Inhibition of DRP1-dependent mitochondrial fission by Mdivi-1 alleviates atherosclerosis through the modulation of M1 polarization.

BACKGROUND: Inflammation and immune dysfunction with classically activated macrophages(M1) infiltration are important mechanisms in the progression of atherosclerosis (AS). Dynamin-related protein 1 (DRP1)-dependent mitochondrial fission is a novel target for alleviating inflammatory diseases. This study aimed to investigate the effects of DRP1 inhibitor Mdivi-1 on AS. METHODS: ApoE-/- mice were fed with a high-fat diet supplemented with or without Mdivi-1. RAW264.7 cells were stimulated by ox-LDL, pretreated with or without MCC950, Mito-TEMPO, or Mdivi-1. The burden of plaques and foam cell formation were determined using ORO staining. The blood lipid profles and inflammatory cytokines in serum were detected by commercial kits and ELISA, respectively. The mRNA expression of macrophage polarization markers, activation of NLRP3 and the phosphorylation state of DRP1 were detected. Mitochondrial reactive oxygen species (mito-ROS), mitochondrial staining, ATP level and mitochondrial membrane potential were detected by mito-SOX, MitoTracker, ATP determination kit and JC-1 staining, respectively. RESULTS: In vivo, Mdivi-1 reduced the plaque areas, M1 polarization, NLRP3 activation and DRP1 phosphorylation at Ser616. In vitro, oxidized low-density lipoprotein (ox-LDL) triggered M1 polarization, NLRP3 activation and abnormal accumulation of mito-ROS. MCC950 and Mito-TEMPO suppressed M1 polarization mediated foam cell formation. Mito-TEMPO significantly inhibited NLRP3 activation. In addition, Mdivi-1 reduced foam cells by inhibiting M1 polarization. The possible mechanisms responsible for the anti-atherosclerotic effects of Mdivi-1 on reducing M1 polarization were associated with suppressing mito-ROS/NLRP3 pathway by inhibiting DRP1 mediated mitochondrial fission. In vitro, similar results were observed by DRP1 knockdown. CONCLUSION: Inhibition of DRP1-dependent mitochondrial fission by Mdivi-1 alleviated atherogenesis via suppressing mito-ROS/NLRP3-mediated M1 polarization, indicating DRP1-dependent mitochondrial fission as a potential therapeutic target for AS.

Long noncoding RNA XIST regulates the EGF receptor to promote TGF-ß1-induced epithelial-mesenchymal transition in pancreatic cancer.

BACKGROUND: This study focuses on the lncRNA XIST (X inactive-specific transcript), an lncRNA involved in multiple human cancers, and investigates the functional significance of XIST and the molecular mechanisms underlying the epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC). METHODS: Clinical specimens from 25 patients as well as 5 human PC cell lines were analyzed for XIST, YAP, and microRNA(miR)-34a by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. To investigate how XIST influences cell proliferation, invasiveness, and apoptosis in PC, we performed the CCK-8 assays, Transwell assays, and flow cytometry. Luciferase reporter assays, qRT-PCR, and Western blot were applied to prove that miR-34a directly binds to XIST. RESULTS: Up-regulation of XIST and Yes associated protein (YAP) and down-regulation of miR-34a were consistently observed in the clinical specimens and PC cell lines. Silencing XIST reduced the expression of YAP and suppressed transforming growth factor (TGF)-ß1-induced EMT, while over-expression of XIST increased the expression of YAP and promoted EMT. In addition, inhibition of epidermal growth factor receptor (EGFR) hampered the XIST-promoted EMT. The results from the luciferase reporter assays confirmed that miR-34a directly targets XIST and suggested that XIST regulates cell proliferation, invasiveness, and apoptosis in PC by sponging miR-34a. CONCLUSIONS: XIST promotes TGF-ß1-induced EMT by regulating the miR-34a-YAP-EGFR axis in PC.

Surgical management of recurrent aneurysms after coiling treatment.

OBJECTIVE: Aneurysms that recur after coiling treatment are difficult to manage. The microsurgical technique in these cases differs significantly from that in regular aneurysm clipping. We present our experience in surgical management of aneurysms that recurred more than 1 month after coiling in a series of 19 patients. MATERIALS AND METHODS: Between January 2004 and December 2014, 1437 patients were treated surgically for intracranial aneurysms in our institution. We performed a retrospective review of the clinical records, operation videos, and cerebral angiograms. We focused on patients in whom the initial aneurysm was treated by coiling, but the results were incomplete or the aneurysm recurred. RESULTS: Nineteen patients underwent surgical clipping for recurrent aneurysm more than 1 month after initial coiling treatment. The sex ratio (male:female) was 0.9, and the average age was 51.3 years (range 35-72 years). One aneurysm was classified as giant (≥ 25 mm), two as large (10-25 mm), and 18 as small (≤ 10 mm). A good outcome (Glasgow Outcome Scale 4 or 5) was observed in 16 of 19 patients (84.2%). CONCLUSION: Microsurgical clipping can be safe and effective in the management of previously coiled residual and recurrent aneurysms.

Transformation of dissolved organic matter in concentrated leachate from nanofiltration during ozone-based oxidation processes (O3, O3/H2O2 and O3/UV).

In this study, the transformation of dissolved organic matter (DOM) in nanofiltration concentrated leachate during three ozone-based oxidation processes (i.e., O3, O3/H2O2 and O3/UV) was investigated. The transformation characteristics of DOM were evaluated by gel filtration chromatography (GFC), XAD-8 resin fractionation, excitation-emission matrix fluorescence spectroscopy (EEM) and Fourier transform infrared spectroscopy (FTIR). Compared with O3-alone process, the removal efficiencies of COD, TOC, and color were improved in O3-combined processes (i.e., O3/H2O2 and O3/UV) approximately by 10-15%, 7-15%, and 15-20%, respectively. Humic acid (HA) was completely degraded and preferentially reacted with the oxidants during ozonation processes. HA was first converted into fulvic acid (FA), and then the majority of these intermediates were further converted to hydrophilic fraction (HyI). The GFC results indicated that the broader molecular weight distribution of DOM was observed, and high molecular weight DOM (i.e., 0.45 µm-100 kDa) was successfully converted to low molecular weight organics in the range of 1-10 kDa after ozonation reactions. The EEM spectra also showed that HA and FA were effectively converted into HyI after ozonation for 90 min. It is suggested that ozone-based oxidation processes could effectively change the DOM distribution and fluorescence features of concentrated leachate.

[Quantitative evaluation of white matter development in fetus with growth restriction by diffusion tensor imaging].

OBJECTIVE: To investigate whether fetal growth restriction (FGR) has an adverse effect on white matter development. METHODS: A total of 28 full-term small for gestational age (SGA) infants were enrolled as study subjects and 15 full-term appropriate for gestational age infants were enrolled as control group. Conventional head magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were performed for all infants. The white matter was divided into 122 regions. The two groups were compared in terms of fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of different brain regions. RESULTS: Compared with the control group, the SGA group had a significantly lower fractional anisotropy in 16 brain regions (P<0.01), a significantly higher mean diffusivity in 7 brain regions (P<0.05), a significantly higher axial diffusivity in 8 brain regions (P<0.05), and a significantly higher radial diffusivity in 16 brain regions (P<0.05). CONCLUSIONS: FGR may cause abnormalities in the maturity and integrity of white matter fiber tracts.

West Eurasian mtDNA lineages in India: an insight into the spread of the Dravidian language and the origins of the caste system.

There is no indication from the previous mtDNA studies that west Eurasian-specific subclades have evolved within India and played a role in the spread of languages and the origins of the caste system. To address these issues, we have screened 14,198 individuals (4208 from this study) and analyzed 112 mitogenomes (41 new sequences) to trace west Eurasian maternal ancestry. This has led to the identification of two autochthonous subhaplogroups--HV14a1 and U1a1a4, which are likely to have originated in the Dravidian-speaking populations approximately 10.5-17.9 thousand years ago (kya). The carriers of these maternal lineages might have settled in South India during the time of the spread of the Dravidian language. In addition to this, we have identified several subsets of autochthonous U7 lineages, including U7a1, U7a2b, U7a3, U7a6, U7a7, and U7c, which seem to have originated particularly in the higher-ranked caste populations in relatively recent times (2.6-8.0 kya with an average of 5.7 kya). These lineages have provided crucial clues to the differentiation of the caste system that has occurred during the recent past and possibly, this might have been influenced by the Indo-Aryan migration. The remaining west Eurasian lineages observed in the higher-ranked caste groups, like the Brahmins, were found to cluster with populations who possibly arrived from west Asia during more recent times.

Antenatal taurine improves neuronal regeneration in fetal rats with intrauterine growth restriction by inhibiting the Rho-ROCK signal pathway.

The Rho-ROCK signal pathway is an important mediator of inhibitory signals that blocks central nervous cell regeneration. Here, we investigated whether antenatal taurine improved neuronal regeneration in fetal rats with intrauterine growth restriction (IUGR) by inhibiting this pathway. Thirty pregnant rats were randomly divided into three groups: control, IUGR, and IUGR + antenatal taurine supplementation (taurine group). The mRNA levels of Ras homolog gene A (Rho A), Rho-associated coiled-coil forming protein kinase 2 (ROCK2), and proliferating cell nuclear antigen (PCNA) were detected using real-time quantitative PCR. RhoA, ROCK2 and PCNA-positive cells were counted using immunohistochemistry. Antenatal taurine supplementation decreased RhoA and Rock2 mRNA expression, increased PCNA mRNA expression, and significantly decreased RhoA, ROCK2-positive and increased PCNA-positive cell counts in IUGR fetal rat brain tissues (p < 0.05). Thus, antenatal taurine supplementation inhibited the expression of key Rho-ROCK signal molecules and improved IUGR fetal brain development.

[Academic discussion of adverse reaction of clinical trials of new traditional Chinese medicines and relevant influencing factors].

Data of clinical trial projects involved by clinical trial institutions certified by the State Food and Drug Administration from 2002 to November 2012 were collected to summarize adverse reactions in project summary/statistical reports, analyze the rate of adverse reactions of clinical trials of new traditional Chinese medicines and relevant influencing factors, and increase the awareness of the safety of new traditional Chinese medicines. A total of 73 050 cases in 209 projects of 14 specialties were collected, including 49 689 cases in the new traditional Chinese medicine group and 271 adverse reaction cases, with an incidence rate of adverse reactions at 0.55%. The adverse reaction rate in 3 months < middle long course ≤ 6 months was the highest (1.04%), whereas that in short course ≤ half a month was the lowest (0.48%). The adverse reaction was closely related with the route of administration, 1.28% for topical > 0.63% for injection > 0.50% for oral. In the administration of only the test drug, the adverse reaction rate of patches was the highest (2.68%), whereas that of aerosols and suppositories was lowest (0). In the combined administration of the test drug and the simulation agent, the adverse reaction rate of external test patch + capsule was the highest (3.38%), whereas that of capsule + oral liquid, pills + granules, tablets + oral liquid, tablets + pills, tablet + capsule was the lowest (0). In the administration of only the test drug, the adverse reaction rate was 0.47%; In the combined administration with simulation agent (drug volume increase), the adverse reaction rate was 0.74%. Different doses caused adverse reaction different rates; The adverse reaction rate of drugs with whole-course dose between 1 100-1 200 g was the highest (3.36%), that for whole-course doses of 500-600, 900-1 000, 1 400-1 500, 1 600-1 700, 1 800-1 900 g was the lowest (0). In conclusion, the adverse reaction rate of new traditional Chinese medicines was still up to 0.55%, with the adverse reaction rate between 0.47% and 0.72% over the 11 years, without significant difference in each year. The adverse reaction rate was closely related to course of treatment, approach of administration, dosage form and medication dosage, with no significant correlation with medication dosage during the course of treatment. The adverse reaction rate increased with the rise in trial duration and drug volume. In the administration of only the test drug, the adverse reaction rates of external formulations and injections were higher than that of oral dosage forms. It is suggested to give more attention to the adverse reactions of drugs with long course of treatment and large volumes, injections and external patches in clinical trials of new traditional Chinese medicines.

Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P < 0.01), respectively, and (2) that taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) µg/g (F = 24.828, P < 0.01), respectively. Overall, our results indicated that taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR.

The regulation of intestinal flora on host's genes may play an essential role in the development of endometrial hyperplastic processes in yang deficiency individuals.

Yang-deficiency constitution (YADC) is linked to a higher vulnerability to various diseases, such as cold coagulation and blood stasis (CCBS) syndrome and infertility. Endometrial hyperplastic processes (EHPs) are a leading cause of infertility in women and are characterized by CCBS. However, it remains unclear whether YADC is related to the development of EHPs. METHODS: We recruited 202 EHPs patients including 147 with YADC (YEH group) and 55 with non-YADC (NYEH group). Fecal samples were collected from 8 YEH patients and 3 NYEH patients and analyzed using 16S rRNA V3-V4 sequencing for gut microbiota analysis. We obtained constitution survey data and a differential gut microbiota dataset from the literature for further analysis. Bioinformatics analysis was conducted using gut microbiota-related genes from public databases. RESULTS: YADC was significantly more prevalent in EHPs than non-YADC (P < 0.001), suggesting it as a potential risk factor for EHPs occurrence (ORpopulation survey = 13.471; ORhealthy women = 5.173). The YEH group had higher levels of inflammation, estrogen, and tamoxifen-related flora compared to NYEH and healthy YADC groups. There was an interaction between inflammation, estrogen, differential flora, and EHPs-related genes, particularly the TNF gene (related to inflammation) and the EGFR gene (related to estrogen), which may play a crucial role in EHPs development. CONCLUSION: YEH individuals exhibit significant changes in their gut microbiota compared to NYEH and healthy YADC. The interaction between specific microbiota and host genes is believed to play a critical role in the progression of EHPs.

The surgical strategy and technical nuances of in situ side-to-side bypass for the management of complex intracranial aneurysms.

Background: Despite continuous advances in microsurgical and endovascular techniques, the treatment of complex aneurysms remains challenging. Aneurysms that are dilemmatic for conventional clipping or endovascular coiling often require bypass as part of a strategy to reduce the risk of ischemic complications. In anatomically favorable sites, the intracranial-intracranial in situ bypass may be an appealing choice. This article details the surgical strategies, operative nuances, and clinical outcomes of this technique with a consecutive series in our department. Methods: A retrospective review of a prospectively maintained neurosurgical patient database was performed to identify all patients treated with side-to-side in situ bypass from January 2016 to June 2022. In total, 12 consecutive patients, including 12 aneurysms, were identified and included in the series. The medical records, surgical videos, neuroimaging studies, and follow-up clinic notes were reviewed for every patient. Results: Of the 12 aneurysms, there were 5 middle cerebral artery aneurysms, 4 anterior cerebral artery aneurysms, and 3 posterior inferior cerebellar artery aneurysms. The morphology of the aneurysms was fusiform in 8 patients and saccular in the remaining 4 patients. There were 3 patients presented with subarachnoid hemorrhage. The treatment modality was simple in situ bypass in 8 cases and in situ bypass combined with other modalities in 4 cases. Bypass patency was confirmed in all cases by intraoperative micro-doppler probe and (or) infrared indocyanine green (ICG) video angiography intraoperatively and with digital subtraction angiography (DSA) or computed tomography angiography (CTA) postoperatively. None of the patients developed a clinically manifested stroke due to the procedure though a callosomarginal artery was intentionally removed in one patient. The median follow-up period was 16.2 months (6-36). All patients had achieved improved or unchanged modified Rankin scale scores at the final follow-ups. Conclusion: Cerebral revascularization technique remains an essential skill for the treatment of complex aneurysms. The in situ bypass is one of the most effective techniques to revascularize efferent territory when vital artery sacrifice or occlusion is unavoidable. The configuration of in situ bypass should be carefully tailored to each case, with consideration of variations in anatomy and pathology of the complex aneurysms.

Mechanism of immune attack in the progression of obesity-related type 2 diabetes.

Obesity and overweight are widespread issues in adults, children, and adolescents globally, and have caused a noticeable rise in obesity-related complications such as type 2 diabetes mellitus (T2DM). Chronic low-grade inflammation is an important promotor of the pathogenesis of obesity-related T2DM. This proinflammatory activation occurs in multiple organs and tissues. Immune cell-mediated systemic attack is considered to contribute strongly to impaired insulin secretion, insulin resistance, and other metabolic disorders. This review focused on highlighting recent advances and underlying mechanisms of immune cell infiltration and inflammatory responses in the gut, islet, and insulin-targeting organs (adipose tissue, liver, skeletal muscle) in obesity-related T2DM. There is current evidence that both the innate and adaptive immune systems contribute to the development of obesity and T2DM.

[Spatio-temporal Change in City-level Greenhouse Gas Emissions from Municipal Solid Waste Sector in China During the Last Decade and Its Potential Mitigation].

The waste sector is a significant source of greenhouse gas(GHG) emissions and clarifying its emission trends and characteristics is the premise for formulating GHG emission reduction strategies. Using the IPCC inventory model, the GHG emissions from the municipal solid waste(MSW) sector in China during 2010 to 2020 were estimated. The results showed that GHG emissions increased from 42.5 Mt in 2010 to 75.3 Mt in 2019, then decreased to 72.1 Mt in 2020. MSW landfills were the main source of GHG emissions. Further, with the increase in the proportion of waste incineration, the proportion of GHG incineration increased rapidly from 16.5% in 2010 to 60.1% in 2020. In terms of regional distribution, East and South China were the regions with the highest emissions, and Guangdong, Shandong, Jiangsu, and Zhejiang were the provinces with the largest GHG emissions. Implementing MSW classification, changing the MSW disposal modes from landfilling to incineration, improving the LFG collection efficiency of landfills, and using biological functional materials as the cover soil to strengthen the methane oxidation efficiency are the main measures to achieve GHG emission reduction in waste sectors.

[Remediation of Three Oxidants on Polycyclic Aromatic Hydrocarbons in Coking Contaminated Soil and Its Response to Indigenous Microorganisms].

To explore the influences of chemical oxidation on the physiological and ecological functions of indigenous microorganisms during contaminated soil remediation, three oxidants, including KMnO4, Na2S2O8, and O3, were selected to investigate their remediation effects on PAHs and the responses to indigenous microorganisms under different liquid-solid ratios, in this study. The results showed that:when the ΣPAHs concentration was 679.1 mg·kg-1 and the dosage of KMnO4 and Na2S2O8 was 1%, the removal efficiency of ΣPAHs reached up to 96.9% and 95.7% under the liquid-solid ratio of 6:1; for the O3 treatment, the removal efficiency of ΣPAHs was the highest(82.3%) at the O3 dosage and the liquid-solid ratio of 72 mg·min-1 and 8:1, respectively. The removal efficiency of low ring(3-4 rings) PAHs was higher than that of high ring(5-6 rings) PAHs under different liquid-solid ratios. The highest removal efficiencies were observed for phenanthrene and acenaphthene, whereas for benzo[a]pyrene, only the KMnO4treatment provided an effective performance, showing the highest removal efficiency of 97.4%. The microbial quantity analysis indicated that the quantity of soil microorganisms in the soil dropped sharply after being treated with KMnO4, decreasing from 108 copies·g-1 to 105 copies·g-1, whereas it changed only slightly after being treated with Na2S2O8 and O3. The community structure analysis showed that Proteobacteria were predominant in the contaminated soil, with the relative abundance of 99.5%. The addition of KMnO4 and Na2S2O8 significantly increased the microbial diversity; in particular, the relative abundance of a variety of microorganisms(such as Ralstonia and Acinetobacter) that can degrade PAHs was remarkably increased. The analysis of microbial metabolic function pathways revealed that chemical oxidation could simultaneously increase the relative abundance of PAHs-degrading bacteria and improve the ability of organic metabolism. Overall, the KMnO4 treatment greatly altered the quantity of microorganisms and the structure of the microbial community and the relative abundance of PAHs-degrading microorganisms at the liquid-solid ratio of 6:1.

Large-scale mtDNA screening reveals a surprising matrilineal complexity in east Asia and its implications to the peopling of the region.

In order to achieve a thorough coverage of the basal lineages in the Chinese matrilineal pool, we have sequenced the mitochondrial DNA (mtDNA) control region and partial coding region segments of 6,093 mtDNAs sampled from 84 populations across China. By comparing with the available complete mtDNA sequences, 194 of those mtDNAs could not be firmly assigned into the available haplogroups. Completely sequencing 51 representatives selected from these unclassified mtDNAs identified a number of novel lineages, including five novel basal haplogroups that directly emanate from the Eurasian founder nodes (M and N). No matrilineal contribution from the archaic hominid was observed. Subsequent analyses suggested that these newly identified basal lineages likely represent the genetic relics of modern humans initially peopling East Asia instead of being the results of gene flow from the neighboring regions. The observation that most of the newly recognized mtDNA lineages have already differentiated and show the highest genetic diversity in southern China provided additional evidence in support of the Southern Route peopling hypothesis of East Asians. Specifically, the enrichment of most of the basal lineages in southern China and their rather ancient ages in Late Pleistocene further suggested that this region was likely the genetic reservoir of modern humans after they entered East Asia.

Activity of long-chain acyl-CoA synthetase is required for maintaining meiotic arrest in Xenopus laevis.

In most vertebrates, fully grown oocytes are arrested in meiotic prophase I and only resume the cell cycle upon external stimuli, such as hormones. The proper arrest and resumption of the meiotic cycle is critical for reproduction. A Galpha(S) signaling pathway essential for the arrest is conserved in organisms from Xenopus to mouse and human. A previous gene association study implicated that mutations of human ACSL6 may be related to premature ovarian failure. However, functional roles of ACSL6 in human infertility have yet to be reported. In the present study, we found that triacsin C, a potent and specific inhibitor for ACSL, triggers maturation in Xenopus and mouse oocytes in the absence of hormone, suggesting ACSL activity is required for the oocyte arrest. In Xenopus, acsl1b may fulfill a major role in the process, because inhibition of acsl1b by knocking down its RNA results in abnormal acceleration of oocyte maturation. Such abnormally matured eggs cannot support early embryonic development. Moreover, direct inhibition of protein palmitoylation, which lies downstream of ACSLs, also causes oocyte maturation. Furthermore, palmitoylation of Galpha(s), which is essential for its function, is inhibited when the ACSL activity is blocked by triacsin C in Xenopus. Thus, disruption of ACSL activity causes inhibition of the Galpha(s) signaling pathway in the oocytes, which may result in premature ovarian failure in human.

Revisiting the role of the Himalayas in peopling Nepal: insights from mitochondrial genomes.

Himalayas was believed to be a formidably geographical barrier between South and East Asia. The observed high frequency of the East Eurasian paternal lineages in Nepal led some researchers to suggest that these lineages were introduced into Nepal from Tibet directly; however, it is also possible that the East Eurasian genetic components might trace their origins to northeast India where abundant East Eurasian maternal lineages have been detected. To trace the origin of the Nepalese maternal genetic components, especially those of East Eurasian ancestry, and then to better understand the role of the Himalayas in peopling Nepal, we have studied the matenal genetic composition extensively, especially the East Eurasian lineages, in Nepalese and its surrounding populations. Our results revealed the closer affinity between the Nepalese and the Tibetans, specifically, the Nepalese lineages of the East Eurasian ancestry generally are phylogenetically closer with the ones from Tibet, albeit a few mitochondrial DNA haplotypes, likely resulted from recent gene flow, were shared between the Nepalese and northeast Indians. It seems that Tibet was most likely to be the homeland for most of the East Eurasian in the Nepalese. Taking into account the previous observation on Y chromosome, now it is convincing that bearer of the East Eurasian genetic components had entered Nepal across the Himalayas around 6 kilo years ago (kya), a scenario in good agreement with the previous results from linguistics and archeology.

Mitochondrial genome evidence reveals successful Late Paleolithic settlement on the Tibetan Plateau.

Due to its numerous environmental extremes, the Tibetan Plateau--the world's highest plateau--is one of the most challenging areas of modern human settlement. Archaeological evidence dates the earliest settlement on the plateau to the Late Paleolithic, while previous genetic studies have traced the colonization event(s) to no earlier than the Neolithic. To explore whether the genetic continuity on the plateau has an exclusively Neolithic time depth, we studied mitochondrial DNA (mtDNA) genome variation within 6 regional Tibetan populations sampled from Tibet and neighboring areas. Our results confirm that the vast majority of Tibetan matrilineal components can trace their ancestry to Epipaleolithic and Neolithic immigrants from northern China during the mid-Holocene. Significantly, we also identified an infrequent novel haplogroup, M16, that branched off directly from the Eurasian M founder type. Its nearly exclusive distribution in Tibetan populations and ancient age (>21 kya) suggest that M16 may represent the genetic relics of the Late Paleolithic inhabitants on the plateau. This partial genetic continuity between the Paleolithic inhabitants and the contemporary Tibetan populations bridges the results and inferences from archaeology, history, and genetics.

Inland post-glacial dispersal in East Asia revealed by mitochondrial haplogroup M9a'b.

BACKGROUND: Archaeological studies have revealed a series of cultural changes around the Last Glacial Maximum in East Asia; whether these changes left any signatures in the gene pool of East Asians remains poorly indicated. To achieve deeper insights into the demographic history of modern humans in East Asia around the Last Glacial Maximum, we extensively analyzed mitochondrial DNA haplogroup M9a'b, a specific haplogroup that was suggested to have some potential for tracing the migration around the Last Glacial Maximum in East Eurasia. RESULTS: A total of 837 M9a'b mitochondrial DNAs (583 from the literature, while the remaining 254 were newly collected in this study) pinpointed from over 28,000 subjects residing across East Eurasia were studied here. Fifty-nine representative samples were further selected for total mitochondrial DNA sequencing so we could better understand the phylogeny within M9a'b. Based on the updated phylogeny, an extensive phylogeographic analysis was carried out to reveal the differentiation of haplogroup M9a'b and to reconstruct the dispersal histories. CONCLUSIONS: Our results indicated that southern China and/or Southeast Asia likely served as the source of some post-Last Glacial Maximum dispersal(s). The detailed dissection of haplogroup M9a'b revealed the existence of an inland dispersal in mainland East Asia during the post-glacial period. It was this dispersal that expanded not only to western China but also to northeast India and the south Himalaya region. A similar phylogeographic distribution pattern was also observed for haplogroup F1c, thus substantiating our proposition. This inland post-glacial dispersal was in agreement with the spread of the Mesolithic culture originating in South China and northern Vietnam.

Indirect Ventral Brainstem Decompression by Posterior C1-C2 Distraction and Fixation for Basilar Invagination.

OBJECTIVE: Basilar invagination usually shows a decrease of clivus axis angle (CAA), which could give rise to progressive neural compression. Exploring a safe and effective fixation technique to achieve atlantoaxial stability and neural decompression remains necessary. In this study, we introduce a modified posterior C1-C2 distraction and fixation technique by which we obtained indirect ventral neural decompression and atlantoaxial stability in a series of patients with decreased CAA. METHODS: Thirty patients of basilar invagination were enrolled in our series. All patients underwent thin-slice computed tomography (CT) scan, magnetic resonance imaging, and dynamic plain radiography examinations before surgery, at discharge and during the follow-ups. Posterior C1-C2 facet joint release and intraoperative reduction by fastening rods were performed in all patients. The CAA was measured on midsagittal CT scans. Patients' neurologic status was evaluated by the Japanese Orthopaedic Association score. RESULTS: No neurovascular injury and serious postoperative complication occurred in all patients. Complete ventral brainstem decompression was achieved in 20 patients and partial in 10 patients. The mean postoperative CAA significantly improved to 132.6 degrees compared with the preoperative 123.6 degrees (P < 0.01). The bone fusion was confirmed in all patients on the basis of the last follow-up spine CT scans. CONCLUSIONS: Indirect ventral brainstem decompression by posterior C1-C2 distraction and fixation is a safe and effective technique for treatment of basilar invagination.