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Abstract Circadian rhythms are present in almost all cells and play a crucial role in regulating various biological processes. Maintaining a stable circadian rhythm is essential for overall health. Disruption of this rhythm can alter the expression of clock genes and cancer-related genes, and affect many metabolic pathways and factors, thereby affecting the function of the immune system and contributing to the occurrence and progression of tumors. This paper aims to elucidate the regulatory effects of BMAL1, clock and other clock genes on immune cells, and reveal the molecular mechanism of circadian rhythm’s involvement in tumor and its microenvironment regulation. A deeper understanding of circadian rhythms has the potential to provide new strategies for the treatment of cancer and other immune-related diseases.

Abstract Stem cells are pivotal players in the intricate dance of embryonic development, tissue maintenance, and regeneration. Their behavior is delicately balanced between maintaining their pluripotency and differentiating as needed. Disruptions in this balance can lead to a spectrum of diseases, underscoring the importance of unraveling the complex molecular mechanisms that govern stem cell fate. Forkhead box O (FOXO) proteins, a family of transcription factors, are at the heart of this intricate regulation, influencing a myriad of cellular processes such as survival, metabolism, and DNA repair. Their multifaceted role in steering the destiny of stem cells is evident, as they wield influence over self-renewal, quiescence, and lineage-specific differentiation in both embryonic and adult stem cells. This review delves into the structural and regulatory intricacies of FOXO transcription factors, shedding light on their pivotal roles in shaping the fate of stem cells. By providing insights into the specific functions of FOXO in determining stem cell fate, this review aims to pave the way for targeted interventions that could modulate stem cell behavior and potentially revolutionize the treatment and prevention of diseases.

In the present study, pre-deformation at liquid nitrogen temperature (77 K) was applied to introduce twins into Ti–Mo alloys with different contents of molybdenum. The microstructural evolution and mechanical properties with different cryogenic pre-deformation amounts (from 0 to 9 %) were characterized and analyzed. The results show that the twinning activities and the evolution of twinning systems are mainly influenced by β phase stability and cryogenic pre-deformation amount. After cryogenic pre-deformation, the primary and secondary twinning of {332}twins are observed in Ti–12Mo and Ti–15Mo alloys but absent in Ti–20Mo alloy. With the cryogenic pre-deformation amounts increasing, the width and quantity of twins increase constantly. Moreover, {112}twinning is activated in Ti–15Mo alloy pre-deformed by 6 % and 9 %. Twins and high-density dislocations induced by cryogenic pre-deformation cause a significant enhancement in strength of all these three alloys. However, the effect of cryogenic pre-deformation on the elongation of alloys is complicated. For Ti–12Mo alloys, the yield strength increases monotonically (from 527 to 778 MPa) with the increase of cryogenic pre-deformation reduction, while the elongation is completely opposite (from 47 to 20 %). For Ti–15Mo alloys, the optimal matching of strength and ductility is achieved when the amount of cryogenic pre-deformation is 6 %, with a tensile strength of 815 MPa and an elongation of 24 %. Compared with the other two alloys, Ti–20Mo alloy gets a smaller increase in strength and a slight decrease in elongation with the amount of cryogenic pre-deformation increasing.

This is an article in the field of mineral processing engineering. Chemical components, mineral compositions and embedded features of the low grade phosphate had been studied. The main valuable mineral in the ore was collophanite and the main gangue mineral was dolomite. The disseminated extents between valuable mineral and gangue mineral were very small so single reverse flotation method had been used in the article which could make the ore utilize by low lowcost. Through many tests and the beneficiation technological processes of the low grade phosphate had been ascertained that the grinding fineness was 65% below 0.074 mm, and once rougher flotation, twice well-chosen and twice scavenging, and the phosphorus ore concentrate had been gained which yield was 43.97%, P2O5 grade 33.86%, MgO grade 1.35% and the recovery of P2O5 was 81.84% when the raw ore’s P2O5 grade was 18.44% and MgO grade was 9.52%. In this way the cost was low and the low grade phosphate could be utilized effectively.

Introduction: Developmental engineering based on endochondral ossification has been proposed as a potential strategy for repairing of critical bone defects. Bone development is driven by growth plate-mediated endochondral ossification. Under physiological conditions, growth plate chondrocytes undergo compressive forces characterized by micro-mechanics, but the regulatory effect of micro-mechanical loading on endochondral bone formation has not been investigated.Methods: In this study, a periodic static compression (PSC) model characterized by micro-strain (with 0.5% strain) was designed to clarify the effects of biochemical/mechanical cues on endochondral bone formation. Hydrogel scaffolds loaded with bone marrow mesenchymal stem cells (BMSCs) were incubated in proliferation medium or chondrogenic medium, and PSC was performed continuously for 14 or 28 days. Subsequently, the scaffold pretreated for 28 days was implanted into rat femoral muscle pouches and femoral condylar defect sites. The chondrogenesis and bone defect repair were evaluated 4 or 10 weeks post-operation.Results: The results showed that PSC stimulation for 14 days significantly increased the number of COL II positive cells in proliferation medium. However, the chondrogenic efficiency of BMSCs was significantly improved in chondrogenic medium, with or without PSC application. The induced chondrocytes (ichondrocytes) spontaneously underwent hypertrophy and maturation, but long-term mechanical stimulation (loading for 28 days) significantly inhibited hypertrophy and mineralization in ichondrocytes. In the heterotopic ossification model, no chondrocytes were found and no significant difference in terms of mineral deposition in each group; However, 4 weeks after implantation into the femoral defect site, all scaffolds that were subjected to biochemical/mechanical cues, either solely or synergistically, showed typical chondrocytes and endochondral bone formation. In addition, simultaneous biochemical induction/mechanical loading significantly accelerated the bone regeneration.Discussion: Our findings suggest that microstrain mechanics, biochemical cues, and in vivo microenvironment synergistically regulate the differentiation fate of BMSCs. Meanwhile, this study shows the potential of micro-strain mechanics in the treatment of critical bone defects.

This is a paper in the field of mineral processing engineering. The mineral characteristics of a vanadium titanium iron concentrate sample from Panxi were studied using sieve analysis, polarizing microscope, X-ray diffractometer, Zeiss Sigma 500 scanning electron microscope, Bruker energy spectrometer, and AMICS automatic mineral analysis system. The main gangue minerals in the sample are magnetite pyrite, granular ilmenite, pyroxene, feldspar, etc. The contents of coarse and fine products TFe, S, SiO2, Al2O3, MgO, and gangue minerals are quite different. A small amount of Fe exists in ilmenite, magnetic pyrite, and non-metallic minerals. Ti mainly exists in the form of titanium magnetite. ilmenite and magnesium aluminum spinel are inlaid on the base of titanium magnetite in lamellar, veinlet, thin strip, grid, and needle shapes, The particle size of the guest crystal mineral is very fine, making it difficult to grind, separate, and post treat the product. The use of grinding magnetic separation can increase the TFe grade of vanadium titanium iron concentrate by 2-3 percentage points. The essence of the improvement is a significant decrease in the content of SiO2, Al2O3, and MgO in the concentrate, with a decrease of SiO2>MgO>Al2O3. The TiO2 content of the concentrate does not change much during the improvement process, with Fe/TiO2 increasing from 4.29 to 4.50, V2O5 grade slightly increasing, and S grade slightly decreasing.

BackgroundThe complex anatomical structure of the upper thoracic spine makes it challenging to achieve surgical exposure, resulting in significant surgical risks and difficulties. Posterior surgery alone fails to adequately address and reconstruct upper thoracic lesions due to limited exposure. While the anterior approach offers advantages in fully exposing the anterior thoracic lesions, the surgical procedure itself is highly intricate. Although there exist various anterior approaches for the upper thoracic spine, the incidence of upper thoracic spine lesions is relatively low. Consequently, there are limited reports on the treatment and reconstruction of upper thoracic spine lesions using the third rib small incision approach in the context of upper thoracic tuberculosis.MethodsWe collected data from four patients with upper thoracic tuberculosis who were admitted to our department between July 2017 and November 2022. The treatment for upper thoracic tuberculosis involved utilizing the third rib small incision approach, which included two cases of thoracic 3–4 vertebral tuberculosis, one case of thoracic 4 vertebral tuberculosis, and one case of thoracic 5 vertebral tuberculosis. Among the patients, three were positioned in the left lateral position, while one was positioned in the right lateral position. Prior to admission, all four patients received a two-week course of oral medication, consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol. After the surgical procedure, they continued receiving anti-tuberculosis treatment for a duration of 12 months.ResultsThe average duration of the surgical procedure was 150 min, with an average blood loss of 500 ml. One patient exhibited symptoms of brachial plexus injury, which gradually improved after careful observation. All patients experienced primary wound healing, and no complications such as pulmonary infection, respiratory failure, or other adverse events were observed. Additionally, one patient showed elevated transaminase levels, leading to a modification in the anti-tuberculosis drug regimen from quadruple therapy to triple therapy.ConclusionThe treatment of upper thoracic tuberculosis through the third rib small incision technique is a very good surgical approach, which has the advantages of safety and effectiveness.

Abstract Background Repair pathway genes play an important role in the development of lung cancer. The study aimed to assess the correlation between single nucleotide polymorphisms (SNPs) in DNA repair gene (GTF2H1 and RAD54L2) and the risk of lung cancer. Methods Five SNPs in GTF2H1 and four SNPs in RAD54L2 in 506 patients with lung cancer and 510 age-and gender-matched healthy controls were genotyped via the Agena MassARRAY platform. The influence of GTF2H1 and RAD54L2 polymorphisms on lung cancer susceptibility was assessed using logistic regression analysis by calculating odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Results RAD54L2 rs9864693 GC genotype increased the risk of lung cancer (OR = 1.33, 95%CI: 1.01–1.77, p = 0.045). Stratified analysis found that associations of RAD54L2 rs11720298, RAD54L2 rs4687592, RAD54L2 rs9864693 and GTF2H1 rs4150667 with lung cancer risk were found in subjects aged ≤ 59 years. Precisely, a protective effect of RAD54L2 rs11720298 on the occurrence of lung cancer was observed in non-smokers and drinkers. GTF2H1 rs4150667 was associated with a decreased risk of lung cancer in subjects with BMI ≤ 24 kg/m2. RAD54L2 rs4687592 was associated with an increased risk of lung cancer in drinkers. In addition, GTF2H1 rs3802967 was associated with a reduced risk of lung squamous cell carcinoma. Conclusion Our study first revealed that RAD54L2 rs9864693 was associated with an increased risk of lung cancer in the Chinese Han population. This study may increase the understanding of the effect of RAD54L2 and GTF2H1 polymorphisms on lung cancer occurrence.

Abstract Ferroptosis, a novel regulated cell death induced by iron-dependent lipid peroxidation, plays an important role in tumor development and drug resistance. Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumorigenesis remain elusive. Here we explored the transcriptomic profiles of lncRNAs in primary CRC tissues and corresponding paired adjacent non-tumor tissues by RNA-seq and found that LINC00239 was significantly overexpressed in colorectal cancer tissues. Abnormally high expression of LINC00239 predicts poorer survival and prognosis in colorectal cancer patients. Concurrently, we elucidated the role of LINC00239 as a tumor-promoting factor in CRC through in vitro functional studies and in vivo tumor xenograft models. Importantly, overexpression of LINC00239 decreased the anti-tumor activity of erastin and RSL3 by inhibiting ferroptosis. Collectively, these data suggest that LINC00239 plays a novel and indispensable role in ferroptosis by nucleotides 1–315 of LINC00239 to interact with the Kelch domain (Nrf2-binding site) of Keap1, inhibiting Nrf2 ubiquitination and increasing Nrf2 protein stability. Considering the recurrence and chemoresistance constitute the leading cause of death in colorectal cancer (CRC), ferroptosis induction may be a promising therapeutic strategy for CRC patients with low LINC00239 expression.

Copper is a vital trace metal in human body, which plays the significant roles in amounts of physiological and pathological processes. The application of copper-selective probe has attracted great interests from environmental tests to life process research, yet a few of sensitive Cu2+ tests based on on-site analysis have been reported. In this paper, a novel fluorescein-based fluorescent probe N4 was designed, synthesized, and characterized, which exhibited high selectivity and sensitivity to Cu2+ comparing with other metal ions in ethanol–water (1/1, v/v) solution. The probe N4 bonded with Cu2+ to facilitate the ring-opening, and an obvious new band at 525 nm in the fluorescence spectroscopy appeared, which could be used for naked-eye detection of Cu2+ within a broad pH range of 6–9. Meanwhile, a good linearity between the fluorescence intensity and the concentrations of Cu2+ ranged 0.1–1.5 eq. was observed, and the limit of detection of N4 to Cu2+ was calculated to be as low as 1.20 μm. In addition, the interaction mode between N4 and Cu2+ was found to be 1:1 by the Job's plot and mass experiment. Biological experiments showed that the probe N4 exhibited low biological toxicity and could be applied for Cu2+ imaging in living cells. The significant color shift associated with the production of the N4-Cu2+ complex at low micromolar concentrations under UV light endows N4 with a promising probe for field testing of trace Cu2+ ions.

Silk fibroin (SF) is considered biocompatible and biodegradable for osteochondral repair. However, it lacks a bioactive domain for cell adhesion, proliferation and differentiation, limiting its therapeutic efficacy. To revamp SF as a biomimicking and bioactive microenvironment to regulate cell behaviours, we engineered an elastin-like polypeptide (ELP, Val-Pro-Gly-Xaa-Gly) to modify SF fibers via simple and green dehydrothermal (DHT) treatment. Our results demonstrated that the ELP successfully bound to SF, and the scaffold was reinforced by the fusion of the silk fiber intersections with ELP (S-ELP-DHT) via the DHT treatment. Both bone mesenchymal stem cells (BMSCs) and chondrocytes exhibited improved spreading and proliferation on the S-ELP-DHT scaffolds. The ex vivo and in vivo experiments further demonstrated enhanced mature bone and cartilage tissue formation using the S-ELP-DHT scaffolds compared to the naked SF scaffolds. These results indicated that a recombinant ELP-modified silk scaffold can mimic three-dimensional (3D) cell microenvironment, and improve bone and cartilage regeneration. We envision that our scaffolds have huge clinical potential for osteochondral repair.

Mineral classification is an important preparation operation in the process of beneficiation. The classification effect directly affects the production capacity of grinding machines, product quality, subsequent separation of the concentrate grade, and recovery. To improve mineral classification accuracy and provide technical ideas for enriching the separation of fine materials, this paper proposes the use of a trapezoidal inclined channel agitated reflux classifier (TARC) to classify ultra-fine ilmenite. The principle of this separating system is based on a hindered settling effect and fluidization theory. This study focuses on the factors influencing the particle separation through the optimization of different experimental conditions. A satisfactory 10 µm classification efficiency of 67.89% could be obtained when the ore pulp concentration was 15%, the agitation speed was 350 r/min, and the underflow flux was 16 cm3/min. The TARC realized a continuous feeding classification of fine particles within a narrow particle size range, with 10 µm as the limit size, and an effective reduction in the entrainment of fine particles in the underflow and coarse particles in the overflow phenomena, thus achieving improved classification efficiency.

Background: Lung cancer is the leading source of cancer-caused disability-adjusted life years. Medical cost burden impacts the well-being of patients through reducing income, cutting daily expenses, curtailing leisure activities, and depleting exhausting savings. The COmprehensive Score for Financial Toxicity (COST) was created and validated by De Souza and colleagues. Our study intends to measure the financial burdens of cancer therapy and investigate the link between financial toxicity and health-related quality of life (HRQoL) in an advanced lung cancer population.Methods: Patients aged ≥ 18 years with confirmed stage III to IV lung cancer were eligible. The COST questionnaire verified by de Souza et al. was used to identify financial toxicity. Multivariable linear regression analysis with log transformation univariate analysis and Pearson correlations were used to perform the analysis.Results: The majority of the patients (90.8%, n = 138/152) had an annual income of $50,000 ($7,775). The cohort's insurance situation was as follows: 64.5% of the cohort had social insurance, 20.4% had commercial insurance, and 22.0% had both. Patients who were younger age (50–59, P < 0.001), employed but on sick leave, and had lower income reported increased levels of financial toxicity (P < 0.05). The risk factors for high financial toxicity: (i) younger age (50–59), (ii)

Phosphatidylinositol 3-kinase (PI3K) signaling plays a central role in various biological processes, and its abnormality leads to a broad spectrum of human diseases, such as cancer, fibrosis, and immunological disorders. However, the mechanisms by which PI3K signaling regulates the behavior of stem cells during regeneration are poorly understood. Planarian flatworms possess abundant adult stem cells (called neoblasts) allowing them to develop remarkable regenerative capabilities, thus the animals represent an ideal model for studying stem cells and regenerative medicine in vivo. In this study, the spatiotemporal expression pattern of Djpi3k, a PI3K ortholog in the planarian Dugesia japonica, was investigated and suggests its potential role in wound response and tissue regeneration. A loss-of-function study was conducted using small molecules and RNA interference technique, providing evidence that PI3K signaling is required for blastema regrowth and cilia maintenance during planarian regeneration and homeostasis. Interestingly, the mitotic and apoptotic responses to amputation are substantially abated in PI3K inhibitor-treated regenerating animals, while knockdown of Djpi3k alleviates the mitotic response and postpones the peak of apoptotic cell death, which may contribute to the varying degrees of regenerative defects induced by the pharmacological and genetic approaches. These observations reveal novel roles for PI3K signaling in the regulation of the cellular responses to amputation during planarian regeneration and provide insights for investigating the disease-related genes in the regeneration-competent organism in vivo.

Protein glycosylation is an important posttranslational modification that plays a crucial role in cellular function. However, its biological roles in tissue regeneration remain interesting and primarily ambiguous. In this study, we profiled protein glycosylation during head regeneration in planarian Dugesia japonica using a lectin microarray. We found that 6 kinds of lectins showed increased signals and 16 kinds showed decreased signals. Interestingly, we found that protein core fucosylation, manifested by Lens culinaris agglutinin (LCA) staining, was significantly upregulated during planarian head regeneration. Lectin histochemistry indicated that the LCA signal was intensified within the wound and blastemal areas. Furthermore, we found that treatment with a fucosylation inhibitor, 2F-peracetyl-fucose, significantly retarded planarian head regeneration, while supplement with L-fucose could improve DjFut8 expression and stimulate planarian head regeneration. In addition, 53 glycoproteins that bound to LCA were selectively isolated by LCA-magnetic particle conjugates and identified by LC-MS/MS, including the neoblast markers DjpiwiA, DjpiwiB, DjvlgA, and DjvlgB. Overall, our study provides direct evidence for the involvement of protein core fucosylation in planarian regeneration.

Copper is an important trace element that plays a crucial role in various physiological and biochemical processes in the body. The level of copper content is significantly related to many diseases, so it is very important to establish effective and sensitive methods for copper detection in vitro and vivo. Copper-selective probes have attracted considerable interest in environmental testing and life-process research, but fewer investigations have focused on the luminescence mechanism and bioimaging for Cu2+ detection. In the current study, a novel fluorescein-based A5 fluorescence probe is synthesized and characterized, and the bioimaging performance of the probe is also tested. We observed that the A5 displayed extraordinary selectivity and sensitivity properties to Cu2+ in contrast to other cations in solution. The reaction between A5 and Cu2+ could accelerate the ring-opening process, resulting in a new band at 525 nm during a larger pH range. A good linearity between the fluorescence intensity and concentrations of Cu2+, ranging from 0.1 to 1.5 equivalent, was observed, and the limit detection of A5 to Cu2+ was 0.11 μM. In addition, the Job’s plot and mass spectrum showed that A5 complexed Cu2+ in a 1:1 manner. The apparent color change in the A5–Cu2+ complex under ultraviolet light at low molar concentrations revealed that A5 is a suitable probe for the detection of Cu2+. The biological test results show that the A5 probe has good biocompatibility and can be used for the cell imaging of Cu2+.

Skin wound repair remains a major challenge in clinical care, and various strategies have been employed to improve the repair process. Recently, it has been reported that macrophages are important for the regeneration of various tissues and organs. However, their influence on wound repair is unclear. Here, we aimed to explore whether macrophages would participate in the wound healing process and to explore new possibilities of treatment for skin defects. We firstly created a mouse full-thickness skin defect model to observe the distribution of macrophages in the regenerating tissue and then detected the influence of macrophages on skin defect repair in both macrophage-depletion and macrophage-mobilization models. We found that the number of macrophages increased significantly after skin defect and persisted during the process of wound repair. The regeneration process was significantly prolonged in macrophage-depleted animals. RT-qPCR and ELISA assays further demonstrated that the expression of growth factors was perturbed in the regenerating tissue. The activation of macrophages by granulocyte-macrophage colony-stimulating factor (GM-CSF) injection could significantly improve wound healing, accompanied with an upregulation of the expression of various growth factors. In conclusion, the current study demonstrated that macrophages are critical for skin regeneration and that GM-CSF exhibited therapeutic potential for wound healing.

Abstract Background Safe and effective hemostatic materials are important for reducing mortality resulting from excessive hemorrhage. In this work, new biomaterials with hemostatic effects were created by fusing the gene coding for RADA-16, a self-assembling peptide with the sequence RADARADARADARADA, to the 3′-end of the open reading frame (ORF) encoding elastin-like polypeptides through gene recombination. Results The fusion proteins, termed 36R, 60R and 96R, were solubly over-expressed in Escherichia coli BL21 (DE3) based on genetic manipulation of the high-efficiency prokaryotic expression vector pET28a (+) and bacterial transformation. Western Blot analysis showed that the over-expressed proteins were the target fusion proteins. The target proteins 36R with 94.72% purity, 60R with 96.91% purity and 96R with 96.37% purity were prepared using an inverse phase transition cycle at 65 °C followed by His-tag affinity chromatography. The proliferation results of the mouse fibroblast cell line L929 and hippocampus neuron cell line HT22 indicated that the fusion proteins did not cause obvious cell toxicity. The lyophilized spongy film of the purified 36R, 60R and 96R could stop the hemorrhage of a 2 × 2 mm bleeding wound in the mouse liver after 27.21 ± 1.92 s, 18.65 ± 1.97 s and 15.85 ± 1.21 s, respectively. The hemostasis time was 21.23 ± 1.84 s for rat-tail collagen and 14.44 ± 1.33 s for RADA-16 lyophilized on gauze. The hemostatic time of three treated groups were all significantly superior to that of the negative control without any hemostasis treatment, which spontaneously stopped bleeding after 37.64 ± 1.34 s. Statistical analysis showed that the spongy film with purified 96R exhibited an exciting hemostatic effect that was superior to rat-tail collagen and close to that of RADA-16 lyophilized on gauze. Conclusions These results revealed that the fusion proteins achieved by gene recombination technology could serve as a promising hemostatic material.

Abstract Growth arrest-specific 6, also known as Gas6, is a human gene encoding the Gas6 protein, which was originally found to be upregulated in growth-arrested fibroblasts. Gas6 is a member of the vitamin K-dependent family of proteins expressed in many human tissues and regulates several biological processes in cells, including proliferation, survival and migration, by binding to its receptors Tyro3, Axl and Mer (TAM). In recent years, the roles of Gas6/TAM signalling in cancer cells and the tumour microenvironment have been studied, and some progress has made in targeted therapy, providing new potential directions for future investigations of cancer treatment. In this review, we introduce the Gas6 and TAM receptors and describe their involvement in different cancers and discuss the roles of Gas6 in cancer cells, the tumour microenvironment and metastasis. Finally, we introduce recent studies on Gas6/TAM targeting in cancer therapy, which will assist in the experimental design of future analyses and increase the potential use of Gas6 as a therapeutic target for cancer.

Abstract Background Salamanders regenerate their limbs after amputation. However, the molecular mechanism of this unique regeneration remains unclear. In this study, isobaric tags for relative and absolute quantification (iTRAQ) coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to quantitatively identify differentially expressed proteins in regenerating limbs 3, 7, 14, 30 and 42 days post amputation (dpa). Results Of 2636 proteins detected in total, 253 proteins were differentially expressed during different regeneration stages. Among these proteins, Asporin, Cadherin-13, Keratin, Collagen alpha-1(XI) and Titin were down-regulated. CAPG, Coronin-1A, AnnexinA1, Cathepsin B were up-regulated compared with the control. The identified proteins were further analyzed to obtain information about their expression patterns and functions in limb regeneration. Functional analysis indicated that the differentially expressed proteins were associated with wound healing, immune response, cellular process, metabolism and binding. Conclusions This work indicated that significant proteome alternations occurred during salamander limb regeneration. The results may provide fundamental knowledge to understand the mechanism of limb regeneration.

Abstract Background Embryonic stem cell (ESC) derivatives hold great promise for the construction of tissue-engineered skin equivalents (TESE). However, harvesting of ESCs destroys viable embryos and may lead to political and ethical concerns over their application. In the current study, we directed mouse parthenogenetic embryonic stem cells (pESCs) to differentiate into fibroblasts, constructed TESE, and evaluated its function in vivo. Methods The stemness marker expression and the pluripotent differentiation ability of pESCs were tested. After embryoid body (EB) formation and adherence culture, mesenchymal stem cells (MSCs) were enriched and directed to differentiate into fibroblastic lineage. Characteristics of derived fibroblasts were assessed by quantitative real-time PCR and ELISA. Functional ability of the constructed TESE was tested by a mouse skin defects repair model. Results Mouse pESCs expressed stemness marker and could form teratoma containing three germ layers. MSCs could be enriched from outgrowths of EBs and directed to differentiate into fibroblastic lineage. These cells express a high level of growth factors including FGF, EGF, VEGF, TGF, PDGF, and IGF1, similar to those of ESC-derived fibroblasts and mouse fibroblasts. Seeded into collagen gels, the fibroblasts derived from pESCs could form TESE. Mouse skin defects could be successfully repaired 15 days after transplantation of TESE constructed by fibroblasts derived from pESCs. Conclusions pESCs could be induced to differentiate into fibroblastic lineage, which could be applied to the construction of TESE and skin defect repair. Particularly, pESC derivatives avoid the limitations of political and ethical concerns, and provide a promising source for regenerative medicine.

Pseudomonas aeruginosa DN1, isolated from petroleum-contaminated soil, showed excellent degradation ability toward diverse polycyclic aromatic hydrocarbons (PAHs). Many studies have been done to improve its degradation ability. However, the molecular mechanisms of PAHs degradation in DN1 strain are unclear. In this study, the whole genome of DN1 strain was sequenced and analyzed. Its genome contains 6,641,902 bp and encodes 6,684 putative open reading frames (ORFs), which has the largest genome in almost all the comparative Pseudomonas strains. Results of gene annotation showed that this strain harbored over 100 candidate genes involved in PAHs degradation, including those encoding 25 dioxygenases, four ring-hydroxylating dioxygenases, five ring-cleaving dioxygenases, and various catabolic enzymes, transcriptional regulators, and transporters in the degradation pathways. In addition, gene knockout experiments revealed that the disruption of some key PAHs degradation genes in DN1 strain, such as catA, pcaG, pcaH, and rhdA, did not completely inhibit fluoranthene degradation, even though their degradative rate reduced to some extent. Three intermediate metabolites, including 9-hydroxyfluorene, 1-acenaphthenone, and 1, 8-naphthalic anhydride, were identified as the dominating intermediates in presence of 50 μg/mL fluoranthene as the sole carbon source according to gas chromatography mass spectrometry analysis. Taken together, the genomic and metabolic analysis indicated that the fluoranthene degradation by DN1 strain was initiated by dioxygenation at the C-1, 2-, C-2, 3-, and C-7, 8- positions. These results provide new insights into the genomic plasticity and environmental adaptation of DN1 strain.

c-Fos is an immediate-early gene that modulates cellular responses to a wide variety of stimuli and also plays an important role in tissue regeneration. However, the sequence and functions of c-Fos are still poorly understood in newts. This study describes the molecular cloning and characterization of the c-Fos gene (Co-c-Fos) of the Chinese fire-bellied newt, Cynops orientalis. The full-length Co-c-Fos cDNA sequence consists of a 1290 bp coding sequence that encoded 429 amino acids. The alignment and phylogenetic analyses reveal that the amino acid sequence of Co-c-Fos shared a conserved basic leucine zipper domain, including a nuclear localization sequence and a leucine heptad repeat. The Co-c-Fos mRNA is widely expressed in various tissues and is highly and uniformly expressed along the newt limb. After limb amputation, the expression of Co-c-Fos mRNA was immediately upregulated, but rapidly declined. However, the significant upregulation of Co-c-Fos protein expression was sustained for 24 h, overlapping with the wound healing stage of C. orientalis limb regeneration. To investigate if Co-c-Fos participate in newt wound healing, a skin wound healing model is employed. The results show that the treatment of T-5224, a selective c-Fos inhibitor, could largely impair the healing process of newt’s skin wound, as well as the injury-induced matrix metalloproteinase-3 upregulation, which is fundamental to wound epithelium formation. These data suggest that Co-c-Fos might participate in wound healing by modulating the expression of its potential target gene matrix metalloproteinase-3. Our study provides important insights into mechanisms that are responsible for the initiation of newt limb regeneration.

Forkhead box C1 (FOXC1) is an essential member of the forkhead box transcription factors and has been highlighted as an important transcriptional regulator of crucial proteins associated with a wide variety of carcinomas. FOXC1 regulates tumor-associated genes and is regulated by multiple pathways that control its mRNA expression and protein activity. Aberrant FOXC1 expression is involved in diverse tumorigenic processes, such as abnormal cell proliferation, cancer stem cell maintenance, cancer migration, and angiogenesis. Herein, we review the correlation between the expression of FOXC1 and tumor behaviors. We also summarize the mechanisms of the regulation of FOXC1 expression and activity in physiological and pathological conditions. In particular, we focus on the pathological processes of cancer targeted by FOXC1 and discuss whether FOXC1 is good or detrimental during tumor progression. Moreover, FOXC1 is highlighted as a clinical biomarker for diagnosis or prognosis in various human cancers. The information reviewed here should assist in experimental designs and emphasize the potential of FOXC1 as a therapeutic target for cancer.

Designing the “ideal” hydrogel/matrix which can load bone morphogenetic protein-2 (BMP-2) in a low dose and with a sustained release is the key for its successful therapeutic application to enhance osteogenesis. The current use of natural collagen sponges as hydrogel/matrix is limited due to the collagen matrix showing weak mechanical strength and unmanageable biodegradability. Furthermore, the efficiency and safe dose usage of the BMP-2 has never been seriously considered other than purely chasing the lowest dose usage and extended-release time. In this paper, we customized a novel enzymatically cross-linked recombinant human-like collagen (HLC) sponge with low immunogenicity, little risk from hidden viruses, and easy production. We obtained a unique vertical pore structure and the porosity of the HLC, which are beneficial for Mesenchymal stem cells (MSCs) migration into the HLC sponge and angiopoiesis. This HLC sponge loading with low dose BMP-2 (1 µg) possessed high mechanical strength along with a burst and a sustained release profile. These merits overcome previous limitations of HLC in bone repair and are safer and more sensitive than commercial collagens. For the first time, we identified that a 5 µg dose of BMP-2 can bring about the side effect of bone overgrowth through this sensitive delivery system. Osteoinduction of the HLC-BMP sponges was proved by an in vivo mouse ectopic bone model and a rat cranial defect repair model. The method and the HLC-BMP sponge have the potential to release other growth factors and aid other tissue regeneration. Additionally, the ability to mass-produce HLC in our study overcomes the current supply shortage, which limits bone repair in the clinic.

Tight oil has been effectively developed thanks to artificial fracture technology. The basic mechanism of effective production through fractures lies in the contact between the fractures (both natural and artificial) and the matrix. In this paper, the natural tight cores from J field in China are used to conduct experimental studies on the different fluid huff-‘n-puff process. A new core-scale fracture lab-simulation method is proposed. Woven metallic wires were attached to the outer surface of the core to create a space between the core holder and core as a high permeable zone, an equivalent fracture. Three different injecting fluids are used, including CO2, N2 and water. The equivalent core scale reservoir numerical models in depletion and huff-n-puff mode are then restored by numerical simulation with the Computer Modeling Group—Compositional & Unconventional Reservoir Simulator (CMG GEM). Simulation cases with eight different fracture patterns are used in the study to understand how fracture mechanistically impact Enhanced Oil Recovery (EOR) in huff n puff mode for the different injected fluids. The results showed: Firstly, regardless of the arrangement of fractures, CO2 has mostly obvious advantages over water and N2 in tight reservoir development in huff-‘n-puff mode. Through EOR mechanism analysis, CO2 is the only fluid that is miscible with oil (even 90% mole fraction CO2 is dissolved in the oil phase), which results in the lowest oil phase viscosity. The CO2 diffusion mechanism is also pronounced in the huff-‘n-puff process. Water may impact on the oil recovery through gravity and the capillary force imbibition effect. N2, cannot recover more crude oil only by elasticity and swelling effects. Secondly, the fracture arrangement in space has the most impact on CO2 huff-‘n-puff, followed by water and finally N2. The fractures primarily supply more efficient and convenient channels and contact relationships. The spatial arrangement of fractures mainly impacts the performance of CO2 through viscosity reduction in the contact between CO2 and crude oil. Similarly, the contact between water in fractures and crude oil in the matrix is also the key to imbibition. In the process of N2 huff-‘n-puff, the elasticity energy is dominant and fracture arrangement in space hardly to improve oil recovery. In addition, when considering anisotropy, water huff-‘n-puff is more sensitive to it, while N2 and CO2 are not. Finally, comparing the relationship between fracture contact area and oil recovery, oil production is insensitive to contact area between fracture and matrix for water and N2 cases.

The selection of appropriate seed cells is crucial for adipose tissue engineering. Here, we reported the stepwise induction of parthenogenetic embryonic stem cells (pESCs) to differentiate into adipogenic cells and its application in engineering injectable adipose tissue with Pluronic F-127. pESCs had pluripotent differentiation capacity and could form teratomas that include the three primary germ layers. Cells that migrated from the embryoid bodies (EBs) were selectively separated and expanded to obtain embryonic mesenchymal stem cells (eMSCs). The eMSCs exhibited similar cell surface marker expression profiles with bone morrow mesenchymal stem cells (BMSCs) and had multipotent differentiation capacity. Under the induction of dexamethasone, indomethacin, and insulin, eMSCs could differentiate into adipogenic cells with increased expression of adipose-specific genes and oil droplet depositions within the cytoplasm. To evaluate their suitability as seed cells for adipose tissue engineering, the CM-Dil labelled adipogenic cells derived from eMSCs were seeded into Pluronic F-127 hydrogel and injected subcutaneously into nude mice. Four weeks after injection, glistering and semitransparent constructs formed in the subcutaneous site. Histological observations demonstrated that new adipose tissue was successfully fabricated in the specimen by the labelled cells. The results of the current study indicated that pESCs have great potential in the fabrication of injectable adipose tissue.

Abstract The emergence of Li–Mg hybrid batteries has been receiving attention, owing to their enhanced electrochemical kinetics and reduced overpotential. Nevertheless, the persistent challenge of uneven Mg electrodeposition remains a significant impediment to their practical integration. Herein, we developed an ingenious approach that centered around epitaxial electrocrystallization and meticulously controlled growth of magnesium crystals on a specialized MgMOF substrate. The chosen MgMOF substrate demonstrated a robust affinity for magnesium and showed minimal lattice misfit with Mg, establishing the crucial prerequisites for successful heteroepitaxial electrocrystallization. Moreover, the incorporation of periodic electric fields and successive nanochannels within the MgMOF structure created a spatially confined environment that considerably promoted uniform magnesium nucleation at the molecular scale. Taking inspiration from the “blockchain” concept prevalent in the realm of big data, we seamlessly integrated a conductive polypyrrole framework, acting as a connecting “chain,” to interlink the “blocks” comprising the MgMOF cavities. This innovative design significantly amplified charge‐transfer efficiency, thereby increasing overall electrochemical kinetics. The resulting architecture (MgMOF@PPy@CC) served as an exceptional host for heteroepitaxial Mg electrodeposition, showcasing remarkable electrostripping/plating kinetics and excellent cycling performance. Surprisingly, a symmetrical cell incorporating the MgMOF@PPy@CC electrode demonstrated impressive stability even under ultrahigh current density conditions (10 mA cm–2), maintaining operation for an extended 1200 h, surpassing previously reported benchmarks. Significantly, on coupling the MgMOF@PPy@CC anode with a Mo6S8 cathode, the assembled battery showed an extended lifespan of 10,000 cycles at 70 C, with an outstanding capacity retention of 96.23%. This study provides a fresh perspective on the rational design of epitaxial electrocrystallization driven by metal–organic framework (MOF) substrates, paving the way toward the advancement of cutting‐edge batteries.