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Many synthetic biology applications rely on programming living cells using gene circuits - the assembly and wiring of genetic elements to control cellular behaviors. Extensive progress has been made in constructing gene circuits with diverse functions and applications. For many circuit functions, however, it remains challenging to ensure that the circuits operate in a predictable manner. Although the notion of predictability may appear intuitive, close inspection suggests that it is not always clear what constitutes predictability. We dissect this concept and how it can be confounded by the complexity of a circuit, the complexity of the context, and the interplay between the two. We discuss circuit engineering strategies, in both computation and experiment, that have been used to improve the predictability of gene circuits.

The rise in markups and market power documented by De Loecker, Eeckhout, and Unger (2020) has recently generated much discussion in economics. We measure the correlation between the change in firm level markups and the change in industry level prices as measured by the Producer Price Index and find little to no relationship both for 1980-2018 and 2018-present. While a “false negative” result due to mismeasurement is possible, it also raises the possibility that firms have not passed along declines in marginal costs to consumers or that there have been significant changes in scale elasticities.

The results of armored vehicle driving training are affected by many factors. In order to evaluate the driving level of drivers more comprehensively and accurately, this paper comprehensively considers many factors and carries out research on the evaluation of driver driving training. By comparing and analyzing various evaluation methods, the appropriate evaluation method is selected according to the characteristics of driving training evaluation. Then the single evaluation index is determined and the evaluation index system of driving training is established. The evaluation model of driving training is established according to the characteristics of evaluation index.

The stability of metastable t-ZrO2 instead of its fraction in an oxide film is a key factor for the protectiveness of the oxide film and corrosion resistance of Zr alloys, and the stability of t-ZrO2 is influenced by alloying elements such as Nb and Sn.

ContextPrimary aldosteronism (PA) patients have a higher degree of arterial stiffness, which can be reversed after adrenalectomy.ObjectiveWe aimed to compare the reversal of arterial stiffness between surgically and medically treated PA patients and to identify the predictors of effective medical treatment.MethodsWe prospectively enrolled 445 PA patients and collected data on baseline clinical characteristics, biochemistry, blood pressure, and pulse wave velocity (PWV) before treatment and 12 months after treatment. In the mineralocorticoid receptor antagonist (MRA)-treated patients, the relationship between the change in PWV after 1 year (ΔPWV) and posttreatment renin activity was explored using the restricted cubic spline (RCS) method.ResultsOf the 445 enrolled PA patients, 255 received adrenalectomy (group 1) and 190 received MRAs. In the RCS model, posttreatment plasma renin activity (PRA) 1.5 ng/mL/h was the best cutoff value. Therefore, we divided the MRA-treated patients into 2 groups: those with suppressed PRA (< 1.5 ng/mL/h, group 2), and those with unsuppressed PRA (≥ 1.5 ng/mL/h, group 3). Only group 1 and group 3 patients had a statistically significant improvement in PWV after treatment (both P < .001), whereas no significant improvement was noted in group 2 after treatment (P = .151). In analysis of variance and post hoc analysis, group 2 had a significantly lower ΔPWV than group 1 (P = .007) and group 3 (P = .031). Multivariable regression analysis of the MRA-treated PA patients identified log-transformed posttreatment PRA, age, and baseline PWV as independent factors correlated with ΔPWV.ConclusionThe reversal of arterial stiffness was found in PA patients receiving adrenalectomy and in medically treated PA patients with unsuppressed PRA.

Osimertinib is an EGFR tyrosine kinase inhibitor (TKI) with proven clinical efficacy; however, acquired resistance presents an obstacle to curing EGFR-driven disease. Recent studies have shown that drug-tolerant persister cells (DTP) have a distinct transcriptional profile that may confer specific vulnerabilities. By definition these cells avoid apoptosis, yet little is known about how their survival is regulated. We found that paradoxically, the proapoptotic gene BIM was upregulated in osimertinib DTPs, and cotreatment with BH3 mimetics could trigger DTP cell death. Furthermore, cIAP proteins, antiapoptotic members of the extrinsic pathway, were significantly elevated in DTPs. cIAP antagonists could block DTP formation as an up-front combination, and could eliminate preformed DTPs. Critically, when treated at the time of maximal osimertinib response, cIAP or MCL1 inhibitor treatment could significantly attenuate the regrowth of EGFRm cell line mouse xenografts. Finally, we show that apoptosis can be maximized in cell lines with acquired osimertinib resistance by combining BH3 or SMAC mimetics with agents that target the resistance driver in these models. Taken together, these data suggest novel therapeutic strategies at the point of minimal residual disease or full osimertinib resistance for patients in this critical area of unmet need. Significance: These studies uncover strategies to use targeted agents that activate apoptosis in non–small cell lung cancer cells that survive initial EGFR TKI treatment.

Hypoxia-induced cardiomyocyte apoptosis is the main contributor to heart diseases. Human leukocyte antigen F-associated transcript 10 (FAT10), the small ubiquitin-like protein family subtype involved in apoptosis, is expressed in the heart and exhibits cardioprotective functions. This study explored the impact of FAT10 on hypoxia-induced cardiomyocyte apoptosis and the involved mechanisms. The cardiomyocyte cell line H9C2 was cultivated in hypoxia-inducing conditions (94% N2, 5% CO2, and 1% O2) and the expression of FAT10 in hypoxia-stimulated H9C2 cells was identified. For this, FAT10 overexpression/interference vectors were exposed to transfection into H9C2 cells with/without the PI3K/AKT inhibitor, miltefosine. The results indicated that hypoxia exposure decreased the FAT10 expression, suppressed H9C2 cell growth, disrupted mitochondrial metabolism, and promoted H9C2 cell apoptosis and oxidative stress. However, these impacts were reversed by the FAT10 overexpression. In addition, the inhibition of PI3K/AKT in FAT10-overexpressing cells suppressed cell proliferation, impaired mitochondrial metabolism, and promoted apoptosis and oxidative stress response. The findings demonstrated that FAT10 inhibited mitochondrial apoptosis and energy metabolism in hypoxia-stimulated H9C2 cells through the PI3K/AKT pathway. This finding can be utilized for developing therapeutic targets for treating heart disorders associated with hypoxia-induced apoptosis.

An imbalance between excitation (E) and inhibition (I) in the brain has been identified as a key pathophysiology of epilepsy over the years. The hippocampus and amygdala in the limbic system play a crucial role in the initiation and conduction of epileptic seizures and are often referred to as the transfer station and amplifier of seizure activities. Existing animal and imaging studies reveal that the hippocampus and amygdala, which are significant parts of the vagal afferent network, can be modulated in order to generate an antiepileptic effect. Using stereo-electroencephalography (SEEG) data, we examined the E/I imbalance in the hippocampus and amygdala of ten drug-resistant epilepsy children treated with acute vagus nerve stimulation (VNS) by estimating the 1/f power slope of hippocampal and amygdala signals in the range of 1–80 Hz. While the change in the 1/f power slope from VNS-BASE varied between different stimulation amplitudes and brain regions, it was more prominent in the hippocampal region. In the hippocampal region, we found a flatter 1/f power slope during VNS-ON in patients with good responsiveness to VNS under the optimal stimulation amplitude, indicating that the E/I imbalance in the region was improved. There was no obvious change in 1/f power slope for VNS poor responders. For VNS non-responders, the 1/f power slope slightly increased when the stimulation was applied. Overall, this study implies that the regulation of E/I imbalance in the epileptic brain, especially in the hippocampal region, may be an acute intracranial effect of VNS.

Limited evidence exists on the combined and mediating effects of systemic inflammation on the association between insulin resistance and cardiovascular events in patients with diabetes and chronic coronary syndrome (CCS). This secondary analysis of a multicenter prospective cohort included 4419 diabetic CCS patients. Triglyceride–glucose index (TyG) and high-sensitivity C-reactive protein (hsCRP) were applied to evaluate insulin resistance and systemic inflammation, respectively. The primary endpoint was major adverse cardiac event (MACE). Associations of TyG and hsCRP with cardiovascular events were estimated using Cox regression. A mediation analysis was performed to assess whether hsCRP mediates the relationship between TyG and cardiovascular events. Within a median 2.1-year follow-up period, 405 MACEs occurred. Patients with high levels of TyG and hsCRP experienced the highest MACE risk (hazard ratio = 1.82, 95% confidence interval: 1.24–2.70, p = 0.002) compared to individuals with low levels of both markers. HsCRP significantly mediated 14.37% of the relationship between TyG and MACE (p < 0.001). In diabetic CCS patients, insulin resistance and systemic inflammation synergically increased the risk of cardiovascular events, and systemic inflammation partially mediated the association between insulin resistance and clinical outcomes. Combining TyG and hsCRP can help identify high-risk patients. Controlling inflammation in patients with insulin resistance may bring added benefits.

Background: Primary gallbladder gastrinoma is an exceptionally uncommon tumor which is a rare form of neuroendocrine neoplasm. Until now, no cases of primary gallbladder gastrinoma and rare cases of primary gastrinoma from the biliary system have been reported. Case presentation: We reported a 50-year-old female with watery diarrhea and intermittently received proton pump inhibitors as treatment. Enhanced computed tomography (CT) imaging and Octreotide imaging uncovered a solitary tumor at the hepatic hilar region. The tumor was found originated from the wall of the gallbladder during the surgery and a subsequent laparoscopic cholecystectomy was exerted. Histological analysis revealed a primary neuroendocrine tumor from the gallbaldder. Conclusion: This case confirmed that primary gallbladder gastrinoma represents a distinct nosological entity. Immunohistochemical analysis plays a pivotal role in the diagnosis process. Due to limited knowledge regarding primary gallbladder gastrinoma, we aim to contribute valuable insights into this rare condition by providing unique information and present the therapeutic value of surgery.

The fall armyworm (FAW), Spodopterafrugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is a major pest of corn worldwide. FAW larval dispersal is an important life strategy that influences FAW population distribution in corn fields and subsequent plant damage. We studied FAW larval dispersal in the laboratory with sticky plates placed around the test plant and a unidirectional airflow source. Crawling and ballooning were the main dispersal means of FAW larvae both within and between corn plants. All larval instars (1st–6th) could disperse by crawling, with crawling being the only dispersal mechanism for 4th–6th instars. By crawling, FAW larvae could reach all aboveground parts of a corn plant as well as adjacent corn plants where leaves overlapped. Ballooning was used primarily by 1st-3rd instar larvae, and the proportion of these larvae that used ballooning decreased with age. Ballooning was largely governed by the larva’s interaction with airflow. Airflow influenced the direction and distance of larval ballooning. With an airflow speed of about 0.05 m/s, 1st instars could travel up to 196 cm from the test plant, indicating that long-distance FAW larval dispersal depends on ballooning. These results increase our understanding of FAW larval dispersal and provide scientific information for the development of FAW monitoring and control strategies.

The emerging class of multi-principal element alloy (MPEA) processes superior mechanical properties and has great potential for applications in extreme environments. In this work, the synergic effect of the Cr content and crystallographic orientation on the deformation behaviors of single-crystal CrCoFeNi MPEAs has been investigated by atomistic simulations. We have found distinct differences in dislocation activities, deformation microstructures, and mechanical behaviors in the model MPEAs, which depend on crystallographic orientations, Cr concentration, and the number of activated slip systems. When multiple slip systems are triggered along [100] and [111] orientations, Shockley partial activation and their interaction are predominant, leading to the formation of sessile dislocations and a dense dislocation network. When only two slip systems of Shockley partials are favored along the [110] direction, the influence of Cr concentration and planner defect energies emerges. At low Cr concentration, the double planar slip of Shockley partials results in deformation-induced nanotwins. At high Cr concentration, the partial dislocations of a single slip plane become dominant, attaining the highest volume fraction of deformation-induced phase transformation. The results provide a fundamental understanding of deformation mechanisms in MPEAs, elucidating the synergic effect of crystal orientation and composition on tunning the mechanical behaviors.

Climate change and human water management are the two main drivers of terrestrial water storage change, from regional to global scale. When thinking about the future, our main tools to project upcoming changes in the terrestrial water fluxes and storage are the Earth System Models (ESMs). Through the representation of physical, chemical and biological processes relevant to the climate dynamics, ESMs are the closest we got to represent the real Earth.Despite important advancements in the development of ESMs, these models are still missing key elements relevant to the representation of the water cycle, notably anthropogenic water management (Nazemi and Howard, 2015). Through the construction of dams and the abstraction of water from surface and groundwater sources, humans can significantly alter the regional and continental water budget, including river discharge and seasonality, groundwater levels and surface evapotranspiration.The objective of our current project is to reduce this gap, by enhancing the Community Earth System Model to support abstractions for all major water use sectors including domestic, livestock, thermoelectric, manufacturing, mining and irrigation. Some unique features of our development are: full coverage of human water usage for both historical (1971-2010) and future scenarios; a sectoral competition scheme when water availability is limited; application of consumption fluxes on surface soil to accentuate role of human water usage on land-atmosphere interactions; full coupling between routing-land-atmosphere-ocean components. At the moment, all abstractions are performed exclusively from surface water.For the scope of this conference, we will present for the first time, the global simulation results for the historical period (1971-2010) in land only mode, including a general performance of the model in normal conditions and some case studies for known historical drought events. References:Nazemi, Ali, and Howard S. Wheater. "On inclusion of water resource management in Earth system models–Part 1: Problem definition and representation of water demand." Hydrology and Earth System Sciences 19.1 (2015): 33-61.

B-cell receptor (BCR) signaling is essential for the diffuse large B-cell lymphoma (DLBCL) subtype that originates from activated B-cells (ABC). ABC-DLBCL cells are sensitive to Bruton tyrosine kinase intervention. However, relapsed or refractory ABC-DLBCL patients had overall response rates of 33-37% for Bruton tyrosine kinase inhibitors, suggesting the evaluation of combination-based treatment for improved efficacy. We investigated the efficacy and mechanism of bromodomain and extra-terminal motif (BET) inhibitor AZD5153 combined with the Bruton tyrosine kinase inhibitor acalabrutinib in ABC-DLBCL preclinical models. AZD5153 is a bivalent BET inhibitor that simultaneously engages the two bromodomains of BRD4. Adding AZD5153 to acalabrutinib demonstrated combination benefits in ABC-DLBCL cell line and patient-derived xenograft models. Differential expression analyses identified PAX5 transcriptional activity as a novel downstream effector of this drug combination. PAX5 is a transcription factor for BCR signaling genes and may be critical to the perpetually active BCR signaling in ABC-DLBCL. Our analyses further indicated significant alterations to BCR, RELB/alternative NFκB, and toll-like receptor/interferon signaling. Validation of these results mapped a positive feedback signaling loop regulated by PAX5. We demonstrate that AZD5153 decreases PAX5 expression, while acalabrutinib disruption to BCR signaling inhibits PAX5 activation. Furthermore, several interferons were decreased by AZD5153 and acalabrutinib in tumors. Adding IFNß1 to cells treated with acalabrutinib partially rescued PAX5 activation. Our results demonstrate AZD5153 enhances the efficacy of acalabrutinib through PAX5 and BCR mechanisms that are critical for ABC-DLBCL.

IntroductionAtrial fibrillation (AF) is a challenging cardiovascular disease worldwide. Wearable electrocardiograph devices (WEDs) have great potential to improve the detection rate of AF in primary care. However, the factors that influence general practitioners’ (GPs) perception and acceptance of WEDs are not well understood. To identify factors that influence the intention of GPs to utilize WEDs in a clinical setting to screen patients for AF.MethodThe research hypotheses and questionnaire items were designed and developed based on the unified theory of acceptance and technology (UTAUT) framework. We used stratified sampling and obtained the data through an online survey. Structural equation modeling was used to analyze the collected data.Results: A total of 1,004 valid questionnaires from GPs across Sichuan province in China were collected. Three factors increased GPs’ intention to utilize WEDs to screen patients for AF, including performance expectancy (β = 0.121, p = 0.004), social influence (β = 0.356, p β = 0.587, p β = −0.059, p β = −0.079, p = 0.155) and facilitating conditions (β = −0.014, p = 0.868) did not affect usage intention. Gender (β = −0.022, p = 0.179), age (β = 0.006, p = 0.699), education level (β = −0.22, p = 0.184) and training (β = 0.007, p = 0.69) were not significantly correlated with usage intention, and these four factors had no moderating effect on the path coefficients.DiscussionGPs’ intention to utilize WEDs is affected by performance expectancy, price perception, perception risk and social influence. Researcher should improve the usability and perception of WEDs for screening and carry out studies to provide high-quality evidence for the security and efficacy of wearable devices.

Purpose The purpose of technology mergers and acquisitions (M&A) is to achieve innovation. The authors use the data from the China Patent Research System of China National Intellectual Property Administration to classify technical correlations into three types: similar, complementary and nonrelatedness (cross-sectoral category). And the authors explore three issues: the market reaction to technology-oriented M&A, the impact of technology-oriented M&A on goodwill and how technology-oriented M&A affects innovation. Design/methodology/approach The authors use data from China Patent Research System of China National Intellectual Property Administration to classify technical correlations into three types: similar, complementary and nonrelatedness (cross-sectoral category). And the authors explore three issues: the market reaction of technology-oriented M&A, the impact of technology-oriented M&A on goodwill and how technology-oriented M&A affects innovation. The empirical research shows that the cross-sectoral M&A is popular in the market and is positively correlated with cumulative abnormal return (CAR) and premium rate of M&A. However, the technology-similarity M&A, which is committed to in-depth exploration of original technology, is negatively correlated with CAR and goodwill. Findings The empirical research shows that cross-sectoral M&A is popular in the market and is positively correlated with CAR and premium rate of M&A. However, the technology-similarity M&A, which is committed to in-depth exploration of original technology, is negatively correlated with CAR and goodwill. In addition, empirical results show that there is an inverted U-shaped relationship between technology-oriented M&A and innovation output, and the inflection points are 41.8%, 48.9% and 38.8%, respectively. Originality/value The research contributions of this paper are as follows: first, most domestic studies simply and roughly measure the degree of technical relevance based on whether the firms belong to the same industry and whether there is common knowledge between them, but the authors provide a more accurate measure of technology-oriented M&A. Second, in the research on the economic consequences of technology-oriented M&As, a large number of literatures have mainly focused on the innovation performance of the acquirer after deals, including the number of patent applications, the number of patent citations, innovation output, etc., and they pay less attention to its impact on the market reaction and goodwill.

Chronic myeloid leukemia (CML) is a hematological tumor derived from hematopoietic stem cells. The aim of this study is to analyze the biological characteristics and identify the diagnostic markers of CML. We obtained the expression profiles from the Gene Expression Omnibus (GEO) database and identified 210 differentially expressed genes (DEGs) between CML and normal samples. These DEGs are mainly enriched in immune-related pathways such as Th1 and Th2 cell differentiation, primary immunodeficiency, T cell receptor signaling pathway, antigen processing and presentation pathways. Based on these DEGs, we identified two molecular subtypes using a consensus clustering algorithm. Cluster A was an immunosuppressive phenotype with reduced immune cell infiltration and significant activation of metabolism-related pathways such as reactive oxygen species, glycolysis and mTORC1; Cluster B was an immune activating phenotype with increased infiltration of CD4 + and CD8 + T cells and NK cells, and increased activation of signaling pathways such as interferon gamma (IFN-γ) response, IL6-JAK-STAT3 and inflammatory response. Drug prediction results showed that patients in Cluster B had a higher therapeutic response to anti-PD-1 and anti-CTLA4 and were more sensitive to imatinib, nilotinib and dasatinib. Support Vector Machine Recursive Feature Elimination (SVM-RFE), Least Absolute Shrinkage Selection Operator (LASSO) and Random Forest (RF) algorithms identified 4 CML diagnostic genes (HDC, SMPDL3A, IRF4 and AQP3), and the risk score model constructed by these genes improved the diagnostic accuracy. We further validated the diagnostic value of the 4 genes and the risk score model in a clinical cohort, and the risk score can be used in the differential diagnosis of CML and other hematological malignancies. The risk score can also be used to identify molecular subtypes and predict response to imatinib treatment. These results reveal the characteristics of immunosuppression and metabolic reprogramming in CML patients, and the identification of molecular subtypes and biomarkers provides new ideas and insights for the clinical diagnosis and treatment.

Osimertinib is an EGFR tyrosine kinase inhibitor (TKI) with proven clinical efficacy; however, acquired resistance presents an obstacle to curing EGFR-driven disease. Recent studies have shown that drug-tolerant persister cells (DTP) have a distinct transcriptional profile that may confer specific vulnerabilities. By definition these cells avoid apoptosis, yet little is known about how their survival is regulated. We found that paradoxically, the proapoptotic gene BIM was upregulated in osimertinib DTPs, and cotreatment with BH3 mimetics could trigger DTP cell death. Furthermore, cIAP proteins, antiapoptotic members of the extrinsic pathway, were significantly elevated in DTPs. cIAP antagonists could block DTP formation as an up-front combination, and could eliminate preformed DTPs. Critically, when treated at the time of maximal osimertinib response, cIAP or MCL1 inhibitor treatment could significantly attenuate the regrowth of EGFRm cell line mouse xenografts. Finally, we show that apoptosis can be maximized in cell lines with acquired osimertinib resistance by combining BH3 or SMAC mimetics with agents that target the resistance driver in these models. Taken together, these data suggest novel therapeutic strategies at the point of minimal residual disease or full osimertinib resistance for patients in this critical area of unmet need.Significance:These studies uncover strategies to use targeted agents that activate apoptosis in non–small cell lung cancer cells that survive initial EGFR TKI treatment.

Supplementary Table 1. Cell lines used. Supplementary Table 2. Antibodies used. Supplementary Figure S1. Osimertinib drug tolerant cells re-aquire apoptotic capacity after drug holiday. Supplementary Figure S2. BH3 mimetics can trigger apoptosis in established DTPs. Supplementary Figure S3. DTPs upregulate cIAP proteins and are sensitive to SMAC mimetic treatment. Supplementary Figure S4. SMAC mimetics inhibit DTP growth in vivo. Supplementary Figure S5. BH3 and SMAC mimetics enhance apoptosis induced by agents targeting resistance drivers. Supplementary Figure S6. Measuring transcript levels for anti-apoptotic genes in osimertinib DTPs.

Supplementary Figure 1. AZD5153 shows reduced BRD4 binding activity when BD2 function is abolished; Supplementary Figure 2. AZD5153 modulates MYC protein levels across hematologic cancer cell lines; Supplementary Figure 3. Gene Ontology (GO) analysis of the down-regulated transcripts by AZD5153 across all cell line types; Supplementary Figure 4. IC50 and percent maximal cell kill by AZD5153 and I-BET762 in five hematologic cell lines; Supplementary Figure 5. Tumor growth inhibition across six hematological xenograft Models

Protein modulation by AZD5153 in hematological cell lines

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The bromodomain and extraterminal (BET) protein BRD4 regulates gene expression via recruitment of transcriptional regulatory complexes to acetylated chromatin. Pharmacological targeting of BRD4 bromodomains by small molecule inhibitors has proven to be an effective means to disrupt aberrant transcriptional programs critical for tumor growth and/or survival. Herein, we report AZD5153, a potent, selective, and orally available BET/BRD4 bromodomain inhibitor possessing a bivalent binding mode. Unlike previously described monovalent inhibitors, AZD5153 ligates two bromodomains in BRD4 simultaneously. The enhanced avidity afforded through bivalent binding translates into increased cellular and antitumor activity in preclinical hematologic tumor models. In vivo administration of AZD5153 led to tumor stasis or regression in multiple xenograft models of acute myeloid leukemia, multiple myeloma, and diffuse large B-cell lymphoma. The relationship between AZD5153 exposure and efficacy suggests that prolonged BRD4 target coverage is a primary efficacy driver. AZD5153 treatment markedly affects transcriptional programs of MYC, E2F, and mTOR. Of note, mTOR pathway modulation is associated with cell line sensitivity to AZD5153. Transcriptional modulation of MYC and HEXIM1 was confirmed in AZD5153-treated human whole blood, thus supporting their use as clinical pharmacodynamic biomarkers. This study establishes AZD5153 as a highly potent, orally available BET/BRD4 inhibitor and provides a rationale for clinical development in hematologic malignancies. Mol Cancer Ther; 15(11); 2563–74. ©2016 AACR.

Differentially expressed genes with AZD5153 treatment

Methyl orange dye (MO) is one of the azo dyes, which is not only difficult to degrade but also hazardous to human health, therefore, it is necessary to develop an efficient photocatalyst to degrade MO. In this paper, a facile and low-cost elemental doping method was used for the surface modification of Ti3C2 MXene, i.e., nitrogen-doped titanium carbide was used as the nitrogen source, and the strategy of combining solvent heat treatment with non-in situ nitrogen doping was used to prepare N-Ti3C2 MXene two-dimensional nanomaterials with high catalytic activity. It was found that the catalytic efficiency of N-Ti3C2 MXene materials was enhanced and improved compared to the non-doped Ti3C2 MXene. In particular, N-Ti3C2 1:8 MXene showed the best photo-catalytic ability, as demonstrated by the fact that the N-Ti3C2 1:8 MXene material successfully degraded 98.73% of MO (20 mg/L) under UV lamp irradiation for 20 min, and its catalytic efficiency was about ten times that of Ti3C2 MXene, and the N-Ti3C2 photo-catalyst still showed good stability after four cycles. This work shows a simplified method for solvent heat-treating non-in situ nitrogen-doped Ti3C2 MXene, and also elaborates on the photo-catalytic mechanism of N-Ti3C2 MXene, showing that the high photo-catalytic effect of N-Ti3C2 MXene is due to the synergistic effect of its efficient charge transfer and surface-rich moieties. Therefore, N-Ti3C2 MXene has a good prospect as a photo-catalyst in the photocatalytic degradation of organic pollutants.

Current rat model of rotator cuff (RC) tear could not mimic the suture anchor (SA) repair technique in the clinical practice. We designed a novel SA for RC repair of rats to establish a clinically relevant animal model. Small suture anchors that fit the rat shoulder were assembled. 60 rats were assigned to the transosseous (TO) repair group or SA repair group (n = 30/group). Micro-computed tomography (Micro-CT) scanning, biomechanical test and histological analysis were implemented at 2, 4, and 8-week post-repair. The failure load and stiffness in the SA group were significantly higher than those of TO group at 4-week post-repair. Micro-computed tomography analysis showed the bone mineral density and trabecular thickness of the SA group were significantly lower than those of TO group. The SA group showed a better insertion continuity at 4-week post-repair compared to TO group. No significant difference in gait parameters was found between groups. Therefore, SA repair is applicable for the rat model of RC tears. The SA repair achieved superior RC tendon healing, but more extensive initial bone damage compared to TO repair, while the shoulder function was comparable. This model could replicate the current repair technique in the clinical situation and be considered for future preclinical studies on healing enhancement for RC tears. Statement of Clinical Significance: With high clinical relevance, this model may facilitate the translation from an animal study into clinical trials.