A tissue-like neurotransmitter sensor for the brain and gut.

Neurotransmitters play essential roles in regulating neural circuit dynamics both in the central nervous system as well as at the peripheral, including the gastrointestinal tract1-3. Their real-time monitoring will offer critical information for understanding neural function and diagnosing disease1-3. However, bioelectronic tools to monitor the dynamics of neurotransmitters in vivo, especially in the enteric nervous systems, are underdeveloped. This is mainly owing to the limited availability of biosensing tools that are capable of examining soft, complex and actively moving organs. Here we introduce a tissue-mimicking, stretchable, neurochemical biological interface termed NeuroString, which is prepared by laser patterning of a metal-complexed polyimide into an interconnected graphene/nanoparticle network embedded in an elastomer. NeuroString sensors allow chronic in vivo real-time, multichannel and multiplexed monoamine sensing in the brain of behaving mouse, as well as measuring serotonin dynamics in the gut without undesired stimulations and perturbing peristaltic movements. The described elastic and conformable biosensing interface has broad potential for studying the impact of neurotransmitters on gut microbes, brain-gut communication and may ultimately be extended to biomolecular sensing in other soft organs across the body.

High-brightness all-polymer stretchable LED with charge-trapping dilution.

Next-generation light-emitting displays on skin should be soft, stretchable and bright1-7. Previously reported stretchable light-emitting devices were mostly based on inorganic nanomaterials, such as light-emitting capacitors, quantum dots or perovskites6-11. They either require high operating voltage or have limited stretchability and brightness, resolution or robustness under strain. On the other hand, intrinsically stretchable polymer materials hold the promise of good strain tolerance12,13. However, realizing high brightness remains a grand challenge for intrinsically stretchable light-emitting diodes. Here we report a material design strategy and fabrication processes to achieve stretchable all-polymer-based light-emitting diodes with high brightness (about 7,450 candela per square metre), current efficiency (about 5.3 candela per ampere) and stretchability (about 100 per cent strain). We fabricate stretchable all-polymer light-emitting diodes coloured red, green and blue, achieving both on-skin wireless powering and real-time displaying of pulse signals. This work signifies a considerable advancement towards high-performance stretchable displays.

Tuning Two-Dimensional Phthalocyanine Dual Site Metal-Organic Framework Catalysts for the Oxygen Reduction Reaction.

Metal-organic frameworks (MOFs) offer an interesting opportunity for catalysis, particularly for metal-nitrogen-carbon (M-N-C) motifs by providing an organized porous structural pattern and well-defined active sites for the oxygen reduction reaction (ORR), a key need for hydrogen fuel cells and related sustainable energy technologies. In this work, we leverage electrochemical testing with computational models to study the electronic and structural properties in the MOF systems and their relationship to ORR activity and stability based on dual transitional metal centers. The MOFs consist of two M1 metals with amine nodes coordinated to a single M2 metal with a phthalocyanine linker, where M1/M2 = Co, Ni, or Cu. Co-based metal centers, in particular Ni-Co, demonstrate the highest overall activity of all nine tested MOFs. Computationally, we identify the dominance of Co sites, relative higher importance of the M2 site, and the role of layer M1 interactions on the ORR activity. Selectivity measurements indicate that M1 sites of MOFs, particularly Co, exhibit the lowest (<4%), and Ni demonstrates the highest (>46%) two-electron selectivity, in good agreement with computational studies. Direct in situ stability characterization, measuring dissolved metal ions, and calculations, using an alkaline stability metric, confirm that Co is the most stable metal in the MOF, while Cu exhibits notable instability at the M1. Overall, this study reveals how atomistic coupling of electronic and structural properties affects the ORR performance of dual site MOF catalysts and opens new avenues for the tunable design and future development of these systems for practical electrochemical applications.

Revealing the Denoising Principle of Zero-Shot N2N-Based Algorithm from 1D Spectrum to 2D Image.

Denoising is a necessary step in image analysis to extract weak signals, especially those hardly identified by the naked eye. Unlike the data-driven deep-learning denoising algorithms relying on a clean image as the reference, Noise2Noise (N2N) was able to denoise the noise image, providing sufficiently noise images with the same subject but randomly distributed noise. Further, by introducing data augmentation to create a big data set and regularization to prevent model overfitting, zero-shot N2N-based denoising was proposed in which only a single noisy image was needed. Although various N2N-based denoising algorithms have been developed with high performance, their complicated black box operation prevented the lightweight. Therefore, to reveal the working function of the zero-shot N2N-based algorithm, we proposed a lightweight Peak2Peak algorithm (P2P) and qualitatively and quantitatively analyzed its denoising behavior on the 1D spectrum and 2D image. We found that the high-performance denoising originates from the trade-off balance between the loss function and regularization in the denoising module, where regularization is the switch of denoising. Meanwhile, the signal extraction is mainly from the self-supervised characteristic learning in the data augmentation module. Further, the lightweight P2P improved the denoising speed by at least ten times but with little performance loss, compared with that of the current N2N-based algorithms. In general, the visualization of P2P provides a reference for revealing the working function of zero-shot N2N-based algorithms, which would pave the way for the application of these algorithms toward real-time (in situ, in vivo, and operando) research improving both temporal and spatial resolutions. The P2P is open-source at https://github.com/3331822w/Peak2Peakand will be accessible online access at https://ramancloud.xmu.edu.cn/tutorial.

Single-cell RNA sequencing and immune repertoire analysis revealed dynamic immune characteristics associated with peripheral blood during sepsis.

Sepsis is a potentially fatal condition arising from an abnormal immune response to an infection, which can result in organ failure and even death. To explore the mechanism underlying the dysregulated immune response during sepsis and identify potential therapeutic targets, single-cell RNA sequencing (scRNA-seq) and immune repertoire analysis were conducted to depict the cellular landscape of peripheral blood cells in septic mice. We observed significant alterations in the number and proportion of peripheral blood cell populations driven by sepsis. By combining single-cell gene expression profiles and B cell receptor (BCR) repertoire analysis, we discerned that infection inflicted serious damage on the antigen presentation ability of B cells and the diversity of BCR in a short time. In addition, we found that the cecal ligation and puncture procedure in mice inhibited the communication signals of CD4+ and CD8+ T cells and decreased the interactions between B cells and other cells. Our study provides detailed insights into the dynamic changes in the biological characteristics of peripheral blood cells driven by sepsis and provides important advances in our understanding of immune disorders during sepsis.

HAPLN3 p.T34A contributes to incomplete penetrance of moyamoya disease in Chinese carrying RNF213 p.R4810K.

BACKGROUND AND PURPOSE: The penetrance of the RNF213 p.R4810K, a founder mutation of moyamoya disease (MMD), is estimated to be only 1/150-1/300. However, the factors affecting its penetrance remain unclear. Therefore, our study aims to identify modifier genes associated with the incomplete penetrance of this founder mutation. METHODS: Whole-exome sequencing (WES) was performed on 36 participants, including 22 MMD patients and 14 non-MMD controls with RNF213 p.R4810K mutation. Fisher's exact test was used to assess the presence of genetic variants that differed significantly between MMD patients and non-MMD controls. In order to exclude false-positive results, another 55 carriers were included to perform Fisher's exact test for the selected sites in the WES discovery stage. Subsequently, human brain microvascular endothelial cells were transfected with wild-type and mutant HAPLN3 for tube formation assays and western blotting to explore the impact of candidate genes on angiogenesis. RESULTS: Analysis of variants from WES data revealed a total of 12 non-synonymous variants. Through bioinformatics analysis, the focus was on the HAPLN3 p.T34A variant with a significant p value of 0.00731 in Fisher's exact test. Validation through Sanger sequencing confirmed the presence of this variant in the WES data. In vitro experiments revealed that silencing HAPLN3 and transfecting HAPLN3 p.T34A significantly enhanced tube formation and increased the relative protein expression of vascular endothelial growth factor in endothelial cells. CONCLUSIONS: These results suggest that HAPLN3 may function as a modifier gene of RNF213 p.R4810K, promoting the development of MMD and contributing to the incomplete penetrance of MMD founder mutations.

Nanomaterial-related hemoglobin-based oxygen carriers, with emphasis on liposome and nano-capsules, for biomedical applications: current status and future perspectives.

Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases.

Organ-on-a-chip: future of female reproductive pathophysiological models.

The female reproductive system comprises the internal and external genitalia, which communicate through intricate endocrine pathways. Besides secreting hormones that maintain the female secondary sexual characteristics, it also produces follicles and offspring. However, the in vitro systems have been very limited in recapitulating the specific anatomy and pathophysiology of women. Organ-on-a-chip technology, based on microfluidics, can better simulate the cellular microenvironment in vivo, opening a new field for the basic and clinical research of female reproductive system diseases. This technology can not only reconstruct the organ structure but also emulate the organ function as much as possible. The precisely controlled fluidic microenvironment provided by microfluidics vividly mimics the complex endocrine hormone crosstalk among various organs of the female reproductive system, making it a powerful preclinical tool and the future of pathophysiological models of the female reproductive system. Here, we review the research on the application of organ-on-a-chip platforms in the female reproductive systems, focusing on the latest progress in developing models that reproduce the physiological functions or disease features of female reproductive organs and tissues, and highlighting the challenges and future directions in this field.

Indolo[2,3-b]quinoxaline as a Low Reduction Potential and High Stability Anolyte Scaffold for Nonaqueous Redox Flow Batteries.

Redox flow batteries (RFBs) are a promising stationary energy storage technology for leveling power supply from intermittent renewable energy sources with demand. A central objective for the development of practical, scalable RFBs is to identify affordable and high-performance redox-active molecules as storage materials. Herein, we report the design, synthesis, and evaluation of a new organic scaffold, indolo[2,3-b]quinoxaline, for highly stable, low-reduction potential, and high-solubility anolytes for nonaqueous redox flow batteries (NARFBs). The mixture of 2- and 3-(tert-butyl)-6-(2-methoxyethyl)-6H-indolo[2,3-b]quinoxaline exhibits a low reduction potential (-2.01 V vs Fc/Fc+), high solubility (>2.7 M in acetonitrile), and remarkable stability (99.86% capacity retention over 49.5 h (202 cycles) of H-cell cycling). This anolyte was paired with N-(2-(2-methoxyethoxy)-ethyl)phenothiazine (MEEPT) to achieve a 2.3 V all-organic NARFB exhibiting 95.8% capacity retention over 75.1 h (120 cycles) of cycling.

Metabolomics approach to growth-age discrimination in mountain-cultivated ginseng (Panax ginseng C. A. Meyer) using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

Mountain-cultivated ginseng is typically harvested after 10 years, while ginseng aged over 15 years is considered wild ginseng. This study aims to differentiate mountain-cultivated ginseng by age, as the fraudulent practice of selling low-aged cultivated ginseng disguised as high-aged one is damaging the market. In this study, LC-MS analyzed 98 ginseng samples, and multivariate statistical analysis identified patterns between samples to select influential components. Machine learning models were developed to identify ginseng samples of different ages. The untargeted metabolomic analysis clearly divided samples aged 4-20 years into three age groups. Twenty-two potential age-dependent biomarkers were discovered to differentiate the three sample groups. Three machine learning models were used to predict new samples, and the optimal model was selected. Some biomarkers could determine age phases according to the differentiation of mountain-cultivated ginseng samples. These biomarkers were thoroughly analyzed for variation trends. The machine learning models established using the screened biomarkers successfully predicted the age group of new samples.

Formation Mechanism of Flower-like Polyacrylonitrile Particles.

Flower-like polyacrylonitrile (PAN) particles have shown promising performance for numerous applications, including sensors, catalysis, and energy storage. However, the detailed formation process of these unique structures during polymerization has not been investigated. Here, we elucidate the formation process of flower-like PAN particles through a series of in situ and ex situ experiments. We have the following key findings. First, lamellar petals within the flower-like particles were predominantly orthorhombic PAN crystals. Second, branching of the lamellae during the particle formation arose from PAN's fast nucleation and growth on pre-existing PAN crystals, which was driven by the poor solubility of PAN in the reaction solvent. Third, the particles were formed to maintain a constant center-to-center distance during the reaction. The separation distance was attributed to strong electrostatic repulsion, which resulted in the final particles' spherical shape and uniform size. Lastly, we employed the understanding of the formation mechanism to tune the PAN particles' morphology using several experimental parameters including incorporating comonomers, changing temperature, adding nucleation seeds, and adjusting the monomer concentration. These findings provide important insights into the bottom-up design of advanced nanostructured PAN-based materials and controlled polymer nanostructure self-assemblies.

NGF monoclonal antibody DS002 alleviates chemotherapy-induced peripheral neuropathy in rats.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the pervasive side effects of chemotherapy, leading to poor quality of life in cancer patients. Discovery of powerful analgesics for CIPN is an urgent and substantial clinical need. Nerve growth factor (NGF), a classic neurotrophic factor, has been identified as a potential therapeutic target for pain. In this study, we generated a humanized NGF monoclonal antibody (DS002) that most effectively blocked the interaction between NGF and tropomyosin receptor kinase A (TrkA). We showed that DS002 blocked NGF binding to TrkA in a dose-dependent manner with an IC50 value of 6.6 nM; DS002 dose-dependently inhibited the proliferation of TF-1 cells by blocking the TrkA-mediated downstream signaling pathway. Furthermore, DS002 did not display noticeable species differences in its binding and blocking abilities. In three chemotherapy-induced rat models of CIPN, subcutaneous injection of DS002 produced a significant prophylactic effect against paclitaxel-, cisplatin- and vincristine-induced peripheral neuropathy. In conclusion, we demonstrate for the first time that an NGF inhibitor effectively alleviates pain in animal models of CIPN. DS002 has the potential to treat CIPN pain in the clinic.

Association of Early Increase in Body Temperature with Symptomatic Intracranial Hemorrhage and Unfavorable Outcome Following Endovascular Therapy in Patients with Large Vessel Occlusion Stroke.

INTRODUCTION: The aim of this study was to investigate for possible associations between an early increase in body temperature within 24 hours of endovascular therapy (EVT) for large vessel occlusion stroke and the presence of symptomatic intracranial hemorrhage (sICH) and other clinical outcomes. METHODS: This was a retrospective study of consecutive patients with large vessel occlusion stroke who were treated with EVT from August 2018 to June 2021. Patients were divided into two groups based on the presence of fever, as defined by a Peak Body Temperature (PBT) of ≥37.3 °C. The presence of sICH and other clinical outcomes were compared between the two groups. RESULTS: The median NIHSS admission score (IQR) was 16.0 (12.0, 21.0), with higher NIHSS scores in the PBT ≥37.3 °C group than in the PBT <37.3 °C group (18 vs 14, respectively; p = 0.002). There were no differences in clinical outcomes at 3 months between patients with PBT <37.3 °C and patients with PBT between 37.3 °C and 38 °C. However, patients with PBT ≥38 °C had an increased risk of sICH (adjusted odds ratio (OR) = 8.8, 95% confidence interval (95% CI): 1.7-46.0; p = 0.01), increased inpatient death or hospice discharge (OR = 10.5, 95% CI: 2.0-53.9; p = 0.005), poorer clinical outcome (OR = 25.6, 95% CI: 5.2-126.8; p < 0.001), and increased 3-month mortality (OR = 6.6, 95% CI: 1.8-24.6; p = 0.01). CONCLUSIONS: Elevated PBT (≥38 °C) within 24 hours of EVT was significantly associated with an increased incidence of symptomatic intracranial hemorrhage, discharge to hospice or inpatient death, poorer clinical outcome and 3-month mortality, and with less functional independence. Further large-scale, prospective and multicenter trials are needed to confirm these findings.

Shortening door-to-puncture time and improving patient outcome with workflow optimization in patients with acute ischemic stroke associated with large vessel occlusion.

OBJECTIVE: We aimed to evaluate door-to-puncture time (DPT) and door-to-recanalization time (DRT) without directing healthcare by neuro-interventionalist support in the emergency department (ED) by workflow optimization and improving patients' outcomes. METHODS: Records of 98 consecutive ischemic stroke patients who had undergone endovascular therapy (EVT) between 2018 to 2021 were retrospectively reviewed in a single-center study. Patients were divided into three groups: pre-intervention (2018-2019), interim-intervention (2020), and post-intervention (January 1st 2021 to August 16th, 2021). We compared door-to-puncture time, door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), last known normal time to-puncture time (LKNPT), and patient outcomes (measured by 3 months modified Rankin Scale) between three groups using descriptive statistics. RESULTS: Our findings indicate that process optimization measures could shorten DPT, DRT, PRT, and LKNPT. Median LKNPT was shortened by 70 min from 325 to 255 min(P < 0.05), and DPT was shortened by 119 min from 237 to 118 min. DRT shortened by 132 min from 338 to 206 min, and PRT shortened by 33 min from 92 to 59 min from the pre-intervention to post-intervention groups (all P < 0.05). Only 21.4% of patients had a favorable outcome in the pre-intervention group as compared to 55.6% in the interventional group (P= 0.026). CONCLUSION: This study demonstrated that multidisciplinary cooperation was associated with shortened DPT, DRT, PRT, and LKNPT despite challenges posed to the healthcare system such as the COVID-19 pandemic. These practice paradigms may be transported to other stroke centers and healthcare providers to improve endovascular time metrics and patient outcomes.

Molecular mechanism of islet ß-cell functional alternations during type 2 diabetes.

In recent years, the incidence rate of type 2 diabetes (T2D) has risen rapidly and has become a global health crisis. Recent experimental and clinical studies have shown that islet ß-cell dysfunction is an important cause of T2D and its related complications. ß-cells undergo dynamic compensation and decompensation in the course of T2D. In this process, metabolic stress responses, such as ER stress, oxidative stress and inflammation, are key regulators of ß-cell functional alternations. In this review, we summarize the research progress on the ß-cell functional dynamics in the course of T2D, in order to deepen the understanding of the molecular mechanism of T2D, and provide reference for its precise diagnosis and clinical intervention.

A Design Strategy for Intrinsically Stretchable High-Performance Polymer Semiconductors: Incorporating Conjugated Rigid Fused-Rings with Bulky Side Groups.

Strategies to improve stretchability of polymer semiconductors, such as introducing flexible conjugation-breakers or adding flexible blocks, usually result in degraded electrical properties. In this work, we propose a concept to address this limitation, by introducing conjugated rigid fused-rings with optimized bulky side groups and maintaining a conjugated polymer backbone. Specifically, we investigated two classes of rigid fused-ring systems, namely, benzene-substituted dibenzothiopheno[6,5-b:6',5'-f]thieno[3,2-b]thiophene (Ph-DBTTT) and indacenodithiophene (IDT) systems, and identified molecules displaying optimized electrical and mechanical properties. In the IDT system, the polymer PIDT-3T-OC12-10% showed promising electrical and mechanical properties. In fully stretchable transistors, the polymer PIDT-3T-OC12-10% showed a mobility of 0.27 cm2 V-1 s-1 at 75% strain and maintained its mobility after being subjected to hundreds of stretching-releasing cycles at 25% strain. Our results underscore the intimate correlation between chemical structures, mechanical properties, and charge carrier mobility for polymer semiconductors. Our described molecular design approach will help to expedite the next generation of intrinsically stretchable high-performance polymer semiconductors.

Improving SERS Sensitivity toward Trace Sulfonamides: The Key Role of Trade-Off Interfacial Interactions among the Target Molecules, Anions, and Cations on the SERS Active Surface.

In recent years, ensuring the rational use and effective control of antibiotics has been a major focus in the eco-environment, which requires an effective monitoring method. However, on-site rapid detection of antibiotics in water environments remains a challenging issue. In this study, surface-enhanced Raman spectroscopy (SERS) was used to systematically achieve selective, rapid, and highly sensitive detection of sulfonamides, based on their fingerprint characteristics. The results show that the trade-off between the competitive and coadsorption behaviors of target molecules and agglomerates (inorganic salts) on the surface of the SERS substrate determines whether the molecules can be detected with high sensitivity. Based on this, the qualitative differentiation and quantitative detection of three structurally similar antibiotics, sulfadiazine, sulfamerazine, and sulfamethazine, were achieved, with the lowest detectable concentration being 1 µg/L for sulfadiazine and 50 µg/L for sulfamerazine and sulfamethazine.

Developing a Peak Extraction and Retention (PEER) Algorithm for Improving the Temporal Resolution of Raman Spectroscopy.

In spectroscopic analysis, push-to-the-limit sensitivity is one of the important topics, particularly when facing the qualitative and quantitative analyses of the trace target. Normally, the effective recognition and extraction of weak signals are the first key steps, for which there has been considerable effort in developing various denoising algorithms for decades. Nevertheless, the lower the signal-to-noise ratio (SNR), the greater the deviation of the peak height and shape during the denoising process. Therefore, we propose a denoising algorithm along with peak extraction and retention (PEER). First, both the first and second derivatives of the Raman spectrum are used to determine Raman peaks with a high SNR whose peak information is kept away from the denoising process. Second, an optimized window smoothing algorithm is applied to the left part of the Raman spectrum, which is combined with the untreated Raman peaks to obtain the denoised Raman spectrum. The PEER algorithm is demonstrated with much better signal extraction and retention and successfully improves the temporal resolution of Raman imaging of a living cell by at least 1 order of magnitude higher than those by traditional algorithms.

Structural Revision of Guttiferone F and 30-epi-Cambogin.

Guttiferone F, a natural polyprenylated polycyclic acylphloroglucinol, was originally assigned as the 30-epimer of garcinol by NMR data analyses. Conversion of guttiferone F in the presence of acid afforded its cyclized form (2a), which was previously assigned as 30-epi-cambogin. However, the absolute configurations of guttiferone F and 2a have not been determined. Reinvestigation of the structures of those two compounds, using X-ray and NMR data analyses and chemical transformation, revealed that the original assignment of the C-30 absolute configuration in guttiferone F and 2a should be inverted. Guttiferone F is indeed garcinol, and 2a, which was previously identified as 30-epi-cambogin, is cambogin.

Multiplex and on-site PCR detection of swine diseases based on the microfluidic chip system.

BACKGROUND: At present, the process of inspection and quarantine starts with sampling at the customs port, continues with transporting the samples to the central laboratory for inspection experiments, and ends with the inspected results being fed back to the port. This process had the risks of degradation of biological samples and generation of pathogenic microorganisms and did not meet the rapid on-site detection demand because it took a rather long time. Therefore, it is urgently needed to develop a rapid and high-throughput detection assay of pathogenic microorganisms at the customs port. The aim of this study was to develop a microfluidic chip to rapidly detect swine pathogenic microorganisms with high-throughput and higher accuracy. Moreover, this chip will decrease the risk of spreading infection during transportation. RESULTS: A series of experiments were performed to establish a microfluidic chip. The resulting data showed that the positive nucleic acid of four swine viruses were detected by using a portable and rapid microfluidic PCR system, which could achieve a on-site real-time quantitative PCR detection. Furthermore, the detection results of eight clinical samples were obtained within an hour. The lowest concentration that amplified of this microfluidic PCR detection system was as low as 1 copies/µL. The results showed that the high specificity of this chip system in disease detection played an important role in customs inspection and quarantine during customs clearance. CONCLUSION: The microfluidic PCR detection system established in this study could meet the requirement for rapid detection of samples at the customs port. This chip could avoid the risky process of transporting the samples from the sampling site to the testing lab, and drastically reduce the inspection cycle. Moreover, it would enable parallel inspections on one chip, which greatly raised the efficiency of inspection.