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Cheng-Rong Wu,1 Hua-Lei Cai,2 Di-Xian Cai,3 Tao-Lan Li,1 Rong Shen,2 Dan Zi2 1Department of Obstetrics and Gynecology, Guizhou Medical University, Guiyang, 550004, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, People’s Republic of China; 3Department of Psychology, Guizhou Medical University, Guiyang, 550004, People’s Republic of ChinaCorrespondence: Hua-Lei CaiDepartment of Obstetrics and Gynecology, The Affiliated Hospital of Guizhou Medical University, No. 28 of Guiyi Street, Yunyan District, Guiyang, 550004, People’s Republic of ChinaTel +86 18198132660Fax +86 851-86855119Email caihualei_dr@163.comObjective: The growth of oviduct mucosa in the uterine cavity was observed by co-culture of oviduct mucosa cells and endometrial cells in different proportions to study the possibility and function of the growth of oviduct mucosa in the uterine cavity.Methods: The extracted cells were identified by immunofluorescence with cytokeratins 19 (CK19) and vimentin. A Cell Counting Kit-8 (CCK8) experiment, cell decidualization induction, and HE staining were performed after the co-culture of two kinds of cells in different proportions.Results: 1) The cells could grow normally when the two cells were co-cultured indirectly. 2) A CCK8 test of oviduct mucosa cells showed that the growth rate of each group was similar after the indirect co-culture of two kinds of cells in different proportions, which was in line with the growth law of normal cells. 3) Immunofluorescence identification of the cells showed that most of the two kinds of cells in the second passage were CK19 positive and were epithelial cells, while most of the cells in the fifth passage expressed positive vimentin antibody and were stroma cells. 4) After cell decidualization induction, the cell morphology of each group showed deciduation-like changes. 5) After decidualization, the cell morphology of each group was similar after HE staining.Conclusion: Oviduct mucosa cells can grow normally in the uterine environment. In the uterine environment with different degrees of endometrial loss, the growth rate of oviduct mucosa cells is not inhibited. Its morphology does not change, and it can undergo decidualization in vitro.Keywords: oviduct mucosa, endometrium, co-culture, endometrial receptivity, intrauterine adhesion

Applying statistical analyses to reanalysis products during the period 1900–2018, this study finds the 11-year solar cycle to have a significant correlation with sea surface temperature (SST) variations in the Northeastern Pacific. The solar influence is first manifested and amplified in the lower stratosphere, which then alters the strength of Hadley circulation in the troposphere. Lastly, the changes in the sinking branch of the Hadley circulation modulate surface heat fluxes to give rise to the SST footprint. The footprint has a structure similar to that of the Pacific meridional mode (PMM) that is known to be an important trigger of the central Pacific (CP) type of the El Niño-Southern Oscillation (ENSO). The 11-year solar cycle is thus shown to contribute to the slow modulation of the CP ENSO and, in particular, to be associated with more CP El Niño (La Niña) events during the active (inactive) phase of the cycle.

In toroidal magnetic fusion devices, fast-ion D-alpha diagnostic (FIDA) is a powerful method to study the fast-ion feature. The fast-ion characteristics can be inferred from the Doppler shifted spectrum of Dα light according to charge exchange recombination process between fast ions and probe beam. Since conceptual design presented in the last HTPD conference, significant progress has been made to apply FIDA systems on the Experimental Advanced Superconducting Tokamak (EAST). Both co-current and counter-current neutral beam injectors are available, and each can deliver 2-4 MW beam power with 50-80 keV beam energy. Presently, two sets of high throughput spectrometer systems have been installed on EAST, allowing to capture passing and trapped fast-ion characteristics simultaneously, using Kaiser HoloSpec transmission grating spectrometer and Bunkoukeiki FLP-200 volume phase holographic spectrometer coupled with Princeton Instruments ProEM 1024B eXcelon and Andor DU-888 iXon3 1024 CCD camera, respectively. This paper will present the details of the hardware descriptions and experimental spectrum.

To investigate the fast ion behavior, a fast ion D-alpha (FIDA) diagnostic system has been installed on EAST. Fast ion features can be inferred from the Doppler shifted spectrum of Balmer-alpha light from energetic hydrogenic atoms. This paper will focus on the validation of FIDA measurements performed using MHD-quiescent discharges in 2015 campaign. Two codes have been applied to calculate the Dα spectrum: one is a Monte Carlo code, Fortran 90 version FIDASIM, and the other is an analytical code, Simulation of Spectra (SOS). The predicted SOS fast-ion spectrum agrees well with the measurement; however, the level of fast-ion part from FIDASIM is lower. The discrepancy is possibly due to the difference between FIDASIM and SOS velocity distribution function. The details will be presented in the paper to primarily address comparisons of predicted and observed spectrum shapes/amplitudes.

The present study was carried out to investigate the neuroprotective effect of luteolin on amyloid beta (Abeta) (25-35)-induced neurotoxicity using cultured rat cortical neurons. After exposure of primary cultures of rat cortical cells to 10 muM Abeta (25-35) for 48 h, cortical cell cultures exhibited marked apoptotic death. Pretreatment with luteolin (1, 10 microM) significantly protected cortical cell cultures against Abeta (25-35)-induced toxicity. Luteolin (1, 10 microM) showed a concentration-dependent inhibition on 10 muM Abeta (25-35)-induced apoptotic neuronal death, as assessed by MTT assay. Furthermore, luteolin reduced apoptotic characteristics by DAPI staining. For Western blot analysis, the results showed that the protective effect of luteolin on Abeta (25-35)-induced neurotoxicity was mediated by preventing of ERK-p, JNK, JNK-p, P38-p and caspase 3 activations in rat primary cortical cultures. Taken together, the results suggest that luteolin prevents Abeta (25-35)-induced apoptotic neuronal death through inhibiting the protein level of JNK, ERK and p38 MAP kinases and caspase 3 activations. [ABSTRACT FROM AUTHOR]

A 5-year-old female diagnosed with severe hemophilia B began experiencing frequent muscular and joint bleeds at 19 months old. Molecular studies, including Sanger sequencing, Giemsa banding, human androgen receptor (HUMARA) assay, array-based comparative genomic hybridization (aCGH), whole-exome sequencing (WES), and multiplex ligation-dependent probe amplification (MLPA), revealed a heterozygous factor IX (F9) intron 3 substitution (c.277+1G>T) inherited from her mother and a de novo heterozygous 441 kb deletion in the Xq28 region, which flanked intron 22 homologous regions 1 (int22h1) and 2 (int22h2). This rare genetic profile explains her severe phenotype and guides hereditary consultation for family planning., (© 2024 Wiley Periodicals LLC.)

In this study, we collected seven prevalent Taiwanese Desmodium plants, including three species with synonymous characteristics, in order to assess their antioxidant phytoconstituents and radical scavenging capacities. Additionally, we compared their inhibitory activities on monoamine oxidase (MAO) and 6-hydroxydopamine (6-OHDA) auto-oxidation. Subsequently, we evaluated the neuroprotective potential of D. pulchellum on 6-OHDA-induced nerve damage in SH-SY5Y cells and delved into the underlying neuroprotective mechanisms. Among the seven Desmodium species, D. pulchellum exhibited the most robust ABTS radical scavenging capacity and relative reducing power; correspondingly, it had the highest total phenolic and phenylpropanoid contents. Meanwhile, D. motorium showcased the best hydrogen peroxide scavenging capacity and, notably, D. sequax demonstrated remarkable prowess in DPPH radical and superoxide scavenging capacity, along with selective inhibitory activity against MAO-B. Of the aforementioned species, D. pulchellum emerged as the frontrunner in inhibiting 6-OHDA auto-oxidation and conferring neuroprotection against 6-OHDA-induced neuronal damage in the SH-SY5Y cells. Furthermore, D. pulchellum effectively mitigated the increase in intracellular ROS and MDA levels through restoring the activities of the intracellular antioxidant defense system. Therefore, we suggest that D. pulchellum possesses neuroprotective effects against 6-OHDA-induced neurotoxicity due to the radical scavenging capacity of its antioxidant phytoconstituents and its ability to restore intracellular antioxidant activities.

Metal oxides are promising (photo)electrocatalysts for sustainable energy technologies due to their good activity and abundant resources. Their applications such as photocatalytic water splitting predominantly involve aqueous interfaces under electrochemical conditions, but in situ probing oxide-water interfaces is proven to be extremely challenging. Here, we present an electrochemical scanning tunneling microscopy (EC-STM) study on the rutile TiO 2 (110)-water interface, and by tuning surface redox chemistry with careful potential control we are able to obtain high quality images of interfacial structures with atomic details. It is interesting to find that the interfacial water exhibits an unexpected double-row pattern that has never been observed. This finding is confirmed by performing a large scale simulation of a stepped interface model enabled by machine learning accelerated molecular dynamics (MLMD) with ab initio accuracy. Furthermore, we show that this pattern is induced by the steps present on the surface, which can propagate across the terraces through interfacial hydrogen bonds. Our work demonstrates that by combining EC-STM and MLMD we can obtain new atomic details of interfacial structures that are valuable to understand the activity of oxides under realistic conditions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The intricate currents of the Northwest Pacific Ocean, with strong manifestations along the westside rim, connect tropical and subtropical gyres and significantly influence East Asian and global climates. The El Niño/Southern Oscillation (ENSO) originates in the tropical Pacific Ocean and disrupts this ocean circulation system. However, the spatiotemporal dependence of the impact of ENSO events has yet to be elucidated because of the complexities of both ENSO events and circulation systems, as well as the increased availability of observational data. We thus combined altimeter and drifter observations to demonstrate the distinct tropical and subtropical influences of the circulation system on ENSO diversity. During El Niño years, the North Equatorial Current, North Equatorial Countercurrent, Mindanao Current, Indonesian Throughflow, and the subtropical Kuroshio Current and its Extension region exhibit strengthening, while the tropical Kuroshio Current weakens. The tropical impact is characterized by sea level changes in the warm pool, whereas the subtropical influence is driven by variations in the wind stress curl. The tropical and subtropical influences are amplified during the Centra Pacific El Niño years compared to the Eastern Pacific El Niño years. As the globe warms, these impacts are anticipated to intensify. Thus, strengthening observation systems and refining climate models are essential for understanding and projecting the enhancing influences of ENSO on the Northwest Pacific Oceanic circulation., (© 2024. The Author(s).)

Enabling real-time monitoring and control of the biomanufacturing processes through product quality insights continues to be an area of focus in the biopharmaceutical industry. The goal is to manufacture products with the desired quality attributes. To realize this rigorous attribute-focused Quality by Design approach, it is critical to support the development of processes that consistently deliver high-quality products and facilitate product commercialization. Time delays associated with offline analytical testing can limit the speed of process development. Thus, developing and deploying analytical technology is necessary to accelerate process development. In this study, we have developed the micro sequential injection process analyzer and the automatic assay preparation platform system. These innovations address the unmet need for an automatic, online, real-time sample acquisition and preparation platform system for in-process monitoring, control, and release of biopharmaceuticals. These systems can also be deployed in laboratory areas as an offline analytical system and on the manufacturing floor to enable rapid testing and release of products manufactured in a good manufacturing practice environment., (© 2024 Wiley Periodicals LLC.)

Introduction: Severe spinal cord injury results in the loss of neurons in the relatively intact spinal cord below the injury area and skeletal muscle atrophy in the paralyzed limbs. These pathological processes are significant obstacles for motor function reconstruction., Objective: We performed tail nerve electrical stimulation (TNES) to activate the motor neural circuits below the injury site of the spinal cord to elucidate the regulatory mechanisms of the excitatory afferent neurons in promoting the reconstruction of locomotor function., Methods: Eight days after T10 spinal cord transection in rats, TNES was performed for 7 weeks. Behavioral scores were assessed weekly. Electrophysiological tests and double retrograde tracings were performed at week 8., Results: After 7 weeks of TNES treatment, there was restoration in innervation, the number of stem cells, and mitochondrial metabolism in the rats' hindlimb muscles. Double retrograde tracings of the tail nerve and sciatic nerve further confirmed the presence of synaptic connections between the tail nerve and central pattern generator (CPG) neurons in the lumbar spinal cord, as well as motor neurons innervating the hindlimb muscles., Conclusion: The mechanisms of TNES induced by the stimulation of primary afferent nerve fibers involves efficient activation of the motor neural circuits in the lumbosacral segment, alterations of synaptic plasticity, and the improvement of muscle and nerve regeneration, which provides the structural and functional foundation for the future use of cutting-edge biological treatment strategies to restore voluntary movement of paralyzed hindlimbs., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Objective: We aimed to explore the heterogeneity of neurons in heart failure with dilated cardiomyopathy (DCM)., Methods: Single-cell RNA sequencing (scRNA-seq) data of patients with DCM and chronic heart failure and healthy samples from GSE183852 dataset were downloaded from NCBI Gene Expression Omnibus, in which neuron data were extracted for investigation. Cell clustering analysis, differential expression analysis, trajectory analysis, and cell communication analysis were performed, and highly expressed genes in neurons from patients were used to construct a protein-protein interaction (PPI) network and validated by GSE120895 dataset., Results: Neurons were divided into six subclusters involved in various biological processes and each subcluster owned its specific cell communication pathways. Neurons were differentiated into two branches along the pseudotime, one of which was differentiated into mature neurons, whereas another tended to be involved in the immune and inflammation response. Genes exhibited branch-specific differential expression patterns. FLNA, ITGA6, ITGA1, and MDK interacted more with other gene-product proteins in the PPI network. The differential expression of FLNA between DCM and control was validated., Conclusion: Neurons have significant heterogeneity in heart failure with DCM, and may be involved in the immune and inflammation response to heart failure., (© 2024. The Author(s).)

Background: Cycloheximide (CXM), an antifungal antibiotic, causes impaired memory consolidation as a side effect partially by disturbing the activities of the central catecholaminergic and cholinergic system. Some reports indicated that puerarin prevented memory impairment in various models in rodents. However, the protective effects of puerarin on the side effects of cycloheximide for memory consolidation impairment have not yet been investigated., Methods: The protective effects of puerarin on CXM-induced memory-consolidation impairment, and memory impairment produced by central administration of AF64A neurotoxin, were investigated using a passive avoidance task in rats. A combination of transmitter receptor agonists and antagonists was used to explore the effects of puerarin on nervous system function. The activity of antioxidant defense systems and neurotransmitter systems in the prefrontal cortex and hippocampus were assayed., Results: Systemic (25 and 50 mg/kg, i.p.) or central (5 and 10 µg/brain, i.c.v.) administration of puerarin attenuated CXM-induced memory-consolidation impairment produced by 1.5 mg/kg CXM (s.c.) in rats. The improvements produced by 50 mg/kg puerarin were blocked by cholinergic antagonists, a 5-HT2 receptor agonist, and an adrenergic receptor antagonist. Puerarin (only at 50 mg/kg, i.p.) reversed the CXM-induced alterations of the levels of norepinephrine in the prefrontal cortex and the levels of monoamines in the hippocampus. Puerarin also increased antioxidant-defense-system activities in the prefrontal cortex and hippocampus, which had been decreased by CXM., Conclusions: We suggested that the attenuating effects of puerarin on CXM-induced memory-consolidation impairment may be due to decrease oxidative damage and the normalition of the neurotransmitter function in the prefrontal cortex and hippocampus., Competing Interests: The authors declare no conflict of interest. Chi-Rei Wu is serving as one of the Editorial Board members of this journal. We declare that Chi-Rei Wu had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Gernot Riedel., (© 2024 The Author(s). Published by IMR Press.)

Upregulation of TGFβ and Cox2 in the tumor microenvironment results in blockade of T-cell penetration into the tumor. Without access to tumor antigens, the T-cell response will not benefit from administration of the immune checkpoint antibodies. We created an intravenous polypeptide nanoparticle that can deliver two siRNAs (silencing TGFβ and Cox2). Systemic administration in mice, bearing a syngeneic orthotopic hepatocellular carcinoma (HCC), delivers the siRNAs to various cells in the liver, and significantly reduces the tumor. At 2 mg/kg (BIW) the nanoparticle demonstrated a single agent action and induced tumor growth inhibition to undetectable levels after five doses. Reducing the siRNAs to 1mg/kg BIW demonstrated greater inhibition in the presence of PD-L1 mAbs. After only three doses BIW, we could still recover a smaller tumor and, in tumor sections, showed an increase in penetration of CD4+ and CD8+ T-cells deeper into the remaining tumor that was not evident in animals treated with non-silencing siRNA. The combination of TGFβ and Cox2 siRNA co-administered in a polypeptide nanoparticle can act as a novel therapeutic alone against HCC and may augment the activity of the immune checkpoint antibodies. Silencing TGFβ and Cox2 converts an immune excluded (cold) tumor into a T-cell inflamed (hot) tumor., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Cancer.)

Hepatocellular carcinoma (HCC) usually recurs after curative surgical resection. Currently, no approved adjuvant therapy has been shown to reduce HCC recurrence rates. In this study, the in vivo effect of sequential combination treatment with recombinant mouse interferon-alpha (rmIFN-α) and an anti-mouse-PD1 antibody on hepatitis B virus (HBV) clearance in mice was evaluated. A Phase I clinical trial was then conducted to assess the safety, tolerability, and inhibitory activity of sequential therapy with ropeginterferon alfa-2b and nivolumab in patients with HCC recurrence who underwent curative surgery for HBV-related HCC. The animal modeling study showed that HBV suppression was significantly greater with the rmIFN-α and anti-PD1 sequential combination treatment in comparison with sole treatment with rmIFN-α or anti-PD1. In the Phase I study, eleven patients completed the sequential therapy with ropeginterferon alfa-2b every two weeks for six doses at 450 µg, followed by three doses of nivolumab every two weeks up to 0.75 mg/kg. A notable decrease in or clearance of HBV surface antigen was observed in two patients. The dose-limiting toxicity of grade 3 alanine transaminase and aspartate aminotransferase increases was observed in one patient. The maximum tolerated dose was then determined. To date, no HCC recurrence has been observed. The treatment modality was well tolerated. These data support the further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC.

The global aging population is expanding at an increasingly rapid pace, with approximately one-fourth of the world's population expected to be composed of elderly individuals by 2050. Aging skin is one of the major characteristics expressed in the elderly. The study comprehensively utilizes both cell and animal experiments to confirm the skin anti-aging effects of Poria cocos ( P. cocos) , which is one of the most important traditional Chinese medicines classified as tonic Chinese medicine, commonly used to treat physical weakness and aging-associated diseases. We demonstrate in this study that P. cocos lanostane triterpenoids extract (Lipucan ® ) ameliorates aging skin and promotes collagen accumulation and hyaluronic acid production in galactose-induced aging rats. Purified lanostane triterpenoids were initially identified as active components in P. cocos , which significantly increased collagen and hyaluronic acid levels in cultured human skin cells.

This study identifies seasonally-reversed trends in Kuroshio strength and sea surface temperatures (SSTs) within the western North Pacific (WNP) since the 1990s, specifically in the 22° N-28° N region. These trends are characterized by increases during summer and decreases during winter. The seasonally-reversed trends are a result of the asymmetric responses of the WNP to a shift towards the positive phase of the Atlantic multidecadal oscillation (AMO) around the same period. The positive AMO induces an anomalous descent over the North Pacific during summer, leading to the direct strengthening of the gyre. However, during winter, it triggers an anomalous descent over the tropical Pacific, which excites a poleward wavetrain impacting the WNP and causing gyre weakening. The associated responses of the East Asian monsoon and China Coastal Current contribute to the observed seasonally-reversed SST trends. It is noteworthy that the seasonally-reversed trends in gyre strength and SSTs are predominantly observed north of 20° N in the WNP. This limitation arises because the anomalous cyclone within the winter poleward wavetrain is located north of this latitude boundary. Specifically, the clearest trends in gyre strength are observed in the northern segment of the Kuroshio, while the manifestation of SST trends in the Taiwan Strait could potentially be attributed to the influence and enhancement of the East Asian monsoon and the China Coastal Current. Due to the limited length of observational data, statistical significance of some of the signals discussed is rather limited. A CESM1 pacemaker experiments is further conducted to confirm the asymmetric responses of the North Pacific to the AMO between the summer and winter seasons., (© 2023. Springer Nature Limited.)

In the process of making mushrooms into vacuum-fried crisps, the resulting blanched broth (BB) and centrifuged broth (CB) are often discarded, thereby increasing the amount of wastewater and treatment costs. This study measured the proximate compositions, bioactive components, taste components, and minerals of freeze-dried BB and CB and then used functional indigestible dextrin (Fibersol-2) as a carrier to make these two broths into instant drinks. The solids of the BB and CB contained protein (16.88-19.21%), fat (0.01-0.23%), ash (12.89-13.50%), carbohydrate (67.28-70.00%), sugars and polyols (40.55-45.68%), free amino acids (6.58-6.69%), 5'-nucleotides (0.98-1.47%), and bioactive components, especially polysaccharides (4.53-7.45%), ergothioneine (both 0.19%), and total phenols (0.15-0.36%). The equivalent umami concentration of BB was 2.77-fold higher than that of the CB. Both BB and CB showed compositions and essential minerals that are rich in taste. Using a nine-point hedonic test, it was found that the solid contents of BB and CB in the instant drink affected the consumer's preference. The flavor and overall preference of instant drinks with 2.5% BB or CB were the best amongst consumers. Overall, the BB and CB were rich in nutrients and bioactive and taste components and could be developed as a functional food in the form of a drink.

Background: After spinal cord transection injury, the inflammatory microenvironment formed at the injury site, and the cascade of effects generated by secondary injury, results in limited regeneration of injured axons and the apoptosis of neurons in the sensorimotor cortex (SMC). It is crucial to reverse these adverse processes for the recovery of voluntary movement. The mechanism of transcranial intermittent theta-burst stimulation (iTBS) as a new non-invasive neural regulation paradigm in promoting axonal regeneration and motor function repair was explored by means of a severe spinal cord transection., Methods: Rats underwent spinal cord transection and 2 mm resection of spinal cord at T10 level. Four groups were studied: Normal (no lesion), Control (lesion with no treatment), sham iTBS (lesion and no functional treatment) and experimental, exposed to transcranial iTBS, 72 h after spinal lesion. Each rat received treatment once a day for 5 days a week; behavioral tests were administered one a week. Inflammation, neuronal apoptosis, neuroprotective effects, regeneration and synaptic plasticity after spinal cord injury (SCI) were determined by immunofluorescence staining, western blotting and mRNA sequencing. For each rat, anterograde tracings were acquired from the SMC or the long descending propriospinal neurons and tested for cortical motor evoked potentials (CMEPs). Regeneration of the corticospinal tract (CST) and 5-hydroxytryptamine (5-HT) nerve fibers were analyzed 10 weeks after SCI., Results: When compared to the Control group, the iTBS group showed a reduced inflammatory response and reduced levels of neuronal apoptosis in the SMC when tested 2 weeks after treatment. Four weeks after SCI, the neuroimmune microenvironment at the injury site had improved in the iTBS group, and neuroprotective effects were evident, including the promotion of axonal regeneration and synaptic plasticity. After 8 weeks of iTBS treatment, there was a significant increase in CST regeneration in the region rostral to the site of injury. Furthermore, there was a significant increase in the number of 5-HT nerve fibers at the center of the injury site and the long descending propriospinal tract (LDPT) fibers in the region caudal to the site of injury. Moreover, CMEPs and hindlimb motor function were significantly improved., Conclusion: Neuronal activation and neural tracing further verified that iTBS had the potential to provide neuroprotective effects during the early stages of SCI and induce regeneration effects related to the descending motor pathways (CST, 5-HT and LDPT). Furthermore, our results revealed key relationships between neural pathway activation, neuroimmune regulation, neuroprotection and axonal regeneration, as well as the interaction network of key genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Wang, Chen, Wu, Yu, Yang, Xu, Guo, Ding, Li, Zeng, Ma, Gong, Wu, Zhang, Zeng and Lai.)

Background: With its high nutritional value and productivity, Italian ryegrass as a biomass feedstock constantly supplies rumen degradable nitrogen and digestible fiber to ruminants. However, biofuel production is easily reduced during ensiling due to the high-moisture content of Italian ryegrass, leading to economic losses. Lactic acid bacteria inoculants could improve lignocellulosic degradation and fermentation quality and decrease dry matter loss during the bioprocessing of silage. Therefore, this study analyzed the effects of Lactobacillus buchneri TSy1-3 (HE), Lactobacillus rhamnosus BDy3-10 (HO), and the combination of HE and HO (M) on fermentation quality, bacterial community and metabolome in high-moisture Italian ryegrass silage during ensiling., Results: The results showed that the pH value was significantly lower in the HO groups than in the other treatments at the end of ensiling, and the dry matter and acetic acid contents were significantly higher in the HO group than in the other inoculated groups. All inoculants decreased the diversity of the bacterial community and significantly increased the relative abundance of Lactobacillus. Inoculation with HO significantly improved the concentrations of organic acids, dipeptides, ferulic acid, apigenin, and laricitrin. Compared with Lactobacillus buchneri TSy1-3 (HE), HO significantly upregulated the flavonoid compounds in the flavone and flavonol biosynthesis pathway., Conclusions: Overall, these findings suggest that inoculation with HO was beneficial for the development of Italian ryegrass as a biomass feedstock, improving fermentation quality, accelerating changes in bacterial community composition and increasing biofunctional metabolites in high-moisture Italian ryegrass silage., (© 2023. The Author(s).)

Ni-based transition metal oxides are promising oxygen-evolution reaction (OER) catalysts due to their abundance and high activity. Identification and manipulation of the chemical properties of the real active phase on the catalyst surface is crucial to improve the reaction kinetics and efficiency of the OER. Herein, we used electrochemical-scanning tunnelling microscopy (EC-STM) to directly observe structural dynamics during the OER on LaNiO 3 (LNO) epitaxial thin films. Based on comparison of dynamic topographical changes in different compositions of LNO surface termination, we propose that reconstruction of surface morphology originated from transition of Ni species on LNO surface termination during the OER. Furthermore, we showed that the change in surface topography of LNO was induced by Ni(OH) 2 /NiOOH redox transformation by quantifying STM images. Our findings demonstrate that in situ characterization for visualization and quantification of thin films is very important for revealing the dynamic nature of the interface of catalysts under electrochemical conditions. This strategy is crucial for in-depth understanding of the intrinsic catalytic mechanism of the OER and rational design of high-efficiency electrocatalysts., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Class I small heat shock proteins (CI sHSPs), OsHsp16.9A and OsHsp18.0, share 74% identity in amino acid sequences and accumulate in response to heat shock treatments. Individual rice transformants overexpressing OsHsp16.9A and OsHsp18.0 exhibit distinct thermoprotection/thermotolerance modes. Under high temperature stress, OsHsp16.9A-overexpressing lines showed higher seed germination rate, seedling survival, and pollen germination than wild-type controls, while OsHsp18.0 overexpression provided higher thermoprotection/thermotolerance for seedling survival. To elucidate the functional roles of OsHsp16.9A, mass spectrometry was used to identify OsHsp16.9A-interacting proteins. OsHsp101 was consistently identified in the OsHsp16.9A protein complex in several mass spectrometry analyses of seed proteins from OsHsp16.9A-overexpressing lines. Both OsHsp16.9A and OsHsp101 proteins accumulated during similar developmental stages of rice seeds and formed a heat-stable complex under high temperature treatments in in vitro assays. Co-localization of OsHsp16.9A and OsHsp101 was observed via ratiometric bimolecular fluorescence complementation analyses. Amino acid mutation studies revealed that OsHsp16.9A glutamate residue 74 and amino acid residues 23-36 were essential for OsHsp16.9A-OsHsp101 interaction. Moreover, overexpressing OsHsp16.9A in OsHsp101 knockdown mutants did not increase the seed germination rate under heat stress, which further confirmed the functional roles of OsHsp16.9A-OsHsp101 interaction in conferring thermotolerance to rice plants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study is started from a photon-magnon model with a competition effect of the level attraction and repulsion, its Hermiticity is mainly decided by a phase-dependent and asymmetric coupling factor, namely φ  = 0 for Hermitian andϕ=πfor non-Hermitian. Then an extensional study predicts the quantum critical behaviors using an Hermitian and even no-Hermitian photon-spins model with an additional second-order drive. The numerical results firstly indicate that this coupling phase φ can function the protective effect on quantum phase transitions (QPTs), and the new tricritical points can not only be modulated by this nonlinear drive, but also be influenced by the dissipation and the collective decoherence. Secondly, this competition effect can also induce a reversal of the value of order parameters between the positive and negative. This study can also bring more important results of QPTs toward the issue of symmetry breaking and non-Hermiticity., (© 2023 IOP Publishing Ltd.)

The innate immune response plays an important role in the pathological process of ischemic stroke. Increasing evidence suggests that the inflammatory response triggered by the innate immune system hinders neurological and behavioural recovery after stroke. The perception of abnormal DNA and its downstream effects are an essential part of the innate immune system. The abnormal DNA is the major inducing factor for innate immune response and is sensed by a series of DNA sensors. In this review, we discussed the multiple roles of DNA sensing in the pathological process of ischemic stroke, with a special focus on DNA sensors Toll-like receptor 9 (TLR9), absent in melanoma 2 (AIM2) and cyclic GMP-AMP synthase (cGAS)., (© 2023 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Silage can be contaminated with mycotoxins and accidental fungi after aerobic exposure. The study assessed the effects of bunker silos (BS), round bales (RB), and silage bags (SB) on the nutritional characteristics, fermentation quality, aerobic stability, mycotoxin levels and microbial communities of whole-plant corn silage (WPCS). After 90 days of fermentation, silages were opened and sampled at 0, 1, 3, 5, 7, and 9 days of exposure. SB group conserved higher lactic acid and dry matter contents and a lower pH value than other groups after 9 days of exposure ( p  < 0.05). The SB group showed the longest aerobic stability (202 h) among all silages ( p  < 0.05). The concentrations of aflatoxin B1, trichothecenes and fumonisin B1 were significantly lower in SB after 9 days of exposure ( p  < 0.05). Acetobacter became the dominant bacteria in BS and RB groups after 5 days of exposure. However, Lactobacillus still dominated the bacterial community in SB group. Acetobacter was positively correlated with pH, acetic acid content, and ammonia-N content ( p  < 0.05). Lactobacillus was positively correlated with Kazachstania and Candida abundances ( p  < 0.01) but negatively correlated with Fusarium abundance ( p  < 0.05). Considering the feed value and food safety of silage in the feeding process, silage bags are recommended for WPCS according to the observed nutritional quality, fermentation index and mycotoxin content., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xia, Huang, Wu, Zhang, Yin, Yang, Chen and Hao.)

Mitochondrial dysfunction has been implicated in Parkinson's disease. Mic60 is a critical component of mitochondrial crista remodeling and participates in maintaining mitochondrial structure and function. This study investigated whether the carnosic acid (CA) of rosemary protects the mitochondria of SH-SY5Y cells against the neurotoxicity of 6-hydroxydopamine (6-OHDA) by regulating Mic60. Our results showed that CA pretreatment reversed the reduction in the Mic60 and citrate synthase proteins, as well as the protein induction of PKA caused by 6-OHDA. Moreover, Mic60 and PINK1 siRNAs blocked the ability of CA to lessen the release of mitochondrial cytochrome c by 6-OHDA. As shown by immunoprecipitation assay, in 6-OHDA-treated cells, the interaction of Mic60 with its phosphorylated threonine residue was decreased, but the interaction with its phosphorylated serine residue was increased. PINK1 siRNA and forskolin, a PKA activator, reversed these interactions. Moreover, forskolin pretreatment prevented CA from rescuing the interaction of PINK1 and Mic60 and the reduction in cytochrome c release and mitophagy impairment in 6-OHDA-treated cells. In conclusion, CA prevents 6-OHDA-induced cytochrome c release by regulating Mic60 phosphorylation by PINK1 through a downregulation of PKA. The regulation of Mic60 by CA can be considered as a protective mechanism for the prevention of Parkinson's disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Extractions of the underground parts of valerian were prepared with water and ethanol (25-95%) at 25-75 °C. Extraction yields, bioactive compounds, and the 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability of lyophilized extracts were determined. The inhibitory effects of the extracts, valerenic acid derivatives and phenolic acids, on metabolic syndrome (MS)-related enzymes activities were further examined. Both roots and rhizomes extracted with 95% ethanol at 75 °C had the highest levels of bioactive compounds. The antioxidant capacity and inhibition of MS-related enzymes of the roots extract were better than those of the rhizomes. The roots extract more strongly inhibited pancreatic lipase (inhibition of 50% of enzyme activity (IC 50 ), 17.59 mg/mL), angiotensin-converting enzyme (ACE, IC 50 , 3.75 mg/mL), α-amylase (IC 50 , 12.53 mg/mL), and α-glucosidase (IC 50 , 15.40 mg/mL). These four phenolic acids inhibited the activity of MS-related enzymes. Valerenic acid demonstrated more of an inhibitory ability for ACE (IC 50 , 0.225 mg/mL, except for caffeic acid) and α-glucosidase (IC 50 , 0.617 mg/mL) than phenolic acids. Valerian extract inhibited key enzyme activities that were associated with obesity (lipase), hypertension (ACE), and type 2 diabetes (α-amylase and α-glucosidase), suggesting that it is a potential candidate for the development of functional supplements.

Long-term reanalysis data were used to assess inter-decadal to decadal modulations of the North Equatorial Current (NEC) bifurcation in the Pacific after the early 1990s. The wind stress curl anomaly (WSCA) in the region of 10° N-15° N and 160° E-170° E (C-BOX) had been found to excite Rossby waves and control NEC bifurcation along the Philippine coast. Our analysis revealed that the WSCA in the C-BOX has been remotely modulated by the Southern Annular Mode (SAM) since the early 1990s. It is shown that the SAM shifted to its positive phase at this transition and began strongly impacting the WSCA in the C-BOX and the NEC bifurcation. During the positive SAM phase after the early 1990s, strong climate variability occurred in the tropical to subtropical area of the North Pacific, with a clear footprint connected to the Antarctic region. Consistent with that finding, we determined that during the positive SAM phase, a dipole sea surface temperature pattern was generated in the South Pacific; this induced an atmospheric Rossby wave train in upper-level wind shear that propagated northward to the North Pacific. Such effects further enhanced downward motion and divergence at the surface, intensifying the easterlies in the equatorial area and the anticyclonic WSCA in the C-BOX. The anticyclonic WSCA in the C-BOX substantially excited downwelling oceanic Rossby waves at the surface, inducing an equatorward trend of NEC bifurcation after the early 1990s., (© 2022. The Author(s).)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and persistently threatens to humanity. With tireless efforts from scientists around the world, understanding of the biology of coronavirus has been greatly enhanced over the past 2 years. Structural biology has demonstrated its powerful impact on uncovering structures and functions for the vast majority of SARS-CoV-2 proteins and guided the development of drugs and vaccines against COVID-19. In this review, we summarize current progress in the structural biology of SARS-CoV-2 and discuss important biological issues that remain to be addressed. We present the examples of structure-based design of Pfizer's novel anti-SARS-CoV-2 drug PF-07321332 (Paxlovid), Merck's nucleotide inhibitor molnupiravir (Lagevrio), and VV116, an oral drug candidate for COVID-19. These examples highlight the importance of structure in drug discovery to combat COVID-19. We also discussed the recent variants of Omicron and its implication in immunity escape from existing vaccines and antibody therapies., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Oral mucositis is a common adverse effect of cancer therapy. Probiotics have been shown to exert anti-inflammatory and immunomodulatory effects. We performed a meta-analysis of randomized controlled trials (RCTs) to investigate whether probiotics can prevent cancer therapy−induced oral mucositis. We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases for trials related to probiotics and oral mucositis published before September 2022; no language restrictions were applied. The primary outcome was the incidence of oral mucositis and severe oral mucositis. Secondary outcomes were the requirement for enteral nutrition during treatment, body weight loss, and decreased quality of life. The study has been registered in PROSPERO (number: CRD 42022302339). Eight RCTs, including 708 patients, were reviewed; however, a meta-analysis of only seven trials could be performed. Three trials using Lactobacilli-based probiotics reported that the incidence of oral mucositis in the probiotic group was significantly low (risk ratio [RR] = 0.84, 95% confidence interval [CI] = 0.77−0.93, p = 0.0004). Seven trials reported a significantly low incidence of severe oral mucositis in the probiotic group (RR = 0.65, 95% CI = 0.53−0.81, p < 0.0001). The requirement of enteral nutrition was significantly low in the probiotic group (odds ratio = 0.34, 95% CI: 0.13−0.92, p < 0.05). This study demonstrated the effectiveness of probiotics in the prevention and mitigation of cancer therapy−induced oral mucositis. We recommend the use of probiotics to prevent and treat oral mucositis during cancer therapy.

Isoflavones have been widely studied and have attracted extensive attention in fields ranging from chemotaxonomy and plant physiology to human nutrition and medicine. Isoflavones are often divided into three subgroups: simple O-substituted derivatives, prenylated derivatives, and glycosides. Simple O-substituted isoflavones and their glycosides, such as daidzein (daidzin), genistein (genistin), glycitein (glycitin), biochanin A (astroside), and formononetin (ononin), are the most common ingredients in legumes and are considered as phytoestrogens for daily dietary hormone replacement therapy due to their structural similarity to 17-β-estradiol. On the basis of the known estrogen-like potency, these above isoflavones possess multiple pharmacological activities such as antioxidant, anti-inflammatory, anticancer, anti-angiogenetic, hepatoprotective, antidiabetic, antilipidemic, anti-osteoporotic, and neuroprotective activities. However, there are very few review studies on the protective effects of these novel isoflavones and their related compounds in cerebral ischemia reperfusion. This review primarily focuses on the biosynthesis, metabolism, and neuroprotective mechanism of these aforementioned novel isoflavones in cerebral ischemia reperfusion. From these published works in in vitro and in vivo studies, simple O-substituted isoflavones could serve as promising therapeutic compounds for the prevention and treatment of cerebral ischemia reperfusion via their estrogenic receptor properties and neuron-modulatory, antioxidant, anti-inflammatory, and anti-apoptotic effects. The detailed mechanism of the protective effects of simple O-substituted isoflavones against cerebral ischemia reperfusion might be related to the PI3K/AKT/ERK/mTOR or GSK-3β pathway, eNOS/Keap1/Nrf-2/HO-1 pathway, TLRs/TIRAP/MyD88/NFκ-B pathway, and Bcl-2-regulated anti-apoptotic pathway. However, clinical trials are needed to verify their potential on cerebral ischemia reperfusion because past studies were conducted with rodents and prophylactic administration.

Background and Aims: Hepatitis B immunoglobulin (HBIG) has been routinely applied in the liver transplantation setting to block HBV reinfection of grafts. However, new monoclonal anti-HBV surface antibodies have been developed to replace HBIG. The epitopes of such monoclonal antibodies may affect the emergence of escape variants and deserve study., Approach and Results: The conformational epitope of sLenvervimab, a surrogate form of Lenvervimab, which is a monoclonal anti-HBsAg antibody currently under phase 3 trial, was investigated by selecting escape mutants from a human liver chimeric mouse. HBV-infected chimeric mice treated with sLenvervimab monotherapy showed an initial decline in circulating HBsAg levels, followed by a quick rebound in 1 month. Sequencing of circulating or liver HBV DNA revealed emerging variants, with replacement of amino acid E164 or T140, two residues widely separated in HBsAg. E164 HBV variants strongly resisted sLenvervimab neutralization in cell culture infection, and the T140 variant moderately resisted sLenvervimab neutralization. Natural HBV variants with amino-acid replacements adjacent to E164 were constructed and examined for sLenvervimab neutralization effects. Variants with K160 replacement also resisted neutralization. These data revealed the conformational epitope of sLenvervimab., Conclusions: Selection of antibody-escape HBV variants in human chimeric mice works efficiently. Analysis of such emerging variants helps to identify anchor amino-acid residues of the conformational epitope that are difficult to discover by conventional approaches., (© 2022 American Association for the Study of Liver Diseases.)

Circular RNAs (circRNAs) are a new and large group of non-coding RNA molecules that are abundantly expressed in the central nervous system. However, very little is known about their roles in traumatic brain injury. In this study, we firstly screened differentially expressed circRNAs in normal and injured brain tissues of mice after traumatic brain injury. We found that the expression of circLphn3 was substantially decreased in mouse models of traumatic brain injury and in hemin-treated bEnd.3 (mouse brain cell line) cells. After overexpressing circLphn3 in bEnd.3 cells, the expression of the tight junction proteins, ZO-1, ZO-2, and occludin, was upregulated, and the expression of miR-185-5p was decreased. In bEnd.3 cells transfected with miR-185-5p mimics, the expression of ZO-1 was decreased. Dual-luciferase reporter assays showed that circLphn3 bound to miR-185-5p, and that miR-185-5p bound to ZO-1. Additionally, circLphn3 overexpression attenuated the hemin-induced high permeability of the in vitro bEnd.3 cell model of the blood-brain barrier, while miR-185-5p transfection increased the permeability. These findings suggest that circLphn3, as a molecular sponge of miR-185-5p, regulates tight junction proteins' expression after traumatic brain injury, and it thereby improves the permeability of the blood-brain barrier. This study was approved by the Animal Care and Use Committee of Chongqing Medical University of China (approval No. 2021-177) on March 22, 2021., Competing Interests: None

We systematically compared the effects of prophylactic anticonvulsant drug use in patients with traumatic brain injury. We searched four electronic databases from their inception until July 13, 2021. Two researchers independently screened, appraised, and extracted the included studies. Network meta-analysis using multivariate random effects and a frequentist framework was adopted for data analysis. The risk of bias of each study was assessed using the Cochrane risk of bias tool, and confidence in evidence was assessed through confidence in network meta-analysis (CINeMA). A total of 11 randomized controlled trials involving 2,450 participants and six different treatments (i.e., placebo, carbamazepine, phenytoin, levetiracetam, valproate, and magnesium sulfate) were included. We found that anticonvulsant drugs as a whole significantly reduced early posttraumatic seizures (PTS) but not late PTS compared with placebo (odd ratios [ORs] = 0.42 and 0.82, 95% confidence intervals [CIs] = 0.21-0.82 and 0.47-1.43). For the findings of network meta-analysis, we observed that phenytoin (ORs = 0.43 and 0.71; 95% CIs = 0.18-1.01 and 0.23-2.20), levetiracetam (ORs = 0.56 and 1.58; 95% CIs = 0.12-2.55 and 0.03-84.42), and carbamazepine (ORs = 0.29 and 0.64; 95% CIs = 0.07-1.18 and 0.08-5.28) were more likely to reduce early and late PTS compared with placebo; however, the treatment effects were not significant. Sensitivity analysis, after excluding a study enrolling only children, revealed that phenytoin had a significant effect in preventing early PTS (OR = 0.33; 95% CI = 0.14-0.78). Our findings indicate that no antiepileptic drug had an effect on early or late PTS superior to that of another; however, the sensitivity analysis revealed that phenytoin might prevent early PTS. Additional studies with large sample sizes and a rigorous design are required to obtain high-quality evidence on prophylactic anticonvulsant drug use in patients with traumatic brain injury., Competing Interests: The authors have declared that no competing interests exist.

Nitric oxide (NO) is an endogenous gasotransmitter regulating alternative physiological processes in the cardiovascular system. To achieve translational application of NO, continued efforts are made on the development of orally active NO prodrugs for long-term treatment of chronic cardiovascular diseases. Herein, immobilization of NO-delivery [Fe 2 (μ-SCH 2 CH 2 COOH) 2 (NO) 4 ] ( DNIC-2 ) onto MIL-88B, a metal-organic framework (MOF) consisting of biocompatible Fe 3+ and 1,4-benzenedicarboxylate (BDC), was performed to prepare a DNIC@MOF microrod for enhanced oral delivery of NO. In simulated gastric fluid, protonation of the BDC linker in DNIC@MOF initiates its transformation into a DNIC@tMOF microrod, which consisted of DNIC-2 well dispersed and confined within the BDC-based framework. Moreover, subsequent deprotonation of the BDC-based framework in DNIC@tMOF under simulated intestinal conditions promotes the release of DNIC-2 and NO. Of importance, this discovery of transformer-like DNIC@MOF provides a parallel insight into its stepwise transformation into DNIC@tMOF in the stomach followed by subsequent conversion into molecular DNIC-2 in the small intestine and release of NO in the bloodstream of mice. In comparison with acid-sensitive DNIC-2 , oral administration of DNIC@MOF results in a 2.2-fold increase in the oral bioavailability of NO to 65.7% in mice and an effective reduction of systolic blood pressure (SBP) to a ΔSBP of 60.9 ± 4.7 mmHg in spontaneously hypertensive rats for 12 h.

Background: Fatigue, a common complaint reported by patients with cancer or in survivorship, has been negatively associated with quality of life, emotional health, and cognitive functions. Acupressure, a traditional Chinese medicine, has been increasingly practiced in clinical and community settings. However, little evidence supports the beneficial effects of acupressure on the reduction of general, physical, and mental fatigue in cancer survivors., Objective: The aim of this study was to examine the effect of acupressure on fatigue in cancer survivors and the moderators of the effect of acupressure on cancer-related fatigue relief., Methods: Databases, namely, PubMed, Embase, CINAHL, and ProQuest, were searched from their inception to July 17, 2020. No language and publication period restrictions were applied. Only randomized controlled trials that examined the effects of acupressure on cancer-related fatigue were included. A random-effects model was used for data analyses., Results: Fourteen articles involving 776 participants with cancers were included. Acupressure considerably alleviated cancer-related general, physical, and mental fatigue (g = -0.87, -0.87, and -0.37) compared with controls. Increasing female percentage of participants significantly reduced the effects of acupressure on fatigue (B = -0.01, P < .001). The executor and operation approach as well as treatment period during chemotherapy did not moderate the effects of acupressure on fatigue relief., Conclusion: Acupressure is effective at alleviating cancer-related fatigue., Implications for Practice: Health professionals and patients can use acupressure to alleviate fatigue during and after chemotherapy. Nursing personnel could incorporate acupressure into clinical practice as part of a multimodal approach to alleviating fatigue in cancer survivors., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The present study investigated the impact of carnosic acid (CA) from rosemary on the levodopa ( L -dopa)-induced dyskinesia (LID) in rats treated with 6-hydroxydopamine (6-OHDA). To establish the model of LID, 6-OHDA-lesioned rats were injected intraperitoneally with 30 mg/kg L -dopa once a day for 36 days. Rats were daily administrated with 3 or 15 mg/kg CA by oral intubation prior to L -dopa injection for 4 days. Rats pretreated with CA had reduced L -dopa-induced abnormal involuntary movements (AIMs) and ALO scores (a sum of axial, limb, and orofacial scores). Moreover, the increases of dopamine D1-receptor, p-DARPP-32, ΔFosB, p-ERK1/2, and p-c-Jun ser63, along with the decrease in p-c-Jun ser73, induced by L -dopa in 6-OHDA-treated rats were significantly reversed by pretreatment with CA. In addition, we used the model of SH-SY5Y cells to further examine the neuroprotective mechanisms of CA on L -dopa-induced cytotoxicity. SH-SY5Y cells were treated with CA for 18 h, and then co-treated with 400 μM L -dopa for the indicated time points. The results showed that pretreatment of CA attenuated the cell death and nuclear condensation induced by L -dopa. By the immunoblots, the reduction of Bcl-2, p-c-Jun ser73, and parkin and the induction of cleaved caspase 3, cleaved Poly (ADP-ribose) polymerase, p-ERK1/2, p-c-Jun ser63, and ubiquitinated protein by L -dopa were improved in cells pretreated with CA. In conclusion, CA ameliorates the development of LID via regulating the D1R signaling and prevents L -dopa-induced apoptotic cell death through modulating the ERK1/2-c-Jun and inducing the parkin. This study suggested that CA can be used to alleviate the adverse effects of LID for PD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lai, Lin, Wu, Tsai and Tsai.)

In previous research, a series of cytotoxic anticancer analogues related to 2-acylamino-1,4-naphthoquinone derivatives has been demonstrated. As microtubule plays an important role in many essential cellular processes such as mitosis, tubulin is an important target of anticancer drug. This study performed molecular docking simulation, pharmacophore model, comparative force field analysis model and comparative similarity indices analysis model to investigate the relationship between inhibitory activities and the properties of compounds, in order to further progress the development of cytotoxic anticancer analogues. These compounds have common H-bond interactions with key residues Lys254 and Lys352, but compounds with large R2 substituent have different docking poses than compounds with small R2 substituent. Some of derivatives such as compound 18 formed the H-bonds with residue Lys254 using the oxygen atoms in R1 substituent and formed π-cation interactions with residue Lys352 using phenyl moiety of 1,4-naphthoquinone. The R1 substituent of these compounds preferred to have disfavoured hydrophobic fields and favourable space towards the direction of residue Asn258, while the R2 substituent of these compounds preferred to have about 2-3 carbon chain length hydrophobic substituent towards the direction of residues Ala316 and Lys352. These results offer some beneficial advices for further study in anticancer drug development process., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

In the present investigation, we compared the radical-scavenging activities and phenolic contents of seven Taiwanese Cirsium species with a spectrophotometric method. We further analyzed their phytochemical profiles with high-performance liquid chromatography-photodiode array detection (HPLC-DAD). We found that the flower part of Cirsium japonicum var. australe (CJF) showed the best radical-scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and the hypochlorite ion, for which the equivalents were 6.44 ± 0.17 mg catechin/g, 54.85 ± 0.66 mmol Trolox/g and 418.69 ± 10.52 mmol Trolox/g respectively. CJF also had the highest contents of total phenolics (5.23 ± 0.20 mg catechin/g) and phenylpropanoids (29.73 ± 0.72 mg verbascoside/g). According to the Pearson's correlation coefficient, there was a positive correlation between the total phenylpropanoid content and ABTS radical-scavenging activities (r = 0.979). The radical-scavenging activities of the phenylpropanoids are closely related to their reducing power (r = 0.986). HPLC chromatograms obtained in validated HPLC conditions confirm that they have different phytochemical profiles by which they can be distinguished. Only CJF contained silicristin (0.66 ± 0.03 mg/g) and silydianin (9.13 ± 0.30 mg/g). CJF contained the highest contents of apigenin (5.56 ± 0.09 mg/g) and diosmetin (2.82 ± 0.10 mg/g). Among the major constituents, silicristin had the best radical-scavenging activities against DPPH (71.68 ± 0.66 mg catechin/g) and ABTS (3.01 ± 0.01 mmol Trolox/g). However, diosmetin had the best reducing power and radical-scavenging activity against the hypochlorite anion (41.57 ± 1.14 mg mmol Trolox/g). Finally, we found that flavonolignans (especial silicristin and silydianin) and diosmetin acted synergistically in scavenging radicals.

Nitric oxide (NO), a pro-neurogenic and antineuroinflammatory gasotransmitter, features the potential to develop a translational medicine against neuropathological conditions. Despite the extensive efforts made on the controlled delivery of therapeutic NO, however, an orally active NO prodrug for a treatment of chronic neuropathy was not reported yet. Inspired by the natural dinitrosyl iron unit (DNIU) [Fe(NO) 2 ], in this study, a reversible and dynamic interaction between the biomimetic [(NO) 2 Fe(μ-SCH 2 CH 2 OH) 2 Fe(NO) 2 ] ( DNIC-1 ) and serum albumin (or gastrointestinal mucin) was explored to discover endogenous proteins as a vehicle for an oral delivery of NO to the brain after an oral administration of DNIC-1 . On the basis of the in vitro and in vivo study, a rapid binding of DNIC-1 toward gastrointestinal mucin yielding the mucin-bound dinitrosyl iron complex (DNIC) discovers the mucoadhesive nature of DNIC-1 . A reversible interconversion between mucin-bound DNIC and DNIC-1 facilitates the mucus-penetrating migration of DNIC-1 shielded in the gastrointestinal tract of the stomach and small intestine. Moreover, the NO-release reactivity of DNIC-1 induces the transient opening of the cellular tight junction and enhances its paracellular permeability across the intestinal epithelial barrier. During circulation in the bloodstream, a stoichiometric binding of DNIC-1 to the serum albumin, as another endogenous protein vehicle, stabilizes the DNIU [Fe(NO) 2 ] for a subsequent transfer into the brain. With aging mice under a Western diet as a disease model for metabolic syndrome and cognitive impairment, an oral administration of DNIC-1 in a daily manner for 16 weeks activates the hippocampal neurogenesis and ameliorates the impaired cognitive ability. Taken together, these findings disclose the synergy between biomimetic DNIC-1 and endogenous protein vehicles for an oral delivery of therapeutic NO to the brain against chronic neuropathy., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Ghrelin is a peptide hormone with strong anti-inflammatory properties. In fact, Ghrelin was reported to improve endothelial dysfunction caused by excessive fat. However, its role in preserving the integrity of brain microvascular, under conditions of lipid dysregulation and inflammation, is not known. The objective of this study is to characterize the role of Ghrelin in the protection of cerebral microvascular integrity, during atherosclerosis, and uncover its underlying molecular mechanism. Our results demonstrated that an atherosclerotic condition, brought on by a high fat diet (HFD), can produce massive increases in serum inflammatory factors, blood lipids, cerebral microvascular leakage, and activation of the p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) (p38 MAPK-JNK) pathway. It also produced significantly damaged pericytes morphology, resulting in pericyte decrease. Ghrelin treatment, on the other hand, protected against cerebral microvascular leakage and pericytes damage. Ghrelin effectively downregulated the expression of pro-inflammatory cytokines, and it also suppressed the p38 MAPK-JNK signaling pathway. Additionally, in isolated mouse cerebral microvascular pericytes, ox-LDL lead to increased apoptosis and secretion of inflammatory factors, along with an elevation in phosphorylated p38 MAPK-JNK proteins. Alternately, Ghrelin administration markedly lowered expression of inflammatory factors, suppressed the p38 MAPK-JNK signaling path, and halted cell apoptosis. However, pretreatment of Hesperetin, a p38 MAPK-JNK agonist, abrogated the Ghrelin-mediated suppression of inflammation and apoptosis in pericytes. Taken together, these results suggest that Ghrelin restored cerebral microvascular integrity and reduced vascular leakage in atherosclerosis mice, in part, by its regulation of inflammatory and apoptotic signaling pathways in pericytes., Competing Interests: Declaration of competing Interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication., (Copyright © 2021. Published by Elsevier Inc.)

Background: Microvascular tissue transfer is a common reconstructive procedure. We designed a bioelectrical impedance assessment (BIA) system for quantitative analysis of tissue status. This study attempts to verify it through the animal model., Methods: The flaps of the rat model were monitored by the BIA system., Results: The BIA variation of the free flap in the rat after the vascular compromise was recorded. The non-vascular ligation limbs of the same rat served as a control group. The bio-impedance in the experimental group was larger than the control group. The bio-impedances of both the thigh / feet flaps in the experimental group were increased over time. In the thigh , the difference in bio-impedance from the control group was first detected at 10 kHz at the 3rd and last at 1 kHz at the 6th h, after vascular compromise. The same finding was observed in the feet . Compared with the control group, the bio-impedance ratio (1 kHz/20 kHz) of the experimental group decreased with time, while their variation tendencies in the thigh and feet were similar., Conclusions: The flap may be monitored by the BIA for vascular status.

As the heavy metal contamination is becoming worse, monitoring the heavy metal content in water or human body gets more and more important. In this research, a cadmium ion-selective field effect transistor (Cd-ISFET) for rapidly detecting cadmium ions has been developed and the mechanism of the sensor is also investigated in depth. Our Cd-ISFET sensor exhibits high sensitivity beyond the ideal Nernst sensitivity, wide dynamic range, low detection limit (∼10 -11 M), which is comparable with inductively coupled plasma mass spectrometry, and easy operation enabling people to detect cadmium ion by themselves. From the analysis of electrical measurement results, this Cd-ISFET is preferred to operate at the bias with the maximum transconductance of the FET to enhance the sensor signal. The AC impedance measurement is carried out to directly investigate the mechanism of an ion-selective membrane (ISM). From impedance results, the real part of the total impedance, which is the resistance, was shown to dominate the sensor signal. The potential drop across the ISM is caused by the heavy metal ion in the membrane, which is employed to the gate of the FET via an extended gate electrode. Cadmium ion detection in one drop of human serum with this sensor was demonstrated. This cost-effective and highly sensitive sensor is promising and can be used by anyone and anywhere to prevent people from cadmium poisoning., (© 2021 Author(s).)