adaptative genetic architecture in Tibetan. TB-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.

Diagnostic value of cardiac miR-126-5p, miR-134-5p, and miR-499a-5p in coronary artery disease-induced sudden cardiac death.

Background: The identification of coronary artery disease-induced sudden cardiac death (CAD-SCD) has always been a medical challenge. MicroRNAs (miRNAs) played vital roles in pathogenesis processes and served as potential biomarkers for cardiovascular and many other diseases. The aim of this study was to investigate the diagnostic value of the specific miRNAs for CAD-SCD. Methods: A total of 30 autopsy-verified CAD-SCD victims were selected, including 18 individuals who experienced more than once asymptomatic myocardial ischemia (CAD-activated SCD) and 12 victims without prominent pathological features of insufficient blood supply (CAD-silent SCD). Meanwhile, 30 traumatic victims were enrolled as controls. Systematic postmortem examinations were performed in all study population. The expressions of cardiac miR-126-5p, miR-134-5p, and miR-499a-5p were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Results: RT-qPCR showed significant downregulations of miR-126-5p and miR-499a-5p in CAD-SCD victims, with no obvious difference in miR-134-5p. Receiver-operating characteristic analysis revealed the diagnostic performance of miR-126-5p (areas under the curve [AUC] = 0.76) and validated miR-499a-5p (AUC = 0.82) as a sensitive marker. Additionally, the decreased expression of the two specific cardio-miRNAs was detected for discriminating CAD-silent SCD and CAD-activated SCD. Compared with the limited diagnostic value of single miR-126-5p and miR-499a-5p, their combination could achieve better discriminative capacity (AUC = 0.82, sensitivity = 91.7%, specificity = 77.8%). Conclusion: Cardiac miR-126-5p and miR-499a-5p presented good diagnostic abilities for CAD-SCD, and their combination could help evaluate CAD condition. These targeted miRNAs as novel biomarkers are expected to be useful to discriminate the detailed causes in real SCD cases.

Research on the Identification Model of Medical Damage.

OBJECTIVES: To understand the perceptions of doctors, patients and forensic examiners on the current situation of medical disputes and medical damage identification in China, and to explore the medical damage identification model that is more conducive for the resolution of medical disputes. METHODS: A questionnaire was designed, and in-service clinicians, forensic examiners and inpatients in Sichuan Province and Chongqing City were randomly selected from April to November 2019. SPSS 22.0 software was used to analyze the data of various survey results. RESULTS: Compared with patients (24.92%), doctors (61.72%) believed that the current doctor-patient relationship was more tense than before; both doctors and patients were more inclined to choose voluntary consultation and people's mediation to resolve medical disputes; forensic examiners have the highest level of cognition of medical and health-related laws and regulations, followed by doctors and patients; 66.72% of doctors and 78.41% of patients believed that medical damage identification was necessary, and they were more inclined to entrust forensic identification institutions; different groups all believed that forensic examiners and doctors should participate in the identification together, 80.94% of doctors believed that the appraisal institutions should be responsible for the forensic opinion, not the appraiser. CONCLUSIONS: It is suggested that the Medical Association identification and forensic identification should learn from each other and formulate basic unified rules for the identification of medical damage. It is suggested to standardize the behavior of medical damage forensic identification institutions and appraisers, to improve their own appraisal level, actively invite clinical medical experts for consultation in identification, and promote the standardized, scientization of forensic identification.

Application of machine learning for ancestry inference using multi-InDel markers.

Ancestry inference through population stratification plays an important role in forensic applications. Specifically, ancestry information inferred from forensic DNA evidence can provide vital clues for criminal investigations. Current advances in ancestry inference mostly focus on ancestry informative markers. Hereinto, multi-InDel was proposed as one of the compound markers performing well in complex ancestral classification in the subpopulation of Asia. However, research on analytical methods necessary to make reliable predictions is lacking. The newly proposed compound markers could be assessed with alternative methods. In this study, promising discriminant methods were explored using multi-InDel markers for forensic ancestry inference. As a prerequisite, the adopted multi-InDel markers were assessed by classical methods for population genetics, such as FST analysis, MDS and STRUCTURE. In addition, dimensionality reduction methods and serial reduction strategies were applied for data visualization. Subsequently, machine learning methods, including logistic regression (LR), support vector machine (SVM), k-nearest neighbors (KNN) and extreme gradient boosting (XGBoost), were evaluated by diverse approaches. As the result of multifarious analyses through comparisons and estimations, XGBoost with one-hot encoding was shown to be more effective in population stratification and ancestry inference for challenging cases with admixed populations.

Awareness on tetrodotoxin of illegal activity: forensic issue from a rare homicide case report and literature review.

The authors describe an extremely rare case of homicide by injecting tetrodotoxin (TTX) as lethal neurotoxin found in puffer fish. After a thorough investigation, the male victim was found to have a broken stalk from syringe needle in the subcutaneous tissue of left buttock and severe asphyxia confirmed by the main pathological findings at autopsy. During tortuous toxicological analysis，TTX was revealed by ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) as well as acute intoxication confirmed from forensic examination. The literature of qualitative and quantitative determination of TTX from human fluids was also reviewed to expect widely acceptable detection strategies. This case highlighted the importance of TTX toxicant with chemical formula name purchased through e-commerce，so as to improve particular emphasis and supervision on harmful substances possibly using hidden information or illegal means. Histopathological and toxicological results demonstrated here provided a reference and other useful information to the challenges of forensic casework. In general, the case report illustrates medico-legal issues of more attention to the possibility of TTX poisoning in rapid death and the need of routine postmortem tox screening in future practice.

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Routine pathological examination of unexplained sudden cardiac death (USCD) lacks significant morphological characteristics. In the field of forensic medicine, molecular biology methods have been used to find the cause of death by detecting genes and research related to the mechanism of sudden cardiac death has been carried out. From the molecular pathology point of view, the application of multiple levels of biomarkers to resolve the causes of USCD has already shown potential and provides an important path for forensic identification of USCD. This article reviews the latest research progress on USCD-related genes, RNA, proteins and USCD, and summarizes forensic application.

Quantitative acetylome analysis reveals involvement of glucosyltransferase acetylation in Streptococcus mutans biofilm formation.

Streptococcus mutans (S. mutans) effectively utilizes dietary sucrose for the exopolysaccharide productions, which are mostly synthesized by the effects of glucosyltransferases (Gtfs). In the present study, the acetylome of S. mutans was identified and quantitative acetylome analysis of the bacterial biofilm growth (SMB) was compared with that of planktonic growth (SMP). The dynamic changes of protein acetylation were quantified using the integrated approach involving TMT labeling and Kac affinity enrichment followed by high-resolution mass spectrometry-based quantitative proteomics. In total, 973 acetylation sites in 445 proteins were identified, among which 617 acetylation sites in 302 proteins were quantitated. The overall analysis indicated that 22.7% of proteins were acetylated. Among the quantified proteins in SMB, the acetylation degree of lysine in 56 sites increased, while that of lysine decreased in 52 sites. In the acetylome of S. mutans, six significantly enriched motifs were identified and obtained including Kac****K, KacF, Kac****R, KacY, KacH, F*Kac. In addition, KEGG pathway-based enrichment analysis indicated significant enrichments in glycolysis/gluconeogenesis, and RNA degradation. Particularly, most downregulated acetylated lysine proteins were glucosyltransferase-SI, glucosyltransferase-I, and glucosyltransferase-S in S. mutans biofilm, which probably reveals a switch-off mechanism for the regulation of glucosyltransferases function during the biofilm development.

The distinctive geographic patterns of common pigmentation variants at the OCA2 gene.

Oculocutaneous Albinism type 2 (OCA2) is a gene of great interest because of genetic variation affecting normal pigmentation variation in humans. The diverse geographic patterns for variant frequencies at OCA2 have been evident but have not been systematically investigated, especially outside of Europe. Here we examine population genetic variation in and near the OCA2 gene from a worldwide perspective. The very different patterns of genetic variation found across world regions suggest strong selection effects may have been at work over time. For example, analyses involving the variants that affect pigmentation of the iris argue that the derived allele of the rs1800407 single nucleotide polymorphism, which produces a hypomorphic protein, may have contributed to the previously demonstrated positive selection in Europe for the enhancer variant responsible for light eye color. More study is needed on the relationships of the genetic variation at OCA2 to variation in pigmentation in areas beyond Europe.

Evaluation of 12 Multi-InDel markers for forensic ancestry prediction in Asian populations.

Various types of genetic markers have been applied to forensic ancestry inference. Biallelic markers, such as SNPs and InDels, have proven to be optimal choices except for the low information content provided by a single locus. Multi-InDel marker is defined as a specific DNA fragment with several InDel markers located tightly in the physical position. Previous research indicates that multi-InDel markers perform well in population analysis and ancestry inference because of higher degree of polymorphism and remarkable population differences. In this study, a panel consisting of 12 multi-InDel markers was employed to evaluate the general performance in forensic practice and the discrimination power for population analysis. Sample types encountered in routine forensic practice were genotyped to validate the feasibility of regular use. A population study was performed on a total of five Asian populations to verify the discrimination power. Moreover, a double-blind test for ancestry prediction was conducted to assess the predictive capability. In conclusion, these results revealed the significance of multi-InDel markers for population structure stratification. The present panel showed the potential as a valid complementary tool in forensic applications.

Revisiting the male genetic landscape of China: a multi-center study of almost 38,000 Y-STR haplotypes.

China has repeatedly been the subject of genetic studies to elucidate its prehistoric and historic demography. While some studies reported a genetic distinction between Northern and Southern Han Chinese, others showed a more clinal picture of small differences within China. Here, we investigated the distribution of Y chromosome variation along administrative as well as ethnic divisions in the mainland territory of the People's Republic of China, including 28 administrative regions and 19 recognized Chinese nationalities, to assess the impact of recent demographic processes. To this end, we analyzed 37,994 Y chromosomal 17-marker haplotype profiles from the YHRD database with respect to forensic diversity measures and genetic distance between groups defined by administrative boundaries and ethnic origin. We observed high diversity throughout all Chinese provinces and ethnicities. Some ethnicities, including most prominently Kazakhs and Tibetans, showed significant genetic differentiation from the Han and other groups. However, differences between provinces were, except for those located on the Tibetan plateau, less pronounced. This discrepancy is explicable by the sizeable presence of Han speakers, who showed high genetic homogeneity all across China, in nearly all studied provinces. Furthermore, we observed a continuous genetic North-South gradient in the Han, confirming previous reports of a clinal distribution of Y chromosome variation and being in notable concordance with the previously observed spatial distribution of autosomal variation. Our findings shed light on the demographic changes in China accrued by a fast-growing and increasingly mobile population.

Sudden Death From Ruptured Intracranial Vascular Malformations During Mechanical Asphyxia: A Domestic Violence Case Report.

Smothering and manual strangulation are not uncommon in domestic violence against women; however, no report on the combination of mechanical asphyxia and intracranial vascular malformations has been previously published. We report a middle-aged woman who was smothered and manually strangled by her husband and subsequently died from subarachnoid hemorrhage due to ruptured intracranial vascular malformations, rather than direct mechanical asphyxiation. Smothering and manual strangulation are considered provocative conditions for rupture and contributory causes of death. In this case study, we underline the importance of meticulous autopsy in cases of mechanical asphyxia and intracranial hemorrhage. Exclusion of underlying diseases that may have caused or contributed to death is also required, despite serious asphyxiation signs and neck injuries. Postmortem angiography is a valuable complement to autopsy to detect vascular pathology, with good prospects for further development in China.