Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia.

BACKGROUND: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting ß2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/µL; <300/µL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS: Of 695 patients randomized, 473 had baseline bEOS ≥300/µL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/µL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

Diagnostic values of soluble triggering receptor expressed on myeloid cells (sTREM-1) and interferon-inducible protein-10 (IP-10) for severe mycoplasma pneumoniae pneumonia in children.

OBJECTIVE: Early diagnosis of Severity Mycoplasma Pneumoniae Pneumonia (SMPP) has been a worldwide concern in clinical practice. Two cytokines, soluble Triggering Receptor Expressed on Myeloid cells (sTREM-1) and Interferon-Inducible Protein-10 (IP-10), were proved to be implicated in bacterial infection diseases. However, the diagnostic value of sTREM-1 and IP-10 in MPP was poorly known. This study aimed to investigate the diagnostic value of sTREM-1 and IP-10 for SMPP. METHODS: In this prospective study, the authors enrolled 44 children with MPP, along with their clinical information. Blood samples were collected, and cytokine levels of sTREM-1 and IP-10 were detected with ELISA assay. RESULTS: Serum levels of sTREM-1 and IP-10 were positively correlated with the severity of MPP. In addition, sTREM-1 and IP-10 have significant potential in the diagnosis of SMPP with an Area Under Curve (AUC) of 0.8564 (p-value = 0.0001, 95% CI 0.7461 to 0.9668) and 0.8086 (p-value = 0.0002, 95% CI 0.6918 to 0.9254) respectively. Notably, the combined diagnostic value of sTREM-1 and IP-10 is up to 0.911 in children with SMPP (p-value < 0.001, 95% CI 0.830 to 0.993). CONCLUSIONS: Serum cytokine levels of sTREM-1 and IP-10 have a great potential diagnostic value in children with SMPP.

Role of the GLP2-Wnt1 axis in silicon-rich alkaline mineral water maintaining intestinal epithelium regeneration in piglets under early-life stress.

Stress-induced intestinal epithelial injury (IEI) and a delay in repair in infancy are predisposing factors for refractory gut diseases in adulthood, such as irritable bowel syndrome (IBS). Hence, it is necessary to develop appropriate mitigation methods for mammals when experiencing early-life stress (ELS). Weaning, as we all know, is a vital procedure that all mammalian newborns, including humans, must go through. Maternal separation (MS) stress in infancy (regarded as weaning stress in animal science) is a commonly used ELS paradigm. Drinking silicon-rich alkaline mineral water (AMW) has a therapeutic effect on enteric disease, but the specific mechanisms involved have not been reported. Herein, we discover the molecular mechanism by which silicon-rich AMW repairs ELS-induced IEI by maintaining intestinal stem cell (ISC) proliferation and differentiation through the glucagon-like peptide (GLP)2-Wnt1 axis. Mechanistic study showed that silicon-rich AMW activates GLP2-dependent Wnt1/ß-catenin pathway, and drives ISC proliferation and differentiation by stimulating Lgr5+ ISC cell cycle passage through the G1-S-phase checkpoint, thereby maintaining intestinal epithelial regeneration and IEI repair. Using GLP2 antagonists (GLP23-33) and small interfering RNA (SiWnt1) in vitro, we found that the GLP2-Wnt1 axis is the target of silicon-rich AMW to promote intestinal epithelium regeneration. Therefore, silicon-rich AMW maintains intestinal epithelium regeneration through the GLP2-Wnt1 axis in piglets under ELS. Our research contributes to understanding the mechanism of silicon-rich AMW promoting gut epithelial regeneration and provides a new strategy for the alleviation of ELS-induced IEI.

Essential oils improve nursery pigs' performance and appetite via modulation of intestinal health and microbiota.

Optimal intestinal health and functionality are essential for animal health and performance, and simultaneously intestinal nutrient transporters and intestinal peptides are also involved in appetite and feed intake control mechanisms. Given the potential of essential oil (EO) in improving animal performance and improving feed palatability, we hypothesized that dietary supplementation of cinnamaldehyde and carvacrol could improve performance and appetite of nursery pigs by modulating intestinal health and microbiota. Cinnamaldehyde (100 mg/kg), carvacrol (100 mg/kg), and their mixtures (including 50 mg/kg cinnamaldehyde and 50 mg/kg carvacrol) were supplemented into the diets of 240 nursery pigs for 42 d, and data related to performance were measured. Thereafter, the influence of EO on intestinal health, appetite and gut microbiota and their correlations were explored. EO supplementation increased (P < 0.05) the body weight, average daily gain (ADG) and average daily feed intake (ADFI) of piglets, and reduced (P < 0.05) diarrhea rates in nursery pigs. Furthermore, EO increased (P < 0.05) the intestinal absorption area and the abundance of tight junction proteins, and decreased (P < 0.05) intestinal permeability and local inflammation. In terms of intestinal development and the mucus barrier, EO promoted intestinal development and increased (P < 0.05) the number of goblet cells. Additionally, we found that piglets in the EO-supplemented group had upregulated (P < 0.05) levels of transporters and digestive enzymes in the intestine, which were significantly associated with daily gain and feed utilization. In addition, EO supplementation somewhat improved appetite in nursery pigs, increased the diversity of the gut microbiome and the abundance of beneficial bacteria, and there was a correlation between altered bacterial structure and appetite-related hormones. These findings indicate that EO is effective in promoting growth performance and nutrient absorption as well as in regulating appetite by improving intestinal health and bacterial structure.

Improving Rate Performance of Encapsulating Lithium-Polysulfide Electrolytes for Practical Lithium-Sulfur Batteries.

The cycle life of high-energy-density lithium-sulfur (Li-S) batteries is severely plagued by the incessant parasitic reactions between Li metal anodes and reactive Li polysulfides (LiPSs). Encapsulating Li-polysulfide electrolyte (EPSE) emerges as an effective electrolyte design to mitigate the parasitic reactions kinetically. Nevertheless, the rate performance of Li-S batteries with EPSE is synchronously suppressed. Herein, the sacrifice in rate performance by EPSE is circumvented while mitigating parasitic reactions by employing hexyl methyl ether (HME) as a co-solvent. The specific capacity of Li-S batteries with HME-based EPSE is nearly not decreased at 0.1 C compared with conventional ether electrolytes. With an ultrathin Li metal anode (50 µm) and a high-areal-loading sulfur cathode (4.4 mgS cm-2 ), a longer cycle life of 113 cycles was achieved in HME-based EPSE compared with that of 65 cycles in conventional ether electrolytes at 0.1 C. Furthermore, both high energy density of 387 Wh kg-1 and stable cycle life of 27 cycles were achieved in a Li-S pouch cell (2.7 Ah). This work inspires the feasibility of regulating the solvation structure of LiPSs in EPSE for Li-S batteries with balanced performance.

Nanofiber-based Stretchable Electrodes for Oriented Culture and Mechanotransduction Monitoring of Smooth Muscle Cells.

Vascular smooth muscle cells (SMCs) are circumferentially oriented perpendicular to the blood vessel and maintain the contractile phenotype in physiological conditions. They can sense the mechanical forces of blood vessels expanding and contracting and convert them into biochemical signals to regulate vascular homeostasis. However, the real-time monitoring of mechanically evoked biochemical response while maintaining SMC oriented growth remains an important challenge. Herein, we developed a stretchable electrochemical sensor by electrospinning aligned and elastic polyurethane (PU) nanofibers on the surface of PDMS film and further modification of conductive polymer PEDOT:PSS-LiTFSI-CoPc (PPLC) on the nanofibers (denoted as PPLC/PU/PDMS). The aligned nanofibers on the electrode surface could guide the oriented growth of SMCs and maintain the contractile phenotype, and the modification of PPLC endowed the electrode with good electrochemical sensing performance and stability under mechanical deformation. By culturing cells on the electrode surface, the oriented growth of SMCs and real-time monitoring of stretch-induced H2O2 release were achieved. On this basis, the changes of H2O2 level released by SMCs under the pathology (hypertension) and intervention of natural product resveratrol were quantitatively monitored, which will be helpful to further understand the occurrence and development of vascular-related diseases and the mechanisms of pharmaceutical intervention.

Determination of key events in mouse hepatocyte maturation at the single-cell level.

Hepatocytes, the liver's predominant cells, perform numerous essential biological functions. However, crucial events and regulators during hepatocyte maturation require in-depth investigation. In this study, we performed single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) to explore the precise hepatocyte development process in mice. We defined three maturation stages of postnatal hepatocytes, each of which establishes specific metabolic functions and exhibits distinct proliferation rates. Hepatic zonation is gradually formed during hepatocyte maturation. Hepatocytes or their nuclei with distinct ploidies exhibit zonation preferences in distribution and asynchrony in maturation. Moreover, by combining gene regulatory network analysis with in vivo genetic manipulation, we identified critical maturation- and zonation-related transcription factors. This study not only delineates the comprehensive transcriptomic profiles of hepatocyte maturation but also presents a paradigm to identify genes that function in the development of hepatocyte maturation and zonation by combining genetic manipulation and measurement of coordinates in a single-cell developmental trajectory.

The default and directed pathways of hepatoblast differentiation involve distinct epigenomic mechanisms.

The effectiveness of multiomics analyses in defining cell differentiation pathways during development is ambiguous. During liver development, hepatoblasts follow a default or directed pathway to differentiate into hepatocytes or cholangiocytes, respectively, and this provides a practical model to address this issue. Our study discovered that promoter-associated histone modifications and chromatin accessibility dynamics, rather than enhancer-associated histone modifications, effectively delineated the "default vs. directed" process of hepatoblast differentiation. Histone H3K27me3 on bivalent promoters is associated with this asymmetric differentiation strategy in mice and humans. We demonstrated that Ezh2 and Jmjd3 exert opposing regulatory roles in hepatoblast-cholangiocyte differentiation. Additionally, active enhancers, regulated by P300, correlate with the development of both hepatocytes and cholangiocytes. This research proposes a model highlighting the division of labor between promoters and enhancers, with promoter-associated chromatin modifications governing the "default vs. directed" differentiation mode of hepatoblasts, whereas enhancer-associated modifications primarily dictate the progressive development processes of hepatobiliary lineages.

Electrolyte Design for Improving Mechanical Stability of Solid Electrolyte Interphase in Lithium-Sulfur Batteries.

Practical lithium-sulfur (Li-S) batteries are severely plagued by the instability of solid electrolyte interphase (SEI) formed in routine ether electrolytes. Herein, an electrolyte with 1,3,5-trioxane (TO) and 1,2-dimethoxyethane (DME) as co-solvents is proposed to construct a high-mechanical-stability SEI by enriching organic components in Li-S batteries. The high-mechanical-stability SEI works compatibly in Li-S batteries. TO with high polymerization capability can preferentially decompose and form organic-rich SEI, strengthening mechanical stability of SEI, which mitigates crack and regeneration of SEI and reduces the consumption rate of active Li, Li polysulfides, and electrolytes. Meanwhile, DME ensures high specific capacity of S cathodes. Accordingly, the lifespan of Li-S batteries increases from 75 cycles in routine ether electrolyte to 216 cycles in TO-based electrolyte. Furthermore, a 417 Wh kg-1 Li-S pouch cell undergoes 20 cycles. This work provides an emerging electrolyte design for practical Li-S batteries.

An Organodiselenide Comediator to Facilitate Sulfur Redox Kinetics in Lithium-Sulfur Batteries with Encapsulating Lithium Polysulfide Electrolyte.

Lithium-sulfur (Li-S) batteries are regarded as promising high-energy-density energy storage devices. However, the cycling stability of Li-S batteries is restricted by the parasitic reactions between Li metal anodes and soluble lithium polysulfides (LiPSs). Encapsulating LiPS electrolyte (EPSE) can efficiently suppress the parasitic reactions but inevitably sacrifices the cathode sulfur redox kinetics. To address the above dilemma, a redox comediation strategy for EPSE is proposed to realize high-energy-density and long-cycling Li-S batteries. Concretely, dimethyl diselenide (DMDSe) is employed as an efficient redox comediator to facilitate the sulfur redox kinetics in Li-S batteries with EPSE. DMDSe enhances the liquid-liquid and liquid-solid conversion kinetics of LiPS in EPSE while maintains the ability to alleviate the anode parasitic reactions from LiPSs. Consequently, a Li-S pouch cell with a high energy density of 359 Wh kg-1 at cell level and stable 37 cycles is realized. This work provides an effective redox comediation strategy for EPSE to simultaneously achieve high energy density and long cycling stability in Li-S batteries and inspires rational integration of multi-strategies for practical working batteries.

Effects of dietary supplementation with a carvacrol-cinnamaldehyde-thymol blend on growth performance and intestinal health of nursery pigs.

BACKGROUND: Stress, herd transfer, and food changes experienced by nursery and fattening pigs can lead to reduced performance, reduced digestion and absorption, and impaired intestinal health. Given the role of essential oils in relieving stress and improving animal welfare, we hypothesized that essential oils may improve pig performance via promoting gut health and gut homeostasis laid by EOs supplementation during nursery continuously impacts performance in fattening pigs. RESULTS: A total of 100 piglets (Landrace × Large White; weighted 8.08 ± 0.34 kg, weaned at d 28) were randomly selected and divided into 2 treatments: (1) basal diet (Con); (2) basal diet supplement with 0.1% complex essential oils (CEO). The experiment period was 42 days. Then weaned piglets' growth performance and indications of intestinal health were assessed. Compared to the Con group, dietary supplemented CEO enhanced BW at 14 d (P < 0.05), and increased ADG during 1 ~ 14 d and 1 ~ 42 d (P < 0.05). Furthermore, CEO group had lower FCR during 1 ~ 42 d (P < 0.05). The CEO group also showed higher VH and VH:CD in duodenum and ileum (P < 0.05). Additionally, dietary CEO supplementation improved gut barrier function, as manifested by increased the mRNA expression of tight-junction protein and decreased serum DAO, ET and D-LA levels (P < 0.05). Finally, CEO supplementation alleviated gut inflammation, increased the activity of digestive enzymes. Importantly, piglets supplemented with CEOs during nursery also had better performance during fattening, suggesting that the establishment of intestinal health will also continuously affect subsequent digestion and absorption capacity. In short, dietary supplemented CEO improved performance and gut health via modulating increased intestine absorptive area, barrier integrity, digestive enzyme activity, and attenuating intestine inflammation. Meanwhile, essential oil supplementation during the nursery period also had a favorable effect on the performance of growing pigs. CONCLUSIONS: Therefore, the strategy of adding CEO to pig diets as a growth promoter and enhancing intestinal health is feasible.

Idiopathic calcinosis cutis of the buttocks: A case report and review of the literature.

RATIONALE: Calcinosis cutis is a rare skin disease, and idiopathic cases are rarely reported. It is characterized by the deposition of insoluble calcium salts in the skin, subcutaneous tissue, superficial muscles, and tendon sheaths. However, no abnormal changes were found in the bone. In this article, we introduce a case of idiopathic calcinosis cutis of the buttocks with a long course and large lesion area. PATIENT CONCERNS: A 51-year-old male patient was admitted to the hospital with a chief complaint of 'Due to the discovery of hard nodules with pruritus in the buttocks for 32 years. The patient was a male who was 51 years old. He has been in good health and reported no history of surgery, trauma, infection, metabolic disease, tumor, or other diseases. There was no family history. It is worth noting that the patient has the occupation of driving trucks, which keeps him sedentary. DIAGNOSES: The accurate diagnosis of calcinosis cutis was confirmed by postoperative histopathological examination with many local calcifications and multinucleated giant cells in subcutaneous tissue. INTERVENTIONS: The patient underwent skin lesion excision and autologous skin grafting under general anesthesia. A medium-thickness skin graft from the left lateral thigh was transplanted into the hip operation area, and a bolus tie-over pressure dressing was applied. After the operation, the patient received anti-infection treatment and was advised to rest in the prone position to prevent extrusion of the operation area. OUTCOMES: The postoperative recovery was good, and there was no recurrence after 4 months of follow-up. LESSONS: The incidence rate of cutaneous calcinosis is not clear. This patient had a large lesion area, long onset time, an invasion of the fat layer, and the onset site was located in the sacrococcygeal region. It is necessary to choose appropriate treatment methods.

A retrospective study of 1064-nm Q-switched Nd:YAG laser therapy for acquired bilateral nevus of Ota-like macules.

BACKGROUND: The therapeutic efficacy of laser treatments for acquired bilateral nevus of Ota-like macules (ABNOM) varies among studies, and few studies have evaluated the factors affecting therapeutic effects. AIMS: To evaluate the efficacy and safety of 1064-nm Q-switched Nd:YAG laser (QSNYL) therapy for ABNOM and to identify the factors influencing the outcome. METHODS: A total of 110 patients with ABNOM were retrospectively evaluated and received two-to-nine treatment sessions. The effects of different factors on the therapeutic effect were analyzed on the basis of the number of treatments, age at first treatment, skin type, lesion color, affected area, number of lesion sites, and presence of concomitant melasma. RESULTS: The curative effect was positively correlated with the treatment time and negatively correlated with the increasing age at first treatment (p < 0.05). The curative effect was better in patients with skin type III than those with type IV ( p < 0.05) and in patients with a lesion area of less than 10 cm2 than those with a larger affected area (p < 0.05). Additionally, the treatment effect was poorer in patients with concomitant melasma (p < 0.05). The treatment effect was not significantly correlated with the lesion color or number of affected sites (p > 0.05). Eleven patients (10%) developed postinflammatory hyperpigmentation (PIH). CONCLUSIONS: Early and repeated QSNYL therapy achieved satisfactory results for ABNOM. The risk of PIH after laser treatment is highest among patients with older age, darker lesion color, and darker skin color. For patients with ABNOM with concurrent melasma, low-energy laser therapy is recommended to reduce the risk of melasma aggravation.

Drinking alkaline mineral water confers diarrhea resistance in maternally separated piglets by maintaining intestinal epithelial regeneration via the brain-microbe-gut axis.

INTRODUCTION: Diarrhea has the fourth-highest mortality rate of all diseases and causes a large number of infant deaths each year. The maternally separated (MS) piglet (newly weaned piglet) is an excellent model to investigate the treatment of diarrhea in infants. Drinking alkaline mineral water has the potential to be therapeutic in gastrointestinal disorders, particularly diarrhea, but the supporting evidence from system studies and the mechanisms involved have yet to be reported. OBJECTIVES: This study aims to determine whether drinking alkaline mineral water confers diarrhea resistance in MS piglets under weaning stress and what the fundamental mechanisms involved are. METHODS: MS piglets were used to create a stress-induced intestinal disorder-diarrhea susceptibility model. A total of 240 MS piglets were randomly divided into two groups (6 pens/group and 20 piglets/pen). IPEC-J2 cell line was used for in vitro evaluation. An alkaline mineral complex (AMC) water was employed, and its effect on the hypothalamus-pituitary-adrenocortical (HPA) axis, gut microbes, gut morphology, and intestinal epithelial cell (IEC) proliferation and differentiation were investigated using a variety of experimental methodology. RESULTS: AMC water reduced diarrhea rate in MS piglets by inhibiting the HPA axis, ameliorating gut microbiota structure, and stimulating IEC proliferation and differentiation. Apparently, the brain-microbe-gut axis is linked with AMC water conferring diarrhea resistance in piglets. Mechanistically, AMC water decreased stress hormones (COR and Hpt) secretion by suppressing HPA axis, which then increased the abundance of beneficial gut microbes; accordingly, maintained the proliferation of IEC and promoted the differentiation of intestinal stem cells (ISC) into goblet cell and Paneth cell by activating the Wnt/ß-catenin signaling pathway. In the absence of gut microbiota (in vitro), AMC activated the LPS-induced Wnt/ß-catenin signaling inhibition in IPEC-J2 cells and significantly increased the number of Lgr5 + cells, whereas had no effect on IPEC-J2 differentiation. CONCLUSION: Drinking alkaline mineral water confers diarrhea resistance in MS piglets by maintaining intestinal epithelial regeneration via the brain-microbe-gut axis; thus, this study provides a potential prevention strategy for young mammals at risk of diarrhea.

Metasilicate-based alkaline mineral water confers diarrhea resistance in maternally separated piglets via the microbiota-gut interaction.

Stress or stress-induced intestinal disturbances, especially diarrhea, are the main triggers for inflammatory bowel disease and irritable bowel syndrome. Diarrhea and intestinal inflammatory disease afflict patients around the world, and it has become a huge burden on the global health care system. Drinking sodium metasilicate-based alkaline mineral water (SM-based AMW) exerts a potential therapeutic effect in gastrointestinal disorders, including gut inflammation, and diarrhea, but the supportive evidence on animal studies and mechanism involved remain unreported. The maternally separated (MS) piglet (Newly weaned piglet) is an excellent model to investigate the treatment of diarrhea in infant. This study aims to determine whether drinking SM-based AMW confers diarrhea resistance in maternally separated (MS) piglets under weaning stress and what the underlying mechanisms are involved. 240 newly weaned piglets were randomly divided into the Control group and the sodium metasilicate pentahydrate (SMP) group. A decreased diarrhea incidence was observed in SMP treatment piglets. The intestine injury and activated stress hormones (COR and ACTH) induced by weaning was alleviated by SM-based AMW. This may be related to the improvement of intestinal microflora structure and function by SMP, especially the increase of s_copri abundance. Meanwhile, SMP maintained the integrity of the duodenal mucus barrier in MS piglets. Importantly, by targeting NF-κB inhibition via the microbiota-gut interaction, SM-based AMW alleviated intestinal inflammation, maintained fluid homeostasis by modulating aquaporins and fluid transporter expression, and enhanced barrier integrity by suppressing MLCK/p-MLC signaling. Therefore, drinking metasilicate-based alkaline mineral water confers diarrhea resistance in MS piglets via the microbiota-gut interaction.

Bibliometric analysis of tumor necrosis factor in post-stroke neuroinflammation from 2003 to 2021.

Objective: Tumor necrosis factor (TNF), a crucial cytokine, has important research value in post-stroke neuroinflammation (PSN). We analyzed the studies that have been conducted in this area and used bibliometric methods to predict research hotspots and identify trends regarding TNF in PSN. Methods: Publications were accessed at the Science Citation Index Expanded 1975-2021 (SCI expanded), Web of Science Core Collection (WoSCC), on May 1, 2022. Additionally, software such as CiteSpace and VOSviewer were utilized for bibliometric analyses. Results: In total, 1391 original articles and reviews on TNF in PSN published from 2003 to 2021 were identified. An upward trend was observed in the number of publications on TNF in PSN. These publications were primarily from 57 countries and 1446 institutions, led by China and the United States with China leading the number of publications (NP) and the US with the number of citations (NC). The League of European Research Universities (LERU) and Journal of Neuroinflammation, respectively were the most prolific branches and journals. Zhang, John H. published the most papers and Finsen, Bente had the most cited papers. One paper by Kettenmann, H. published in 2011 reached the highest level of Global Citation Score (GCS). The keyword co-occurrence and reference co-citation analyses suggest that poststroke therapy and potential mechanistic pathways are important topics related to PSN in recent years. Reference burst detection suggests new burst hotspots after 2015, focusing on pathway modulation and discovery of therapeutic targets, suggesting a substantial development in the study of TNF in PSN research. Conclusion: The present bibliometric analysis shows a continuous trend of increasing literature related to TNF in PSN, and shows that TNF plays an important role in PSN involves multiple immune mechanisms and may contribute as a potential target for neuroprotective therapeutics after stroke. Prior to 2011, most of the research was focused on discovering the specific role of TNF in PSN, and in recent years studies have mainly targeted the exploration of the signaling pathways. Future research prospects may lie in finding key therapeutic targets in pathway of TNF in PSN.

Weakening the Solvating Power of Solvents to Encapsulate Lithium Polysulfides Enables Long-Cycling Lithium-Sulfur Batteries.

Long cycling lifespan is a prerequisite for practical lithium-sulfur batteries yet is restricted by side reactions between soluble polysulfides and the lithium-metal anode. The regulation on solvation structure of polysulfides renders encapsulating polysulfides electrolytes (EPSE) as a promising solution to suppress the parasitic reactions. The solvating power of the solvents in the outer solvent shell of lithium polysulfides is critical for the encapsulation effect of EPSE. Herein, 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (HFE) is demonstrated as a superior outer-shell solvent to construct EPSE. Based on the large steric hindrance of the fluorohydrocarbon chains, the electron-withdrawing perfluoro segment (CF2  further endows HFE with prominently weak solvating power. The HFE-EPSE improves the lifespan from 54 to 135 cycles for lithium-sulfur batteries with an ultrathin lithium-metal anode (50 µm) and high-areal-loading sulfur cathode (4.4 mg cm-2 ). Furthermore, a 334 Wh kg-1 lithium-sulfur pouch cell (2.4 Ah level) with HFE-EPSE stably undergoes 25 cycles. This work demonstrates the role of weakening solvating power of outer-shell solvents to construct superior EPSE and inspires the significance of the solvation chemistry of polysulfides to achieve practical lithium-sulfur batteries.

Effects of alkaline mineral complex water supplementation on growth performance, inflammatory response, and intestinal barrier function in weaned piglets.

The purpose of the present study was to investigate the effects of drinking water alkaline mineral complex (AMC) supplementation on growth performance, intestinal morphology, inflammatory response, immunity, antioxidant defense system, and barrier functions in weaned piglets. In a 15-d trial, 240 weaned piglets (9.35 ± 0.86 kg) at 28 d of age (large white × landrace × Duroc) were randomly divided into two groups: the control (Con) group and the AMC group. Drinking water AMC supplementation improved (P < 0.01) final body weight (BW) and average daily gain (ADG) in weaned piglets compared to the Con group. Importantly, AMC reduced (P < 0.01) the feed-to-gain (F:G) ratio. AMC water improved the physical health conditions of piglets under weaning stress, as reflected by the decreased (P < 0.05) hair score and conjunctival score. Moreover, there was no significant (P > 0.05) difference in relatively small intestinal length, organ (liver, spleen, and kidney) indices, or gastrointestinal pH value in weaned piglets between the two groups. Of note, AMC significantly promoted the microvilli numbers in the small intestine and effectively ameliorated the gut morphology damage induced by weaning stress, as evidenced by the increased (P < 0.05) villous height (VH) and ratio of VH to crypt depth. Additionally, AMC lessened the levels of lipopolysaccharide (LPS, P < 0.01) and the contents of IL1ß (P<0.05), and TNF-α (P<0.05) in the weaned piglet small intestine. Conversely, the gut immune barrier marker, secretory immunoglobulin A (sIgA) levels in serum and small intestine mucosa were elevated after AMC water treatment (P < 0.01). Furthermore, AMC elevated the antioxidant mRNA levels of (P < 0.05) SOD 1-2, (P < 0.01) CAT, and (P < 0.01) GPX 1-2 in the small intestine. Likewise, the mRNA levels of the small intestine tight junction factors Occludin (P < 0.01), ZO-1 (P < 0.05), Claudin 2 (P < 0.01), and Claudin 5 (P<0.01) in the AMC treatment group were notably higher than those in the Con group. In conclusion, drinking water AMC supplementation has an accelerative effect on growth performance by elevating gut health by improving intestinal morphology, the inflammatory response, the antioxidant defense system, and barrier function in weaned piglets.

The piglet suffers vital physiological, environmental, and social challenges when it is weaned from the sow that can predispose the piglet to subsequent diseases and other production losses, and these challenges are responsible for serious economic losses to the swine industry. Weaning stress induces intestinal injury, decreased immunity, and digestive system dysfunction, which then reduces feed intake and inhibits the growth performance of piglets. It is well known that alternatives to antibiotics for preventing weaning stress in weaned farm animals are sorely needed. The biologically beneficial effects of alkaline mineral water are widely reported. Alkaline mineral complex (AMC), as an immunomodulator, is considered to have antistress effects in the swine industry. In addition, treatment through drinking water is considered to be an efficient and low-cost feasible disease control strategy. Drinking water AMC supplementation is expected to exert health benefits in pigs; however, the responses of weaned piglets to water supplemented with AMC have not been fully explored. Thus, this study explored the effects of drinking water AMC supplementation on growth performance and gut health in weaned piglets. Our results showed that AMC water supplementation conspicuously enhanced the growth performance by improving the gut health.

Astragalus polysaccharide mitigates transport stress-induced hepatic metabolic stress via improving hepatic glucolipid metabolism in chicks.

In the modern poultry industry, newly hatched chicks are unavoidably transported from the hatching to the rearing foster. Stress caused by multiple physical and psychological stressors during transportation is particularly harmful to the liver. Astragalus polysaccharide (APS) possesses multiple benefits against hepatic metabolic disorders. Given that transport stress could disturb hepatic glucolipid metabolism and the role of APS in metabolic regulation, we speculated that APS could antagonize transport stress-induced disorder of hepatic glucolipid metabolism. Firstly, newly hatched chicks were transported for 0, 2, 4, and 8 h, respectively. Subsequently, to further investigate the effects of APS on transport stress-induced hepatic glucolipid metabolism disturbance, chicks were pretreated with water or APS and then subjected to transport treatment. Our study suggested that APS could relieve transport stress-induced lipid deposition in liver. Meanwhile, transport stress also induced disturbances in glucose metabolism, reflected by augmented mRNA expression of key molecules in gluconeogenesis and glycogenolysis. Surprisingly, APS could simultaneously alleviate these alterations via peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)/Sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK) pathway. Moreover, APS treatment regulated the level of peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma (PPARγ), thereby alleviating transport stress-induced alterations of VLDL synthesis, cholesterol metabolism, lipid oxidation, synthesis, and transport-related molecules. These findings indicated that APS could prevent the potential against transport stress-induced hepatic glucolipid metabolism disorders via PGC-1α/SIRT1/AMPK/PPARα/PPARγ signaling system.

In the modern poultry industry, newly hatched chicks are unavoidably transported from the hatching to the rearing foster. During transportation, chicks are frequently subjected to various physical and psychological stressors, which can lead to alterations in blood composition, hormones, metabolites, enzymes, and behavior. These alterations adversely affect animal health and welfare. Stress caused by transportation is especially harmful to liver, which can cause significant effects on liver function, and disturb hepatic lipid metabolism and glucose metabolic. The current study demonstrated that Astragalus polysaccharide (APS) possesses multiple benefits against hepatic metabolic disorders. Administration of APS to chicks before transport could prevent transport-induced stress and hepatic glucolipid metabolism disorders.

Melatonin Attenuates Vascular Smooth Muscle Contraction Through the γ-Secretase/Notch Intracellular Domain/Myocardin Pathway.

ABSTRACT: Inositol 1, 4, 5-trisphosphate (IP3) signaling-mediated calcium release drives the contraction of vascular smooth muscles and hence regulates blood vessel volume and blood pressure. Melatonin supplementation has been suggested to be beneficial for hypertension. To determine whether the blood pressure-lowering effect of melatonin was accounted for by IP3 signaling, we evaluated the vasoconstriction response and IP3 signaling in isolated mouse thoracic aortic rings during melatonin incubation. C57BL/6 mice were given intraperitoneal injections daily with melatonin, and the systolic blood pressure and contractility of aortic rings from melatonin-treated mice were decreased, and the contraction suppression effect of melatonin was attributed to the impaired expression of contractile proteins in vascular smooth muscle cells rather than IP3 signaling. Our results further showed that melatonin increased the expression of γ-secretase, which could cleave and release the notch intracellular domain, and the notch intracellular domain prevented the transcription of contractile genes by interfering with the interaction between serum response factor and myocardin, the master regulator of contractile protein. In this article, we report a novel mechanism by which melatonin regulates smooth muscle contractility that does not depend on IP3 signaling.