Search

Abstract Background As a new type of intravenous anesthetic, ciprofol has the advantages of fast onset of action, fast recovery and high clearance rate. This study aimed to investigate the effectiveness and safety of ciprofol versus traditional propofol for anesthesia and sedation in and out of the operating room. Methods We searched the literature in PubMed, Web of Science, Cochrane Library, and Embase databases from January 2021 to December 2023. All clinical studies comparing the sedative effects of propofol and ciprofol, both inside and outside the operating room, were included in our trial. The main outcome measures were induction time and incidence of injection-site pain. Data are merged using risk ratio and standardized mean difference with 95% confidence interval. Subgroup analysis, meta-regression, sensitivity analysis, and publication bias were performed. The study protocol was prospectively registered with PROSPERO (CRD42023447747). Results A total of 15 randomized, controlled trials involving 2002 patients were included in this study. Compared with propofol, ciprofol has a longer induction time in the operating room but a shorter induction time in non-operating room settings. Ciprofol can effectively reduce the risk of injection-site pain and respiratory depression both inside and outside the operating room. In addition, the risk of drug-related hypotension induced with ciprofol in the operating room is lower, but the awakening time is also longer. Meta-regression analysis showed that neither age nor BMI were potential sources of heterogeneity. Funnel plot, egger and begg tests showed no significant publication bias. Sensitivity analyzes indicate that our results are robust and reliable. Conclusion Ciprofol has absolute advantages in reducing the risk of injection-site pain and respiratory depression, both in and outside operating room. Intraoperative use of ciprofol reduces the risk of drug-related hypotension and may also reduce the risk of intraoperative physical movements. However, ciprofol may have longer induction and awakening time than propofol.

Bone, renowned for its elegant hierarchical structure and unique mechanical properties, serves as a constant source of inspiration for the development of synthetic materials. However, achieving accurate replication of bone features in artificial materials with remarkable structural and mechanical similarity remains a significant challenge. In this study, we employed a cascade of continuous fabrication processes, including biomimetic mineralization of collagen, bidirectional freeze-casting, and pressure-driven fusion, to successfully fabricate a macroscopic bulk material known as artificial compact bone (ACB). The ACB material closely replicates the composition, hierarchical structures, and mechanical properties of natural bone. It demonstrates a lamellated alignment of mineralized collagen (MC) microfibrils, similar to those found in natural bone. Moreover, the ACB exhibits a similar high mineral content (70.9 %) and density (2.2 g/cm3) as natural cortical bone, leading to exceptional mechanical properties such as high stiffness, hardness, and flexural strength that are comparable to those of natural bone. Importantly, the ACB also demonstrates excellent mechanical properties in wet, outstanding biocompatibility, and osteogenic properties in vivo, rendering it suitable for a broad spectrum of biomedical applications, including orthopedic, stomatological, and craniofacial surgeries.

Utilizing biomaterials in tissue engineering has shown considerable promise for tissue regeneration, particularly through delivering multimodel cell-regulatory signals, including the material-related signals and extrinsic stimuli. In this research, we developed a magnetic-responsive aligned nanofiber fibrin hydrogel (MAFG), integrating the structured alignment of nanofibers and the pliability of fibrin hydrogel with an external magnetic field. This design aimed to enhance the regenerative response in spinal cord injury treatment. A medium-strength magnetic field, aligned with the spinal cord, was applied to aid motor function recovery in rats with spinal cord injuries. The use of MAFG in this context not only intensified the effect of the magnetic field but also encouraged the activation and differentiation of native neural stem cells. Furthermore, this method effectively steered macrophage polarization towards a beneficial M2 phenotype, addressing immune dysregulation at the injury site. The parallel application of magnetic field stimulation through MAFG in a spinal cord injury model contributed to the concurrent promotion of neurogenesis, angiogenesis, and immunomodulation, resulting in marked improvement in motor function in rats. This investigation underscores the therapeutic potential of magnetic field stimulation and highlights how aligning this stimulation with the spinal cord can significantly enhance the regenerative milieu at the injury site.

Rehabilitation and regenerative medicine are two promising approaches for spinal cord injury (SCI) recovery, but their combination has been limited. Conductive biomaterials could bridge regenerative scaffolds with electrical stimulation by inducing axon regeneration and supporting physiological electrical signal transmission. Here, we developed aligned conductive hydrogel fibers by incorporating carbon nanotubes (CNTs) into methacrylate acylated gelatin (GelMA) hydrogel via rotating liquid bath electrospinning. The electrospun CNT/GelMA hydrogel fibers mimicked the micro-scale aligned structure, conductivity, and soft mechanical properties of neural axons. For in vitro studies, CNT/GelMA hydrogel fibers supported PC12 cell proliferation and aligned adhesion, which was enhanced by electrical stimulation (ES). Similarly, the combination of aligned CNT/GelMA hydrogel fibers and ES promoted neuronal differentiation and axon-like neurite sprouting in neural stem cells (NSCs). Furthermore, CNT/GelMA hydrogel fibers were transplanted into a T9 transection rat spinal cord injury model for in vivo studies. The results showed that the incorporating CNTs could remain at the injury site with the GelMA fibers biodegraded and improve the conductivity of regenerative tissue. The aligned structure of the hydrogel could induce the neural fibers regeneration, and the ES enhanced the remyelination and axonal regeneration. Behavioral assessments and electrophysiological results suggest that the combination of aligned CNT/GelMA hydrogel fibers and ES could significantly restore motor function in rats. This study demonstrates that conductive aligned CNT/GelMA hydrogel fibers can not only induce neural regeneration as a scaffold but also support ESto promote spinal cord injury recovery. The conductive hydrogel fibers enable merging regenerative medicine and rehabilitation, showing great potential for satisfactory locomotor recovery after SCI.

Abstract Background Facial nerve injury often results in poor prognosis due to the challenging process of nerve regeneration. Neuregulin-1, a human calmodulin, is under investigation in this study for its impact on the reparative capabilities of Dental Pulp Stem Cells (DPSCs) in facial nerve injury. Methods Lentivirus was used to transfect and construct Neuregulin-1 overexpressed DPSCs. Various techniques assessed the effects of Neuregulin-1: osteogenic induction, lipid induction, Reverse Transcription Polymerase Chain Reaction, Western Blot, Cell Counting Kit-8 assay, wound healing, immunofluorescence, Phalloidin staining, nerve stem action potential, Hematoxylin-eosin staining, transmission electron microscopy, and immunohistochemistry. Results Neuregulin-1 effectively enhanced the proliferation, migration, and cytoskeletal rearrangement of DPSCs, while simultaneously suppressing the expression of Ras homolog gene family member A (RhoA) and Microfilament actin (F-actin). These changes facilitated the neural differentiation of DPSCs. Additionally, in vivo experiments showed that Neuregulin-1 expedited the restoration of action potential in the facial nerve trunk, increased the thickness of the myelin sheath, and stimulated axon regeneration. Conclusion Neuregulin-1 has the capability to facilitate the repair of facial nerve injuries by promoting the regenerative capacity of DPSCs. Thus, Neuregulin-1 is a significant potential gene in the reparative processes of nerve damage.

An edge $e$ of a matching covered graph $G$ is removable if $G-e$ is also matching covered. Carvalho, Lucchesi, and Murty showed that every brick $G$ different from $K_4$ and $\overline{C_6}$ has at least $\Delta-2$ removable edges, where $\Delta$ is the maximum degree of $G$. In this paper, we generalize the result to irreducible near-bricks, where a graph is irreducible if it contains no single ear of length three or more.

The jackfruit seed dietary fiber was modified by high temperature cooking combined with ultrasonic enzymatic method. Single factor combined with response surface method was applied to optimize the modification process conditions. The structure of soluble dietary fiber (SDF) before and after modification was compared and analyzed by scanning electron microscope (SEM), X-ray diffraction (XRD), thermogravimetry (TGA) and Fourier transform infrared spectrometer (FTIR). The functional properties of SDF before and after modification were determined with water holding capacity, expansion capacity, oil holding capacity and adsorption capacity for nitrite ion, glucose, bile salt and cholesterol as indicators. The results showed that the optimum modification conditions of DF were as follows: The ratio of material to liquid 1:21 g/mL, cooking temperature 121 ℃, cooking time 43 min, cellulase amount 8%, ultrasonic-assisted enzymatic (UAE) power 360 W, UAE temperature 40 ℃, UAE time 52 min. Under these conditions, the yield of SDF was 24.39%±0.03%, the yield of unmodified SDF was 16.93%±0.60%. Compared with unmodified SDF, FTIR results showed that the cellulose components of jackfruit seeds were redistributed. SEM indicated a more porous structure. XRD results showed an increase in crystallinity, and TGA results showed better thermal stability. The water holding capacity, expansion capacity, oil retention capacity, nitrite ion adsorption capacity, glucose adsorption capacity, bile salt adsorption capacity, and cholesterol adsorption capacity of modified SDF were significantly better than those of unmodified SDF (P

Abstract Background Job stress has significant influence on the mental health of health care providers. The mental health and job stress of operating room nurses remain unclear. This study aimed to evaluate the mental health and job stress of nurses in surgical system in China, to provide evidences for clinical nurse management and care. Methods The nurses in the surgical system of our hospital were investigated by questionnaire in December 2022. The general information questionnaire, symptom check list 90 (SCL-90) and nurses’ job stressor scale (NJSS) were used for data collection. Pearson correlation and logistic analysis were conducted to evaluate the related influencing factors. Results A total of 171 nurses in surgical system were investigated. The mental health level of nurses in operating room was low. The job pressure of the nurses in the operating room was in the middle level. The nursing profession and work, workload and distribution, working environment and resources, patient care, management and interpersonal relationship were all positively correlated with SCL-90 score of nurses in operating room. Logistic regression analysis indicated that age, year of work experience, professional ranks and titles both are the influencing factors of SCL-90 score and of nurses in operating room. Conclusions The mental health of nurses in surgical system is affected by work pressure, ages, working years and professional titles. These factors should be considered in the psychological intervention of nurses in operating room in order to improve the health of clinical nurses.

Nerve guidance conduits (NGCs) have been widely accepted as a promising strategy for peripheral nerve regeneration. Fabricating ideal NGCs with good biocompatibility, biodegradability, permeability, appropriate mechanical properties (space maintenance, suturing performance, etc.), and oriented topographic cues is still current research focus. From the perspective of translation, the technique stability and scalability are also an important consideration for industrial production. Recently, blow-spinning technique shows great potentials in nanofibrous scaffolds fabrication, possessing high quality, high fiber production rates, low cost, ease of maintenance, and high reliability. In this study, we proposed for the first time the preparation of a novel NGC via blow-spinning technique to obtain optimized performances and high productivity. A new collagen nanofibrous neuro-tube with the bilayered design was developed, incorporating inner oriented and outer random topographical cues. The bilayer structure enhances the mechanical properties of the conduit in dry and wet, displaying good radial support and suturing performance. The porous nature of the blow-spun collagen membrane enables good nutrient delivery and metabolism. The in vitro and in vivo evaluations indicated the bilayer-structure conduit could promoted Schwann cells growth, neurotrophic factors secretion, and axonal regeneration and motor functional recovery in rat.

Triple-negative breast cancer (TNBC) is currently the worst prognostic subtype of breast cancer, and there is no effective treatment other than chemotherapy. Processing of precursors 1 (POP1) is the most substantially up-regulated RNA-binding protein (RBP) in TNBC. However, the role of POP1 in TNBC remains clarified. A series of molecular biological experiments in vitro and in vivo and clinical correlation analyses were conducted to clarify the biological function and regulatory mechanism of POP1 in TNBC. Here, we identified that POP1 is significantly up-regulated in TNBC and associated with poor prognosis. We further demonstrate that POP1 promotes the cell cycle and proliferation of TNBC in vitro and vivo. Mechanistically, POP1 directly binds to the coding sequence (CDS) region of CDKN1A mRNA and degrades it. The degradation process depends on the N6-methyladenosine (m6A) modification at the 497th site of CDKN1A and the recognition of this modification by YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Moreover, the m6A inhibitor STM2457 potently impaired the proliferation of POP1-overexpressed TNBC cells and improved the sensitivity to paclitaxel. In summary, our findings reveal the pivotal role of POP1 in promoting TNBC proliferation by degrading the mRNA of CDKN1A and that inhibition of m6A with STM2457 is a promising therapeutic strategy for TNBC.

Above-ground biomass (AGB) is a critical criterion for assessing the ecological value and productivity of grasslands. Quickly and accurately estimating the AGB of grasslands has become a matter of great concern in grassland ecosystem research. By combining ground ASD hyperspectral data and airborne hyperspectral data, this study successfully extracted the sensitive bands of canopy reflectance and calculated the various vegetation indexes, thus providing information of more dimensions for above-ground biomass estimation. Biomass inversion-based yield modeling results reveal that the 377 nm raw band reflectance of the ASD data and the narrow-band vegetation index of the Resonon data exhibit outstanding performance in yield modeling. Comparative analysis indicates that the Resonon hyperspectral data demonstrate a distinct advantage in assessing meadow steppe yield, and the quadratic polynomial model based on its narrow-band SAVI achieves an R2 of 0.553 and an RMSE of 37.53.

3D bioprinting holds great promise toward fabricating biomimetic living constructs in a bottom-up assembly manner. To date, various emergences of living constructs have been bioprinted for in vitro applications, while the conspicuous potential serving for in vivo implantable therapies in spinal cord injury (SCI) has been relatively overlooked. Herein, living nerve-like fibers are prepared via extrusion-based 3D bioprinting for SCI therapy. The living nerve-like fibers are comprised of neural stem cells (NSCs) embedded within a designed hydrogel that mimics the extracellular matrix (ECM), assembled into a highly spatial ordered architecture, similar to densely arranged bundles of the nerve fibers. The pro-neurogenesis ability of these living nerve-like fibers is tested in a 4 mm-long complete transected SCI rat model. Evidence shows that living nerve-like fibers refine the ecological niche of the defect site by immune modulation, angiogenesis, neurogenesis, neural relay formations, and neural circuit remodeling, leading to outstanding functional reconstruction, revealing an evolution process of this living construct after implantation. This effective strategy, based on biomimetic living constructs, opens a new perspective on SCI therapies.

Spinal cord injury (SCI) is an overwhelming and incurable disabling condition, for which increasing forms of multifunctional biomaterials are being tested, but with limited progression. The promising material should be able to fill SCI-induced cavities and direct the growth of new neurons, with effective drug loading to improve the local micro-organism environment and promote neural tissue regeneration. In this study, a double crosslinked biomimetic composite hydrogel comprised of acellularized spinal cord matrix (ASCM) and gelatin-acrylated-β-cyclodextrin-polyethene glycol diacrylate (designated G-CD-PEGDA) hydrogel, loaded with WAY-316606 to activate canonical Wnt/β-catenin signaling, and reinforced by a bundle of three-dimensionally printed aligned polycaprolactone (PCL) microfibers, was constructed. The G-CD-PEGDA component endowed the composite hydrogel with a dynamic structure with a self-healing capability which enabled cell migration, while the ASCM component promoted neural cell affinity and proliferation. The diffusion of WAY-316606 could recruit endogenous neural stem cells and improve neuronal differentiation. The aligned PCL microfibers guided neurite elongation in the longitudinal direction. Animal behavior studies further showed that the composite hydrogel could significantly recover the motor function of rats after SCI. This study provides a proficient approach to produce a multifunctional system with desirable physiological, chemical, and topographical cues for treating patients with SCI.

The disruption and reconstruction of the TREM2+ tissue resident macrophage (TRM) barrier on the surface of synovial lining play a key role in the activation and "remission" of rheumatoid arthritis (RA), which engender the prediction of this immunologic barrier as a potential driver for the achievement of "cure" in RA. However, strategies to promote the reconstruction of this barrier have not been reported, and the effect of patching this barrier remains unidentified. On the other hand, appropriate piezoelectric stimulation can reprogram macrophages, which has never been exerted on this barrier TRM yet. Herein, we design piezoelectric tetragonal BaTiO3 (BTO) ultrasound-driven nanorobots (USNRs) by the solvothermal synthesis method, which demonstrates satisfactory electro-mechanical conversion effects, paving the way to generate controllable electrical stimulation under ultrasound to reprogram the barrier TRM by minimally invasive injection into joint cavity. It is demonstrated that the immunologic barrier could be patched by this USNR effectively, thereby eliminating the hyperplasia of vessels and nerves (HVN) and synovitis. Additionally, TREM2 deficiency serum-transfected arthritis (STA) mice models are applied and proved the indispensable role of TREM2 in RA curing mediated by USNR. In all, our work is an interesting and important exploration to expand the classical tetragonal BTO nanoparticles in the treatment of autoimmune diseases, providing a new idea and direction for the biomedical application of piezoelectric ceramics.

Tamoxifen (TAM) resistance remains a major obstacle in the treatment of advanced breast cancer (BCa). In addition to the competitive inhibition of the estrogen receptor (ER) signaling pathway, damping of mitochondrial function by increasing reactive oxygen species (ROS) is critical for enhancing TAM pharmacodynamics. Here, we showed that RelB contributes to TAM resistance by inhibiting TAM-provoked ferroptosis. TAM-induced ROS level promoted ferroptosis in TAM-sensitive cells, but the effect was alleviated in TAM-resistant cells with high constitutive levels of RelB. Mechanistically, RelB inhibited ferroptosis by transcriptional upregulating glutathione peroxidase 4 (GPX4). Consequently, elevating RelB and GPX4 in sensitive cells increased TAM resistance, and conversely, depriving RelB and GPX4 in resistant cells decreased TAM resistance. Furthermore, suppression of RelB transcriptional activation resensitized TAM-resistant cells by enhancing ferroptosis in vitro and in vivo. The inactivation of GPX4 in TAM-resistant cells consistently resensitized TAM by increasing ferroptosis-mediated cell death. Together, this study uncovered that inhibition of ferroptosis contributes to TAM resistance of BCa via RelB-upregulated GPX4.

Nur77 modulators have emerged as a promising therapeutic approach for hepatocellular carcinoma. In this study, a structure-based rational drug design approach was used to design and synthesise a series of 4-((8-hydroxy-2-methylquinolin-4-yl)amino)benzoylhydrazone derivatives based on the binding characteristics of our previously reported 10g and the native ligand 3NB at the binding Site C of Nur77. Cell-based cytotoxicity assays revealed that compound TMHA37 demonstrated the highest cytotoxicity against all tested cancer cells. The induced fit docking and binding pose metadynamics simulation suggested that TMHA37 was the most promising Nur77 binder at Site C. Molecular dynamics simulation validated the stable binding of TMHA37 to Nur77’s Site C but not to Sites A or B. Specifically, TMHA37 bound strongly to Nur77-LBD (KD = 445.3 nM) and could activate Nur77’s transcriptional activity. Furthermore, TMHA37 exhibited antitumor effects by blocking the cell cycle at G2/M phase and inducing cell apoptosis in a Nur77-dependent manner.

Summary: Depletion of CD8+ T cells is a major obstacle in immunotherapy; however, the relevant mechanisms remain largely unknown. Here, we showed that prostate cancer (PCa) cell-derived exosomes hamper CD8+ T cell function by transporting interleukin-8 (IL-8). Compared to the low IL-8 levels detected in immune cells, PCa cells secreted the abundance of IL-8 and further accumulated in exosomes. The delivery of PCa cell-derived exosomes into CD8+ T cells exhausted the cells through enhanced starvation. Mechanistically, exosomal IL-8 overactivated PPARα in recipient cells, thereby decreasing glucose utilization by downregulating GLUT1 and HK2 but increasing fatty acid catabolism via upregulation of CPT1A and ACOX1. PPARα further activates uncoupling protein 1 (UCP1), leading to fatty acid catabolism for thermogenesis rather than ATP synthesis. Consequently, inhibition of PPARα and UCP1 restores CD8+ T cell proliferation by counteracting the effect of exosomal IL-8. This study revealed that the tumor exosome-activated IL-8-PPARα-UCP1 axis harms tumor-infiltrating CD8+ T cells by interfering with energy metabolism.

Abstract This study analyzed the impact of factors affecting overall survival in patients with pT2N0M0 esophageal squamous carcinoma (ESCC) and developed a nomogram to predict overall survival (OS). We reviewed the clinical data of 413 patients with pathological T2N0M0 ESCC after radical esophagectomy in two hospitals. Data from one institution was used as the training cohort. A nomogram was established using Cox proportional hazard regression for identifying the prognostic factors affecting for OS in ESCC patients. The area under the curve (AUC), calibration curves and decision curve analysis (DCA) were used to evaluate prognostic efficacy, which was validated in an independent validation cohort. In the training cohort (N = 304), the median OS was 69.33 months, and the 3-, 5- and 10-year OS rates were 76.80%, 67.00% and 56.90%, respectively. The median OS of the validation cohort (N = 109) was 73.50 months, and the 3-, 5- and 10-year OS rates were 77.00%, 67.80% and 55.60%, respectively. According to Cox univariate and multivariate analyses, sex, age, tumor length and the number of resected lymph nodes were identified as predictors of OS. We developed nomograms and performed internal and external validation. The time-dependent receiver operating characteristic (ROC) curve and area under the curve (AUC) value, calibration curve and decision curve analysis (DCA) showed good prediction ability of the nomogram. The developed nomogram can effectively predict OS after esophagectomy in patients with pT2N0M0 ESCC.

With transistors scaling down to 3 nm node and beyond, short channel effect (SCE) as well as power consumption dissipation present immense challenges for further scaling down of the transistor. Hence the Gate all around field effect transistor (GAA-FET) is proposed to replace the Fin field effect transistor (FinFET) in 3 nm technology node and beyond due to its better gate control over the channel with surrounding gate structure, thus providing improved SCE constraint ability. Traditional transistors suffer from the problems of “Boltzmann Tyranny” and cannot overcome the subthreshold swing (SS) limit of 60 mV/dec at room temperature. To maintain high $I_{on}$ and avoid $I_{off}$ from increasing too much, supply voltage ( $V_{DD}$ ) of the conventional transistor cannot scale down proportionally with the dimension of the transistor. The concept of negative capacitance (NC) has been demonstrated to be able to obtain sub-60 mV/dec SS with the ability of amplifying the potential of the channel region without $V_{DD} $ increment. The novel device structure of negative capacitance gate all around field effect transistor(NC GAA-FET) can combine both the advantages of GAA-FET and NC-FET, and is the most promising ultra-low power consumption device and promises to sustain the Moore’s law further beyond what is predicted now. Whereas, according to our knowledge, there have been few review papers about NC GAA-FET till now. Herein, we summarize the recent developments of the NC GAA-FET both in simulation and experimental aspects, which we believe will bring about profound changes to the further development of NC GAA-FET devices.

The concept of photonic modes is the cornerstone in optics and photonics, which can describe the propagation of the light. The Maxwell’s equations play the role in calculating the mode field based on the structure information, while this process needs a great deal of computations, especially in the handle with a three-dimensional model. To overcome this obstacle, we introduce the multi-modal diffusion model to predict the photonic modes in one certain structure. The Contrastive Language–Image Pre-training (CLIP) model is used to build the connections between photonic structures and the corresponding modes. Then we exemplify Stable Diffusion (SD) model to realize the function of optical fields generation from structure information. Our work introduces multi-modal deep learning to construct complex mapping between structural information and optical field as high-dimensional vectors, and generates optical field images based on this mapping.

We investigate the emergence of unconventional corner mode in a two-dimensional (2D) topolectrical circuits induced by asymmetric couplings. The non-Hermitian skin effect of two kinked one-dimensional (1D) lattices with multiple asymmetric couplings are explored. Then we extend to the 2D model, derive conditions for the non-Hermitian hybrid skin effect and show how the corner modes are formed by non-reciprocal pumping based on 1D topological modes. We provide explicit electrical circuit setups for realizing our observations via realistic LTspice simulation. Moreover, we show the time varying behaviors of voltage distributions to confirm our results. Our study may help to extend the knowledge on building the topological corner modes in the non-Hermitian presence.

In the original publication [...]

Background: Posterior internal fixation is the main method used for the treatment of thoracolumbar fractures. Fractures often occur in the upper 1/3 of the vertebral body. However, they can also occur in the middle or lower 1/3 of the vertebral body. At present, there is no report discussing the potential effects of sagittal location on instrument biomechanics or surgical strategy. The object of this study was to investigate the effect of the sagittal location of the fracture region of the vertebral body on the biomechanics of the internal fixation system and surgical strategy.Methods: A finite element model of the T11-L3 thoracolumbar segment was established based on a healthy person’s CT scan. Different sagittal fracture location finite element models were created by resection of the upper 1/3, middle 1/3, and lower 1/3 of the L1 vertebral body. Three surgical strategies were utilized in this study, namely, proximal 1 level and distal 1 level (P1-D1), proximal 2 level and distal 1 level (P2-D1), and proximal 1 level and distal 2 levels (P1-D2). Nine fixation finite element models were created by combining fracture location and fixation strategies. Range of motion, von Mises stress, and stress distribution were analyzed to evaluate the effects on the instrument biomechanics and the selection of surgical strategy.Results: In all three different fixation strategies, the maximum von Mises stress location on the screw did not change with the sagittal location of the fracture site; nevertheless, the maximum von Mises stress differed. The maximum rod stress was located at the fracture site, with its value and location changed slightly. In the same fixation strategy, a limited effect of sagittal location on the range of motion was observed. P2D1 resulted in a shorter range of motion and lower screw stress for all sagittal locations of the fracture compared with the other strategies; however, rod stress was similar between strategies.Conclusion: The sagittal location of a fracture may affect the intensity and distribution of stress on the fixation system but does not influence the selection of surgical strategy.

Abstract Radiation is a curative treatment for localized prostate cancer (PCa). Unfortunately, radiotherapeutic efficacy is often diminished when patients develop more aggressive or metastatic phenotypes. Recent studies have demonstrated that extracellular vesicles participate in cancer therapeutic resistance by delivering small bioactive molecules, such as small non‐coding RNAs. Here, we show that stromal cell‐derived small extracellular vesicles (sEVs) facilitate the radioresistance of PCa cells by transporting interleukin‐8 (IL‐8). Indeed, prostatic stromal cells secrete more IL‐8 than AR‐positive PCa cells, which can be accumulated in sEVs. Intriguingly, the uptake of stromal cells‐derived sEVs by radiosensitive PCa cells enhanced their radioresistance, which could be attenuated by silencing CXCL8 in stromal cells or inhibiting its receptor CXCR2 in PCa cells. sEV‐mediated radioresistance has been validated in zebrafish and mouse xenograft tumours. Mechanistically, the uptake of stromal sEVs triggers the AMPK‐activated autophagy pathway in PCa cells under the irradiation condition. Consequently, inactivating AMPK efficiently resensitized radiotherapy either by utilizing an AMPK inhibitor or silencing AMPKα in PCa cells. Furthermore, chloroquine (CQ), a lysosomal inhibitor, sufficiently resensitized radiotherapy via blockade of autophagolysosome fusion, leading to autophagosome accumulation in PC cells. Collectively, these results suggest that stromal cells enhance the radioresistance of PCa cells mainly through sEVs that deliver IL‐8.

Designing efficient sensing-memory-computing systems remains a challenge. Here, the authors propose a self-powered vertical tribo-transistor based on MXenes to implement the multi-sensing-memory-computing function and the interaction of multisensory integration.

Remarkable advances in fast magic-angle spinning (MAS) techniques significantly improve the resolution of 1H solid-state nuclear magnetic resonance (NMR) spectra. Here, we introduce a heteronuclear-filtered 1H homonuclear multi-quantum (MQ) correlation strategy available at a MAS rate of 100 kHz by combining 1H{X} heteronuclear-filtered methods and 1H homonuclear MQ correlation experiments. The proposed strategy was applied to selectively extract 1H signals of aluminum lactate (Al-Lac) in a mixture of Al-Lac and zinc lactate (Zn-Lac) using 27Al-filtered methods (i.e., 1H{27Al} heteronuclear multiple quantum correlation (HMQC) or 1H{27Al} symmetry-based resonance-echo saturation-pulse double-resonance (S-RESPDOR)). We demonstrate that incorporating these 27Al-filtered methods into two-dimensional (2D) 1H–1H double-quantum (DQ)/single-quantum (SQ), triple-quantum (TQ)/SQ, and even three-dimensional (3D) 27Al/1H(DQ)/1H(SQ) experiments can facilitate the acquisition of spectra without signal overlap and targeted characterization of the 1H species surrounding 27Al sites. The proposed strategy is considered to efficiently extract key structural information from complex spin systems.

Background: The therapeutic efficacy of cytokine-induced killer (CIK) cells versus dendritic cells (DC) co-cultured with CIK cells (DC-CIK) in treating esophageal cancer (EC) remains unclear due to the absence of a direct comparison of these two regimens. This study evaluated the comparative efficacy and safety of CIK cells versus DC-CIK using network meta-analysis in treating EC.Material and methods: We identified eligible studies from previous meta-analyses, then conducted an updated search to retrieve additional trials between February 2020 and July 2021. The primary outcomes included overall survival (OS), objective response rate (ORR), and disease control rate (DCR), and the secondary outcomes included quality of life improved rate (QLIR) and adverse events (AEs). A network meta-analysis of 12 studies was conducted using ADDIS software.Results: Twelve studies were identified, including six comparing CIK or DC-CIK plus chemotherapy (CT) with CT alone. Immunotherapy plus CT significantly improved overall survival (OS) (odds ratio [OR] 4.10, 95% confidence interval [CI] 1.23–13.69), objective response rate (ORR) (OR 2.72, 95% CI 1.79–4.11), disease control rate (DCR) (OR 3.45, 95% CI 2.32–5.14), and quality of life improvement rate (QLIR) (OR 3.54, 95% CI 2.31–5.41). DC-CIK+CT decreased the risk of leukopenia compared with CT alone. However, no statistical difference was detected between CIK-CT and DC-CIK+CT.Conclusion: Based on the available evidence, we concluded that CIK cell treatment is superior to CT alone, but CIK-CT and DC-CIK+CT may be comparable in treating EC. However, comparing CIK-CT and DC-CIK+CT is only based on indirect evidence, so it is undoubtedly necessary to conduct studies to compare CIK-CT with DC-CIK+CT in EC patients directly.

Objective: The aim of this research was to investigate the effect of vascular endothelial growth factor A (VEGFA)-overexpressing rat dental pulp stem cells (rDPSCs) combined with laminin-coated and yarn-encapsulated poly(l-lactide-co-glycolide) (PLGA) nerve guidance conduit (LC-YE-PLGA NGC) in repairing 10 mm facial nerve injury in rats. Study Design: rDPSCs isolated from rat mandibular central incisor were cultured and identified in vitro and further transfected with the lentiviral vectors (Lv-VEGFA). To investigate the role and mechanisms of VEGFA in neurogenic differentiation in vitro, semaxanib (SU5416), Cell Counting Kit-8 (CCK-8), real-time quantitative polymerase chain reaction (qPCR) and Western blotting were performed. Ten-millimeter facial nerve defect models in rats were established and bridged by LC-YE-PLGA NGCs. The repair effects were detected by transmission electron microscopy (TEM), compound muscle action potential (CMAP), immunohistochemistry and immunofluorescence. Results: Extracted cells exhibited spindle-shaped morphology, presented typical markers (CD44+CD90+CD34−CD45−), and presented multidirectional differentiation potential. The DPSCs with VEGFA overexpression were constructed successfully. VEGFA enhanced the proliferation and neural differentiation ability of rDPSCs, and the expression of neuron-specific enolase (NSE) and βIII-tubulin was increased. However, these trends were reversed with the addition of SU5416. This suggests that VEGFA mediates the above effects mainly through vascular endothelial growth factor receptor 2 (VEGFR2) binding. The LC-YE-NGC basically meet the requirements of facial nerve repair. For the in vivo experiment, the CMAP latency period was shorter in DPSCS-VEGFA-NGC group in comparison with other experimental groups, while the amplitude was increased. Such functional recovery correlated well with an increase in histological improvement. Further study suggested that VEGFA-modified DPSCs could increase the myelin number, thickness and axon diameter of facial nerve. NSE, βIII-tubulin and S100 fluorescence intensity and immunohistochemical staining intensity were significantly enhanced. Conclusion: VEGFA-modified rDPSCs combined with LC-YE-PLGA NGCs have certain advantages in the growth and functional recovery of facial nerves in rats.

Repairing load-bearing bone defects in children remains a big clinical challenge. Mineralized collagen (MC) can effectively simulate natural bone composition and hierarchical structure and has a good biocompatibility and bone conductivity. Polylactic acid (PLA) is regarded as a gold material because of its mechanical properties and degradability. In this study, we prepare MC/PLA composite scaffolds via in situ mineralization and freeze-drying. Cell, characterization, and animal experiments compare and evaluate the biomimetic properties and repair effects of the MC/PLA scaffolds. Phalloidin and DAPI staining results show that the MC/PLA scaffolds are not cytotoxic. CCK-8 and scratch experiments prove that the scaffolds are superior to MC and hydroxyapatite (HA)/PLA scaffolds in promoting cell proliferation and migration. The surface and interior of the MC/PLA scaffolds exhibit rich interconnected pore structures with a porosity of ≥70%. The XRD patterns are typical HA waveforms. X-ray, micro-CT, and H&E staining reveal that the defect boundary disappears, new bone tissue grows into MC/PLA scaffolds in a large area, and the scaffolds are degraded after six months of implantation. The MC/PLA composite scaffold has a pore structure and composition similar to cancellous bone, with a good biocompatibility and bone regeneration ability.

The modulation of Schottky barrier, which dominates the carrier injection in vertical organic field-effect transistors, strongly depends on the source electrode. Here, Chen et al. utilize MXene as a source electrode, achieving a subthreshold swing down to 73 mv/dec and a large gate control ability.

Objective: To observe the effect of electroacupuncture (EA) combined with oriented conductive bioprotein hydrogel (OCBH) on the recovery of nerve function in rats with complete spinal cord injury (SCI) and to explore its effect and mechanism on the formation and changes of glial scars. Methods: A total of 72 female Sprague–Dawley rats were randomly divided into groups according to the treatment received. A rat model of complete SCI was constructed using a spinal cord transection. Behavioral assessments, hematoxylin-eosin (H&E) staining, immunofluorescence staining, and Western blotting were performed at a fixed period after the operation. Results: The material group and the material + EA group obtained better results in the behavioral assessments (all P

Complex hierarchical architectures are ubiquitous in natural hard tissues, which comprise an elaborate assembly of hard and soft phases spanning from the nanoscale to the macroscale. The elegant architectures grant unique performance in terms of strength and toughness, but the biomimetic fabrication of synthetic materials with highly consistent structural and mechanical characteristics with natural counterparts remains a great challenge. Here, a centimeter‐size artificial lamellar bone is successfully fabricated for the first time via a well‐orchestrated “multiscale cascade regulation” strategy combining multiple techniques of molecular self‐assembly, electrospinning, and pressure‐driven fusion from molecular to macroscopic levels. The bulk artificial lamellar bone that is composed of hierarchically assembled mineralized collagen fibrils with a waiver of any synthetic polymer highly resembles the chemical composition, multiscale structural organization, and rotated plywood‐like structure of natural lamellae, thus achieving a good combination of lightweight and high‐stiffness (Ey ≈ 15.2 GPa), ‐strength (σf ≈ 118.4 MPa), and ‐toughness (KJC ≈ 9.3 MPa m1/2). This multiscale cascade regulation strategy can break through the limitations of a single technique and enable the construction of elaborate composite materials with multiscale step‐by‐step regulations of hierarchically structural organizations for unique mechanical properties.

Background: The nuclear receptor Nur77 has been demonstrated to play a vital role in the inflammatory response and cellular metabolisms, and its ligands exhibit efficacy in the treatment of inflammation-related diseases (e.g., improving mouse acute lung injury (ALI) and obesity. Recently, ω-3 polyunsaturated fatty acid-ethanolamine derivatives (ω-3 PUFA-EAs), including DPA-EA and DHA-EA, have been reported as new Nur77-targeting anti-inflammatory agents. However, the lipid-lowering effect of ω-3 PUFA-EAs is still unknown, and lipid profile changes induced by Nur77-targeting anti-inflammatory agents also remain unclear.Objective: This study aimed to evaluate the lipid-lowering effect and the underlying mechanism of DPA-EA acting as Nur77-targeting anti-inflammatory agents. It also aimed to investigate the in vitro and in vivo lipid-lowering effects of the DPA-EA and DHA-EA mixture prepared from algae oil.Methods: The in vitro lipid-lowing effect of DPA-EA and its mixture with DHA-EA was first evaluated in palmitic acid-stimulated HepG2 Cells. To confirm the lipid-lowering effect and explore the underlying mechanism, we performed untargeted lipidomic analysis using ultra-performance liquid chromatography/triple quadrupole-time-of-flight (TOF) mass spectrometry coupled with multivariate statistical analysis, with another Nur77-targeting anti-inflammatory compound Celastrol (Cel) as a reference. Finally, we examined the anti-obesity effect of the DPA-EA and DHA-EA mixture synthesized from algae oil in a high-fat diet (HFD)-fed mice model.Results: DPA-EA significantly alleviated lipid accumulation with lower toxicity than Celastrol. Nur77-targeting compounds DPA-EA and Celastrol could simultaneously reduce 14 lipids (9 TGs, 2 PCs, 1 PA, 1 SM, and 1 LacCer) and increase 13 lipids (4 DGs, 6 LPEs, 2 PEs, and 1PC) in Pal-stimulated HepG2 cells. However, Cer lipids were more sensitive to DPA-EA, while the over-downregulation of SM lipids might be associated with the off-target toxicity of Celastrol. The mixture of DPA-EA and DHA-EA synthesized from algae oil could significantly decrease TG, TC, and LDL levels and increase HDL levels in HFD-fed mice, exerting an excellent anti-obesity effect.Conclusion: Nur77-targeting anti-inflammatory compound DAP-EA could promote the hydrolysis of PEs and TGs to ameliorate lipid accumulation. The DPA-EA and DHA-EA mixture prepared from algae oil might be a potential therapeutic agent for obesity and other inflammation-related diseases.

For decades, researches have concentrated on the mechanical properties, biodegradation, and biocompatibility of implants used in the therapy of large size bone defect. In vivo studies demonstrate that bioabsorbable bone substitute materials can reduce the risk of common symptoms such as inflammation and osteonecrosis caused by bio-inert materials after long-term implantation. Several organic, inorganic, and composite materials have been approved for clinical application, based on their unique characteristics and advantages. Although some artificial bioabsorbable bone substitute materials have been used for years, there are still some disadvantages existing, such as low mechanical strength, high brittleness, and low degradation rate. Therefore, novel bioabsorbable composite materials biomaterials have been developed for bone defect repair. In this review, we provide an overview of the development of artificial bioabsorbable bone substitute materials and highlight the advantages and disadvantages. Furthermore, recent advances in bioabsorbable bone substitute materials used in bone defect repair are outlined. Finally, we discuss current challenges and further developments in the clinical application of bioabsorbable bone substitute materials.

Nerve guidance conduits with hollow lumen fail to regenerate critical-sized peripheral nerve defects (15 mm in rats and 25 mm in humans), which can be improved by a beneficial intraluminal microenvironment. However, individual cues provided by intraluminal filling materials are inadequate to eliminate the functional gap between regenerated nerves and normal nerves. Herein, an aligned fibrin/functionalized self-assembling peptide (AFG/fSAP) interpenetrating nanofiber hydrogel that exerting synergistic topographical and biochemical cues for peripheral nerve regeneration is constructed via electrospinning and molecular self-assembly. The hydrogel possesses an aligned structure, high water content, appropriate mechanical properties and suitable biodegradation capabilities for nerve repair, which enhances the alignment and neurotrophin secretion of primary Schwann cells (SCs) in vitro, and successfully bridges a 15-mm sciatic nerve gap in rats in vivo. The rats transplanted with the AFG/fSAP hydrogel exhibit satisfactory morphological and functional recovery in myelinated nerve fibers and innervated muscles. The motor function recovery facilitated by the AFG/fSAP hydrogel is comparable with that of autografts. Moreover, the AFG/fSAP hydrogel upregulates the regeneration-associated gene expression and activates the PI3K/Akt and MAPK signaling pathways in the regenerated nerve. Altogether, the AFG/fSAP hydrogel represents a promising approach for peripheral nerve repair through an integration of structural guidance and biochemical stimulation.

Abstract Background The interaction between programmed death receptor (PD-1) and its ligand (PD-L1) is essential for suppressing activated T-lymphocytes. However, the precise mechanisms underlying PD-L1 overexpression in tumours have yet to be fully elucidated. Here, we describe that RelB participates in the immune evasion of prostate cancer (PCa) via cis/trans transcriptional upregulation of PD-L1. Methods Based on transcriptome results, RelB was manipulated in multiple human and murine PCa cell lines. Activated CD4+ and CD8+ T cells were cocultured with PCa cells with different levels of RelB to examine the effect of tumourous RelB on T cell immunity. Male mice were injected with murine PCa cells to validate the effect of RelB on the PD-1/PD-L1-mediated immune checkpoint using both tumour growth and metastatic experimental models. Results PD-L1 is uniquely expressed at a high level in PCa with high constitutive RelB and correlates with the patients’ Gleason scores. Indeed, a high level of PD-L1 is associated with RelB nuclear translocation in AR-negative aggressive PCa cells. Conversely, the silencing of RelB in advanced PCa cells resulted in reduced PD-L1 expression and enhanced susceptibility of PCa cells to the T cell immune response in vitro and in vivo. Mechanistically, a proximal NF-κB enhancer element was identified in the core promoter region of the human CD274 gene, which is responsible for RelB-mediated PD-L1 transcriptional activation. This finding provides an informative insight into immune checkpoint blockade by administering RelB within the tumour microenvironment. Conclusion This study deciphers the molecular mechanism by which tumourous RelB contributes to immune evasion by inhibiting T cell immunity via the amplification of the PD-L1/PD-1-mediated immune checkpoint.

Cell types have been established during organogenesis based on early mouse embryos. However, our understanding of cell types and molecular mechanisms in the early embryo development of Mongolian sheep has been hampered. This study presents the first comprehensive single-cell transcriptomic characterization at E16 in Ujumqin sheep and Hulunbuir short-tailed sheep. Thirteen major cell types were identified at E16 in Ujumqin sheep, and eight major cell types were identified at E16 in Hulunbuir short-tailed sheep. Function enrichment analysis showed that several pathways were significantly enriched in the TGF-beta signaling pathway, the Hippo signaling pathway, the platelet activation pathway, the riboflavin metabolism pathway, the Wnt signaling pathway, regulation of the actin cytoskeleton, and the insulin signaling pathway in the notochord cluster. Glutathione metabolism, glyoxylate, and dicarboxylate metabolism, the citrate cycle, thyroid hormone synthesis, pyruvate metabolism, cysteine and methionine metabolism, thermogenesis, and the VEGF signaling pathway were significantly enriched in the spinal cord cluster. Steroid biosynthesis, riboflavin metabolism, the cell cycle, the Hippo signaling pathway, the Hedgehog signaling pathway, the FoxO signaling pathway, the JAK-STAT signaling pathway, and the Wnt signaling pathway were significantly enriched in the paraxial mesoderm cluster. The notochord cluster, spinal cord cluster, and paraxial mesoderm cluster were found to be highly associated with tail development. Pseudo-time analysis demonstrated that the mesenchyme can translate to the notochord in Ujumqin sheep. Molecular assays revealed that the Hippo signaling pathway was enriched in Ujumqin sheep. This comprehensive single-cell map revealed previously unrecognized signaling pathways that will further our understanding of the mechanism of short-tailed sheep formation.

The healing of bone defects after a fracture remains a key issue to be addressed. Globally, more than 20 million patients experience bone defects annually. Among all artificial bone repair materials that can aid healing, implantable scaffolds made from a mineralized collagen (MC) base have the strongest bionic properties. The MC/PLGA scaffold, created by adding Poly (lactic-co-glycolic acid) copolymer (PLGA) and magnesium metal to the MC substrate, plays a powerful role in promoting fracture healing because, on the one hand, it has good biocompatibility similar to that of MC; on the other hand, the addition of PLGA provides the scaffold with an interconnected porous structure, and the addition of magnesium allows the scaffold to perform anti-inflammatory, osteogenic, and angiogenic activities. Using the latest 3D printing technology for scaffold fabrication, it is possible to model the scaffold in advance according to the requirement and produce a therapeutic scaffold suitable for various bone-defect shapes with less time and effort, which can promote bone tissue healing and regeneration to the maximum extent. This study reviews the material selection and technical preparation of MC/PLGA scaffolds, and the progress of their research on bone defect treatment.

Increasing numbers of behavioral observations have shown that many organisms can sense magnetic fields in the environment. However, the underlying mechanisms of magnetosensation remain elusive, and a major problem is the lack of an animal model convenient for detecting magnetic responses, especially in vertebrates. We have previously reported that the physical performance of mice decreased after 1 month of exposure to a hypomagnetic field, which probably includes a light-independent mechanism. In this study, we investigated the effects of a static magnetic field on the locomotion of Xenopus tadpoles (stage 48) using a real-time recording system. Because it is speculated that the photosensing system is related to magnetosensation, we triggered the tadpoles to swim by a 30 s light pulse after a 5 min adaptation in the dark and measured the swimming activities of the tadpoles under static magnetic field exposure in both the dark and bright conditions. Compared to the sham control treatment, the presence of a magnet inhibited the movement of the tadpoles under both bright and dark conditions, as shown by reductions in swimming distance, speed, and counts of path adjustment. Moreover, the directional preference for path adaptation was altered when swimming in the dark. These results suggest that tadpoles in the dark can exert a rapid locomotion response to changes in the environmental magnetic field, providing evidence for an intrinsic, light-independent rapid magnetoresponse pathway in tadpoles. In addition, this rapid vertebrate locomotion assay paradigm will be a practical tool to facilitate further investigation of the mechanisms of biomagnetic effects.

We demonstrate the construction of the optical system in the atomic clock-beyond atomic fountain based on 87Rb atom. The optical system includes a high-stability laser system and an optical lattice. The high-stability laser system with the new scheme of frequency locking and shift is introduced in detail, which is an important laser source for laser cooling. The optimized frequency and intensity stability are achieved to 4 × 10–14τ−1/2 (τ is the averaging time) and 4 × 10–5τ−1/2, respectively, which are highly stable. On the basis of the conventional atomic fountain clock, the optical lattice is specially investigated along the direction of gravity and its characteristics are studied systematically. For the optimized and novel exploration, we predict the achievable stability of 3.6×10−14τ−1/2 and it has the potential to be improved to 3.6×10−15τ−1/2. The realizability of the construction due to the stabilized laser and optical lattice makes the beyond fountain promising candidate for the next-generation high performance microwave atomic clock.

The practical implementation of the employment promotion effect of the digital economy is closely linked to rural laborers’ digital skills (DS). Therefore, this study uses the Mprobit model to empirically test the impact of DS on rural labor employment choices. The results show that: (1) the acquisition of DS by the rural labor force significantly increases the rate of off-farm employment and entrepreneurship but has no significant effect on farm employment, with work skills having the most significant positive impact on the rural labor force off-farm employment and online business skills having the most significant positive impact on rural labor force entrepreneurship. (2) The mechanism test reveals that DS influences the employment choices of the rural labor force by alleviating the information access constraint and financing constraints faced by rural labor. (3) Heterogeneity analysis shows that males and rural laborers in rich regions can benefit from entrepreneurship. In contrast, females and low-skilled and rural laborers in middle and poor regions can benefit more from off-farm employment. Our findings provide empirical evidence on effectively cultivating DS to increase the diversity of employment choices for the rural workforce and highlight the importance of improving DS.

Chemotherapeutic resistance is a major obstacle in the control of advanced breast cancer (BCa). We have previously shown that small extracellular vesicles (sEVs) can transmit adriamycin resistance between BCa cells. Here, we describe that sEV‐mediated TGF‐β1 intercellular transfer is involved in the drug‐resistant transmission. sEVs were isolated and characterized from both sensitive and resistant cells. sEVs derived from the resistant cells were incubated with the sensitive cells and resulted in transmitting the resistant phenotype to the recipient cells. Cytokine antibody microarray revealed that most metastasis‐associated cytokines present at the high levels in sEVs from the resistant cells compared with their levels in sEVs from the sensitive cells, particularly TGF‐β1 is enriched in sEVs from the resistant cells. The sEV‐mediated TGF‐β1 intercellular transfer led to increasing Smad2 phosphorylation and improving cell survival by suppressing apoptosis and enhancing cell mobility. Furthermore, sEV‐mediated drug‐resistant transmission by delivering TGF‐β1 was validated using a zebrafish xenograft tumor model. These results elaborated that sEV‐mediated TGF‐β1 intercellular transfer contributes to adriamycin resistance in BCa.

Background: Periodontitis is associated with periodontal tissue damage and teeth loss. Nonalcoholic fatty liver disease (NAFLD) has an intimate relationship with periodontitis. Nevertheless, interacted mechanisms between them have not been clear. This study was intended for the exploration of shared gene signatures and latent therapeutic targets in periodontitis and NAFLD.Methods: Microarray datasets of periodontitis and NAFLD were obtained from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network analysis (WGCNA) was utilized for the acquisition of modules bound up with NAFLD and periodontitis. We used ClueGO to carry out biological analysis on shared genes to search their latent effects in NAFLD and periodontitis. Another cohort composed of differential gene analysis verified the results. The common microRNAs (miRNAs) in NAFLD and periodontitis were acquired in the light of the Human microRNA Disease Database (HMDD). According to miRTarbase, miRDB, and Targetscan databases, latent target genes of miRNAs were forecasted. Finally, the miRNAs–mRNAs network was designed.Results: Significant modules with periodontitis and NAFLD were obtained via WGCNA. GO enrichment analysis with GlueGo indicated that damaged migration of dendritic cells (DCs) might be a common pathophysiologic feature of NAFLD and periodontitis. In addition, we revealed common genes in NAFLD and periodontitis, including IGK, IGLJ3, IGHM, MME, SELL, ENPP2, VCAN, LCP1, IGHD, FCGR2C, ALOX5AP, IGJ, MMP9, FABP4, IL32, HBB, FMO1, ALPK2, PLA2G7, MNDA, HLA-DRA, and SLC16A7. The results of differential analysis in another cohort were highly accordant with the findings of WGCNA. We established a comorbidity model to explain the underlying mechanism of NAFLD secondary to periodontitis. Finally, the analysis of miRNA pointed out that hsa-mir-125b-5p, hsa-mir-17-5p, and hsa-mir-21-5p might provide potential therapeutic targets.Conclusion: Our study initially established a comorbidity model to explain the underlying mechanism of NAFLD secondary to periodontitis, found that damaged migration of DCs might be a common pathophysiological feature of NAFLD and periodontitis, and provided potential therapeutic targets.

Abstract Lagopsis supina (Steph) IK. Gal. was a traditional Chinese medicinal plant for promoting blood circulation and removing blood stasis (PBCRBS), anti-inflammatory and diuresis with little scientific validation. The aims of this study were first to evaluate the PBCRBS and anti-inflammatory effects of L. supina in a rat model of traumatic blood stasis (TBS). We demonstrated that an ethanolic extract of L. supina (LS, 460 mg/kg/d) possessed significant PBCRBS and remarkable inhibitory effect on inflammation cytokines, which were associated with renovated amount of the injured muscle fibers, alleviate the degree of the damaged tissue edema, decreased the number of inflammatory cells, increased the number of the capillary hyperplasia by hematoxylin and eosin (HE), as well as remarkably down-regulated ( p < 0.05 or p < 0.01) the levels of inflammation cytokines, including TNF-α, IL-6, IL-8, and IL-10 by ELISA. This finding provide a pharmacological basis and partial interpretation for the clinical application of L. supina, which has therapeutic properties for blood stasis syndrome (BSS) and inflammation-related diseases.

Abstract Background The incidence of adenocarcinoma of the esophagogastric junction (AEG) is rising every year; however, the mode of operation for Siewert II AEG is still controversial. Accumulating evidence has shown that transabdominal surgery is better than transthoracic surgery for Siewert II AEG with esophageal invasion < 3 cm. In patients with obesity, a large tumor size, and high transection of the esophagus, the transabdominal esophageal hiatus approach for lower mediastinal lymph node dissection and posterior mediastinal anastomosis is difficult. Thus, total laparoscopic radical resection of Siewert II AEG is carried out through the left diaphragm and left chest auxiliary hole for the optimal surgical field of vision and space. In this prospective study, we assessed the feasibility of carrying out the procedure abdominally through the left diaphragm and auxiliary hole. Methods Ten patients with Siewert II AEG were recruited between April and June 2019. Siewert II AEG was treated by total laparoscopy through the left diaphragm and left chest auxiliary hole. Clinicopathological features, surgical data, and adverse events were collected and analyzed in this prospective study. Results The average duration of the operation was 348 ± 37.52 min, lower mediastinal dissection took 20.6 min, the OrVil anastomosis time was 29.8 min, the time necessary to suture the seromuscular layer through the left thoracic auxiliary hole was 11 min, the safety margin was 3.2 cm, and the total number of lymph nodes dissected was 40.6. The number of lower mediastinal lymph nodes dissected was 6.2. The rate of lymph node metastasis in the N110 group was 9 ± 12.45%, and the average intraoperative blood loss was 170 ± 57.47 mL. No anastomotic leakage or anastomotic stricture occurred after the operation. The time of intestinal function recovery was 2 days, and the first time of enteral nutrition through a jejunal nutrition tube was 2.4 days. No tumor recurrence was found in 10 patients at 1 year postoperatively. Conclusion Total laparoscopic radical resection through the left diaphragm and left thoracic auxiliary hole for Siewert II AEG patients is feasible and safe. Thus, it may be a good surgical alternative for patients with esophageal tumors invading less than 3 cm. Trial registration ChiCTR, ChiCTR2000034286. Registered 8 July 2020, http://www.chictr.org.cn/showproj.aspx?proj=55866 .