An anti-fouling wearable molecular imprinting sensor based on semi-interpenetrating network hydrogel for the detection of tryptophan in sweat.

The challenge of heavy biofouling in complex sweat environments limits the potential of electrochemical sweat sensors for noninvasive physiological assessment. In this study, a novel semi-interpenetrating hydrogel of PSBMA/PEDOT:PSS was engineered by interlacing PEDOT:PSS conductive polymer with zwitterionic PSBMA network. This versatile hydrogel served as the foundation for developing an anti-fouling wearable molecular imprinting sensor capable of sensitive and robust detection of tryptophan (Trp) in complex sweat. The incorporation of PEDOT:PSS conductive polymer into the semi-interpenetrating hydrogel introduced diverse physical crosslinks, including hydrogen bonding, electrostatic interactions, and chain entanglement. This incorporation considerably boosted the hydrogel's mechanical robustness and imparted commendable self-healing property. At the same time, the synergistic coupling between the well-balanced charge of the zwitterionic network and the high conductivity of the PEDOT:PSS polymer facilitated efficient charge transfer. The formation of the desired molecular imprinting membrane of semi-interpenetrating hydrogel was triggered by self-polymerization of dopamine (DA) in the presence of Trp. The designed biosensor demonstrated good sensitivity, selectivity and stability in detecting the target Trp. Notably, it also exhibited exceptional anti-fouling abilities, allowing for accurate Trp detection in complex real sweat samples, yielding results comparable to commercial enzyme-linked immunoassay (ELISA).

Development of a compact impact two-degree-of-freedom linear-rotary piezoelectric motor using one piezoelectric actuator.

A compact impact two-degree-of-freedom linear-rotary piezoelectric motor is proposed using a single actuator. The proposed piezoelectric actuator has a pair of deformation counteracting helical interdigitated electrodes on its outside surface, which can be divided into two parts. When the two parts of the piezoelectric actuator are driving under the same driving voltage signals, the motor can realize independent linear motion. When the two parts of the piezoelectric actuator are driving under the driving voltage signals with opposite duty cycles, the motor can realize independent rotary motion. The fabricated piezoelectric motor can produce a maximum average linear velocity of 1.9 and -2.3 mm/s with a saw-shaped driving signal of 400 Vp-p (peak-to-peak driving voltage) at 9 kHz. Experiments also show that the fabricated piezoelectric motor can realize a maximum average rotary velocity of 2440 and -2235 mrad/s with a driving signal of 400 Vp-p at 9 kHz. The maximum load force and torque of the prototype are about 0.4 N and 1.5 mN m, respectively. The proposed motor provides a wide driving frequency and realizes high velocity in both linear and rotary motions.

Laser Welding Multimodel Quality Forecast Method Based on Dynamic Geometric Features of the Molten Pool.

Laser welding quality forecast is highly significant during the laser manufacturing process. However, extracting the dynamic characteristics of the molten pool in the short laser welding process makes predicting of the welding quality in real time difficult. Accordingly, this study proposes a multimodel quality forecast (MMQF) method based on dynamic geometric features of molten pool to forecast the welding quality in real time. For extraction of geometric features of molten pool, an improved fully convolutional neural network is proposed to segment the collected dynamic molten pool images during the entire welding process. In addition, several dynamic geometric features of the molten pool are extracted by using the minimum enclosed rectangle algorithm with an evaluation of the performance by several statistical indexes. With regard to forecasting the welding quality, a nonlinear quadratic kernel logistic regression model is proposed by mapping the linear inseparable features to the high dimensional space. Experimental results show that the MMQF method can make an effective and stable forecast of welding quality. It performs well under small data and can satisfy the requirement of real-time forecast.

A Wearable Electrochemical Sensor Based on Anti-Fouling and Self-Healing Polypeptide Complex Hydrogels for Sweat Monitoring.

Although continuous monitoring of constituents in complex sweat is crucial for noninvasive physiological evaluation, biofouling on the sweat sensor surface and inadequate flexible self-healing materials restrict its applications. Herein, a fully self-healing and strong anti-biofouling polypeptide complex hydrogel (AuNPs/MoS2/Pep hydrogel) with excellent electrochemical performances was created. The anti-fouling electrochemical sweat sensor was fabricated based on the AuNPs/MoS2/Pep hydrogel to address these issues. It was found that the polypeptide hydrogel was designed to form a network structure and carried abundant hydrophilic groups, resulting in a AuNPs/MoS2/Pep hydrogel with superior anti-biofouling properties in sweat for 30 min and even long-term stability in undiluted human sweat. In addition, SEM, TEM, UV, XPS, and infrared spectrogram demonstrated that the binding force of π-π stacking force between MoS2 and naphthalene groups in the designed peptide endowed the polypeptide complex hydrogel with an excellent self-healing property. Furthermore, the polypeptide complex hydrogel preserved wearable device function of continuously monitoring uric acid (UA) and ascorbic acid (AA) in sweat in situ. This novel fabricated sweat sensor with high anti-biofouling ability, excellent self-healing property, and sensitive and selective analytical capability describes a new opportunity for health monitoring in situ.

A low-fouling electrochemical biosensor for biomarker detection in serum based on designed α/ß-peptides with anti-enzymolysis and antifouling capabilities.

The zwitterionic peptides, especially those composed of glutamic (E) and lysine (K) groups have drawn enormous attention as antifouling biomaterials owing to their strong hydration capability and biocompatibility. However, the susceptibility of α-amino acid K to the proteolytic enzymes in human serum limited the broad application of such peptides in biological media. Herein, a new multifunctional peptide with favorable stability in human serum was designed, and it was composed of three sections with immobilizing, recognizing and antifouling capabilities, respectively. The antifouling section was composed of alternating E and K amino acids, but the enzymolysis-susceptive amino acid α-K was replaced by the unnatural ß-K. Compared with the conventional peptide composed of all α-amino acids, the α/ß-peptide exhibited significantly enhanced stability and longer antifouling performance in human serum and blood. The electrochemical biosensor based on the α/ß-peptide showed a favorable sensitivity to its target IgG, with a quite wide linear range from 100 pg mL-1 to 10 µg mL-1 and a low detection limit (33.7 pg mL-1, S/N = 3), and it was promising for the detection of IgG in complex human serum. The tactic of designing antifouling α/ß-peptides offered an efficient way to develop low-fouling biosensors with robust operation in complex body fluids.

Smart Task Assistance in Mixed Reality for Astronauts.

Mixed reality (MR) registers virtual information and real objects and is an effective way to supplement astronaut training. Spatial anchors are generally used to perform virtual-real fusion in static scenes but cannot handle movable objects. To address this issue, we propose a smart task assistance method based on object detection and point cloud alignment. Specifically, both fixed and movable objects are detected automatically. In parallel, poses are estimated with no dependence on preset spatial position information. Firstly, YOLOv5s is used to detect the object and segment the point cloud of the corresponding structure, called the partial point cloud. Then, an iterative closest point (ICP) algorithm between the partial point cloud and the template point cloud is used to calculate the object's pose and execute the virtual-real fusion. The results demonstrate that the proposed method achieves automatic pose estimation for both fixed and movable objects without background information and preset spatial anchors. Most volunteers reported that our approach was practical, and it thus expands the application of astronaut training.

A wearable sensor based on multifunctional conductive hydrogel for simultaneous accurate pH and tyrosine monitoring in sweat.

Flexible and wearable sweat sensors have drawn extensive attention by virtue of their continuous and real-time monitoring of molecular level information. However, current sweat-based sensors still pose several challenges, such as low accuracy for analytes detection, susceptibility to microorganism and poor mechanical performance. Herein, we demonstrated a noninvasive wearable sweat sensing patch composed of an electrochemical sensing system, and a pilocarpine-based iontophoretic system to stimulate sweat secretion. The electrochemical sensor based on tannic acid-Ag-carbon nanotube-polyaniline (TA-Ag-CNT-PANI) composite hydrogel was designed for on-body detection of pH and tyrosine (Tyr), a disease marker associated with multiple disorders, such as tyrosinemia and bulimia nervosa. The wearable sweat sensor can not only monitor the pH and Tyr in sweat simultaneously, but also further calibrate Tyr detection results with the measured pH value, so as to eliminate the effect of Tyr response variance at different pH and enhance the accuracy of the sensor. Furthermore, the presence of tannic acid chelated-Ag nanoparticles (TA-Ag NPs) and carbon nanotubes (CNTs) significantly improved the conductivity and flexibility of the hydrogel and endowed the composite hydrogel with antibacterial capability. Of note, the constructed wearable sensor was capable of monitoring Tyr with enhanced accuracy in various sweats.

Peptide nucleic acid and antifouling peptide based biosensor for the non-fouling detection of COVID-19 nucleic acid in saliva.

The electrochemical biosensor with outstanding sensitivity and low cost is regarded as a viable alternative to current clinical diagnostic techniques for various disease biomarkers. However, their actual analytical use in complex biological samples is severely hampered due to the biofouling, as they are also highly sensitive to nonspecific adsorption on the sensing interfaces. Herein, we have constructed a non-fouling electrochemical biosensor based on antifouling peptides and the electroneutral peptide nucleic acid (PNA), which was used as the recognizing probe for the specific binding of the viral RNA of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Different from the negatively charged DNA probes that will normally weaken the biosensors' antifouling capabilities owing to the charge attraction of positively charged biomolecules, the neutral PNA probe will generate no side-effects on the biosensor. The biosensor demonstrated remarkable sensitivity in detecting SARS-CoV-2 viral RNA, possessing a broad linear range (1.0 fM - 1.0 nM) and a detection limit down to 0.38 fM. Furthermore, the sensing performance of the constructed electrochemical biosensor in human saliva was nearly similar to that in pure buffer, indicating satisfying antifouling capability. The combination of PNA probes with antifouling peptides offered a new strategy for the development of non-fouling sensing systems capable of assaying trace disease biomarkers in complicated biological media.

Case report: The remarkable response of pembrolizumab combined with RC48 in the third-line treatment of metastatic urothelial carcinoma.

Background: Systemic chemotherapy has been the mainstay treatment for locally advanced or metastatic urothelial carcinoma (UC). In the past few years, novel immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) have improved the treatment of advanced UC. Case presentation: Here, we report systemic therapy of a 68-year-old male diagnosed with HER2 positive (immunohistochemistry 3+), programmed cell death ligand 1(PD-L1) negative metastatic UC, and renal insufficiency. He had encountered numerous metastases and failed first-line platinum-based chemotherapy and second-line treatment with pembrolizumab and trastuzumab. During third-line treatment with RC48 (a HER2 targeting ADC) combined with pembrolizumab, he achieved a rapid partial response (PR) in the first evaluation and subsequent complete response (CR) on PET/CT and long-term progression-free survival (>12 months) at the last follow-up on 25 August 2022. There are no grade 3 or 4 adverse events or aggravations of renal insufficiency during the third-line therapy. Discussion: RC48 combined with pembrolizumab demonstrated outstanding efficacy and safety in this HER2-positive metastatic UC patient. ADC combined with ICI is a promising anti-tumor strategy that deserves further exploration in advanced UC.

Unexpected response of nitrogen deposition to nitrogen oxide controls and implications for land carbon sink.

Terrestrial ecosystems in China receive the world's largest amount of reactive nitrogen (N) deposition. Recent controls on nitrogen oxides (NOx = NO + NO2) emissions in China to tackle air pollution are expected to decrease N deposition, yet the observed N deposition fluxes remain almost stagnant. Here we show that the effectiveness of NOx emission controls for reducing oxidized N (NOy = NOx + its oxidation products) deposition is unforeseen in Eastern China, with one-unit reduction in NOx emission leading to only 55‒76% reductions in NOy-N deposition, as opposed to the high effectiveness (around 100%) in both Southern China and the United States. Using an atmospheric chemical transport model, we demonstrate that this unexpected weakened response of N deposition is attributable to the enhanced atmospheric oxidizing capacity by NOx emissions reductions. The decline in N deposition could bear a penalty on terrestrial carbon sinks and should be taken into account when developing pathways for China's carbon neutrality.

High fraction of soluble trace metals in fine particles under heavy haze in central China.

Atmospheric trace metals are a key component of particulate matter and significantly influence the atmospheric process and human health. The dissolved fraction of trace metals represents their bioavailability and exhibits high chemical activity. However, the optimum measurement method for detecting the soluble fraction of trace metals is still undetermined. The impact of variations in pollution on the soluble fraction is largely unrevealed. Therefore, in this work, a one-month field observation was conducted in Central China and different extraction solvents were used to determine the proper measurement method for the soluble fraction of trace metals and investigate the variation pattern under different pollution conditions. The findings show that solvents with acidity near that of aerosol water can better reflect the actual soluble fraction of trace metals in fine particulate matter. The soluble fraction of trace metals tends to increase with pollution level increased, demonstrating unexpectedly high health risks and chemical activity under heavy haze conditions. Our results indicate that remediation and trace metal pollution control are urgently needed.

Designed multifunctional peptides with two recognizing branches specific for one target to achieve highly sensitive and low fouling electrochemical protein assay in human serum.

Herein, an antifouling electrochemical biosensor based on designed multifunctional peptides with two recognizing branches specific for one target was proposed to improve the target recognition efficiency and sensitivity. The designed multifunctional peptide contains two different recognizing branches (with sequences FYWHCLDE and FYCHTIDE) for immunoglobulin G (IgG), an antifouling sequence (EKEKEK) and an anchoring sequence (CPPPP), which can be immobilized onto the gold nanoparticles (AuNPs) and poly(3,4-ethylenedioxythiophene) (PEDOT) modified electrode surface. Owing to the synergistic effect of the two recognizing branches, the dual-recognizing peptide-based biosensor exhibited significantly enhanced sensitivity. Under the optimal experimental conditions, the biosensor for IgG exhibited a linear response range of 0.1 pg/mL to 0.1 µg/mL, with a limit of detection of 0.031 pg/mL (about 2 orders of magnitude lower than that of the normal biosensor). Moreover, the biosensor was also capable of assaying IgG in real biological samples such as human serum without suffering from significant biofouling. This strategy for biosensor construction not only ensures the ultra-sensitivity for target detection, but also effectively avoids biofouling on sensing interfaces in complex biological media.

Sulfate Formation Apportionment during Winter Haze Events in North China.

There is a large gap between the simulated and observed sulfate concentrations during winter haze events in North China. Although multiphase sulfate formation mechanisms have been proposed, they have not been evaluated using chemical transport models. In this study, the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) was used to apportion sulfate formation. It was found that Mn-catalyzed oxidation on aerosol surfaces was the dominant sulfate formation pathway, accounting for 92.3 ± 3.5% of the sulfate formation during haze events. Gas-phase oxidation contributed 3.1 ± 0.5% to the sulfate formation due to the low OH levels. The H2O2 oxidation in aerosol water accounted for 4.2 ± 3.6% of the sulfate formation, caused by the rapid consumption of H2O2. The contributions of O3, NO2 oxidation, and transition metal ion-catalyzed reactions in aerosol water could be negligible owing to the low aerosol water content, low pH, and high ionic strength. The contributions from in-cloud reactions were negligible due to the barrier provided by stable stratification during winter haze events.

d-Amino Acid-Based Antifouling Peptides for the Construction of Electrochemical Biosensors Capable of Assaying Proteins in Serum with Enhanced Stability.

The susceptibility of peptides to proteolytic degradation in human serum significantly hindered the potential application of peptide-based antifouling biosensors for long-term assaying of clinical samples. Herein, a robust antifouling biosensor with enhanced stability was constructed based on peptides composed of d-amino acids (d-peptide) with prominent proteolytic resistance. The electrode was electropolymerized with poly(3,4-ehtylenedioxythiophene) and electrodeposited with Au nanoparticles (AuNPs), and the d-peptide was then immobilized onto the AuNPs, and a typical antibody specific for immunoglobulin M (IgM) was immobilized. Because of the effect of d-amino acids, the d-peptide-modified electrode surface showed prominent antifouling capability and high tolerance to enzymatic hydrolysis. Moreover, the d-peptide-modified electrode exhibited much stronger long-term stability, as well as antifouling ability in human serum than the electrode modified with normal peptides. The electrochemical biosensor exhibited a sensitive response to IgM linearly within the range of 100 pg mL-1 to 1.0 µg mL-1 and a very low detection limit down to 37 pg mL-1, and it was able to detect IgM in human serum with good accuracy. This work provided a new strategy to develop robust peptide-based biosensors to resist the proteolytic degradation for practical application in complex clinical samples.

Prebiotics Inulin Metabolism by Lactic Acid Bacteria From Young Rabbits.

Inulin as a commercial prebiotic could selectively promote the growth of beneficial gut microbes such as lactic acid bacteria (LAB). Whether LAB in rabbit gut possesses the capability to metabolize and utilize inulin is little known. Therefore, this study recovered 94 LAB strains from neonate rabbits and found that only 29% (28/94) could metabolize inulin with both species- and strain-specificity. The most vigorous inulin-degrading strain, Lacticaseibacillus paracasei YT170, could efficiently utilize both short-chain and long-chain components through thin-layer chromatography analysis. From genomic analysis, a predicted fosRABCDXE operon encoding putative cell wall-anchored fructan ß-fructosidase, five fructose-transporting proteins and a pts1BCA operon encoding putative ß-fructofuranosidase and sucrose-specific IIBCA components were linked to long-chain and short-chain inulin utilization respectively. This study provides a mechanistic rationale for effect of inulin administration on rabbits and lays a foundation for synbiotic applications aimed at modulating the intestinal microbiota of young rabbits.

An electrochemical biosensor for alpha-fetoprotein detection in human serum based on peptides containing isomer D-Amino acids with enhanced stability and antifouling property.

The development of antifouling biosensors capable of detecting biomarkers at low concentrations in complex bio-fluids with many interference components is of great importance in the diagnosis and treatment of diseases. Certain zwitterionic peptides composed of natural L-amino acids have been used for the construction of low fouling biosensors and demonstrated excellent antifouling performances, but they are prone to enzymatic degradation in biological media, such as serum that contains a variety of enzymes. In this work, a novel antifouling peptide with the sequence of cppPPEKEKEkek was designed, and three unnatural D-amino acids were set at both ends of the peptide to enhance its tolerance to enzymatic degradation. An electrochemical biosensor was constructed by coupling the antifouling peptide with a conducting polymer polyaniline (PANI) to achieve accurate detection of alpha-fetoprotein (AFP) in clinical samples. Owing to the presence of the designed peptide with partial D-amino acids (pD-peptide), the biosensing interface showed significantly high antifouling performance and enhanced stability in human serum. Meanwhile, the pD-peptide based biosensor exhibited high sensitivity toward the target AFP, with the linear range from 0.1 fg mL-1 to 1.0 ng mL-1 and the limit of detection of 0.03 fg mL-1 (S/N = 3). This strategy of enhancing the stability (tolerance to enzymolysis) of antifouling peptides in biological samples provided an effective way to develop antifouling biosensors for practical applications.

4.9% Au stabilizes Ag in an atomically homogenous bimetallic alloy for anisotropic nanocrystals with enhanced stability under light irradiation.

Instability problems encountered by Ag nanocrystals largely limit their use in practical applications. In AuAg bimetallic alloys, the stability of Ag can be greatly enhanced, whereas doping a high fraction of Au to the alloy usually leads to the loss of the superior properties of Ag and undesirable degradation of the quality factor of the plasmonic resonance. Herein, we provide experimental evidence that the atomically homogenous AuAg alloy nanocrystals with Au fraction as low as 4.9% (at%) possess comparable stability to pure Au, while the superior plasmonic properties of Ag are largely reserved. The study is based on the synthetic strategy developed for the overgrowth on the Au nanorods of atomically homogenous AuAg alloy shells with a tunable Au/Ag ratio but constant size and anisotropic shape. The stability of over 800 individual alloy nanocrystals in the absence of surfactants is simultaneously characterized at the single-particle level for over 10 h under light irradiation. The stability transition is explained in correlation with the charge redistribution of Ag occurring at the same critical Au fraction. We note that such bimetallic alloy nanocrystals with a low Au fraction possessing both high stability and high quality of resonance are preferred in fundamental researches and practical applications.

Free-standing electrochemical biosensor for carcinoembryonic antigen detection based on highly stable and flexible conducting polypyrrole nanocomposite.

A flexible free-standing electrochemical biosensor to detect carcinoembryonic antigen (CEA) is described based on a conducting polypyrrole (PPy) nanocomposite film electrode. The conducting PPy composite was constructed by the sandwiched structure formed by PPy doped with pentaerythritol ethoxylate (PEE) and 2-naphthalene sulfonate (2-NS-PPy) separately via electropolymerization. Gold nanoparticles (AuNPs) were fixed on the PPy composite film by electrodeposition and then connected to CEA aptamer through self-assembly to construct a free-standing electrochemical biosensor breaking away from additional soft substrates and current collector. This PPy composite film-based electrochemical biosensor exhibits satisfying sensing performance for CEA detection, with a linear range from 10-10 g/mL to 10-6 g/mL and a detection limit of 0.033 ng/mL, good specificity and long-term sensing stability (96.8% of the original signal after 15 days). The biosensor also presents acceptable reproducibility with 1.7% relative standard deviation. Moreover, this electrochemical biosensor owns the deformation stability that could bear various deformations (twisting, folding, and knotting) without affecting device's sensing performance. It can even maintain 99.4% of the original signal under 25% strain deformation. Due to the superior sensing performance, high stability (mechanical deformation and long-term storage), and flexibility, this free-standing electrochemical biosensor proves huge potential in application of flexible and wearable electronics.

Sulfate formation is dominated by manganese-catalyzed oxidation of SO2 on aerosol surfaces during haze events.

The formation mechanism of aerosol sulfate during wintertime haze events in China is still largely unknown. As companions, SO2 and transition metals are mainly emitted from coal combustion. Here, we argue that the transition metal-catalyzed oxidation of SO2 on aerosol surfaces could be the dominant sulfate formation pathway and investigate this hypothesis by integrating chamber experiments, numerical simulations and in-field observations. Our analysis shows that the contribution of the manganese-catalyzed oxidation of SO2 on aerosol surfaces is approximately one to two orders of magnitude larger than previously known routes, and contributes 69.2% ± 5.0% of the particulate sulfur production during haze events. This formation pathway could explain the missing source of sulfate and improve the understanding of atmospheric chemistry and climate change.