Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population: A prospective, multicenter, randomized, two-stage study.

BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.

MgH2 nanoparticles confined in reduced graphene oxide pillared with organosilica: a novel type of hydrogen storage material.

Hydrogen is a promising alternative fuel that can push forward the energy transition because of its high energy density (142 MJ kg-1), variety of potential sources, low weight and low environmental impact, but its storage for automotive applications remains a formidable challenge. MgH2, with its high gravimetric and volumetric density, presents a compelling platform for hydrogen storage; however, its utilization is hindered by the sluggish kinetics of hydrogen uptake/release and high temperature operation. Herein we show that a novel layered heterostructure of reduced graphene oxide and organosilica with high specific surface area and narrow pore size distribution can serve as a scaffold to host MgH2 nanoparticles with a narrow diameter distribution around ∼2.5 nm and superior hydrogen storage properties to bulk MgH2. Desorption studies showed that hydrogen release starts at relatively low temperature, with a maximum at 348 °C and kinetics dependent on particle size. Reversibility tests demonstrated that the dehydrogenation kinetics and re-hydrogenation capacity of the system remains stable at 1.62 wt% over four cycles at 200 °C. Our results prove that MgH2 confinement in a nanoporous scaffold is an efficient way to constrain the size of the hydride particles, avoid aggregation and improve kinetics for hydrogen release and recharging.

ALKBH5 deficiency attenuates oxygen-glucose deprivation-induced injury in mouse brain microvascular endothelial cells in an m6A dependent manner.

Structural and functional alterations in brain microvascular endothelial cells (BMECs) caused by oxygen-glucose deprivation (OGD) are involved in the pathogenesis of various brain disorders. AlkB homolog 5 (ALKBH5) is a primary m6A demethylase that regulates various cell processes, but its distinct roles in BMEC function remain to be clarified. In the present study, in mouse middle cerebral artery occlusion (MCAO) model, knockout of ALKBH5 reduced neurological deficits, infarct volumes and tissue apoptosis caused by ischemia/reperfusion injury. Evans blue leakage and decreased expression of the tight junction protein ZO-1 and Occludin were also attenuated by ALKBH5 knockout. During the exploration of the underlying mechanisms of the role of ALKBH5 in BMECs, we found that the expression of ALKBH5 was induced at both the mRNA and protein levels by hypoxia; however, its protein stability was impaired by OGD treatment. Knockdown of ALKBH5 expression increased total m6A levels and alleviated OGD-induced BMEC injury. At the same time, the selective ALKBH5 inhibitor Cpd 20m also exhibited a protective effect on cell injury. In contrast, overexpression of ALKBH5 increased the sensitivity of BMECs to OGD. Interestingly, the m6A sequencing data revealed that knockdown of ALKBH5altered the expression of many genes via m6A upregulation. The gene expression alterations were verified by real-time PCR. Taken together, our results suggest that ALKBH5, as well as its target genes, plays important roles in the regulation of brain microvascular endothelial cell function through its RNA demethylase activity.

The jacktree genome and population genomics provides insights for the mechanisms of the germination obstacle and the conservation of endangered ornamental plants.

Sinojackia Hu represents the first woody genus described by Chinese botanists, with all species classified as endangered ornamental plants endemic to China. Their characteristic spindle-shaped fruits confer high ornamental value to the plants, making them favored in gardens and parks. Nevertheless, the fruits likely pose a germination obstacle, contributing to the endangered status of this lineage. Here we report the chromosome-scale genome of S. xylocarpa, and explore the mechanisms underlying its endangered status, as well as its population dynamics throughout evolution. Population genomic analysis has indicated that S. xylocarpa experienced a bottleneck effect following the recent glacial period, leading to a continuous population reduction. Examination of the pericarp composition across six stages of fruit development revealed a consistent increase in the accumulation of lignin and fiber content, responsible for the sturdiness of mature fruits' pericarps. At molecular level, enhanced gene expression in the biosynthesis of lignin, cellulose and hemicellulose was detected in pericarps. Therefore, we conclude that the highly lignified and fibrotic pericarps of S. xylocarpa, which inhibit its seed germination, should be its threatening mechanism, thus proposing corresponding strategies for improved conservation and restoration. This study serves as a seminal contribution to conservation biology, offering valuable insights for the study of other endangered ornamental plants.

Multiple pulp stones emerge across all teeth during mixed dentition: A case report.

BACKGROUND: This paper reports a rare presentation of multiple pulp stones (PSs) emerging in all teeth during mixed dentition. It offers valuable insights into the clinical diagnosis, treatment, and prognosis of multiple PSs, shedding light on their occurrence during the mixed dentition period. CASE SUMMARY: A 10-year-old girl presented with repeated pain in the mandibular right posterior teeth. Intraoral examination revealed carious lesions, abnormal tooth shapes, and anomalies in tooth number. Radiographic examinations showed multiple PSs with diverse shapes, sizes, and quantities in all teeth, alongside anomalies in tooth shape and number. Root canal therapy was initiated, but the patient initially lacked timely follow-up. Upon return for treatment completion, an extracted tooth revealed irregular calculus within the pulp cavity. CONCLUSION: This case underscores the importance of considering multiple PSs in mixed dentition, necessitating comprehensive evaluation and management strategies.

Tau pathology mediate the plasma biomarkers and cognitive function in patients with mild cognitive impairment.

Glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) are putative non-amyloid biomarkers indicative of ongoing inflammatory and neurodegenerative disease processes. Hence, this study aimed to demonstrate the relationship between plasma biomarkers (GFAP and NfL) and 18F-AV-1451 tau PET images, and to explore their effects on cognitive function. Ninety-one participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and 20 participants from the Shanghai Action of Prevention Dementia for the Elderly (SHAPE) cohort underwent plasma biomarker testing, 18F-AV-1451 tau PET scans and cognitive function assessments. Within the ADNI, there were 42 cognitively normal (CN) individuals and 49 with mild cognitive impairment (MCI). Similarly, in the SHAPE, we had 10 CN and 10 MCI participants. We calculated the standardized uptake value ratios (SUVRs) for the regions of interest (ROIs) in the 18F-AV-1451 PET scans. Using plasma biomarkers and regional SUVRs, we trained machine learning models to differentiate between MCI and CN subjects with ADNI database and validated in SHAPE. Results showed that eight selected variables (including left amygdala SUVR, right amygdala SUVR, left entorhinal cortex SUVR, age, education, plasma NfL, plasma GFAP, plasma GFAP/ NfL) identified by LASSO could differentiate between the MCI and CN individuals, with AUC ranging from 0.783 to 0.926. Additionally, cognitive function was negatively associated with the plasma biomarkers and tau deposition in amygdala and left entorhinal cortex. Increased tau deposition in amygdala and left entorhinal cortex were related to increased plasma biomarkers. Moreover, tau pathology mediated the effect of plasma biomarkers level on the cognitive decline. The present study provides valuable insights into the association among plasma markers (GFAP and NfL), regional tau deposition and cognitive function. This study reports the mediation effect of brain regions tau deposition on the plasma biomarkers level and cognitive function, indicating the significance of tau pathology in the MCI patients.

Encapsulating CoNi nanoparticles into nitrogen-doped carbon nanotube arrays as bifunctional oxygen electrocatalyst for rechargeable zinc-air batteries.

The high theoretical specific energy and environmental friendliness of zinc-air batteries (ZABs) have garnered significant attention. However, the practical application of ZABs requires overcoming the sluggish kinetics associated with oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Herein, 3D self-supported nitrogen-doped carbon nanotubes (N-CNTs) arrays encapsulated by CoNi nanoparticles on carbon fiber cloth (CoNi@N-CNTs/CFC) are synthesized as bifunctional catalysts for OER and ORR. The 3D interconnected N-CNTs arrays not only improve the electrical conductivity, the permeation and gas escape capabilities of the electrode, but also enhance the corrosion resistance of CoNi metals. DFT calculations reveal that the co-existence of Co and Ni synergistically reduces the energy barrier for OOH conversion to OH, thereby optimizing the Gibbs free energy of the catalysts. Additionally, analysis of the change in energy barrier during the rate-determining step suggests that the primary catalytic active center is Ni site for OER. As a result, CoNi@N-CNTs/CFC exhibits superior catalytic activity with an overpotential of 240 mV at 10 mA cm-2 toward OER, and the onset potential of 0.92 V for ORR. Moreover, utilization of CoNi@N-CNTs/CFC in liquid and solid-state ZABs exhibited exceptional stability, manifesting a consistent cycling operation lasting for 100 and 15 h, respectively.

Automatic renal carcinoma biopsy guidance using forward-viewing endoscopic optical coherence tomography and deep learning.

Percutaneous renal biopsy is commonly used for kidney cancer diagnosis. However, the biopsy procedure remains challenging in sampling accuracy. Here we introduce a forward-viewing optical coherence tomography probe for differentiating tumor and normal tissues, aiming at precise biopsy guidance. Totally, ten human kidney samples, nine of which had malignant renal carcinoma and one had benign oncocytoma, were used for system evaluation. Based on their distinct imaging features, carcinoma could be efficiently distinguished from normal renal tissues. Additionally, oncocytoma could be differentiated from carcinoma. We developed convolutional neural networks for tissue recognition. Compared to the conventional attenuation coefficient method, convolutional neural network models provided more accurate carcinoma predictions. These models reached a tissue recognition accuracy of 99.1% on a hold-out set of four kidney samples. Furthermore, they could efficiently distinguish oncocytoma from carcinoma. In conclusion, our convolutional neural network-aided endoscopic imaging platform could enhance carcinoma diagnosis during percutaneous renal biopsy procedures.

The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt-Induced Hypertension.

The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure (BP). We administered hydroxylamine hydrochloride (HA), a cystathionine-ß-synthase (CBS) inhibitor, into the PVN to suppress endogenous hydrogen sulfide (H2S) and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the NS+PVN vehicle group, the NS+PVN HA group, the HS+PVN vehicle group, and the HS+PVN HA group, with 10 rats in each group. The rats in the NS (normal salt) groups were fed a normal-salt diet containing 0.3% NaCl, while the HS (high salt) groups were fed a high-salt diet containing 8% NaCl. The mean arterial pressure (MAP) was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini-pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H2S in the PVN and plasma norepinephrine (NE) using ELISA. Additionally, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time PCR. In the current study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of high salt-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.

Ultrahigh Responsivity and Robust Semiconducting Fiber Enabled by Molecular Soldering-Governed Defect Engineering for Smart Textile Optoelectronics.

Semiconducting fibers (SCFs) are of significant interest to design next-generation wearable and comfortable optoelectronics that seamlessly integrate with textiles. However, the practical applications of current SCFs are always limited by poor optoelectronic performance and low mechanical robustness caused by uncontrollable multiscale structural defects. Herein, a versatile in situ molecular soldering-governed defect engineering strategy is proposed to construct ultrahigh responsivity and robust wet-spun MoS2 SCFs, by using a π-conjugated dithiolated molecule to simultaneously patch microscale sulfur vacancies within MoS2 nanosheets, diminish mesoscale interlayer voids/wrinkles, promote macroscale orientation, build long-range photoelectron percolation bridges, and provide n-doping effect. The derived MoS2 SCFs exhibit over two orders of magnitude higher responsivity (144.3 A W-1) than previously reported fiber photodetectors, 37.3-fold faster photoresponse speed (52 ms) than pristine counterpart, and remarkable bending robustness (retain 94.2% of the initial photocurrent after 50 000 bending-flattening cycles). Such superior robustness and photodetection capacity of MoS2 SCFs further enable large-scale weaving of reliable smart textile optoelectronic systems, such as direction-identifiable wireless light alarming system, modularized mechano-optical communication system, and indoor light-controlled IoT system. This work offers a universal strategy for the scalable production of mechanically robust and high-performance SCFs, opening up exciting possibilities for large-scale integration of wearable optoelectronics.

Machine Learning-Aided Design of Highly Conductive Anion Exchange Membranes for Fuel Cells and Water Electrolyzers.

Alkaline anion exchange membrane (AEM)-based fuel cells (AEMFCs) and water electrolyzers (AEMWEs) are vital for enabling the efficient and large-scale utilization of hydrogen energy. However, the performance of such energy devices is impeded by the relatively low conductivity of AEMs. The conventional trial-and-error approach to designing membrane structures has proven to be both inefficient and costly. To address this challenge, a fully connected neural network (FCNN) model is developed based on acid-catalyzed AEMs to analyze the relationship between structure and conductivity among 180,000 AEM variations. Under machine learning guidance, anilinium cation-type membranes are designed and synthesized. Molecular dynamics simulations and Mulliken charge population analysis validated that the presence of a large anilinium cation domain is a result of the inductive effect of N+ and benzene rings. The interconnected anilinium cation domains facilitated the formation of a continuous ion transport channel within the AEMs. Additionally, the incorporation of the benzyl electron-withdrawing group heightened the inductive effect, leading to high conductivity AEM variant as screened by the machine learning model. Furthermore, based on the highly active and low-cost monomers given by machine learning, the large-scale synthesis of anilinium-based AEMs confirms the potential for commercial applications.

Aflatoxin B1 as a complicit in intestinal damage caused by Eimeria ovinoidalis in lambs: Novel insights to reveal parasite-gut battle.

Mycotoxins, unavoidable contaminants in feed and feed ingredients, have the potential to influence the incidence and severity of various diseases upon ingestion. Sheep coccidiosis is an enteric disease caused by protozoa of Eimeria spp. However, the extent to which the presence of aflatoxin b1 (AFB1) synergistically exacerbates damage to intestinal health in lambs with Eimeria remains unclear. 50-day-old female lambs were randomly assigned to a 2 × 2 factorial arrangement of treatments for 15 days to assess the impact of AFB1 exposure on lambs with or without Eimeria (E.) ovinoidalis infection. Our findings reveal that AFB1 synergistically intensifies damage to intestinal health in lambs challenged by E. ovinoidalis. This is evidenced by disruptions to the intestinal microbiota and reductions in the production of short-chain fatty acids. AFB1 further aggravates damage to the cecal mechanical barrier. Additionally, AFB1 contributes to the entry of lipopolysaccharide into the bloodstream, activating the inflammatory response. Interestingly, AFB1 exposure history results in an early peak of oocyst excretion and a decreased number of oocyst excretion in E. ovinoidalis infected lambs. This may be closely linked to the destruction of the intestinal epithelial cell structure and its apoptosis, as indicated by a decreased ratio of Bcl-2 to Bax and increased caspase-3 levels. Mechanistically, proteomics analysis identified mitochondrial dysfunction (inhibition of the oxidative phosphorylation pathway) as the primary factor intensifying intestinal epithelial cell destruction caused by coccidia, exacerbated by AFB1 through the inhibiting the conversion of NADH to NAD+ in the cecum of lambs via down-regulation of the PGC-1α/NRF1/TFAM pathway. Overall, these results offer novel insights into the AFB1 complicity in accelerating intestinal damage caused by E. ovinoidalis in lambs. Targeting the mitochondrial oxidative phosphorylation pathway of the intestine may represent a new therapeutic strategy against the detrimental effects of mycotoxin and coccidia.

Volatomic differences among Vitis amurensis cultivars and its hybrids with V. vinifera revealed the effects of genotype, region, and vintage on grape aroma.

Vitis amurensis grape, an East Asian Vitis species, has excellent cold and disease resistance and exhibits high winemaking potential. In this study, the aroma compounds in grapes from five V. amurensis cultivars ('Beiguohong', 'Beiguolan', 'Shuangfeng', 'Shuanghong', 'Shuangyou') and three interspecific hybrids ('Beibinghong', 'Xuelanhong', 'Zuoyouhong') from two regions (Zuojia and Ji'an, Jilin, China) were identified via HS-SPME-GC/MS. The results showed that V. amurensis grapes had a greater concentration of aroma compounds than the interspecific hybrid berries. 'Beibinghong' was relatively rich in terpenes, although their concentrations were all lower than the threshold. 'Shuangfeng' contained more concentrations of free C6/C9 compounds, alcohols, aromatics and aldehydes/ketones than the other cultivars. The aroma characteristics of 'Beiguolan' and 'Shuanghong' were relatively similar. The grapes from the lower temperature and more fertile soil of Zuojia contained more C6/C9 compounds, norisoprenoids and alcohols, while aromatics were more abundant in the grapes from Ji'an, which was warmer than the Zuojia region. Herbaceous, floral, fruity and sweet were the main aroma series of V. amurensis grapes. Our study could provide a reference for the development and utilization of V. amurensis grapes and lay a foundation for the development of wild grape cultivars and the production of wines with characteristic styles.

The mediating effect of the amygdala-frontal circuit on the association between depressive symptoms and cognitive function in Alzheimer's disease.

Depressive symptoms occur commonly in Alzheimer's disease (AD). Although abnormalities in the amygdala-frontal circuit have been linked to emotional dysregulation and cognitive impairment, the neurological basis underlying these associations in AD patients with depressive symptoms (ADD) is unclear. We aimed to investigate the relationship between the amygdala-frontal circuit and depressive symptoms and cognitive function in ADD. We recruited 60 ADD, 60 AD patients without depressive symptoms (ADND), and 60 healthy controls (HC). Functional connectivity (FC) maps of the bilateral amygdala were compared. Fractional anisotropy (FA) of the amygdala-frontal circuit connected by the uncinate fasciculus (UF) was calculated using automated fiber quantification (AFQ). In addition, mediation analysis was performed to explore the effects of the amygdala-frontal circuit on the relationship between depressive symptoms and cognitive function. We found decreased bilateral amygdala FC with the inferior frontal gyrus (IFG) in the ADD group compared to the ADND and HC groups. Moreover, FA in the left frontal UF (nodes 64-97) was significantly lower in the ADD group than ADND group. Notably, amygdala-based FC with IFG and the left frontal UF FA mediated the relationship between depressive symptoms and cognitive function in ADD, with mediating effects ranging between 15 and 18%. Our study is the first to demonstrate the mediating effect of functional and microstructural abnormalities in the amygdala-frontal circuit in ADD. The findings suggest that the amygdala-frontal circuit may underlie emotional dysregulation in ADD, providing potential targets for treatment strategies.

Neutrophil migration participates in the side effect of recombinant human tissue plasminogen activator.

AIMS: Ischemic stroke remains a challenge in medical research because of the limited treatment options. Recombinant human tissue plasminogen activator (rtPA) is the primary treatment for recanalization. However, nearly 50% of the patients experience complications that result in ineffective reperfusion. The precise factors contributing to ineffective reperfusion remain unclear; however, recent studies have suggested that immune cells, notably neutrophils, may influence the outcome of rtPA thrombolysis via mechanisms such as the formation of neutrophil extracellular traps. This study aimed to explore the nonthrombolytic effects of rtPA on neutrophils and highlight their contribution to ineffective reperfusion. METHODS: We evaluated the effects of rtPA treatment on middle cerebral artery occlusion in rats. We also assessed neutrophil infiltration and activation after rtPA treatment in vitro and in vivo in a small cohort of patients with massive cerebral ischemia (MCI). RESULTS: rtPA increased neutrophil infiltration into the brain microvessels and worsened blood-brain barrier damage during ischemia. It also increased the neutrophil counts of the patients with MCI. CONCLUSION: Neutrophils play a crucial role in promoting ischemic injury and blood-brain barrier disruption, making them potential therapeutic targets.

Multifunctional Film Assembled from N-Doped Carbon Nanofiber with Co-N4-O Single Atoms for Highly Efficient Electromagnetic Energy Attenuation.

Single-atom materials have demonstrated attractive physicochemical characteristics. However, understanding the relationships between the coordination environment of single atoms and their properties at the atomic level remains a considerable challenge. Herein, a facile water-assisted carbonization approach is developed to fabricate well-defined asymmetrically coordinated Co-N4-O sites on biomass-derived carbon nanofiber (Co-N4-O/NCF) for electromagnetic wave (EMW) absorption. In such nanofiber, one atomically dispersed Co site is coordinated with four N atoms in the graphene basal plane and one oxygen atom in the axial direction. In-depth experimental and theoretical studies reveal that the axial Co-O coordination breaks the charge distribution symmetry in the planar porphyrin-like Co-N4 structure, leading to significantly enhanced dielectric polarization loss relevant to the planar Co-N4 sites. Importantly, the film based on Co-N4-O/NCF exhibits light weight, flexibility, excellent mechanical properties, great thermal insulating feature, and excellent EMW absorption with a reflection loss of - 45.82 dB along with an effective absorption bandwidth of 4.8 GHz. The findings of this work offer insight into the relationships between the single-atom coordination environment and the dielectric performance, and the proposed strategy can be extended toward the engineering of asymmetrically coordinated single atoms for various applications.

[Determination of the derivatization reactivity between α/ß-dicarbonyl compounds and standard citrullinated peptides based on matrix-assisted laser desorption ionization-time-of-flight mass spectrometry].

Protein citrullination is an irreversible post-translational modification process regulated by peptidylarginine deiminases (PADs) in the presence of Ca2+. This process is closely related to the occurrence and development of autoimmune diseases, cancers, neurological disorders, cardiovascular and cerebrovascular diseases, and other major diseases. The analysis of protein citrullination by biomass spectrometry confronts great challenges owing to its low abundance, lack of affinity tags, small mass-to-charge ratio change, and susceptibility to isotopic and deamidation interferences. The methods commonly used to study the protein citrullination mainly involve the chemical derivatization of the urea group of the guanine side chain of the peptide to increase the mass-to-charge ratio difference of the citrullinated peptide. Affinity-enriched labels are then introduced to effectively improve the sensitivity and accuracy of protein citrullination by mass spectrometry. 2,3-Butanedione or phenylglyoxal compounds are often used as derivatization reagents to increase the mass-to-charge ratio difference of the citrullinated peptide, and the resulting derivatives have been observed to contain α-dicarbonyl structures. To date, however, no relevant studies on the reactivity of dicarbonyl compounds with citrullinated peptides have been reported. In this study, we determined whether six α-dicarbonyl and two ß-dicarbonyl compounds undergo derivatization reactions with standard citrullinated peptides using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Among the α-dicarbonyl compounds, 2,3-butanedione and glyoxal reacted efficiently with several standard citrullinated peptides, but yielded a series of by-products. Phenylglyoxal, methylglyoxal, 1,2-cyclohexanedione, and 1,10-phenanthroline-5,6-dione also derivated efficiently with standard citrullinated peptides, generating a single derivative. Thus, a new derivatization method that could yield a single derivative was identified. Among the ß-dicarbonyl compounds, 1,3-cyclohexanedione and 2,4-pentanedione successfully reacted with the standard citrullinated peptides, and generated a single derivative. However, their reaction efficiency was very low, indicating that the ß-dicarbonyl compounds are unsuitable for the chemical derivatization of citrullinated peptides. The above results indicate that the α-dicarbonyl structure is necessary for realizing the efficient and specific chemical derivatization of citrullinated peptides. Moreover, the side chains of the α-dicarbonyl structure determine the structure of the derivatives, derivatization efficiency, and generation (or otherwise) of by-products. Therefore, the specific enrichment and precise identification of citrullinated peptides can be achieved by synthesizing α-dicarbonyl structured compounds containing affinity tags. The proposed method enables the identification of citrullinated proteins and their modified sites by MS, thereby providing a better understanding of the distribution of citrullinated proteins in different tissues. The findings will be beneficial for studies on the mechanism of action of citrullinated proteins in a variety of diseases.

tRNA-derived fragment 3'tRF-AlaAGC modulates cell chemoresistance and M2 macrophage polarization via binding to TRADD in breast cancer.

BACKGROUND: Drug resistance, including Adriamycin-based therapeutic resistance, remains a challenge in breast cancer (BC) treatment. Studies have revealed that macrophages could play a pivotal role in mediating the chemoresistance of cancer cells. Accumulating evidence suggests that tRNA-Derived small RNAs (tDRs) are associated the physiological and pathological processes in multiple cancers. However, the underlying mechanisms of tDRs on chemoresistance of BC in tumor-associated macrophages remain largely unknown. METHODS: The high-throughput sequencing technique was used to screen tDRs expression profile in BC cells. Gain- and loss-of-function experiments and xenograft models were performed to verify the biological function of 3'tRF-Ala-AGC in BC cells. The CIBERSORT algorithm was used to investigate immune cell infiltration in BC tissues. To explore the role of 3'tRF-Ala-AGC in macrophages, M2 macrophages transfected with 3'tRF-Ala-AGC mimic or inhibitor were co-cultured with BC cells. Effects on Nuclear factor-κb (NF-κb) pathway were investigated by NF-κb nuclear translocation assay and western blot analysis. RNA pull-down assay was performed to identify 3'tRF-Ala-AGC interacting proteins. RESULTS: A 3'tRF fragment of 3'tRF-AlaAGC was screened, which is significantly overexpressed in BC specimens and Adriamycin-resistant cells. 3'tRF-AlaAGC could promote cell malignant activity and facilitate M2 polarization of macrophages in vitro and in vivo. Higher expression of M2 macrophages were more likely to have lymph node metastasis and deeper invasion in BC patients. Mechanistically, 3'tRF-AlaAGC binds Type 1-associated death domain protein (TRADD) in BC cells, and suppression of TRADD partially abolished the enhanced effect of 3'tRF-AlaAGC mimic on phenotype of M2. The NF-κb signaling pathway was activated in BC cells co-cultured with M2 macrophages transfected with 3'tRF-AlaAGC mimic. CONCLUSIONS: 3'tRF-AlaAGC might modulate macrophage polarization via binding to TRADD and increase the effect of M2 on promoting the chemoresistance in BC cells through NF-κb signaling pathway.

Ion release of the glass ionomer restoration with silver diamine fluoride dentin pretreatment.

OBJECTIVE: To assess the fluoride and silver ion release of glass ionomer cement (GIC) restorations, including conventional GIC (CGIC) and resin-modified GIC (RMGIC) restorations, with 38 % silver diamine fluoride (SDF) solution dentin pretreatment. METHODS: Eighty dentin blocks were allocated into 4 groups and restored with SDF+CGIC, CGIC, SDF+RMGIC and RMGIC, respectively. Each block was stored in deionized water at 37 °C for 2 years. Fluoride and silver ion concentration in storage solution was measured using ion-selective electrode and inductively coupled plasma-optical emission spectrometry for up to 2 years. The cross-sectional surfaces of restored dentin blocks were assessed by X-Ray diffraction analysis (XRD), scanning electron microscope (SEM) with energy-dispersive X-ray spectroscopy (EDS) after 1 week and 2 years, respectively. RESULTS: The mean ± standard deviation (SD) of accumulative fluoride releasing in SDF+CGIC, CGIC, SDF+RMGIC and RMGIC for 2 years were 0.13±0.005 mg, 0.09±0.006 mg, 0.15±0.008 mg and 0.05±0.003 mg, respectively (Groups SDF+RMGIC > SDF+CGIC > CGIC >RMGIC, p < 0.05). The mean ± SD of accumulative silver releasing in SDF+CGIC, CGIC, SDF+RMGIC and RMGIC for 2 years were 0.03±0.009 mg, 0.00±0.00 mg, 0.01±0.003 mg, and 0.00±0.00 mg, respectively (Groups SDF+CGIC > SDF+RMGIC > CGIC&RMGIC, p < 0.05). Groups SDF+CGIC and SDF+RMGIC showed sustainably higher fluoride and silver releasing compared to Groups CGIC and RMGIC (p < 0.05). XRD analysis indicated the fluorapatite and silver chloride were observed only in Groups SDF+CGIC and SDF+RMGIC, but not in Groups CGIC and RMGIC. SEM images of the cross-sectional view of the dentin blocks showed silver crystals within dentinal tubules 1 week and 2-year in Groups with SDF pretreatment. CONCLUSION: The 38 % SDF dentin pretreatment sustainably increased the fluoride and silver release of GIC and RMGIC restorations for up to 2 years.

Synergistic restriction of polysulfides enabled by cobalt@carbon spheres embedded CNTs: A facile approach for constructing sulfur cathodes with high sulfur content.

Despite the bright fortune of lithium-sulfur (Li-S) batteries as one of the next-generation energy storage systems owing to the ultrahigh theoretical energy density and earth-abundance of sulfur, crucial challenges including polysulfide shuttling and low sulfur content of sulfur cathodes need to be overcome before the commercial survival of sulfur cathodes. Herein, cobalt/carbon spheres embedded CNTs (Co-C-CNTs) are rationally designed as multifunctional hosts to synergistically address the drawbacks of sulfur cathodes. The host is synthesized by a facile pyrolysis using Co(OH)2 template and followed with the controllable etching process. The hierarchical porous structure owning high pore volume and surface area can buffer the volume change, physically confine polysulfides, and provide conductive networks. Besides, partially remained metallic cobalt nanoparticles are favorable for chemical adsorption and conversion of polysulfides, as validated by density functional theory simulations. With the combination of above merits, the S@Co-C-CNTs cathodes with a high sulfur content of 80 wt% present a superior initial capacity (1568 mAh g-1 at 0.1C) with ultrahigh 93.6% active material utilization, and excellent rate performance (649 mAh g-1 at 2C), providing feasible strategies for the optimization of cathodes in metal-sulfur batteries.