Search

Abstract Airborne warning and control systems (AWACS) serve as critical command and control centres in air combat operations, making them prime targets for strategic attacks. These enemy attacks typically rely on the accurate determination of AWACS combat positions using different direction‐finding devices. In particular, passive monopulse angle measurement systems locate AWACS by measuring the angles of signals emitted by AWACS radiation sources, thus rendering them vulnerable to attacks. Given the criticality of the airborne radars of AWACS in battle command and control operations, they must function continuously to monitor air and sea targets. Hence, AWACS cannot effectively evade electronic reconnaissance systems through tactics such as radar shutdown. To explore alternative measures, the authors investigate the deception mechanisms of an integrated frequency diverse array AWACS (FDA‒AWACS) against passive monopulse angle measurements. Using an established FDA signal model, the principles underlying two common monopulse angle measurement methods are first outlined. Subsequently, the angle estimation formulae typically used by these monopulse angle measurement systems to interpret received FDA radiation signals are derived. Additionally, the transmit beampatterns, amplitude patterns, and angle measurement deception capabilities of several typical FDAs are examined. Simulation results indicate that the FDA‒AWACS can theoretically deceive passive monopulse angle measurement systems to a certain extent. However, one‐dimensional uniform linear FDAs and other arrays using sinusoidal frequency offsets exhibit limited deception abilities. In contrast, arrays utilising cubic and quartic frequency offset achieve angle measurement errors exceeding 2° in far‐field scenarios.

Abstract We investigated the clinical characteristics of primary aldosteronism (PA) screened from patients with hypertension in China. The participants were hypertensive patients who were suspected of PA and registered in the China Primary Aldosteronism Prospective Study. Plasma aldosterone‐to‐renin ratio (ARR) was used as the screening test. In patients screened positive for PA, that is, an ARR exceeding the thresholds and plasma aldosterone concentration (PAC) > 100 pg/mL, a confirmatory test was performed for diagnosis. Patients with PA underwent a CT scan and adrenal venous sampling for subtyping. Of the 1497 screened patients, 754 (50.4%) had an ARR exceeding the diagnostic threshold and 637 (84.5% of those eligible) were registered. These registered hypertensive patients with suspected PA had a mean (standard deviation) age of 52.6 ± 12.1 years, and included 442 (58.6%) women. In multiple stepwise logistic regression, the significant odds ratios for the presence of diagnosed (n = 490) versus suspected and non‐diagnosed PA (n = 147) were 4.54 (95% CI: 2.78‐7.39) for a history of hypokalemia, 0.79 (95% CI: 0.64‐0.98) for a 0.9 mmol/l higher serum total cholesterol, and 2.25 (95% CI: 1.63‐3.10) for a doubling of PAC in the supine or standing/sitting position. In multiple stepwise logistic regression, the significant odds ratios for the presence of unilateral (n = 135) versus bilateral PA (n = 53) were 3.04 (95% CI: 1.90‐4.87) for a 0.4 mmol/l lower minimum serum potassium concentration and 1.86 (95% CI: 1.20‐2.86) for a 0.3 mmol/l higher serum high‐density lipoprotein cholesterol. PA might be a biochemical continuum in the adrenal hypersecretion of aldosterone as well as hypokalemia.

Abstract This study employs China's Yangtze River Economic Belt strategy as a quasi‐natural experiment to investigate the impact of prioritizing green development on economic growth. Our empirical findings show that the strategy significantly reduces urban industrial wastewater discharge. It helps transition the region's industries towards technology‐driven service sectors while maintaining a steady economic growth rate. On average, cities in the Yangtze River Economic Belt see a 21.9% decrease in annual industrial wastewater discharge, a 1.9% increase in economic growth rate, a 4.9% rise in the proportion of service industries' contribution to GDP, and a 2.4% increase in the number of employees in productive service industries. Moreover, our empirical results highlight the heterogeneity in the effects of the strategy across different regions, which can be attributed to factors such as population density, infrastructure, levels of human capital, and government governance. The implementation of the Yangtze River Economic Belt strategy offers valuable insights for developing countries on how to balance between economic development and environmental protection.

Abstract Background Activin A, a noteworthy member of the TGF‐β superfamily. Activin A can regulate the biological functions of various immune cells, such as macrophages, neutrophils, NK cells, etc. The purpose of this study is to investigate the regulatory effect and related mechanisms of activin A on CD8+ T cells. Methods This study established a mouse subcutaneous transplantation model of hepatoma to explore whether activin A has a regulatory effect of CD8+ T cells. And reveal the biological characteristics of ActRIIA high CD8+ T cells. Results We discovered that CD8+ T cells express ActRIIA, ActRIIB, and Smad2,3,4. Unlike high‐dose activin A, low‐dose activin A increased the content of CD8+ T cells while also suppressing tumor growth. In addition, low‐dose activin A promoted expression of perforin, granzyme B, CD69, CD11c, CD49b, Ki67 and ActRIIA in CD8+ T cells. And the results indicated that high‐dose activin A promotes the expression of PPM1A in T cells, while low‐dose activin A has no effect on these cells. The tumor contained more ActRIIA high CD8+ T cells compared to the peripheral blood and spleen. ActRIIA high CD8+ T cells highly express cytotoxic molecules and cytokines. And ActRIIA high CD8+ T cells not only expressed high levels of activation/co‐stimulatory markers CD69, CD278, and CD28, but also high levels of inhibitory markers CD366 and KLRG1. Different chemokine receptors displayed varying levels of expression in ActRIIA high CD8+ T cells. Additionally, these cells have a high proliferative potential. Finally, overexpression of Mettl3 inhibited the expression of ActRIIA in CD8+ T cells. Conclusions This study demonstrated that low‐dose activin A enhanced the anti‐tumor effect of CD8+ T cells, and ActRIIA high CD8+ T cells actively contribute to tumor immunity.

Abstract Parrot feather (Myriophyllum aquaticum) is an introduced, noninvasive amphibious plant found in coastal provinces, but it has the potential to become an invasive species in China. The plant is heterophyllous, with both emergent (aerial) and submerged (aquatic) leaves, and has two distinct root types: aquatic (adventitious) and edaphic (sediment) root systems. This morphological plasticity allows M. aquaticum to effectively absorb nutrients from different layers of the environment, making it a suitable model plant for exploring nutrient dynamics in both water and soil systems and investigating how wetland plants respond to cultural eutrophication. We designed an outdoor mesocosm experiment to assess plant growth traits and root topological indices in response to different nitrogen (N) and phosphorus (P) concentrations. The results indicated that the plant has a high tolerance to N loading. In contrast, the P content had greater impacts than the N content on plant growth and root topological indices, indicating that the P content was the main influencing factor affecting and suppressing the development of M. aquaticum. The aquatic or edaphic root branching did not change, but the aquatic root topology of M. aquaticum exhibited similar stable trends with increasing P concentration, indicating typical herringbone branching; additionally, its edaphic roots exhibited decreasing topological indices, indicating more typical dichotomous branching with increasing P concentration. The plant has a high tolerance to N, and it may become invasive following the current trend of increasing cultural eutrophication.

Abstract A comparative study of two force perception skill learning approaches for robot‐assisted spinal surgery, the impedance model method and the imitation learning (IL) method, is presented. The impedance model method develops separate models for the surgeon and patient, incorporating spring‐damper and bone‐grinding models. Expert surgeons' feature parameters are collected and mapped using support vector regression and image navigation techniques. The imitation learning approach utilises long short‐term memory networks (LSTM) and addresses accurate data labelling challenges with custom models. Experimental results demonstrate skill recognition rates of 63.61%–74.62% for the impedance model approach, relying on manual feature extraction. Conversely, the imitation learning approach achieves a force perception recognition rate of 91.06%, outperforming the impedance model on curved bone surfaces. The findings demonstrate the potential of imitation learning to enhance skill acquisition in robot‐assisted spinal surgery by eliminating the laborious process of manual feature extraction.

Abstract Background Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for noninvasive cancer diagnostics, particularly in the context of metastatic non‐small‐cell lung cancer (NSCLC). Detecting targetable variants through ctDNA analysis offers the potential to guide treatment decisions, especially in cases where tissue samples are insufficient or unavailable. Method In this study, we developed and validated a next‐generation sequencing panel targeting 101 cancer‐related genes (101‐test) to detect somatic variants in ctDNA from a large cohort of Chinese patients with metastatic NSCLC. The performance of the 101‐test was assessed by evaluating its limit of detection (LOD), accuracy, and precision in identifying molecular variants. Additionally, the concordance between ctDNA and tissue samples for detecting targetable variants was analyzed in 904 patients. Results The 101‐test demonstrated a LOD of 0.38% for single‐nucleotide variants (SNVs), 0.33% for insertions and deletions (InDels), and 0.33% for fusions. Sensitivity was 98.3% for SNVs, 100% for InDels, and 100% for fusions when compared to digital droplet PCR (ddPCR)/breakpoint PCR reference methods. The by‐variant sensitivity for somatic variants was 97.5%, with a specificity of 99.9% between tumor‐only and tumor‐normal analyses. In a real‐world cohort, the concordance between ctDNA and tissue samples for identifying targetable variants was 72.2% (457/633). Notably, the EGFR S768I variant, recently recommended by clinical guidelines, achieved an 80% concordance rate. Furthermore, 4.3% of patients (27/633) with targetable variants were identified exclusively through ctDNA testing. Conclusion The ctDNA‐based 101‐test is a highly sensitive and specific tool for detecting targetable variants in metastatic NSCLC, particularly in cases with insufficient tissue samples. The findings support the use of ctDNA testing as a reliable and complementary method to traditional tissue‐based molecular analysis, enhancing the precision of treatment strategies for NSCLC patients.

Abstract Cephalopods can change their skin color by using high‐speed electron transduction among receptors, neural networks, and pigmentary effectors. However, it remains challenging to realize a neuroelectrical transmission system like that found in cephalopods, where electrons/ions transmit on nanoscale, which is crucial for fast adaptive electrochromic tuning. Inspired by that, hereby an ideal, rapidly responsive, and multicolor electrochromic biomimetic skin is introduced. Specifically, the biomimetic skin comprises W18O49 nanowires (NWs) that are either colorless or blue, Au nanoparticles@polyaniline (Au NPs@PANI) ranging from green to pink, and a flexible conductive substrate. As the applied voltage changes from 0.4 V to ‐0.7 V and back to 0 V, the color of the biomimetic skin transforms from green to blue and ultimately to pink. This color change is attributed to the electrically induced redox reaction of Au NPs@PANI and W18O49 NWs, triggered by the transfer of electrons and ions. Furthermore, the high versatility and adaptability of electrical stimulus enable the creation of a highly interactive electrochromic biomimetic skin system through the integration of sensitive acoustic sensors, providing a perfect environment‐responsive platform. This work provides a biomimetic multicolor electrochromic skin that depends on electron/ion transfer on nanoscale, expands potential uses for camouflage skin.

Abstract Traditional light‐driven metal‐organic‐frameworks (MOFs)‐based micromotors (MOFtors) are typically constrained to two‐dimensional (2D) motion under ultraviolet or near‐infrared light and often demonstrate instability and susceptibility to ions in high‐saline environments. This limitation is particularly relevant to employing micromotors in water purification, as real wastewater is frequently coupled with high salinity. In response to these challenges, ultrastable MOFtors capable of three‐dimensional (3D) motion under a broad spectrum of light through thermophoresis and electrophoresis are successfully synthesized. The MOFtors integrated photocatalytic porphyrin MOFs (PCN‐224) with a photothermal component made of polypyrrole (PPy) by three distinct methodologies, resulting in micromotors with different motion behavior and catalytic performance. Impressively, the optimized MOFtors display exceptional maximum velocity of 1305 ± 327 µm s−1 under blue light and 2357 ± 453 µm s−1 under UV light. In harsh saline environments, these MOFtors are not only maintain high motility but also exhibit superior tetracycline hydrochloride (TCH) removal efficiency of 3578 ± 510 mg g−1, coupling with sulfate radical‐based advanced oxidation processes and peroxymonosulfate. This research underscores the significant potential of highly efficient MOFtors with robust photocatalytic activity in effectively removing TCH in challenging saline conditions, representing a substantial advancement in applying MOFtors within real‐world water treatment technologies.

SETDB2 is a H3K9 histone methyltransferase required for accurate chromosome segregation. Its H3K9 histone methyltransferase activity was reported to be associated with chromosomes during metaphase. Here, we confirm that SETDB2 is required for mitosis and accurate chromosome segregation. However, these functions are independent of its histone methyltransferase activity. Further analysis showed that SETDB2 can interact with BUBR1, and is required for CDC20 binding to BUBR1 and APC/C complex and CYCLIN B1 degradation. The ability of SETDB2 to regulate the binding of CDC20 to BUBR1 or APC/C complex, and stabilization of CYCLIN B1 are also independent of its histone methyltransferase activity. These results suggest that SETDB2 interacts with BUBR1 to promote binding of CDC20 to BUBR1 and APC3, then degrades CYCLIN B1 to ensure accurate chromosome segregation and mitosis, independently of its histone methyltransferase activity.

Abstract Deep lakes are critical for freshwater storage, yet they are struggling against major ecological issues from climate change and nutrient pollution. A comprehensive understanding of internal feedback mechanisms is crucial for regulating nutrients in these lakes. A five‐year study was conducted on the diatom community and environment in Lake Fuxian, China's largest deep freshwater lake, which is becoming eutrophic. The results indicate a shift in the diatom community from a stable state dominated by a single species to a rapid seasonal fluctuation, and there is a significant increase in diatom biomass. Specifically, stable stratification and low nutrient concentrations are limiting the growth of diatom biomass and maintaining the dominance of Cyclotella. Nutrients in the hypolimnion were replenished in the epilimnion during the extreme cold of winter, triggering a shift in the diatom community. This shift may imply that future climate change will exacerbate the positive feedback of hypoxia‐nutrient release of algal blooms, potentially triggering a regime shift in the ecosystem of the entire lake. This study underscores the fact that climate change alters the internal feedback mechanisms of deep lakes, reducing ecosystem stability, and provides a scientific basis for further clarification of protection measures for deep lakes.

Abstract Tumor‐infiltrating CD4+ T cells orchestrate the adaptive immune response through remarkable plasticity, and the expression patterns of exhaustion‐related inhibitory receptors in these cells differ significantly from those of CD8+ T cells. Thus, a better understanding of the molecular basis of CD4+ T cell exhaustion and their responses to immune checkpoint blockade (ICB) is required. Here, we integrated multiomics approaches to define the phenotypic and molecular profiles of exhausted CD4+ T cells in oropharyngeal squamous cell carcinoma (OPSCC). Two distinct immune‐promoting (Module 1) and immunosuppressive (Module 2) functional modules in tumor‐infiltrating CD4+ T cells were identified, and both the immune‐promoting function of Module 1 cells and immunosuppressive function of Module 2 cells were positively associated with their corresponding exhaustion states. Furthermore, the application of ICBs targeting effector CD4+ T cells in Module 1 (αPD‐1) and Treg cells in Module 2 (αCTLA‐4) in mouse models could help reinvigorate the effector function of Module 1‐exhausted CD4+ T cells and reduce the immunosuppressive function of Module 2‐exhausted CD4+ T cells, ultimately promoting OPSCC tumor regression. Taken together, our study provides a crucial cellular basis for the selection of optimal ICB in treating OPSCC.

Abstract Dynamic ageing process of cross‐linked polyethylene (XLPE) cable insulation under combined electro‐thermal effect is investigated by the construction of theoretical analysis model and the practice of operation‐simulated ageing test. Firstly, theoretical analysis model is constructed from time and spatial dimensions. From the time dimension, in the light of the impeding trend of internal stress to external stress, the XLPE ageing process of Steady state ‐Transition state ‐Steady state (STS) is proposed to illustrate the dynamic ageing process of XLPE. From the spatial dimension, the insulation is divided into three scales to quantify the ageing. Secondly, to practice the theoretical analysis model, an operation‐simulated ageing test was conducted on two high voltage alternating current cables with service years of 15 and 30 for 540 days. Subsequently, relevant diagnostic measurements were applied to analyse the influence of physicochemical characteristics on the dielectric and heat transfer performances of the cables. The results show that the degradation of the actual operating cable is an extremely slow process. On the one hand, the response in physical changes of morphology counterbalances the external stress, maintaining the stability. On the other hand, once the chemical changes occur, negative feedback mechanism tends to impede the occurrence of further degradation by regulating fields distribution.

Abstract Background To develop and validate a multivariable risk prediction model for ketosis‐prone type 2 diabetes mellitus (T2DM) based on clinical characteristics. Methods A total of 964 participants newly diagnosed with T2DM were enrolled in the modeling and validation cohort. Baseline clinical data were collected and analyzed. Multivariable logistic regression analysis was performed to select independent risk factors, develop the prediction model, and construct the nomogram. The model's reliability and validity were checked using the receiver operating characteristic curve and the calibration curve. Results A high morbidity of ketosis‐prone T2DM was observed (20.2%), who presented as lower age and fasting C‐peptide, and higher free fatty acids, glycated hemoglobin A1c and urinary protein. Based on these five independent influence factors, we developed a risk prediction model for ketosis‐prone T2DM and constructed the nomogram. Areas under the curve of the modeling and validation cohorts were 0.806 (95% confidence interval [CI]: 0.760–0.851) and 0.856 (95% CI: 0.803–0.908). The calibration curves that were both internally and externally checked indicated that the projected results were reasonably close to the actual values. Conclusions Our study provided an effective clinical risk prediction model for ketosis‐prone T2DM, which could help for precise classification and management.

Abstract Smart sensors with excellent performance are accelerating the development of biomedicine and the Internet of Energy. Nanodielectrics exhibit unique electrical and mechanical properties. As the predominant materials in optical magnetic field sensor (MFS), they can not only exert the anti‐interference of optical sensing, but improve the measuring characteristics of optical sensors. For instance, the optical fibre quantum probe for the magnetic field can obtain a higher sensitivity of 0.57 nT/Hz1/2, while the measurement range of the sensor that uses Co‐doped ZnO nanorods as cladding is 17–180 mT. Here, these exciting recent achievements in the realm of optical sensing methods for magnetic field detection are reviewed, with a focus on nanodielectrics, which provide an emerging opportunity to achieve higher sensitivity and a wider measurement range of MFS.

Abstract Bone defects are encountered substantially in clinical practice, and bionic scaffolds represent a promising solution for repairing bone defects. However, it is difficult to fabricate scaffolds with bionic structures and reconstruct the microenvironment to fulfill the satisfying repair effects. In this review article, we first discuss various strategies for the design and construction of bionic scaffolds to promote bone defect repair, especially including the structural construction of the scaffold and the integration of bioactive substances together with the application of external stimuli. We then discuss the roles of artificial intelligence and medical imaging in aiding clinical treatment. Finally, we point out the challenges and future outlooks in developing multifunctional bone repair scaffolds, aiming to provide insights for improving bone regeneration efficacy and accelerating clinical translation.

Abstract Objectives This study aimed to investigate the survival outcomes and potential prognostic factors of patients with temporal bone squamous cell carcinoma (TBSCC) treated at our institution. Methods We retrospectively included patients who were diagnosed with TBSCC between 2008 and 2019. The Kaplan–Meier (KM) method was used to describe overall survival (OS), and the association between baseline characteristics and prognoses was examined using Cox proportional hazards models. Results Fifty consecutive patients with TBSCC were included in this study. The results showed that patients with advanced modified Pittsburgh (MPB)‐ T classifications had a poorer prognosis (T3 vs. T1‐2: HR: 2.81, 95% CI: 0.34–23.43; T4 vs. T1‐2: HR: 7.25, 95% CI: 0.95–55.41; p = 0.041). Meanwhile, middle ear squamous cell carcinoma (MESCC) showed a significantly worse prognosis than external auditory canal squamous cell carcinoma (EACSCC, HR: 2.65, 95% CI: 1.04–6.76, p = 0.04). Conclusions MESCC and advanced MPB‐T classifications might be considered predictors of unfavorable outcomes in patients with TBSCC, indicating that special attention should be paid to the original tumor subsite and tumor extension in the management of patients with TBSCC.

Objective Adolescent idiopathic scoliosis (AIS) is a three‐dimensional structural deformity of the spine caused by the disruption of the biomechanical balance of the spine. However, the current biomechanical modeling and analysis methods of scoliosis cannot really describe the real state of the spine. This study aims to propose a high‐precision biomechanical modeling and analysis method that can reflect the spinal state under gravity and provide a theoretical basis for therapeutics. Methods Combining CT and X‐ray images of AIS patients, this study constructed an adjusted three‐dimensional model and FE model of the spine corresponding to the patient's gravity position, including vertebral bodies, intervertebral discs, ribs, costal cartilage, ligaments, and facet cartilage. Then, the displacement and stress of the spine under gravity were analyzed. Results A model of the T1‐Sacrum with 1.7 million meshes was constructed. After adding the gravity condition, the maximum displacement point was at T1 of thoracic vertebra (20.4 mm). The analysis indicates that the stress on the lower surface of the vertebral body in thoracolumbar scoliosis tended to be locally concentrated, especially on the concave side of the primary curvature's vertebral body (the maximum stress on the lower surface of T9 is 32.33 MPa) and the convex side of the compensatory curvature's vertebral body (the maximum stress on the lower surface of L5 is 41.97 MPa). Conclusion This study provides a high‐precision modeling and analysis method for scoliosis with full consideration of gravity. The reliability of the method was verified based on patient data. This model can be used to analyze the biomechanical characteristics of patients in the treatment plan design stage.

Abstract Oil and gas pipelines that go through an active normal fault often deform largely and cause serious disasters. On the basis of the beam theory of the elastic foundation and assuming a shape function for the deformed pipeline, a new analytical method is proposed to calculate the pipeline strain under a normal fault. The length of the deformed pipeline is calculated by using a simplified structural mechanical model. Moreover, a three‐dimensional solid finite element model (3D FEM) is developed to calculate the pipeline strain under different working conditions. The developed analytical solution and the numerical results of 3D FEM are compared with the results of the two traditional methods (the dissipated energy method and the Karamitros method). The strain development law predicted by the proposed method and the 3D FEM is in good agreement with that of the dissipated energy method and the Karamitros method. Compared with the existing models, the new analytical method is simpler and more efficient.

Abstract Background Tumor treating fields (TTFields) is an FDA‐approved adjuvant therapy for glioblastoma. The distribution of an applied electric field has been shown to be governed by distinct tissue structures and electrical conductivity. Of all the tissues the skull plays a significant role in modifying the distribution of the electric field due to its large impedance. In this study, we studied how remodeling of the skull would affect the therapeutic outcome of TTFields, using a computational approach. Methods Head models were created from the head template ICBM152 and five realistic head models. The electric field distribution was simulated using the default TTFields array layout. To study the impact of the skull on the electric field, we compared three cases, namely, intact skull, defective skull, and insulating process, wherein a thin electrical insulating layer was added between the transducer and the hydrogel. The electric field strength and heating power were calculated using the FEM (finite element method). Results Removing the skull flap increased the average field strength at the tumor site, without increasing the field strength of “brain”. The ATVs of the supratentorial tumors were enhanced significantly. Meanwhile, the heating power of the gels increased, especially those overlapping the skull defect site. Insulation lightly decreased the electric field strength and significantly decreased the heating power in deep tumor models. Conclusion Our simulation results showed that a skull defect was beneficial for superficial tumors but had an adverse effect on deep tumors. Skull removal should be considered as an optional approach in future TTFields therapy to enhance its efficacy. An insulation process could be used as a joint option to reduce the thermogenic effect of skull defect. If excessive increase in heating power is observed in certain patients, insulating material could be used to mitigate overheating without sacrificing the therapeutic effect of TTFields.

Abstract Background Immune checkpoint blockade therapy with anti‐programmed cell death (PD)‐1 antibodies provides therapeutic effect for many patients of various cancers but remains inadequate in colorectal cancer (CRC) patients. The present study aims to assess the efficacy of oncolytic adenovirus (OncoAd) in enhancing the anti‐PD‐1 treatment of CRC. Methods The estimating relative subsets of RNA transcripts algorithm was used for estimating the infiltrated immune cells in melanoma and CRC tissues. The efficacy of OncoAd with anti‐PD‐1 monotherapy was performed in a CT26 CRC mouse model in vivo. Flow cytometric analysis of peripheral blood and tumor tissues determined the difference anti‐tumor immune efficacy of OncoAd with anti‐PD‐1 monotherapy. Results The Cancer Genome Atlas database indicated that CD8+ T cells and regulatory T cells were significantly elevated in melanoma compared to CRC cohorts. Moreover, intratumor injection of oncolytic adenovirus enhanced T cell infiltration and decreased Treg percentages in the CT26 CRC colorectal cancer mouse model. Combinatorial OncoAd with anti‐PD‐1 antibody treatment markedly enhanced the anti‐tumor efficacy of anti‐PD‐1 by significantly decreasing the tumor volume and reducing tumor growth in a CRC mouse model. To the end, OncoAd treatment increased the CD8/Treg ratio, indicating that OncoAd intratumor injection ameliorate the anti‐tumor immune response of anti‐PD‐1 therapy. Conclusion The present study elucidates that OncoAd promotes intratumor T cell infiltration and improves anti‐PD‐1 immunotherapy, thereby providing a potent combinatorial therapeutic strategy for CRC.

Abstract Electrical impedance tomography (EIT) as a bedside, noninvasive, radiation‐free technology, could quantify alveolar collapse and over‐distension and provide real‐time ventilation images of lungs. Clinical studies have shown potential benefit in reducing lung injury by EIT to guide mechanical ventilation setting in acute respiratory distress syndrome (ARDS). The respiratory management of ARDS with venous−venous extracorporeal membrane oxygenation (VV ECMO) remains a challenge for ICU doctors. Moreover, EIT has gained great interests in the respiratory management in VV ECMO therapy. Here, EIT was used for respiratory management in the presented case of a 36‐year‐old gravida with systemic lupus erythematosus, who developed severe hypoxia caused by diffuse alveolar hemorrhage. Although the patient received mechanical ventilation, VV ECMO was further used for the refractory respiratory failure. EIT was applied to titrate positive end‐expiratory pressure (PEEP), guide prone position and early mobilization, dynamic evaluating lung development during ECMO therapy. She was successfully rescued after comprehensive therapy. In summary, an EIT‐guided whole‐process respiratory management strategy that included PEEP titration, prone position, early mobilization, and dynamic lung ventilation monitoring was proposed. This case demonstrated that EIT‐guided whole‐process respiratory management strategy was feasible in the respiratory failure patient with VV ECMO therapy.

Abstract The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR‐related protein 9 (Cas9) genome editing system has attracted much attention due to its powerful genome editing capacity. However, CRISPR‐Cas9 components are easily degraded by acids, enzymes, and other substances in the body fluids after entering the organism, thus efficiently delivering the CRISPR‐Cas9 system into targeted organs or cells has been a central theme for promoting the application of CRISPR‐Cas9 technology. Although several physical methods and viral vectors have been developed for CRISPR‐Cas9 delivery, their clinical application still suffers from disadvantages, such as the risks of mutagenesis, cell damage, and poor specificity. As an alternative, non‐viral nanocarriers hold great promise for circumventing these challenges. Furthermore, with aim to realize more efficient and precise genome editing and reduce the undesirable side effects, stimuli‐responsive nanocarriers are designed for the spatiotemporal CRISPR‐Cas9 delivery in responsive to various stimuli. In this review, we will summarize the recent progress in delivery strategies for CRISPR‐Cas9 genome editing. The mechanisms and advantages of these strategies were reviewed, providing a comprehensive review of the rational design of materials and techniques for efficient and precise genome editing. At last, the potential challenges of current CRISPR‐Cas9 delivery are discussed.

Objective Musculoskeletal pain is having growing impacts worldwide with clinical challenge in pain management. The purpose of the present study is to investigate the preferences of orthopedic surgeons of China for using medicine in musculoskeletal pain. Methods A questionnaire was developed, including the following domains, personal information, medication preference for pain treatment, and perceptions of topical medicine. Ten participants were selected to confirm the consistency of questionnaire. A cross‐sectional survey was conducted in orthopedic physicians with different specialties in different regions of China via the online survey platform. The participants' survey results were analyzed one‐way and multi‐way using chi‐square test and logistic regression. Results The pre‐survey analysis results of 10 randomly selected investigators were a mean weighted kappa coefficient of 0.76 (range 0.61–0.89), which indicated the substantial consistency of the present questionnaire. A total of 1099 orthopedic surgeons (mean age, 41.67 ± 8.31 years) responded to our survey, most of whom were male (90.72%), and most of whom worked in level III hospitals (63.24%) and trained in modern medicine (71.43%). Most surgeons who participated in the survey had used topical analgesics in their clinical work (95.81%), and most preferred to use topical analgesics (39.50%) or a combination of oral analgesics (28.87%). Primary reasons for preferring topical analgesics were as follows: less adverse reactions (68.01%); ease of use (60.90%); and not interfering with other oral medications (49.60%). The preference for prescribing topical analgesics increased with the education level of the respondent, where statistically significant differences were seen (P

Objective One of the major difficulties in spinal surgery is the injury of important tissues caused by tissue misclassification, which is the source of surgical complications. Accurate recognization of the tissues is the key to increase safety and effect as well as to reduce the complications of spinal surgery. The study aimed at tissue recognition in the spinal operation area based on electrical impedance and the boundaries of electrical impedance between cortical bone, cancellous bone, spinal cord, muscle, and nucleus pulposus. Methods Two female white swines with body weight of 40 kg were used to expose cortical bone, cancellous bone, spinal cord, muscle, and nucleus pulposus under general anesthesia and aseptic conditions. The electrical impedance of these tissues at 12 frequencies (in the range of 10–100 kHz) was measured by electrochemical analyzer with a specially designed probe, at 22.0–25.0°C and 50%–60% humidity. Two types of tissue recognition models ‐ one combines principal component analysis (PCA) and support vector machine (SVM) and the other combines combines SVM and ensemble learning ‐ were constructed, and the boundaries of electrical impedance of the five tissues at 12 frequencies of current were figured out. Linear correlation, two‐way ANOVA, and paired T‐test were conducted to analyze the relationship between the electrical impedance of different tissues at different frequencies. Results The results suggest that the differences of electrical impedance mainly came from tissue type (p

Objective To evaluate the rate of increase in thickness and cross‐section area (CSA) of the ossification in thoracic myelopathy with or without cervical and lumbar spinal ligament ossification. Methods A total of 24 patients with 170 segments (47 ligamentum flavum [OLF] and 123 cases of ossification of the posterior longitudinal ligament [OPLL]) of spinal ligament ossification between January 2012 and March 2019 at a single institution were retrospectively reviewed. Demographic data, classification of OPLL, Sato classification of OLF, pre‐ and postoperative neurological function and complications were recorded. The thickness and CSA at the segment of maximum compression were measured with Image J software on the axial CT image. Results Twelve female and 12 male patients with thoracic myelopathy and spinal ligament ossification were enrolled in the study. The mean age of the patients was 54.0 ± 11.9 years with an average follow‐up of 22.2 ± 23.5 months. Overall, the mean rate of progression in thickness and CSA was 1.2 ± 1.6 and 18.4 ± 50.6 mm2/year, respectively. Being female, aging (≥45 years), and lower BMI (

Abstract Large deformability and high sensitivity is difficult to be realized simultaneously in flexible sensors. Herein, taking advantage of the high permittivity and highly active surfaces of the ultrasmall barium titanate nanoparticles (BT NPs) and the high stretchability of the p(BA‐GMA) elastomer matrix, we propose a high‐performance soft stretchable sensor. The addition of the ultrasmall BT NPs can not only increase the permittivity and capacitance of polyacrylate‐matrix composite dielectric material to obtain a high sensitivity, but also basically maintains the excellent mechanical properties of the polymer matrix. The dielectric constants of the composite films increase from 5.68 to 13.13 at 10 kHz with the increase of BT NPs content from 0 to 15 vol.%, which results in a high capacitance of 236.16 pF for 15 vol.% BT/p(BA‐GMA) sensor. Combining the high permittivity and the large deformability (a maximal deformation of 87.2%), the 15 vol.% BT/p(BA‐GMA) sensor has high sensitivity and shows high linearity and stable output even if under dynamic measurement. The dual‐mode sensor that utilizes the orthogonality of capacitance‐resistance is designed, which shows excellent performance in monitoring human body movements and noncontact measurement. The results present that the BT/p(BA‐GMA)‐based sensor has high stability and reliability not exceed 65°C, which can meet the application requirements in dynamic monitoring.

Abstract Microwave heating (MW) and freeze fracturing (FF) have been widely used for enhancing the permeability of coal reservoirs. In this paper, the effects of combined MW–FF treatments on coals are experimentally investigated through nuclear magnetic resonance. T2 distributions and fractal dimensions of coals under MW, FF, and the combined MW–FF treatments are compared and analyzed. The results show that the T2 area, porosity, and fractal dimensions of coals increase to varying degrees after MW, FF, and MW–FF treatment. The T2 spectrum peaks increase from 2 to 3 and macrofractures can be observed after the coal was treated with the combined MW–FF treatments. However, these phenomena are not observed under MW or FF treatment. The combined MW–FF treatments can effectively fracture coals with less microwave energy and less liquid nitrogen freezing cycle owing to its intensive thermal shock fracturing. Therefore, the combined MW–FF treatment is favorable for fracturing the coals and hence favorable for the CBM production.

Abstract Most commonly used dielectric elastomers (DEs) such as acrylic dielectric elastomers VHBTM 4910 need a high actuation voltage and pre‐stretching to obtain a large actuation strain, and present high mechanical loss caused by viscoelasticity. In this work, we fabricated a new acrylic elastomer by UV curing based on CN9021 and lauryl acrylate. By manipulating crosslinker content, crosslink density changed and physical entanglements of the new material can be affected. Therefore, mechanical properties such as Young's Modulus and mechanical loss of the new material can be controlled, and little change of its glass transition temperature was induced. Results of the actuation test show that the new DE is capable of 9.0% actuation area strain under 11 kV/mm and a good performance under oscillating voltage with different waveforms and frequencies.

Abstract Dorzagliatin is a novel allosteric glucokinase activator targeting both pancreatic and hepatic glucokinase currently under clinical investigation for treatment of type 2 diabetes (T2D). This study aimed to investigate the effect of renal impairment (RI) on dorzagliatin’s pharmacokinetics (PKs) and safety, and to guide appropriate clinical dosing in patients with diabetic kidney disease, including end‐stage renal disease (ESRD). Based on the results from physiologically‐based pharmacokinetic modeling, the predicted outcome of RI on dorzagliatin PK property would be minimum that the plasma exposure area under concentration (AUC) of dorzagliatin in patients with ESRD would increase at about 30% with minimal change in peak concentration (Cmax) comparing to those in healthy volunteers (HVs). To definitively confirm the prediction, a two‐part RI study was designed and conducted based on regulatory guidance starting with the patients with ESRD matched with HVs. Results of the RI study showed minimum difference between patients with ESRD and HVs with respect to dorzagliatin exposure with geometric mean ratio of ESRD to HV at 0.81 for Cmax and 1.11 for AUC. The elimination half‐life, volume of distribution, and systemic clearance for dorzagliatin were similar between the two groups. Dorzagliatin was well‐tolerated in patients with ESRD during the study. Therefore, RI showed no significant impact on dorzagliatin PK, suggesting that dorzagliatin can be readily used in patients with T2D at all stages of RI without need for dose adjustment.

Abstract Constructing a conductive carbon‐based artificial interphase layer (AIL) to inhibit dendritic formation and side reaction plays a pivotal role in achieving longevous Zn anodes. Distinct from the previously reported carbonaceous overlayers with singular dopants and thick foreign coatings, a new type of N/O co‐doped carbon skin with ultrathin feature (i.e., 20 nm thickness) is developed via the direct chemical vapor deposition growth over Zn foil. Throughout fine‐tuning the growth conditions, mosaic nanocrystalline graphene can be obtained, which is proven crucial to enable the orientational deposition along Zn (002), thereby inducing a planar Zn texture. Moreover, the abundant heteroatoms help reduce the solvation energy and accelerate the reaction kinetics. As a result, dendrite growth, hydrogen evolution, and side reactions are concurrently mitigated. Symmetric cell harvests durable electrochemical cycling of 3040 h at 1.0 mA cm−2/1.0 mAh cm−2 and 136 h at 30.0 mA cm−2/30.0 mAh cm−2. Assembled full battery further realizes elongated lifespans under stringent conditions of fast charging, bending operation, and low N/P ratio. This strategy opens up a new avenue for the in situ construction of conductive AIL toward pragmatic Zn anode.

The performance of software defect prediction (SDP) models determines the priority of test resource allocation. Researchers also use interpretability techniques to gain empirical knowledge about software quality from SDP models. However, SDP methods designed in the past research rarely consider the impact of data transformation methods, simple but commonly used preprocessing techniques, on the performance and interpretability of SDP models. Therefore, in this paper, we investigate the impact of three data transformation methods (Log, Minmax, and Z-score) on the performance and interpretability of SDP models. Through empirical research on (i) six classification techniques (random forest, decision tree, logistic regression, Naive Bayes, K-nearest neighbors, and multilayer perceptron), (ii) six performance evaluation indicators (Accuracy, Precision, Recall, F1, MCC, and AUC), (iii) two interpretable methods (permutation and SHAP), (iv) two feature importance measures (Top-k feature rank overlap and difference), and (v) three datasets (Promise, Relink, and AEEEM), our results show that the data transformation methods can significantly improve the performance of the SDP models and greatly affect the variation of the most important features. Specifically, the impact of data transformation methods on the performance and interpretability of SDP models depends on the classification techniques and evaluation indicators. We observe that log transformation improves NB model performance by 7%–61% on the other five indicators with a 5% drop in Precision. Minmax and Z-score transformation improves NB model performance by 2%–9% across all indicators. However, all three transformation methods lead to substantial changes in the Top-5 important feature ranks, with differences exceeding 2 in 40%–80% of cases (detailed results available in the main content). Based on our findings, we recommend that (1) considering the impact of data transformation methods on model performance and interpretability when designing SDP approaches as transformations can improve model accuracy, and potentially obscure important features, which lead to challenges in interpretation, (2) conducting comparative experiments with and without the transformations to validate the effectiveness of proposed methods which are designed to improve the prediction performance, and (3) tracking changes in the most important features before and after applying data transformation methods to ensure precise and traceable interpretability conclusions to gain insights. Our study reminds researchers and practitioners of the need for comprehensive considerations even when using other similar simple data processing methods.

Abstract Background A universally acknowledged cancer staging system considering all aspects of the T‐, N‐, and M‐classifications for middle ear squamous cell carcinoma (MESCC) remains absent, limiting the clinical management of MESCC patients. Materials and Methods A total of 214 MESCC patients were extracted from the SEER (the Surveillance, Epidemiology, and End Results) database between 1973 and 2016. The relationships between patient’s characteristics and prognoses were analyzed by Kaplan–Meier and Cox proportional hazards regression models. Novel staging schemes for MESCC were designed by adjusted hazard ratio (AHR) modeling method according to the combinations of Stell’s T‐classification and the eighth AJCC N‐ and M‐classifications, of which performances were evaluated based on five criteria: hazard consistency, hazard discrimination, explained variation, likelihood difference, and balance. Results T‐classification was the most significant prognostic factor for MESCC patients in multivariable analysis (p = 0.021). The N‐ and M‐classifications also had obvious prognostic effect but were not statistically significant by multivariate analysis due to the limited metastasis events. Three novel staging schemes (AHR‐Ⅰ–Ⅲ models, different combination of T‐ and N‐classifications) and ST (solely derived from Stell’s T‐classification) were developed, among which the AHR‐Ⅰ staging scheme performed best. Conclusions Tumor extension, quantified by Stell’s T‐classification, is the most significant prognostic factor for MESCC patients. However, our AHR‐Ⅰ staging scheme, a comprehensive staging scheme that integrating T‐, N‐, and M‐classifications, might be an optimal option for clinical practitioners to predict MESCC patients’ prognosis and make proper clinical decisions.

Summary The natural plant product bisabolene serves as a precursor for the production of a wide range of industrially relevant chemicals. However, the low abundance of bisabolene in plants renders its isolation from plant sources non‐economically viable. Therefore, creation of microbial cell factories for bisabolene production supported by synthetic biology and metabolic engineering strategies presents a more competitive and environmentally sustainable method for industrial production of bisabolene. In this proof‐of‐principle study, for the first time, we engineered the oleaginous yeast Yarrowia lipolytica to produce α‐bisabolene, β‐bisabolene and γ‐bisabolene through heterologous expression of the α‐bisabolene synthase from Abies grandis, the β‐bisabolene synthase gene from Zingiber officinale and the γ‐bisabolene synthase gene from Helianthus annuus respectively. Subsequently, two metabolic engineering approaches, including overexpression of the endogenous mevalonate pathway genes and introduction of heterologous multidrug efflux transporters, were employed in order to improve bisabolene production. Furthermore, the fermentation conditions were optimized to maximize bisabolene production by the engineered Y. lipolytica strains from glucose. Finally, we explored the potential of the engineered Y. lipolytica strains for bisabolene production from the waste cooking oil. To our knowledge, this is the first report of bisabolene production in Y. lipolytica using metabolic engineering strategies. These findings provide valuable insights into the engineering of Y. lipolytica for a higher‐level production of bisabolene and its utilization in converting waste cooking oil into various industrially valuable products.

Summary The effect of a microbial consortium‐based (MCB) biocontrol product, composed of Bacillus subtilis, Trichoderma harzianum strain and diatomaceous earth as a carrier, on potato yield, and potential modes of action for its effect were investigated. The MCB product (300 kg ha−1) was added to furrows in which the potato seed tubers each year for 3 years (2016, 2017 and 2018), while potato planting without the MCB product treatment served as the control. A metagenomic analysis indicated that bacterial phylotypes dominated the microbial community, with a relatively small contribution of archaea and fungal taxa. The relative abundance of beneficial bacterial taxa increased significantly in response to the MCB product treatment. Notably, a higher relative abundance of bacterial taxa with carbon fixation, carbon‐degrading and nitrogen metabolism properties were observed in the MCB product‐treated potato rhizosphere. This was also reflected in the identification of a greater abundance of genes encoding enzymes involved in nitrogen metabolism, carbon fixation and carbon degradation pathways in the conducted metagenomic analysis. The greater relative abundance of these beneficial bacterial taxa in the rhizosphere of MCB product‐treated plots, as well as the higher abundance of genes associated with the indicated cellular processes, were associated with an increase in tuber yield. The observed changes in microbial community structure at an early stage of tuber development appears to have a beneficial impact on tuber yield.

Abstract Introduction There are few analyses of the 15 red blood group system antigen coding genes found in the Yunnan Yi nationality. This has caused many poteintial dangers relating to clinical blood transfusion. In this report, the coding genes and distribution of 15 blood group antigens system in the Yi nationality were tested and compared with those of Han nationality and other ethnic minorities. Methods The samples came from the healthy subjects in the first people's Hospital of Qujing, Yunnan Province. Two hundred and three Yunnan Yi and 197 Han nationality individuals were included. Thirty‐three blood group antigens with a low frequency from the 15 blood group systems of Yunnan Yi blood donors were genotyped and analyzed by PCR‐SSP. Sanger sequencing was used to detect A4GALT from the Yunnan Yi nationality. The χ2 test was used to analyze observed and expected values of gene distribution to verify conformation to the Hardy‐Weinberg equilibrium law. Fisher's exact test was used to analyze gene frequency distribution, and the statistical significance was set at p 0.05). Compared with Tibetan (Tibet), Zhuang (Nanning), and Dong (Guangxi), the gene distribution frequencies of Rh blood group system phenotype CC were significantly lower in the Yunnan Yi nationality (p

Abstract Due to climate change and increasing anthropogenic activities, lakes are disturbed frequently, usually by press (e.g., diffused pollution, rising temperatures) or pulse (e.g., storms, rainfall, pollution events) disturbances. Both press and pulse disturbances can affect abiotic and biotic environments, changing the structure of ecosystems and affecting ecosystem services. To confront with the effects of climate change and increasing anthropogenic activities, understanding the different effects of press and pulse disturbances on lake ecosystems is essential. This study assessed the effect of press and pulse disturbances of phosphorus on a microcosmic aquatic ecosystem by measuring the total phosphorus (TP), algae density, and physiological indicators of submerged macrophytes. We found that the microcosmic aquatic ecosystem responded differently to press and pulse disturbances. Our results suggested that it had a lower resistance to pulse phosphorus disturbances than to press phosphorus disturbances. There were significantly higher nutrient concentrations and algal densities in the pulse treatment than in the press treatment. Positive feedback was found between the biomass of submerged macrophytes and the water quality. There was a higher submerged macrophytes biomass at low TP concentration and algal density. In the context of climate change, press and pulse disturbances could have severe impacts on lake ecosystems. Our findings will provide some insight for further research and lake management.

Abstract Solar‐thermal conversion is considered as a green and simple means to improve the performance of energy storage materials, but often limited by the intrinsic photothermal properties of materials and crude structure design. Herein, inspired by the unique light trapping effect of wide leaf spiral grass during photosynthesis, a biomimetic structural photothermal energy storage system is developed, to further promote the solar thermal‐driven pseudo capacitance improvement. In this system, three‐dimensional printed tortional Kelvin cell arrays structure with interesting light trapping property functions as “spiral leaf blades” to improve the efficiency of light absorption, while graphene quantum dots/MXene nanohybrids with wide photothermal response range and strong electrochemical activity serve as “chloroplast” for photothermal conversion and energy storage. As expected, the biomimetic structure‐enhanced photothermal supercapacitor achieves an ideal solar thermal‐driven pseudo capacitance enhancement (up to 304%), an ultrahigh areal capacitance of 10.47 F cm−2, remarkable photothermal response (surface temperature change of 50.1 °C), excellent energy density (1.18 mWh cm−2) and cycling stability (10000 cycles). This work not only offers a novel enhancement strategy for photothermal applications, but also inspires new structure designs for multifunctional energy storage and conversion devices.

Abstract Nitrogen doping has readily emerged as an efficient solution to boost potassium‐ion storage of carbonaceous materials. Nevertheless, the capacity and lifespan enhancement of derived electrodes is still plagued by the incompetent in coordinating the dopant configurations. In the realm of emerging potassium‐ion hybrid capacitor (PIHC) device, dictating nitrogen doping to enhance pseudocapacitive behavior and improve K+ diffusion kinetics of carbonaceous anodes is scarcely demonstrated. Herein, we report the design of hierarchical N‐doped carbon nanopolyhedron@nanosheet composite via a salt‐confined synthetic strategy with tunable doping configurations toward advanced PIHC anode. A harmonized edge‐ to graphitic‐nitrogen ratio in such dual‐carbon materials enables outstanding rate capability (130 mAh g−1 at 10.0 A g−1) and cyclic performance (with a capacity retention of 80% after 2000 cycles at 5.0 A g−1) in half‐cell tests. As expected, the thus‐assembled PIHC full device with a working voltage of 4.2 V presents a high energy/power density (146 Wh kg−1/8000 W kg−1) and favorable cyclicability. This work is anticipated to offer an innovative insight into the coordination of nitrogen doping configurations in heteroatom‐doped carbon anode targeting high‐performance PIHC applications.

Abstract Reports of the Intergovernmental Panel on Climate Change (IPCC) indicate that temperature rise is still the general trend of the global climate in the 21st century. Invasive species may benefit from the increase in temperature, as climate can be viewed as a resource, and the increase in the available resources favors the invasibility of invasive species. This study aimed to assess the overwintering growth of the cosmopolitan invasive plant water hyacinth (Eichhornia crassipes) at its northern boundary. Using E. crassipes as a model plant, a cross‐year mesocosm experiment was conducted to determine 17 plant functional traits, including growth, morphological, root topological, photosynthetic, and stoichiometric traits, under climate warming (ambient, temperature rises of 1.5°C and 3.0°C), and water drawdown or water withdrawal (water depths of 1, 10, and 20 cm) treatments. The overwintering growth of E. crassipes was facilitated by climate warming and proper water drawdown, and climate warming played a leading role. A temperature rises of 3.0°C and a water depth of 10 cm were the most suitable conditions for the overwintering and rooting behavior of the plant. Controlling the temperature to within 1.5°C, an ambitious goal for China, still facilitated the overwintering of E. crassipes. With climate warming, the plant can overwinter successfully, which possibly assists it in producing and spreading new ramets in the vernal flood season. The new rooting behavior induced by ambient low temperature may be viewed as a unique growth adaptation strategy for a niche change, as it helps these plants invade empty niches left by dead free‐floating plants on the water surface following winter freezes. With continued global warming, the distribution of the plant may expand northward, and eradication of the plant during the winter water drawdown period may be a more effective strategy.

Background Salt‐sensitive hypertension is highly prevalent and associated with cardiorenal damage. Large clinical trials have demonstrated that SGLT2 (sodium‐glucose cotransporter 2) inhibitors exert hypotensive effect and cardiorenal protective benefits in patients with hypertension with and without diabetes. However, the underlying mechanism remains elusive. Methods and Results Dahl salt‐sensitive rats and salt‐insensitive controls were fed with 8% high‐salt diet and some of them were treated with canagliflozin. The blood pressure, urinary sodium excretion, and vascular function were detected. Transient receptor potential channel 3 (TRPC3) knockout mice were used to explain the mechanism. Canagliflozin treatment significantly reduced high‐salt‐induced hypertension and this effect was not totally dependent on urinary sodium excretion in salt‐sensitive hypertensive rats. Assay of vascular function and proteomics showed that canagliflozin significantly inhibited vascular cytoplasmic calcium increase and vasoconstriction in response to high‐salt diet. High salt intake increased vascular expression of TRPC3 in salt‐sensitive rats, which could be alleviated by canagliflozin treatment. Overexpression of TRPC3 mimicked salt‐induced vascular cytosolic calcium increase in vitro and knockout of TRPC3 erased the antihypertensive effect of canagliflozin. Mechanistically, high‐salt‐induced activation of NCX1 (sodium‐calcium exchanger 1) reverse mode increased cytoplasmic calcium level and vasoconstriction, which required TRPC3, and this process could be blocked by canagliflozin. Conclusions We define a previously unrecognized role of TRPC3/NCX1 mediated vascular calcium dysfunction in the development of high‐salt‐induced hypertension, which can be improved by canagliflozin treatment. This pathway is potentially a novel therapeutic target to antagonize salt‐sensitive hypertension.

Due to the congestion in urban rail transit during peak hours, this study proposes a hierarchical coordinated passenger inflow control model for overloaded metro lines from three dimensions, namely line, station and ticket gate. The hierarchical structure divides the system into three control layers and the model is established using the linear programming method. An improved particle swarm optimisation (PSO) algorithm, combining the interior penalty function and the basic PSO algorithm, is used to find the optimal objective value. In addition, the objective function with the penalty function to transform the constrained optimisation problem into an unconstrained optimisation problem is developed to solve the model. Finally, a real‐world instance with operation data of the Beijing Metro Line 5 is implemented to demonstrate the performance and effectiveness of the proposed approaches.

Abstract Permeability anisotropy of shale and tight gas reservoirs is critical for applications in unconventional gas recovery, but laboratory measurements are still limited. This paper presents an experimental method for determining permeability anisotropy of shale and tight reservoirs. The method uses gas production data from a canister and an analytical solution of continuity equation in anisotropic core sample. Axial permeability and transverse permeability of the core are estimated by matching experimental data with analytical solution. The proposed method is verified by comparing with true values and calculated values through numerical simulations that cover variations in rock permeability. The method is applied to real data measured in canister degassing tests (CDT) involving two different directional shale core samples. Then, the experimental results are compared with the results from pulse pressure decay (PPD) method. Both the verification from numerically calculated results and the comparison between PPD results and CDT results exhibit the practicality of the proposed method. At last, the effects of permeability anisotropy, porosity, initial gas pressure, rock dimensions, and adsorption on the profiles of gas production are investigated.

Abstract Bioactive materials are a kind of materials with unique bioactivities, which can change the cellular behaviors and elicit biological responses from living tissues. Bioactive materials came into the spotlight in the late 1960s when the researchers found that the materials such as bioglass could react with surrounding bone tissue for bone regeneration. In the following decades, advances in nanotechnology brought the new development opportunities to bioactive nanomaterials. Bioactive nanomaterials are not a simple miniaturization of macroscopic materials. They exhibit unique bioactivities due to their nanoscale size effect, high specific surface area, and precise nanostructure, which can significantly influence the interactions with biological systems. Nowadays, bioactive nanomaterials have represented an important and exciting area of research. Current and future applications ensure that bioactive nanomaterials have a high academic and clinical importance. This review summaries the recent advances in the field of bioactive nanomaterials, and evaluate the influence factors of bioactivities. Then, a range of bioactive nanomaterials and their potential biomedical applications are discussed. Furthermore, the limitations, challenges, and future opportunities of bioactive nanomaterials are also discussed.

Abstract Background Waardenburg syndrome (WS) is a rare autosomal‐dominant syndrome and is characterized by sensorineural hearing loss and pigment abnormalities. It is subdivided into four types according to the clinical characteristics. MITF is one of the major pathogenic genes for type II. The aim of this study was to investigate MITF mutations and the clinical characteristics of WS type 2 (WS2) in four Chinese families. Method Clinical diagnoses were based on detailed clinical findings. Six WS2 patients from four unrelated Chinese families were enrolled. Massively parallel DNA sequencing was used to find pathogenic genes and Sanger sequencing was used to confirm the variants detected. Results Sensorineural hearing loss was observed in four of six patients, three had heterochromia iridis, and five have freckled faces. We identified three novel MITF heterozygous mutations (c.831dupC, c.650G>A, and c.711‐2A>G) and one recurrent heterozygous mutation (c.328C>T) in the four WS2 families. Intra‐familial phenotypic variability and incomplete penetrance were found in WS2 patients with pathogenic variants of MITF. Conclusion Genetic diagnosis was performed for the involved four families based on the clinical manifestations. Four heterozygous mutations were identified in the MITF gene. Our findings expanded the phenotypic and genotypic spectrum of WS.

Abstract The evolution of rock permeability has been studied exhaustively, and a broad array of permeability models has been proposed. These models are normally derived under the assumption of elastic deformation when subjected to external stress. Under this assumption, these models define fracture permeability as a function of either gas pressure or effective stress. However, experimental observations indicate that rock fracture may experience unrecoverable deformation during the loading process. The goal of this study is to resolve this contradiction. In this study, derivation of fracture permeability correlation for elastoplastic contact of rough surfaces is presented. The proposed method for describing permeability evolution not only considers the topography of fracture surfaces but also and, more importantly, integrates the plastic deformation of rock fracture. Subsequently, the deformation and permeability change of shale sample containing a single rough‐walled fracture is experimentally investigated. The results show that the permeabilities obtained during the loading process are larger than the permeabilities obtained during the unloading process under the same stress conditions and that the fracture deformation cannot be fully recovered during the unloading process. At last, the proposed permeability model is applied to the experimental results and it is shown that the proposed model can predict the laboratory permeability data.

FAM175B is a reported regulator of p53 and suppresses tumorigenesis in numerous types of cancer, but very little is known about its function in esophageal squamous cell carcinomas (ESCCs), almost 70% of which exhibit mutations in p53. Here, we report that FAM175B expression is downregulated in high‐grade intraepithelial neoplasia (t = 2.44, P = 0.031) and ESCC (t = 5.664, P

Abstract As alternatives, metallic/nonmetallic bone graft materials play significant roles in bone defect surgery to treat external trauma or bone disease. However, to date, there are rather limited long‐term implantable materials owning to in situ molding incapability of metallics and poor mechanical property of nonmetallics. Here, Bi‐based low melting point alloy, with unique properties of injectability, solid‐liquid phase transition, mechanical capability, and biocompatibility, present obvious long‐lasting bone affinity as the excellent artificial bone‐substitute. It is particularly necessary to point out that the targeted injected Bi alloy remains in its original position for up to 210 days without moving, as well as, displays good osseointegration ability to resolve repeated revision trauma caused by losing bone repair material. Additionally, with outstanding electrical and thermal conductivity, an unconventional way using Bi alloy to realize very beneficial hyperthermia analgesia via non‐invasive wireless energy delivery is first proposed, which avoids adverse effects on bone remodeling inflicted by traditional drugs. The significantly decreased expression of pain sensitizing factor, such as, interleukin‐6, neuropeptide substance, and transient receptor potential vanilloid 1 reveals the potential mechanism of hyperthermia analgesia. The present findings suggest the combination therapy of Bi alloy in bone repair and analgesia, which owns far‐reaching clinical application value.

Abstract The industrial application of lithium metal anode requires less side reaction between active lithium and electrolyte, which demands the sustainability of the electrolyte‐induced solid‐electrolyte interface. Here, through a new diluted lithium difluoro(oxalato)borate‐based (LiDFOB) high concentration electrolyte system, it is found that the oxidation behavior of aggregated LiDFOB salt has a great impact on solid‐electrolyte interphase (SEI) formation and Li reversibility. Under the operation window of Cu/LiNi0.8Co0.1Mn0.1O2 full cells (rather than Li/Cu configuration), a polyether/coordinated borate containing solid‐electrolyte interphase with inner Li2O crystalline can be observed with the increasing concentration of salt, which can be ascribed to the reaction between aggregated electron‐deficient borate species and electron‐rich alkoxide SEI components. The high Li reversibility (99.34%) and near‐theoretical lithium deposition enable the stable cycling of LiNi0.8Co0.1Mn0.1O2/Li cells (N/P < 2, 350 Wh kg−1) under high cutoff voltage condition of 4.6 V and lean electrolyte condition (E/C ≈ 3.2 g Ah−1).