Humidity Adaptive Antifreeze Hydrogel Sensor for Intelligent Control and Human-Computer Interaction.

Conductive hydrogels have emerged as ideal candidate materials for strain sensors due to their signal transduction capability and tissue-like flexibility, resembling human tissues. However, due to the presence of water molecules, hydrogels can experience dehydration and low-temperature freezing, which greatly limits the application scope as sensors. In this study, an ionic co-hybrid hydrogel called PBLL is proposed, which utilizes the amphoteric ion betaine hydrochloride (BH) in conjunction with hydrated lithium chloride (LiCl) thereby achieving the function of humidity adaptive. PBLL hydrogel retains water at low humidity (<50%) and absorbs water from air at high humidity (>50%) over the 17 days of testing. Remarkably, the PBLL hydrogel also exhibits strong anti-freezing properties (-80 °C), high conductivity (8.18 S m-1 at room temperature, 1.9 S m-1 at -80 °C), high gauge factor (GF approaching 5.1). Additionally, PBLL hydrogels exhibit strong inhibitory effects against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), as well as biocompatibility. By synergistically integrating PBLL hydrogel with wireless transmission and Internet of Things (IoT) technologies, this study has accomplished real-time human-computer interaction systems for sports training and rehabilitation evaluation. PBLL hydrogel exhibits significant potential in the fields of medical rehabilitation, artificial intelligence (AI), and the Internet of Things (IoT).

FUNDC1/PFKP-mediated mitophagy induced by KD025 ameliorates cartilage degeneration in osteoarthritis.

Osteoarthritis (OA) is the most common joint disease, but no disease-modifying drugs have been approved for OA treatment. Mitophagy participates in mitochondrial homeostasis regulation by selectively clearing dysfunctional mitochondria, which might contribute to cartilage degeneration in OA. Here, we provide evidence of impaired mitophagy in OA chondrocytes, which exacerbates chondrocyte degeneration. Among the several classic mitophagy-regulating pathways and receptors, we found that FUNDC1 plays a key role in preserving chondrocyte homeostasis by inducing mitophagy. FUNDC1 knockdown in vitro and knockout in vivo decreased mitophagy and exacerbated mitochondrial dysfunction, exacerbating chondrocyte degeneration and OA progression. FUNDC1 overexpression via intra-articular injection of adeno-associated virus alleviated cartilage degeneration in OA. Mechanistically, our study demonstrated that PFKP interacts with and dephosphorylates FUNDC1 to induce mitophagy in chondrocytes. Further analysis identified KD025 as a candidate drug for restoring chondrocyte mitophagy by increasing the FUNDC1-PFKP interaction and thus alleviating cartilage degeneration in mice with DMM-induced OA. Our study highlights the role of the FUNDC1-PFKP interaction in chondrocyte homeostasis via mitophagy induction and identifies KD025 as a promising agent for treating OA by increasing chondrocyte mitophagy.

YIPF5 (p.W218R) mutation induced primary microcephaly in rabbits.

Primary microcephaly (PMCPH) is a rare autosomal recessive neurodevelopmental disorder with a global prevalence of PMCPH ranging from 0.0013% to 0.15%. Recently, a homozygous missense mutation in YIPF5 (p.W218R) was identified as a causative mutation of severe microcephaly. In this study, we constructed a rabbit PMCPH model harboring YIPF5 (p.W218R) mutation using SpRY-ABEmax mediated base substitution, which precisely recapitulated the typical symptoms of human PMCPH. Compared with wild-type controls, the mutant rabbits exhibited stunted growth, reduced head circumference, altered motor ability, and decreased survival rates. Further investigation based on model rabbit elucidated that altered YIPF5 function in cortical neurons could lead to endoplasmic reticulum stress and neurodevelopmental disorders, interference of the generation of apical progenitors (APs), the first generation of progenitors in the developing cortex. Furthermore, these YIPF5-mutant rabbits support a correlation between unfolded protein responses (UPR) induced by endoplasmic reticulum stress (ERS), and the development of PMCPH, thus providing a new perspective on the role of YIPF5 in human brain development and a theoretical basis for the differential diagnosis and clinical treatment of PMCPH. To our knowledge, this is the first gene-edited rabbit model of PMCPH. The model better mimics the clinical features of human microcephaly than the traditional mouse models. Hence, it provides great potential for understanding the pathogenesis and developing novel diagnostic and therapeutic approaches for PMCPH.

Breast tumor-on-chip: from the tumor microenvironment to medical applications.

With the development of microfluidic technology, tumor-on-chip models have gradually become a new tool for the study of breast cancer because they can simulate more key factors of the tumor microenvironment compared with traditional models in vitro. Here, we review up-to-date advancements in breast tumor-on-chip models. We summarize and analyze the breast tumor microenvironment (TME), preclinical breast cancer models for TME simulation, fabrication methods of tumor-on-chip models, tumor-on-chip models for TME reconstruction, and applications of breast tumor-on-chip models and provide a perspective on breast tumor-on-chip models. This review will contribute to the construction and design of microenvironments for breast tumor-on-chip models, even the development of the pharmaceutical field, personalized/precision therapy, and clinical medicine.

Transcriptome analysis reveals the neuroactive receptor genes response to Streptococcus agalactiae infection in tilapia, Oreochromis niloticus.

The detailed crosstalk between the neuroendocrine and immune systems in Oreochromis niloticus, an economically important fish, in response to pathogenic infections, remains unclear. This study revealed the head kidney transcriptional profiles of O. niloticus upon infections with Streptococcus agalactiae, a prevalent pathogen known to cause severe meningitis. Twelve cDNA libraries of O. niloticus head kidney, representing four treatment time points (0, 6, 24, and 48 h), were constructed and a total of 2,528 differentially expressed genes were identified based on pairwise comparisons. KEGG pathway analysis revealed a significant enrichment of the 'neuroactive ligand-receptor interaction' pathway (ko04080), with 13 genes exhibiting differential expression during S. agalactiae infection. Among these, six neuroactive receptor genes (lepr, nr3c1, ptger4, thrb, tspo, and ß2-ar) were selected, cloned, and characterized. Although these genes are ubiquitously expressed, and in head kidney leukocytes, their expression was mainly observed in T cells, Mo/Mφ, and NCCs, which are characterized by antimicrobial responses. Furthermore, we examined the response patterns of these six neuroactive receptor genes to gram-positive (S. agalactiae) and gram-negative (Aeromonas hydrophila) bacteria in four different tissues. Notably, lepr, ptger4, tspo, and ß2-ar were upregulated in all selected tissues in response to S. agalactiae and A. hydrophila infections. However, nr3c1 and thrb were downregulated in response to S. agalactiae infection in the head kidney and spleen, whereas nr3c1 was upregulated, and thrb was unresponsive to A. hydrophila infection. Our findings provide a theoretical foundation for understanding new links between the neuroendocrine and immune systems during bacterial infection in teleost fish.

Online Handwritten Signature Verification Method Based on Uni-Feature Correlation Coefficient between Signatures.

Online handwritten signature verification is a crucial direction of research in the field of biometric recognition. Recently, many studies concerning online signature verification have attempted to improve performance using multi-feature fusion. However, few studies have provided the rationale for selecting a certain uni-feature to be fused, and few studies have investigated the contributions of a certain uni-feature in the multi-feature fusion process. This lack of research makes it challenging for future researchers in related fields to gain inspiration. Therefore, we use the uni-feature as the research object. In this paper, the uni-feature is one of the X and Y coordinates of the signature trajectory point, pen pressure, pen tilt, and pen azimuth feature. Aiming to solve the unequal length of feature vectors and the low accuracy of signature verification when using uni-features, we innovatively introduced the idea of correlation analysis and proposed a dynamic signature verification method based on the correlation coefficient of uni-features. Firstly, an alignment method of two feature vector lengths was proposed. Secondly, the correlation coefficient calculation formula was determined by analyzing the distribution type of the feature data, and then the correlation coefficient of the same uni-feature between the genuine signatures or between the genuine and forged signatures was calculated. Finally, the signature was verified by introducing a Gaussian density function model and combining it with the signature verification discrimination threshold. Experimental results showed that the proposed method could improve the performance of dynamic signature verification based on uni-features. In addition, the pen pressure feature had the best signature verification performance, with the highest signature verification accuracy of 93.46% on the SVC 2004 dataset.

Fast thermo-optical modulators with doped-silicon heaters operating at 2 µm: erratum.

We correct the errors in the performance of the MRR modulator in our paper [Opt. Express29, 23508, (2021)10.1364/OE.430756]. The FWHM of the MRR device should be 0.22nm instead of 0.11nm. And thus, the Q factor, power consumption, and FOM need to be corrected. After the correction, the performance of our devices was still the best among 2µm-waveband TO modulators. All the conclusions are not changed.

Microring resonator based on polarization multiplexing for simultaneous sensing of refractive index and temperature on silicon platform.

Silicon photonic integrated sensors based on microring resonators are a promising candidate to achieve high-performance on-chip sensing. In this work, a novel dual-parameters sensor based on polarization multiplexing on silicon-on-insulator (SOI) platform is proposed and demonstrated experimentally, simultaneously achieving refractive index (RI) and temperature sensing with high sensitivity and large detection range (DR). The experimental results show that the RI sensitivity and temperature sensitivity of the TM-operated sensor are 489.3 nm/RIU and 20.0 pm/°C, respectively, and that of the TE-operated sensor are 102.6 nm/RIU and 43.3 pm/°C, respectively. Moreover, the DR of the fabricated sensor is 0.0296 RIU, which is 4.2 times that of the conventional TM-operated sensor based on the microring resonator. The dual-parameters sensor based on polarization multiplexing can successfully realize the simultaneous measurement of the RI and the temperature, showing potential applications of silicon photonic on-chip sensors in reality.

Thermo-optically tunable slot waveguide-based dual mode-splitting resonators with enhanced sharp lineshapes.

Slot waveguide plays an essential role in achieving high-performance on-chip photonic sensors and nonlinear devices. Ideally, slot waveguide features a large evanescent field ratio and strong electric field intensity in the slot, leading to a high waveguide sensitivity. Unfortunately, the microring resonator (MRR) based on the slot waveguide suffers the less steep spectral slope due to the low quality factor induced by the huge optical propagation loss of the slot waveguide. In this work, a novel dual mode-splitting resonator based on the slot waveguide is proposed and demonstrated to steepen the slope of lineshapes. The device is implemented by two racetrack resonators based on a slot waveguide and a feedback waveguide to introduce coherent optical mode interference, which could induce mode-splitting resonance (MR) with sharp asymmetry line shape and large extinction ratio (ER). The proposed device is fabricated by the standard complementary metal-oxide-semiconductor (CMOS) technologies on silicon-on-insulator (SOI) platform, and the characterization results show dual MRs with an ER of 45.0 dB and a slope rate (SR) of 58.3 dB/nm, exhibiting a much steeper lineshape than that of the conventional MRR with slot waveguide. And the resonance can be tuned efficiently by applying various voltages of the TiN microheater. Investigations in dual MRs devices promote many potential applications in the field of optical switching, optical modulating, and on-chip optical sensing.

Compact digital system for an iodine-stabilized laser.

A compact digital control system based on an all-programmable system-on-chip iodine-stabilized laser is presented for realization of the meter. The system is composed of ZYNQ7000, peripheral circuits, and human-computer interaction, which can operate independently. An nth-harmonic extraction algorithm with less resource consumption is used in this system. The digital system overcomes the problems of complex debugging, large volume, and manual locking. Additionally, customers can set up, calibrate, and upgrade the system by themselves. Its stability is similar to that of the current analog system, with long-term stability of up to 10-13. The repeatability of the two lasers with the digital system is approximately 1.5×10-11, and the absolute frequencies satisfy the international recommendation.

The pathogenic potential and genetic attributes of Escherichia coli in milk from dairy cows with subclinical mastitis.

The centrality of milk and dairy products to the human diet allows potential pathogens to pose a threat to human health. Pathogenic Escherichia coli is a zoonotic foodborne pathogen with many virulence genes which cause variations in its pathogenicity. The current study aimed to investigate the pathogenic potential of E. coli from milk of dairy cows with subclinical mastitis and evaluate the genetic relatedness to E. coli from human sources. The majority of the E. coli isolates belonged to the A (55.0%) and B2 (22.5%) phylogenetic groups and the most prevalent virulence genes were colV (90.0%), fyuA (75.0%) and vat (42.5%). Mice injected with G4-BD23 (P < 0.05) and G5-BD3 had lower survival rates than controls and visible pathological changes to lung and kidney. Nineteen MLST types were identified in 40 dairy E. coli isolates and three STs (ST10, ST48 and ST942) were shared with those from human sources. Some dairy E. coli isolates were phylogenetically related to human E. coli isolates indicating pathogenic potential.

Transcriptome provides potential insights into how calcium affects the formation of stone cell in Pyrus.

BACKGROUND: The content of stone cells in pears has a great influence on taste. Stone cells are formed by the accumulation of lignin. The treatment of exogenous calcium can affect the lignin synthesis, but this Ca-mediated mechanism is still unclear. In this study, the author performed a comparative transcriptomic analysis of callus of pears (Pyrus x bretschneideri) treated with calcium nitrate Ca (NO3)2 to investigate the role of calcium in lignin synthesis. RESULTS: There were 2889 differentially expressed genes (DEGs) detected between the Control and Ca (NO3)2 treatment in total. Among these 2889 DEGs, not only a large number of genes related to Ca single were found, but also many genes were enriched in secondary metabolic pathway, especially in lignin synthesis. Most of them were up-regulated during the development of callus after Ca (NO3)2 treatment. In order to further explore how calcium nitrate treatment affects lignin synthesis, the author screened genes associated with transduction of calcium signal in DEGs, and finally found CAM, CML, CDPK, CBL and CIPK. Then the author identified the PbCML3 in pears and conducted relevant experiments finding the overexpression of PbCML3 would increase the content of pear stone cells, providing potential insights into how Ca treatment enhances the stone cell in pears. CONCLUSIONS: Our deep analysis reveals the effects of exogenous calcium on calcium signal and lignin biosynthesis pathway. The function of PbCML3 on stone cells formation was verified in pear.

Low-loss silicon nitride strip-slot mode converter based on MMI.

Slot waveguide has attracted a lot of attention due to its ability to confine light in the low refractive index region, while strip waveguide acts as the basic component of guiding light due to its relatively low optical loss. In the multifunctional photonic integrated chips, it is critical to achieve the low loss transition between the strip waveguide and the slot waveguide. In this work, a silicon nitride strip-slot mode converter with high efficiency, large bandwidth, and large fabrication tolerance are proposed and demonstrated through the numerical investigation and experiments. The coupling efficiency of the mode converter is up to - 0.1 dB (97.7%), which enables the extremely low transition loss between the strip waveguide and the slot waveguide. Moreover, the fabrication process of silicon nitride photonic devices with high performance is introduced, which is fully compatible with the CMOS technology. Photonic devices based on silicon nitride with the characteristics of the low optical loss and the temperature insensitivity represent a new paradigm in realizing silicon-based photonic multifunctional chips.

Wide-range, ultra-compact, and high-sensitivity ring resonator biochemical sensor with CMOS-compatible hybrid plasmonic waveguide.

A ring resonator-based biochemistry sensor with a wide range, ultra-compact footprint, and high sensitivity is proposed, which utilizes a suspended slot hybrid plasmonic (SSHP) waveguide. The waveguide consists of a suspended Si nanowire separated from a Cu metal surface by a nanoscale air gap. The hybridization of fundamental mode of a Si channel waveguide with the surface plasmon polariton (SPP) mode of Cu-Si interface achieves a strong light confinement, high waveguide sensitivity (Sw), and low optical loss, showing a great potential in integrated optical sensor. The sensitivity, the detection limit and the detection range of the SSHP waveguide-based biochemistry sensor with a miniaturized radius of 1 µm are numerically demonstrated as 458.1 nm/RIU, 3.7 × 10-5 RIU and 0.225 RIU, respectively. These superior performances as well as the fully CMOS compatibility enable the integrated optical sensing applications.

Fast thermo-optical modulators with doped-silicon heaters operating at 2 µm.

The 2-µm-waveband has been recognized as a potential telecommunication window for next-generation low-loss, low-latency optical communication. Thermo-optic (TO) modulators and switches, which are essential building blocks in a large-scale integrated photonic circuit, and their performances directly affect the energy consumption and reconfiguration time of an on-chip photonic system. Previous TO modulation based on metallic heaters at 2-µm-waveband suffer from slow response time and high power consumption. In this paper, high-performance thermo-optical Mach-Zehnder interferometer and ring resonator modulators operating at 2-µm-waveband were demonstrated. By embedding a doped silicon (p++-p-p++) junction into the waveguide, our devices reached a record modulation efficiency of 0.17 nm/mW for Mach-Zehnder interferometer based modulator and its rise/fall time was 3.49 µs/3.46 µs which has been the fastest response time reported in a 2-µm-waveband TO devices so far. And a lowest Pπ power of 3.33 mW among reported 2-µm TO devices was achieved for a ring resonator-based modulator.

Angelica polysaccharide attenuates LPS-induced inflammation response of primary dairy cow claw dermal cells via NF-κB and MAPK signaling pathways.

BACKGROUND: Laminitis, an inflammation of the claw laminae, is one of the major causes of bovine lameness, which can lead to enormous economic losses and animal welfare problems in dairy farms. Angelica polysaccharide (AP) is proved to possess anti-inflammatory properties. But the role of AP on inflammatory response of the claw dermal cells has not been reported. The aim of this study was to investigate the anti-inflammatory effects of AP on lipopolysaccharide (LPS)-induced primary claw dermal cells of dairy cow and clarify the potential mechanisms. In the current research, the primary claw dermal cells were exposed to gradient concentrations of AP (10, 50, 100 µg/mL) in the presence of 10 µg/mL LPS. The levels of cytokines and nitric oxide (NO) were detected with ELISA and Griess colorimetric method. The mRNA expressions of TLR4, MyD88 and chemokines were measured with qPCR. The activation of NF-κB and MAPK signaling pathways was detected with western blotting. RESULTS: The results indicated that AP reduced the production of inflammatory mediators (TNF-α, IL-1ß, IL-6 and NO), downregulated the mRNA expression of TLR4, MyD88 and some pro-inflammatory chemokines (CCL2, CCL20, CXCL2, CXCL8, CXCL10), and suppressed the NF-κB and MAPK signaling pathways evidenced by inhibition of the phosphorylation of IκBα, p65 and ERK, JNK, p38. CONCLUSIONS: Our results demonstrated that AP may exert its anti-inflammatory effects on claw dermal cells of dairy cow by regulating the NF-κB and MAPK signaling pathways.

BHLHE40 modulates post-traumatic stress disorder behaviors with the involvement of the PI3K/AKT signaling pathway.

Post-traumatic stress disorder (PTSD) is closely related to the exposure to traumatic events and results in the structural and functional changes of hippocampus. Human basic helix-loop-helix family member e40 (BHLHE40) was reported to be implicated with neuron maturity and neuronal differentiation. The present study aimed to reveal the role of BHLHE40 on single-prolonged stress (SPS) model of PTSD in mice. The morris water maze test, open field test and contextual fear test were conducted to assess memory deficits, anxiety-like behaviors, and freezing of mice. Western blot was performed to identify proteins and reveal their levels in hippocampal tissues. We found that mice receiving SPS exhibited increased anxiety-like behaviors, memory deficits, and prolonged freezing time. The protein levels of BHLHE40 were downregulated in the hippocampal tissues of SPS mice. SPS reduced the protein levels of glutamate receptors, while overexpression of BHLHE40 promoted glutamate receptor protein levels in SPS mice. Moreover, BHLHE40 overexpression activated the PI3K/AKT pathway. BHLHE40 overexpression ameliorated the SPS-induced PTSD-like behavioral deficits. Overall, BHLHE40 promotes glutamate receptor protein levels to ameliorate PTSD-like behaviors with the involvement of the PI3K/AKT pathway. This novel discovery may provide a potential target for the improvement of PTSD.

Identification of the neuropeptide precursor genes potentially involved in the larval settlement in the Echiuran worm Urechis unicinctus.

BACKGROUND: In marine invertebrate life cycles, which often consist of planktonic larval and benthonic adult stages, settlement of the free-swimming larva to the sea floor in response to environmental cues is a key life cycle transition. Settlement is regulated by a specialized sensory-neurosecretory system, the larval apical organ. The neuroendocrine mechanisms through which the apical organ transduces environmental cues into behavioral responses during settlement are not fully understood yet. RESULTS: In this study, a total of 54 neuropeptide precursors (pNPs) were identified in the Urechis unicinctus larva and adult transcriptome databases using local BLAST and NpSearch prediction, of which 10 pNPs belonging to the ancient eumetazoa, 24 pNPs belonging to the ancient bilaterian, 3 pNPs belonging to the ancient protostome, 9 pNPs exclusive in lophotrochozoa, 3 pNPs exclusive in annelid, and 5 pNPs only found in U. unicinctus. Furthermore, four pNPs (MIP, FRWamide, FxFamide and FILamide) which may be associated with the settlement and metamorphosis of U. unicinctus larvae were analysed by qRT-PCR. Whole-mount in situ hybridization results showed that all the four pNPs were expressed in the region of the apical organ of the larva, and the positive signals were also detected in the ciliary band and abdomen chaetae. We speculated that these pNPs may regulate the movement of larval cilia and chaeta by sensing external attachment signals. CONCLUSIONS: This study represents the first comprehensive identification of neuropeptides in Echiura, and would contribute to a complete understanding on the roles of various neuropeptides in larval settlement of most marine benthonic invertebrates.

Development of a UHPLC-MS method for inhibitor screening against α-L-1,3-fucosidase.

α-L-Fucosidase (AFU) is a promising therapeutic target for the treatment of inflammation, cancer, cystic fibrosis, and fucosidosis. Some of the existing analytical methods for the assessment of AFU activity are lacking in sensitivity and selectivity, since most of them are based on spectrofluorimetric methods. More recently, mass spectrometry (MS) has evolved as a key technology for enzyme assays and inhibitor screening as it enables accurate monitoring of the conversion of substrate to product in enzymatic reactions. In this study, UHPLC-MS has been utilized to develop a simple, sensitive, and accurate assay for enzyme kinetics and inhibition studies of AFU3, a member of the AFU family. A reported method for analyzing saccharide involving a porous graphitic carbon column, combined with reduction by NaBH4/CH3OH, was used to improve sensitivity. The conversion of saccharide into alditol could reach nearly 100% in the NaBH4 reduction reaction. In addition, the bioanalytical quantitative screening method was validated according to US-FDA guidance, including selectivity, linearity, precision, accuracy, stability, and matrix effect. The developed method displayed a good accuracy, high sensitivity (LOD = 0.05 mg L-1), and good reproducibility (RSD < 15%). The assay accurately measured an IC50 value of 0.40 µM for the known AFU inhibitor, deoxyfuconojirimycin, which was consistent with results reported in the literature. Further validation of the assay was achieved through the determination of a high Z'-factor value of 0.89. The assay was applied to screen a marine-derived chemical library against AFU3, which revealed two marine-oriented pyrimidine alkaloids as potential AFU3 inhibitors. Graphical abstract.

Optimized Ultrasound Conditions for Enhanced Sensitivity of Molecular Beacons in the Detection of MDR1 mRNA in Living Cells.

P-glycoprotein (P-gp), aprognostic indicator for chemotherapy failure, is encoded by multidrug resistance gene (MDR1). MDR1 mRNA expression could serve as a guidance for personalized medicine. However, the traditional PCR process for mRNA measurement is complicated and cannot realize the real-time detection of mRNA in living single cells. In this work, optimized gold nanoparticle-based molecular beacons were employed to determine MDR1 mRNA levels in living cancer cells. To improve detection sensitivity, ultrasound (US) irradiation was applied to facilitate and enhance cellular uptake of hairpin DNA-coated gold nanoparticle (hDAuNP). The US conditions including irradiation power, exposure time, duty cycle, and incubation time were optimized. The slight difference in MDR1 expression manipulated by siRNA silence could be recognized by US assisted hDAuNP beacons; a 10-fold increase of detection sensitivity was achieved compared with the nonultrasound assistance. Meanwhile, the detection cycle could be shortened from 12 to 2 h. Furthermore, this hDAuNP beacon can serve as an antisense agent to down-regulate P-gp expression and to reverse drug resistance of MCF-7/Adr cells to doxorubicin. Our results demonstrated that the MDR1 hDAuNP beacon assisted by US irradiation had great potential to predict chemotherapy sensitivity and to overcome multidrug resistance in cancer cells and was thus a promising tool for individualized medicine.