Self-Powered Biomimetic Pressure Sensor Based on Mn-Ag Electrochemical Reaction for Monitoring Rehabilitation Training of Athletes.

Self-powered pressure detection using smart wearable devices is the subject of intense research attention, which is intended to address the critical need for prolonged and uninterrupted operations. Current piezoelectric and triboelectric sensors well respond to dynamic stimuli while overlooking static stimuli. This study proposes a dual-response potentiometric pressure sensor that responds to both dynamic and static stimuli. The proposed sensor utilizes interdigital electrodes with MnO2/carbon/polyvinyl alcohol (PVA) as the cathode and conductive silver paste as the anode. The electrolyte layer incorporates a mixed hydrogel of PVA and phosphoric acid. The optimized interdigital electrodes and sandpaper-like microstructured surface of the hydrogel electrolyte contribute to enhanced performance by facilitating an increased contact area between the electrolyte and electrodes. The sensor features an open-circuit voltage of 0.927 V, a short-circuit current of 6 µA, a higher sensitivity of 14 mV/kPa, and outstanding cycling performance (>5000 cycles). It can accurately recognize letter writing and enable capacitor charging and LED lighting. Additionally, a data acquisition and display system employing the proposed sensor, which facilitates the monitoring of athletes' rehabilitation training, and machine learning algorithms that effectively guide rehabilitation actions are presented. This study offers novel solutions for the future development of smart wearable devices.

Cynarin ameliorates dextran sulfate sodium-induced acute colitis in mice through the STAT3/NF-κB pathway.

OBJECTIVE: Cynarin is a derivative of hydroxycinnamic acid presented in various medicinal plants, such as Cynara scolymus L. and Onopordum illyricum L. To date, the antioxidant and antihypertensive activities of cynarin have been reported. However, whether cynarin has a therapeutic impact on ulcerative colitis (UC) is unclear. Therefore, the aim of this study was to explore the potential effect of cynarin on dextran sulfate sodium (DSS)-induced acute colitis in vivo and on lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced RAW264.7 and J774A.1 cellular inflammation model in vitro. METHODS AND RESULTS: In this study, we investigated that cynarin alleviated clinical symptoms in animal models, including disease activity index (DAI) and histological damage. Furthermore, cynarin can attenuate colon inflammation through decreasing the proportion of neutrophils in peripheral blood, reducing the infiltration of neutrophils, and macrophages in colon tissue, inhibiting the release of pro-inflammatory cytokines and suppressing the expression of STAT3 and p65. In cellular inflammation models, cynarin inhibited the expression of M1 macrophage markers, such as TNF-α, IL-1ß, and iNOS. Besides, cynarin suppressed the expression of STAT3 and p65 as well as the phosphorylation of STAT3, p65. Cynarin inhibited the polarization of RAW264.7 and J774A.1 cells toward M1 and alleviated LPS/IFN-γ-induced cellular inflammation. CONCLUSION: Considering these results, we conclude that cynarin mitigates experimental UC partially through inhibiting the STAT3/NF-кB signaling pathways and macrophage polarization toward M1. Accordingly, cynarin might be a potential and effective therapy for UC.

Cucumber seed polypeptides regulate RANKL-induced osteoclastogenesis through OPG/RANKL/RANK and NF-κB.

Postmenopausal osteoporosis (PMOP) is a common disease that endangers the health of elderly women. Cucumber seeds have shown excellent therapeutic effects on PMOP, but the mechanism of cucumber seed peptide (CSP) remains unclear. The expression levels of NF-κB and osteoclast-related genes were detected by RT-qPCR. The levels of apoptosis-related proteins were detected by Western blotting. Nuclear translocation of NF-κB p65 and osteoclast formation were detected by immunofluorescence and tartrate-resistant acid phosphatase (TRAP) staining, respectively. ELISA was used to detect the expression levels of OPG, M-CSF, and RANKL. Hematoxylin-eosin (H&E) and TRAP staining were used to observe the effects of CSP on bone formation. In RAW264.7 cells, CSP (0.4 mg/L, 4 mg/L, and 40 mg/L) effectively inhibited the expression of osteoclast-related genes (Cathepsin-K, MT1-MMP, MMP-9, and TRAP). TRAP-positive multinucleated giant cells gradually decreased. Furthermore, NF-κB pathway activation downstream of RANK was inhibited. In bone marrow stromal cells (BMSCs), the expression levels of M-CSF and RANKL gradually decreased, and OPG gradually increased with increasing CSP concentrations. Treatment of RAW264.7 cells with pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) prevented the formation of osteoclasts. Treatment with different concentrations of CSP effectively decreased the levels of RANKL and M-CSF in rat serum and increased the expression of OPG in the oophorectomy (OVX) rat model. Furthermore, different concentrations of CSP could ameliorate the loss of bone structure and inhibit the formation of osteoclasts in rats. CSP inhibits osteoclastogenesis by regulating the OPG/RANKL/RANK pathway and inhibiting the NF-kB pathway.

A highly sensitive flexible capacitive pressure sensor with hierarchical pyramid micro-structured PDMS-based dielectric layer for health monitoring.

Herein, a flexible pressure sensor with high sensitivity was created using a dielectric layer featuring a hierarchical pyramid microstructure, both in simulation and fabrication. The capacitive pressure sensor comprises a hierarchically arranged dielectric layer made of polydimethylsiloxane (PDMS) with pyramid microstructures, positioned between copper electrodes at the top and bottom. The achievement of superior sensing performance is highly contingent upon the thickness of the dielectric layer, as indicated by both empirical findings and finite-element analysis. Specifically, the capacitive pressure sensor, featuring a dielectric layer thickness of 0.5 mm, exhibits a remarkable sensitivity of 0.77 kPa-1 within the pressure range below 1 kPa. It also demonstrates an impressive response time of 55 ms and recovery time of 42 ms, along with a low detection limit of 8 Pa. Furthermore, this sensor showcases exceptional stability and reproducibility with up to 1,000 cycles. Considering its exceptional achievements, the pressure sensor has been effectively utilized for monitoring physiological signals, sign language gestures, and vertical mechanical force exerted on objects. Additionally, a 5 × 5 sensor array was fabricated to accurately and precisely map the shape and position of objects. The pressure sensor with advanced performance shows broad potential in electronic skin applications.

Flash entropy search to query all mass spectral libraries in real time.

Public repositories of metabolomics mass spectra encompass more than 1 billion entries. With open search, dot product or entropy similarity, comparisons of a single tandem mass spectrometry spectrum take more than 8 h. Flash entropy search speeds up calculations more than 10,000 times to query 1 billion spectra in less than 2 s, without loss in accuracy. It benefits from using multiple threads and GPU calculations. This algorithm can fully exploit large spectral libraries with little memory overhead for any mass spectrometry laboratory.

Alternative Identification of Glycosides Using MS/MS Matching with an In Silico-Modified Aglycone Mass Spectra Library.

Glycosylation of metabolites serves multiple purposes. Adding sugars makes metabolites more water soluble and improves their biodistribution, stability, and detoxification. In plants, the increase in melting points enables storing otherwise volatile compounds that are released by hydrolysis when needed. Classically, glycosylated metabolites were identified by mass spectrometry (MS/MS) using [M-sugar] neutral losses. Herein, we studied 71 pairs of glycosides with their respective aglycones, including hexose, pentose, and glucuronide moieties. Using liquid chromatography (LC) coupled to electrospray ionization high-resolution mass spectrometry, we detected the classic [M-sugar] product ions for only 68% of glycosides. Instead, we found that most aglycone MS/MS product ions were conserved in the MS/MS spectra of their corresponding glycosides, even when no [M-sugar] neutral losses were observed. We added pentose and hexose units to the precursor masses of an MS/MS library of 3057 aglycones to enable rapid identification of glycosylated natural products with standard MS/MS search algorithms. When searching unknown compounds in untargeted LC-MS/MS metabolomics data of chocolate and tea, we structurally annotated 108 novel glycosides in standard MS-DIAL data processing. We uploaded this new in silico-glycosylated product MS/MS library to GitHub to enable users to detect natural product glycosides without authentic chemical standards.

Ultrahigh-sensitivity multi-parameter tacrolimus solution detection based on an anchor planar millifluidic microwave biosensor.

To detect drug concentration in tacrolimus solution, an anchor planar millifluidic microwave (APMM) biosensor is proposed. The millifluidic system integrated with the sensor enables accurate and efficient detection while eliminating interference caused by the fluidity of the tacrolimus sample. Different concentrations (10-500 ng mL-1) of the tacrolimus analyte were introduced into the millifluidic channel, where it completely interacts with the radio frequency patch electromagnetic field, thereby effectively and sensitively modifying the resonant frequency and amplitude of the transmission coefficient. Experimental results indicate that the sensor has an extremely low limit of detection (LoD) of 0.12 pg mL-1 and a frequency detection resolution (FDR) of 1.59 (MHz (ng mL-1)). The greater the FDR and the lower the LoD, the more the feasibility of a label-free biosensing method. Regression analysis revealed a strong linear correlation (R2 = 0.992) between the concentration of tacrolimus and the frequency difference of the two resonant peaks of APMM. In addition, the difference in the reflection coefficient between the two formants was measured and calculated, and a strong linear correlation (R2 = 0.998) was found between the difference and tacrolimus concentration. Five measurements were performed on each individual sample of tacrolimus to validate the biosensor's high repeatability. Consequently, the proposed biosensor is a potential candidate for the early detection of tacrolimus drug concentration levels in organ transplant recipients. This study presents a simple method for constructing microwave biosensors with high sensitivity and rapid response.

Isochlorogenic acid A alleviates dextran sulfate sodium-induced ulcerative colitis in mice through STAT3/NF-кB pathway.

Isochlorogenic acid A (ICGA-A) is a dicaffeoylquinic acid widely found in various medicinal plants or vegetables, such as Lonicerae japonicae Flos and chicory, and multiple properties of ICGA-A have been reported. However, the therapeutic effect of ICGA-A on colitis is not clear, and thus were investigated in our present study, as well as the underlying mechanisms. Here we found that ICGA-A alleviated clinical symptoms of dextran sodium sulfate (DSS) induced colitis model mice, including disease activity index (DAI) and histological damage. In addition, DSS-induced inflammation was significantly attenuated in mice given ICGA-A supplementation. ICGA-A reduced the fraction of neutrophils in peripheral blood and the infiltration of neutrophils and macrophages in colon tissue, and reduced pro-inflammatory cytokine production and tight junctions in mouse models. Furthermore, ICGA-A down-regulated expression of STAT3 and up-regulated the protein level of IκBα. Our in vitro studies confirmed that ICGA-A inhibited the mRNA expression of pro-inflammatory cytokines. ICGA-A blocked the phosphorylation of STAT3, p65, and IκBα, suppressed the expression STAT3 and p65. In addition, the present study also demonstrated that ICGA-A had no obvious toxicity on normal cells and organs. Taken together, we conclude that ICGA-A mitigates experimental ulcerative colitis (UC) at least in part by inhibiting the STAT3/NF-кB signaling pathways. Hence, ICGA-A may be a promising and effective drug for treating UC.

Engineering Multiple Microstructural Defects for Record-Breaking Thermoelectric Properties of Chalcopyrite Cu1- x Agx GaTe2.

Defect engineering for vacancies, holes, nano precipitates, dislocations, and strain are efficient means of suppressing lattice thermal conductivity. Multiple microstructural defects are successfully designed in Cu1- x Agx GaTe2 (0 ≤ x ≤ 0.5) solid solutions through high-ratio alloying and vibratory ball milling, to achieve ultra-low thermal conductivity and record-breaking thermoelectric performance. Extremely low total thermal conductivities of 1.28 W m-1  K-1 at 300 K and 0.40 W m-1  K-1 at 873 K for the Cu0.5 Ag0.5 GaTe2 are observed, which are ≈79% and ≈58% lower than that of the CuGaTe2 matrix. Multiple phonon scattering mechanisms are collectively responsible for the reduction of thermal conductivity in this work. On one hand, large amounts of nano precipitates and dislocations are formed via vibrating ball milling followed by the low-temperature hot press, which can enhance phonon scattering. On the other hand, the difference in atomic sizes, distorted chemical bonds, elements fluctuation, and strained domains are caused by the high substitution ratio of Ag and also function as a center for the strong phonon scattering. As a result, the Cu0.7 Ag0.3 GaTe2 exhibits a record high ZTmax of ≈1.73 at 873 K and ZTave of ≈0.69 between 300-873 K, which are the highest values of CuGaTe2 -based thermoelectric materials.

Microfluidic microwave biosensor based on biomimetic materials for the quantitative detection of glucose.

This paper presents a microwave microfluidic biosensor for monitoring blood glucose levels. The glucose sensor is a triple ring microstrip patch antenna integrated with a biomimetic microfluidic device capable of measuring a fixed volume of glucose solution. The sensor was utilized to detect 50-500 mg/dL glucose solutions. The interaction of the glucose solution with the electromagnetic field on the patch's surface influences both the resonance frequency and the magnitude of reflection coefficient. The results indicate that the microfluidic device can reduce experimental error and enhance the correlation between glucose concentration, resonant frequency, and reflection coefficient. Finally, the microfluidic sensor had a sensitivity of 0.25 MHz/(mg/dL), a detection limit as low as 7.7 mg/dL, and correlation coefficients of resonance frequency and reflection coefficient with a glucose concentration of 0.996 and 0.984, respectively. The experiment on the sensor's stability verifies the sensor's excellent stability and rapid response (~ 150 ms). Consequently, the device can be used to differentiate the concentration of glucose solutions, as well as to detect blood glucose levels at an early stage.

A high-performance wearable pressure sensor based on an MXene/PVP composite nanofiber membrane for health monitoring.

Flexible and wearable pressure sensors have attracted extensive attention in domains, such as electronic skin, medical monitoring and human-machine interaction. However, developing a pressure sensor with high sensitivity, mechanical stability and a wide detection range remains a huge challenge. In this work, a flexible capacitive pressure sensor, based on a Ti3C2T x (MXene)/polyvinyl pyrrolidone (PVP) composite nanofiber membrane (CNM), prepared via an efficient electrospinning process, is presented. The experimental results show that even a small mass fraction of MXene can effectively decrease the compression modulus of the PVP nanofiber membrane, thus enhancing the sensing performance. Specifically, the sensor based on (0.1 wt% MXene)/PVP CNM has a high sensitivity (0.5 kPa-1 at 0-1.5 kPa), a fast response/recovery time (45/45 ms), a wide pressure detection range (0-200 kPa), a low detection limit (∼9 Pa) and an excellent mechanical stability (8000 cycles). Due to its superior performance, the sensor can monitor subtle changes in human physiology and other signals, such as pulse, respiration, human joint motions and airflow. In addition, a 4 × 4 sensor array is fabricated that can accurately map the shape and position of objects with good resolution. The high-performance flexible pressure sensor, as developed in this work, shows good application prospects in advanced human-computer interface systems.

The diversity of vaginal microbiome in women infected with single HPV and multiple genotype HPV infections in China.

Introduction: The human papillomavirus (HPV) is the leading cause of cervical cancer globally. However, its microbial composition and association with the types of HPV infection remain elusive. Methods: This study was designed to characterize the vaginal microbiota of 53 HPV-infected and 16 normal women (control group) by using high-throughput sequencing with the Illumina platform. Results: In this study, the five leading phyla were Firmicutes (73.9%), Actinobacteriota (12.8%), Proteobacteria (6.2%), Fusobacteria (3.5%), and Bacteroidota (3.1%). We found that single HPV genotype-positive women had higher α-microbial diversity compared with HPV-negative and multiple HPV-positive women. In women with a single HPV genotype infection, the HPV-16 infection had significantly higher α-diversity than other genotype infections. In multiple HPV genotype-positive women, the highest α-diversity was found in women positive for HR-HR HPV genotype infection, compared with other infections. Furthermore, in single- and multiple-genotype infections, the abundance of s_unclassified_g_Lactobacillus decreased whereas the abundance of s_Gardnerella_vaginalis increased compared with control. Additionally, s_unclassified_f_Rhizobiaceae and s_sneathia_sanguinegens were only found in HPV-infected women. Conclusion: This study showed that the type of HPV infection was associated with the composition of the vaginal microbiota. Further studies on HPV genotypes and vaginal microbiota are necessary to uncover more mysteries of their association and provide a promising therapeutic target as well as low-cost future therapeutic strategies.

Spectral entropy outperforms MS/MS dot product similarity for small-molecule compound identification.

Compound identification in small-molecule research, such as untargeted metabolomics or exposome research, relies on matching tandem mass spectrometry (MS/MS) spectra against experimental or in silico mass spectral libraries. Most software programs use dot product similarity scores. Here we introduce the concept of MS/MS spectral entropy to improve scoring results in MS/MS similarity searches via library matching. Entropy similarity outperformed 42 alternative similarity algorithms, including dot product similarity, when searching 434,287 spectra against the high-quality NIST20 library. Entropy similarity scores proved to be highly robust even when we added different levels of noise ions. When we applied entropy levels to 37,299 experimental spectra of natural products, false discovery rates of less than 10% were observed at entropy similarity score 0.75. Experimental human gut metabolome data were used to confirm that entropy similarity largely improved the accuracy of MS-based annotations in small-molecule research to false discovery rates below 10%, annotated new compounds and provided the basis to automatically flag poor-quality, noisy spectra.

Coupling proteomics and metabolomics for the unsupervised identification of protein-metabolite interactions in Chaetomium thermophilum.

Protein-metabolite interactions play an important role in the cell's metabolism and many methods have been developed to screen them in vitro. However, few methods can be applied at a large scale and not alter biological state. Here we describe a proteometabolomic approach, using chromatography to generate cell fractions which are then analyzed with mass spectrometry for both protein and metabolite identification. Integrating the proteomic and metabolomic analyses makes it possible to identify protein-bound metabolites. Applying the concept to the thermophilic fungus Chaetomium thermophilum, we predict 461 likely protein-metabolite interactions, most of them novel. As a proof of principle, we experimentally validate a predicted interaction between the ribosome and isopentenyl adenine.

Enhancement effect of nanoscale zero-valent iron addition on microbial degradation of BDE-209 in contaminated mangrove sediment.

Chemical and biological methods have been employed to remedy polybrominated diphenyl ether contamination, but the removal of decabromodiphenyl ether (BDE-209) by either method still has limitations. The present study aims to evaluate the combined effect of nanoscale zero-valent iron (nZVI) (from 0.1 to 10%) reduction and microbial debromination on BDE-209 removal in mangrove sediments under an anaerobic condition. During the 12-months incubation, nZVI significantly enhanced BDE-209 removal, with 17.03% to 41.99% reduction in sterilized sediments. The reduction was even higher in non-sterilized sediments with living indigenous microorganisms, achieving 15.80%, 33.50%, 55.83% and 66.95% removal of BDE-209 at 0 (control without nZVI), 0.1%, 1% and 10% nZVI, respectively. In control sterilized sediments, no debromination was found, and debromination occurred according to spiked levels of nZVI, with BDE-153 being the dominant congener. The concentrations of debrominated congeners in non-sterilized sediments also increased with nZVI levels, but were significantly higher than the respective sterilized sediment. The relative proportions of different debrominated congeners in non-sterilized sediments depended on nZVI levels, with BDE-99 being the dominant congener in low nZVI amended sediments but shifted to BDE-153 under high nZVI. Higher concentrations of ferrous iron (Fe2+) were detected in both sterilized and non-sterilized sediments spiked with more nZVI, and their concentrations significantly correlated with BDE-209 removal. Growth of total bacteria in sediments with 1% and 10% nZVI was inhibited within first two months, but their numbers resumed to that in the control at the end of 12 months. The present study demonstrates the synergy between chemical and microbiological methods, and a combination of nZVI and indigenous microorganisms could be an efficient and feasible mean to remedy BDE-209 in contaminated sediments.

Nanoarchitectonics of p-type BiSbTe with improved figure of merit via introducing PbTe nanoparticles.

Bi0.4Sb1.6Te3 (BST) is known to be a unique p-type commercial thermoelectric (TE) alloy used at room temperatures, but its figure of merit (ZT) is relatively low for wide industrial applications. To improve its ZT value is vitally important. Here, we show that the incorporation of 0.5 wt% PbTe nanoparticles into BST concurrently causes a large enhancement of power factor (PF) and a significant reduction of lattice thermal conductivity κ L. The increase in PF mainly benefits from the optimization of carrier concentration, maintenance of high carrier mobility and constant rise in Seebeck coefficient. The decrease in κ L can be attributed to the enhanced phonon scattering by the dispersed PbTe nanoparticles and the interfaces between PbTe and the BST matrix by using the Callaway model. Specifically, an ultralow κ L of 0.26 W m-1 K-1 at 429 K is achieved for the composites incorporating 0.5 wt% PbTe nanoinclusions. Consequently, an excellent ZT = 1.6 at 482 K and a high average ZT ave = 1.38 at 300-500 K are achieved, indicating that incorporation of PbTe in BST is an effective approach to improve its thermoelectric performance.

Correction: Nanoarchitectonics of p-type BiSbTe with improved figure of merit via introducing PbTe nanoparticles.

[This corrects the article DOI: 10.1039/D1RA07138F.].

Vaginal Microbiota and HPV Infection: Novel Mechanistic Insights and Therapeutic Strategies.

Cervical cancer is a global public health concern. The complex interaction of genetic and environmental factors is critical for the progress of cervical cancer. Growing evidence suggests that microbes, human papillomavirus (HPV), and the immune system interact closely with each other to govern homeostasis of the vaginal environment and the health of the lower genital tract of females. Certain vaginal microbial strains may play either a protective or a pathogenic role in carcinogenesis of the cervix after HPV persistent infection. Probiotics can therefore present a putative therapeutic approach for cervical cancer. However, work in this field remains limited. Recent technological developments have allowed us to identify microbes and their products using culture-independent molecular detection techniques. In this review, we discuss the composition of the vaginal bacterial community, its commensal flora and the protective impact this has on the health of the female genital tract. This review will also describe critical immune factors in lower genital tract health and summarize the role of the vaginal microbiota in cervical carcinogenesis. Knowledge in this field has provided researchers with the clues and tools to propose the use of probiotics as a potential line of treatment for cervical cancer and has provided valuable insights into host-pathogen interaction dynamics within the female genital tract.

Effects of Sb Deviation from Its Stoichiometric Ratio on the Micro- and Electronic Structures and Thermoelectric Properties of Cu12Sb4S13.

Thermoelectric material tetrahedrite Cu12Sb4S13 has attracted much attention because of its intrinsic low lattice thermal conductivity, excellent electrical transport property, and environment-friendly constituents. However, its thermoelectric figure merit, ZT, is limited because of the low Seebeck coefficient (S) and power factor (PF). Hence, it is indispensable to enhance its S and PF to increase its ZT. Here, we show that when Sb deviation from its stoichiometric ratio in the Cu12Sb4S13 band structure is modulated, it gives rise to increased density of states and enhancement of the Seebeck coefficient. Moreover, carrier concentration is tuned by changing sulfur and copper vacancies through controlling the Cu3SbS4 phase with an atomic ratio of Sb, leading to increased electrical conductivity. In addition, as large as ∼60% reduction of lattice thermal conductivity is obtained by intensified phonon scattering using an impurity phase/element and vacancy-like defects induced by different Sb contents. As a result, a high ZT = 0.86 is achieved at 723 K for the Cu12Sb4+δS13 sample with δ = 0.2, which is ∼50% larger than that of stoichiometric Cu12Sb4S13 studied here, indicating that ZT of Cu12Sb4S13 can be improved through simple modulation of the Sb stoichiometric ratio.

Identification of metabolites from tandem mass spectra with a machine learning approach utilizing structural features.

MOTIVATION: Untargeted mass spectrometry (MS/MS) is a powerful method for detecting metabolites in biological samples. However, fast and accurate identification of the metabolites' structures from MS/MS spectra is still a great challenge. RESULTS: We present a new analysis method, called SubFragment-Matching (SF-Matching) that is based on the hypothesis that molecules with similar structural features will exhibit similar fragmentation patterns. We combine information on fragmentation patterns of molecules with shared substructures and then use random forest models to predict whether a given structure can yield a certain fragmentation pattern. These models can then be used to score candidate molecules for a given mass spectrum. For rapid identification, we pre-compute such scores for common biological molecular structure databases. Using benchmarking datasets, we find that our method has similar performance to CSI: FingerID and those very high accuracies can be achieved by combining our method with CSI: FingerID. Rarefaction analysis of the training dataset shows that the performance of our method will increase as more experimental data become available. AVAILABILITY AND IMPLEMENTATION: SF-Matching is available from http://www.bork.embl.de/Docu/sf_matching. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.