Trends in under-five mortality rate in China, 1996-2020: a Joinpoint regression and correlation analysis.

OBJECTIVES: To analyse annual trends of the under-five mortality rate (U5MR) and main cause-specific U5MR in China from 1996 to 2020 and to assess the potential correlation of the healthcare system and health expenditure with the U5MR in China. DESIGN: A retrospective observational study using national data from 1996 to 2020. Joinpoint regression was employed to model U5MR trends and Pearson correlation analysis was conducted to examine the relationship between healthcare system factors, health expenditure and U5MR. SETTING: Nationwide study covering both rural and urban populations across China over a 25-year period. RESULTS: The U5MR in China experienced a three-stage decline from 1996 to 2020 with an average annual percentage rate change (AAPC) of -7.27 (p<0.001). The AAPC of the rural U5MR (-7.07, p<0.001) was higher than that in urban areas (-5.57, p<0.001). Among the five main causes, the decrease in pneumonia-caused U5MR was the fastest while the decreases in congenital heart disease and accidental asphyxia were relatively slow. The rates of hospital delivery (r=-0.981, p<0.001), neonatal visits (r=-0.848, p<0.001) and systematic health management (r=-0.893, p<0.001) correlated negatively with U5MR. The proportion of government health expenditure in the total health expenditure (THE) correlated negatively with the national U5MR (r=-0.892, p<0.001) while the proportion of out-of-pocket health expenditure in THE correlated positively (r=0.902, p<0.001). CONCLUSION: China made significant advances in reducing U5MR from 1996 to 2020. The rural-urban gap in U5MR has narrowed, though rural areas remain a key concern. To further reduce U5MR, China should focus on rural areas, pay more attention to congenital heart disease and accidental asphyxia, further improve its health policies, and continue to increase the government health expenditure.

Magnetocaloric effect of topological excitations in Kitaev magnets.

Traditional magnetic sub-Kelvin cooling relies on the nearly free local moments in hydrate paramagnetic salts, whose utility is hampered by the dilute magnetic ions and low thermal conductivity. Here we propose to use instead fractional excitations inherent to quantum spin liquids (QSLs) as an alternative, which are sensitive to external fields and can induce a very distinctive magnetocaloric effect. With state-of-the-art tensor-network approach, we compute low-temperature properties of Kitaev honeycomb model. For the ferromagnetic case, strong demagnetization cooling effect is observed due to the nearly free Z2 vortices via spin fractionalization, described by a paramagnetic equation of state with a renormalized Curie constant. For the antiferromagnetic Kitaev case, we uncover an intermediate-field gapless QSL phase with very large spin entropy, possibly due to the emergence of spinon Fermi surface and gauge field. Potential realization of topological excitation magnetocalorics in Kitaev materials is also discussed, which may offer a promising pathway to circumvent existing limitations in the paramagnetic hydrates.

Clinical significance of preoperative nutritional status in elderly gastric cancer patients undergoing radical gastrectomy: A single-center retrospective study.

BACKGROUND: The population of elderly patients with gastric cancer is increasing, which is a major public health issue in China. Malnutrition is one of the greatest risk factors for adverse clinical outcomes in elderly patients with gastric cancer. AIM: To investigate the preoperative nutritional status and its association with delayed discharge of elderly gastric cancer patients following radical gastrectomy. METHODS: A total of 783 patients aged 65 years and older harboring gastric adenocarcinoma and following radical gastrectomy were retrospectively analyzed from the prospectively collected database of Zhongshan Hospital of Fudan University between January 2018 and May 2020. RESULTS: The overall rate of malnutrition was 31.8%. The incidence of postoperative complications was significantly higher in the malnourished group compared to the well-nourished group (P < 0.001). Nutritional characteristics in the malnourished group, including body mass index, prognostic nutritional index (PNI), albumin, prealbumin, and hemoglobin, were all significantly lower than those in the well-nourished group. The percentage of patients who received postoperative total nutrient admixture was lower in the malnourished group compared to the well-nourished group (22.1% vs 33.5%, P = 0.001). Age ≥ 70 years (HR = 1.216, 95%CI: 1.048-1.411), PNI < 44.5 (HR = 1.792, 95%CI: 1.058-3.032), operation time ≥ 160 minutes (HR = 1.431, 95%CI: 1.237-1.656), and postoperative complications grade III or higher (HR = 2.191, 95%CI: 1.604-2.991) were all recognized as independent risk factors associated with delayed discharge. CONCLUSION: Malnutrition is relatively common in elderly patients undergoing gastrectomy. Low PNI is an independent risk factor associated with delay discharge. More strategies are needed to improve the clinical outcome of these patients.

Discovery of benzoheterocyclic-substituted amide derivatives as apoptosis signal-regulating kinase 1 (ASK1) inhibitors.

Three series of benzoheterocyclic-substituted amide derivatives were designed and synthesized as potent ASK1 inhibitors in this work. After undergoing continuous structural optimization, compound 17a was discovered to be a novel inhibitor of ASK1 with good potency (kinase, IC50 = 26 nM), noteworthy liver microsomal stability (human, T1/2 = 340.4 min), good pharmacokinetic parameters (rat, T1/2 p.o. = 2.11 h, AUClast p.o. = 10 900 h ng mL-1) and high oral bioavailability (rat, F = 97.9%), while also being inactive towards hERG (IC50 > 10 µM).

Steering Muscle-Based Bio-Syncretic Robot Through Bionic Optimized Biped Mechanical Design.

Bio-syncretic robots consisting of artificial structures and living muscle cells have attracted much attention owing to their potential advantages, such as high drive efficiency, miniaturization, and compatibility. Motion controllability, as an important factor related to the main performance of bio-syncretic robots, has been explored in numerous studies. However, most of the existing bio-syncretic robots still face challenges related to the further development of steerable kinematic dexterity. In this study, a bionic optimized biped fully soft bio-syncretic robot actuated by two muscle tissues and steered with a direction-controllable electric field generated by external circularly distributed multiple electrodes has been developed. The developed bio-syncretic robot could realize wirelessly steerable motion and effective transportation of microparticle cargo on artificial polystyrene and biological pork tripe surfaces. This study may provide an effective strategy for the development of bio-syncretic robots and other related studies, such as nonliving soft robot design and muscle tissue engineering.

Shear stiffening gel-enabled twisted string for bio-inspired robot actuators.

A rotary motor combined with fibrous string demonstrates excellent performance because it is powerful, lightweight, and prone to large strokes; however, the stiffness range and force-generating capability of twisted string transmission systems are limited. Here, we present a variable stiffness artificial muscle generated by impregnating shear stiffening gels (STGs) into a twisted string actuator (TSA). A high twisting speed produces a large impact force and causes shear stiffening of the STG, thereby improving the elasticity, stiffness, force capacity, and response time of the TSA. We show that at a twisting speed of 4186 rpm, the elasticity of an STG-TSA reached 30.92 N/mm, whereas at a low twisting speed of 200 rpm, it was only 10.51 N/mm. In addition, the STG-TSA exhibited a more prominent shear stiffening effect under a high stiffness load. Our work provides a promising approach for artificial muscles to coactivate with human muscles to effectively compensate for motion.

From Skin Movement to Wearable Robotics: The Case of Robotic Gloves.

Previous research on wearable robotics focused on developing actuation mechanisms while overlooking influences of skin movement. During finger flexion, skins on the opisthenar and finger back are stretched. Impeding such skin movement will obstruct normal finger motions. In this research, a statistical study on skin movement is proposed and conducted to quantify skin movement on human hands. Results of 30 subjects (15 men and 15 women) reveal that skin at the finger back extends by an average of 29.3 ± 7.2% in fist clenching. Based on this study, design guidelines for robotic gloves are proposed, and nominal strain values at different hand regions are tabulated for references in robotic glove design. To explore the influence of skin movement on wearable robotics, an elastomer-constrained flat tube actuator is proposed based on which two prototype robotic gloves are developed: one with an ergonomic strap interface that has small constraint to skin motion, and the other based on the commonly used fabric glove that is supposed to have large constraint to skin motion. With the same power input to the robotic gloves, the strap-based design achieves a finger motion range of 2.5 times and a gripping force of 4.3 times that of the conventional fabric glove.

Giant magnetocaloric effect in spin supersolid candidate Na2BaCo(PO4)2.

Supersolid, an exotic quantum state of matter that consists of particles forming an incompressible solid structure while simultaneously showing superfluidity of zero viscosity1, is one of the long-standing pursuits in fundamental research2,3. Although the initial report of 4He supersolid turned out to be an artefact4, this intriguing quantum matter has inspired enthusiastic investigations into ultracold quantum gases5-8. Nevertheless, the realization of supersolidity in condensed matter remains elusive. Here we find evidence for a quantum magnetic analogue of supersolid-the spin supersolid-in the recently synthesized triangular-lattice antiferromagnet Na2BaCo(PO4)2 (ref. 9). Notably, a giant magnetocaloric effect related to the spin supersolidity is observed in the demagnetization cooling process, manifesting itself as two prominent valley-like regimes, with the lowest temperature attaining below 100 mK. Not only is there an experimentally determined series of critical fields but the demagnetization cooling profile also shows excellent agreement with the theoretical simulations with an easy-axis Heisenberg model. Neutron diffractions also successfully locate the proposed spin supersolid phases by revealing the coexistence of three-sublattice spin solid order and interlayer incommensurability indicative of the spin superfluidity. Thus, our results reveal a strong entropic effect of the spin supersolid phase in a frustrated quantum magnet and open up a viable and promising avenue for applications in sub-kelvin refrigeration, especially in the context of persistent concerns about helium shortages10,11.

Ningetinib plus gefitinib in EGFR-mutant non-small-cell lung cancer with MET and AXL dysregulations: A phase 1b clinical trial and biomarker analysis.

BACKGROUND: MET and AXL dysregulations are implicated in acquired resistance to EGFR-TKIs in NSCLC. But consensus on the optimal definition for MET/AXL dysregulations in EGFR-mutant NSCLC is lacking. Here, we investigated the efficacy and tolerability of ningetinib (a MET/AXL inhibitor) plus gefitinib in EGFR-mutant NSCLC, and evaluated the clinical relevance of MET/AXL dysregulations by different definitions. METHODS: Patients in this phase 1b dose-escalation/dose-expansion trial received ningetinib 30 mg/40 mg/60 mg plus gefitinib 250 mg once daily. Primary endpoints were tolerability (dose-escalation) and objective response rate (dose-expansion). MET/AXL status were analyzed using FISH and IHC. RESULTS: Between March 2017 and January 2021, 108 patients were enrolled. The proportion of MET focal amplification, MET polysomy, MET overexpression, AXL amplification and AXL overexpression is 18.1 %, 5.6 %, 55.8 %, 8.1 % and 45.3 %, respectively. 6.8 % patients have concurrent MET amplification and AXL overexpression. ORR is 30.8 % for tumors with MET amplification, 0 % for MET polysomy, 24.1 % for MET overexpression, 20 % for AXL amplification and 27.6 % for AXL overexpression. For patients with concurrent MET amplification and AXL overexpression, ningetinib plus gefitinib provides an ORR of 80 %, DCR of 100 % and median PFS of 4.7 months. Tumors with higher MET copy number and AXL expression tend to have higher likelihood of response. Biomarker analyses show that MET focal amplification and overexpression are complementary in predicting clinical benefit from MET inhibition, while AXL dysregulations defined by an arbitrary level may dilute the efficacy of AXL blockade. CONCLUSIONS: This study demonstrates that combined blockade of MET, AXL and EGFR is a feasible strategy for a subset of EGFR-mutant NSCLC. TRIAL REGISTRATION: Chinadrugtrials.org.cn, CTR20160875.

Identification and Measurement of Biomarkers at Single Microorganism Level for In Situ Monitoring Deep Ultraviolet Disinfection Process.

Since the COVID-19 disease has been further aggravated, the prevention of pathogen transmission becomes a vital issue to restrain casualties. Recent research outcomes have shown the possibilities of the viruses existing on inanimate surfaces up to few days, which carry the risk of touch propagation of the disease. Deep ultraviolet germicide irradiation (UVGI) with the wavelength of 255-280nm has been verified to efficiently disinfect various types of bacteria and virus, which could prevent the aggravation of pandemic spread. Even though considerable experiments and approaches have been applied to evaluate the disinfection effects, there are only few reports about how the individual bio-organism behaves after ultraviolet C (UVC) irradiation, especially in the aspect of mechanical changes. Furthermore, since the standard pathway of virus transmission and reproduction requires the host cell to assemble and transport newly generated virus, the dynamic response of infectious cell is always the vital aspect of virology study. In this work, high power LEDs array has been established with 270nm UVC irradiation to evaluate disinfection capability on various types of bio-organism, and incubator embedded atomic force microscopy (AFM) is used to investigate the single bacterium and virus under UVGI. The real-time tracking of the living Vero cells infected with adenovirus has also been presented in this study. The results show that after sufficient UVGI, the outer shell of bacteria and viruses remain intact in structure, however the bio-organisms lost the capability of reproduction and normal metabolism. The experiment results also indicate that once the host cell is infected with adenovirus, the rapid production of newborn virus capsid will gradually destroy the cellular normal metabolism and lose mechanical integrity.

The multiple reference range of mean uterine artery pulsatility index for natural and in vitro fertilization singletons during 11-14 gestational weeks.

Background: Ultrasonography of the uterine artery (UtA) in the first and second trimesters of pregnancy can assess uterine-placental blood perfusion and guide early clinical prevention. Establishing normal ranges of the UtA pulsatility index (UtA-PI) at 11-14 weeks of pregnancy is helpful for the early identification of high-risk pregnant women and improving the prognosis. This study aimed to establish a reference range of UtA-PI based on crown-rump length (CRL) for spontaneous and in vitro fertilization (IVF) singleton pregnancy during 11-14 weeks, respectively. Methods: A prospective study was performed at Peking Union Medical College Hospital. Healthy, low-risk women with a singleton pregnancy at 11-14 gestational weeks were consecutively recruited for this study from December 2017 to December 2020. All participants underwent routine prenatal ultrasound examination. The CRL of the fetus and the UtA-PI were measured in both uterine arteries, and average values were calculated. The LMS method was used to fit the percentile (P)5, P10, P25, P50, P75, P90, and P95 curves of the UtA-PI value of spontaneous and IVF singleton pregnancy with CRL changes, respectively. Results: A total of 1,962 pregnant women with normal fetuses were included in this study, including 1,792 pregnancies conceived naturally and 170 IVF fetuses. The UtA-PI reference range in the spontaneous pregnancy group was consistently higher than that in the IVF group during 11-14 weeks, and showed a statistically significant difference in UtA-PI for spontaneous and IVF pregnancies (P<0.001). According to the LMS method, each percentile curve of UtA-PI decreased with the increase of CRL in both the natural pregnancy group and the IVF group. The P95 range of UtA-PI for pregnant women with naturally conceived and IVF pregnancy was 2.74 to 2.11 and 2.50 to 1.94, respectively. The overall change of UtA-PI differentials of the two groups showed a downward trend and decreased slightly with the increase of CRL. Conclusions: This study provided a single-center, large sample of data and constructed a CRL-based reference value of UtA-PI for spontaneous and IVF singleton pregnancy, which provides a reliable basis for early UtA evaluation and early clinical decision-making during 11-14 gestational weeks.

Plaquette Singlet Transition, Magnetic Barocaloric Effect, and Spin Supersolidity in the Shastry-Sutherland Model.

Inspired by recent experimental measurements [Guo et al., Phys. Rev. Lett. 124, 206602 (2020PRLTAO0031-900710.1103/PhysRevLett.124.206602); Jiménez et al., Nature (London) 592, 370 (2021)NATUAS0028-083610.1038/s41586-021-03411-8] on frustrated quantum magnet SrCu_{2}(BO_{3})_{2} under combined pressure and magnetic fields, we study the related spin-1/2 Shastry-Sutherland model using state-of-the-art tensor network methods. By calculating thermodynamics, correlations, and susceptibilities, we find, in zero magnetic field, not only a line of first-order dimer-singlet to plaquette-singlet phase transition ending with a critical point, but also signatures of the ordered plaquette-singlet transition with its critical end point terminating on this first-order line. Moreover, we uncover prominent magnetic barocaloric responses, a novel type of quantum correlation induced cooling effect, in the strongly fluctuating supercritical regime. Under finite fields, we identify a quantum phase transition from the plaquette-singlet phase to the spin supersolid phase that breaks simultaneously lattice translational and spin rotational symmetries. The present findings on the Shastry-Sutherland model are accessible in current experiments and would shed new light on the critical and supercritical phenomena in the archetypal frustrated quantum magnet SrCu_{2}(BO_{3})_{2}.

Decentralized access control for secure microservices cooperation with blockchain.

With the rapid advancement of cloud-native computing, the microservice with high concurrency and low coupling has ushered in an unprecedented period of vigorous development. However, due to the mutability and complexity of cooperation procedures, it is difficult to realize high-efficient security management on these microservices. Traditional centralized access control has the defects of relying on a centralized cloud manager and a single point of failure. Meanwhile, decentralized mechanisms are defective by inconsistent policies defined by different participants. This paper first proposes a blockchain-based distributed access control policies and scheme, especially for microservices cooperation with dynamic access policies. We store the authorized security policies on the blockchain to solve the inconsistent policy problem while enabling individual management of personalized access policies by the providers rather than a central authority. Then we propose a graph-based decision-making scheme to achieve an efficient access control for microservices cooperation. Through the evaluations and experiments, it shows that our solution can realize effective distributed access control at an affordable cost.

Insight into interface electronic structure of ZnIn2S4/TiO2 heterostructure for enhanced photoelectrochemical glycerol oxidation.

Developing a high-efficiency photoelectrochemical (PEC) electrode for the glycerol oxidation reaction (GOR) is important for producing valuable products. The PEC performance could be enhanced by rationally designing heterostructures with inhibited recombination of charge carriers. Nevertheless, the interface electronic structure of heterostructures has not been comprehensively analyzed. In this work, the PEC GOR performance of ZnIn2S4/TiO2 heterostructure photoanode showed 1.7 folds enhancement than that of pure TiO2 photoanode at 1.23 V vs. RHE. The ZnIn2S4/TiO2 heterostructure was simulated by constructing ZnIn2S4 on the TiO2 single crystal, which was beneficial for investigating the interface electronic structure of heterostructure. Single-particle spectroscopy demonstrated a significantly increased lifetime of charge carriers. Combined with the in-situ X-ray photoelectron spectroscopy, Kelvin probe force microscopy, work function, and electron paramagnetic resonance, the interface electronic structure of the ZnIn2S4/TiO2 heterostructure was proposed with a Z-scheme mechanism. This work provides a comprehensive strategy for analyzing the interface electronic structure of heterostructures.

Uncover rock-climbing fish's secret of balancing tight adhesion and fast sliding for bioinspired robots.

The underlying principle of the unique dynamic adaptive adhesion capability of a rock-climbing fish (Beaufortia kweichowensis) that can resist a pull-off force of 1000 times its weight while achieving simultaneous fast sliding (7.83 body lengths per second (BL/S)) remains a mystery in the literature. This adhesion-sliding ability has long been sought for underwater robots. However, strong surface adhesion and fast sliding appear to contradict each other due to the need for high surface contact stress. The skillfully balanced mechanism of the tight surface adhesion and fast sliding of the rock-climbing fish is disclosed in this work. The Stefan force (0.1 mN/mm2) generated by micro-setae on pectoral fins and ventral fins leads to a 70 N/m2 adhesion force by conforming the overall body of the fish to a surface to form a sealing chamber. The pull-off force is neutralized simultaneously due to the negative pressure caused by the volumetric change of the chamber. The rock-climbing fish's micro-setae hydrodynamic interaction and sealing suction cup work cohesively to contribute to low friction and high pull-off-force resistance and can therefore slide rapidly while clinging to the surface. Inspired by this unique mechanism, an underwater robot is developed with incorporated structures that mimic the functionality of the rock-climbing fish via a micro-setae array attached to a soft self-adaptive chamber, a setup which demonstrates superiority over conventional structures in terms of balancing tight underwater adhesion and fast sliding.

Investigation of the Relationship between Electronic Structures and Bioactivities of Polypyridyl Ru(II) Complexes.

Ruthenium (Ru)-based organometallic drugs have gained attention as chemotherapeutic and bioimaging agents due to their fewer side effects and excellent physical optical properties. Tuning the electronic structures of Ru complexes has been proven to increase the cytotoxicity of cancer cells and the luminescent efficiency of the analytical probes. However, the relationship between electronic structures and bioactivities is still unclear due to the potential enhancement of both electron donor and acceptor properties. Thus, we investigated the relationship between the electronic structures of Ru(II) complexes and cytotoxicity by optimizing the electron-withdrawing (complex 1), electron-neutral (complex 2), and electron-donating (complex 3) ligands through DFT calculations, bioactivities tests, and docking studies. Our results indicated that it was not sufficient to consider only either the effect of electron-withdrawing or electron-donating effects on biological activities instead of the total electronic effects. Furthermore, these complexes with electron-donating substituents (complex 3) featured unique "off-on" luminescent emission phenomena caused by the various "HOMO-LUMO" distributions when they interacted with DNA, while complex with electron-withdrawing substituent showed an "always-on" signature. These findings offer valuable insight into the development of bifunctional chemotherapeutic agents along with bioimaging ability.

BejaGNN: behavior-based Java malware detection via graph neural network.

As a popular platform-independent language, Java is widely used in enterprise applications. In the past few years, language vulnerabilities exploited by Java malware have become increasingly prevalent, which cause threats for multi-platform. Security researchers continuously propose various approaches for fighting against Java malware programs. The low code path coverage and poor execution efficiency of dynamic analysis limit the large-scale application of dynamic Java malware detection methods. Therefore, researchers turn to extracting abundant static features to implement efficient malware detection. In this paper, we explore the direction of capturing malware semantic information by using graph learning algorithms and present BejaGNN (Behavior-based Java malware detection via Graph Neural Network), a novel behavior-based Java malware detection method using static analysis, word embedding technique, and graph neural network. Specifically, BejaGNN leverages static analysis techniques to extract ICFGs (Inter-procedural Control Flow Graph) from Java program files and then prunes these ICFGs to remove noisy instructions. Then, word embedding techniques are adopted to learn semantic representations for Java bytecode instructions. Finally, BejaGNN builds a graph neural network classifier to determine the maliciousness of Java programs. Experimental results on a public Java bytecode benchmark demonstrate that BejaGNN achieves high F1 98.8% and is superior to existing Java malware detection approaches, which verifies the promise of graph neural network in Java malware detection.

Quantum Topological Neuristors for Advanced Neuromorphic Intelligent Systems.

Neuromorphic artificial intelligence systems are the future of ultrahigh performance computing clusters to overcome complex scientific and economical challenges. Despite their importance, the advancement in quantum neuromorphic systems is slow without specific device design. To elucidate biomimicking mammalian brain synapses, a new class of quantum topological neuristors (QTN) with ultralow energy consumption (pJ) and higher switching speed (µs) is introduced. Bioinspired neural network characteristics of QTNs are the effects of edge state transport and tunable energy gap in the quantum topological insulator (QTI) materials. With augmented device and QTI material design, top notch neuromorphic behavior with effective learning-relearning-forgetting stages is demonstrated. Critically, to emulate the real-time neuromorphic efficiency, training of the QTNs is demonstrated with simple hand gesture game by interfacing them with artificial neural networks to perform decision-making operations. Strategically, the QTNs prove the possession of incomparable potential to realize next-gen neuromorphic computing for the development of intelligent machines and humanoids.

Proximate deconfined quantum critical point in SrCu2(BO3)2.

The deconfined quantum critical point (DQCP) represents a paradigm shift in quantum matter studies, presenting a "beyond Landau" scenario for order-order transitions. Its experimental realization, however, has remained elusive. Using high-pressure 11B nuclear magnetic resonance measurements on the quantum magnet SrCu2(BO3)2, we here demonstrate a magnetic field-induced plaquette singlet to antiferromagnetic transition above 1.8 gigapascals at a notably low temperature, Tc ≃ 0.07 kelvin. First-order signatures of the transition weaken with increasing pressure, and we observe quantum critical scaling at the highest pressure, 2.4 gigapascals. Supported by model calculations, we suggest that these observations can be explained by a proximate DQCP inducing critical quantum fluctuations and emergent O(3) symmetry of the order parameters. Our findings offer a concrete experimental platform for investigation of the DQCP.

Implantable metaverse with retinal prostheses and bionic vision processing.

We present an implantable metaverse featuring retinal prostheses in association with bionic vision processing. Unlike conventional retinal prostheses, whose electrodes are spaced equidistantly, our solution is to rearrange the electrodes to match the distribution of ganglion cells. To naturally imitate the human vision, a scheme of bionic vision processing is developed. On top of a three-dimensional eye model, our bionic vision processing is able to visualize the monocular image, binocular image fusion, and parallax-induced depth map.