Gut microbial alterations in arginine metabolism determine bone mechanical adaptation.

Although mechanical loading is essential for maintaining bone health and combating osteoporosis, its practical application is limited to a large extent by the high variability in bone mechanoresponsiveness. Here, we found that gut microbial depletion promoted a significant reduction in skeletal adaptation to mechanical loading. Among experimental mice, we observed differences between those with high and low responses to exercise with respect to the gut microbial composition, in which the differential abundance of Lachnospiraceae contributed to the differences in bone mechanoresponsiveness. Microbial production of L-citrulline and its conversion into L-arginine were identified as key regulators of bone mechanoadaptation, and administration of these metabolites enhanced bone mechanoresponsiveness in normal, aged, and ovariectomized mice. Mechanistically, L-arginine-mediated enhancement of bone mechanoadaptation was primarily attributable to the activation of a nitric-oxide-calcium positive feedback loop in osteocytes. This study identifies a promising anti-osteoporotic strategy for maximizing mechanical loading-induced skeletal benefits via the microbiota-metabolite axis.

Rescuing SERCA2 pump deficiency improves bone mechano-responsiveness in type 2 diabetes by shaping osteocyte calcium dynamics.

Type 2 diabetes (T2D)-related fragility fractures represent an increasingly tough medical challenge, and the current treatment options are limited. Mechanical loading is essential for maintaining bone integrity, although bone mechano-responsiveness in T2D remains poorly characterized. Herein, we report that exogenous cyclic loading-induced improvements in bone architecture and strength are compromised in both genetically spontaneous and experimentally-induced T2D mice. T2D-induced reduction in bone mechano-responsiveness is directly associated with the weakened Ca2+ oscillatory dynamics of osteocytes, although not those of osteoblasts, which is dependent on PPARα-mediated specific reduction in osteocytic SERCA2 pump expression. Treatment with the SERCA2 agonist istaroxime was demonstrated to improve T2D bone mechano-responsiveness by rescuing osteocyte Ca2+ dynamics and the associated regulation of osteoblasts and osteoclasts. Moreover, T2D-induced deterioration of bone mechano-responsiveness is blunted in mice with osteocytic SERCA2 overexpression. Collectively, our study provides mechanistic insights into T2D-mediated deterioration of bone mechano-responsiveness and identifies a promising countermeasure against T2D-associated fragility fractures.

Alcohol imination catalyzed by carbon nanostructures synthesized by C(sp2)-C(sp3) free radical coupling.

Imines are important intermediates for synthesizing various fine chemicals, with the disadvantage of requiring the use of expensive metal-containing catalysts. We report that the dehydrogenative cross-coupling of phenylmethanol and benzylamine (or aniline) directly forms the corresponding imine with a yield of up to 98%, and water as the sole by-product, in the presence of a stoichiometric base, using carbon nanostructures as the "green" metal-free carbon catalysts with high spin concentrations, which is synthesized by C(sp2)-C(sp3) free radical coupling reactions. The catalytic mechanism is attributed to the unpaired electrons of carbon catalysts to reduce O2 to O2·-, which triggers the oxidative coupling reaction to form imines, whereas the holes in the carbon catalysts receive electrons from the amine to restore the spin states. This is supported by density functional theory calculations. This work will open up an avenue for synthesizing carbon catalysts and offer great potential for industrial applications.

Electron Spin Catalysis with Graphene Belts.

Here, we report kinetic studies using electron spin resonance spectroscopy on spin catalysis reactions caused by using graphene belts which were synthesized by a radical coupling method. The results show that σ-type free radical species provide the dominant sites for catalytic activity through the spin-spin interaction, although there are some other influencing factors. The spin catalysis mechanism can be applied both in the oxygen reduction reaction (ORR) and in organic synthesis. The graphene belt spin catalyst shows excellent performance with a high ORR half-wave potential of 0.81 V and long-term stability with almost no loss of activity after 50 000 cycles in alkaline media. It also shows excellent performance in a benzylamine coupling with molecular oxygen to generate the corresponding imine at an average conversion of ≈97.7 % and an average yield of ≈97.9 %. This work opens up a new research direction for understanding aerobic processes in the field of spin catalysis.

Progress in the Development of Detection Strategies Based on Olfactory and Gustatory Biomimetic Biosensors.

The biomimetic olfactory and gustatory biosensing devices have broad applications in many fields, such as industry, security, and biomedicine. The development of these biosensors was inspired by the organization of biological olfactory and gustatory systems. In this review, we summarized the most recent advances in the development of detection strategies for chemical sensing based on olfactory and gustatory biomimetic biosensors. First, sensing mechanisms and principles of olfaction and gustation are briefly introduced. Then, different biomimetic sensing detection strategies are outlined based on different sensing devices functionalized with various molecular and cellular components originating from natural olfactory and gustatory systems. Thereafter, various biomimetic olfactory and gustatory biosensors are introduced in detail by classifying and summarizing the detection strategies based on different sensing devices. Finally, the future directions and challenges of biomimetic biosensing development are proposed and discussed.

Odor-induced modification of oscillations and related theta-higher gamma coupling in olfactory bulb neurons of awake and anesthetized rats.

Olfactory gamma oscillations (40-100 Hz) are generated spontaneously in animals and represent the activity of local olfactory bulb (OB) networks, which play important roles in cognitive mechanisms. In addition, high-frequency oscillations (HFO, 130-180 Hz) have attracted widespread attention and are novel neuronal oscillations with a frequency range closer to high gamma oscillations (60-100 Hz, HGOs). Both HGOs and HFOs are distinctly regulated by θ rhythm in the hippocampus. To understand their mediation mechanisms in the OB, we investigated whether local field potential (LFP) oscillations including HGOs and HFOs and even their coupling with theta rhythm are modified by odor stimulation in both freely moving and anesthetized rats. Therefore, we combined electrophysiological technology and cross-frequency coupling analysis approaches to determine the difference in the odor-modulated LFP oscillations between awake and anesthetized rats. The obtained results indicate that LFP oscillations including HGOs and HFOs were differently modified by odor stimulation in animals of both states. However, θ-HGO and θ-HFO coupling were modified in only awake animals. It is suggested that these oscillations and their interactions with theta oscillations may play crucial roles in olfactory network activity. This could pave the way for further understanding the underlying mechanisms of oscillations in OB neurons towards odor sensation.

In Vivo Bioelectronic Nose Based on a Bioengineered Rat Realizes the Detection and Classification of Multiodorants.

Inspired by the powerful capability of the biological olfactory system, we developed an in vivo bioelectronic nose based on a bioengineered rat by recording electrophysiological-responsive signals from the olfactory bulb with implanted multichannel microelectrodes. The bioengineered rat was prepared by overexpressing a selected olfactory receptor (OR3) on the rat olfactory epithelium, and multichannel electrophysiological signals were obtained from the mitral/tufted (M/T) cell population of the olfactory bulb. The classification of target multiodorants was realized by analyzing the redundant stimuli-responsive firing information. Ligand odorants induced significant firing changes with specific response patterns compared with nonligand odorants. The responsive curves were dependent on the concentration of target ligand odorants ranging from 10-6 to 10-3 M, and the detection limit was as low as 10-5 M. In addition, different ligand odorants were successfully discriminated via principal component analysis. This in vivo bioelectronic nose provides a novel approach for the detection of specific target odorants and has promising application potential in the field of rapid on-site odor discrimination.

Label-Free Detection of Saxitoxin with Field-Effect Device-Based Biosensor.

Saxitoxin (STX) is a highly toxic and widely distributed paralytic shellfish toxin (PSP), posing a serious hazard to the environment and human health. Thus, it is highly required to develop new STX detection approaches that are convenient, desirable, and affordable. This study presented a label-free electrolyte-insulator-semiconductor (EIS) sensor covered with a layer-by-layer developed positively charged Poly (amidoamine) (PAMAM) dendrimer. An aptamer (Apt), which is sensitive to STX was electrostatically immobilized onto the PAMAM dendrimer layer. This results in an Apt that is preferably flat inside a Debye length, resulting in less charge-screening effect and a higher sensor signal. Capacitance-voltage and constant-capacitance measurements were utilized to monitor each step of a sensor surface variation, namely, the immobilization of PAMAM dendrimers, Apt, and STX. Additionally, the surface morphology of PAMAM dendrimer layers was studied by using atomic force microscopy and scanning electron microscopy. Fluorescence microscopy was utilized to confirm that Apt was successfully immobilized on a PAMAM dendrimer-modified EIS sensor. The results presented an aptasensor with a detection range of 0.5-100 nM for STX detection and a limit of detection was 0.09 nM. Additionally, the aptasensor demonstrated high selectivity and 9-day stability. The extraction of mussel tissue indicated that an aptasensor may be applied to the detection of STX in real samples. An aptasensor enables marine toxin detection in a rapid and label-free manner.

Preparation and application of taste bud organoids in biomedicine towards chemical sensation mechanisms.

Taste is one of the most basic and important sensations that is able to monitor the food quality and avoid intake of potential danger materials. Whether as an inevitable symptom of aging or a complication of cancer treatment, taste loss very seriously affects the patient's life quality. Taste bud organoids provide an alternative and convenient approach for the research of taste functions and the underlying mechanisms due to their characteristics of availability, strong maneuverability, and high similarity to the in-vivo taste buds. This review gives a systemic and comprehensive introduction to the preparation and application of taste bud organoids towards chemical sensing mechanisms. First, the basic structures and functions of taste buds will be briefly introduced. Then, the currently available approaches for the preparation of taste bud organoids are summarized and discussed, which are mainly divided into two categories, that is, the stem/progenitor cell-derived approach and the tissue-derived approach. Next, different applications of taste bud organoids in biomedicine are outlined based on their central roles such as disease modeling, biological sensing, gene regulation, and signal transduction. Finally, the current challenges, future development trends, and prospects of research in taste bud organoids are proposed and discussed.

An electrochemical PAH-modified aptasensor for the label-free and highly-sensitive detection of saxitoxin.

Saxitoxin (STX), is one of the most dangerous and widespread paralytic shellfish toxins, causing a severe threat to the ecosystem and human health. So, it is important and highly essential to develop novel techniques for STX detection in a convenient, desirable, and low-cost manner. Herein, this study developed an electrolyte-insulator-semiconductor (EIS) sensor covered with a layer-by-layer prepared, positively-charged weak polyelectrolyte layer of poly (allylamine hydrochloride) (PAH) for the label-free detection of STX. The specific aptamer (Apt) sensitive to STX was electrostatically adsorbed onto the PAH layer. This leads to a preferentially flat orientation of the Apt within the Debye length, thus yielding a reduced charge-screening influence and a higher sensor signal. Each step of sensor surface modification, i.e. PAH adsorption, immobilization of Apt, and attachment of STX, was monitored by capacitance-voltage (C-V) and constant-capacitance (ConCap) measurements. Furthermore, atomic force microscopy (AFM) was employed to characterize the surface morphology and roughness of the PAH layer. Fluorescence microscopy was used to confirm the effective immobilization of Apt onto the PAH-modified EIS sensor. The results showed that the detection range of this aptasensor for STX detection was 0.5-100 nM and the detection limit was as low as 0.05 nM. Furthermore, this aptasensor showed good selectivity and 9 days' stability. The mussel tissue extraction test suggested that this aptasensor can be used to detect STX in real samples. This aptasensor provides a convenient approach for moderate, rapid, and label-free detection of marine biological toxins.

Olfactory Optogenetics: Light Illuminates the Chemical Sensing Mechanisms of Biological Olfactory Systems.

The mammalian olfactory system has an amazing ability to distinguish thousands of odorant molecules at the trace level. Scientists have made great achievements on revealing the olfactory sensing mechanisms in decades; even though many issues need addressing. Optogenetics provides a novel technical approach to solve this dilemma by utilizing light to illuminate specific part of the olfactory system; which can be used in all corners of the olfactory system for revealing the olfactory mechanism. This article reviews the most recent advances in olfactory optogenetics devoted to elucidate the mechanisms of chemical sensing. It thus attempts to introduce olfactory optogenetics according to the structure of the olfactory system. It mainly includes the following aspects: the sensory input from the olfactory epithelium to the olfactory bulb; the influences of the olfactory bulb (OB) neuron activity patterns on olfactory perception; the regulation between the olfactory cortex and the olfactory bulb; and the neuromodulation participating in odor coding by dominating the olfactory bulb. Finally; current challenges and future development trends of olfactory optogenetics are proposed and discussed.

An Electrochemical Ti3C2Tx Aptasensor for Sensitive and Label-Free Detection of Marine Biological Toxins.

Saxitoxin (STX) belongs to the family of marine biological toxins, which are major contaminants in seafood. The reference methods for STX detection are mouse bioassay and chromatographic analysis, which are time-consuming, high costs, and requirement of sophisticated operation. Therefore, the development of alternative methods for STX analysis is urgent. Electrochemical analysis is a fast, low-cost, and sensitive method for biomolecules analysis. Thus, in this study, an electrolyte-insulator-semiconductor (EIS) sensor based on aptamer-modified two-dimensional layered Ti3C2Tx nanosheets was developed for STX detection. The high surface area and rich functional groups of MXene benefited the modification of aptamer, which had specific interactions with STX. Capacitance-voltage (C-V) and constant-capacitance (ConCap) measurement results indicated that the aptasensor was able to detect STX with high sensitivity and good specificity. The detection range was 1.0 nM to 200 nM and detection limit was as low as 0.03 nM. Moreover, the aptasensor was found to have a good selectivity and two-week stability. The mussel tissue extraction test suggested the potential application of this biosensor in detecting STX in real samples. This method provides a convenient approach for low-cost, rapid, and label-free detection of marine biological toxins.

Synthesis of a Removable Cytoprotective Exoskeleton by Tea Polyphenol Complexes for Living Cell Encapsulation.

Cell encapsulation is a chemical tool for endowing living cells with exogenous properties and enhancing their in vitro tolerance against lethal factors, which has shown promising prospects and potential applications in many fields such as cell transplantation, drug delivery, and tissue engineering. One-pot precipitation of a polyphenol-metal complex on cells protects cells from UV irradiation and lytic enzymes. However, the involvement of metal ions brings side effects on cell viability and growth. Moreover, an external removal agent is needed for cell division and growth. Herein, a polymer shell composed of hydrogen bonded constituents without affecting cell viability and growth by the precipitation of tea polyphenol and polyvinyl pyrrolidone is reported. The formation of the polymer shell was verified by the Au nanoparticle's laser scanning confocal reflectance and quartz crystal microbalance measurement. The thickness of the shell was managed by the concentration of the complex. When exposed to UV irradiation for 15 or 30 min, polymer-coating-protected Saccharomyces cerevisiae (yeast) had much higher cell viability than the native one. Exposed to a high temperature environment (60 °C), most of the coated yeasts survived in contrast to uncoated ones. For the cell division and growth curve, the polymer coating with various thicknesses had no difference to the native one, which indicated no suppression of cell growth and no external side effects involved. As applied to mammalian HeLa cells under UV irradiation for 15 min, the coated cells had an obvious higher cell viability than that of untreated ones. Therefore, the tea polyphenol-poly(vinylpyrrolidone) shell is a versatile tool for chemically controlling the external properties of cells without side effects on cell viability and growth.

Recent progress in micro/nano biosensors for shellfish toxin detection.

Shellfish toxins, as one kind of marine toxin, have attracted worldwide attention due to their severe threat to food safety and human health. Therefore, it is highly essential and urgent to develop a low-cost and convenient method to detect these toxins. With the rapid advance in microfabrication processes, micro/nano biosensors provide novel approaches to address this issue. In addition to their features of low cost, portability, easy operation, high efficiency and high bioactivity, micro/nano biosensors have great potential to realize on-the-spot, rapid detection of shellfish toxins. This review focuses on the most recent advances in the development of micro/nano biosensors for shellfish toxin detection. These biosensors are mainly classified into five categories according to their transducer detection principles, which include optical devices, electrochemical sensors, electrochemiluminescence, field-effect transistors, and acoustic devices. Sensor strategies, toxin analytes, biosensitive elements, coupling methods and field detection performance are highlighted to discuss the applications of shellfish toxin detection. With advances in sensor technology, biomaterials, microfabrication and miniaturized electronics, micro/nano biosensors applied to in-field fast detection of shellfish toxins are expected to play a critical role in food safety, environmental monitoring, and foreign trade in the foreseeable future. Finally, the current challenges and future development trends of micro/nano biosensors for shellfish toxin detection are discussed.

LiMnO2@rGO nanocomposites for high-performance lithium-ion battery cathodes.

Composites of reduced graphene oxide (rGO) and layered LiMnO2 (LiMnO2@rGO) were successfully synthesized and demonstrated via a one-pot hydrothermal route at a temperature of 200 °C for 12 h. The obtained LiMnO2@rGO was characterized by x-ray diffraction, transmission electron microscopy, Fourier transform infrared spectra and Raman spectra. Electrochemical performance tests of LiMnO2@rGO and LiMnO2 cathodes exhibited that after graphene oxide was loaded, the discharge capacity and cycling performance were greatly improved, the maximum discharge capacity reached 185.6 mAh g-1 at the current density of 100 mA g-1 with retention capacity higher than 80% even after 100 cycles between 2 and 4.5 V vs. Li+/Li, which is much better than most previous reports (table S1). The principles of the corresponding phenomenon were fully explained by the low electron conductivity, high structural stability and lithium diffusion coefficient of LiMnO2@rGO, which was also proved by cyclic voltammetry testing, electrochemical impedance spectroscopy and relevant equivalent circuit fitting. This work not only provides significant insights into the relationship between the structure and electrochemical performance of electrodes, but also shows the great potential of LiMnO2@rGO composite electrodes applied as the cathode materials of lithium-ion batteries.

Applications of Functional Metal-Organic Frameworks in Biosensors.

In recent decades, fast advancements in the fields of metal-organic frameworks (MOFs) are providing unprecedented opportunities for the development of novel functional MOFs for various biosensing applications. Exciting progress is achieved due to the combination of MOFs with various functional components, which introduces novel structures and new features to the MOFs-based biosensing applications, such as higher stability, higher sensitivity, higher flexibility, and higher specificity. This review aims to be a comprehensive summary of the most recent advances in the development of functional MOFs for various biosensing applications, placing special attention on important contributions in recent 3 years. In this review, the most recent developments in design and synthesis of functional MOFs for biosensing applications are summarized. MOFs-based biosensing applications are outlined according to the central roles of MOFs in biosensors, which include carriers of sensitive elements, enzyme-mimic elements, electrochemical signaling, optical signaling, and gas sensing. Finally, the current challenges and future development trends of functional MOFs for biosensing applications are proposed and discussed.

Electrochemically Activated Conductive Ni-Based MOFs for Non-enzymatic Sensors Toward Long-Term Glucose Monitoring.

Continuous intensive monitoring of glucose is one of the most important approaches in recovering the quality of life of diabetic patients. One challenge for electrochemical enzymatic glucose sensors is their short lifespan for continuous glucose monitoring. Therefore, it is of great significance to develop non-enzymatic glucose sensors as an alternative approach for long-term glucose monitoring. This study presented a highly sensitive and selective electrochemical non-enzymatic glucose sensor using the electrochemically activated conductive Ni3(2,3,6,7,10,11-hexaiminotriphenylene)2 MOFs as sensing materials. The morphology and structure of the MOFs were investigated by scanning SEM and FTIR, respectively. The performance of the activated electrode toward the electrooxidation of glucose in alkaline solution was evaluated with cyclic voltammetry technology in the potential range from 0.2 V to 0.6 V. The electrochemical activated Ni-MOFs exhibited obvious anodic (0.46 V) and cathodic peaks (0.37 V) in the 0.1 M NaOH solution due to the Ni(II)/Ni(III) transfer. A linear relationship between the glucose concentrations (ranging from 0 to 10 mM) and anodic peak currents with R2 = 0.954 was obtained. It was found that the diffusion of glucose was the limiting step in the electrochemical reaction. The sensor exhibited good selectivity toward glucose in the presence of 10-folds uric acid and ascorbic acid. Moreover, this sensor showed good long-term stability for continuous glucose monitoring. The good selectivity, stability, and rapid response of this sensor suggests that it could have potential applications in long-term non-enzymatic blood glucose monitoring.

Scanning Electrochemical Photometric Sensors for Label-Free Single-Cell Imaging and Quantitative Absorption Analysis.

A new photoelectrochemical imaging method termed scanning electrochemical photometric sensor (SEPS) is proposed in this work. It was derived from light-addressable potentiometric sensor (LAPS) and scanning photoinduced impedance microscopy (SPIM) using a front-side laser illumination at a field-effect structure. When the laser beam scans across the sensor substrate, local photocurrent changes at inversion due to the light absorption of analytes can be recorded. It will be shown that SEPS could be used for label-free living cell imaging with micro-resolution as well as real-time quantitative absorption analysis, which would broaden the applications of traditional LAPS/SPIM from potentiometric/impedance measurements to local optical analysis.

A sperm-cell-based biosensor using a fluorescence probe for responsive signal readout toward bitter flavor detection.

Bitter flavor detection has attracted extensive attention in industry and basic research due to pharmacological and food safety issues. Opportunities exist to extend the conventional methods of bitter flavor evaluation in performance and operation. This study proposes a novel sperm-cell-based biosensor (SCB) that utilizes living mouse spermatids as the primary sensing element, employs Fluo 4-AM as a transducer and works in conjunction with flow cytometry to realize the rapid quantitative detection of bitter compounds. The preparation conditions of the SCB were optimized with different quinine concentrations, and quinine and two other bitter compounds were employed to verify the sensing properties. Furthermore, the responses of the SCB to five basic flavor types were characterized to evaluate the sensor specificity. The SCB enabled preliminary classification of three bitter substances by using principal component analysis (PCA). The results revealed that the SCB is convenient, inexpensive and easy to use and can respond to bitter compounds in a dose-dependent manner with high sensitivity, high specificity and a low limit of detection, providing a novel and efficient approach for comprehensive evaluation of bitter substances in many fields, such as the pharmaceutical and food industries and in biosafety.

Label-Free Detection of E. coli O157:H7 DNA Using Light-Addressable Potentiometric Sensors with Highly Oriented ZnO Nanorod Arrays.

The detection of bacterial deoxyribonucleic acid (DNA) is of great significance in the quality control of food and water. In this study, a light-addressable potentiometric sensor (LAPS) deposited with highly oriented ZnO nanorod arrays (NRAs) was used for the label-free detection of single-stranded bacterial DNA (ssDNA). A functional, sensitive surface for the detection of Escherichia coli (E. coli) O157:H7 DNA was prepared by the covalent immobilization of the specific probe single-stranded DNA (ssDNA) on the LAPS surface. The functional surface was exposed to solutions containing the target E. coli ssDNA molecules, which allowed for the hybridization of the target ssDNA with the probe ssDNA. The surface charge changes induced by the hybridization of the probe ssDNA with the target E. coli ssDNA were monitored using LAPS measurements in a label-free manner. The results indicate that distinct signal changes can be registered and recorded to detect the target E. coli ssDNA. The lower detection limit of the target ssDNA corresponded to 1.0 × 102 colony forming units (CFUs)/mL of E. coli O157:H7 cells. All the results demonstrate that this DNA biosensor, based on the electrostatic detection of ssDNA, provides a novel approach for the sensitive and effective detection of bacterial DNA, which has promising prospects and potential applications in the quality control of food and water.