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Background Chinese indigenous rabbits have distinct characteristics, such as roughage resistance, stress resistance and environmental adaptability, which are of great significance to the sustainable development of the rabbit industry in China. Therefore, it is necessary to study the genetic diversity and population structure of this species and develop genomic resources. Results In this study, we used restriction site-associated DNA sequencing (RAD-seq) to obtain 1,006,496 SNP markers from six Chinese indigenous rabbit breeds and two imported rabbit breeds. Jiuyishan and Fujian Yellow rabbits showed the highest nucleotide diversity (π) and decay of linkage disequilibrium (LD), as well as higher observed heterozygosity (Ho) and expected heterozygosity (He), indicating higher genetic diversity than other rabbits. The inbreeding coefficient ( F IS ) of New Zealand rabbits and Belgian rabbits was higher than that of other rabbits. The neighbour-joining (NJ) tree, principal component analysis (PCA), and population structure analysis of autosomes and Y chromosomes showed that Belgian, New Zealand, Wanzai, Sichuan White, and Minxinan Black rabbits clustered separately, and Fujian Yellow, Yunnan Colourful, and Jiuyishan rabbits clustered together. Wanzai rabbits were clearly separated from other populations (K = 3), which was consistent with the population differentiation index ( F ST ) analysis. The selection signature analysis was performed in two populations with contrasting coat colours. With Sichuan White and New Zealand rabbits as the reference populations and Minxinan Black and Wanzai rabbits as the target populations, 408, 454, 418, and 518 genes with a selection signature, respectively, were obtained. Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the genes with a selection signature. The results showed that the genes with a selection signature were enriched in the melanogenesis pathway in all four sets of selection signature analyses. Conclusions Our study provides the first insights into the genetics and genomics of Chinese indigenous rabbit breeds and serves as a valuable resource for the further effective utilization of the species.

The domestic Bactrian camel is a valuable livestock resource in arid desert areas. Therefore, it is essential to understand the roles of important genes responsible for its characteristics. We used restriction site-associated DNA sequencing (RAD-seq) to detect single nucleotide polymorphism (SNP) markers in seven domestic Bactrian camel populations. In total, 482,786 SNPs were genotyped. The pool of all remaining others were selected as the reference population, and the Nanjiang, Sunite, Alashan, Dongjiang, Beijiang, Qinghai, and Hexi camels were the target populations for selection signature analysis. We obtained 603, 494, 622, 624, 444, 588, and 762 selected genes, respectively, from members of the seven target populations. Gene Ontology classifications and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed, and the functions of these genes were further studied using Genecards to identify genes potentially related to the unique characteristics of the camel population, such as heat resistance and stress resistance. Across all populations, cellular process, single-organism process, and metabolic process were the most abundant biological process subcategories, whereas cell, cell part, and organelle were the most abundant cellular component subcategories. Binding and catalytic activity represented the main molecular functions. The selected genes in Alashan camels were mainly enriched in ubiquitin mediated proteolysis pathways, the selected genes in Beijiang camels were mainly enriched in MAPK signaling pathways, the selected genes in Dongjiang camels were mainly enriched in RNA transport pathways, the selected genes in Hexi camels were mainly enriched in endocytosis pathways, the selected genes in Nanjiang camels were mainly enriched in insulin signaling pathways, while the selected genes in Qinghai camels were mainly enriched in focal adhesion pathways; these selected genes in Sunite camels were mainly enriched in ribosome pathways. We also found that Nanjiang ( HSPA4L and INTU ), and Alashan camels ( INO80E ) harbored genes related to the environment and characteristics. These findings provide useful insights into the genes related to the unique characteristics of domestic Bactrian camels in China, and a basis for genomic resource development in this species.

The androgen receptor (AR) is a nuclear hormone receptor, and its activation through binding to androgens is essential for prostate development, morphogenesis, growth, and tumorigenesis. Although significant efforts have been devoted to understanding the critical role of AR, the cellular properties and functions of the AR-expressing cells acting as prostatic progenitors in controlling prostatic cell differentiation and growth still remain elusive. Additionally, dynamic paracrine interactions between urogenital mesenchyme and epithelia initiated by the AR activation through prostate development are also largely unknown. Recently, we modified the mouse Ar gene locus, which enables us to genetically label AR-expressing cells spatiotemporally and trace them through prostate development, morphogenesis, and growth in combination with a double-fluorescent reporter mouse model. The membrane-bound green fluorescent protein (mGFP)-expressing cells were revealed in both urogenital sinus mesenchyme (UGM) and epithelium (UGE) at embryonic day E18.5 when Tamoxifen was administrated at E13.5 to activate CreER recombinase directed by the endogenous Ar promoter. The AR-expressing cells and their descendants were further detected at postnatal days 10, 35, and 56, and through three cycles of prostatic regeneration by repeated androgen deprivation and replacement. Deletion of β-catenin through the AR-driven CreER in embryonic AR-expressing cells impairs prostate development and morphogenesis. Specifically, altered β-catenin expression results in loss of prostatic glandular cell polarity and activation of Fas death signaling pathways. These lines of experimental evidence demonstrate the biological relevance and significance of this new genetic tool to assess and visualize AR-mediated signaling pathways through prostatic development, growth, and tumorigenesis.

Restriction site‐associated DNA sequencing (RAD‐seq) is one of the most effective high‐throughput sequencing technologies for SNP development and utilization and has been applied to studying the origin and evolution of various species. The domestic Bactrian camels play an important role in economic trade and cultural construction. They are precious species resources and indispensable animals in China's agricultural production. Recently, the rapid development of modern transportation and agriculture, and the deterioration of the environment have led to a sharp decline in the number of camels. Although there have been some reports on the evolution history of the domestic Bactrian camel in China, the origin, evolutionary relationship, and genetic diversity of the camels are unclear due to the limitations of sample size and sequencing technology. Therefore, 47 samples of seven domestic Bactrian camel species from four regions (Inner Mongolia, Gansu, Qinghai, and Xinjiang) were prepared for RAD‐seq analysis to study the evolutionary relationship and genetic diversity. In addition, seven domestic Bactrian camel species are located in different ecological zones, forming different characteristics and having potential development value. A total of 6,487,849 SNPs were genotyped. On the one hand, the filtered SNP information was used to conduct polymorphism mapping construction, LD attenuation analysis, and nucleotide diversity analysis. The results showed that the number of SNPs in Dongjiang camel was the highest, the LD coefficient decayed the fastest, and the nucleotide diversity was the highest. It indicates that Dongjiang camel has the highest genetic diversity. On the other hand, the filtered SNPs information was used to construct the phylogenetic tree, and FST analysis, inbreeding coefficient analysis, principal component analysis, and population structure analysis were carried out. The results showed that Nanjiang camel and Beijiang camels grouped together, and the other five Bactrian camel populations gathered into another branch. It may be because the mountains in the northern part of Xinjiang and the desert in the middle isolate the two groups from the other five groups. In this paper, 47 samples of seven domestic Bactrian camel species from four regions (Inner Mongolia, Gansu, Qinghai, and Xinjiang) were prepared for RAD‐seq analysis to study the evolutionary relationship and genetic diversity. In addition, seven domestic Bactrian camel species are located in different ecological zones, forming different characteristics and having potential development value.

Dysregulation of Hippo signaling is observed in pancreatic adenocarcinoma (PAAD). Moreover, overactivation of YAP is crucial for tumor progression. Although the inhibitory phospho-cascade is functional, the reason for YAP hyperactivation in PAAD remains unclear. Recent studies have revealed that the ubiquitin modification of YAP also plays an important role in the Hippo/YAP axis and cancer progression. To gain a better understanding of the potential mechanisms underlying the ubiquitination and deubiquitination of YAP, we carried out siRNA screening for critical deubiquitinases in PAAD. By using a deubiquitinase (DUB) library, we identified valosin-containing protein-interacting protein 1 (VCPIP1) as an important effector of YAP function and PAAD progression. Inhibition of VCPIP1 hampered PAAD progression via Hippo signaling. Clinical data revealed that VCPIP1 was elevated in PAAD and correlated with poor survival in PAAD patients. Biochemical assays demonstrated that VCPIP1 interacted with YAP, inhibiting K48-linked polyubiquitination and thereby increasing YAP stability. YAP directly binds to the VCPIP1 promoter region, enhancing its transcription in PAAD. Our study revealed a forward feedback loop between VCPIP1 and Hippo signaling in PAAD, indicating that VCPIP1 is a potential therapeutic drug target in PAAD.

Reintroduction has been recognized as a vital approach to protecting and restoring wild populations of rare and endangered species. Although numerous reintroduction programs have been launched worldwide, in-depth studies on population establishment, dynamics, distribution patterns, and challenges remain limited. The Milu ( ), endemic to China and once declared Extinct in the Wild by the IUCN, has become one of the most successful examples of global endangered species reintroduction since the initiation of its recovery program in 1985. Focusing on the reintroduction project in the Poyang Lake basin-China's largest freshwater lake-this study analyzed 14 years of monitoring data to examine the processes of population re-establishment, demographic trends, and spatiotemporal distribution of the species, while also identifying major ongoing challenges. Findings reveal the following: (1) the acclimatization process was essential for 10 individuals first reintroduced in 2013, and then 30 individuals joined to the growing population, followed by the largest-scale release of 47 in 2018, which finally led to eight consecutive years of natural reproduction, with a theoretically estimated population of 89 individuals until August 2025; (2) among 1697 individual sightings in 238 monitoring events, 952 records can be distinguished between male and female individuals (sex ratio = 1:1.63), yielding a mean herd size of 7.28 ± 0.68 individuals per sighting event-although numbers rose slightly in 2024, a declining trend was observed from 2019 to 2023 (from 11.26 to 5.13); (3) the Milu have expanded their range across eastern Poyang Lake, demonstrating a behavioral patterns of migrating out of the lake zone during flood seasons and returning in dry season; (4) the restoration of the Milu population is a systematic endeavor, in which government support and the participation of conservation professionals, scientists, volunteers, media, and the public are critical factors; and (5) ongoing threats such as human disturbance (e.g., habitat degradation) and climate change continue to jeopardize long-term population viability. This study offers important scientific insights into the recovery of endangered wildlife globally and underscores the essential role of governmental commitment, long-term monitoring, and multi-stakeholder collaboration in species reintroduction efforts.

Background Breast cancer is the most prevalent cancer in women globally. Over-activated estrogen receptor (ER) α signaling is considered the main factor in luminal breast cancers, which can be effectively managed with selective estrogen receptor modulators (SERMs) like tamoxifen. However, approximately 30–40% of ER + breast cancer cases are recurrent after tamoxifen therapy. This implies that the treatment of breast cancer is still hindered by resistance to tamoxifen. Recent studies have suggested that post-translational modifications of ERα play a significant role in endocrine resistance. The stability of both ERα protein and its transcriptome is regulated by a balance between E3 ubiquitin ligases and deubiquitinases. According to the current knowledge, approximately 100 deubiquitinases are encoded in the human genome, but it remains unclear which deubiquitinases play a critical role in estrogen signaling and endocrine resistance. Thus, decoding the key deubiquitinases that significantly impact estrogen signaling, including the control of ERα expression and stability, is critical for the improvement of breast cancer therapeutics. Methods We used several ER positive breast cancer cell lines, DUB siRNA library screening, xenograft models, endocrine-resistant (ERα-Y537S) model and performed immunoblotting, real time PCR, RNA sequencing, immunofluorescence, and luciferase activity assay to investigate the function of USP36 in breast cancer progression and tamoxifen resistance. Results In this study, we identify Ubiquitin-specific peptidase 36 (USP36) as a key deubiquitinase involved in ERα signaling and the advancement of breast cancer by deubiquitinases siRNA library screening. In vitro and in vivo studies showed that USP36, but not its catalytically inactive mutant (C131A), could promote breast cancer progression through ERα signaling. Conversely, silencing USP36 inhibited tumorigenesis. In models resistant to endocrine therapy, silencing USP36 destabilized the resistant form of ERα (Y537S) and restored sensitivity to tamoxifen. Molecular studies indicated that USP36 inhibited K48-linked polyubiquitination of ERα and enhanced the ERα transcriptome. It is interesting to note that our results suggest USP36 as a novel biomarker for treatment of breast cancer. Conclusion Our study revealed the possibility that inhibiting USP36 combined with tamoxifen could provide a potential therapy for breast cancer.

Background The Hippo pathway is crucial in organ size control and tumorigenesis. Dysregulation of the Hippo/YAP axis is commonly observed in gastric cancer, while effective therapeutic targets for the Hippo/YAP axis are lacking. Identification of reliable drug targets and the underlying mechanisms that could inhibit the activity of the Hippo/YAP axis and gastric cancer progression is urgently needed. Methods We used several gastric cancer cell lines and xenograft models and performed immunoblotting, qPCR, and in vivo studies to investigate the function of CXCR7 in gastric cancer progression. Results In our current study, we demonstrate that the membrane receptor CXCR7 (C-X-C chemokine receptor 7) is an important modulator of the Hippo/YAP axis. The activation of CXCR7 could stimulate gastric cancer cell progression through the Hippo/YAP axis in vitro and in vivo, while pharmaceutical inhibition of CXCR7 via ACT-1004–1239 could block tumorigenesis in gastric cancer. Molecular studies revealed that the activation of CXCR7 could dephosphorylate YAP and facilitate YAP nuclear accumulation and transcriptional activation in gastric cancer. CXCR7 functions via G-protein Gα q/11 and Rho GTPase to activate YAP activity. Interestingly, ChIP assays showed that YAP could bind to the promoter region of CXCR7 and facilitate its gene transcription, which indicates that CXCR7 is both the upstream signalling and downstream target of the Hippo/YAP axis in gastric cancer. Conclusion In general, we identified a novel positive feedback loop between CXCR7 and the Hippo/YAP axis, and blockade of CXCR7 could be a plausible strategy for gastric cancer. Highlight 1: Our study reveals a novel feedback loop between the Hippo pathway and CXCR7 in coordinating tumorigenesis in gastric cancer. 2: Our study reveals that blockade of CXCR7, which impedes membrane signal transduction, could be a promising strategy for gastric cancer therapeutics. 3: Our model that YAP facilitates GPCR transcription, while GPCR in turn facilitates the Hippo/YAP axis, is likely to be a general phenomenon in the cancer research field, which could reveal a broad phenomenon between Hippo signalling and GPCR.

Diabetes is a chronic metabolic disease characterized by hyperglycaemia and a number of potential complications that significantly reduce the patient's quality of life. In this study, we produced an antidiabetic functional food from Tartary buckwheat fermented by TK9 and TK1501. The results of an orthogonal experimental design indicated that the three factors with the largest effects on the growth of TK9 and TK1501 in solid-state fermentation (SSF) were in the order: water ratio>inoculum size>time of fermentation. Under the optimal fermentation conditions comprising a 1:1.5 water ratio, 24 h of SSF and a 10 CFU/g inoculum, the Tartary buckwheat fermented by TK9 and TK1501 yielded viable probiotic counts of (2.3±0.7)·10 and (3.3±0.4)·10 CFU/g, respectively. The nutritional potential, as well as antioxidant and antidiabetic properties of ethanolic extracts from fermented Tartary buckwheat were investigated. The highest α-glucosidase inhibitory activity, with an IC of 0.51 mg/mL, was present in Tartary buckwheat fermented by TK9. However, Tartary buckwheat fermented by TK1501 had the highest dipeptidyl peptidase IV (DPP-IV) inhibition, with an IC of 2.47 mg/mL. Therefore, fermentation by both TK9 and TK1501 has the potential to yield a product that can help regulate the levels of blood glucose as part of a diabetic diet.

Background Breast cancer is the most common cancer in women worldwide. More than 70% of breast cancers are estrogen receptor (ER) alpha positive. Compared with ER alpha-negative breast cancer, which is more aggressive and has a shorter survival time, ER alpha-positive breast cancer could benefit from endocrine therapy. Selective estrogen receptor modulators, such as tamoxifen, are widely used in endocrine therapy. Approximately half of ER alpha-positive breast cancer patients will eventually develop endocrine resistance, making it a major clinical challenge in therapy. Thus, decoding the throughput of estrogen signaling, including the control of ER alpha expression and stability, is critical for the improvement of breast cancer therapeutics. Methods TRIM3 and ER alpha protein expression levels were measured by western blotting, while the mRNA levels of ER alpha target genes were measured by RT–PCR. A CCK-8 assay was used to measure cell viability. RNA sequencing data were analyzed by Ingenuity Pathway Analysis. Identification of ER alpha signaling activity was accomplished with luciferase assays, RT–PCR and western blotting. Protein stability assays and ubiquitin assays were used to detect ER alpha protein degradation. Ubiquitin-based immunoprecipitation assays were used to detect the specific ubiquitination modification on the ER alpha protein. Results In our current study, we found that TRIM3, an E3 ligase, can promote ER alpha signaling activity and breast cancer progression. TRIM3 depletion inhibits breast cancer cell proliferation and migration, while unbiased RNA sequencing data indicated that TRIM3 is required for the activity of estrogen signaling on the -genome-wide scale. The immunoprecipitation assays indicated that TRIM3 associates with ER alpha and promotes its stability, possibly by inducing K63-linked polyubiquitination of ER alpha. In conclusion, our data implicate a nongenomic mechanism by which TRIM3 stabilizes the ER alpha protein to control ER alpha target gene expression linked to breast cancer progression. Conclusion Our study provides a novel posttranslational mechanism in estrogen signaling. Modulation of TRIM3 expression or function could be an interesting approach for breast cancer treatment. Graphical abstract 2noEgdU1b5aSV4mMoG9Uyp Video abstract