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Abstract Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration.

Abstract This study aims to evaluate the role of trefoil factor 3 (TFF3) peptides in type 2 diabetes mellitus (T2DM) from an inflammatory perspective. The focus was on exploring how TFF3 affects the function of T cells. TFF3 overexpression model was constructed using lentivirus in Jurkat cell lines. We evaluated the impact of TFF3 on the proliferation, apoptosis, and IL-17A levels of Jurkat cells cultured in high glucose. The T2DM model was induced in TFF3 knockout (KO) mice through streptozotocin combined with high-fat diet. The measurements included glucose tolerance, insulin tolerance, inflammation markers, Th17 cell proportion, and pancreatic pathological changes. The T2DM modeling led to splenomegaly in mice, and increased expression of TFF3 in their spleens. Overexpression of TFF3 increased the proportion of IL-17+ T cells and the levels of Th17-related cytokines in Jurkat cells. There was no difference in body weight and blood glucose levels between wild-type and TFF3 KO mice. However, T2DM mice lacking the TFF3 gene showed improved glucose utilization, ameliorated pancreatic pathology, decreased inflammation levels, and reduced Th17 cell ratio. TFF3 may be involved in the chronic inflammatory immune response in T2DM. Its mechanism may be related to the regulation of the RORγt/IL-17 signaling pathway and its impact on T cell proliferation and apoptosis.

Abstract Low-dimensional materials exhibit unique quantum confinement effects and morphologies as a result of their nanoscale size in one or more dimensions, making them exhibit distinctive physical properties compared to bulk counterparts. Among all low-dimensional materials, due to their atomic level thickness, two-dimensional materials possess extremely large shape anisotropy and consequently are speculated to have large optically anisotropic absorption. In this work, we demonstrate an optoelectronic device based on the combination of two-dimensional material and carbon dot with wide bandgap. High-efficient luminescence of carbon dot and extremely large shape anisotropy (>1500) of two-dimensional material with the wide bandgap of >4 eV cooperatively endow the optoelectronic device with multi-functions of optically anisotropic blue-light emission, visible light modulation, wavelength-dependent ultraviolet-light detection as well as blue fluorescent film assemble. This research opens new avenues for constructing multi-function-integrated optoelectronic devices via the combination of nanomaterials with different dimensions.

This study applies a transformative sport service research approach to examine student-athletes’ wellness within a collegiate sport setting. Sixteen semi-structured interviews were completed during the COVID-19 pandemic and the stop of play in Canada (early 2021). Findings denoted wellness was influenced by this time period as well as organizational factors which are within the purview of existing management practices. The study details the service environment to understand physical and mental well-being while taking into consideration the general and organizational environments which influence the student-athletes. Findings demonstrate that eudaimonic-related experiences (e.g., learning, development, relationship) are related to student-athletes' mental well-being. This research underpins the role of education, policies, and communication, which draws several implications for the service environment in a collegiate sport setting and the key stakeholders involved in producing an environment to enhance student-athletes’ experience. The paper elaborates on the importance of the service environment and provides evidence of what student-athletes suggest management can change and focus their efforts on towards creating a transformative service environment. Theoretical implications for the transformative service research are put forward, including the co-creative aspects to determine programming which could contribute towards student-athletes wellness. Broader suggestions for change within the sport system and future research are also advanced.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide, but current treatment options remain limited and cause serious life-threatening side effects. Aberrant FGFR4 signaling has been validated as an oncogenic driver of HCC, and EZH2, the catalytic subunit of the PRC2 complex, is a potential factor that contributes to acquired drug resistance in many tumors, including HCC. However, the functional relationship between these two carcinogenic factors, especially their significance for HCC treatment, remains unclear. In this study, we systematically evaluated the feasibility of a combination therapy targeting FGFR4 and EZH2 for HCC. Methods RNA sequencing data of patients with Liver hepatocellular carcinoma (LIHC) from The Cancer Genome Atlas (TCGA) were analyzed to determine FGFR4 and EZH2 expression and their interaction with prognosis. Moreover, the HCC cell lines, zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors were treated with FGFR4 inhibitor (Roblitinib) and/or EZH2 inhibitor (CPI-169) and then subjected to cell proliferation, viability, apoptosis, and tumor growth analyses to evaluate the feasibility of combination therapy for HCC both in vitro and in vivo. Furthermore, RNA-Seq was performed in combination with ChIP-Seq data analysis to investigate the critical mechanism underlying the combination treatment with Roblitinib and CPI-169. Results EZH2 accumulated through the non-canonical NF-kB signaling in response to FGFR4 inhibitor treatment, and the elevated EZH2 levels led to the antagonism of HCC against Roblitinib (FGFR4 inhibitor). Notably, knockdown of EZH2 sensitized HCC cells to Roblitinib, while the combination treatment of Roblitinib and CPI-169 (EZH2 inhibitor) synergistically induced the HCC cell apoptosis in vitro and suppressed the zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors development in vivo. Moreover, Roblitinib and CPI-169 synergistically inhibited HCC development via repressing YAP signaling. Conclusions Collectively, our study highlighted the potential of the therapeutic combination of FGFR4 and EZH2 inhibitors, which would provide new references for the further development of clinical treatment strategies for HCC.

Abstract Background Although biomedical implants have been widely used in orthopedic treatments, two major clinical challenges remain to be solved, one is the bacterial infection resulting in biofilm formation, and the other is aseptic loosening during implantation due to over-activated osteoclastogenesis. These factors can cause many clinical issues and even lead to implant failure. Thus, it is necessary to endow implants with antibiofilm and aseptic loosening-prevention properties, to facilitate the integration between implants and bone tissues for successful implantation. To achieve this goal, this study aimed to develop a biocompatible titanium alloy with antibiofilm and anti-aseptic loosening dual function by utilizing gallium (Ga) as a component. Methods A series of Ti-Ga alloys were prepared. We examined the Ga content, Ga distribution, hardness, tensile strength, biocompatibility, and anti-biofilm performance in vitro and in vivo. We also explored how Ga3+ ions inhibited the biofilm formation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) and osteoclast differentiation. Results The alloy exhibited outstanding antibiofilm properties against both S. aureus and E. coli in vitro and decent antibiofilm performance against S. aureus in vivo. The proteomics results demonstrated that Ga3+ ions could disturb the bacterial Fe metabolism of both S. aureus and E. coli, inhibiting bacterial biofilm formation. In addition, Ti-Ga alloys could inhibit receptor activator of nuclear factor-κB ligand (RANKL)-dependent osteoclast differentiation and function by targeting iron metabolism, then suppressing the activation of the NF-κB signaling pathway, thus, showing their potential to prevent aseptic loosening. Conclusion This study provides an advanced Ti-Ga alloy that can be used as a promising orthopedic implant raw material for various clinical scenarios. This work also revealed that iron metabolism is the common target of Ga3+ ions to inhibit biofilm formation and osteoclast differentiation.

Abstract Background Globally, millions of patients suffer from regenerative deficiencies, such as refractory wound healing, which is characterized by excessive inflammation and abnormal angiogenesis. Growth factors and stem cells are currently employed to accelerate tissue repair and regeneration; however, they are complex and costly. Thus, the exploration of new regeneration accelerators is of considerable medical interest. This study developed a plain nanoparticle that accelerates tissue regeneration with the involvement of angiogenesis and inflammatory regulation. Methods Grey selenium and sublimed sulphur were thermalized in PEG-200 and isothermally recrystallised to composite nanoparticles (Nano-Se@S). The tissue regeneration accelerating activities of Nano-Se@S were evaluated in mice, zebrafish, chick embryos, and human cells. Transcriptomic analysis was performed to investigate the potential mechanisms involved during tissue regeneration. Results Through the cooperation of sulphur, which is inert to tissue regeneration, Nano-Se@S demonstrated improved tissue regeneration acceleration activity compared to Nano-Se. Transcriptome analysis revealed that Nano-Se@S improved biosynthesis and ROS scavenging but suppressed inflammation. The ROS scavenging and angiogenesis-promoting activities of Nano-Se@S were further confirmed in transgenic zebrafish and chick embryos. Interestingly, we found that Nano-Se@S recruits leukocytes to the wound surface at the early stage of regeneration, which contributes to sterilization during regeneration. Conclusion Our study highlights Nano-Se@S as a tissue regeneration accelerator, and Nano-Se@S may provide new inspiration for therapeutics for regenerative-deficient diseases. Graphical Abstract

Existing clinical treatments for tendinopathy mainly focus on reducing pain, whereas inhibiting or reversing disease progression remains challenging. Local therapeutic drugs, such as glucocorticoids, cause adverse effects on the metabolism of tendon tissues and injection-related complications. Therefore, new administration modalities for tendinopathy need to be developed. In this study, we designed a hydrogel-based microneedle (MN) system for the long-term transdermal delivery of our novel biological cell-free fat extract (CEFFE) to treat tendinopathies. We found that CEFFE-loaded MNs (CEFFE-MNs) had good biosafety and inhibited lipopolysaccharide (LPS)-induced apoptosis and matrix degradation in Achilles tendon cells of rats. The Achilles tendons of rats returned to their maximum mechanical strength after applying CEFFE-MNs. The administration of CEFFE-MNs had better anti-apoptosis and tendon repair-promoting effects than CEFEF injections in vivo. Transcriptome sequencing indicated that the anti-apoptosis effect of CEFFE-MNs was highly related to tumor necrosis factor (TNF) signaling. CEFFE-MNs inhibited the expression of TNF, TNF receptor 1, and downstream nuclear factor-kappa B signaling. Additionally, CEFFE-MNs rescued LPS-induced mitochondrial dynamics in tendon cells via the TNF-Drp1 axis. Our study reports a novel CEFFE-MN system that exhibits long-term anti-inflammatory and anti-apoptotic effects, suggesting it as a new treatment route for tendinopathy with broad clinical translation prospects.

Bauhinia is a widely planted urban tree plant in tropical cities, which are frequently dwelling in a habitat exposed to inevitable streetlamp lighting. It is of practical meaning to figure out the lighting spectra that benefit nutrient utilization in corporation with a proper exponential fertilization regime. In this study, Bauhinia brachycarpa and B. variegata seedlings were cultured with exponential fertilization at the rate of 80 mg nitrogen (N) plant-1 (N-phosphorus-potassium, 10-7-9) with an unfertilized control, and both were exposed to light-emitting diode spectra of R1BG5 (13.9% red, 77.0% green, 9.2% blue), R2BG3 (26.2% red, 70.2% green, 3.5% blue), and R3BG1 (42.3% red, 57.3% green, 0.4% blue). The R3BG1 spectrum resulted in smaller growing size and dry mass but higher nutrient concentration and root water content compared to the other two spectra. Exponential fertilization increased fresh mass for two Bauhinia species but only increased dry mass in B. brachycarpa. Compared to B. variegata, B. brachycarpa was verified to have a higher capacity to accommodate exogeneous nutrient input through exponential fertilization. The R3BG1 spectrum was recommended for the illumination in streetlamps for Bauhinia because this spectrum can promote nutrient uptake without too fast rate of growth relative to other spectra with lower red-light proportions.

Current in vitro models for osteosarcoma investigation and drug screening, including two-dimensional (2D) cell culture and tumour spheroids (i.e. cancer stem-like cells), lack extracellular matrix (ECM). Therefore, results from traditional models may not reflect real pathological processes in genuine osteosarcoma histological structures. Here, we report a three-dimensional (3D) bioprinted osteosarcoma model (3DBPO) that contains osteosarcoma cells and shrouding ECM analogue in a 3D frame. Photo-crosslinkable bioinks composed of gelatine methacrylamide and hyaluronic acid methacrylate mimicked tumour ECM. We performed multi-omics analysis, including transcriptomics and DNA methylomics, to determine differences between the 3DBPO model and traditional models. Compared with 2D models and tumour spheroids, our 3DBPO model showed significant changes in cell cycle, metabolism, adherens junctions, and other pathways associated with epigenetic regulation. The 3DBPO model was more sensitive to therapies targeted to the autophagy pathway. We showed that simulating ECM yielded different osteosarcoma cell metabolic characteristics and drug sensitivity in the 3DBPO model compared with classical models. We suggest 3D printed osteosarcoma models can be used in osteosarcoma fundamental and translational research, which may contribute to novel therapeutic strategy discovery.

Abstract The CCCTC-binding factor (CTCF) protein and its modified forms regulate gene expression and genome organization. However, information on CTCF acetylation and its biological function is still lacking. Here, we show that CTCF can be acetylated at lysine 20 (CTCF-K20) by CREB-binding protein (CBP) and deacetylated by histone deacetylase 6 (HDAC6). CTCF-K20 is required for the CTCF interaction with CBP. A CTCF point mutation at lysine 20 had no effect on self-renewal but blocked the mesoderm differentiation of mouse embryonic stem cells (mESCs). The CTCF-K20 mutation reduced CTCF binding to the promoters and enhancers of genes associated with early cardiac mesoderm differentiation, resulting in diminished chromatin accessibility and decreased enhancer-promoter interactions, impairing gene expression. In summary, this study reveals the important roles of CTCF-K20 in regulating CTCF genomic functions and mESC differentiation into mesoderm.

Selenium (Se) is an essential trace element involved in nearly all human physiological processes but suffers from a narrow margin between benefit and toxicity. The nanoform of selenium has been proven shown to be more bioavailable and less toxic, yet significant challenges remain regarding the efficient and feasible synthesis of biologically active nanoselenium. In addition, although nanoselenium has shown a variety of biological activities, more interesting nanoselenium features are expected. In this work, hydrosoluble nanoselenium termed Nano-Se in the zero oxidation state was synthesized between gray Se and PEG. A zebrafish screen was carried out in zebrafish larvae cocultured with Nano-Se. Excitingly, Nano-Se promoted the action of the FGFR, Wnt, and VEGF signaling pathways, which play crucial roles in tissue regeneration. As expected, Nano-Se not only achieved the regeneration of zebrafish tail fins and mouse skin but also promoted the repair of skin in diabetic mice while maintaining a profitable safe profile. In brief, the Nano-Se reported here provided an efficient and feasible method for bioactive nanoselenium synthesis and not only expanded the application of nanoselenium to regenerative medicine but also likely reinvigorated efforts for discovering more peculiarunique biofunctions of nanoselenium in a great variety of human diseases.

Objective: To evaluate the interbody fusion efficacy and biocompatibility of a graft-free cage made of polyetheretherketone/calcium silicate composite/porous tantalum (PEEK/CS/pTa cage) compared with a PEEK/CS cage with an autogenous bone graft in a goat model. Methods: PEEK/CS/pTa and PEEK/CS cages were prepared through an injection-moulding method. The PEEK/CS composites and porous tantalum were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive spectroscopy (EDS) mapping. Then, adult goats were chosen for C2/C3 and C3/C4 discectomy via the anterior cervical approach and randomly implanted with PEEK/CS/pTa and PEEK/CS/cages with autogenous bone grafts. The fusion performance and osseointegration of the cages were evaluated by X-ray imaging, magnetic resonance imaging (MRI) scanning, and bone histomorphometry analysis. Moreover, the concentrations of Ca and Si in urine, serum, tissue around the fusion segments and major organs of the goats were determined by inductively coupled plasma–optical emission spectrometry (ICP–OES). Histological observation of major organs of the goats was used to evaluate the biosafety of PEEK/CS/pTa and PEEK/CS cages. Results: X-ray and MRI imaging suggested that both PEEK/CS/pTa cages and PEEK/CS cages maintained similar average intervertebral space heights. The tissue volumes in the fusion area were comparable between the two groups of cages at 26 weeks after surgery. Histological morphometric data showed that PEEK/CS/pTa cages and PEEK/CS cages with autogenous bone grafts had similar bone contact and osseointegration at 12 and 26 weeks. Element determination of serum, urine, spinal cord, dura matter, bone and organs showed that the CS/PEEK cages did not cause abnormal systemic metabolism or accumulation of calcium and silicon in local tissues and major organs of goats after implantation. No obvious pathological changes were found in the heart, liver, spleen, liver or kidney tissues. Conclusion: Overall, these results suggested that the graft-free PEEK/CS/pTa cage showed similar bony fusion performance to the PEEK/CS cages with autogenous bone grafts. The cages releasing calcium and silicon had good biological safety in vivo.The translational potential of this article: This study provided a new graft-free interbody fusion solution to patients with degenerative disc diseases, which could avert potential donor-site complications. This study also provided a detailed assessment of element excretion and accumulation of Ca and Si in vivo, which validated the biosafety of this new type of bioactive interbody fusion cage.

Abstract Background Renal injury is one of the common microvascular complications of diabetes, known as diabetic kidney disease (DKD) seriously threatening human health. Previous research has reported that the Chinese Medicine Fufang-Zhenzhu-Tiaozhi (FTZ) capsule protected myocardia from injury in diabetic minipigs with coronary heart disease (DM-CHD). And we found significant renal injury in the minipigs. Therefore, we further investigated whether FTZ prevents renal injury of DM-CHD minipig and H2O2-induced oxidative injury of HK-2 cells. Methods DM-CHD model was established by streptozotocin injection, high fat/high-sucrose/high-cholesterol diet combined with balloon injury in the coronary artery. Blood lipid profile, fasting blood glucose (FBG), and SOD were measured with kits. The levels of blood urea nitrogen (BUN), serum creatinine (Scr), urine trace albumin (UALB), urine creatinine (UCR) (calculate UACR), cystatin (Cys-C), and β-microglobulin (β-MG) were measured by ELISA kits to evaluate renal function. TUNEL assay was performed to observe the apoptosis. qPCR was used to detect the mRNA expression levels of HO-1, NQO1, and SOD in kidney tissue. The protein expressions of Nrf2, HO-1, NQO1, Bax, Bcl-2, and Caspase 3 in the kidney tissue and HK-2 cells were detected by western blot. Meanwhile, HK-2 cells were induced by H2O2 to establish an oxidative stress injury model to verify the protective effect and mechanisms of FTZ. Results In DM-CHD minipigs, blood lipid profile and FBG were elevated significantly, and the renal function was decreased with the increase of BUN, Scr, UACR, Cys-c, and β-MG. A large number of inflammatory and apoptotic cells in the kidney were observed accompanied with lower levels of SOD, Bcl-2, Nrf2, HO-1, and NQO1, but high levels of Bax and Cleaved-caspase 3. FTZ alleviated glucose-lipid metabolic disorders and the pathological morphology of the kidney. The renal function was improved and the apoptotic cells were reduced by FTZ administration. FTZ could also enhance the levels of SOD, Nrf2, HO-1, and NQO1 proteins to promote antioxidant effect, down-regulate the expression of Bax and Caspase3, as well as up-regulate the expression of Bcl-2 to inhibit cell apoptosis in the kidney tissue and HK-2 cells. Conclusions We concluded that FTZ prevents renal injury of DM-CHD through activating anti-oxidative capacity to reduce apoptosis and inhibiting inflammation, which may be a new candidate for DKD treatment. Graphical Abstract

Breast cancer stem cells (BCSCs) is a subpopulation of cancer cells with self-renewal and differentiation capacity, have been suggested to give rise to tumor heterogeneity and biologically aggressive behavior. Accumulating evidence has shown that BCSCs play a fundamental role in tumorigenesis, progression, and recurrence. The development of immunotherapy, primarily represented by programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, has greatly changed the treatment landscape of multiple malignancies. Recent studies have identified pervasive negative associations between cancer stemness and anticancer immunity. Stemness seems to play a causative role in the formation of cold tumor immune microenvironment (TIME). The multiple functions of long non-coding RNAs (lncRNAs) in regulating stemness and immune responses has been recently highlighted in breast cancer. The review focus on lncRNAs and keys pathways involved in the regulation of BCSCs and TIME. Potential clinical applications using lncRNAs as biomarkers or therapies will be discussed.

Correlated sampling has wide-ranging applications in Monte Carlo calculations. When branching random walks are involved, as commonly found in many algorithms in quantum physics and electronic structure, population control is typically not applied with correlated sampling due to technical difficulties. This hinders the stability and efficiency of correlated sampling. In this paper, we study schemes for allowing birth/death in correlated sampling and propose an algorithm for population control. The algorithm can be realized in several variants depending on the application. One variant is a static method that creates a reference run and allows other correlated calculations to be added a posteriori. Another optimizes the population control for a set of correlated, concurrent runs dynamically. These approaches are tested in different applications in quantum systems, including both the Hubbard model and electronic structure calculations in real materials.

Abstract Diabetic osteoporosis (DOP) is the leading complication continuously threatening the bone health of patients with diabetes. A key pathogenic factor in DOP is loss of osteocyte viability. However, the mechanism of osteocyte death remains unclear. Here, we identified ferroptosis, which is iron-dependent programmed cell death, as a critical mechanism of osteocyte death in murine models of DOP. The diabetic microenvironment significantly enhanced osteocyte ferroptosis in vitro, as shown by the substantial lipid peroxidation, iron overload, and aberrant activation of the ferroptosis pathway. RNA sequencing showed that heme oxygenase-1 (HO-1) expression was notably upregulated in ferroptotic osteocytes. Further findings revealed that HO-1 was essential for osteocyte ferroptosis in DOP and that its promoter activity was controlled by the interaction between the upstream NRF2 and c-JUN transcription factors. Targeting ferroptosis or HO-1 efficiently rescued osteocyte death in DOP by disrupting the vicious cycle between lipid peroxidation and HO-1 activation, eventually ameliorating trabecular deterioration. Our study provides insight into DOP pathogenesis, and our results provide a mechanism-based strategy for clinical DOP treatment.

Abstract Trefoil factor 3 (TFF3) is the last small-molecule peptide found in the trefoil factor family, which is mainly secreted by intestinal goblet cells and exerts mucosal repair effect in the gastrointestinal tract. Emerging evidence indicated that the TFF3 expression profile and biological effects changed significantly in pathological states such as cancer, colitis, gastric ulcer, diabetes mellitus, non-alcoholic fatty liver disease, and nervous system disease. More importantly, mucosal protection would no longer be the only effect of TFF3, it gradually exhibits carcinogenic activity and potential regulatory effect of nervous and endocrine systems, but the inner mechanisms remain unclear. Understanding the molecular function of TFF3 in specific diseases might provide a new insight for the clinical development of novel therapeutic strategies. This review provides an up-to-date overview of the pathological effects of TFF3 in different disease and discusses the binding proteins, signaling pathways, and clinical application.

Abstract Background With life span extending, breast cancer (BC) survivors may face the possibility of developing second primary cancer (SPC) and considerably shorten survivorship. However, little is known about multiple primary cancer (MPC) patients with nonmetastatic breast cancer as a first primary malignancy (BCFPM). Methods Here, we retrospectively analyzed data on cancer survivors with BCFPM diagnosed between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The prognostic factors for breast cancer‐specific survival (BCSS) were ascertained by the stepwise regression analysis and a competing risk model, and were integrated to the establishment of prognostic nomogram, of which the accuracy was measured by the calibration curve and the concordance index (C‐index). Results In total, 8616 patients were identified with 4.6% of 3‐year breast cancer‐ specific death (BCSD) and 8.6% of 5‐year BCSD. The most common SPC among BCFPM patients were female BC and lung cancer. Besides, the median latency time between BC and SPC was 22 months. At a ratio of 7:3, all patients were randomly categorized into a training cohort (n = 6032) and a validation cohort (n = 2584). By a proportional subdistribution hazards regression analysis, the following factors were considered to own independent prognostic abilities of BCSS: subtypes, grade, T classification, N classification, radiation, and sites of SPC. The nomogram could accurately predict 3‐year and 5‐year breast cancer‐associated survival of BCFPM patients with high internal and external validated C‐index, 0.715 (95% CI, 0.691–0.739), and 0.683 (95% CI, 0.642–0.724), respectively. Conclusions BC survivors remained a high risk of developing SPC and considerably shortened survival time. In this study, a favorable nomogram was constructed to as a prediction model for 3‐year and 5‐year BCSS of BCFPM patients, largely intending to prolong the life of these patients by assisting clinicians to make individualized follow‐up plans.

Correlated electron states are at the root of many important phenomena including unconventional superconductivity (USC), where electron pairing arises from repulsive interactions. Computing the properties of correlated electrons, such as the critical temperature T_{c} for the onset of USC, efficiently and reliably from the microscopic physics with quantitative methods remains a major challenge for almost all models and materials. In this theoretical work, we combine matrix product states (MPS) with static mean field (MF) to provide a solution to this challenge for quasi-one-dimensional (Q1D) systems: two- and three-dimensional materials comprised of weakly coupled correlated 1D fermions. This MPS+MF framework for the ground state and thermal equilibrium properties of Q1D fermions is developed and validated for attractive Hubbard systems first, and further enhanced via analytical field theory. We then deploy it to compute T_{c} for superconductivity in 3D arrays of weakly coupled, doped, and repulsive Hubbard ladders. The MPS+MF framework thus enables the quantitative study of USC and high-T_{c} superconductivity—and potentially many more correlated phases—in fermionic Q1D systems based directly on their microscopic parameters, in ways inaccessible to previous methods. This approach further allows one to treat competing macroscopic orders, such as superconducting and insulating ones, on an equal footing. Benchmarks of the framework using auxiliary-field quantum Monte Carlo techniques show that the overestimation of, e.g., T_{c} due to its mean-field component, is near constant in microscopic parameters. These features of the MPS+MF approach to correlated fermions open up the possibility of designing deliberately optimized Q1D superconductors, from experiments in ultracold gases to synthesizing new materials.

This study applies a transformative sport service research approach to examine student-athletes' wellness within a collegiate sport setting. Sixteen semi-structured interviews were completed during the COVID-19 pandemic and the stop of play in Canada (early 2021). Findings denoted wellness was influenced by this time period as well as organizational factors which are within the purview of existing management practices. The study details the service environment to understand physical and mental well-being while taking into consideration the general and organizational environments which influence the student-athletes. Findings demonstrate that eudaimonic-related experiences (e.g., learning, development, relationship) are related to student-athletes' mental well-being. This research underpins the role of education, policies, and communication, which draws several implications for the service environment in a collegiate sport setting and the key stakeholders involved in producing an environment to enhance student-athletes' experience. The paper elaborates on the importance of the service environment and provides evidence of what student-athletes suggest management can change and focus their efforts on towards creating a transformative service environment. Theoretical implications for the transformative service research are put forward, including the co-creative aspects to determine programming which could contribute towards student-athletes wellness. Broader suggestions for change within the sport system and future research are also advanced. [ABSTRACT FROM AUTHOR]

Senile osteoporosis is characterized by age-related bone loss and bone microarchitecture deterioration. However, little is known to date about the mechanism that maintains bone homeostasis during aging. In this study, we identify adenosine monophosphate-activated protein kinase alpha 1 (AMPKα1) as a critical factor regulating the senescence and lineage commitment of mesenchymal stem cells (MSCs). A phospho-mutant mouse model shows that constitutive AMPKα1 activation prevents age-related bone loss and promoted MSC osteogenic commitment with increased bone-derived insulin-like growth factor 1 (IGF-1) secretion. Mechanistically, upregulation of IGF-1 signalling by AMPKα1 depends on cAMP-response element binding protein (CREB)-mediated transcriptional regulation. Furthermore, the essential role of the AMPKα1/IGF-1/CREB axis in promoting aged MSC osteogenic potential is confirmed using three-dimensional (3D) culture systems. Taken together, these results can provide mechanistic insight into the protective effect of AMPKα1 against skeletal aging by promoting bone-derived IGF-1 secretion. [ABSTRACT FROM AUTHOR]

This study extends the traditional problem of a seismic response of elastic foundations under isothermal conditions when considering thermal effects. Firstly, a free-field model of the elastic foundation is established under the incidence of plane P-waves. Then, utilizing the principles of wave propagation in a homogeneous and isotropic thermoelastic medium and the principle of Helmholtz vector decomposition, the influence of thermal physical parameters such as thermal conductivity, medium temperature on seismic ground motion of the free--field on elastic foundation is investigated, which provides a reasonable explanation for the ground motion of a site under thermal effects. [ABSTRACT FROM AUTHOR]

Antibiotics are among the most used weapons in fighting microbial infections and have greatly improved the quality of human life. However, bacteria can eventually evolve to exhibit antibiotic resistance to almost all prescribed antibiotic drugs. Photodynamic therapy (PDT) develops little antibiotic resistance and has become a promising strategy in fighting bacterial infection. To augment the killing effect of PDT, the conventional strategy is introducing excess ROS in various ways, such as applying high light doses, high photosensitizer concentrations, and exogenous oxygen. In this study, we report a metallacage-based PDT strategy that minimizes the use of ROS by jointly using gallium-metal organic framework rods to inhibit the production of bacterial endogenous NO, amplify ROS stress, and enhance the killing effect. The augmented bactericidal effect was demonstrated both in vitro and in vivo. This proposed enhanced PDT strategy will provide a new option for bacterial ablation. [ABSTRACT FROM AUTHOR]