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Background China is one of the world’s fastest-aging countries. Population aging and social-economic development show close relations. This study aims to illustrate the spatial-temporal distribution and movement of gravity centers of population aging and social-economic factors and thier spatial interaction across the provinces in China. Methods Factors of elderly population rate (EPR), elderly dependency ratio (EDR), per capita gross regional product (GRP pc ), and urban population rate (UPR) were collected. Distribution patterns were detected by using global spatial autocorrelation, Kernel density estimation, and coefficient of variation. Further, Arc GIS software was used to find the gravity centers and their movement trends yearly from 2002 to 2018. The spatial interaction between the variables was investigated based on bivariate spatial autocorrelation analysis. Results The results showed a larger variety of global spatial autocorrelation indexed by Moran’s I and stable trends of dispersion degree without obvious convergence in EPR and EDR. Furthermore, the gravity centers of the proportion of EPR and EDR moved northeastward. In contrast, the economic and urbanization factors showed a southwestward movement, which exhibited an reverse trend compared to population aging indicators. Moreover, the movement rates of EPR and EDR (15.12 and 18.75 km/year, respectively) were higher than that of GRP pc (13.79 km/year) and UPR (6.89 km/year) annually during the study period. Further, the bivariate spatial autocorrelation variation is in line with the movement trends of gravity centers which showed a polarization trend of population aging and social-economic factors that the difference between southwest and northeast directions and exhibited a tendency to expand in China. Conclusions In sum, our findings revealed the difference in spatio-temporal distribution and variation between population aging and social-economic factors in China. It further indicates that the opposite movements of gravity centers and the change of the BiLISA in space which may result in the increase of the economic burden of the elderly care in northern China. Hence, future development policy should focus on the social-economic growth and distribution of old-aged supporting resources, especially in northern China.

Sensitivity and pressure range are two significant parameters of pressure sensors. Existing pressure sensors have difficulty achieving both high sensitivity and a wide pressure range. Therefore, we propose a new pressure sensor with a ternary nanocomposite Fe 2 O 3 /C@SnO 2 . The sea urchin-like Fe 2 O 3 structure promotes signal transduction and protects Fe 2 O 3 needles from mechanical breaking, while the acetylene carbon black improves the conductivity of Fe 2 O 3 . Moreover, one part of the SnO 2 nanoparticles adheres to the surfaces of Fe 2 O 3 needles and forms Fe 2 O 3 /SnO 2 heterostructures, while its other part disperses into the carbon layer to form SnO 2 @C structure. Collectively, the synergistic effects of the three structures (Fe 2 O 3 /C, Fe 2 O 3 /SnO 2 and SnO 2 @C) improves on the limited pressure response range of a single structure. The experimental results demonstrate that the Fe 2 O 3 /C@SnO 2 pressure sensor exhibits high sensitivity (680 kPa −1 ), fast response (10 ms), broad range (up to 150 kPa), and good reproducibility (over 3500 cycles under a pressure of 110 kPa), implying that the new pressure sensor has wide application prospects especially in wearable electronic devices and health monitoring. Pressure sensors with high sensitivity and large pressure range is crucial to their various applications in electronic engineering. Here, Wang et al. propose a new design based on a ternary nanocomposite material and show high pressure sensitivity of 680 kPa −1 and fast response of 10 ms up to 150 kPa.

The development of facile tailoring approach to adjust the intrinsic activity and stability of atomically-precise metal nanoclusters catalysts is of great interest but remians challenging. Herein, the well-defined Au 8 nanoclusters modified by single-atom sites are rationally synthesized via a co-eletropolymerization strategy, in which uniformly dispersed metal nanocluster and single-atom co-entrenched on the poly-carbazole matrix. Systematic characterization and theoretical modeling reveal that functionalizing single-atoms enable altering the electronic structures of Au 8 clusters, which amplifies their electrocatalytic reduction of CO 2 to CO activity by ~18.07 fold compared to isolated Au 8 metal clusters. The rearrangements of the electronic structure not only strengthen the adsorption of the key intermediates *COOH, but also establish a favorable reaction pathway for the CO 2 reduction reaction. Moreover, this strategy fixing nanoclusters and single-atoms on cross-linked polymer networks efficiently deduce the performance deactivation caused by agglomeration during the catalytic process. This work contribute to explore the intrinsic activity and stability improvement of metal clusters. Tailoring catalytic performance of atomically-precise metal nanoclusters catalysts is of great interest but remains challenging. Here, the authors report a co-eletropolymerization strategy to modify well-defined Au 8 nanoclusters by single-atom sites to enhance its electrocatalytic activity for the reduction of CO 2 towards CO.

Environmental problems have always received immense attention from scientists. Toxicants pollution is a critical environmental concern that has posed serious threats to human health and agricultural production. Heavy metals and pesticides are top of the list of environmental toxicants endangering nature. This review focuses on the toxic effect of heavy metals (cadmium (Cd), lead (Pb), copper (Cu), and zinc (Zn)) and pesticides (insecticides, herbicides, and fungicides) adversely influencing the agricultural ecosystem (plant and soil) and human health. Furthermore, heavy metals accumulation and pesticide residues in soils and plants have been discussed in detail. In addition, the characteristics of contaminated soil and plant physiological parameters have been reviewed. Moreover, human diseases caused by exposure to heavy metals and pesticides were also reported. The bioaccumulation, mechanism of action, and transmission pathways of both heavy metals and pesticides are emphasized. In addition, the bioavailability in soil and plant uptake of these contaminants has also been considered. Meanwhile, the synergistic and antagonistic interactions between heavy metals and pesticides and their combined toxic effects have been discussed. Previous relevant studies are included to cover all aspects of this review. The information in this review provides deep insights into the understanding of environmental toxicants and their hazardous effects.

Achieving the activation of drugs within cellular systems may provide targeted therapies. Here we construct a tumour-selective cascade activatable self-detained system (TCASS) and incorporate imaging probes and therapeutics. We show in different mouse models that the TCASS system accumulates in solid tumours. The molecules show enhanced accumulation in tumour regions via the effect of recognition induced self-assembly. Analysis of the molecular penetration in tumour tissue shows that in vivo self-assembly increases the penetration capability compared to typical soft or hard nanomaterials. Importantly, the in vivo self-assembled molecules exhibit a comparable clearance pathway to that of small molecules, which are excreted from organs of the reticuloendothelial system (liver and kidney), while are relatively slowly eliminated from tumour tissues. Finally, this system, combined with the NIR probe, shows high specificity and sensitivity for detecting bladder cancer in isolated intact patient bladders. The activation of drugs within cellular systems may provide targeted therapies for cancer. Here, the authors make a drug delivery system that is activated within the cell and exploits XIAP expression to cleave a linker region, resulting in the self-assembly of the system and drug release within cancer cells.

Background： Sacroiliac （SI） screw fixation is a demanding technique, with a high rate of screw malposition due to the complex pelvic anatomy. TiRobot- is an orthopedic surgery robot which can be used for SI screw fixation. This study aimed to evaluate the accuracy of robot-assisted placement of SI screws compared with a freehand technique. Methods：Thirty patients requiring posterior pelvic ring stabilization were randomized to receive freehand or robot-assisted SI screw fixation, between January 2016 and June 2016 at Beijing Jishuitan Hospital. Forty-five screws were placed at levels S1 and S2. In both methods, the primary end point screw position was assessed and classified using postoperative computed tomography. Fisher＇s exact probability test was used to analyze the screws＇positions. Secondary end points, such as duration of trajectory planning, surgical time after reduction of the pelvis, insertion time for guide wire, number of guide wire attempts, and radiation exposure without pelvic reduction, were also assessed. Results： Twenty-three screws were placed in the robot-assisted group and 22 screws in the freehand group; no postoperative complications or revisions were reported. The excellent and good rate of screw placement was 100% in the robot-assisted group and 95% in the freehand group. The P value （0.009） showed the same superiority in screw distribution. The fluoroscopy time after pelvic reduction in the robot-assisted group was significantly shorter than that in the freehand group （median [Q1, Q3]： 6.0 [6.0, 9.0] s vs. median [Q1, Q3]： 36.0 [21.5, 48.0] s; χ2 = 13.590, respectively, P 〈 0.001）; no difference in operation time after reduction of the pelvis was noted （χ2 = 1.990, P = 0.158）. Time for guide wire insertion was significantly shorter for the robot-assisted group than that for the freehand group （median [Q1, Q3]： 2.0 [2.0, 2.7] min vs. median [Q1, Q3]： 19.0 [15.5, 45.0] min; χ2 = 20.952, respectively, P 〈 0.001）. The number of guide wire attempts in the robot-assisted group was significantly less than that in the freehand group （median [Q1, Q3]： 1.0 [1.0,1.0] time vs. median [Q1, Q3]： 7.0 [1.0, 9.0] times; χ2 = 15.771, respectively, P 〈 0.001）. The instrumented SI levels did not differ between both groups （from S1 to S2, χ2 = 4.760, P = 0.093）. Conclusions： Accuracy of the robot-assisted technique was superior to that of the freehand technique. Robot-assisted navigation is safe for unstable posterior pelvic ring stabilization, especially in S1, but also in S2. SI screw insertion with robot-assisted navigation is clinically feasible.

Background Studies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population. Methods The data came from the National Health and Nutrition Examination Survey (NHANES 2001–2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan–Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use. Results 1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found. Conclusion The relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population.

Besides genome editing, CRISPR-Cas12a has recently been used for DNA detection applications with attomolar sensitivity but, to our knowledge, it has not been used for the detection of small molecules. Bacterial allosteric transcription factors (aTFs) have evolved to sense and respond sensitively to a variety of small molecules to benefit bacterial survival. By combining the single-stranded DNA cleavage ability of CRISPR-Cas12a and the competitive binding activities of aTFs for small molecules and double-stranded DNA, here we develop a simple, supersensitive, fast and high-throughput platform for the detection of small molecules, designated CaT-SMelor ( C RISPR-Cas12a- and aT F-mediated s mall m ol e cu l e detect or ). CaT-SMelor is successfully evaluated by detecting nanomolar levels of various small molecules, including uric acid and p -hydroxybenzoic acid among their structurally similar analogues. We also demonstrate that our CaT-SMelor directly measured the uric acid concentration in clinical human blood samples, indicating a great potential of CaT-SMelor in the detection of small molecules. Bacterial allosteric transcription factors can sense and respond to a variety of small molecules. Here the authors present CaT-SMelor which uses Cas12a and allosteric transcription factors to detect small molecules in the nanomolar range.

Clinically, multimodal therapies are adopted worldwide for the management of cancer, which continues to be a leading cause of death. In recent years, immunotherapy has firmly established itself as a new paradigm in cancer care that activates the body’s immune defense to cope with cancer. Immunotherapy has resulted in significant breakthroughs in the treatment of stubborn tumors, dramatically improving the clinical outcome of cancer patients. Multiple forms of cancer immunotherapy, including immune checkpoint inhibitors (ICIs), adoptive cell therapy and cancer vaccines, have become widely available. However, the effectiveness of these immunotherapies is not much satisfying. Many cancer patients do not respond to immunotherapy, and disease recurrence appears to be unavoidable because of the rapidly evolving resistance. Moreover, immunotherapies can give rise to severe off-target immune-related adverse events. Strategies to remove these hindrances mainly focus on the development of combinatorial therapies or the exploitation of novel immunotherapeutic mediations. Nanomaterials carrying anticancer agents to the target site are considered as practical approaches for cancer treatment. Nanomedicine combined with immunotherapies offers the possibility to potentiate systemic antitumor immunity and to facilitate selective cytotoxicity against cancer cells in an effective and safe manner. A myriad of nano-enabled cancer immunotherapies are currently under clinical investigation. Owing to gaps between preclinical and clinical studies, nano-immunotherapy faces multiple challenges, including the biosafety of nanomaterials and clinical trial design. In this review, we provide an overview of cancer immunotherapy and summarize the evidence indicating how nanomedicine-based approaches increase the efficacy of immunotherapies. We also discuss the key challenges that have emerged in the era of nanotechnology-based cancer immunotherapy. Taken together, combination nano-immunotherapy is drawing increasing attention, and it is anticipated that the combined treatment will achieve the desired success in clinical cancer therapy.

As a traditional therapeutic method, electroacupuncture (EA) has been adopted as an alternative therapy for stroke recovery. Here, we aimed to evaluate whether EA therapy at points of Quchi (LI11) and Zusanli (ST36) alleviated neuronal apoptosis by PTEN signaling pathway after ischemic stroke. A total of 72 male Sprague–Dawley rats were randomized into three groups, including sham group, MCAO group, and EA group. EA was initiated after 24 h of reperfusion for 3 consecutive days. At 72 h following ischemia/reperfusion, neurological deficits, infarct volumes, and TUNEL staining were evaluated and the PTEN pathway-related proteins together with apoptosis-related proteins were detected. The results indicated that EA treatment significantly decreased cerebral infarct volume, neurological deficits and alleviated proportion of apoptotic cells in cerebral ischemic rats. Furthermore, EA significantly up-regulated the phosphorylation levels of PDK1, Akt(Thr308), GSK-3β, and down-regulated the phosphorylation levels of PTEN, Akt(Ser473) in the peri-infarct cortex. EA treatment significantly reduced the up-regulation of caspase-3, cleaved-caspase-3, Bim, and reversed the reduction of Bcl-2 induced by the ischemic stroke. These findings suggest that EA treatment at points of Quchi (LI11)- and Zusanli (ST36)-induced neuroprotection might involve inhibition of apoptosis via PTEN pathway.