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Abstract Background This study investigates the distribution and characteristics of linezolid and vancomycin susceptibilities among Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) and explores the underlying resistance mechanisms. Methods A total of 2842 Enterococcus clinical isolates from patients were retrospectively collected, and their clinical data were further analyzed. The minimum inhibitory concentrations (MICs) of vancomycin and linezolid were validated by broth dilution method. The resistance genes optrA, cfr, vanA, vanB and vanM were investigated using polymerase chain reaction (PCR). Housekeeping genes and resistance genes were obtianed through whole-genome sequencing (WGS). Results Of the 2842 Enterococcus isolates, 88.5% (2516) originated from urine, with E. faecium accounted for 60.1% of these. The vanA gene was identified in 27/28 vancomycin resistant Enterococcus (VRE) isolates, 4 of which carried both vanA and vanM genes. The remaining strain was vanM positive. The optrA gene was identified in all E. faecalis isolates among linezolid resistant Enterococcus (LRE). E. faecium showed a higher multiple antibiotic resistance index (MAR index) compared to E. faecalis. The multi-locus sequence typing (MLST) showed the sequence type of E. faecium mainly belongs to clonal complex (CC) 17, nearly E. faecalis isolates analyzed were differentiated into 7 characteristics of sequence types (STs), among which ST16 of CC16 were the major lineage. Conclusion Urine was the primary source of VRE and LRE isolates in this study. E. faecium showed higher levels of resistance compared to E. faecalis. OptrA gene was detected in 91.6% of LRE, which could explain linezolid resistance, and van genes were detected in all vancomycin resistant Enterococcus strains, while vanA was a key resistance mechanism in VRE identified in this study.

Objective To investigate the reasonable serological detection method by analyzing the characteristics of anti-K and anti-Wra from a patient who received treatment with daratumumab. Methods Unexpected antibody screening and identification were performed by saline method, polybrene, cardioagglutinin, dithiothreitol (DTT) treatment, trypsin treatment and papain treatment in the patient's plasma and acid elution solution. Heat elution test was detected after absorbing patient serum with K antigen negative red blood cells. The characteristics of antibodies were analyzed and their titer was continuously detected. Cross matching was performed after excluding interference of daratumumab. Results Anti-K and anti-Wra were detected in saline and polybrene in the patient's plasma. The patient's elution solution contained daratumumab. DTT or trypsin treatment excluded interference of daratumumab but papain treatment did not. DTT treatment destroyed K antigen and missed the detection of IgG antibodies in the Kell system. Trypsin treatment did not affect K antigen and can detect IgG antibodies of Kell system(anti-k)in the serum of the patient treated with daratumumab. Anti K was IgM and the titer was 4 by saline method and it decreased to no agglutination in room temperature after 39 days. Anti-Wra was IgG and the titer by polybrene method was 4, and it decreased to 1 after 39 days. After 76 days, neither anti-K nor anti-Wra could be detected. Transfusions of K and Wra antigen negative red blood cells were safe and effective. Conclusion DTT treatment can exclude interference of daratumumab, but attention should be paid to missed detection of anti-K. To avoid interference of daratumumab and identify unexpected antibody, multiple methods such as DTT treatment, polybrene and trypsin treatment in combination are recommended.

ABSTRACTThe development of simple and high-throughput approaches to yield solid-state nanopores on large surface membranes may facilitate the prevalence of nanopore analysis technology and in-vitro diagnosis using portable devices. However, solid-state nanopores are typically realized by complex and high-end nanofabrication equipments. Here, we present a method to achieve nanopores on polymer membranes using silver nanoparticles (AgNPs) as templates and intense pulsed light (IPL) as a heating source. The density and size of nanopores are controllable by adjusting the spin coating rate, the concentration of nanoparticle suspension, and the size of nanoparticles (NPs). The temperature of the AgNPs can rapidly reach 1132 K under instant heating of photothermal effect through light irradiation in 2 ms, resulting in localized melting and decomposition of an underneath polycarbonate (PC) membrane to yield nanopores with sizes ranging from 10 to 270 nm. After removing the nanoparticle residues, the flexible membrane with nanopores can be integrated into a flow cell to achieve a nanopore sensor that has been used to measure the translocation behaviors of bovine serum albumin (BSA). The results have demonstrated the capability of the sensor in protein denaturation identification. This low-cost and high-throughput technique to fabricate solid-state nanopores on flexible polymeric membranes may facilitate the development of more nanopore-based flexible sensors that can be integrated with other flexible components for wearable diagnosis.

Abstract Background QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life (t1/2) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies. Methods In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated. Results Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR) and median duration of response were 16.9% (79/468) and 11.7 months (8.3—not reached [NR]), respectively; and the ORRs were 14.0% (17/121) in NSCLC, 24.5% (27/110) in NPC, 27.3% (15/55) in CC, 7.4% (2/27) in colorectal cancer, 23.1% (6/26) in small cell lung cancer. For immunotherapy-naive patients, QL1706 exhibited promising antitumor activities, especially in NSCLC, NPC, and CC, with ORRs of 24.2%, 38.7%, and 28.3%, respectively. Conclusions QL1706 was well tolerated and demonstrated promising antitumor activity in solid tumors, especially in NSCLC, NPC, and CC patients. It is currently being evaluated in randomized phase II (NCT05576272, NCT05179317) and phase III (NCT05446883, NCT05487391) trials. Trial Registration ClinicalTrials.gov Identifier: NCT04296994 and NCT05171790.

This study focuses on the main urban area of Yangzhou City and conducts a quantitative comparative analysis of traffic accessibility during normal weather and extreme precipitation conditions (typhoon) based on GPS trajectories of buses. From both temporal and spatial dimensions, it comprehensively examines the impact of extreme precipitation on bus travel speed, travel time, and the commuting range of residents in the main urban area of Yangzhou City. (1) Through the mining and analysis of multi-source heterogeneous big data (bus GPS trajectory data, bus network data, rainfall remote sensing data, and road network data), it is found that the rainstorm weather greatly affects the average speed and travel time of buses. In addition, when the intensity of heavy rainfall increases (decreases), the average bus speed and travel time exhibit varying degrees of spatio-temporal change. During the morning and evening rush hour commuting period of rainstorm weather, there are obvious differences in the accessibility change in each typical traffic community in the main urban area of Yangzhou city. In total, 90% of the overall accessibility change value is concentrated around −5 min~5 min, and the change range is concentrated around −25~10%. (2) To extract the four primary traffic districts (Lotus Pond, Slender West Lake, Jinghua City, and Wanda Plaza), we collected Points of Interest (POI) data from Amap and Baidu heat map, and a combination analysis of the employment–residence ratio model and proximity methods was employed. The result show that the rainstorm weather superimposed on the morning peak hour has different degrees of impact on the average speed of the above-mentioned traffic zones, with the most obvious impact on the Lotus Pond and the smallest impact on Wanda Plaza. Under the rainstorm weather, the traffic commute in the main urban area of Yangzhou in the morning and evening peak hour is basically normal. The results of this paper can help to quantify the impact of typhoon-rainstorm weather events on traffic commuting in order to provide a scientific basis for the traffic management department to effectively prevent traffic jams, ensure the reliability of the road network, and allow the traffic management department to more effectively manage urban traffic.

Minimizing toxicity of herpes simplex virus 1 (HSV) based tools for anterograde tracing is important for functional studies. Here the authors generate an anterograde monosynaptic tracer system based on HSV amplicon, which shows fast tracing, bright labeling, low toxicity, input-defined postsynaptic neurons’ anterograde monosynaptic tracing feature, and has potential for functional mapping.

Abstract MicroRNAs (miRNAs) are small non-coding RNAs with ~ 22 nucleotides, playing important roles in the post-transcriptional regulation of gene expression. The expression profiles of many miRNAs are closely related to the occurrence and progression of cancer and can be used as biomarkers for cancer diagnosis and prognosis. However, their intrinsic properties, such as short length, low abundance and high sequence homology, represent great challenges in miRNA detection of clinical samples. To overcome these challenges, we developed a simple, ultrasensitive detection platform of electrochemical miRNAs chip (e-miRchip) with a novel signal amplification strategy using silver nanoparticle reporters (AgNRs) for multiplexed, direct, electronic profiling of miRNAs. A two-step hybridization strategy was used to detect miRNAs, where the target miRNA hybridizes with a stem-loop probe to unlock the probe first, and the opened stem-loop can further hybridize with AgNRs for signaling amplification. To enhance the detection sensitivity, the gold nanoflower electrodes (GNEs) were constructed in the microaperture arrays of the e-miRchips by electroplating. With the optimal size of the GNEs, the e-miRchip showed excellent performance for miR-21 detection with a detection limit of 0.56 fM and a linear range extended from 1 fM to 10 pM. The e-miRchip also exhibited good specificity in differentiating the 3-base mismatched sequences of the target miRNA. In addition, the e-miRchip was able to directly detect miR-21 expression in the total RNA extracts or cell lysates collected from lung cancer cells and normal cells. This work demonstrated the developed e-miRchip as an efficient and promising miniaturized point-of-care diagnostic device for the early diagnosis and prognosis of cancers. Graphical Abstract

Abstract Masks are essential personal protective equipment during pandemics. Conventional masks that act as physical barriers due to size‐dependence filtration and electrostatic absorption may quickly lose their protection effectiveness due to surface degradation, generating massive obsoleted masks and ecological contamination. Here, a self‐purifying smart mask that combines active protection to airborne particles and hazardous gases while conducting real‐time monitoring is developed. Electrospun ZIF‐8/polyacrylonitrile membranes are used to replace melt‐blown non‐woven fabrics without additional electret processes. The active ingredients of ZIF‐8 can interact with intercepted pathogens and total volatile organic compounds (TVOC), resulting in pathogen death and TVOC decomposition. When the electrospinning time exceeds 1 h, the membranes can block particulate matters with a filtration efficiency of over 99.58% and absorb TVOC with an efficiency of 92.57%. Its high disinfection performance can maintain for at least 72 h with an antibacterial rate of 99.07%. In addition, flexible circuits integrated with masks can quantify filtration effectiveness and monitor environmental parameters. The mask with the capability to renew its surface can enhance the endurance of masks for daily use and reduce the usage of single‐use masks. They can accommodate diverse demands in public health emergencies, occupational disease prevention, and biohazard defense.

Abstract Background Aldh1a1 neurons are a subtype of gamma-aminobutyric acid (GABA) inhibitory neurons that use Aldh1a1 rather than glutamate decarboxylase (GAD) as an enzyme for synthesizing GABA transmitters. However, the behaviors and circuits of this newly identified subtype of inhibitory interneurons remain unknown. Methods We generated a mutant mouse line in which cyclization recombination enzyme (CRE) was expressed under the control of the Aldh1a1 promotor (Aldh1a1-CRE mice). Using this mutant strain of mice together with the heterozygous male Alzheimer’s disease (AD) related model mice (APPswe/PSEN1dE9, or AD mice) and a genetically modified retrograde and anterograde synaptic tracing strategy, we have studied a specific synaptic circuit of Aldh1a1 neurons with system-level function and disease progression in AD mice. Results We demonstrate that Aldh1a1 neurons encode delay of gratification that measures self-control skills in decision making by projecting inhibitory synapses directly onto excitatory glutamate neurons in the intermediate lateral septum (EGNIS) and receiving synaptic inputs from layer 5b pyramidal neurons in the medial prefrontal cortex (L5PN). L5PN → Aldh1a1 synaptic transmission undergoes long-term potentiation (LTP). Pathway specific inhibition by either genetic silencing presynaptic terminals or antagonizing postsynaptic receptors impairs delay of gratification, resulting in the impulsive behaviors. Further studies show that reconstitution of Aldh1a1-deficient neurons with the expression of exogenous Aldh1a1 (eAldh1a1) restores Aldh1a1 → EGNIS synaptic transmission and rescues the impulsive behaviors in AD mice. Conclusions These results not only identify a specific function and circuit of Aldh1a1 neurons but also provide a cellular point of entry to an important but understudied synaptic mechanism for the induction of impulsive behaviors at an early stage of AD.

Regulatory T (Treg) cells are important modulators of the tumor microenvironment. Here the authors perform transcriptome profiling of immune cells from patients with renal clear cell carcinoma to find a Treg signature that correlates with poorer prognosis, with CD177 being implicated as the main mediator for related alterations in Treg activity and tumor outcome.

The live streaming market is becoming increasingly competitive, and relative performance information regarding broadcasters is available to all participants in the live streaming industry, exacerbating the level of competition. Using data from 42,166 live streams by 293 broadcasters, we investigated two benefits of relative performance information in relation to the live streaming business and how these effects vary when the broadcaster appears competent, trustworthy, likable, or attractive. On the basis of economic and social comparison theory, as well as insights from the herd behavior and beauty premium literature, we predicted and found that relative performance information can improve live streaming performance by either increasing broadcaster effort (the effort-eliciting effect) or encouraging viewer participation (the informational effect), with these effects being stronger when broadcasters look more competent, trustworthy, likable, or attractive. The findings of this study contribute to the live streaming literature by demonstrating that providing relative performance information in the live streaming business can yield both effort-eliciting and informational benefits.

With the continuous promotion of China’s electricity market reform, the introduction of competition in the power generation market provides a new research direction for the generation expansion planning (GEP) problem, which is of great significance in the promotion of the optimization of the power energy structure. In the context of marketization, the electricity price expectation during the planning period is a key factor of GEP for independent power generation groups. There is some literature showing that the electricity price expectation in the planning period can be estimated according to certain laws of market supply and demand, while it seems to us that a future Pay as Bid (PAB) mechanism is better to determine the electricity price expectation. In this paper, to explore the impact of these two different electricity price formation mechanisms on the evolution of the generation market, a multi-agent framework is first established to describe the interaction process among the generation market agents; then, a GEP model for independent power generation groups is developed in the market competition environment, and four representative scenarios are finally designed for detailed comparative studies. Based on these case studies, the conclusion can be summarized as: (1) the PAB bidding mechanism has a lower electricity price and higher market installed capacity almost all the time during the whole planning period for all four scenarios; (2) it is more important that PAB can reduce the impact of parameter uncertainty in the laws of market supply and demand, which can obtain more reliable and reasonable results regarding the long-term evolution of the generation market.

Summary: The suppressive function of regulatory T (Treg) cells is tightly controlled by nutrient-fueled mechanistic target of rapamycin complex 1 (mTORC1) activation, yet its dynamics and negative regulation remain unclear. Here we show that Treg-specific depletion of vacuolar protein sorting 33B (Vps33B) in mice results in defective Treg cell suppressive function and acquisition of effector phenotype, which in turn leads to disturbed T cell homeostasis and boosted antitumor immunity. Mechanistically, Vps33B binds with lysosomal nutrient-sensing complex (LYNUS) and promotes late endosome and lysosome fusion and clearance of the LYNUS-containing late endosome/lysosome, and therefore suppresses mTORC1 activation. Vps33B deficiency in Treg cells results in disordered endosome lysosome fusion, which leads to accumulation of LYNUS that causes elevated mTORC1 activation and hyper-glycolytic metabolism. Taken together, our study reveals that Vps33B maintains Treg cell suppressive function through sustaining endolysosomal homeostasis and therefore restricting amino acid-licensed mTORC1 activation and metabolism.

Exploiting negative capacitance effects in organic thin-film transistors (OTFTs) is advantageous for enhancing device performance. Here, the authors report solution-processed sub-thermionic OTFTs and circuits with ferroelectric hafnium oxides that show ultra-low power and ultra-high gain.

In the face of the new reform of China’s “unified electricity market”, the frequency regulation ancillary service market in each region of China is still divided between using the MCP and PAB pricing mechanisms. The purpose of this paper is to explore the different impact the laws of the above two pricing mechanisms have on the frequency regulation market and to provide relevant suggestions for this electricity market reform. This paper simulates the competitive activities of the frequency regulation market based on the multi-agent simulation model, conducts a comparative experiment by changing the pricing mechanism to a single variable based on the rules of the Sichuan frequency regulation market in China, and concludes that MCP can make the market fast and stable, and that its market settlement price is low, which is suitable for the “unified electricity market”. Although PAB makes the market settlement price high, it can ensure the retention of high-performance units in the market, and the stable settlement price makes this model able to accurately reflect the “price signal”, making it suitable for late adoption in the “unified electricity market”.

Wearable flexible sensors attached on the neck have been developed to measure the vibration of vocal cords during speech. However, high-frequency attenuation caused by the frequency response of the flexible sensors and absorption of high-frequency sound by the skin are obstacles to the practical application of these sensors in speech capture based on bone conduction. In this paper, speech enhancement techniques for enhancing the intelligibility of sensor signals are developed and compared. Four kinds of speech enhancement algorithms based on a fully connected neural network (FCNN), a long short-term memory (LSTM), a bidirectional long short-term memory (BLSTM), and a convolutional-recurrent neural network (CRNN) are adopted to enhance the sensor signals, and their performance after deployment on four kinds of edge and cloud platforms is also investigated. Experimental results show that the BLSTM performs best in improving speech quality, but is poorest with regard to hardware deployment. It improves short-time objective intelligibility (STOI) by 0.18 to nearly 0.80, which corresponds to a good intelligibility level, but it introduces latency as well as being a large model. The CRNN, which improves STOI to about 0.75, ranks second among the four neural networks. It is also the only model that is able to achieves real-time processing with all four hardware platforms, demonstrating its great potential for deployment on mobile platforms. To the best of our knowledge, this is one of the first trials to systematically and specifically develop processing techniques for bone-conduction speed signals captured by flexible sensors. The results demonstrate the possibility of realizing a wearable lightweight speech collection system based on flexible vibration sensors and real-time speech enhancement to compensate for high-frequency attenuation.

Simultaneous monitoring of diverse salivary parameters can reveal underlying mechanisms of intraoral biological processes and offer profound insights into the evolution of oral diseases. However, conventional analytical devices with bulky volumes, rigid formats, and discrete sensing mechanisms deviate from the requirements of continuous biophysiological quantification, resulting in huge difficulty in precise clinical diagnosis and pathogenetic study. Here, we present a flexible hybrid electronic system integrated with functional nanomaterials to continuously sense Ca2+, pH, and temperature for wireless real-time oral health monitoring. The miniaturized system with an island-bridge structure that is designed specifically to fit the teeth is only 0.4 g in weight and 31.5×8.5×1.35 mm3 in dimension, allowing effective integration with customized dental braces and comfort attachment on teeth. Characterization results indicate high sensitivities of 30.3 and 60.6 mV/decade for Ca2+ and pH with low potential drifts. The system has been applied in clinical studies to conduct Ca2+ and pH mappings on carious teeth, biophysiological monitoring for up to 12 h, and outcome evaluation of dental restoration, providing quantitative data to assist in the diagnosis and understanding of oral diseases. Notably, caries risk assessment of 10 human subjects using the flexible system validates the important role of saliva buffering capacity in caries pathogenesis. The proposed flexible system may offer an open platform to carry diverse components to support both clinical diagnosis and treatment as well as fundamental research for oral diseases and induced systemic diseases.

The occurrence and distribution of polycyclic aromatic hydrocarbons (PAHs) in a city of Central China were determined in the settled dust and its extracted water phase from different land use types and bus stops in Nanchang City. The physicochemical properties of its water extracted dissolved organic matter (WEOM) were characterized to investigate the effect of fluorescence organic matter on the dust-water partitioning coefficients (Kd) using three-dimensional excitation-emission matrix fluorescence spectroscopy combined parallel factor analysis. Results showed that the range of ∑PAHs in settled dust and the extracted water phase was 0.05–15.92 μg·g−1 and 2–211 ng·L−1, respectively. These PAHs mostly came from the combustion of biomass. The risk assessment showed that PAHs in dust had no obvious health risk (less than the magnitude of 10−6). Additionally, the high molecular weight (HMW) PAHs and the low molecular weight (LMW) PAHs were preferentially adsorbed by dust and the dissolved portion, respectively. It was confirmed by the relatively high logKd values of 4.23 for the HMW-PAHs. Pearson correlation analysis suggested that the higher concentration of dissolved organic carbon and humic-like substance were in favor of PAHs in dust released into waters. This study can provide information on pollution control when considering the impact of fluorescent organic matter on the fate and transport of PAHs.

Species diversity is a crucial index used to evaluate the stability and complexity of forest ecosystems. Studying the relationship between stand structure and understory herbaceous plants species diversity is useful for managers to formulate the best forest structure optimization method with the goal of improving herbaceous species diversity. In this research, Platycladus orientalis plantations in Beijing were taken as the research object. Pearson’s correlation analysis was used to explore the single-factor correlation between stand structure and understory herbaceous plants species diversity; furthermore, a typical correlation analysis and multiple linear regression were used to explore the multi-factor correlation and analyze the dominant stand structure parameters affecting understory herbaceous plants species diversity. In the range of stand structures studied, the results showed that canopy density was negatively correlated with the Shannon–Wiener index and Simpson index (p < 0.01), and tree density was negatively correlated with the Shannon–Wiener index (p < 0.05). In terms of stand spatial structure, the mingling degree was positively correlated with the Shannon–Wiener index, Simpson index, Margalef richness index and Pielou evenness index (p < 0.05), while the uniform angle was negatively correlated with the Pielou evenness index (p < 0.05). The correlation coefficient of the first group of typical variables in the typical correlation analysis was 0.90 (p < 0.05); from this group of typical variables, it can be concluded that canopy density is the most influential indicator affecting the comprehensive index of understory herbaceous plants species diversity, with a load of −0.690, and the Shannon–Wiener index and Simpson index are the most responsive indicators of changes in the comprehensive index of stand structure, with loads of 0.871 and 0.801, respectively. In the process of the management of Platycladus orientalis plantations under a low altitude, south slope, thin soil layer and hard soil parent material, in order to improve the herbaceous species diversity, the canopy density of the overstory and tree density should be appropriately reduced. Additionally, it is necessary to regulate the horizontal spatial structure of stands. When the trees are randomly distributed and the mingling degree is high, the species diversity of herbs can be increased.

Plant root hairs are cylindrical tubular projections from root epidermal cells. They increase the root surface area, which is important for the acquisition of water and nutrients, microbe interactions, and plant anchorage. The root hair specification, the effect of root hairs on nutrient acquisition and the mechanisms of nutrients (calcium, iron, magnesium, nitrogen, phosphorus, and potassium) that affect root hair development and growth were reviewed. The gene regulatory network on root hair specification in the plant kingdom was highlighted. More work is needed to clone the genes of additional root hair mutants and elucidate their roles, as well as undertaking reverse genetics and mutant complementation studies to add to the current knowledge of the signaling networks, which are involved in root hair development and growth regulated by nutrients.

Asymptomatic/subclinical gonococcal infections in females continue to be prevalent within the general population, thus emerging as a global health problem. However, the reasons for these clinical manifestations are unknown. Our group had previously found out that in females, asymptomatic gonococcal infections correlate with higher serum progesterone (P4) levels and lower IL-1β levels in cervical secretions. We used murine infection model and THP-1 cells to determine whether P4 exerts anti-inflammatory effects on gonococcal infections. In the murine infection model, P4 (1 mg/day) inhibited the inflammatory effects induced by gonococcal infections which led to decreased neutrophil infiltration, reduced polymorphonuclear neutrophils (PMNs) numbers, IL-1β, TNF-α, and IL-6 levels in vaginal secretions. In addition, P4 down-regulated the mRNA and protein levels of NLRP3, associated with lower mRNA levels of pro-IL-1β, repressed caspase-1 activity in genital tissues and THP-1 cells. Moreover, P4 suppressed the phosphorylation levels of NF-κB and attenuated Neisseria gonorrhoeae (N. gonorrhoeae, gonococci or GC)-induced ROS generation. This is consistent with the two signals required for activation of the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome. In conclusion, our result shows that P4 suppresses the gonococci induced-inflammation, especially through the NLRP3 inflammasome pathway, and partially explains the pathogenesis of asymptomatic GC infection in women.

Electronic skin made of thin, soft, stretchable devices that can mimic the human skin and reconstruct the tactile sensation and perception offers great opportunities for prosthesis sensing, robotics controlling, and human-machine interfaces. Advanced materials and mechanics engineering of thin film devices has proven to be an efficient route to enable and enhance flexibility and stretchability of various electronic skins; however, the density of devices is still low owing to the limitation in existing fabrication techniques. Here, we report a high-throughput one-step process to fabricate large tactile sensing arrays with a sensor density of 25 sensors/cm2 for electronic skin, where the sensors are based on intrinsically stretchable piezoelectric lead zirconate titanate (PZT) elastomer. The PZT elastomer sensor arrays with great uniformity and passive-driven manner enable high-resolution tactile sensing, simplify the data acquisition process, and lower the manufacturing cost. The high-throughput fabrication process provides a general platform for integrating intrinsically stretchable materials into large area, high device density soft electronics for the next-generation electronic skin.

ProblemTo investigate the relation of inflammation-related parameters and pregnancy outcome in women with the early threatened abortion.Method of study630 women with early threatened abortion were divided into two groups based on the pregnancy outcome. All of them had the blood routine examination before treating. The differences between two groups were analyzed by the Chi-squared test, Student T test, Mann-Whitney U test, Binary Logistic Regression, Marginal Structural Model and Threshold effect analysis.ResultsWe found that there is no significant difference in the pregnancy outcome for NLR (OR:0.92, CI95%:0.72, 1.17) and PLR (OR:1.00, CI%:0.99, 1.01). However, a difference had a statistical significance in the pregnancy outcome when LMR less than 2.19 (OR:0.39, CI95%:0.19,0.82).ConclusionsThis study suggested that higher LMR was related to the lower risk of miscarriage in the women with early threatened abortion in a way.

Multivariate cryptography is one of the most promising candidates for post-quantum cryptography. Applying machine learning techniques in this paper, we experimentally investigate the side-channel security of the multivariate cryptosystems, which seriously threatens the hardware implementations of cryptographic systems. Generally, registers are required to store values of monomials and polynomials during the encryption of multivariate cryptosystems. Based on maximum-likelihood and fuzzy matching techniques, we propose a template-based least-square technique to efficiently exploit the side-channel leakage of registers. Using QUAD for a case study, which is a typical multivariate cryptosystem with provable security, we perform our attack against both serial and parallel QUAD implementations on field programmable gate array (FPGA). Experimental results show that our attacks on both serial and parallel implementations require only about 30 and 150 power traces, respectively, to successfully reveal the secret key with a success rate close to 100%. Finally, efficient and low-cost strategies are proposed to resist side-channel attacks.

Abstract Coupling soft bodies and dynamic motions with multifunctional flexible electronics is challenging, but is essential in satisfying the urgent and soaring demands of fully soft and comprehensive robotic systems that can perform tasks in spite of rigorous spatial constraints. Here, the mobility and adaptability of liquid droplets with the functionality of flexible electronics, and techniques to use droplets as carriers for flexible devices are combined. The resulting active droplets (ADs) with volumes ranging from 150 to 600 µL can conduct programmable functions, such as sensing, actuation, and energy harvesting defined by the carried flexible devices and move under the excitation of gravitational force or magnetic force. They work in both dry and wet environments, and adapt to the surrounding environment through reversible shape shifting. These ADs can achieve controllable motions at a maximum velocity of 226 cm min−1 on a dry surface and 32 cm min−1 in a liquid environment. The conceptual system may eventually lead to individually addressable ADs that offer sophisticated functions for high‐throughput molecule analysis, drug assessment, chemical synthesis, and information collection.

Summary: Kibra is a synaptic scaffold protein regulating learning and memory. Alterations of Kibra-encoding gene WWC1 cause various neuronal disorders, including Alzheimer’s disease and Tourette syndrome. However, the molecular mechanism underlying Kibra’s function in neurons is poorly understood. Here we discover that Kibra, via its N-terminal WW12 tandem domains, binds to a postsynaptic density enriched protein, Dendrin, with a nanomolar dissociation constant. On the basis of the structure of Kibra WW12 in complex with Dendrin PY motifs, we developed a potent peptide inhibitor capable of specifically blocking the binding between Kibra and Dendrin in neurons. Systematic administration of the inhibitory peptide attenuated excitatory synaptic transmission, completely blocked long-term potentiation induction, and impaired spatial learning and memory. A Kibra mutation found in Tourette syndrome patients causes defects in binding to Dendrin. Thus, Kibra can modulate spatial learning and memory via binding to Dendrin. : Ji et al. report that the memory-related molecule Kibra, via its WW tandem domains, specifically binds to the synaptic protein Dendrin with a low-nanomolar dissociation constant to modulate spatial learning and memory. Keywords: Kibra, Dendrin, WW domains, tandem repeats, scaffold protein, synaptic complex, synaptic transmission, learning and memory, psychiatric disorder, Tourette syndrome

Lithium-sulfur batteries (LSBs), with large specific capacity (1,675 mAh g−1), are regarded as the most likely alternative to the traditional Lithium-ion batteries. However, the intrinsical insulation and dramatic volume change of sulfur, as well as serious shuttle effect of polysulfides hinder their practical implementation. Herein, we develop three-dimensional micron flowers assembled by nitrogen doped carbon (NC) nanosheets with sulfur encapsulated (S@NC-NSs) as a promising cathode for Li-S to overcome the forementioned obstacles. The in situ generated S layer adheres to the inner surface of the hollow and micro-porous NC shell with fruitful O/N containing groups endowing both efficient physical trapping and chemical anchoring of polysulfides. Meanwhile, such a novel carbon shell helps to bear dramatic volume change and provides a fast way for electron transfer during cycling. Consequently, the S@NC-NSs demonstrate a high capacity (1,238 mAh g−1 at 0.2 C; 1.0 C = 1,675 mA g−1), superior rate performance with a capacity retention of 57.8% when the current density increases 25 times from 0.2 to 5.0 C, as well as outstanding cycling performance with an ultralow capacity fading of only 0.064% after 200 cycles at a high current density of 5.0 C.

As a new multicarrier modulation system, orthogonal wavelet packet multiplexing (OWPM) system also has the problem of high peak to average power ratio (PAPR). In order to resolve the problem that of high computational complexity and inadequate effect of PAPR suppression for Partial Transmit Sequence (PTS) and high BER for the method of m-law companding transform, an algorithm of PAPR reduction based on improved m-law companding transform and PTS technology is put forward in the paper. Simulation results show that the proposed algorithm compared with the original algorithm has corresponding improvement of performance, and the combined processing with m-law companding transformation and PTS technology, on the condition that not to affect the original bit error rate(BER) of system, can better reduce PAPR, while decrease the computational complexity.

Increased concentrations of airborne particulate matter in megacities within China, caused by rapid economic growth, urbanization and industrialization, have become a major health concern. High energy consumption, emissions from a large fleet of on-road vehicles and intense industrial activities all contributed to the deterioration of urban air quality in China. In this study, we investigated the bioaccessibility of twelve particulate-bound trace elements (Al, Co, Cd, Cr, Cu, Fe, K, Mg, Mn, Ni, Pb, and Zn) using simulated lung fluids (Gamble’s solution (pH = 7.4) and artificial lysosomal fluid (ALF) (pH = 4.5)) following the collection of PM in Shanghai, a megacity in China, to gain a better understanding of their fate upon inhalation by adults and children. All the trace elements showed higher bioaccessibility in ALF, compared to that in the Gamble’s solution, due to lower pH and higher ionic strength of the former over the latter. In most cases, the kinetic response of trace elements in terms of their solubility followed a curvilinear pattern and approached near steady-state characteristics after a protracted period of incubation in the lung fluids. Health risk assessment was conducted for adults and children based on the measured bioaccessible fractions of trace elements, which showed significant excess lifetime cancer risk to both children and adults.

Heart rate variability (HRV) can reflect the changes in the autonomic nervous system (ANS) that are affected by apnea or hypopnea events among patients with obstructive sleep apnea hypopnea syndrome (OSAHS). To evaluate the possibility of using HRV to screen for OSAHS, we investigated the relationship between HRV and polysomnography (PSG) diagnostic indices using electrocardiography (ECG) and PSG data from 25 patients with OSAHS and 27 healthy participants. We evaluated the relationship between various PSG diagnostic indices (including the apnea hypopnea index [AHI], micro-arousal index [MI], oxygen desaturation index [ODI]) and heart rate variability (HRV) parameters using Spearman's correlation analysis. Moreover, we used multiple linear regression analyses to construct linear models for the AHI, MI, and ODI. In our analysis, the AHI was significantly associated with relative powers of very low frequency (VLF [%]) (r = 0.641, P = 0.001), relative powers of high frequency (HF [%]) (r = -0.586, P = 0.002), ratio between low frequency and high frequency powers (LF/HF) (r = 0.545, P = 0.049), normalized powers of low frequency (LF [n.u.]) (r = 0.506, P = 0.004), and normalized powers of high frequency (HF [n.u.]) (r = -0.506, P = 0.010) among patients with OSAHS. The MI was significantly related to standard deviation of RR intervals (SDNN) (r = 0.550, P = 0.031), VLF [%] (r = 0.626, P = 0.001), HF [%] (r = -0.632, P = 0.001), LF/HF (r = 0.591, P = 0.011), LF [n.u.] (r = 0.553, P = 0.004), HF [n.u.] (r = -0.553, P = 0.004), and absolute powers of very low frequency (VLF [abs]) (r = 0.525, P = 0.007) among patients with OSAHS. The ODI was significantly correlated with VLF [%] (r = 0.617, P = 0.001), HF [%] (r = -0.574, P = 0.003), LF [n.u.] (r = 0.510, P = 0.012), and HF [n.u.] (r = -0.510, P = 0.012) among patients with OSAHS. The linear models for the PSG diagnostic indices were AHI = -38.357+1.318VLF [%], MI = -13.389+11.297LF/HF+0.266SDNN, and ODI = -55.588+1.715VLF [%]. However, the PSG diagnostic indices were not related to the HRV parameters among healthy participants. Our analysis suggests that HRV parameters are powerful tools to screen for OSAHS patients in place of PSG monitoring.

Bioresorbable electronics (or transient electronics) devices can be potentially used to replace build-to-last devices in consumer electronics, implantable devices, and data security, leading to reduced electronic waste and surgical processes through controllable dissolution. Recent development of printing bioresorbable electronics leads to bioresorbable conductive pastes or inks that can be used to make interconnects, circuit traces, and sensors, offering alternative solutions for the predominant complementary metal oxide semiconductor (CMOS) processes in fabrication of bioresorbable electronics. However, the conductivities offered by current bioresorbable pastes and processing techniques are still much lower than those of the bulk metals, demanding further improvement in both paste composition and process optimization. This paper aims at exploring several influential factors such as paste compositions and processing techniques in determining conductivities of bioresorbable patterns. Experimental results reveal that an optimized paste constituent with a ratio of Zn:PVP:glycerol:methanol = 7:0.007:2:1 by weight can generate stable conductive pastes suitable for a screen printing process. In addition, a high conductivity of 60,213.6 S/m can be obtained by combining hot rolling and photonic sintering. The results demonstrate that large-scale transient electronics can be obtained by combining screen printing, hot rolling and photonic sintering approaches with optimized paste compositions, offering important experimental proofs and approaches for further improving the conductivity of bioresorbable pastes or inks that can accommodate the demands for mass fabrication and practical use in electronic industry.

Using a fix-effect modeling method, this study investigates the effect of foreign bank entry on the performance of indigenous banks in China during the post-deregulation period 1996-2004 Contrary to the results of Claessens’s etal(2001), this research shows that it is the loss of market share(as measured by the ratio of foreign bank assets to China’s entire bank assets) rather than the increase of bank branches which has a greater effect on China’s domestic banks. Moreover our results support the view of Lensink and Hermes(2004) that as China’s banking sector is not well developed, domestic banks have incurred higher costs and margins when learning banking techniques and practices from foreign banks due to the spill-over effect. As a result, China’s domestic banks may transfer their implementation costs to their consumers or clients by raising margins and thus gaining higher profits. It is therefore difficult to draw a conclusion as to whether the foreign bank entry has enhanced the competitiveness of Chinese domestic banks and thus improved the efficiency of financial sector.

In laparoscopic gynecologic surgery, ultrasound has been typically implemented to diagnose urological and gynecological conditions. We applied laparoscopic ultrasonography (using Esaote 7.5~10MHz laparoscopic transducer) on the retrospective analyses of 42 women subjects during laparoscopic extirpation and excision of gynecological tumors in our hospital from August 2011 to August 2013. The objective of our research is to develop robust segmentation technique for isolation and identification of the uterus from the ultrasound images, so as to assess, locate and guide in removing the lesions during laparoscopic operations. Our method enables segmentation of the uterus by the active contour algorithm. We evaluated 42 in-vivo laparoscopic images acquired from the 42 patients (age 39.1 ± 7.2 years old) and selected images pertaining to 4 cases of congenital uterine malformations and 2 cases of pelvic adhesions masses. These cases (n = 6) were used for our uterus segmentation experiments. Based on them, the active contour method was compared with the manual segmentation method by a medical expert using linear regression and the Bland-Altman analysis (used to measure the correlation and the agreement). Then, the Dice and Jaccard indices are computed for measuring the similarity of uterus segmented between computational and manual methods. Good correlation was achieved whereby 84%-92% results fall within the 95% confidence interval in the Student t-test) and we demonstrate that the proposed segmentation method of uterus using laparoscopic images is effective.

Terminal alkynes react with Cp2Zr(H)Cl (Cp = h5-C5H5) to give organozirconium complexes, which are trapped with alkylsulfenyl chlorides to afford (E)-vinyl alkyl sulfides in good yield.

Terminal alkynes react with Cp2Zr(H)Cl (Cp = μ5-C5H5) to give organozirconium complexes, which are trapped with alkylsulfenyl chlorides to afford (E)-vinyl alkyl sulfides in good yield.

Wearable technology has attracted significant public attention and has generated huge societal and economic impact, leading to changes of both personal lifestyles and formats of healthcare. An important type of devices in wearable technology is flexible and stretchable skin sensors used primarily for biophysiological signal sensing and biomolecule analysis on skin. These sensors offer mechanical compatibility to human skin and maximum compliance to skin morphology and motion, demonstrating great potential as promising alternatives to current wearable electronic devices based on rigid substrates and packages. The mechanisms behind the design and applications of these sensors are numerous, involving profound knowledge about the physical and chemical properties of the sensors and the skin. The corresponding materials are diverse, featuring thin elastic films and unique stretchable structures based on traditional hard or ductile materials. In addition, the fabrication techniques that range from complementary metal-oxide semiconductor (CMOS) fabrication to innovative additive manufacturing have led to various sensor formats. This paper reviews mechanisms, materials, fabrication techniques, and representative applications of flexible and stretchable skin sensors, and provides perspective of future trends of the sensors in improving biomedical sensing, human machine interfacing, and quality of life.