Measurements of the gravitational constant using two independent methods.

The Newtonian gravitational constant, G, is one of the most fundamental constants of nature, but we still do not have an accurate value for it. Despite two centuries of experimental effort, the value of G remains the least precisely known of the fundamental constants. A discrepancy of up to 0.05 per cent in recent determinations of G suggests that there may be undiscovered systematic errors in the various existing methods. One way to resolve this issue is to measure G using a number of methods that are unlikely to involve the same systematic effects. Here we report two independent determinations of G using torsion pendulum experiments with the time-of-swing method and the angular-acceleration-feedback method. We obtain G values of 6.674184 × 10-11 and 6.674484 × 10-11 cubic metres per kilogram per second squared, with relative standard uncertainties of 11.64 and 11.61 parts per million, respectively. These values have the smallest uncertainties reported until now, and both agree with the latest recommended value within two standard deviations.

Nomogram for predicting venous thromboembolism after spinal surgery.

PURPOSE: This study aimed to establish a nomogram to predict the risk of venous thromboembolism (VTE), identifying potential risk factors, and providing theoretical basis for prevention of VTE after spinal surgery. METHODS: A retrospective analysis was conducted on 2754 patients who underwent spinal surgery. The general characteristics of the training group were initially screened using univariate logistic analysis, and the LASSO method was used for optimal prediction. Subsequently, multivariate logistic regression analysis was performed to identify independent risk factors for postoperative VTE in the training group, and a nomogram for predict risk of VTE was established. The discrimination, calibration, and clinical usefulness of the nomogram were separately evaluated using the C-index, receiver operating characteristic curve, calibration plot and clinical decision curve, and was validated using data from the validation group finally. RESULTS: Multivariate logistic regression analysis identified 10 independent risk factors for VTE after spinal surgery. A nomogram was established based on these independent risk factors. The C-index for the training and validation groups indicating high accuracy and stability of the model. The area under the receiver operating characteristic curve indicating excellent discrimination ability; the calibration curves showed outstanding calibration for both the training and validation groups. Decision curve analysis showed the clinical net benefit of using the nomogram could be maximized in the probability threshold range of 0.01-1. CONCLUSION: Patients undergoing spinal surgery with elevated D-dimer levels, prolonger surgical, and cervical surgery have higher risk of VTE. The nomogram can provide a theoretical basis for clinicians to prevent VTE.

Effects of different preservation schemes on isolated rat artery.

Allogeneic blood vessels are regarded as one of the best natural substitutes for diseased blood vessels due to their good vascular compliance and histocompatibility. Since the supply and demand of allograft blood vessels do not always match in time and space, a good preservation scheme for isolated blood vessels is essential. The abdominal aortas of 110 male Sprague-Dawley (SD) rats were randomly divided into three groups, including cold storage group (4°C) (CSG), frozen storage group (FSG) and ambient storage group (25 ± 2°C) (ASG). Seven time points of preservation for 1, 3, 5, 7, 14, 30 and 90 days were set for detection. The changes in vascular physiological function were evaluated by MTT test and vasoconstriction ability detection, and the changes in vascular wall structure were evaluated by the tension tolerance test and pathological staining. The vascular function of CSG was better than FSG within first the 7 days, but the result was opposite since the 14th day. The vascular wall structure, collagen and elastic fibres of vessels, in CSG, showed oedema within 30 days, and continuous disintegration and rupture at 90 days. The vessel wall structure of FSG remained intact within 90 days. The tensile strength of the vessels in CSG was better than that in FSG within 5 days, and there was no statistical difference between the two groups between the 7th and 30th day, and then, the FSG was higher than CSG on the 90th day. Both cold storage and frozen storage could be applied as safe and effective preservation schemes for isolated rat artery within first 30 days. Cold storage is recommended when the storage time is <14 days, and then, frozen storage is better.

Stanniocalcin-1 secreted by human umbilical mesenchymal stem cells regulates interleukin-10 expression via the PI3K/AKT/mTOR pathway in alveolar macrophages.

Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure caused by infection, trauma, shock, aspiration or drug reaction. The pathogenesis of ARDS is characterized as an unregulated inflammatory storm, which causes endothelial and epithelial layer damage, leading to alveolar fluid accumulation and pulmonary edema. Previous studies have shown the potential role of mesenchymal stem cells (MSC) in combating the inflammatory cascade by increasing the anti-inflammatory mediator interleukin-10 (IL-10). However, the involved mechanisms are unclear. Here we investigated whether a key immunomodulatory regulator, stanniocalcin-1 (STC-1), was secreted by MSC to activate phosphoinositide 3-kinase/protein kinase B (PI3K/AKT)/ mammalian target of rapamycin (mTOR) signaling pathway to increase IL-10 expression in alveolar macrophages. Lipopolysaccharide (LPS)-stimulated alveolar macrophages co-cultured with human umbilical mesenchymal stem cells (HUMSC) secreted high levels of IL-10. HUMSC co-cultured with alveolar macrophages expressed high STC-1 levels and increased PI3K, AKT and mTOR phosphorylation after LPS activation in alveolar macrophages. STC-1 knockdown in HUMSC decreased the phosphorylation of PI3K, AKT and mTOR and suppressed IL-10 expression in alveolar macrophages. Rapamycin (an mTOR inhibitor) reduced IL-10 secretion in alveolar macrophages. These results, together with our previous study and others, indicate that the PI3K/AKT/mTOR pathway is involved in the regulation of IL-10 production by STC-1 secreted by HUMSC in alveolar macrophages.

The coagulation-related genes for prognosis and tumor microenvironment in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a malignancy characterized by challenging early diagnosis and poor prognosis. It is believed that coagulation has an impact on the tumor microenvironment of PDAC. The aim of this study is to further distinguish coagulation-related genes and investigate immune infiltration in PDAC. METHODS: We gathered two subtypes of coagulation-related genes from the KEGG database, and acquired transcriptome sequencing data and clinical information on PDAC from The Cancer Genome Atlas (TCGA) database. Using an unsupervised clustering method, we categorized patients into distinct clusters. We investigated the mutation frequency to explore genomic features and performed enrichment analysis, utilizing Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) to explore pathways. CIBERSORT was used to analyze the relationship between tumor immune infiltration and the two clusters. A prognostic model was created for risk stratification, and a nomogram was established to assist in determining the risk score. The response to immunotherapy was assessed using the IMvigor210 cohort. Finally, PDAC patients were recruited, and experimental samples were collected to validate the infiltration of neutrophils using immunohistochemistry. In addition, and identify the ITGA2 expression and function were identified by analyzing single cell sequencing data. RESULTS: Two coagulation-related clusters were established based on the coagulation pathways present in PDAC patients. Functional enrichment analysis revealed different pathways in the two clusters. Approximately 49.4% of PDAC patients experienced DNA mutation in coagulation-related genes. Patients in the two clusters displayed significant differences in terms of immune cell infiltration, immune checkpoint, tumor microenvironment and TMB. We developed a 4-gene prognostic stratified model through LASSO analysis. Based on the risk score, the nomogram can accurately predict the prognosis in PDAC patients. We identified ITGA2 as a hub gene, which linked to poor overall survival (OS) and short disease-free survival (DFS). Single-cell sequencing analysis demonstrated that ITGA2 was expressed by ductal cells in PDAC. CONCLUSIONS: Our study demonstrated the correlation between coagulation-related genes and the tumor immune microenvironment. The stratified model can predict the prognosis and calculate the benefits of drug therapy, thus providing the recommendations for clinical personalized treatment.

Efficacy of levocetirizine in isolated rat tracheal smooth muscle.

Histamine receptor-1 (H1) antagonists like levocetirizine are frequently used nowadays to treat rhinitis patients who experience rhinorrhea and sneezing. The trachea may be affected by the H1 antagonist when it is used to treat nasal symptoms, either orally or through inhalation. The purpose of this study was to ascertain in vitro effects of levocetirizine on isolated tracheal smooth muscle. As a parasympathetic mimetic, methacholine (10-6 M) causes contractions in tracheal smooth muscle, which is how we tested effectiveness of levocetirizine on isolated rat tracheal smooth muscle. We also tested the drug's impact on electrically induced tracheal smooth muscle contractions. The impact of menthol (either before or after) on the contraction brought on by 10-6 M methacholine was also investigated. According to the results, the addition of levocetirizine at concentrations of 10-5 M or more caused a slight relaxation in response to methacholine's 10-6 M contraction. Levocetirizine could prevent spike contraction brought on by electrical field stimulation (EFS). As the concentration rose, it alone had a neglect effect on the trachea's basal tension. Before menthol was applied, levocetirizine might have also inhibited the function of the cold receptor. According to this study, levocetirizine might potentially impede the parasympathetic function of the trachea. If levocetirizine was used prior to menthol addition, it also reduced the function of cold receptors.

Enhanced High Thermal Conductivity Cellulose Filaments via Hydrodynamic Focusing.

Nanocellulose is regarded as a green and renewable nanomaterial that has attracted increased attention. In this study, we demonstrate that nanocellulose materials can exhibit high thermal conductivity when their nanofibrils are highly aligned and bonded in the form of filaments. The thermal conductivity of individual filaments, consisting of highly aligned cellulose nanofibrils, fabricated by the flow-focusing method is measured in dried condition using a T-type measurement technique. The maximum thermal conductivity of the nanocellulose filaments obtained is 14.5 W/m-K, which is approximately five times higher than those of cellulose nanopaper and cellulose nanocrystals. Structural investigations suggest that the crystallinity of the filament remarkably influence their thermal conductivity. Smaller diameter filaments with higher crystallinity, that is, more internanofibril hydrogen bonds and less intrananofibril disorder, tend to have higher thermal conductivity. Temperature-dependence measurements also reveal that the filaments exhibit phonon transport at effective dimension between 2D and 3D.

Effects of different preservation methods of human iliac veins.

With the progress of vascular anastomosis technology, the radical resection surgery of cancer combining with vascular resection and reconstruction has been focused by surgeon. As a natural substitute material for blood vessel, vascular allografts have good vascular compliance and histocompatibility. Generally, the donated veins could not be used immediately, and need to be well preserved. So, it is greatly significant to do research in the preservation effects of different preservation methods on veins. In this study, the effects of different preservative methods of human iliac veins were compared and analyzed in terms of cell viability, vascular wall structure and tension resistance. The donated human iliac veins were randomly divided into three groups: Cold Storage Group (4 °C) (CSG), Frozen Storage Group (-186 °C) (FSG)and Fresh Control Group (FCG). Six detection time-points of preservation for 1, 3, 5, 7, 14, 28 days were set respectively. There are ten samples in each group and each time-point separately. Survival and apoptosis of vascular cell were evaluated by MTT assay and Tunel fluorescence staining. Tensile test was used to evaluate mechanical properties of vessels. The changes of vascular endothelial cells, smooth muscle cells, collagen fibers and elastic fibers were evaluated by HE staining, Masson staining and EVG staining. Furthermore, the changes of organelles were observed by transmission electron microscope. With the extension of preservation period, the vascular cell viability and tension resistance of two groups decreased, and the apoptotic cells increased gradually. The apoptosis index of CSG was higher than FSG at each time point (P < 0.05). In terms of cell viability, CSG was higher within 3 days (P < 0.05), both groups were same between 3 and 14 days, and then CSG lower than FSG after 14 days (P < 0.05). In terms of tension resistance, CSG was stronger than FSG (P < 0.05) in first 7 days, both groups were same in 2nd week, and then CSG was weaker in 4th week (P < 0.05). In terms of vascular wall structure, in CSG, vascular endothelial cells were damaged and shed, smooth muscle cells were edema after 14 days, but the cell membrane and intercellular connection were still intact. In 4th week, endothelial cells were completely damaged and shed, the boundary of smooth muscle cell membrane was unclear, intercellular connection was damaged. Moreover, organelles were destroyed and disappeared, perinuclear condensation of chromatin was observed, and some cells had incomplete nuclear membrane or nuclear fragmentation; However, there were no obvious changes in the FSG within 28 days. Finally, local exfoliation and destruction of endothelial cells and edema-like changes of organelles were observed; the collagen fibers and elastic fibers of blood vessels in the two groups had no obvious damage and change within 28 days. For excised human iliac vein, cold and frozen storage can effectively preserve the cell viability, wall structure and tension resistance of blood vessels. With the extension of preservation time, the related performance of vessels declined in varying degrees. Within first week, the effect of cold storage is better than frozen storage, but frozen storage is significantly better than cold storage after 2 weeks.

PAICS/DYRK3 Multienzyme Interactions as Coregulators of Purinosome Formation and Metabolism on Radioresistance in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a prevalent type of oral cancer. While therapeutic innovations have made strides, radioresistance persists as a significant hindrance in OSCC treatment. Despite identifying numerous targets that could potentially suppress the oncogenic attributes of OSCC, the exploration of oncogenic protein kinases for cancer therapy remains limited. Consequently, the functions of many kinase proteins in OSCC continue to be largely undetermined. In this research, we aim to disclose protein kinases that target OSCC and elaborate their roles and molecular mechanisms. Through the examination of the kinome library of radiotherapy-resistant/sensitive OSCC cell lines (HN12 and SAS), we identified a key gene, the tyrosine phosphorylation-regulated kinase 3 (DYRK3), a member of the DYRK family. We developed an in vitro cell model, composed of radiation-resistant OSCC, to scrutinize the clinical implications and contributions of DYRK3 and phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS) signaling in OSCC. This investigation involves bioinformatics and human tissue arrays. We seek to comprehend the role of DYRK3 and PAICS signaling in the development of OSCC and its resistance to radiotherapy. Various in vitro assays are utilized to reveal the essential molecular mechanism behind radiotherapy resistance in connection with the DYRK3 and PAICS interaction. In our study, we quantified the concentrations of DYRK3 and PAICS proteins and tracked the expression levels of key pluripotency markers, particularly PPAT. Furthermore, we extended our investigation to include an analysis of Glut-1, a gene recognized for its linkage to radioresistance in oral squamous cell carcinoma (OSCC). Furthermore, we conducted an in vivo study to affirm the impact of DYRK3 and PAICS on tumor growth and radiotherapy resistance, focusing particularly on the role of DYRK3 in the radiotherapy resistance pathway. This focus leads us to identify new therapeutic agents that can combat radiotherapy resistance by inhibiting DYRK3 (GSK-626616). Our in vitro models showed that inhibiting PAICS disrupts purinosome formation and influences the survival rate of radiation-resistant OSCC cell lines. These outcomes underscore the pivotal role of the DYRK3/PAICS axis in directing OSCC radiotherapy resistance pathways and, as a result, influencing OSCC progression or therapy resistance. Our findings also reveal a significant correlation between DYRK3 expression and the PAICS enzyme in OSCC radiotherapy resistance.

Validation of Fespixon in Postoperative Scar Cosmesis Using Quantitative Digital Photography Analysis.

BACKGROUND: Unsightly scarring after surgery remains a dilemma. One of the challenges is the lack of objective scar assessment tools. OBJECTIVES: This study aimed to evaluate the efficacy of a novel medicine, Fespixon, for prevention and/or alleviation of post-skin incision scarring. A second aim was to demonstrate the practicality of our digital image analysis system to see if this could serve as a sensitive tool to assess scar improvement. METHODS: A prospective, placebo-controlled trial involving patients with postoperative transverse scars was conducted. Each patient received a topical formulation of Fespixon on the left part of the scar and placebo cream on the right. In addition to recording the subjective modified Vancouver Scar Scale and visual analog scale scores, we utilized digital photography for monthly scar analysis, with CIELAB and hue serving as the colorimetric information, and with contrast, correlation, homogeneity, and entropy providing texture information. RESULTS: Forty-six participants (mean age, 52 years) were enrolled in the trial. All the parameters of subjective assessment showed superior results for the Fespixon-treated side, with significant differences in pigmentation, vascularity, pliability, height, itchiness, and patient satisfaction (P = .043, .013, .026, .002, .039, .012, respectively). The trends in color and texture showed increased relative difference ratios, with significant differences in most of the eigenvalues towards the Fespixon-treated side, including CIELAB-L* (P = .000), hue-R,G,B (red, blue, green) values (P = .034, .001, .011), contrast (P = .000), homogeneity (P = .000), correlation (P = .011), and entropy (P = .000). CONCLUSIONS: We validated the efficacy of Fespixon for postoperative scar healing based not only on subjective assessments but also on objective quantitative analyses. The results also indicated that our digital photography quantitative analysis system is an ideal tool for quantification of scar appearance.

Arm locking using laser frequency comb.

The space-borne gravitational wave (GW) detectors, e.g., LISA, TaiJi, and TianQin, will open the window in the low-frequency regime (0.1 mHz to 1 Hz) to study the highly energetic cosmic events, such as coalescences and mergers of binary black holes and neutron stars. For the sake of successful observatory of GWs, the required strain sensitivity of the detector is approximately 10-21/Hz1/2 in the science band, 7 orders of magnitude better than the state of the art of the ultra-stable laser. Arm locking is therefore proposed to reduce the laser phase noise by a few orders of magnitude to relax the burden of time delay interferometry. During the past two decades, various schemes have been demonstrated by using single or dual arms between the spacecraft, with consideration of the gain, the nulls in the science band, and the frequency pulling characteristics, etc. In this work, we describe an updated version of single arm locking, and the noise amplification due to the nulls can be flexibly restricted with the help of optical frequency comb. We show that the laser phase noise can be divided by a specific factor with optical frequency comb as the bridge. The analytical results indicate that, the peaks in the science band have been greatly reduced. The performance of the noise suppression shows that the total noise after arm locking can well satisfy the requirement of time delay interferometry, even with the free-running laser source. When the laser source is pre-stabilized to a Fabry-Perot cavity or a Mach-Zehnder interferometer, the noise can reach the floor determined by the clock noise, the spacecraft motion, and the shot noise. We also estimate the frequency pulling characteristics of the updated single arm locking, and the results suggest that the pulling rate can be tolerated, without the risk of mode hopping. Arm locking will be a valuable solution for the noise reduction in the space-borne GW detectors. We demonstrate that, with the precise control of the returned laser phase noise, the noise amplification in the science band can be efficiently suppressed based on the updated single arm locking. Not only does our method allow the suppression of the peaks, the high gain, and low pulling rate, it can also serve for full year, without the potential risk of locking failure due to the arm length mismatch. We then discuss the unified demonstration of the updated single arm locking, where both the local and the returned laser phase noises can be tuned to generate the expected arm-locking sensor actually. Finally, the time-series simulations in Simulink have been carried out, and the results indicate a good agreement with the theory, showing that the presented method is reasonable and feasible. Our work could provide a back-up strategy for the arm locking in the future space-borne GW detectors.

Constraining the Symmetron Model with the HUST-2020 Torsion Pendulum Experiment.

The search for dynamically screening the coupling between the scalar field and matter in high-density environment is achievable with the symmetron model. The high-accuracy and short-range gravity experiment is proposed to test the symmetron model. In this Letter, the data of the HUST-2020 torsion pendulum experiment testing the inverse-square law at submillimeter range is analyzed to constrain the symmetron model. The results show that the HUST-2020 experiment is uniquely sensitive to probe the symmetron model with a mass scale of µ=7.2×10^{-3} eV, and the self-coupling parameter λ≲105 is excluded at mass scale M=0.3 TeV. Especially, at the dark energy scale µ=2.4×10^{-3} eV, the constraint at M=1.3 TeV is improved by about 10 times the previous constraints on the torsion pendulum experiment.

Quantitative Measurement of Adult Human Larynx post General Anesthesia with Intubation.

Introduction: Post-anaesthetic sore throat (PAST) is a well-recognized consequence of tracheal intubation; however, quantitative morphometric measurements remain challenging. This study aimed to introduce a special laser projection device that can facilitate computer-assisted, digitalized analysis and provide important information on laryngeal mucosa change, pre and post-surgery under general anesthesia with intubation. Materials and methods: The laryngeal images were captured and divided into the control group and the intubation group. Image processing techniques were used to quantify the post-extubation laryngeal variation, with its distinct color space and texture features. Meanwhile, the maximum length of the vocal fold, vocal width at the midpoint, and maximum cross-sectional area of the glottic space were determined and calculated. These parameters were analyzed and compared pre and post-surgery. Results: A total of 69 subjects were enrolled in this study, comprising 32 subjects in the healthy group and 37 subjects in the intubation group. The color space and texture analysis with contrast and correlation profiles all shows trend toward higher measures in the intubation group than in the healthy group, with statistical significance and outstanding discrimination ability, especially in the interarytenoid region. The incidence of PAST was approximately 46% (17 patients). The gender difference, type of surgery, and the fixation position of the tube were not significantly related to the PAST occurrence. All the eigenvalues showed significant differences pre and post-surgery in the interarytenoid region and a significant trend toward red and increased contrast texture profiles was revealed. Furthermore, the glottic area showed a significant decrease of 25.29%, while the vocal width showed a significant increase post extubation. Conclusion: Our equipment and processing can measure subtle laryngeal changes that would allow a clinician to diagnose postoperative laryngeal inflammation in a simpler and less invasive way. The trend toward red, the increased contrast texture and vocal width, and the reduced glottic space were all compatible with post-intubation inflammatory response, especially in the interarytenoid region. This is important to know so that one can take appropriate steps to alleviate PAST in the future.

Positive regulation of ataxia-telangiectasia-mutated protein (ATM) by E2F transcription Factor 1 (E2F-1) in cisplatin-resistant nasopharyngeal carcinoma cells.

OBJECTIVE: To explore the mechanism of E2F transcription Factor 1 (E2F-1)-mediated ataxia-telangiectasia-mutated protein (ATM) in cisplatin (DDP)-resistant nasopharyngeal carcinoma (NPC). METHODS: E2F-1 and ATM expression was assessed in DDP-resistant NPC cell lines (CNE2/DDP and HNE1/DDP) and parental cells. Then, DDP-resistant NPC cells were transfected with control shRNA (short hairpin RNA) or E2F-1 shRNAs with or without ATM lentiviral activation particles. The half maximal inhibitory concentration (IC50) was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, and the cell cycle and cell proliferation were measured by flow cytometry and EdU staining, respectively. In addition, the expression of genes and proteins was quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. RESULTS: Both E2F-1 and ATM expression in DDP-resistant NPC cells was much higher than that in parental cells. E2F-1 shRNA reduced ATM expression in DDP-resistant NPC cells, but ATM overexpression had no significant effect on E2F-1. ATM overexpression enhanced DDP resistance in DDP-resistant NPC cells with increased IC50 values, which was reversed by E2F-1 inhibition. Meanwhile, ATM overexpression resulted in upregulation of ABCA2 and ABCA5 in DDP-resistant NPC cells, induced elevations in the transition of the cells into S-phase, and increased cell proliferation with enhanced expression of cyclin E1, CDK2, and Ki67, which was reversed by E2F-1 shRNAs. CONCLUSION: Downregulation of E2F-1, possibly by regulating ATM, could block the cell cycle in the G1 phase and reduce the proliferation of CNE2/DDP cells, thereby reversing the resistance of human NPC cells to DDP.

A combination of the percentages of IFN-γ+CD4+T cells and granzyme B+CD19+B cells is associated with acute hepatic rejection: a case control study.

BACKGROUND: T cells and B cells play a key role in alloimmune responses. We aimed to characterize the shift of T cell subsets and B cell subsets during acute hepatic rejection, and further determine whether they could serve as a prognostic marker. METHODS: Blood samples together with the clinical data from liver transplant recipients with and without acute hepatic rejection were collected and analyzed as well as from a validation cohort. RESULTS: Upon activation the expression of TGF-ß and granzyme B in CD19+B cells, and the expression of IL-2 and IFN-γ in CD4+T cells were higher in acute hepatic rejection. However, only the frequencies of granzyme B+CD19+B cells and IFN-γ+CD4+T cells correlated with liver function in addition to with each other. A combination of the two cell subsets as a novel marker could classify rejection versus non-rejection (area under the curve 0.811, p = 0.001) with the cut-off value of 62.93%, which was more sensitive for worse histological changes (p = 0.027). Moreover, the occurrence rate of acute rejection was higher in the group with the novel marker > 62.93% (p = 0.000). The role of the novel marker was further confirmed in a validation cohort, which was identified to be the only significant independent risk factor for acute rejection (odds ratio: 0.923; 95% CI confidence interval: 0.885-0.964; p = 0.000). CONCLUSIONS: A combination of the percentages of IFN-γ+CD4+T cells and granzyme B+CD19+B cells can distinguish rejection from non-rejection, which can be used as a potential prognostic marker for acute rejection in liver transplant recipients.

Phylotranscriptomics reveals the complex evolutionary and biogeographic history of the genus Tsuga with an East Asian-North American disjunct distribution.

The disjunct distribution between East Asia and North America is one of the best established biogeographic patterns. A robust phylogeny is fundamental for understanding the biogeographic histories of taxa with this distribution pattern. Tsuga (hemlock) is a genus of Pinaceae with a typical intercontinental disjunct distribution in East Asia and eastern and western North America, and its phylogeny has not been completely reconstructed in previous studies. In this study, we reconstructed a highly resolved phylogeny of Tsuga using 881 nuclear genes, 60 chloroplast genes and 23 mitochondrial genes and explored its biogeographic and reticulate evolutionary history. The results of phylogenetic analysis, molecular dating and ancestral area reconstruction indicate that Tsuga very likely originated from North America in the late Oligocene and dispersed from America to East Asia via the Bering Land Bridge during the middle Miocene. In particular, we found complex reticulate evolutionary pattern among the East Asian hemlock species. T. sieboldii possibly originated from hybridization with the ancestor of T. chinensis from mainland China and T. forrestii as the paternal donor and the ancestor of T. diversifolia and T. ulleungensis as the maternal donor. T. chinensis (Taiwan) could have originated by hybridization together with T. sieboldii and then evolved independently after dispersal to the Taiwan Island, subsequently experiencing mitochondrial DNA introgression with T. chinensis from mainland China. Moreover, our study found that T. chinensis from western China is more closely related to T. forrestii than to T. chinensis from eastern China. The nonmonophyletic T. chinensis needs taxonomic reconsideration.

Isoorientin inhibits epithelial-to-mesenchymal properties and cancer stem-cell-like features in oral squamous cell carcinoma by blocking Wnt/ß-catenin/STAT3 axis.

Oral squamous cell carcinoma (OSCC) is among the most prevalent cancers of the head and neck. This study revealed that isoorientin attenuates OSCC cell stemness and epithelial-mesenchymal transition potential through the inhibition of JAK/signal transducer and activator of transcription 3 (STAT3) and Wnt/ß-catenin signaling in cell lines. Our findings indicated that isoorientin is a potential inhibitor of ß-catenin/STAT3 in vitro and in vivo. We analyzed possible synergism between isoorientin and cisplatin in OSCC. A sulforhodamine B assay, colony formation assay, tumorsphere-formation assay, and Wnt reporter activity assay were used for determining cell invasion, cell migration, drug cytotoxicity, and cell viability with potential molecular mechanisms in vitro. Isoorientin reduced the expression of p-STAT3, ß-catenin, and p-GSK3 as well as downstream effectors TCF1/TCF7 and LEF1 and significantly reduced ß-catenin colocalization in the nucleus. Isoorientin markedly strengthened the cytotoxic effects of cisplatin against SAS and SCC-25. Therefore, combining isoorientin and cisplatin treatments can potentially improve the anticancer effect of cisplatin. Isoorientin inhibited the tumorigenicity and growth of OSCC through the abrogation of Wnt/ß-catenin/STAT3 signaling in vivo. Thus, isoorientin disrupted the ß-catenin signaling pathway through the inactivation of STAT3 signaling. In conclusion, targeting OSCC-SC-mediated stemness with isoorientin to eradicate OSCC-SCs may be an effective strategy for preventing relapse and metastasis of OSCC and providing long-term survival benefits.

Combined Test of the Gravitational Inverse-Square Law at the Centimeter Range.

Experiments measuring the Newtonian gravitational constant G can offer uniquely sensitive probes of the test of the gravitational inverse-square law. An analysis of the non-Newtonian effect in two independent experiments measuring G is presented, which permits a test of the 1/r^{2} law at the centimeter range. This work establishes the strongest bound on the magnitude α of Yukawa-type deviations from Newtonian gravity in the range of 5-500 mm and improves the previous bounds by up to a factor of 7 at the length range of 60-100 mm.

Adipose-derived stem cell induced-tissue repair or wound healing is mediated by the concomitant upregulation of miR-21 and miR-29b expression and activation of the AKT signaling pathway.

BACKGROUND: Adipose-derived stem cells (ADSCs), a subpopulation of mesenchymal stem cells, are characterized by their potential to differentiate into multiple cell lineages. Due to their abundance and relative ease of procurement, ADSCs are widely used for tissue repair and regeneration. However, the molecular mechanisms of the therapeutic effect of ADSCs remain unknown. METHODS: MicroRNAs have emerged as important signaling molecules in skin wound healing, and their roles in ADSC-based therapies must be addressed. Here, we investigated the potential of ADSCs in improving cutaneous wound healing in vitro and in vivo. RESULTS: We simulated the microenvironment of the wound site by coculturing human dermal fibroblasts (HDFs) with ADSCs. We found that cocultured HDFs expressed significantly higher levels of miR-29b and miR-21 and had higher proliferation and migration rates than ADSCs cultured without HDFs. Moreover, increased expression of Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type III Alpha 1 Chain (COL3A1), alpha-smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), and Phosphoinositide 3-kinase (PI3K), p-Akt and decreased expression of Phosphatase and tensin homolog (PTEN) and matrix metalloproteinase (MMP)-1 was detected, suggesting extracellular remodeling and fibroblast activation and proliferation. We validated the in vitro results by using a rodent skin excisional wound model and implanted ADSC sheets in the wound. Compared with the controls, wounds implanted with ADSC sheets had significantly higher rates of wound-closure; increased expression of α-SMA, VEGF, PI3k, PTEN, COL1A1, and COL3A1; decreased expression of PTEN and MMP1; and upregulated levels of miR-29b and miR-21 in the skin. CONCLUSION: In summary, we evidenced that ADSCs facilitate the increase in miR-29b and miR-21 levels and promote the activation and proliferation of dermal fibroblasts and extracellular matrix (ECM) remodeling, with the associated release of VEGF. Thus, the ADSC-mediated increase in microRNAs is essential in tissue repair and has a therapeutic potential in cutaneous wound healing.

Systematic profiling of diagnostic and prognostic value of autophagy-related genes for sarcoma patients.

BACKGROUND: Autophagy-related genes (ARGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of ARGs and their clinical significance in sarcoma patients is lacking. METHODS: Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed ARGs (DEARGs) were determined by matching the DEG and HADb gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEARGs was conducted, and associations with tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for disease-free survival (DFS), were established and validated in an independent set. RESULTS: In total, 84 DEARGs and two clusters were identified. TME scores, five immune checkpoints, and several types of immune cells were found to be significantly different between two clusters. Two prognostic signatures incorporating DEARGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.818 and 0.747 for the OS and DFS nomograms, respectively. CONCLUSION: This comprehensive analyses of the ARG landscape in sarcoma showed novel ARGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.