3D Printing of Robust High-Performance Conducting Polymer Hydrogel-Based Electrical Bioadhesive Interface for Soft Bioelectronics.

Electrical bioadhesive interface (EBI), especially conducting polymer hydrogel (CPH)-based EBI, exhibits promising potential applications in various fields, including biomedical devices, neural interfaces, and wearable devices. However, current fabrication techniques of CPH-based EBI mostly focus on conventional methods such as direct casting, injection, and molding, which remains a lingering challenge for further pushing them toward customized practical bioelectronic applications and commercialization. Herein, 3D printable high-performance CPH-based EBI precursor inks are developed through composite engineering of PEDOT:PSS and adhesive ionic macromolecular dopants within tough hydrogel matrices (PVA). Such inks allow the facile fabrication of high-resolution and programmable patterned EBI through 3D printing. Upon successive freeze-thawing, the as-printed PEDOT:PSS-based EBI simultaneously exhibits high conductivity of 1.2 S m-1 , low interfacial impedance of 20 Ω, high stretchability of 349%, superior toughness of 109 kJ m-3 , and satisfactory adhesion to various materials. Enabled by these advantageous properties and excellent printability, the facile and continuous manufacturing of EBI-based skin electrodes is further demonstrated via 3D printing, and the fabricated electrodes display excellent ECG and EMG signal recording capability superior to commercial products. This work may provide a new avenue for rational design and fabrication of next-generation EBI for soft bioelectronics, further advancing seamless human-machine integration.

Isoindigo-Thiophene D-A-D-Type Conjugated Polymers: Electrosynthesis and Electrochromic Performances.

Four novel isoindigo-thiophene D-A-D-type precursors are synthesized by Stille coupling and electrosynthesized to yield corresponding hybrid polymers with favorable electrochemical and electrochromic performances. Intrinsic structure-property relationships of precursors and corresponding polymers, including surface morphology, band gaps, electrochemical properties, and electrochromic behaviors, are systematically investigated. The resultant isoindigo-thiophene D-A-D-type polymer combines the merits of isoindigo and polythiophene, including the excellent stability of isoindigo-based polymers and the extraordinary electrochromic stability of polythiophene. The low onset oxidation potential of precursors ranges from 1.10 to 1.15 V vs. Ag/AgCl, contributing to the electrodeposition of high-quality polymer films. Further kinetic studies illustrate that isoindigo-thiophene D-A-D-type polymers possess favorable electrochromic performances, including high optical contrast (53%, 1000 nm), fast switching time (0.8 s), and high coloration efficiency (124 cm2 C-1). These features of isoindigo-thiophene D-A-D-type conjugated polymers could provide a possibility for rational design and application as electrochromic materials.

Nonlinear optical property and application of yttrium oxide in erbium-doped fiber lasers.

Yttrium oxide (Y2O3) has garnered some attention in view of its potential to be integrated into a wide range of high-strength structural components, microelectronic and optoelectronic devices. However, the nonlinear optical research of this promising material has not been implemented yet. In this paper, not only the electronic band structures of Y2O3 are theoretically calculated but also the optical nonlinearity of Y2O3 is validated by using the fiber laser as a platform. Meanwhile, the influence of sample thickness on laser performance is further explored by using Y2O3 saturable absorbers with different thickness. Results indicate that Y2O3 not only has impressive optical nonlinearity but also is beneficial to the investigation of ultrafast photons by adjusting the thickness of Y2O3. Therefore, Y2O3 can be used as a potential saturable absorber candidate for in-depth research and application.

Enhanced immunity and hemocytes proliferation by three immunostimulants in tri-spine horseshoe crab Tachypleus tridentatus.

Tachypleus amebocyte lysate (TAL) is crucial in medical testing, but its industry in China has been restricted due to the decline of horseshoe crab population in recent years. Exploring methods of enhancing immunity and rapid hemocytes proliferation is urgent for the industrial horseshoe crab culture. In this study, ß-glucan (G), peptidoglycan (P), and squalene (S) were injected to horseshoe crabs at two concentrations (5 and 10 mg/kg), in order to compare their effects on total hemocyte count (THC), reactive oxygen species (ROS), and non-specific immune enzyme activities. Results showed that the THC, superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC) were significantly increased by three immunostimulants at different points of time; ROS was significantly increased except at two squalene groups; lysozyme (LZM) and alkaline phosphatase (AKP) activity were increased except at low dose (5 mg/kg) squalene group; malondialdehyde (MDA) activity was decreased in all treatments; and hemocyanin concentration (HC) changed little during the experiment. At the 48th hour, THC, ROS, SOD, CAT, T-AOC, LZM, and AKP activities were significantly higher in the two peptidoglycan groups than those in the control group; the low dose ß-glucan and squalene groups showed significantly higher SOD and CAT, but their THC and AKP were not significantly different from those of the control group. In general, all three immunostimulants stimulated the hemolymph parameters of horseshoe crabs, notably, peptidoglycan could significantly increase the THC and enzyme activities, suggesting that peptidoglycan can be developed as an efficient immunostimulant for horseshoe crabs.

Highly fluorescent triazolopyridine-thiophene D-A-D oligomers for efficient pH sensing both in solution and in the solid state.

Conjugated fluorophores have been extensively used for fluorescence sensing of various substances in the field of life processes and environmental science, due to their noninvasiveness, sensitivity, simplicity and rapidity. Most existing conjugated fluorophores exhibit excellent light-emitting performance in dilute solutions, but their properties substantially decrease or even completely vanish due to severe aggregation quenching in the solid state. Herein, we synthesize a series of triazolopyridine-thiophene donor-acceptor-donor (D-A-D) type conjugated molecules with high absolute fluorescence quantum yields (ΦF) ranging from 80% to 89% in solution. These molecules also show unusual light-emitting properties in the solid state with ΦF of up to 26%. We find that owing to the protonation-deprotonation process of the pyridine ring, these compounds display obvious changes in both fluorescence wavelength and intensity upon addition of acids, and these changes can be readily recovered by the successive introduction of bases. By harnessing this phenomenon, we further show that these fluorophores can be employed for efficient and reversible fluorescence sensing of hydrogen ions in a broad pH range (0.0-7.0). With the fabrication of pH testing papers and ink-printed complex patterns including butterflies and letters on substrates, we demonstrate the application of such sensors to fluorescence indication or solid state pH detection for real samples such as volatile acidic/basic gas and water-quality analysis.

Integrated Transcriptome Sequencing Analysis Reveals Role of miR-138-5p/ TBL1X in Placenta from Gestational Diabetes Mellitus.

BACKGROUND/AIMS: The placenta has been suggested to play a crucial role in the pathology of gestational diabetes mellitus (GDM). Placenta-specific microRNAs (miRNAs) and the corresponding targeting genes involved in the pathology of GDM still remain to be elucidated. We aimed to identify the dysregulated miRNAs and the corresponding mRNA targets through an integrated miRNA and mRNA transcriptomic profiles analysis and investigate the role of differentially expressed miR-138-5p/TBL1X in GDM. METHODS: RNA sequencing (RNA-seq) was performed in 16 placentas from GDM and control group. Differentially expressed mRNAs and miRNAs in GDM were validated by quantitative PCR (qPCR). The wound healing assay and transwell migration assay were used to analyze cell migration ability. The cell proliferation was determined by CCK8 assay. Luciferase assay was used to confirm the direct binding of the targeted TBL1X with miR-138-5p. RESULTS: Totally, 281 mRNAs and 32 miRNAs were found to be differentially expressed in the GDM placentas. The biological relationships of the miRNA/mRNA pairs were related to cellular development and function and organ morphology. Among the aberrantly expressed molecules, we selected miR-138-5p from the bioinformatics analysis and found that miR-138-5p significantly inhibited the migration and proliferation of trophoblasts (HTR-8/SVneo) by targeting the 3'-UTR of TBL1X. Furthermore, the aberrant expression of miR-138-5p and TBL1X was significantly correlated with the weight of the placenta. CONCLUSION: We present the first integrative analysis of miRNA and mRNA expression profiles in GDM placenta and uncover a more detailed role for miR-138-5p, as well as its target TBL1X in the pathology of GDM.

ФC31 Integrase-Mediated Isolation and Characterization of Novel Safe Harbors for Transgene Expression in the Pig Genome.

Programmable nucleases have allowed the rapid development of gene editing and transgenics, but the technology still suffers from the lack of predefined genetic loci for reliable transgene expression and maintenance. To address this issue, we used ФC31 integrase to navigate the porcine genome and identify the pseudo attP sites suitable as safe harbors for sustained transgene expression. The combined ФC31 integrase mRNA and an enhanced green fluorescence protein (EGFP) reporter donor were microinjected into one-cell zygotes for transgene integration. Among the resulting seven EGFP-positive piglets, two had transgene integrations at pseudo attP sites, located in an intergenic region of chromosome 1 (chr1-attP) and the 6th intron of the TRABD2A gene on chromosome 3 (chr3-attP), respectively. The integration structure was determined by TAIL-PCR and Southern blotting. Primary fibroblast cells were isolated from the two piglets and examined using fluorescence-activated cell sorting (FACS) and enzyme-linked immunosorbent assay (ELISA), which demonstrated that the chr1-attP site was more potent than chr3-attP site in supporting the EGFP expression. Both piglets had green feet under the emission of UV light, and pelleted primary fibroblast cells were green-colored under natural light, corroborating that the two pseudo attP sites are beneficial to transgene expression. The discovery of these two novel safe harbors for robust and durable transgene expression will greatly facilitate the use of transgenic pigs for basic, biomedical and agricultural studies and applications.

Small cell carcinoma of the cervix at 32-week gestation: a case report and review of the literature.

Small cell carcinoma of the cervix (SCCC) in late pregnancy is extremely rare and often misdiagnosed. We describe a case report of a patient who was diagnosed with SCCC at 32 weeks of gestation. During Cesarean section, a radical hysterectomy was performed; the uterus and cervical stroma were excised, the pelvic lymph node was bilaterally dissected, and the para-aortic lymph node was biopsied. During the surgery, a metastatic mass measuring 3 x 2.5 x 2.5 cm in size was found in the left cervical stroma with enlarged obturator lymph nodes. The patient was subsequently diagnosed with stage IIa cervical cancer. The efficacy of radiotherapy and chemotherapy was poor due to the very late stage of the SCCC and the patient died from metastatic disease. Therefore, we suggest that cervical liquid-based cytology, in combination with immunocytochemical and molecular analyses, should be performed for the early detection of SCCC when abnormal vaginal bleeding is present during pregnancy.

Hydrogel Extinguishants.

The exploitation of clean and efficient fire extinguishing materials has substantial implications for improving disaster prevention, mitigation, and relief capabilities, maintaining public safety, and protecting people's lives and property as well as the natural environment. Natural polymer hydrogel with high water containment, excellent film formation, high heat insulation, ecofriendliness, and degradability has huge potential in achieving new breakthroughs for developing clean and efficient fire extinguishing materials and products. In recent years, the exploitation of hydrogel extinguishing materials and the fabrication of products has attracted great attention, gradually replacing traditional fire extinguishing products. In this perspective, an in-depth review of the evolution of hydrogels applied for fire extinguishing and prevention is presented. Firstly, the extinguishing principles of hydrogel extinguishants are explained. Secondly, the preparation strategies and evaluation system of the hydrogel extinguishants are emphatically discussed. Although great progress has been made in developing high-performance hydrogel extinguishants, it remains challenging to develop cost-effective, degradable, and easy-to-use hydrogel extinguishants. Additionally, we highlight the importance of considering the commercial aspects of hydrogel extinguishants. Looking into the future, hydrogel extinguishants are promising, but continued investment in research and development is necessary to overcome the challenges.

3D printing of highly conductive and strongly adhesive PEDOT:PSS hydrogel-based bioelectronic interface for accurate electromyography monitoring.

PEDOT: PSS hydrogel-based bioelectronic interfaces have gained significant attention in various fields including biomedical devices, wearable devices, and epidermal electronics. However, the development of high-performance bioelectronic interfaces that integrate excellent conductivity, strong adhesion, and advanced processing compatibility remains a challenge. Herein, we develop a high-performance bioelectronic interface by 3D printing of a novel poly(vinyl alcohol-formaldehyde) (PVAF)-PEDOT:PSS composite ink. Such a PEDOT:PSS-PVAF ink exhibits favorable rheological properties for direct-ink-writing 3D printing, enabling the fabrication of high-resolution patterns and three-dimensional structures with high aspect ratios. Hydrogel bioelectronic interface printed by such PEDOT:PSS-PVAF ink simultaneously achieves high conductivity (over 100 S m-1), strong adhesion (31.44 ± 7.07 kPa), as well as stable electrochemical performance (charge injection capacity of 13.72 mC cm-2 and charge storage capacity of 18.80 mC cm-2). We further integrate PEDOT:PSS-PVAF hydrogel bioelectronic interface to fabricate adhesive skin electrodes for electromyography (EMG) signal recording. The resultant EMG skin electrodes demonstrate superior performance and stability compared to commercial products, maintaining high signal-to-noise ratio of > 10 dB under varying weights and repetitive motions. These advantageous performance of PEDOT:PSS-PVAF based hydrogel bioelectronic interfaces may be helpful for diverse bioelectronic applications like healthcare monitoring and epidermal bioelectronics.

Structural and physicochemical effects on the starch quality of the high-quality wheat genotype caused by delayed sowing.

Background: Bread wheat is one of the most important food crops associated with ensuring food security and human nutritional health. The starch quality is an important index of high-quality wheat. It is affected by a complex series of factors; among which, suitable sowing time is a key factor. Aim and methods: To analyze the integrative effects of sowing time on the starch quality of high-quality wheat, in the present study, we selected a high-quality bread wheat cultivar Jinan 17 and investigated the effect of different sowing times on the starch properties and the related genes by analyzing X-ray diffraction patterns, apparent amylose content, thermal properties, pasting properties, in vitro starch digestibility, and qRT-PCR. Meanwhile, we also investigated the agronomic and yield performance that may be associated with the starch properties. Results: Delayed sowing had little effect on starch crystalline morphology, but there was a tendency to reduce the formation of crystals within wheat starch granules: (1) delayed sowing for 15 days altered the thermal properties of starch, including onset, peak and termination temperatures, and enthalpy changes; (2) delayed sowing for 30 days changed the thermal characteristics of starch relatively insignificant; (3) significant differences in pasting characteristics occurred: peak viscosity and hold-through viscosity increased, while final viscosity, breakdown viscosity, and setback viscosity tended to increase and then decrease, suggesting that delayed sowing caused changes in the surface of the starch granules resulting in a decrease in digestibility. Analysis of related genes showed that several key enzymes in starch biosynthesis were significantly affected by delayed sowing, leading to a reduction in apparent straight-chain starch content. In addition to starch properties, thousand-kernel weight also increased under delayed sowing conditions compared with normal sowing. Conclusion: The impact of delayed sowing on starch quality is multifaceted and complex, from the fine structure, and functional properties of the starch to the regulation of key gene expression. Our study holds significant practical value for optimizing wheat planting management and maximizing the potential in both quality and yield.

Pseudo attP sites in favor of transgene integration and expression in cultured porcine cells identified by Streptomyces phage phiC31 integrase.

Phage PhiC31 integrase integrates attB-containing plasmid into pseudo attP site in eukaryotic genomes in a unidirectional site-specific manner and maintains robust transgene expression. Few studies, however, explore its potential in livestock. This study aims to discover the molecular basis of PhiC31 integrase-mediated site-specific recombination in pig cells. We show that PhiC31 integrase can mediate site-specific transgene integration into the genome of pig kidney PK15 cells. Intramolecular recombination in pig PK15 cell line occurred at maximum frequency of 82% with transiently transfected attB- and attP-containing plasmids. An optimal molar ratio of pCMV-Int to pEGFP-N1-attB at 5:1 was observed for maximum number of cell clones under drug selection. Four candidate pseudo attP sites were identified by TAIL-PCR from those cell clones with single-copy transgene integration. Two of them gave rise to higher integration frequency occurred at 33%. 5' and 3' junction PCR showed that transgene integration mediated by PhiC31 integrase was mono-allelic. Micro- deletion and insertion were observed by sequencing the integration border, indicating that double strand break was induced by the recombination. We then constructed rescue reporter plasmids by ABI-REC cloning of the four pseudo attP sites into pBCPB + plasmid. Transfection of these rescue plasmids and pCMV-Int resulted in expected intramolecular recombination between attB and pseudo attP sites. This proved that the endogenous pseudo attP sites were functional substrates for PhiC31 integrase-mediated site-specific recombination. Two pseudo attP sites maintained robust extracellular and intracellular EGFP expression. Alamar blue assay showed that transgene integration into these specific sites had little effect on cell proliferation. This is the first report to document the potential use of PhiC31 integrase to mediate site-specific recombination in pig cells. Our work established an ideal model to study the position effect of identical transgene located in diverse chromosomal contexts. These findings also form the basis for targeted pig genome engineering and may be used to produce genetically modified pigs for agricultural and biomedical uses.

Self-Healable PEDOT:PSS-PVA Nanocomposite Hydrogel Strain Sensor for Human Motion Monitoring.

Strain sensors based on conducting polymer hydrogels are considered highly promising candidates for wearable electronic devices. However, existing conducting polymer hydrogels are susceptible to aging, damage, and failure, which can greatly deteriorate the sensing performance of strain sensors based on these substances and the accuracy of data collection under large deformation. Developing conductive polymer hydrogels with concurrent high sensing performance and self-healing capability is a critical yet challenging task to improve the stability and lifetime of strain sensors. Herein, we design a self-healable conducting polymer hydrogel by compositing poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) nanofibers and poly(vinyl alcohol) (PVA) via both physical and chemical crosslinking. This PEDOT:PSS-PVA nanocomposite hydrogel strain sensor displays an excellent strain monitoring range (>200%), low hysteresis (<1.6%), a high gauge factor (GF = 3.18), and outstanding self-healing efficiency (>83.5%). Electronic skins based on such hydrogel strain sensors can perform the accurate monitoring of various physiological signals, including swallowing, finger bending, and knee bending. This work presents a novel conducting polymer hydrogel strain sensor demonstrating both high sensing performance and self-healability, which can satisfy broad application scenarios, such as wearable electronics, health monitoring, etc.

Flexible Supercapacitors Based on Stretchable Conducting Polymer Electrodes.

Supercapacitors are widely used in various fields due to their high power density, fast charging and discharging speeds, and long service life. However, with the increasing demand for flexible electronics, integrated supercapacitors in devices are also facing more challenges, such as extensibility, bending stability, and operability. Despite many reports on stretchable supercapacitors, challenges still exist in their preparation process, which involves multiple steps. Therefore, we prepared stretchable conducting polymer electrodes by depositing thiophene and 3-methylthiophene on patterned 304 stainless steel (SS 304) through electropolymerization. The cycling stability of the prepared stretchable electrodes could be further improved by protecting them with poly(vinyl alcohol)/sulfuric acid (PVA/H2SO4) gel electrolyte. Specifically, the mechanical stability of the polythiophene (PTh) electrode was improved by 2.5%, and the stability of the poly(3-methylthiophene (P3MeT) electrode was improved by 7.0%. As a result, the assembled flexible supercapacitors maintained 93% of their stability even after 10,000 cycles of strain at 100%, which indicates potential applications in flexible electronics.

An asymmetric PCR-based, reliable and rapid single-tube native DNA engineering strategy.

BACKGROUND: Widely used restriction-dependent cloning methods are labour-intensive and time-consuming, while several types of ligase-independent cloning approaches have inherent limitations. A rapid and reliable method of cloning native DNA sequences into desired plasmids are highly desired. RESULTS: This paper introduces ABI-REC, a novel strategy combining asymmetric bridge PCR with intramolecular homologous recombination in bacteria for native DNA cloning. ABI-REC was developed to precisely clone inserts into defined location in a directional manner within recipient plasmids. It featured an asymmetric 3-primer PCR performed in a single tube that could robustly amplify a chimeric insert-plasmid DNA sequence with homologous arms at both ends. Intramolecular homologous recombination occurred to the chimera when it was transformed into E.coli and produced the desired recombinant plasmids with high efficiency and fidelity. It is rapid, and does not involve any operational nucleotides. We proved the reliability of ABI-REC using a double-resistance reporter assay, and investigated the effects of homology and insert length upon its efficiency. We found that 15 bp homology was sufficient to initiate recombination, while 25 bp homology had the highest cloning efficiency. Inserts up to 4 kb in size could be cloned by this method. The utility and advantages of ABI-REC were demonstrated through a series of pig myostatin (MSTN) promoter and terminator reporter plasmids, whose transcriptional activity was assessed in mammalian cells. We finally used ABI-REC to construct a pig MSTN promoter-terminator cassette reporter and showed that it could work coordinately to express EGFP. CONCLUSIONS: ABI-REC has the following advantages: (i) rapid and highly efficient; (ii) native DNA cloning without introduction of extra bases; (iii) restriction-free; (iv) easy positioning of directional and site-specific recombination owing to formulated primer design. ABI-REC is a novel approach to DNA engineering and gene functional analysis.

Multi-omics reveals response mechanism of liver metabolism of hybrid sturgeon under ship noise stress.

Underwater noise from ship engines can affect the metabolism and immune system of various fish species. Meanwhile, changes in the metabolic pathways in liver are important for fish to adapt to adverse environments. We used a combined multi-omics analysis to investigate the response mechanism of hybrid sturgeon to continuously played ship noise. A control group and a noise group (simulated ship noise: 12 h) were set up, and liver tissues were extracted for high-throughput transcriptome and metabolome sequencing. The results show that a total of 588 differentially expressed genes (DEGs) and 58 DEGs metabolites were detected. The joint analysis of transcriptome and metabolome showed that under noise stress, apoptosis and cell motility were intensified, DNA replication, RNA transcription and translation, and protein synthesis were inhibited, and lipid metabolism, nucleotide metabolism, and vitamin D3 metabolic pathways were also inhibited. Interestingly, the initiation of a partial immune responses ensured their normal immunity abilities. Moreover, material and energy requirements of the organism under noise stress were guaranteed by upregulation of carbohydrate and amino acid metabolic pathways.

3D Printing of Stretchable, Adhesive and Conductive Ti3C2Tx-Polyacrylic Acid Hydrogels.

Stretchable, adhesive, and conductive hydrogels have been regarded as ideal interfacial materials for seamless and biocompatible integration with the human body. However, existing hydrogels can rarely achieve good mechanical, electrical, and adhesive properties simultaneously, as well as limited patterning/manufacturing techniques posing severe challenges to bioelectronic research and their practical applications. Herein, we develop a stretchable, adhesive, and conductive Ti3C2Tx-polyacrylic acid hydrogel by a simple pre-crosslinking method followed by successive direct ink writing 3D printing. Pre-polymerization of acrylic acid can be initiated by mechanical mixing with Ti3C2Tx nanosheet suspension, leading to the formation of viscous 3D printable ink. Secondary free radical polymerization of the ink patterns via 3D printing can achieve a stretchable, adhesive, and conductive Ti3C2Tx-polyacrylic acid hydrogel. The as-formed hydrogel exhibits remarkable stretchability (~622%), high electrical conductivity (5.13 S m-1), and good adhesion strength on varying substrates. We further demonstrate the capability of facilely printing such hydrogels into complex geometries like mesh and rhombus patterns with high resolution and robust integration.

Low Hysteresis and Fatigue-Resistant Polyvinyl Alcohol/Activated Charcoal Hydrogel Strain Sensor for Long-Term Stable Plant Growth Monitoring.

Flexible strain sensor as a measurement tool plays a significant role in agricultural development by long-term stable monitoring of the dynamic progress of plant growth. However, existing strain sensors still suffer from severe drawbacks, such as large hysteresis, insufficient fatigue resistance, and inferior stability, limiting their broad applications in the long-term monitoring of plant growth. Herein, we fabricate a novel conductive hydrogel strain sensor which is achieved through uniformly dispersing the conductive activated charcoal (AC) in high-viscosity polyvinyl alcohol (PVA) solution forming a continuous conductive network and simple preparation by freezing-thawing. The as-prepared strain sensor demonstrates low hysteresis (<1.5%), fatigue resistance (fatigue threshold of 40.87 J m−2), and long-term sensing stability upon mechanical cycling. We further exhibit the integration and application of PVA-AC strain sensor to monitor the growth of plants for 14 days. This work may offer an effective strategy for monitoring plant growth with conductive hydrogel strain sensor, facilitating the advancement of agriculture.

Effects of Ocean Acidification on Molting, Oxidative Stress, and Gut Microbiota in Juvenile Horseshoe Crab Tachypleus tridentatus.

Anthropogenic elevation of atmospheric carbon dioxide (CO2) drives global-scale ocean acidification (OA), which has aroused widespread concern for marine ecosystem health. The tri-spine horseshoe crab (HSC) Tachypleus tridentatus has been facing the threat of population depletion for decades, and the effects of OA on the physiology and microbiology of its early life stage are unclear. In this study, the 1st instar HSC larvae were exposed to acidified seawater (pH 7.3, pH 8.1 as control) for 28 days to determine the effects of OA on their growth, molting, oxidative stress, and gut microbiota. Results showed that there were no significant differences in growth index and molting rate between OA group and control group, but the chitinase activity, ß-NAGase activity, and ecdysone content in OA group were significantly lower than those of the control group. Compared to the control group, reactive oxygen species (ROS) and malondialdehyde (MDA) contents in OA group were significantly increased at the end of the experiment. Superoxide dismutase (SOD), catalase (CAT), and alkaline phosphatase (AKP) activities increased first and then decreased, glutathione peroxidase (GPX) decreased first and then increased, and GST activity changed little during the experiment. According to the result of 16S rRNA sequencing of gut microbiota, microbial-mediated functions predicted by PICRUSt showed that "Hematopoietic cell lineage," "Endocytosis," "Staphylococcus aureus infection," and "Shigellosis" pathways significantly increased in OA group. The above results indicate that OA had no significant effect on growth index and molting rate but interfered with the activity of chitinolytic enzymes and ecdysone expression of juvenile horseshoe crabs, and caused oxidative stress. In addition, OA had adverse effects on the immune defense function and intestinal health. The present study reveals the potential threat of OA to T. tridentatus population and lays a foundation for the further study of the physiological adaptation mechanism of juvenile horseshoe crabs to environmental change.

A study of the sequential treatment of acute heart failure with sacubitril/valsartan by recombinant human brain natriuretic peptide: A randomized controlled trial.

ABSTRACT: This study aimed to investigate the effects of the basic treatment for heart failure and sequential treatment with rh-brain natriuretic peptide (rhBNP) alone or the combination of rhBNP and sacubitril/valsartan. Cardiac structure, pulmonary artery pressure, inflammation and oxidative stress in patients with acute heart failure were evaluated.Three hundred patients with acute heart failure were included. According to the random number table method, the patients were divided into 3 groups of 100 patients per group: the standard treatment group (treated with an angiotensin-converting enzyme inhibitor, ß receptor blocker, and corticosteroid antagonist), rhBNP group (basic treatment combined with rhBNP) and sequential treatment group (basic treatment for heart failure combined with rhBNP followed by sacubitril/valsartan). The changes in NT-probrain natriuretic peptide (BNP) levels, cardiac troponin T (cTnT) levels, cardiac structure, pulmonary artery pressure, and the levels inflammatory factors and oxidative stress factors were compared among the 3 groups at 1, 4, 12, and 36 weeks after treatment.The sequential treatment group displayed superior outcomes than the standard treatment group and the rhBNP group in terms of left atrium diameter, left ventricular end diastolic volume, left ventricular ejection fraction, pulmonary artery pressure, NT-proBNP levels, and cTnT levels, which respond to damage to the heart structure and myocardium. This result may be related to the decreased levels of inflammatory factors and the correction of oxidative stress imbalance.Sacubitril/valsartan significantly reduce the serum levels of inflammatory factors in patients with acute heart failure while decreasing the levels of oxidizing factors and increasing the levels of antioxidant factors. These changes may be one of the explanations for the better cardiac structure and better pulmonary artery pressure observed in the sequential treatment group.