Pharmacokinetics and safety evaluation of intravenously administered Pseudomonas phage PA_LZ7 in a mouse model.

IMPORTANCE: Phage therapy is gaining traction as an alternative to antibiotics due to the rise of multi-drug-resistant (MDR) bacteria. This study assessed the pharmacokinetics and safety of PA_LZ7, a phage targeting MDR Pseudomonas aeruginosa, in mice. After intravenous administration, the phage showed an exponential decay in plasma and its concentration dropped significantly within 24 h for all dosage groups. Although there was a temporary increase in certain plasma cytokines and spleen weight at higher dosages, no significant toxicity was observed. Therefore, PA_LZ7 shows potential as an effective and safe candidate for future phage therapy against MDR P. aeruginosa infections.

Successful treatment of eyebrow intradermal nevi by shearing combined with electrocautery and curettage: Two case reports.

BACKGROUND: An intradermal nevus is a common skin tumour, and the classical method of removal has a risk of recurrence and scarring. It is a challenge for dermatologists to treat eyebrow intradermal nevi quickly and efficiently. This study focused on investigating the efficacy and safety of shearing combined with electrocautery and curettage in the treatment of eyebrow intradermal nevi. CASE SUMMARY: We describe two adult patients with eyebrow intradermal nevi treated by shearing combined with electrocautery and curettage. Both patients were followed up regularly after surgery. At follow-up, no recurrence of eyebrow intradermal nevus and no obvious scars or hypopigmentation were found in either patient. The results indicated that shearing combined with electrocautery and curettage could remove eyebrow intradermal nevus without side effects and confirmed the efficacy and safety of this modality for treating these skin lesions. CONCLUSION: Shearing combined with electrocautery and curettage has superior merits, including simple operation, good cosmetic effects, and high patient satisfaction, presenting great application potential for treating intracutaneous nevus.

Case report: Inspiration from a rare fatal heart perforation after percutaneous vertebroplasty.

The principal benefit of employing percutaneous vertebroplasty (PVP) for managing osteoporotic vertebral compression fractures lies in its capacity to facilitate early mobilization in elderly patients, thereby effectively avoiding the potential catastrophic complications associated with prolonged bedridden states. However, bone cement leakage, as the most common complication of PVP, may have fatal consequences. Here, we report a case involving an 85-year-old male patient with L1 vertebral compression fracture who underwent PVP at our hospital and was discharged on the same day of the surgical intervention. Subsequently, the patient experienced symptoms of chest tightness and palpitations. Cardiac ultrasound examination revealed pericardial effusion, while pulmonary computed tomographic angiography (CTA) demonstrated a strip high-density shadow in the right ventricular area. Finally, it was determined that the perforation of the right ventricular wall was caused by bone cement embolism. Through this comprehensive case report, we aim to deepen the understanding of orthopedic doctors on the importance of preventing bone cement leakage.

Engineered phage with cell-penetrating peptides for intracellular bacterial infections.

IMPORTANCE: Salmonella infection is a significant threat to global public health, and the increasing prevalence of antibiotic resistance exacerbates the situation. Therefore, finding new and effective ways to combat this pathogen is essential. Phages are natural predators of bacteria and can be used as an alternative to antibiotics to kill specific bacteria, including drug-resistant strains. One significant limitation of using phages as antimicrobial agents is their low cellular uptake, which limits their effectiveness against intracellular bacterial infections. Therefore, finding ways to enhance phage uptake is crucial. Our study provides a straightforward strategy for displaying cell-penetrating peptides on non-model phages, offering a promising novel and effective therapeutic approach for treating intracellular and drug-resistant bacteria. This approach has the potential to address the global challenge of antibiotic resistance and improve public health outcomes.

Color-Tunable Binary Copolymers Manipulated by Intramolecular Aggregation and Hydrogen Bonding.

Construction of color-tunable luminescent polymeric materials with enhanced emission intensity and room-temperature phosphorescence (RTP) performance regulated by a single chromophore component is highly desirable in the scope of photoluminescent materials. Herein, a set of binary copolymers were facilely synthesized using free radical polymerization by selecting different types of polymer matrix and N-substituted naphthalimides (NPA) as chromophores. Surprisingly, the fluorescence emission of copolymers could be remarkably enhanced, because of the intramolecular aggregation of NPA manipulated by a single polymer chain in both solution and solid state. Moreover, RTP signals of binary copolymers were all clearly observed in the air without any processing procedure, because of the embedding of phosphors into hydrogen bonding networks after copolymerization with vinyl-based acrylamide monomers. Taking advantages of the synergistic effect of copolymerization-induced aggregation and copolymerization-induced rigidification to promote optical performance, UV stimulus-responsive luminescent polymer films with processability, flexibility, and adjustable emission wavelength were simply prepared using a drop-casting method in large scale, the setting of which is the basis for application in the fields of organic optoelectronics, information security, and bioimaging/sensing.

Tale of COF-on-MOF Composites with Structural Regulation and Stepwise Luminescence Enhancement.

Integrating metal-organic framework (MOF)-covalent organic framework (COF) allows versatile engineering of hybrid materials with properties superior to pristine components, especially COFs suffered from aggregation-caused quenching (ACQ), unlocking more possibilities to improve the luminescence of COFs. In this work, we prepared various MOF@COF composites with different COF layer thicknesses, in which stable UiO-66-NH2 served as the inner substrate and 1,3,5-benzenetricarboxaldehyde (BT), and 3,3'-dihydroxybenzidine (DH) were used to construct a COF layer. In addition to the conventional preparation method, we increased the ratio of BT and DH to be 1:2.5, and impressively, the morphologies of acquired UC (1:2.5) materials were quite different from the previous reticular structure and gradually extended from the spherical structure to the prickly structure with the increase of COF monomers. Remarkably, all of the UC materials possessed better luminescence properties than individual COF due to the limited COF layers. Meanwhile, UC-1 materials with an optimal COF layer displayed the strongest emission. In comparison with a single COF, the quantum yields of UC-1 and UC-1 (1:2.5) were increased nearly 7 times and 5 times, respectively. Moreover, the fluorescence of UC-1 materials was progressively enhanced via selective F- sensing. This work is expected to shed light on the potential hybridization of MOF-COF with structural adjustment, morphological design, and luminescence enhancement.

Tunable fluorescence emission based on multi-layered MOF-on-MOF.

Luminescent metal-organic frameworks (MOFs) have garnered considerable attention in various fields. Herein, we proposed a hierarchical confinement strategy based on MOF-on-MOF to tune luminescence emission ranging from blue to red including white light in a flexible way. The easily available ZIF-8 MOF was used as a host for the confinement of two kinds of size-matching dyes (perylene and rhodamine B) to obtain a layered ZIF-8@dye@ZIF-8@dye via in situ encapsulation and seed-mediated synthesis. ZIF-8@dye@ZIF-8@dye materials with different fluorescence emission in dispersed and solid states were both obtained by tuning the initial encapsulation concentration of dye and changing the structure of the inner and outer ZIF-8@dye layers. To our delight, ZIF-8@0.125perylene@ZIF-8@25RhB with white light emission in the dispersed state was obtained; meanwhile, ZIF-8@0.125perylene + 25RhB and mechanically mixed ZIF-8@0.125perylene + ZIF-8@25RhB could not realize white light emission under the same conditions, indicating that the proposed hierarchical confinement strategy facilitated white light regulation. Similarly, the emission of ZIF-8@dye@ZIF-8@dye in the solid state has also been investigated; ZIF-8@perylene@ZIF-8@3RhB with white light emission was obtained, while white light emission could not be achieved in ZIF-8@perylene + 3RhB and ZIF-8@perylene + ZIF-8@3RhB, which further indicated the importance of the hierarchical confinement strategy based on MOF-on-MOF. The proposed hierarchical confinement strategy may also inspire the development of other functional optical MOF materials.

Network Pharmacology-Based Analysis on the Effects and Mechanism of the Wang-Bi Capsule for Rheumatoid Arthritis and Osteoarthritis.

Wang-Bi capsule (WB) is a traditional Chinese medicine (TCM)-based herbal formula, and it has been used in the treatment of rheumatoid arthritis (RA) in China for many years. Additionally, WB is also used as a supplement to the treatment of osteoarthritis (OA) in clinical practice. Our research aimed to reveal the therapeutic effects and underling mechanism of WB on RA and OA through computational system pharmacology analysis and experimental study. Based on network pharmacology analysis, a total of 173 bioactive compounds interacted with 417 common gene targets related to WB, RA, and OA, which mainly involved the PI3K-Akt signaling pathway. In addition, the serine-threonine protein kinase 1 (AKT1) might be a core gene protein for the action of WB, which was further emphasized by molecular docking. Moreover, the anti-inflammatory activity of WB in vitro was confirmed by reducing NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells. The anti-RA and OA effects of WB in vivo were confirmed by ameliorating the disease symptoms of collagen II-induced RA (CIA) and monosodium iodoacetate-induced OA (MIA) in rats, respectively. Furthermore, the role of the PI3K-Akt pathway in the action of WB was preliminarily verified by western blot analysis. In conclusion, our study elucidated that WB is a potentially effective strategy for the treatment of RA and OA, which might be achieved by regulating the PI3K-Akt pathway. It provides us with systematic insights into the effects and mechanism of WB on RA and OA.

The Carboxyl Terminal Regions of P0 Protein Are Required for Systemic Infections of Poleroviruses.

P0 proteins encoded by poleroviruses Brassica yellows virus (BrYV) and Potato leafroll virus (PLRV) are viral suppressors of RNA silencing (VSR) involved in abolishing host RNA silencing to assist viral infection. However, other roles that P0 proteins play in virus infection remain unclear. Here, we found that C-terminal truncation of P0 resulted in compromised systemic infection of BrYV and PLRV. C-terminal truncation affected systemic but not local VSR activities of P0 proteins, but neither transient nor ectopic stably expressed VSR proteins could rescue the systemic infection of BrYV and PLRV mutants. Moreover, BrYV mutant failed to establish systemic infection in DCL2/4 RNAi or RDR6 RNAi plants, indicating that systemic infection might be independent of the VSR activity of P0. Partially rescued infection of BrYV mutant by the co-infected PLRV implied the functional conservation of P0 proteins within genus. However, although C-terminal truncation mutant of BrYV P0 showed weaker interaction with its movement protein (MP) when compared to wild-type P0, wild-type and mutant PLRV P0 showed similar interaction with its MP. In sum, our findings revealed the role of P0 in virus systemic infection and the requirement of P0 carboxyl terminal region for the infection.

Harmine reinforces the effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells.

The overall outcomes for patients with advanced liver cancer are far from satisfactory, and the development of more effective therapeutic strategies for liver cancer is required. Sulforhodamine blue and colony formation assays were performed to detect the proliferation of liver certain cancer cells, including HepG2 and Hep3B. Western blotting was also preformed to detect the expression of indicated proteins, including cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerase, dual-specificity tyrosine phosphorylation kinase 1A (DYRK1A), PARP-1/2, GAPDH, myeloid cell leukemia-1, phosphorylated-AKT (Ser473), caspase-3, α-tubulin and AKT. PI staining was used to detect cell death. In the present study, DYRK1A knockdown significantly enhanced the anti-liver cancer effect of regorafenib in vitro. Furthermore, DYRK1A inhibitor harmine together with regorafenib provided synergistic anti-liver cancer activity by suppressing cell proliferation. In addition, harmine significantly enhanced regorafenib-induced cell death in liver cancer cells. It has been reported that AKT signaling is activated in regorafenib-resistant cancer cells and plays a crucial role in the regulation of cellular sensitivity to regorafenib. In the present study, AKT was activated in regorafenib-treated cells, and harmine could suppress the activation of AKT and reinforce the anti-cancer effects of regorafenib via regulating AKT in liver cancer cells. These data indicated that harmine enhanced the anti-cancer effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells via regulating the activation of AKT, and harmine plus regorafenib may be a potential therapeutic regimen for treating patients with liver cancer.

Thermal and wine processing enhanced Clematidis Radix et Rhizoma ameliorate collagen â ¡ induced rheumatoid arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Clematidis Radix et Rhizoma, a kind of traditional Chinese medicine, is derived from Clematis chinensis Osbeck, Clematis hexapetala Pall. and Clematis manshurica Rupr. This herb shows great effects on expelling wind and dispelling dampness in ancient and it has anti-inflammatory and analgesic activity in modern clinical application. AIM OF THE STUDY: This experiment aimed to research anti-rheumatoid arthritis effect of crude and wine processed RC based on glycolysis metabolism to provide new ideas treating RA. MATERIALS AND METHODS: Network pharmacology was applied to preliminarily forecast the potential pathways of common targets of RC and RA. RAW264.7 macrophages were induced by LPS, NO production, glucose uptake, lactate production, ROS and MMP were detected as instructions in vitro. ELISA was used to measure the content of HK2, PKM2 and LDHA involving in glycolysis process. Gut microbiota was analyzed by 16S rRNA gene amplicon sequencing in CIA rats. RESULTS: Crude and wine processed RC had good anti-inflammatory effect by reducing NO in RAW264.7 macrophages and ameliorating inflammatory infiltration and cartilage surface erosion in CIA rats. Whether in LPS-induced macrophages or CIA rats, crude and wine processed RC could inhibit glycolysis by down-regulating the expression of PKM2, causing less glucose uptake and lactic acid, which lead to less ROS and higher MMP to normal. PI3K-AKT and HIF-1α pathways were deduced to possibly play a crucial part in controlling glycolysis metabolism by network pharmacology analysis. Besides, it was displayed that Firmicutes and Bacteroidetes were prominent gut microbiota in CIA rats feces. CC-H and PZ-H groups could both increase the relative abundance of Firmicutes and decrease Bacteroidetes. These microbiota also played a role in RA pathological process via involving in energy metabolism, carbohydrate metabolism and immune system. CONCLUSION: Crude and wine processed RC have a good influence in ameliorating rheumatoid arthritis by inhibiting glycolysis and modulating gut microbiota together.

Tracing investigation and analysis of a Clostridium botulinum food poisoning incident in Bayingolin Mongolian Autonomous Prefecture, Xinjiang / 中华预防医学杂志

To analyze a suspected case of Clostridium botulinum food poisoning in Bayingolin Mongolian Autonomous Prefecture, Xinjiang and to help validating the diagnosis and providing technical support for clinical treatment. The basic information and clinical manifestations of food poisoning cases were investigated by using the epidemiological method of food safety accidents. The botulinum toxin genes in the samples were detected by real-time PCR and inoculation of KM mouse. The enriched bacteria were further purified and validated. PFGE and cluster analysis were performed on five isolates. Clostridium botulinum type A was detected in two homemade fermented bean samples and stool lavage fluid samples of three patients from enriched samples by toxin test and real-time PCR, and were further validated after isolation of Clostridium botulinum. PFGE showed 100% homology among five isolates. Five isolates of bacteria isolated from the stool lavage fluid of three patients and two homemade fermented bean curd were identified as the same source through PFGE. The cause of this food poisoning cases is food pollution of Clostridium botulinum type A.

Comparative Analysis of Biological Characteristics among P0 Proteins from Different Brassica Yellows Virus Genotypes.

Brassica yellows virus (BrYV) is a tentative species of the genus Polerovirus, which has at least three genotypes (A, B, and C) in China. The P0 protein of BrYV-A (P0BrA) has been identified as a viral suppressor of RNA silencing (VSR), which can also induce cell death in infiltrated Nicotiana benthamiana leaves. In this study, we demonstrated that the cell death induced by P0BrA was accompanied by the accumulation of reactive oxygen species (ROS) and increased Pathogenesis-related protein genes-1 (PR1) expression. Meanwhile, this cell death phenotype was delayed by salicylic acid (SA) pretreatment. Biological function comparison of the three P0 proteins showed that transiently expressed P0BrB or P0BrC induced a significantly delayed and milder cell death response compared with P0BrA. However, like P0BrA, they also suppressed local and systemic RNA silencing. Six residues of P0BrA essential for inducing cell death were identified by comparative analysis and amino acid substitution assay. We also show that all three BrYV genotypes have synergistic interactions with pea enation mosaic virus 2 (PEMV 2) in N. benthamiana. This study provides theoretical guidance for controlling the viral disease caused by poleroviruses in the future.

A Simple Method for the Acquisition and Transmission of Brassica Yellows Virus from Transgenic Plants and Frozen Infected Leaves by Aphids.

Brassica yellows virus (BrYV) is a tentative species of the genus Polerovirus, which occurs widely, and mostly damages Brassicaceae plants in East Asia. Because BrYV cannot be transmitted mechanically, an insect-based transmission method is required for further virus research. Here, a reliable and unrestricted method is described, in which non-viruliferous aphids (Myzus persicae) acquired BrYV from transgenic Arabidopsis thaliana, harboring the full-length viral genome germinated from seeds and its frozen leaves. The aphids then transmitted the virus to healthy plants. There was no significant difference in acquisition rates between fresh and frozen infected leaves, although the transmission rate from frozen infected leaves was lower compared to fresh infected leaves. This simple novel method may be used to preserve viral inocula, evaluate host varietal resistance to BrYV, and investigate interactions among BrYV, aphids, and hosts.

Piezo-type mechanosensitive ion channel component 1 (Piezo1) in human cancer.

Piezo-type mechanosensitive ion channel component 1 (Piezo1) is a mechanosensitive ion channel protein that is evolutionarily conserved and multifunctional. It plays an important role as an oncogenic mediator in several malignant tumors. It mediates the proliferation, migration, and invasion of a variety of cancer cells through various mechanisms. Multiple studies have shown that the expression of Piezo1 is related to the clinical characteristics of senescence and cancer patients, making Piezo1 useful as a new biomarker for the diagnosis and prognosis of a variety of human cancers. Manipulating the expression or function of Piezo1 is a potential therapeutic strategy for different diseases. Piezo1 may be a promising tumor biomarker and therapeutic target. Here we review the biological function, mechanism of action, and potential clinical significance of Piezo1 in oncogenesis and progression.

Sesamin protects against DSS-induced colitis in mice by inhibiting NF-κB and MAPK signaling pathways.

OBJECTIVE: To investigate the protective effects and mechanisms of sesamin (SES) on dextran sulfate sodium (DSS)-induced experimental colitis in mice. METHODS: SES (50, 100, and 200 mg kg-1) were orally administered to C57BL/6 male mice after DSS instillation. The anti-inflammatory effect of SES on colonic damage was assessed by clinical, macroscopic, microscopic, and inflammatory signaling pathways. RESULTS AND CONCLUSIONS: It could be found that bodyweight and colon length of mice treated with DSS was significantly decreased while that were increased by SES treatment. SES treatment reduced the DAI values and improved the histopathology of the colon in the DSS-treated mice. SES also reduced TNF-α, IL-1ß and IL-6 production caused by DSS. We also measured the expression of the phosphorylation of p65, IκB, p38, ERK and JNK protein and found that SES can alleviate colon damage via the NF-κB and MAPK signaling pathways. The findings of this study suggested that SES had anti-inflammatory effects on intestinal inflammation and can be used as a new therapeutic candidate for inflammatory bowel disease.

Exploring the Possible Mechanism and Drug Targets of Huang-Qi-Gui-Zhi-Wu-Wu Decoction for the Treatment of Chemotherapy-Induced Peripheral Neuropathy on Network Pharmacology.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment, which may influence its successful completion. The Huang-Qi-Gui-Zhi-Wu-Wu decoction (HQGZWWD) has been widely used to treat CIPN in China although the pharmacological mechanisms involved have not been clarified. Using the network pharmacology approach, this study investigated the potential pathogenesis of CIPN and the therapeutic mechanisms exerted by the HQGZWWD herbal formula in CIPN. The targets of HQGZWWD were identified using traditional Chinese medicine (TCM) databases (TCMSP and ETCM) and prediction platforms (PharmMapper and TargetNet), and the genes of CIPN were collected by DisGeNET, GeneCards, and literature search. The common target interaction network between herbal formula and diseases was constructed by using Cytoscape. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal the mechanism and efficacy of HQGZWWD in the treatment of CIPN. A total of 153 CIPN-related genes were screened, and a protein-protein interaction (PPI) network with 96 nodes and 424 edges was constructed. Sixty-three active components were retrieved from HQGZWWD, with a herb-composite compound-target network including 748 nodes and 5448 edges. Forty-one targets belong to the above two networks. The analysis of network results and literature review shows that the main pathological processes of CIPN may be the inflammatory response and nerve injury, and HQGZWWD plays a therapeutic role in CIPN by regulating inflammatory response and repairing nerve injury, thus verifying the reliable efficacy of this herbal formula. In addition, we found two new potential therapeutic targets (CDK7 and GSTM2) warranting further investigation. This study fully illustrates that TCM has the characteristics of a multicompound, multitarget, and multipathway treatment, which is of great significance to study the curative effect of herbal formulations.

[Cut-off value of white blood cell count in the diagnosis of early-onset sepsis in neonates].

OBJECTIVE: To study the clinical significance and cut-off value of white blood cell (WBC) count in the diagnosis of early-onset sepsis (EOS) in neonates. METHODS: A retrospective analysis was performed on 306 neonates with EOS who were admitted from January 2019 to March 2020. A total of 580 children without infection who were admitted during the same period of time were enrolled as the control group. General status and WBC count were compared between the two groups. The diagnostic value of WBC count was analyzed based on the diagnostic and therapeutic protocol of neonatal sepsis in 2003 (referred to as the 2003 diagnostic and therapeutic protocol) and the expert consensus on the diagnosis and treatment of neonatal sepsis (2019 edition) (referred to as the 2019 expert consensus). RESULTS: According to the two different diagnosis and treatment protocols, the statistical analysis showed that WBC count had a relatively positive rate (51.3% and 32.0% respectively) but a relatively high specificity (93.3% and 98.6% respectively). The receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve of WBC count in the 2003 diagnostic and therapeutic protocol was larger than that in the 2019 expert consensus (P<0.05). CONCLUSIONS: The cut-off value of WBC ≥25×109/L in the 2003 diagnostic and therapeutic protocol is more reasonable in the diagnosis of EOS.

Homotherapy for heteropathy active components and mechanisms of Qiang-Huo-Sheng-Shi decoction for treatment of rheumatoid arthritis and osteoarthritis.

Qiang-Huo-Sheng-Shi decoction (QHSSD), a classic traditional Chinese herbal formula, which has been reported to be effective in rheumatoid arthritis (RA) and osteoarthritis (OA). However, the concurrent targeting mechanism of how the aforementioned formula is valid in the two distinct diseases OA and RA, which represents the homotherapy-for-heteropathy principle in traditional Chinese medicine (TCM), have not yet been clarified. In the present study, network pharmacology was adopted to analyze the potential molecular mechanism, and therapeutic effective components of QHSSD on both OA and RA. A total of 153 active ingredients in QHSSD were identified, 142 of which associated with 59 potential targets for the two diseases were identified. By constructing the protein-protein interaction network and the compound-target-disease network, 72 compounds and 10 proteins were obtained as the hub targets of QHSSD against OA and RA. The hub genes of ESR1, PTGS2, PPARG, IL1B, TNF, MMP2, IL6, CYP3A4, MAPK8, and ALB were mainly involved in osteoclast differentiation, the NF-κB and TNF signaling pathways. Moreover, molecular docking results showed that the screened active compounds had a high affinity for the hub genes. This study provides new insight into the molecular mechanisms behind how QHSSD presents homotherapy-for-heteropathy therapeutic efficacy in both OA and RA. For the first time, a two-disease model was linked with a TCM formula using network pharmacology to identify the key active components and understand the common mechanisms of its multi-pathway regulation. This study will inspire more innovative and important studies on the modern research of TCM formulas.

Paternal Origins and Migratory Episodes of Domestic Sheep.

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution.