Similarities and differences: species and diet impact gut microbiota of captive pheasants.

The fecal microbiota plays an important role in maintaining animal health and is closely related to host life activities. In recent years, there have been an increasing number of studies on the fecal microbiota from birds. An exploration of the effects of species and living environments on the composition of gut microbiota will provide better protection for wildlife. In this study, non-injury sampling and 16S rDNA high-throughput sequencing were used to investigate the bacterial composition and diversity of the fecal microbiota in silver pheasants (Lophura nycthemera) and golden pheasants (Chrysolophus pictus) from Tianjin Zoo and Beijing Wildlife Park. The results showed that the abundance of Firmicutes was the highest in all fecal samples. At the genus level, Bacteroides was the common dominant bacteria, while there were some differences in other dominant bacteria genera. There were significant differences in fecal microbial composition between the golden pheasants from Tianjin Zoo and Beijing Wildlife Park. The metabolic analysis and functional prediction suggested that the gut microbiota composition and host metabolism were influenced by dietary interventions and living conditions. The results of this study provide the basis for further research of intestinal microbial of L. nycthemera and C. pictus, and valuable insights for conservation of related species.

Investigation of the mechanism of nephrotoxicity of nux-vomica by PTGS2/CYP2C9-mediated arachidonic acid pathway and Jian Pi Tong Luo compound's protective effect.

The clinical effectiveness of nux-vomica in treating rheumatism and arthralgia is noteworthy; however, its nephrotoxicity has sparked global concerns. Hence, there is value in conducting studies on detoxification methods based on traditional Chinese medicine compatibility theory. Blood biochemistry, enzyme-linked immunosorbent assay, and pathological sections were used to evaluate both the nephrotoxicity of nux-vomica and the efficacy of the Jian Pi Tong Luo (JPTL) compound in mitigating this toxicity. Kidney metabolomics, using ultra-high-performance liquid chromatography-quadrupole-time-of-flight-MS (UPLC-Q-TOF-MS), was applied to elucidate the alterations in small-molecule metabolites in vivo. In addition, network pharmacology analysis was used to verify the mechanism and pathways underlying the nephrotoxicity associated with nux-vomica. Finally, essential targets were validated through molecular docking and western blotting. The findings indicated significant nephrotoxicity associated with nux-vomica, while the JPTL compound demonstrated the ability to alleviate this toxicity. The mechanism potentially involves nux-vomica activating the "PTGS2/CYP2C9-phosphatidylcholine-arachidonic acid metabolic pathway." This study establishes a scientific foundation for the clinical use of nux-vomica and lays groundwork for further research and safety assessment of toxic Chinese herbal medicines.

Electronic inhomogeneity and phase fluctuation in one-unit-cell FeSe films.

One-unit-cell FeSe films on SrTiO3 substrates are of great interest owing to significantly enlarged pairing gaps characterized by two coherence peaks at ±10 meV and ±20 meV. In-situ transport measurement is desired to reveal novel properties. Here, we performed in-situ microscale electrical transport and combined scanning tunneling microscopy measurements on continuous one-unit-cell FeSe films with twin boundaries. We observed two spatially coexisting superconducting phases in domains and on boundaries, characterized by distinct superconducting gaps ( Δ 1 ~15 meV vs. Δ 2 ~10 meV) and pairing temperatures (Tp1~52.0 K vs. Tp2~37.3 K), and correspondingly two-step nonlinear V ~ I α behavior but a concurrent Berezinskii-Kosterlitz-Thouless (BKT)-like transition occurring at T BKT ~28.7 K. Moreover, the onset transition temperature T c onset ~54 K and zero-resistivity temperature T c zero ~31 K are consistent with Tp1 and T BKT , respectively. Our results indicate the broadened superconducting transition in FeSe/SrTiO3 is related to intrinsic electronic inhomogeneity due to distinct two-gap features and phase fluctuations of two-dimensional superconductivity.

Impact of Environmental Food Intake on the Gut Microbiota of Endangered Père David's Deer: Primary Evidence for Population Reintroduction.

Reintroduction has been successful in re-establishing several endangered wild animals in their historical habitats, including Père David's deer (Elaphurus davidianus). Continuous monitoring of reintroduced individuals is essential for improving the sustainability of ex situ conservation efforts. Despite an increased recognition of the significance of the gut microbiome for animal health, the correlation between diet and the gut microbiome in E. davidianus is unclear. In this study, 15 fresh fecal samples of E. davidianus were collected from Tianjin Qilihai Wetland and the association between dietary and gut microbiota composition was evaluated. Microscopic observations showed that Nymphoides peltata [relative density (RD = 0.3514), Phragmites australis (RD = 0.2662), Setaria viridis (RD = 0.1211), and Typha orientalis (RD = 0.1085) were the main dietary plants in the fecal samples. High-throughput 16S rRNA sequencing showed a predominance of the phyla Firmicutes and Proteobacteria and the genus Psychrobacillus (26.53%) in the gut microbiota. The RD of N. peltata was significantly positively correlated with the abundance of Firmicutes (p = 0.005) and the genus UCG-005 (p = 0.024). This study indicates a close association between food digestion and nutrient intake, providing basic monitoring data for the full reintroduction and recovery of wild E. davidianus.

Indisulam exerts anticancer effects via modulation of transcription, translation and alternative splicing on human cervical cancer cells.

Indisulam is a synthetic sulfonamides drug with anticancer activity in various tumors. However, the effect and molecular mechanism of indisulam have still not been studied in human cervical cancer. We treated human cervical cancer cell lines (HeLa and C33A) with indisulam, evaluated its efficacy, and investigated its molecular targets. Indisulam inhibited tumor growth and induced RBM39 degradation in a dose-dependent manner. RNA-seq and proteomics analysis revealed that indisulam disrupted transcriptional regulation pathways related to mRNA splicing and apoptosis. More importantly, indisulam caused mis-splicing of RNA transcripts including p73 isoforms ΔNp73 and TAp73 which have opposite roles in apoptosis regulation. Indisulam increased TAp73 expression and triggered mitochondrial apoptosis independent of p53 status in HeLa cells. In summary, our data suggests that indisulam has therapeutic potential in cervical cancer, representing an attractive strategy in p53-disrupted cancers and should be further investigated.

Visualizing Atomic Quantum Defects in Ultrathin 1T-PtTe2.

Defects are of significant importance to determine and improve the distinct properties of 2D materials, such as electronic, optical, and catalytic performance. In this report, we observe four types of point defects in atomically thin flakes of 1T-PtTe2 by using low-temperature scanning tunnelling microscopy and spectroscopy (STM/S). Through the combination of STM imaging and simulations, such defects are identified as a single tellurium vacancy from each side of the top PtTe2 layer and a single platinum vacancy from the topmost and next layer. The density functional theory (DFT) calculations reveal that the platinum vacancies from both the monolayer and bilayer exhibit a local magnetic moment. In bilayer PtTe2, the interlayer coulomb screening effect reduces the local magnetic momentum of the single platinum vacancy. Our research provides meaningful guidance for further experiments about the effects of intrinsic defects on potential functions of thin 1T-PtTe2, such as catalysis and spintronic applications.

How do living conditions affect the gut microbiota of endangered Père David's deer (Elaphurus davidianus)? Initial findings from the warm temperate zone.

Reintroduction is an effective strategy in the conservation of endangered species under scientific monitoring. Intestinal flora plays an important role in the envir onmental adaptation of endangered Père David's deer (Elaphurus davidianus). In this study, 34 fecal samples from E. davidianus were collected from different habitats in Tianjin city of China to investigate differences in the intestinal flora under captive and semi-free-ranging conditions. Based on 16S rRNA high-throughput sequencing technology, a total of 23 phyla and 518 genera were obtained. Firmicutes was dominant in all individuals. At the genus level, UCG-005 (13.05%) and Rikenellaceae_RC9_gut_group (8.94%) were dominant in captive individuals, while Psychrobacillus (26.53%) and Pseudomonas (11.33%) were dominant in semi-free-ranging individuals. Alpha diversity results showed that the intestinal flora richness and diversity were significantly (P < 0.001) higher in captive individuals than in semi-free-ranging individuals. Beta diversity analysis also showed a significant difference (P = 0.001) between the two groups. In addition, some age- and sex-related genera such as Monoglobus were identified. In summary, the structure and diversity of intestinal flora showed significant habitat variation. This is the first time an analysis has been undertaken of the structural differences of the intestinal flora in Père David's deer, under different habitats in the warm temperate zone, providing a reference basis for the conservation of endangered species.

A novel PTEN mutant caused by polymorphism in cis-regulatory elements is involved in chemosensitivity in breast cancer.

Phosphatase and tensin homolog (PTEN) is one of the most important tumor suppressor genes. Although studies have shown the association between cancer and genetic polymorphisms of PTEN, the underlying molecular mechanisms of breast cancer (BC) chemosensitivity that results from PTEN polymorphism is still unclear. This study aims to investigate potential links between PTEN polymorphisms in cis-regulatory elements and BC chemosensitivity in the Chinese population. A total of 172 BC patients who received neoadjuvant chemotherapy were included in the study, including 104 chemosensitive cases and 68 chemoresistant cases. The results showed a significant association between the rs786204926 polymorphism and BC chemosensitivity. Logistic multivariate regression analysis showed that age, lymph node metastasis, and the rs786204926 genotype were risk factors for BC chemoresistance. The G allele of rs786204926 is more prone to increasing the risk of chemosensitivity in BC. Additionally, analysis using Alamut Visual showed a preference of the G allele of rs786204926 to produce a novel PTEN mutant with an insertion of 18 bases from intron 4. While the transcriptional level of PTEN remained similar in chemosensitivity and chemoresistant samples, its protein level changed significantly. Interestingly, there were significant differences in both transcription and protein levels of the novel PTEN mutant between the two groups. Furthermore, we found that the mutant was more susceptible to dephosphorylation compared with wildtype PTEN, leading to chemosensitivity through the PI3K-AKT signaling pathway. These findings indicate that novel PTEN mutants caused by polymorphisms in cis-regulatory elements may be involved in BC chemosensitivity.

Mutant p53 in cancer: from molecular mechanism to therapeutic modulation.

TP53, a crucial tumor suppressor gene, is the most commonly mutated gene in human cancers. Aside from losing its tumor suppressor function, mutant p53 (mutp53) often acquires inherent, novel oncogenic functions, which is termed "gain-of-function". Emerging evidence suggests that mutp53 is highly associated with advanced malignancies and poor prognosis, which makes it a target for development of novel cancer therapies. Herein, we provide a summary of our knowledge of the mutp53 types and mutp53 spectrum in cancers. The mechanisms of mutp53 accumulation and gain-of-function are also summarized. Furthermore, we discuss the gain-of-function of mutp53 in cancers: genetic instability, ferroptosis, microenvironment, and stemness. Importantly, the role of mutp53 in the clinic is also discussed, particularly with regard to chemotherapy and radiotherapy. Last, emphasis is given to emerging strategies on how to target mutp53 for tumor therapy. Thus, this review will contribute to better understanding of the significance of mutp53 as a target for therapeutic strategies.

Early Antimicrobial Evaluation of Nanostructured Surfaces Based on Bacterial Biological Properties.

Nanostructured physical antibacterial surfaces are of great interest due to the increasing antibiotic resistance. In this work, the titania nanotube (TNT) array, a potential physical antibacterial surface, was used for antimicrobial evaluation. The early antibacterial properties of TNTs were assessed based on three growth phases of Staphylococcus aureus (S. aureus), and the physical factors influencing the antibacterial properties were comprehensively discussed. The results show apparent early antibacterial effects of TNTs, including the anti-initial attachment during the lag phase, the inhibition of proliferation and bactericidal effect during the logarithmic phase, and the inhibition of biofilm formation during the stationary phase. These antimicrobial effects are closely related to the combined influence of various physical properties of TNTs, such as diameter, hydrophilicity, roughness, and charge. The present work suggests that the evaluation of the early antimicrobial behavior of biomaterials should pay more attention on the biological characteristics of bacteria.

An Experimental and Analytical Study on a Damage Constitutive Model of Engineered Cementitious Composites under Uniaxial Tension.

Engineered cementitious composites (ECC) exhibit ultra-high ductility and post-cracking resistance, which makes it an attractive material in civil engineering. First, a monotonic uniaxial tensile test was performed, considering the effects of polyvinyl alcohol (PVA) fiber volume content and water-binder ratio. Then, the effects of the above variables on the tensile characteristics including the tensile stress-strain relationship, deformation capacity, and fracture energy were investigated based on test results; and when the water-binder ratio is 0.28 and the fiber volume content is 2%, the deformation performance of ECC is improved most significantly. Next, combined with damage mechanics theory, the damage evolution mechanism of ECC in monotonic uniaxial tension was revealed, based on which the damage factor and damage evolution equation of ECC were developed and the expressions of model parameters were proposed. Moreover, the comparison between the proposed model and test results demonstrated the accuracy of the proposed model. Finally, to further verify the feasibility of the proposed model, a finite element (FE) simulation analysis of the tensile performance of high-strength stainless steel wire rope (HSSWR) reinforced ECC by adopting the proposed model was compared with test results and the simulation analysis results by using anther existing model, the "trilinear model of ECC". The comparison shows that the proposed model in this paper can predict more accurately.

Overexpression of splicing factor poly(rC)-binding protein 1 elicits cycle arrest, apoptosis induction, and p73 splicing in human cervical carcinoma cells.

PURPOSE: Splicing factor poly(rC)-binding protein 1 (PCBP1) is a novel tumor suppressor that is downregulated in several cancers thereby regulating tumor formation and metastasis. However, the involvement of PCBP1 in apoptosis of cancer cells and the molecular mechanism remains elusive. On this basis, we sought to investigate the role of splicing factor PCBP1 in the apoptosis in human cervical cancer cells. METHODS: To investigate PCBP1 functions in vitro, we overexpressed PCBP1 in human cervical cancer cells. A series of cytological function assays were employed to study to the role of PCBP1 in cell proliferation, cell cycle arrest and apoptosis. RESULTS: Overexpression of PCBP1 was found to greatly repress proliferation of HeLa cells in a time-dependent manner. It also induced a significant increase in G2/M phase arrest and apoptosis. Furthermore, overexpressed PCBP1 favored the production of long isoforms of p73, thereby inducing upregulated ratio of Bax/Bcl-2, the release of cytochrome c and the expression of caspase-3. CONCLUSION: Our results revealed that PCBP1 played a vital role in p73 splicing, cycle arrest and apoptosis induction in human cervical carcinoma cells. Targeting PCBP1 may be a potential therapeutic strategy for cervical cancer therapy.

Ursolic acid inhibits Th17 cell differentiation via STAT3/RORγt pathway and suppresses Schwann cell-mediated Th17 cell migration by reducing CXCL9/10 expression.

Th17 cells represent important immune cells. Ursolic acid (UA) can regulate immune cell activities. This study was aimed to explore the effects of UA on Th17 cell differentiation and Schwann cell(SCs)-mediated migration and the potential mechanism. Naïve CD4+ T cells were isolated from rat peripheral blood, induced for Th17 cell differentiation, and treated with UA. The proportion of Th17 cells was detected by flow cytometry assay. SCs were co-cultured with Th17 cells. Th17 cell migration was detected by Transwell assay. The molecule expression was determined by Western blot and qRT-PCR. UA inhibited the Th17 cell differentiation and suppressed the STAT3/RORγt pathway. STAT3 overexpression up-regulated p-STAT3 and RORγt expression and promoted Th17 cell differentiation under the UA treatment. In LPS- and IFN-γ-stimulated-SCs, UA suppressed the expression of chemokines CXCL9/10, but had no significant effect of CCL20 expression. The expression CXCL9/10 receptor CXCR3 was higher in Th17 cells than that in Treg cells, while the expression CCL20 receptor CCR6 was lower in Th17 cells than that in Treg cells. UA, anti-CXCR3, and anti-CCR6 treatment inhibited SCs-mediated Th17 cell migration, and anti-CXCR3 exerted stronger inhibitory effect than Anti-CCR6. UA inhibited Th17 cell differentiation through STAT3/RORγt pathway and suppressed Th17 cell migration through down-regulating CXCL9/10 expression in SCs.

In vivo urinary compatibility of Mg-Sr-Ag alloy in swine model.

A biodegradable metallic ureteral stent with suitable mechanical properties and antibacterial activity remains a challenge. Here we reveal the scientific significance of a biodegradable Mg-Sr-Ag alloy with a favorable combination of balanced mechanical properties, adjustable indwelling time in urinary tract and evident antibacterial activity via in vivo experiments in a swine model. Attributed to the rheo-solidification process, equiaxial microstructure and significantly refined grains (average grain size: 27.1 µm) were achieved. Mg17Sr2 and Mg4Ag were found as the primary precipitates in the matrix, due to which the alloy obtained ca. 111% increase in ultimate tensile strength in comparison to pure magnesium. Both the in vitro and in vivo results demonstrated the satisfactory biocompatibility of the alloy. Histological evaluation and bioindicators analysis suggested that there was no tissue damage, inflammation and lesions in the urinary system caused by the degradation process. The stent also improved the post-operative bladder functions viewed from the urodynamic results. Our findings highlight the potential of this alloy as antibacterial biodegradable urinary implant material.

Facile synthesis of multi-functional nano-composites by precise loading of Cu2+ onto MgO nano-particles for enhanced osteoblast differentiation, inhibited osteoclast formation and effective bacterial killing.

Biomaterials with multi-functions including enhancing osteogenesis, inhibiting osteoclastogenesis and effectively removing bacteria are urgently needed in the treatment of osteoporotic bone defects. In this study, MgO nano-particles were employed as a platform for precise Cu2+ loading. By immersing MgO into CuSO4 solution with a pre-defined concentration (0.1, 1 or 10 mM), 1 mg MgO adsorbed 3.25, 32.5 or 325 µg Cu2+ from the solution. As-synthesized nano-composites were referred as MgO-0.1Cu, MgO-1Cu or MgO-10Cu depending on the concentration of employed CuSO4 solution. The results revealed that MgO-xCu (x = 0.1, 1 and 10) nano-composites were lamella-shaped and composed of amorphous Cu(OH)2, crystalline Mg(OH)2 and minor MgO. The extracellular release of Cu2+ was rather limited due the capture of Cu2+ by Mg(OH)2. In vitro results revealed that MgO-xCu (x = 0.1, 1 and 10) nano-composites modulated osteoblast, osteoclast and bacterium response in a Cu2+ loading amount-dependent manner. MgO-0.1Cu nano-composite exhibited stimulatory function on osteoblast proliferation without influencing osteoblast maturation, osteoclast formation and bacterial survival. MgO-1Cu nano-composite enhanced osteoblast proliferation and differentiation, inhibited osteoclast formation and effectively killed bacteria. When larger amount of Cu2+ was loaded, MgO-10Cu nano-composite exhibited stronger stimulatory effect on osteoblast maturation, enhanced inhibitory function on osteoclast formation and promoted bactericidal performance, although it showed a certain degree of initial cyto-toxicity. Together, the results suggest that MgO nano-particles could be employed as potential platform for precise Cu2+ loading and intracellular Cu2+ delivery. MgO-xCu (x = 1 and 10) nano-composites are promising to be employed as multi-functional fillers in bone tissue engineering scaffolds for osteoporotic bone regeneration.

RNA-binding protein 39: a promising therapeutic target for cancer.

RNA-binding motif protein 39 (RBM39), as a key factor in tumor-targeted mRNA and protein expression, not only plays a vital role in tumorigenesis, but also has broad development prospects in clinical treatment and drug research. Moreover, since RBM39 was identified as a target of sulfonamides, it has played a key role in the emerging field of molecule drug development. Hence, it is of great significance to study the interaction between RBM39 and tumors and the clinical application of drug-targeted therapy. In this paper, we describe the possible multi-level regulation of RBM39, including gene transcription, protein translation, and alternative splicing. Importantly, the molecular function of RBM39 as an important splicing factor in most common tumors is systematically outlined. Furthermore, we briefly introduce RBM39's tumor-targeted drug research and its clinical application, hoping to give reference significance for the molecular mechanism of RBM39 in tumors, and provide reliable ideas for in-depth research for future therapeutic strategies.

LncRNA CASC15 promotes the proliferation of papillary thyroid carcinoma cells by regulating the miR-7151-5p/WNT7A axis.

Long noncoding RNAs (lncRNAs) play crucial roles in the regulation of human thyroid cancer (TC), including papillary thyroid carcinoma (PTC); PTC is the most common pathological subtype of TC. To date, the expression, function, and mechanism of the lncRNA CASC15 in PTC remain unclear. The present study results showed that CASC15 was overexpressed in PTC tissues compared with normal tissues and acted as a potent oncogene to promote the proliferation and tumorigenesis of PTC cells both in vitro and in vivo. Mechanistic studies demonstrated that CASC15 could serve as an endogenous miRNA sponge to absorb and downregulate miR-7151-5p, thereby preventing the inhibition of WNT7A during PTC progression. Furthermore, the study demonstrated that CASC15 activated the WNT/ß­catenin signaling pathway by upregulating WNT7A in PTC. Taken together, our findings identified CASC15 as a potential diagnostic marker or therapeutic target for PTC progression. DATA AVAILABILITY: Please contact the corresponding author for a data request.

Aberrant Bcl-x splicing in cancer: from molecular mechanism to therapeutic modulation.

Bcl-x pre-mRNA splicing serves as a typical example to study the impact of alternative splicing in the modulation of cell death. Dysregulation of Bcl-x apoptotic isoforms caused by precarious equilibrium splicing is implicated in genesis and development of multiple human diseases, especially cancers. Exploring the mechanism of Bcl-x splicing and regulation has provided insight into the development of drugs that could contribute to sensitivity of cancer cells to death. On this basis, we review the multiple splicing patterns and structural characteristics of Bcl-x. Additionally, we outline the cis-regulatory elements, trans-acting factors as well as epigenetic modifications involved in the splicing regulation of Bcl-x. Furthermore, this review highlights aberrant splicing of Bcl-x involved in apoptosis evade, autophagy, metastasis, and therapy resistance of various cancer cells. Last, emphasis is given to the clinical role of targeting Bcl-x splicing correction in human cancer based on the splice-switching oligonucleotides, small molecular modulators and BH3 mimetics. Thus, it is highlighting significance of aberrant splicing isoforms of Bcl-x as targets for cancer therapy.

The response of macrophages and their osteogenic potential modulated by micro/nano-structured Ti surfaces.

Current understanding on the interactions between micro/nano-structured Ti surfaces and macrophages is still limited. In this work, TiO2 nano-structures were introduced onto acid-etched Ti surfaces by alkali-heat treatment, ion exchange and subsequent heat treatment. By adjusting the concentration of NaOH during alkali-heat treatment, nano-flakes, nano-flakes mixed with nano-wires or nano-wires could formed on acid-etched Ti surfaces. The micro- and micro/nano-structured Ti surfaces possessed similar surface chemical and phase compositions. In vitro results indicate that the morphology of macrophages was highly dependent on the morphological features of nano-structures. Nano-flakes and nano-wires were favorable to induce the formation of lamellipodia and filopodia, respectively. Compared to micro-structured Ti surface, micro/nano-structured Ti surfaces polarized macrophages to their M2 phenotype and enhanced the gene expressions of osteogenic growth factors in macrophages. The M2 polarized macrophages promoted the maturation of osteoblasts. Compared to that with nano-flakes or nano-wires, the surface with mixed features of nano-flakes and nano-wires exhibited stronger anti-inflammatory and osteo-immunomodulatory effects. The findings presented in the current work suggest that introducing micro/nano-topographies onto Ti-based implant surfaces is a promising strategy to modulate the inflammatory response and mediate osteogenesis.