The reactivity of organic radicals in the performic, peracetic, perpropionic acids-based advanced oxidation process: A case study of sulfamethoxazole.

Advanced oxidation processes (AOPs) based on peracetic acid (PAA) displayed great potential in removing emerging contaminants by generating HO• and organic radicals. Performic and perpropionic acids (PFA and PPA) also act as disinfectants, but their application potential has not been investigated yet. Here, we investigated the degradation mechanism and kinetics of sulfamethoxazole (SMX) by HO•, RC(O)O• species (including HC(O)O•, CH3C(O)O• and CH3CH2C(O)O•) and RC(O)OO• species (including HC(O)OO•, CH3C(O)OO• and CH3CH2C(O)OO•). The results show that the calculated reaction rate constants of SMX follow the order of HC(O)O• > CH3C(O)O• > CH3CH2C(O)O• > HO• > HC(O)OO• > CH3C(O)OO• > CH3CH2C(O)OO•. The reactivity towards SMX is strongly correlated with the redox potentials of reactive radicals. Hence, the RCOO• species play dominant roles in the purification of SMX in PFA/PAA/PPA-based AOPs. The degradation of SMX mainly proceeds via addition at the benzene ring, the hydrogen abstraction from the -NH2 group as well as the single electron transfer reaction. This study highlights the fundamental aspects of PFA, PAA, and PPA in the purification of sulfamethoxazole and enhances the role of organic radicals in the AOPs based on organic peracetic acids.

Cultural psychological factors in posttraumatic symptom development and expression: a study protocol.

Introduction: Cultural factors were shown to be particularly relevant for the development and expression of posttraumatic stress. Recently, the concept of cultural scripts of trauma has been introduced, which proposes that trauma sequelae elements may be sequentially linked and specifically associated with cultural factors. Furthermore, a cascade model is proposed, including trauma exposure, demographic characteristics, cultural affiliation, and trauma-related value orientations as influencing factors of posttraumatic development. The purpose of this Network Project is to investigate cultural psychological factors that contribute to the expression of posttraumatic stress.Methods: The present Network Project implements a mixed methods approach and will be conducted in 5 different study sites, including Switzerland, Israel, Georgia, China, and East Africa. In sub-study I, the cultural scripts of traumatic stress inventories (CSTIs) will be developed. These scales provide a pool of trauma sequelae elements for each cultural group. For this purpose, focus groups with trauma survivors and trauma experts will be conducted and analysed using qualitative research methods. Sub-study II implements a validation analysis of the CSTIs and the empirical investigation of a cultural cascade model. This quantitative approach will include a larger sample of individuals who experienced traumatic life events.Discussion: This contribution is timely and enriches the knowledge of trauma and culture. Future publications of this Network Project will address trauma sequelae from a cultural perspective and provide diagnostic and psychotherapeutic implications.

This paper presents a Network Project that investigates cultural factors in posttraumatic sequelae.The Network Project encompasses an innovative research design with both qualitative and quantitative methods.New developments in the field of cultural clinical psychology are introduced, including cultural scripts of trauma and a cascade model of cultural factors in posttraumatic symptom expression.

Combining metabolomics and transcriptomics to analyze key response metabolites and molecular mechanisms of Aspergillus fumigatus under cadmium stress.

The co-cultivation of fungi with microalgae facilitates microalgae harvesting and enhances heavy metal adsorption. However, the mechanisms of fungal tolerance to cadmium (Cd) have not yet been studied in detail. In this study, functional groups of fungi were analyzed under Cd stress using Fourier transform infrared spectrometer (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), and transmission electron microscope (TEM) to explore their morphology. Confocal laser scanning microscope (CLSM) was used to characterize the changes in the content of extracellular polysaccharides and proteins, and a decrease in the ratio of glutathione (GSH) to oxidized glutathione (GSSG) was monitored. The GSH and GSSG contents in mycelium were 7.4 and 7.9 times higher than that in the control, respectively. After 72 h of Cd treatment, the fungal extracellular polysaccharide and extracellular protein contents increased by 16 and 11.4 mg/g, respectively, compared to the control. This provided several functional groups for the complexation of Cd ions to enhance fungal Cd tolerance. The metabolomic and transcriptomic results revealed a total of 358 differential metabolites after 20, 48, and 72 h in the positive and negative ion modes, and the number of differential metabolites specific to each group was 104, 14, and 89, respectively. There were 927, 1167, and 1287 up-regulated genes, and 1301, 1480, and 1683 down-regulated genes at 20, 48, and 72 h, respectively. Energy metabolism, amino acid metabolism, and the ABC transport system are the key metabolic pathways for tolerance enhancement and heavy metal detoxification in fungi. The expression of S-cysteinosuccinic acid was significantly up-regulated after Cd stress and associated with enhanced fungal tolerance and resistance to Cd.

Sclerostin modulates mineralization degree and stiffness profile in the fibrocartilaginous enthesis for mechanical tissue integrity.

Fibrocartilaginous entheses consist of tendons, unmineralized and mineralized fibrocartilage, and subchondral bone, each exhibiting varying stiffness. Here we examined the functional role of sclerostin, expressed in mature mineralized fibrochondrocytes. Following rapid mineralization of unmineralized fibrocartilage and concurrent replacement of epiphyseal hyaline cartilage by bone, unmineralized fibrocartilage reexpanded after a decline in alkaline phosphatase activity at the mineralization front. Sclerostin was co-expressed with osteocalcin at the base of mineralized fibrocartilage adjacent to subchondral bone. In Scx-deficient mice with less mechanical loading due to defects of the Achilles tendon, sclerostin+ fibrochondrocyte count significantly decreased in the defective enthesis where chondrocyte maturation was markedly impaired in both fibrocartilage and hyaline cartilage. Loss of the Sost gene, encoding sclerostin, elevated mineral density in mineralized zones of fibrocartilaginous entheses. Atomic force microscopy analysis revealed increased fibrocartilage stiffness. These lines of evidence suggest that sclerostin in mature mineralized fibrochondrocytes acts as a modulator for mechanical tissue integrity of fibrocartilaginous entheses.

Mechanical force-activated CD109 on periodontal ligament stem cells governs osteogenesis and osteoclast to promote alveolar bone remodeling.

Mechanical force-mediated bone remodeling is crucial for various physiological and pathological processes involving multiple factors, including stem cells and the immune response. However, it remains unclear how stem cells respond to mechanical stimuli to modulate the immune microenvironment and subsequent bone remodeling. Here, we found that mechanical force induced increased expression of CD109 on periodontal ligament stem cells (PDLSCs) in vitro and in periodontal tissues from the force-induced tooth movement rat model in vivo, accompanied by activated alveolar bone remodeling. Under mechanical force stimulation, CD109 suppressed the osteogenesis capacity of PDLSCs through the JAK/STAT3 signaling pathway, whereas it promoted PDLSC-induced osteoclast formation and M1 macrophage polarization through paracrine. Moreover, inhibition of CD109 in vivo by lentivirus-shRNA injection increased the osteogenic activity and bone density in periodontal tissues. On the contrary, it led to decreased osteoclast numbers and pro-inflammatory factor secretion in periodontal tissues and reduced tooth movement. Mechanistically, mechanical force-enhanced CD109 expression via the repression of miR-340-5p. Our findings uncover a CD109-mediated mechanical force response machinery on PDLSCs, which contributes to regulating the immune microenvironment and alveolar bone remodeling during tooth movement.

Publication Trends and Research Hotspots of the Cardiorenal Syndrome: A Bibliometrics and Visual Analysis from 2003 to 2023.

INTRODUCTION: Cardiorenal syndrome encompasses a range of disorders involving both the heart and kidneys, wherein dysfunction in one organ may induce dysfunction in the other, either acutely or chronically. METHODS: This study conducted a literature search on cardiorenal syndrome from January 1, 2003, to September 8, 2023. Meanwhile, a quantitative analysis of the developmental trajectory, research hotspots and evolutionary trends in the field of cardiorenal syndrome through bibliometric analysis and knowledge mapping was carried out. RESULTS: The annual publication trend analysis revealed a consistent annual increase in cardiorenal syndrome literature over the last 20 years. The IL6, REN, and INS genes were identified as the current research hotspots. CONCLUSION: The field of cardiorenal syndrome exhibits promising potential to grow and is emerging as a prominent research area. Future endeavours should prioritise a comprehensive understanding of the field and foster multi-centre co-operation among different countries and regions.

Amelioration of gait and balance disorders by rosuvastatin is associated with changes in cerebrovascular reactivity in older patients with hypertensive treatment.

To investigate the effect of rosuvastatin on gait and balance disorder progression and elucidate the role of cerebrovascular reactivity (CVR) on this effect. From April 2008 to November 2010, 943 hypertensive patients aged ≥60 years were enrolled from the Shandong area of China. Patients were randomized into rosuvastatin and placebo groups. Gait, balance, CVR, fall and stroke were assessed. During an average 72 months of follow-up, the decreasing trends for step length, step speed, and Berg balance scale scores and the increasing trends for step width and chair rising test were slower in the rosuvastatin group when compared to the placebo group. The hazard ratio of incident balance impairment and falls was 0.542 [95% confidence interval (CI) 0.442-0.663] and 0.532 (95% CI 0.408-0.694), respectively, in the rosuvastatin group compared with placebo group. For CVR progression, the cerebrovascular reserve capacity and breath-holding index were increased and the pulsatility index decreased in the rosuvastatin group, while the cerebrovascular reserve capacity and breath-holding index were decreased, and pulsatility index increased in the placebo group. The changes in gait stability and balance function were independently associated with the changes in the CVR. The odds risks of balance impairment and falls were 2.178 (95% CI: 1.491-3.181) and 3.227 (95% CI: 1.634-6.373), respectively, in the patients with CVR impairment and patients without CVR impairment. Rosuvastatin ameliorated gait and balance disorder progression in older patients with hypertension. This effect might result from the improvement in the CVR. This double-blind clinical trial recruited 943 hypertensive patients aged ≥60 years who were randomly administered rosuvastatin and placebo interventions. The data indicates that rosuvastatin significantly ameliorated the progressions of gait and balance disorders in older hypertensive patients. The cerebrovascular reactivity might play an important mediating role in this amelioration.

Meroterpenoids from Marine Sponge Hyrtios sp. and Their Anticancer Activity against Human Colorectal Cancer Cells.

Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their structures were elucidated by NMR and MS data. Compounds 2-4 exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC50 values of 41.6, 45.0, and 37.3 µM, respectively. Furthermore, compounds 3 and 4 significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial-mesenchymal transition (EMT). Our findings suggest that compounds 3 and 4 may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT.

Clinical characterization of hemophagocytic lymphohistiocytosis caused by immune checkpoint inhibitors: a review of published cases.

OBJECTIVE: An association exists between immune checkpoint inhibitors and hemophagocytic lymphohistiocytosis (HLH). Therefore, the main objective of this study was to collect data on this rare but potentially life-threatening immune-related adverse reaction to identify the medications that cause it, the clinical characteristics, and effective treatments. METHODS: Literature in English and Chinese on immune checkpoint inhibitors causing HLH published from August 2014 to March 2024 was analyzed. Immune checkpoint inhibitors, immunotherapy, anti-PD-1, PD-L1 inhibitors, HLH, hemophagocytic lymphohistiocytosis, hemophagocytic syndrome keywords were used to find the literature on China Knowledge Network, Wanfang, PubMed and Emabase Databases. RESULTS AND DISCUSSION: Twenty-four studies were included, with a total of 27 patients (18 males and 9 females) with a mean age of 58 years (range 26-86). The mean time to the onset of symptoms was 10.3 weeks (7 days-14 months). The main clinical characteristics were fever, cytopenia, splenomegaly, methemoglobinemia, hypofibrinogenemia, and bone marrow biopsy showed phagocytosis. Twenty-two patients improved after the treatment with steroids, cytokine blocking therapy and symptomatic treatment, four patients died, and one patient was not described. CONCLUSION: HLH should be not underestimated as a potentially serious adverse effect of immune checkpoint inhibitors since appropriate treatments may save the life of patients.

A life cycle cost analysis of different shore power incentive policies on both shore and ship sides based on system dynamics and a Chinese port case.

Shore power (SP) is widely recognized as an efficient strategy for reducing air pollution in port areas. Unfortunately, the adoption of SP has been relatively low, resulting in limited emission reductions and financial losses. To address these challenges, this paper focuses on enhancing the utilization rate of SP, which is meaningful for emission control and environmental protection. This paper combines system dynamics with a study of the benefits of SP, which bridges the research gap to some extent. We propose a system dynamics model that assesses the impact of various incentive policies on the economic and environmental benefits of SP. The model considers the life cycle cost and comprises four subsystems. By conducting a case study on Nansha Port, we find that price subsidies are more effective than construction subsidies in overcoming economic barriers. Furthermore, we observe that the overall economic benefits only increase when the electricity price decreases. This is because lowering the electricity price enhances the profitability of ships without negatively affecting port revenue. Additionally, it is the proportion of the electricity price and service price that determines the overall economic benefits, rather than the SP price itself. Hence, it is recommended to provide preferential subsidies for the electricity price.

rs2736098, a synonymous polymorphism, is associated with carcinogenesis and cell count in multiple tissue types by regulating TERT expression.

rs2736098 is a synonymous polymorphism in TERT (telomerase reverse transcriptase), an enzyme involved in tumor onset of multiple tissues, and should play no roles in carcinogenesis. However, a search in cancer somatic mutation database indicated that the mutation frequency at rs2736098 is much higher than the average one for TERT. Moreover, there are significant H3K4me1 and H3K27Ac signals, two universal histone modifications for active enhancers, surrounding rs2736098. Therefore, we hypothesized that rs2736098 might be within an enhancer region, regulate TERT expression and influence cancer risk. Through luciferase assay, it was verified that the enhancer activity of rs2736098C allele is significantly higher than that of T in multiple tissues. Transfection of plasmids containing TERT coding region with two different alleles indicated that rs2736098C allele can induce a significantly higher TERT expression than T. By chromatin immunoprecipitation, it was observed that the fragment spanning rs2736098 can interact with USF1 (upstream transcription factor 1). The two alleles of rs2736098 present evidently different binding affinity with nuclear proteins. Database and literature search indicated that rs2736098 is significantly associated with carcinogenesis in multiple tissues and count of multiple cell types. All these facts indicated that rs2736098 is also an oncogenic polymorphism and plays important role in cell proliferation.

Host-induced gene silencing in wild apple germplasm Malus hupehensis confers resistance to the fungal pathogen Botryosphaeria dothidea.

Host-induced gene silencing (HIGS) is an inherent mechanism of plant resistance to fungal pathogens, resulting from cross-kingdom RNA interference (RNAi) mediated by small RNAs (sRNAs) delivered from plants into invading fungi. Introducing artificial sRNA precursors into crops can trigger HIGS of selected fungal genes, and thus has potential applications in agricultural disease control. To investigate the HIGS of apple (Malus sp.) during the interaction with Botryosphaeria dothidea, the pathogenic fungus causing apple ring rot disease, we evaluated whether apple miRNAs can be transported into and target genes in B. dothidea. Indeed, miR159a from Malus hupehensis, a wild apple germplasm with B. dothidea resistance, silenced the fungal sugar transporter gene BdSTP. The accumulation of miR159a in extracellular vesicles (EVs) of both infected M. hupehensis and invading B. dothidea suggests that this miRNA of the host is transported into the fungus via the EV pathway. Knockout of BdSTP caused defects in fungal growth and proliferation, whereas knockin of a miR159a-insensitive version of BdSTP resulted in increased pathogenicity. Inhibition of miR159a in M. hupehensis substantially enhanced plant sensitivity to B. dothidea, indicating miR159a-mediated HIGS against BdSTP being integral to apple immunity. Introducing artificial sRNA precursors targeting BdSTP and BdALS, an acetolactate synthase gene, into M. hupehensis revealed that double-stranded RNAs were more potent than engineered MIRNAs in triggering HIGS alternative to those natural of apple and inhibiting infection. These results provide preliminary evidence for cross-kingdom RNAi in the apple-B. dothidea interaction and establish HIGS as a potential disease control strategy in apple.

Bioinformatic Analysis of Codon Usage Bias of HSP20 Genes in Four Cruciferous Species.

Heat shock protein 20 (HSP20) serves as a chaperone and plays roles in numerous biological processes, but the codon usage bias (CUB) of its genes has remained unexplored. This study identified 140 HSP20 genes from four cruciferous species, Arabidopsis thaliana, Brassica napus, Brassica rapa, and Camelina sativa, that were identified from the Ensembl plants database, and we subsequently investigated their CUB. As a result, the base composition analysis revealed that the overall GC content of HSP20 genes was below 50%. The overall GC content significantly correlated with the constituents at three codon positions, implying that both mutation pressure and natural selection might contribute to the CUB. The relatively high ENc values suggested that the CUB of the HSP20 genes in four cruciferous species was relatively weak. Subsequently, ENc exhibited a negative correlation with gene expression levels. Analyses, including ENc-plot analysis, neutral analysis, and PR2 bias, revealed that natural selection mainly shaped the CUB patterns of HSP20 genes in these species. In addition, a total of 12 optimal codons (ΔRSCU > 0.08 and RSCU > 1) were identified across the four species. A neighbor-joining phylogenetic analysis based on coding sequences (CDS) showed that the 140 HSP20 genes were strictly and distinctly clustered into 12 subfamilies. Principal component analysis and cluster analysis based on relative synonymous codon usage (RSCU) values supported the fact that the CUB pattern was consistent with the genetic relationship at the gene level and (or) species levels. These results will not only enrich the HSP20 gene resource but also advance our understanding of the CUB of HSP20 genes, which may underlie the theoretical basis for exploration of their genetic and evolutionary pattern.

The characteristics and risk factors of fatal falls among adults aged 60 and above in Southwest China.

Falls constitute a leading cause of unintentional injury deaths among older adults. This study aimed to examine the comprehensive characteristics of fatal falls among older individuals in Yunnan Province, China, to highlight the challenges faced in elderly care. A total of 22,798 accidental fall-related deaths were extracted from China's National Disease Surveillance Points System aged 60 and above between 2015 and 2019. Quantitative and textual data were analyzed to assess the incidence rates of initiating factors, locations, symptoms, and overall survival (OS) outcomes after falling. Hypertension emerged as the most significant intrinsic factor, especially among individuals aged between 70 and 79, female older adults, and urban residents (P < 0.001). Home was identified as the most common location where fatal falls occurred (61.19%). The head was the most commonly injured body region (58.75%). The median of OS for all fatal falls was 2 days (0.13, 30), of which deaths occurred within 24 h [9287 (49.36%)]. There were instances where timely discovery after falling did not occur in 625 cases; their median of OS was significantly shorter compared to those discovered promptly after falling (P < 0.001). Targeted interventions focusing on fall prevention and post-fall care are equally crucial for the well-being of older adults.

The Mh-miR393a-TIR1 module regulates Alternaria alternata resistance of Malus hupehensis mainly by modulating the auxin signaling.

miRNAs govern gene expression and regulate plant defense. Alternaria alternata is a destructive fungal pathogen that damages apple. The wild apple germplasm Malus hupehensis is highly resistant to leaf spot disease caused by this fungus. Herein, we elucidated the regulatory and functional role of miR393a in apple resistance against A. alternata by targeting Transport Inhibitor Response 1. Mature miR393 accumulation in infected M. hupehensis increased owing to the transcriptional activation of MIR393a, determined to be a positive regulator of A. alternata resistance to either 'Orin' calli or 'Gala' leaves. 5' RLM-RACE and co-transformation assays showed that the target of miR393a was MhTIR1, a gene encoding a putative F-box auxin receptor that compromised apple immunity. RNA-seq analysis of transgenic calli revealed that MhTIR1 upregulated auxin signaling gene transcript levels and influenced phytohormone pathways and plant-pathogen interactions. miR393a compromised the sensitivity of several auxin-signaling genes to A. alternata infection, whereas MhTIR1 had the opposite effect. Using exogenous indole-3-acetic acid or the auxin synthesis inhibitor L-AOPP, we clarified that auxin enhances apple susceptibility to this pathogen. miR393a promotes SA biosynthesis and impedes pathogen-triggered ROS bursts by repressing TIR1-mediated auxin signaling. We uncovered the mechanism underlying the miR393a-TIR1 module, which interferes with apple defense against A. alternata by modulating the auxin signaling pathway.

Porous Collagen Sponge Loaded with Large Efficacy-Potentiated Exosome-Mimicking Nanovesicles for Diabetic Skin Wound Healing.

Diabetic skin wounds are difficult to heal quickly due to insufficient angiogenesis and prolonged inflammation, which is an urgent clinical problem. To address this clinical problem, it becomes imperative to develop a dressing that can promote revascularization and reduce inflammation during diabetic skin healing. Herein, a multifunctional collagen dressing (CTM) was constructed by loading large efficacy-potentiated exosome-mimicking nanovesicles (L-Meseomes) into a porous collagen sponge with transglutaminase (TGase). L-Meseomes were constructed in previous research with the function of promoting cell proliferation, migration, and angiogenesis and inhibiting inflammation. CTM has a three-dimensional porous network structure with good biocompatibility, swelling properties, and degradability and could release L-Meseome slowly. In vitro experiments showed that CTM could promote the proliferation of fibroblasts and the polarization of macrophages to the anti-inflammatory phenotype. For in vivo experiments, on the 21st day after surgery, the wound healing rates of the control and CTM were 83.026 ± 4.17% and 93.12 ± 2.16%, respectively; the epidermal maturation and dermal differentiation scores in CTM were approximately four times that of the control group, and the skin epidermal thickness of the CTM group was approximately 20 µm, which was closest to that of normal rats. CTM could significantly improve wound healing in diabetic rats by promoting anti-inflammation, angiogenesis, epidermal recovery, and dermal collagen deposition. In summary, the multifunctional collagen dressing CTM could significantly promote the healing of diabetic skin wounds, which provides a new strategy for diabetic wound healing in the clinic.

Physiological regulation of microalgae under cadmium stress and response mechanisms of time-series analysis using metabolomics.

The investigation of heavy metal wastewater treatment utilizing microalgae adsorption has been extensively demonstrated. However, the response mechanism based on metabolomics to analyze the time-series changes of microalgae under Cd stress has not been described in detail. In this study, SEM/TEM demonstrated that Cd accumulated on the cell surface of microalgae and was bioconcentrated in the cytoplasm, vesicles, and chloroplasts. Carbonyl/quinone/ketone/carboxyl groups (OCO), membrane polysaccharides (OH), and phospholipids (PO) were involved in the interaction of Cd ions, and the chlorophyll content underwent a process of decreasing in the early stage (1.62 mg/g at 48 h) and recovering to the normal level in the late stage, and the contents of MDA, GSH, and SOD were all increased (29.7 nmol/g, 0.23 mg/g, and 30.01 u/106 cells) and then gradually returned to the steady state. The results of EPS content and fluorescent labeling showed that Cd induced the overexpression and synthesis of extracellular polysaccharides and proteins, which is one of the defense mechanisms participating in the reduction of cellular damage by complexed Cd. Metabolomics results indicated that the malate synthesis pathway was activated after Cd-20 h, and the microalgal cells began to shift the metabolic pathway to storage lipid or polysaccharide biosynthesis. In the Calvin cycle, the expression of D-Sedoheptulose 7-phosphate in Cd-20 h_vs_ck and Cd-72 h_vs_Cd-20 h firstly declined and then increased, and the photosynthesis system was suppressed at the beginning, and then gradually returned to normal to maintain the successful development of the dark reaction. The results of time series analysis revealed that the response of microalgae to Cd was categorized into fast response and slow response to regulate cell adsorption and growth metabolism.

An indel introduced by Neanderthal introgression, rs3835124:ATTTATT > ATT, might contribute to prostate cancer risk by regulating PDK1 expression.

INTRODUCTION: Prostate cancer is one of the most common cancer types in males and rs12621278:A > G has been suggested to be associated with this disease by previous genome-wide association studies. One thousand genomes project data analysis indicated that rs12621278:A > G is within two long-core haplotypes. However, the origin, causal variant(s), and molecular function of these haplotypes were remaining unclear. MATERIALS AND METHODS: Population genetics analysis and functional genomics work was performed for this locus. RESULTS: Phylogeny analysis verified that the rare haplotype is derived from Neanderthal introgression. Genome annotation suggested that three genetic variants in the core haplotypes, rs116108611:G > A, rs139972066:AAAAAAAA > AAAAAAAAA, and rs3835124:ATTTATT > ATT, are located in functional regions. Luciferase assay indicated that rs139972066:AAAAAAAA > AAAAAAAAA and rs116108611:G > A are not able to alter ITGA6 (integrin alpha 6) and ITGA6 antisense RNA 1 expression, respectively. In contrast, rs3835124:ATTTATT > ATT can significantly influence PDK1 (pyruvate dehydrogenase kinase 1) expression, which was verified by expression quantitative trait locus analysis. This genetic variant can alter transcription factor cut like homeobox 1 interaction efficiency. The introgressed haplotype was observed to be subject to positive selection in East Asian populations. The molecular function of the haplotype suggested that Neanderthal should be with lower PDK1 expression and further different energy homeostasis from modern human. CONCLUSION: This study provided new insight into the contribution of Neanderthal introgression to human phenotypes.