Spike timing-based coding in neuromimetic tactile system enables dynamic object classification.

Rapid processing of tactile information is essential to human haptic exploration and dexterous object manipulation. Conventional electronic skins generate frames of tactile signals upon interaction with objects. Unfortunately, they are generally ill-suited for efficient coding of temporal information and rapid feature extraction. In this work, we report a neuromorphic tactile system that uses spike timing, especially the first-spike timing, to code dynamic tactile information about touch and grasp. This strategy enables the system to seamlessly code highly dynamic information with millisecond temporal resolution on par with the biological nervous system, yielding dynamic extraction of tactile features. Upon interaction with objects, the system rapidly classifies them in the initial phase of touch and grasp, thus paving the way to fast tactile feedback desired for neuro-robotics and neuro-prosthetics.

Brownian Motion Paving the Way for Molecular Translocation in Nanopores.

Tracing fast nanopore-translocating analytes requires a high-frequency measurement system that warrants a temporal resolution better than 1 µs. This constraint may practically shift the challenge from increasing the sampling bandwidth to dealing with the rapidly growing noise with frequencies typically above 10 kHz, potentially making it still uncertain if all translocation events are unambiguously captured. Here, a numerical simulation model is presented as an alternative to discern translocation events with different experimental settings including pore dimension, bias voltage, the charge state of the analyte, salt concentration, and electrolyte viscosity. The model allows for simultaneous analysis of forces exerting on a large analyte cohort along their individual trajectories; these forces are responsible for the analyte movement leading eventually to the nanopore translocation. Through tracing the analyte trajectories, the Brownian force is found to dominate the analyte movement in electrolytes until the last moment at which the electroosmotic force determines the final translocation act. The mean dwell time of analytes mimicking streptavidin decreases from ≈6 to ≈1 µs with increasing the bias voltage from ±100 to ±500 mV. The simulated translocation events qualitatively agree with the experimental data with streptavidin. The simulation model is also helpful for the design of new solid-state nanopore sensors.

Investigation on biomechanical responses in bilateral semicircular canals and nystagmus in vestibulo-ocular reflex experiments under different forward-leaning angles.

Different head positions affect the responses of the vestibular semicircular canals (SCCs) to angular movement. Specific head positions can relieve vestibular disorders caused by excessive stimulating SCCs. In this study, we quantitatively explored responses of human SCCs using numerical simulations of fluid-structure interaction and vestibulo-ocular reflex (VOR) experiments under different forward-leaning angles of the head, including 0°, 10°, 20°, 30°, 40°, 50°, and 60°. It was found that the horizontal nystagmus slow-phase velocity and corresponding biomechanical responses of the cupula in horizontal SCC increased with the forward-leaning angles of the head, reached a maximum when the head was tilted 30° forward, and then gradually decreased. However, no obvious vertical or torsional nystagmus was observed in the VOR experiments. In the numerical model of bilateral SCCs, the biomechanical responses of the cupula in the left anterior SCC and the right anterior SCC showed the same trends; they decreased with the forward-leaning angles, reached a minimum at a 40° forward tilt of the head, and then gradually increased. Similarly, the biomechanical responses of the cupula in the left posterior SCC and in the right posterior SCC followed a same trend, decreasing with the forward-leaning angles, reaching a minimum at a 30° forward tilt of the head, and then gradually increasing. Additionally, the biomechanical responses of the cupula in both the anterior and posterior SCCs consistently remained lower than those observed in the horizontal SCCs across all measured head positions. The occurrence of these numerical results was attributed to the consistent maintenance of mutual symmetry in the bilateral SCCs with respect to the mid-sagittal plane containing the axis of rotation. This symmetry affected the distribution of endolymph pressure, resulting in biomechanical responses of the cupula in each pair of symmetrical SCCs exhibiting same tendencies under different forward-leaning angles of the head. These results provided a reliable numerical basis for future research to relieve vestibular diseases induced by spatial orientation of SCCs.

Sex-specific associations of bisphenol A and its substitutes with body fat distribution among US adults: NHANES 2011-2016.

Bisphenol A (BPA) and its structural analogs (bisphenol S (BPS) and bisphenol F (BPF)) are widely consumed endocrine disrupting chemicals that may contribute to the etiology of obesity. To date, few studies have directly investigated the sex-related associations between bisphenols and body fat distribution in adults. In this study, we included 2669 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 to evaluate and compare sex-specific differences of the associations of BPA, BPS, and BPF with body fat distribution. We found that there were significant positive correlations between BPS and body fat indices (STFAT [adjustedß=1.94, 95% CI: (0.24, 3.64)], TAF [0.18 (0.04, 0.32)], SAT [0.15 (0.03, 0.27)], android fat mass [0.20 (0.004, 0.40)], BMI [1.63 (0.61, 2.65)], and WC [3.19 (0.64, 5.73)] in the highest quartiles of BPS), but not in BPA and BPF. Stratified analyses suggested that the significant associations of BPS with body fat indices were stronger in women than men (STFAT [adjustedß=3.75, 95% CI: (1.04, 6.45) vs. adjustedß=-0.06, 95% CI: (-2.23, 2.11), P for interaction < 0.001], TAF [ 0.32 (0.09, 0.54) vs. 0.01 (-0.17, 0.19), P for interaction < 0.001], SAT [0.27 (0.09, 0.45) vs. 0.01 (-0.14, 0.16), P for interaction < 0.001], android fat mass [0.41 (0.12, 0.71) vs. -0.02 (-0.28, 0.24), P for interaction < 0.001], gynoid fat mass [0.56 (0.11, 1.01) vs. -0.05 (-0.41, 0.31), P for interaction = 0.002], BMI [2.76 (1.08, 4.44) vs. 0.47 (-0.80, 1.74), P for interaction < 0.001], and WC [5.51 (1.44, 9.58) vs. 0.61 (-2.67, 3.88), P for interaction < 0.001]), and positive associations between BPS with fat distribution were also observed in non-smoking women. Our study indicated that in women, higher concentration of urinary BPS was associated with increased body fat accumulation, except for visceral adipose tissue mass. These findings emphasize the role of environmental BPS exposure in the increasing fat deposits, and confirm the need for more prospective cohort studies on a sex-specific manner.

Gram-Negative Bacteria and Lipopolysaccharides as Risk Factors for the Occurrence of Diabetic Foot.

CONTEXT: Imbalance of the skin microbial community could impair skin immune homeostasis and thus trigger skin lesions. Dysbiosis of skin microbiome may be involved in the early pathogenesis of diabetic foot (DF). However, the potential mechanism remains unclear. OBJECTIVE: To investigate the dynamic composition and function of the foot skin microbiome with risk stratification for DF and assess whether dysbiosis of the skin microbiome induces diabetic skin lesions. METHODS: We enrolled 90 consecutive subjects who were divided into 5 groups based on DF risk stratification: very low, low, moderate, and high risk for ulcers and a healthy control group. Integrated analysis of 16S ribosomal RNA and metagenomic sequencing of cotton swab samples was applied to identify the foot skin microbiome composition and functions in subjects. Then a mouse model of microbiota transplantation was used to evaluate the effects of the skin microbiome on diabetic skin lesions. RESULTS: The results demonstrated that, with the progression of diabetic complications, the proportion of gram-negative bacteria in plantar skin increased. At the species level, metagenome sequencing analyses showed Moraxella osloensis to be a representative core strain in the high-risk group. The major microbial metabolites affecting diabetic skin lesions were increased amino acid metabolites, and antibiotic resistance genes in microorganisms were abundant. Skin microbiota from high-risk patients induced more inflammatory cell infiltration, similar to the lipopolysaccharide (LPS)-stimulated response, which was inhibited by Toll-like receptor 4 (TLR4) antagonists. CONCLUSIONS: The skin microbiome in patients with diabetes undergoes dynamic changes at taxonomic and functional levels with the progression of diabetic complications. The increase in gram-negative bacteria on the skin surface through LPS-TLR4 signal transduction could induce inflammatory response in early diabetic skin lesions.

Plasmon-Enhanced Fluorescence of Single Quantum Dots Immobilized in Optically Coupled Aluminum Nanoholes.

Fluorescence-based optical sensing techniques have continually been explored for single-molecule detection targeting myriad biomedical applications. Improving signal-to-noise ratio remains a prioritized effort to enable unambiguous detection at single-molecule level. Here, we report a systematic simulation-assisted optimization of plasmon-enhanced fluorescence of single quantum dots based on nanohole arrays in ultrathin aluminum films. The simulation is first calibrated by referring to the measured transmittance in nanohole arrays and subsequently used for guiding their design. With an optimized combination of nanohole diameter and depth, the variation of the square of simulated average volumetric electric field enhancement agrees excellently with that of experimental photoluminescence enhancement over a large range of nanohole periods. A maximum 5-fold photoluminescence enhancement is statistically achieved experimentally for the single quantum dots immobilized at the bottom of simulation-optimized nanoholes in comparison to those cast-deposited on bare glass substrate. Hence, boosting photoluminescence with optimized nanohole arrays holds promises for single-fluorophore-based biosensing.

Sestrin 2 Deficiency Exacerbates Noise-Induced Cochlear Injury Through Inhibiting ULK1/Parkin-Mediated Mitophagy.

Aims: Noise damage to auditory hair cells is associated with oxidative stress and mitochondrial dysfunction. This study aimed to investigate the possible effect of sestrin 2 (SESN2), an endogenous antioxidant protein, on noise-induced hearing loss (NIHL) and the underlying mechanisms. Results: We identified SESN2 as a protective factor against oxidative stress in NIHL through activation of Parkin-mediated mitophagy. Consistently, SESN2 expression was increased and mitophagy was induced during the early stage after a temporary threshold shift due to noise exposure or hydrogen peroxide(H2O2) stimulation; conversely, SESN2 deficiency blocked mitophagy and exacerbated acoustic trauma. Mechanistically, SESN2 interacted with Unc-51-like protein kinase 1(ULK1), promoting ULK1 protein-level stabilization by interfering with its proteasomal degradation. This stabilization is essential for mitophagy initiation, since restoring ULK1 expression in SESN2-silenced cells rescued mitophagy defects. Innovation and Conclusion: Our results provide novel insights regarding SESN2 as a therapeutic target against noise-induced cochlear injury, possibly through improved mitophagy. Antioxid. Redox Signal. 38, 115-136.

Effect of Remimazolam Tosilate on Respiratory Depression in Elderly Patients Undergoing Gastroscopy: A Multicentered, Prospective, and Randomized Study.

Background: Remimazolam tosilate (RT) is a new type of γ-aminobutyric acid subtype A (GABAA) receptor agonist, having the possibility to be an ideal sedative drug for procedural sedation. At present, there are few studies on the effect of RT on respiratory depression in elderly patients. We aimed to evaluate the effect of RT on respiratory depression in elderly patients undergoing gastroscopy. Methods: This prospective, randomized, single-blinded trial recruited patients from eight centers in China between May 2022 and July 2022. A total of 346 elderly patients undergoing gastroscopy were randomly divided into RT group (0.2 mg/kg) or propofol group (1.5 mg/kg), respectively. The primary outcome was the incidence of respiratory depression. Secondary outcomes include the incidence of sedative-related adverse events, the success rate of sedation, time to fully alert, time to loss of consciousness (LOC), time to ready for discharge, as well as the the patients, endoscopists and anethetists' satisfaction. Results: The incidence of respiratory depression was significantly reduced in the RT group compared with the propofol group (9.8% vs 17.9%, P=0.042). The time of LOC and fully alert in the RT group were longer than that in the propofol group (P < 0.05). The incidences of hypotention (50.9% vs 32.4%, P=0.001) and hypotension requiring treatment (5.8% vs 1.7%, P=0.031) were significantly higher in the propofol group than that in the RT group. The incidence and severity of injection pain were more frequently recorded in the propofol group than that in the RT group (40.5% vs 12.1%, P<0.05). There were no statistically significant differences between the two groups in terms of sedation success rates, time to ready for discharge, endoscopists and anethetists' satisfaction and other sedative-related adverse events. Conclusion: RT may be a suitable alternative sedative agent for elderly patients undergoing gastroscopy due to its safety profile.

Research progress on the mechanism by which skin macrophage dysfunction mediates chronic inflammatory injury in diabetic skin.

Macrophages, the main immune cells in the skin, form an innate immune barrier. Under physiological conditions, skin maintains immune barrier function through macrophage phagocytosis and antigen presentation. Parenchymal and stromal cell regeneration plays an important role in skin injury repair and uses macrophage plasticity to influence and stabilize the skin microenvironment. Diabetic skin lesions are the most common diabetes complication and are involved in the early pathophysiology of diabetic foot. Therefore, studying the initial link in diabetic skin lesions is a research hot spot in the early pathogenesis of diabetic foot. Skin inflammation caused by hyperglycaemia, oxidative stress and other injuries is an important feature, but the specific mechanism is unknown. Recent studies have suggested that chronic inflammatory injury is widely involved in a variety of skin diseases, and whether it plays an important role in diabetic skin lesions is unclear. In this review, current research hotspots were combined with the pathogenesis of diabetic skin lesions and analysed from the perspectives of the physiological function of skin macrophages, the impairment of skin macrophages in diabetes, and the mechanism of chronic inflammatory injury in macrophages to provide a theoretical basis for early screening and evaluation of diabetic foot.

A Generalized Transformer-Based Pulse Detection Algorithm.

Pulse-like signals are ubiquitous in the field of single molecule analysis, e.g., electrical or optical pulses caused by analyte translocations in nanopores. The primary challenge in processing pulse-like signals is to capture the pulses in noisy backgrounds, but current methods are subjectively based on a user-defined threshold for pulse recognition. Here, we propose a generalized machine-learning based method, named pulse detection transformer (PETR), for pulse detection. PETR determines the start and end time points of individual pulses, thereby singling out pulse segments in a time-sequential trace. It is objective without needing to specify any threshold. It provides a generalized interface for downstream algorithms for specific application scenarios. PETR is validated using both simulated and experimental nanopore translocation data. It returns a competitive performance in detecting pulses through assessing them with several standard metrics. Finally, the generalization nature of the PETR output is demonstrated using two representative algorithms for feature extraction.

Docking and Activity of DNA Polymerase on Solid-State Nanopores.

Integration of motor enzymes with biological nanopores has enabled commercial DNA sequencing technology; yet studies of the similar principle applying to solid-state nanopores are limited. Here, we demonstrate the real-life monitoring of phi29 DNA polymerase (DNAP) docking onto truncated-pyramidal nanopore (TPP) arrays through both electrical and optical readout. To achieve effective docking, atomic layer deposition of hafnium oxide is employed to reduce the narrowest pore opening size of original silicon (Si) TPPs to sub-10 nm. On a single TPP with pore opening size comparable to DNAP, ionic current measurements show that a polymerase-DNA complex can temporally dock onto the TPP with a certain docking orientation, while the majority become translocation events. On 5-by-5 TPP arrays, a label-free optical detection method using Ca2+ sensitive dye, are employed to detect the docking dynamics of DNAP. The results show that this label-free detection strategy is capable of accessing the docking events of DNAP on TPP arrays. Finally, we examine the activity of docked DNAP by performing on-site rolling circle amplification to synthesize single-stranded DNA (ssDNA), which serves as a proof-of-concept demonstration of utilizing this docking scheme for emerging nanopore sensing applications.

Extracellular Hsp90α, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes.

INTRODUCTION: Atherosclerosis is the main pathological change in diabetic angiopathy, and vascular inflammation plays an important role in early atherosclerosis. Extracellular heat shock protein 90 (eHsp90) is secreted into the serum and is involved in various physiological and pathophysiological processes. However, the specific mechanism of eHsp90 in early atherosclerosis remains unclear. This study explored the relationship between Hsp90 and diabetic lower extremity arterial disease and investigated the expression of eHsp90 in vascular endothelial cells under environmental stimulation and the function and mechanism of eHsp90α involved in diabetic atherosclerosis. RESEARCH DESIGN AND METHODS: One hundred and three selected patients were divided into three groups: the diabetes mellitus group (n=27), the diabetic lower extremity arterial disease group (n=46), and the diabetic critical limb ischemia group (n=30). The relationships among serum Hsp90, oxidative stress indexes, and patient outcomes and the correlations among the indexes were analyzed. H&E staining and immunohistochemistry were used to observe the vasculature of amputated feet from patients with diabetic foot. An oxidative stress endothelial injury model was established under high glucose in vitro to explore the role of eHsp90 release in atherosclerosis progression. RESULTS: The level of serum Hsp90 was upregulated with aggravation of diabetic vascular disease. Hsp90α was correlated with malondialdehyde to some extent and was an independent risk factor in the progression of diabetic vascular disease, with predictive ability. The expression area of Hsp90α was consistent with the area of inflammatory infiltration in the vessel lumen. Vascular endothelial cells were found to increase eHsp90α secretion under stress. Then inhibition of eHsp90α can reduce the degree of cellular inflammation and damage. Endothelial cell-conditioned medium and recombinant human Hsp90α increased monocyte migration via the low-denisity lipoprotein receptor-related protein 1 (LRP1) receptor to promote disease progression. CONCLUSIONS: eHsp90α plays a critical role in the early inflammatory injury stage of atherosclerosis. TRIAL REGISTRATION NUMBER: NCT04787770.

Self-Limited Formation of Bowl-Shaped Nanopores for Directional DNA Translocation.

Solid-state nanopores of on-demand dimensions and shape can facilitate desired sensor functions. However, reproducible fabrication of arrayed nanopores of predefined dimensions remains challenging despite numerous techniques explored. Here, bowl-shaped nanopores combining properties of ultrathin membrane and tapering geometry are manufactured using a self-limiting process developed on the basis of standard silicon technology. The upper opening of the bowl-nanopores is 60-120 nm in diameter, and the bottom orifice reaches sub-5 nm. Current-voltage characteristics of the fabricated bowl-nanopores display insignificant rectification indicating weak ionic selectivity, in accordance to numerical simulations showing minor differences in electric field and ionic velocity upon the reversal of bias voltages. Simulations reveal, concomitantly, high-momentum electroosmotic flow downward along the concave nanopore sidewall. Collisions between the left and right tributaries over the bottom orifice drive the electroosmotic flow both up into the nanopore and down out of the nanopore through the orifice. The resultant asymmetry in electrophoretic-electroosmotic force is considered the cause responsible for the experimentally observed strong directionality in λ-DNA translocation with larger amplitude, longer duration, and higher frequencies for the downward movements from the upper opening than the upward ones from the orifice. Thus, the resourceful silicon nanofabrication technology is shown to enable nanopore designs toward enriching sensor applications.

A Guide to Signal Processing Algorithms for Nanopore Sensors.

Nanopore technology holds great promise for a wide range of applications such as biomedical sensing, chemical detection, desalination, and energy conversion. For sensing performed in electrolytes in particular, abundant information about the translocating analytes is hidden in the fluctuating monitoring ionic current contributed from interactions between the analytes and the nanopore. Such ionic currents are inevitably affected by noise; hence, signal processing is an inseparable component of sensing in order to identify the hidden features in the signals and to analyze them. This Guide starts from untangling the signal processing flow and categorizing the various algorithms developed to extracting the useful information. By sorting the algorithms under Machine Learning (ML)-based versus non-ML-based, their underlying architectures and properties are systematically evaluated. For each category, the development tactics and features of the algorithms with implementation examples are discussed by referring to their common signal processing flow graphically summarized in a chart and by highlighting their key issues tabulated for clear comparison. How to get started with building up an ML-based algorithm is subsequently presented. The specific properties of the ML-based algorithms are then discussed in terms of learning strategy, performance evaluation, experimental repeatability and reliability, data preparation, and data utilization strategy. This Guide is concluded by outlining strategies and considerations for prospect algorithms.

Deep Learning of Nanopore Sensing Signals Using a Bi-Path Network.

Temporal changes in electrical resistance of a nanopore sensor caused by translocating target analytes are recorded as a sequence of pulses on current traces. Prevalent algorithms for feature extraction in pulse-like signals lack objectivity because empirical amplitude thresholds are user-defined to single out the pulses from the noisy background. Here, we use deep learning for feature extraction based on a bi-path network (B-Net). After training, the B-Net acquires the prototypical pulses and the ability of both pulse recognition and feature extraction without a priori assigned parameters. The B-Net is evaluated on simulated data sets and further applied to experimental data of DNA and protein translocation. The B-Net results are characterized by small relative errors and stable trends. The B-Net is further shown capable of processing data with a signal-to-noise ratio equal to 1, an impossibility for threshold-based algorithms. The B-Net presents a generic architecture applicable to pulse-like signals beyond nanopore currents.

Surfactant-Free Stabilization of Aqueous Graphene Dispersions Using Starch as a Dispersing Agent.

Attention to graphene dispersions in water with the aid of natural polymers is increasing with improved awareness of sustainability. However, the function of biopolymers that can act as dispersing agents in graphene dispersions is not well understood. In particular, the use of starch to disperse pristine graphene materials deserves further investigation. Here, we report the processing conditions of aqueous graphene dispersions using unmodified starch. We have found that the graphene content of the starch-graphene dispersion is dependent on the starch fraction. The starch-graphene sheets are few-layer graphene with a lateral size of 3.2 µm. Furthermore, topographical images of these starch-graphene sheets confirm the adsorption of starch nanoparticles with a height around 5 nm on the graphene surface. The adsorbed starch nanoparticles are ascribed to extend the storage time of the starch-graphene dispersion up to 1 month compared to spontaneous aggregation in a nonstabilized graphene dispersion without starch. Moreover, the ability to retain water by starch is reduced in the presence of graphene, likely due to environmental changes in the hydroxyl groups responsible for starch-water interactions. These findings demonstrate that starch can disperse graphene with a low oxygen content in water. The aqueous starch-graphene dispersion provides tremendous opportunities for environmental-friendly packaging applications.

SCN11A gene deletion causes sensorineural hearing loss by impairing the ribbon synapses and auditory nerves.

BACKGROUND: The SCN11A gene, encoded Nav1.9 TTX resistant sodium channels, is a main effector in peripheral inflammation related pain in nociceptive neurons. The role of SCN11A gene in the auditory system has not been well characterized. We therefore examined the expression of SCN11A in the murine cochlea, the morphological and physiological features of Nav1.9 knockout (KO) ICR mice. RESULTS: Nav1.9 expression was found in the primary afferent endings beneath the inner hair cells (IHCs). The relative quantitative expression of Nav1.9 mRNA in modiolus of wild-type (WT) mice remains unchanged from P0 to P60. The number of presynaptic CtBP2 puncta in Nav1.9 KO mice was significantly lower than WT. In addition, the number of SGNs in Nav1.9 KO mice was also less than WT in the basal turn, but not in the apical and middle turns. There was no lesion in the somas and stereocilia of hair cells in Nav1.9 KO mice. Furthermore, Nav1.9 KO mice showed higher and progressive elevated ABR threshold at 16 kHz, and a significant increase in CAP thresholds. CONCLUSIONS: These data suggest a role of Nav1.9 in regulating the function of ribbon synapses and the auditory nerves. The impairment induced by Nav1.9 gene deletion mimics the characters of cochlear synaptopathy.

Oridonin ameliorates noise-induced hearing loss by blocking NLRP3 - NEK7 mediated inflammasome activation.

Inflammation is involved in noise-induced hearing loss (NIHL), but the mechanism is still unknown. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which triggers the inflammatory cascade, has been implicated in several inflammatory diseases in response to oxidative stress. However, whether the NLRP3 inflammasome is a key factor for permanent NIHL is still unknown. In this study, quantitative real-time polymerase chain reaction (qPCR), western blot, and enzyme-linked immunosorbent assays (ELISAs) demonstrated that the expression levels of activated caspase-1, interleukin (IL)-1ß, IL-18, and NLRP3 were significantly increased in the cochleae of mice exposed to broadband noise (120 dB) for 4 h, compared with the control group. These results indicate that the activation of inflammasomes in the cochleae of mice during the pathological process of NIHL as well as NLRP3, a sensor protein of reactive oxygen species (ROS), may be key factors for inflammasome assembly and subsequent inflammation in cochleae. Moreover, many recent studies have revealed that NEK7 is an important component and regulator of NLRP3 inflammasomes by interacting with NLRP3 directly and that these interactions can be interrupted by oridonin. Here, we further determined that treatment with oridonin could indeed interrupt the interaction between NLRP3 and NEK7 as well as inhibit the downstream inflammasome activation in mouse cochleae after noise exposure. Furthermore, we tested anakinra, another inflammatory inhibitor, and it was shown to partially alleviate the degree of hearing impairment in some frequencies in an NIHL mouse model. These discoveries suggest that inhibiting NLRP3 inflammasomes and the downstream signaling pathway may provide a new strategy for the clinical treatment of NIHL.

The role of the microbiome in diabetes mellitus.

The microbiome is greatly significant for immune system development and homeostasis. Dysbiosis in gut microbial composition and function is linked to immune responses and the development of metabolic diseases, including diabetes mellitus (DM). However, skin microbiome changes in diabetic patients and their role in DM are poorly elucidated. In this review, we summarize recent findings about the association between the gut and skin microbiota and DM, highlighting their roles in the proinflammatory status of DM. Moreover, although there is evidence that the connection between the gut and skin causes the same activated innate immune response, additional studies are needed to explore the mechanism. These findings might inform future DM prevention, diagnosis and treatment.

Dynamics of DNA Clogging in Hafnium Oxide Nanopores.

Interfacing solid-state nanopores with biological systems has been exploited as a versatile analytical platform for analysis of individual biomolecules. Although clogging of solid-state nanopores due to nonspecific interactions between analytes and pore walls poses a persistent challenge in attaining the anticipated sensing efficacy, insufficient studies focus on elucidating the clogging dynamics. Herein, we investigate the DNA clogging behavior by passing double-stranded (ds) DNA molecules of different lengths through hafnium oxide(HfO2)-coated silicon (Si) nanopore arrays, at different bias voltages and electrolyte pH values. Employing stable and photoluminescent-free HfO2/Si nanopore arrays permits a parallelized visualization of DNA clogging with confocal fluorescence microscopy. We find that the probability of pore clogging increases with both DNA length and bias voltage. Two types of clogging are discerned: persistent and temporary. In the time-resolved analysis, temporary clogging events exhibit a shorter lifetime at higher bias voltage. Furthermore, we show that the surface charge density has a prominent effect on the clogging probability because of electrostatic attraction between the dsDNA and the HfO2 pore walls. An analytical model based on examining the energy landscape along the DNA translocation trajectory is developed to qualitatively evaluate the DNA-pore interaction. Both experimental and theoretical results indicate that the occurrence of clogging is strongly dependent on the configuration of translocating DNA molecules and the electrostatic interaction between DNA and charged pore surface. These findings provide a detailed account of the DNA clogging phenomenon and are of practical interest for DNA sensing based on solid-state nanopores.