Genetic history and biological adaptive landscape of the Tujia people inferred from shared haplotypes and alleles.

BACKGROUND: High-quality genomic datasets from under-representative populations are essential for population genetic analysis and medical relevance. Although the Tujia are the most populous ethnic minority in southwestern China, previous genetic studies have been fragmented and only partially reveal their genetic diversity landscape. The understanding of their fine-scale genetic structure and potentially differentiated biological adaptive features remains nascent. OBJECTIVES: This study aims to explore the demographic history and genetic architecture related to the natural selection of the Tujia people, focusing on a meta-Tujia population from the central regions of the Yangtze River Basin. RESULTS: Population genetic analyses conducted on the meta-Tujia people indicate that they occupy an intermediate position in the East Asian North-South genetic cline. A close genetic affinity was identified between the Tujia people and neighboring Sinitic-speaking populations. Admixture models suggest that the Tujia can be modeled as a mixture of northern and southern ancestries. Estimates of f3/f4 statistics confirmed the presence of ancestral links to ancient Yellow River Basin millet farmers and the BaBanQinCen-related groups. Furthermore, population-specific natural selection signatures were explored, revealing highly differentiated functional variants between the Tujia and southern indigenous populations, including genes associated with hair morphology (e.g., EDAR) and skin pigmentation (e.g., SLC24A5). Additionally, both shared and unique selection signatures were identified among ethnically diverse but geographically adjacent populations, highlighting their extensive admixture and the biological adaptations introduced by this admixture. CONCLUSIONS: The study unveils significant population movements and genetic admixture among the Tujia and other ethno-linguistically diverse East Asian groups, elucidating the differentiated adaptation processes across geographically diverse populations from the current genetic landscape.

SIRT1 Regulates Mitochondrial Damage in N2a Cells Treated with the Prion Protein Fragment 106-126 via PGC-1α-TFAM-Mediated Mitochondrial Biogenesis.

Mitochondrial damage is an early and key marker of neuronal damage in prion diseases. As a process involved in mitochondrial quality control, mitochondrial biogenesis regulates mitochondrial homeostasis in neurons and promotes neuron health by increasing the number of effective mitochondria in the cytoplasm. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that regulates neuronal mitochondrial biogenesis and quality control in neurodegenerative diseases via deacetylation of a variety of substrates. In a cellular model of prion diseases, we found that both SIRT1 protein levels and deacetylase activity decreased, and SIRT1 overexpression and activation significantly ameliorated mitochondrial morphological damage and dysfunction caused by the neurotoxic peptide PrP106-126. Moreover, we found that mitochondrial biogenesis was impaired, and SIRT1 overexpression and activation alleviated PrP106-126-induced impairment of mitochondrial biogenesis in N2a cells. Further studies in PrP106-126-treated N2a cells revealed that SIRT1 regulates mitochondrial biogenesis through the PGC-1α-TFAM pathway. Finally, we showed that resveratrol resolved PrP106-126-induced mitochondrial dysfunction and cell apoptosis by promoting mitochondrial biogenesis through activation of the SIRT1-dependent PGC-1α/TFAM signaling pathway in N2a cells. Taken together, our findings further describe SIRT1 regulation of mitochondrial biogenesis and improve our understanding of mitochondria-related pathogenesis in prion diseases. Our findings support further investigation of SIRT1 as a potential target for therapeutic intervention of prion diseases.

Polystyrene nanoplastics enhance poxvirus preference for migrasome-mediated transmission.

Since the emergence of a global outbreak of mpox in 2022, understanding the transmission pathways and mechanisms of Orthopoxviruses, including vaccinia virus (VACV), has become paramount. Nanoplastic pollution has become a significant global issue due to its widespread presence in the environment and potential adverse effects on human health. These emerging pollutants pose substantial risks to both living organisms and the environment, raising serious health concerns related to their proliferation. Despite this, the effects of nanoparticles on viral transmission dynamics remain unclear. This study explores how polystyrene nanoparticles (PS-NPs) influence the transmission of VACV through migrasomes. We demonstrate that PS-NPs accelerate the formation of migrasomes early in the infection process, facilitating VACV entry as soon as 15 h post-infection (hpi), compared to the usual onset at 36 hpi. Immunofluorescence and transmission electron microscopy (TEM) reveal significant co-localization of VACV with migrasomes induced by PS-NPs by 15 hpi. This interaction coincides with an increase in lipid droplet size, attributed to higher cholesterol levels influenced by PS-NPs. By 36 hpi, migrasomes exposed to both PS-NPs and VACV exhibit distinct features, such as retraction fibers and larger lipid droplets, emphasizing their critical role in cargo transport during viral infections. These results suggest that PS-NPs may act as modulators of viral transmission dynamics through migrasomes, with potential implications for antiviral strategies and environmental health.

Iron-doped nanozymes with spontaneous peroxidase-mimic activity as a promising antibacterial therapy for bacterial keratitis.

The development of non-antibiotic pharmaceuticals with biocompatible and efficient antibacterial properties is of great significance for the treatment of bacterial keratitis. In this study, we have developed antibacterial iron-doped nanozymes (Fe3+-doped nanozymes, FNEs) with distinguished capacity to fight against bacterial infections. The iron-doped nanozymes are composed of Fe3+ doped zeolitic imidazolate framework-8 (Fe/ZIF-8) and polyethylene imide (PEI), which were functionally coated on the surface of Fe/ZIF-8 and imparted the FNEs with improved water dispersibility and biocompatibility. FNEs possess a significant spontaneous peroxidase-mimic activity without the need for external stimulation, thus elevating cellular reactive oxygen species level by catalyzing local H2O2 at the infection site and resulting in bacteria damaged to death. FNEs eliminated 100% of Staphylococcus aureus within 6 h, and significantly relieved inflammation and bacterial infection levels in mice bacterial keratitis, exhibiting higher bioavailability and a superior therapeutic effect compared to conventional antibiotic eye drops. In addition, the FNEs would not generate drug resistance, suggesting that FNEs have great potential in overcoming infectious diseases caused by antimicrobial resistant bacteria.

Circadian metabolites for evaluating the timing of bloodstain deposition: A preliminary study.

Metabolites, as products of cellular metabolism, can provide a wealth of biological information and are less susceptible to degradation than other biomarkers due to their low molecular weight. Due to these properties, metabolites can be used as valuable biomarkers for forensic investigations. Knowing the timing of deposition of bloodstain could help to reconstruct crime scenes, draw conclusions about the time of the crime, and narrow down the circle of possible suspects. Previous studies have indicated that the concentration of some metabolites in blood is subject to circadian changes. However, the circadian metabolites of bloodstains have been still unclear. A total of sixty-four bloodstain samples were prepared under real conditions in three time categories (morning/noon (09:00 h ∼ 17:00 h), afternoon/evening (18:00 h ∼ 23:00 h) and night/early morning (24:00 h ∼ 08:00 h)). Fifty metabolites of bloodstains with significant differences were identified in the three time categories. Twenty-eight of these metabolites exhibited significant circadian changes. Finally, three independently contributing circadian metabolites were selected to build the logistic regression model, with an area under the curve of 0.91, 0.84 and 0.87 for the prediction of bloodstain deposition time in the morning/noon, afternoon/evening and night/early morning, respectively. The study indicated that circadian metabolites can be used for evaluating the timing of bloodstain deposition. This would provide a valuable perspective for analyzing the deposition time of biological traces in forensic investigations.

Dual-ROS-scavenging and dual-lingering nanozyme-based eye drops alleviate dry eye disease.

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings.

Ts2O Promoted Deoxygenative C-H Dithiocarbonation of Quinoline N-Oxides with Potassium O-Alkyl Xanthates.

A simple, efficient, and practical method for the synthesis of S-quinolyl xanthates was developed via Ts2O-promoted deoxygenative C-H dithiocarbonation of quinoline N-oxides with various potassium O-alkyl xanthates. The reaction performed well under transition-metal-free, base-free, and room-temperature conditions with wide substrate tolerance. Employing potassium O-tert-butyl xanthate (tBuOCS2K) as a nucleophile, some valuable quinoline-2-thiones were unexpectedly obtained in a one-pot reaction without any additional base.

Biophilic Positive Carbon Dot Exerts Antifungal Activity and Augments Corneal Permeation for Fungal Keratitis.

Fungal keratitis (FK) is an infectious eye disease that poses a significant risk of blindness. However, the effectiveness of conventional antifungal drugs is limited due to the intrinsic ocular barrier that impedes drug absorption. There is an urgent need to develop new therapeutic strategies to effectively combat FK. Herein, we synthesized an ultrasmall positively charged carbon dot using a simple stage-melting method. The carbon dot can penetrate the corneal barrier by opening the tight junctions, allowing them to reach the lesion site and effectively kill the fungi. The results both in vitro and in vivo demonstrated that it exhibited good biocompatibility and antifungal activity, significantly improving the therapeutic effect in a mouse model of FK. Therefore, this biophilic ultrasmall size and positive carbon dot, characterized by its ability to penetrate the corneal barrier and its antifungal properties, may offer valuable insights into the design of effective ocular nanomedicines.

Persulfate-Promoted Carbamoylation/Cyclization of Alkenes: Synthesis of Amide-Containing Quinazolinones.

The incorporation of amide groups into biologically active molecules has been proven to be an efficient strategy for drug design and discovery. In this study, we present a simple and practical method for the synthesis of amide-containing quinazolin-4(3H)-ones under transition-metal-free conditions. This is achieved through a carbamoyl-radical-triggered cascade cyclization of N3-alkenyl-tethered quinazolinones. Notably, the carbamoyl radical is generated in situ from the oxidative decarboxylative process of oxamic acids in the presence of (NH4)2S2O8.

Immobilization of Pb in waste water and soil by tourmaline-biochar composites (TBs): Characteristics and mechanisms.

Novel tourmaline-biochar composites (TBs) were synthesized by introducing tourmaline (TM) into pomelo peel biochar (BC). The surface properties of TBs and BC were studied and the adsorption performances for Pb2+ were investigated. Compared to pristine BC, the adsorption ability for Pb2+ on TBs was enhanced with the increase of TM in TBs, and up to 514.62 mg/g on 5%TB. The enrichment of inorganic metals caused by TM in TBs made the precipitation and cation ion exchange become the main mechanisms in adsorbing Pb2+, and the amounts of adsorbing Pb2+ by those two mechanisms on TBs were 1.10-1.48 times and 1.20-1.30 times those of BC, respectively. Furthermore, applying TBs to practical contaminated soil increased the soil pH and electrical conductivity (EC) after 15 days of incubation. The increased content of residual-Pb and reduced exchangeable-Pb and DTPA-Pb indicated that TBs were favorable for the immobilization of Pb in soil. This study gives a new perspective on the synthesis of tourmaline-biochar composite and their application in Pb-polluted water and soil.

Dual-Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease.

Dry eye disease (DED) is a major ocular pathology worldwide, causing serious ocular discomfort and even visual impairment. The incidence of DED is gradually increasing with the high-frequency use of electronic products. Although inflammation is core cause of the DED vicious cycle, reactive oxygen species (ROS) play a pivotal role in the vicious cycle by regulating inflammation from upstream. Therefore, current therapies merely targeting inflammation show the failure of DED treatment. Here, a novel dual-atom nanozymes (DAN)-based eye drops are developed. The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer. The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS, inhibiting NLRP3 inflammasome activation, decreasing proinflammatory cytokines expression, and suppressing cell apoptosis. Consequently, the DAN effectively alleviate ocular inflammation, promote corneal epithelial repair, recover goblet cell density and tear secretion, thus breaking the DED vicious cycle. Our findings open an avenue to make the DAN as an intervention form to DED and ROS-mediated inflammatory diseases.

Ball milling synthesis of S-quinolyl xanthates via coupling of haloquinolines with potassium O-alkyl xanthates.

An environmentally benign protocol that provides various S-quinolyl xanthates via a ball milling enabled cross coupling reaction of haloquinolines and readily available potassium O-alkyl xanthates is first reported. The reaction proceeded well under mild, transition metal- and solvent-free conditions, making it an attractive method for the introduction of xanthates into the quinoline scaffold.

Regulation of tourmaline-mediated Fenton-like system by biochar: Free radical pathway to non-free radical pathway.

The heterogeneous Fenton-like systems induced by Fe-containing minerals have been largely applied for the degradation of organic pollutants. However, few studies have been conducted on biochar (BC) as an additive to Fenton-like systems mediated by iron-containing minerals. In this study, the addition of BC prepared at different temperatures was found to significantly enhance the degradation of contaminants in the tourmaline-mediated Fenton-like system (TM/H2O2) using Rhodamine B (RhB) as the target contaminant. Furthermore, the hydrochloric acid-modified BC prepared at 700 °C (BC700(HCl)) could achieve complete degradation of high concentrations of RhB in the BC700(HCl)/TM/H2O2 system. Free radical quenching experiments showed that TM/H2O2 system removed contaminants mainly mediated by the free radical pathway. After adding BC, the removal of contaminants is mainly mediated by the non-free radical pathway in BC700(HCl)/TM/H2O2 system which was confirmed by the Electron paramagnetic resonance (EPR) experiments and electrochemical impedance spectroscopy (EIS). In addition, BC700(HCl) had broad feasibility in the degradation of other organic pollutants (Methylene Blue (MB) 100%, Methyl Orange (MO) 100%, and tetracycline (TC) 91.47%) in the tourmaline-mediated Fenton-like system. Possible pathways for the degradation of RhB by the BC700(HCl)/TM/H2O2 system were also proposed.

Elaborating the mechanism of lead adsorption by biochar: Considering the impacts of water-washing and freeze-drying in preparing biochar.

This paper examined the impacts of different pretreatments on the characteristics of biochar and its adsorption behavior for Pb2+. Biochar with combined pretreatment of water-washing and freeze-drying (W-FD-PB) performed a maximum adsorption capacity for Pb2+ of 406.99 mg/g, higher than that of 266.02 mg/g on water-washing pretreated biochar (W-PB) and 188.21 mg/g on directly pyrolyzed biochar (PB). This is because the water-washing process partially removed the K and Na, resulting in the relatively enriched Ca and Mg on W-FD-PB. And the freeze-drying pretreatment broke the fiber structure of pomelo peel, favoring the development of a fluffy surface and large specific surface area during pyrolysis. Quantitative mechanism analysis implied that cation ion exchange and precipitation were the driving forces in Pb2+ adsorption on biochar, and both mechanisms were enhanced during Pb2+ adsorption on W-FD-PB. Furthermore, adding W-FD-PB to Pb-contaminated soil increased the soil pH and significantly reduced the availability of Pb.

Estimation of bloodstain deposition time within a 24-h day-night cycle with rhythmic mRNA based on a machine learning algorithm.

Estimating the time that bloodstains are left at a crime scene can provide invaluable evidence for law enforcement investigations, including determining the time of the crime, linking the perpetrator to the crime scene, narrowing the pool of possible suspects, and verifying witness statements. There have been some attempts to estimate the time since deposition of bloodstains, i.e., how much time has passed since the bloodstain was left at a crime scene. However, most studies focus on the time interval of days. As far as we know, previous study have been conducted to estimate the deposition time of blood within a 24-h day-night cycle. To date, there is a lack of studies on whether rhythmic mRNA of blood is suitable for bloodstain samples. In this study, we estimated the bloodstain deposition time within a 24-h day-night cycle based on the expression of messenger RNAs (mRNAs) by real-time quantitative polymerase chain reaction. Bloodstain samples were prepared from eight individuals at eight time points under real and uncontrolled conditions. Four mRNAs expressed rhythmically and were used to construct a regression model using the k-nearest neighbor (KNN) algorithm, resulting in a mean absolute error of 3.92 h. Overall, using the rhythmic mRNAs, a machine learning model was developed which has allowed us to predict the deposition time of bloodstains within the 24-h day-night cycle in East Asian populations. This study demonstrates that mRNA biomarkers can be used to estimate the bloodstain deposition time within a 24-h period. Furthermore, rhythmic mRNA biomarkers provide a potential method and perspective for estimating the deposition time of forensic traces in forensic investigation. Case samples in forensic analysis are usually limited or degraded, so the stability and sensitivity of rhythmic biomarkers need to be further investigated.

Cardiolipin externalization mediates prion protein (PrP) peptide 106-126-associated mitophagy and mitochondrial dysfunction.

Proper mitochondrial performance is imperative for the maintenance of normal neuronal function to prevent the development of neurodegenerative diseases. Persistent accumulation of damaged mitochondria plays a role in prion disease pathogenesis, which involves a chain of events that culminate in the generation of reactive oxygen species and neuronal death. Our previous studies have demonstrated that PINK1/Parkin-mediated mitophagy induced by PrP106-126 is defective and leads to an accumulation of damaged mitochondria after PrP106-126 treatment. Externalized cardiolipin (CL), a mitochondria-specific phospholipid, has been reported to play a role in mitophagy by directly interacting with LC3II at the outer mitochondrial membrane. The involvement of CL externalization in PrP106-126-induced mitophagy and its significance in other physiological processes of N2a cells treated with PrP106-126 remain unknown. We demonstrate that the PrP106-126 peptide caused a temporal course of mitophagy in N2a cells, which gradually increased and subsequently decreased. A similar trend in CL externalization to the mitochondrial surface was seen, resulting in a gradual decrease in CL content at the cellular level. Inhibition of CL externalization by knockdown of CL synthase, responsible for de novo synthesis of CL, or phospholipid scramblase-3 and NDPK-D, responsible for CL translocation to the mitochondrial surface, significantly decreased PrP106-126-induced mitophagy in N2a cells. Meanwhile, the inhibition of CL redistribution significantly decreased PINK1 and DRP1 recruitment in PrP106-126 treatment but had no significant decrease in Parkin recruitment. Furthermore, the inhibition of CL externalization resulted in impaired oxidative phosphorylation and severe oxidative stress, which led to mitochondrial dysfunction. Our results indicate that CL externalization induced by PrP106-126 on N2a cells plays a positive role in the initiation of mitophagy, leading to the stabilization of mitochondrial function.

How Green Mindfulness and Green Shared Vision Interact to Influence Green Creative Behavior.

Aim: The study is based on the self-determination theory and aims to investigate the mediating role of green intrinsic motivation and the moderating role of green shared vision in the association between frontline managers' green mindfulness and green creative behavior to leverage their capacity to think creatively and act sustainably. Methods: The study employs a time-lagged, multi-source research methodology to collect data from frontline managers of service businesses in the tourism and hospitality industry. Data are analyzed using SmartPLS Structural Equation Model to evaluate the structural and measurement models. The authors evaluated the measurement model by employing the criteria of internal consistency: reliability and Cronbach's alpha, validity: convergent and discriminant validity; and the structural model using the path coefficient, coefficient of determination, predictive relevance, and goodness-of-fit metrics. Results: Our findings indicate that green mindfulness significantly improves frontline managers' green creative behavior. Additionally, green intrinsic motivation mediates the connection between green mindfulness and green creative behavior. In addition, the direct effect of green mindfulness on green intrinsic motivation as well as the indirect effect of green mindfulness on green creative behavior through green intrinsic motivation, are both significantly moderated by green shared vision. Discussion: To the best of the authors' knowledge, this is one of the few efforts that outstretch the boundary conditions of green mindfulness and green creative behavior through the mediating role of green intrinsic motivation and the moderating role of green shared vision.

Stable tissue-mimicking phantoms for longitudinal multimodality imaging studies that incorporate optical, CT, and MRI contrast.

Significance: Tissue phantoms that mimic the optical and radiologic properties of human or animal tissue play an important role in the development, characterization, and evaluation of imaging systems. Phantoms that are easily produced and stable for longitudinal studies are highly desirable. Aim: A new type of long-lasting phantom was developed with commercially available materials and was assessed for fabrication ease, stability, and optical property control. Magnetic resonance imaging (MRI) and x-ray computed tomography (CT) contrast properties were also evaluated. Approach: A systematic investigation of relationships between concentrations of skin-like pigments and composite optical properties was conducted to realize optical property phantoms in the red and near-infrared (NIR) wavelength range that also offered contrast for CT and MRI. Results: Phantom fabrication time was < 1 h and did not involve any heating or cooling processes. Changes in optical properties were < 2 % over a 12-month period. Phantom optical and spectral features were similar to human soft tissue over the red to NIR wavelength ranges. Pigments used in the study also had CT and MRI contrasts for multimodality imaging studies. Conclusions: The phantoms described here mimic optical properties of soft tissue and are suitable for multimodality imaging studies involving CT or MRI without adding secondary contrast agents.

Peroxidase-like MoS2/Ag nanosheets with synergistically enhanced NIR-responsive antibacterial activities.

Pathogenic microbial infections have been threatening public health all over the world, which makes it highly desirable to develop an antibiotics-free material for bacterial infection. In this paper, molybdenum disulfide (MoS2) nanosheets loaded with silver nanoparticles (Ag NPs) were constructed to inactive bacteria rapidly and efficiently in a short period under a near infrared (NIR) laser (660 nm) in the presence of H2O2. The designed material presented favorable features of peroxidase-like ability and photodynamic property, which endowed it with fascinating antimicrobial capacity. Compared with free MoS2 nanosheets, the MoS2/Ag nanosheets (denoted as MoS2/Ag NSs) exhibited better antibacterial performance against Staphylococcus aureus by the generated reactive oxygen species (ROS) from both peroxidase-like catalysis and photodynamic, and the antibacterial efficiency of MoS2/Ag NSs could be further improved by increasing the amount of Ag. Results from cell culture tests proved that MoS2/Ag3 nanosheets had a negligible impact on cell growth. This work provided new insight into a promising method for eliminating bacteria without using antibiotics, and could serve as a candidate strategy for efficient disinfection to treat other bacterial infections.

Recent Advances in Thallium Removal from Water Environment by Metal Oxide Material.

Thallium is widely used in industrial and agricultural development. However, there is still a lack of systematic understanding of its environmental hazards and related treatment methods or technologies. Here, we critically assess the environmental behavior of thallium in aqueous systems. In addition, we first discuss the benefits and limitations of the synthetic methods of metal oxide materials that may affect the practicality and scalability of TI removal from water. We then assess the feasibility of different metal oxide materials for TI removal from water by estimating the material properties and contaminant removal mechanisms of four metal oxides (Mn, Fe, Al, and Ti). Next, we discuss the environmental factors that may inhibit the practicality and scalability of Tl removal from water. We conclude by highlighting the materials and processes that could serve as more sustainable alternatives to TI removal with further research and development.