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Heat stress (HS) poses a great challenge to the poultry industry by inducing oxidative damage to the liver, endangering the health and production of broilers. As an important type of seaweed polyphenols, phlorotannin has been shown to have antioxidant properties. The present study evaluated the protective effects of dietary phlorotannin on HS-induced liver injury in broilers based on oxidative damage parameters. A total of 108 twenty-one days old male Arbor Acres plus (AA+) broilers were randomly divided into three groups: TN group (thermoneutral, 24 ± 1 °C, fed with basal diet), HS group (HS, 33 ± 1 °C for 8 h/day, fed with basal diet), and HS + phlorotannin group (HS + 600 mg/kg phlorotannin). Each group has six replicate cages with six birds per cage. The feeding experiment lasted 21 days. At the termination of the feeding experiment (42 days old), samples were collected for analysis of morphological and biochemical features. The results showed that HS decreased the liver index, serum albumin (ALB) content, hepatic antioxidant enzymes activities of catalase (CAT), total superoxide dismutase (T-SOD), glutathione S-transferase (GST), and glutathione peroxidase (GSH-Px) ( p < 0.05), while increasing the hepatic histopathology score, apoptosis rate, and malondialdehyde (MDA) content ( p < 0.05) in 42-day-old broilers. Compared with the HS group, dietary phlorotannin improved the activities of antioxidant enzymes (GST and GSH-Px) but decreased the histopathology score and apoptosis rate in the liver ( p < 0.05). Moreover, HS down-regulated hepatic mRNA expression of CAT1 , NQO1 , HO-1 , and SLC7A11 ( p < 0.05), while up-regulated hepatic mRNA expression of Keap1 , MafG , IκBα , NF-κB P65 , IFN-γ , TFR1 , ACSL4 , Bax, and Caspase-9 ( p < 0.05). Compared with HS group, dietary phlorotannin up-regulated hepatic mRNA expression of Nrf2 , CAT1 , MafF , GSTT1 , NQO1 , HO-1 , GCLC , GPX1 , TNF-α , Fpn1, and SLC7A11 ( p < 0.05), while down-regulated hepatic mRNA expression of IκBα , Bax , Caspase-9, and TFR1 ( p < 0.05). In conclusion, dietary supplementation of 600 mg/kg phlorotannin could alleviate HS-induced liver injury via regulating oxidative status, apoptosis, and ferroptosis in broilers; these roles of phlorotannin might be associated with the regulation of the Nrf2 signaling pathway.

The Zr-2.5Nb alloy is a typical pressure tube material in heavy water nuclear reactors, and an increase of hydrogen isotope content in the alloy during service can pose major safety risks; hot vacuum extraction-mass spectrometry is an efficient method for evaluating hydrogen isotope concentrations in the Zr-2.5Nb alloy. This work investigates the kinetics and thermodynamic properties of deuterium (D) absorption and desorption of the Zr-2.5Nb alloy using the constant volume adsorption method and the hot vacuum extraction method. In addition to the previously reported volume contraction model, it was observed that at 600 °C and above, the reaction between D 2 and Zr-2.5Nb is dominated by diffusion, while the reaction is predominantly influenced by surface adsorption and dissociation below 600 °C. Phase transition sequence of Zr-2.5Nb deuterides during non-isothermal desorption was established using quantitatively calibrated thermal desorption spectra combined with the phase transition process of deuteride decomposition. These results can provide important references for optimizing the process parameters of the hot vacuum extraction-mass spectrometry method.

Objective: To study the effect of cluster nursing care based on 10S continuous quality improvement (CQI) on the incidence of postoperative delirium in patients with BPH., Methods: This study included 96 BPH patients undergoing transurethral resection of the prostate (TURP) in our department from August 2021 to February 2023. We randomly divided the patients into two groups of equal number to receive routine postoperative nursing care (the control group) and postoperative cluster nursing care based on the 10S DQI mode (the observation group), respectively. We recorded and compared the delirium scores of the patients at 2, 6, 12 and 24 hours after operation, their status of recovery, scores on Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and quality of life (QOL), and incidence of complications between the two groups., Results: Compared with the controls, the patients in the observation group showed significantly lower delirium scores at 2 h (12.72±3.54 vs 10.65±2.87, P<0.05), 6 h (20.17±4.92 vs 14.19±4.64, P<0.01), 12 h (16.82±4.24 vs 10.69±3.18, P<0.01) and 24 h (13.61±2.86 vs 9.13±2.12, P<0.01) after operation, and shorter time to ambulation (［3.65±1.41］ vs ［2.84±0.83］ d, P<0.01) and time of postoperative catheterization (［6.28±1.65］ vs ［4.28±1.14］ d, P<0.01), bladder irrigation (［3.41±1.08］ vs ［2.25±0.71］ d, P<0.01) and hospitalization (［10.33±2.41］ vs ［7.82±2.06］ d, P<0.01). No statistically significant differences were observed between the two groups in either the SAS and SDS scores (P >0.05) or the QOL scores before operation (P >0.05), but the former two were dramatically decreased (P<0.01) while the latter one increased in the observation group postoperatively (P<0.01). Postoperative complications included delirium, bladder spasm, urethral pain, and secondary bleeding, with a significantly lower total incidence rate in the observation than in the control group (12.50% vs 52.08%, P<0.01)., Conclusion: Cluster nursing care based on 10S CQI can promote the postoperative recovery of BPH patients, improve their psychological status and quality of life, and reduce the incidence of delirium and complications.

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Polydnaviruses (PDVs), obligatory symbionts with parasitoid wasps, function as host immune suppressors and growth and development regulator. PDVs can induce host haemocyte apoptosis, but the underlying mechanism remains largely unknown. Here, we provided evidence that, during the early stages of parasitism, the activated Cotesia vestalis bracovirus (CvBV) reduced the overall number of host haemocytes by inducing apoptosis. We found that one haemocyte-highly expressed CvBV gene, CvBV-26-4 , could induce haemocyte apoptosis. Further analyses showed that CvBV-26-4 has four homologs from other Cotesia bracoviruses and BV from wasps in the genus Glyptapanteles , and all four of them possessed a similar structure containing 3 copies of a well-conserved motif (Gly-Tyr-Pro-Tyr, GYPY). Mass spectrometry analysis revealed that CvBV-26-4 was secreted into plasma by haemocytes and then degraded into peptides that induced the apoptosis of haemocytes. Moreover, ectopic expression of CvBV-26-4 caused fly haemocyte apoptosis and increased the susceptibility of flies to bacteria. Based on this research, a new family of bracovirus genes, Bracovirus apoptosis-inducing proteins ( BAPs ), was proposed. Furthermore, it was discovered that the development of wasp larvae was affected when the function of CvBV BAP was obstructed in the parasitized hosts. The results of our study indicate that the BAP gene family from the bracoviruses group is crucial for immunosuppression during the early stages of parasitism.

Selenium (Se) is an indispensable trace element with versatile functions in antioxidant defense in poultry. In our previous study, we synthesized a novel type of biogenic selenium nanoparticle based on alginate oligosaccharides (SeNPs-AOS), and found that the particles are sized around 80 nm with an 8% Se content, and the dietary addition of 5 mg/kg of SeNPs-AOS could effectively alleviate the deleterious effects of heat stress (HS) in broilers, but it is still unclear whether SeNPs-AOS can improve the meat quality. Therefore, the aim of this study was to evaluate the protective effects of SeNPs-AOS on breast meat quality in heat-stressed broilers, and explore the relevant mechanisms. Birds at the age of 21 days were randomly divided into four groups with six replicates per group (eight broilers per replicate) according to a 2 × 2 experimental design, using HS (33 ± 2 °C, 10 h/day vs. thermoneutral, TN, under 23 ± 1.5 °C) and SeNPs-AOS (5 mg/kg feed vs. no inclusion) as variables. The results showed that dietary SeNPs-AOS decreased the cooking loss ( p < 0.05), freezing loss ( p < 0.001), and shear force ( p < 0.01) of breast muscle in heat-stressed broilers. The non-targeted metabolomics analysis of the breast muscle identified 78 differential metabolites between the HS and HS + SeNPs-AOS groups, mainly enriched in the arginine and proline metabolism, β-alanine metabolism, D-arginine and D-ornithine metabolism, pantothenate, and CoA biosynthesis pathways ( p < 0.05). Meanwhile, supplementation with SeNPs-AOS increased the levels of the total antioxidant capacity (T-AOC), the activities of catalase (CAT) and glutathione peroxidase (GSH-Px), and decreased the content of malondialdehyde (MDA) in the breast muscle ( p < 0.05) in broilers under HS exposure. Additionally, SeNPs-AOS upregulated the mRNA expression of CAT , GPX1 , GPX3 , heme oxygenase-1 ( HO-1 ), masculoaponeurotic fibrosarcoma G ( MafG) , MafK , selenoprotein W ( SELENOW) , SELENOK , ferritin heavy polypeptide-1 ( FTH1 ), Ferroportin 1 ( Fpn1 ), and nuclear factor erythroid 2-related factor 2 ( Nrf2) ( p < 0.05), while it downregulated Kelch-like ECH-associated pro-36 tein 1 ( Keap1 ) and prostaglandin-endoperoxide Synthase 2 ( PTGS2 ) expression ( p < 0.05) in broilers under HS. These findings demonstrated that the dietary addition of SeNPs-AOS mitigated HS-induced oxidative damage and metabolite changes in the breast muscle of broilers, which may be related to the regulation of the Nrf2 signaling pathway and selenoprotein synthesis. In addition, SeNPs-AOS upregulated the breast muscle gene expression of anti-ferroptosis-related molecules in broilers under HS, suggesting that SeNPs-AOS can be used as novel Se supplements against HS in broilers., Competing Interests: The authors declare no conflicts of interest.

Selenium (Se) is an essential trace element for maintaining health due to its ideal antioxidant properties. We previously prepared a new type of biogenic selenium nanoparticles based on alginate oligosaccharides (SeNPs-AOS), and this study aimed to investigate the protective effects of SeNPs-AOS (Se particle size = 80 nm, Se content = 8%) on organ health in broilers challenged with HS. A total of 192 21-day-old Arbor Acres broilers were randomly divided into four groups according to a 2 × 2 experimental design, including a thermoneutral zone group (TN, raised under 23 ± 1.5 °C); TN + SeNPs-AOS group (TN group supplemented 5 mg/kg SeNPS-AOS); HS group (HS, raised under 33 ± 2 °C for 10 h/day); and HS + SeNPs-AOS group (HS group supplemented 5 mg/kg SeNPS-AOS). There were six replicates in each group (eight broilers per replicate). The results showed that SeNPs-AOS improved the splenic histomorphology, enhanced the activity of catalase (CAT) and glutathione peroxidase (GSH-Px) of the spleen, as well as upregulating the splenic mRNA expression of antioxidant-related genes in broilers under HS. In addition, SeNPs-AOS reversed the pathological changes in bursa caused by HS increased the activity of GST, GSH-Px, and CAT and upregulated the mRNA expression of Nrf2 and antioxidant-related genes in the bursa of heat-stressed broilers. In addition, dietary SeNPs-AOS improved the hepatic damage, increased the activity of GSH-Px in the liver, and upregulated the mRNA expression of antioxidant-related genes while downregulating the Keap1 gene expression of the liver in broilers during HS. Moreover, dietary SeNPs-AOS upregulated the anti-ferroptosis-related genes expression of liver in broilers under HS. In conclusion, dietary SeNPs-AOS could relieve HS-induced oxidative damage to the spleen, bursa of Fabricius and liver in broilers by upregulating the Nrf2-mediated antioxidant gene expression and SeNPs-AOS could also upregulate the expression of hepatic Nrf2-related anti-ferroptosis genes in heat-stressed broilers. These findings are beneficial for the development of new nano-antioxidants in broilers.

The poor biostability and bioavailability of proanthocyanidins limit their application. In this study, it was hypothesized that encapsulation in lecithin-based nanoliposomes using ultrasonic technology improves the above properties. Based on preliminary experiments, the effects of lecithin mass ratio (1-9%, wt.), pH (3.2-6.8), ultrasonic power (0-540 W), and time (0-10 min) on biostability and bioavailability of purified kiwi leaves proanthocyanidins (PKLPs) were determined. Nanoliposomes prepared optimally with lecithin (5%, wt.), pH = 3.2, ultrasonic power (270 W), and time (5 min) demonstrated a significantly (p < 0.05) improved physicochemical stability, homogeneity, and high encapsulation efficiency (73.84%) relative to control. The PKLPs bioaccessibility during in vitro digestion increased by 2.28-3.07-fold, with a remarkable sustained release and delivery to the small intestine. Similar results were obtained by in vivo analyses, showing over 200% increase in PKLPs bioaccessibility compared to the control. Thus, PKLPs-loaded nanoliposomes are promising candidates for foods and supplements for novel applications., 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 Ltd. All rights reserved.)

Background: Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia-reperfusion (I/R) injury, which is one of the main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1 + ) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia., Methods: Exosomes were enriched from young Sca-1 + or Sca-1 - cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment., Results: Sca-1 + exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1 - , at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1 + exosomes had higher miR-150-5p levels, compared to Sca-1 - exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1 + exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology., Conclusion: This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1 + exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning., (© 2023. The Author(s).)

Polydnavirus (PDV) is a parasitic factor of endoparasitic wasps and contributes greatly to overcoming the immune response of parasitized hosts. Protein tyrosine phosphatases (PTPs) regulate a wide variety of biological processes at the post-transcriptional level in mammals, but knowledge of PDV PTP action during a parasitoid−host interaction is limited. In this study, we characterized a PTP gene, CvBV&#95;12-6, derived from Cotesia vestalis bracovirus (CvBV), and explored its possible regulatory role in the immune response of the host Plutella xylostella. Our results from qPCR show that CvBV&#95;12-6 was highly expressed in hemocytes at an early stage of parasitization. To explore CvBV&#95;12-6 function, we specifically expressed CvBV&#95;12-6 in Drosophila melanogaster hemocytes. The results show that Hml-Gal4 > CvBV&#95;12-6 suppressed the phenoloxidase activity of hemolymph in D. melanogaster, but exerted no effect on the total count or the viability of the hemocytes. In addition, the Hml-Gal4 > CvBV&#95;12-6 flies exhibited decreased antibacterial abilities against Staphylococcus aureus. Similarly, we found that CvBV&#95;12-6 significantly suppressed the melanization of the host P. xylostella 24 h post parasitization and reduced the viability, but not the number, of hemocytes. In conclusion, CvBV&#95;12-6 negatively regulated both cellular and humoral immunity in P. xylostella, and the related molecular mechanism may be universal to insects.

The extensive use of tetracycline antibiotics has led to the widespread presence of tetracycline-resistance genes in Gram-negative bacteria and this poses serious threats to human and animal health. In our previous study, we reported a method for rapid detection of Tet(X)-producers using MALDI-TOF MS. However, there have been multiple machineries involved in tetracycline resistance including efflux pump, and ribosomal protection protein. Our previous demonstrated the limitation in probing the non-Tet(X)-producing tetracycline-resistant strains. In this regard, we further developed a MALDI-TOF MS method to detect and differentiate Tet(X)-producers and non-Tet(X)-producing tetracycline-resistant strains. Test strains were incubated with tigecycline and oxytetracycline in separate tubes for 3 h and then analyzed spectral peaks of tigecycline, oxytetracycline, and their metabolite. Strains were distinguished using MS ratio for [metabolite/(metabolite+ tigecycline or oxytetracycline)]. Four control strains and 319 test strains were analyzed and the sensitivity was 98.90% and specificity was 98.34%. This was consistent with the results obtained from LC-MS/MS analysis. Interestingly, we also found that the reactive oxygen species (ROS) produced by tetracycline-susceptible strains were able to promote the degradation of oxytetracycline. Overall, the MALDI Tet(X)-plus test represents a rapid and reliable method to detect Tet(X)-producers, non-Tet(X)-producing tetracycline-resistant strains, and tetracycline-susceptible strains.

Aim: The aim of this study is to demonstrate the expression and clinicopathological significance of complement C1q B chain ( C1QB ) in cervical cancer., Methods: In total, 120 cervical cancer tissues, as well as 20 samples each of high-grade squamous intraepithelial lesions (HSILs), low-grade squamous intraepithelial lesions (LSILs), and benign cervical tissue, were collected to evaluate the expression of C1QB protein via immunohistochemical staining. We conducted an integrated analysis of C1QB mRNA expression in cervical cancer using public microarrays and RNA-seq data sets by calculating standard mean differences (SMDs). Simultaneously, we explored the relations of C1QB with clinicopathological parameters and the expression of P16, Ki-67, and P53., Results: The expression of C1QB protein was higher in cervical cancer samples than that in benign cervical tissue, LSIL, and HSIL samples ( p < 0.05). A combined SMD of 0.65 (95% CI: [0.52, 0.79], p < 0.001) revealed upregulation of C1QB mRNA in cervical cancer. C1QB expression may also be related to the depth of infiltration, lymphovascular invasion, and perineural invasion in cervical cancer ( p < 0.05). We also found that C1QB protein expression was positively correlated with P16 and Ki-67 expression in cervical cancer ( p < 0.05). The gene set enrichment analysis showed that C1QB may participate in apoptosis and autophagy. A relationship was predicted between C1QB expression and drug sensitivity to cisplatin, paclitaxel, and docetaxel., Conclusion: We confirmed the overexpression of C1QB in cervical cancer at both mRNA and protein levels for the first time. C1QB may serve as an oncogene in the tumorigenesis of cervical cancer, but this possibility requires further study., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Si-Tong Lin et al.)

Chelonus formosanus Sonan is an important egg-larval parasitoid of noctuid moths and a potential candidate for understanding interactions between host and parasitoid mediated by polydnavirues (PDVs). We sequenced and annotated the mitochondrial genome of C. formosanus, which is 15,466 bp in length and possesses 38 mitochondrial genes. However, unlike most animal mitochondrial genomes, it contains one extra trnF gene. There are five transfer RNA (tRNA) rearrangement events compared with the ancestral gene order, which is a novel rearrangement type in Hymenoptera for all published mitogenomes so far. Phylogenetic trees supported C. formosanus from the subfamily Cheloninae was closely related to the subfamily Cardiochilinae and Microgastrinae., (© 2022 The Authors. Archives of Insect Biochemistry and Physiology published by Wiley Periodicals LLC.)

Neoneuromus ignobilis is an archaic holometabolous aquatic predatory insect. However, a lack of genomic resources hinders the use of whole genome sequencing to explore their genetic basis and molecular mechanisms for adaptive evolution. Here, we provided a high-contiguity, chromosome-level genome assembly of N. ignobilis using high coverage Nanopore and PacBio reads with the Hi-C technique. The final assembly is 480.67 MB in size, containing 12 telomere-ended pseudochromosomes with only 17 gaps. We compared 42 hexapod species genomes including six independent lineages comprising 11 aquatic insects, and found convergent expansions of long wavelength-sensitive and blue-sensitive opsins, thermal stress response TRP channels, and sulfotransferases in aquatic insects, which may be related to their aquatic adaptation. We also detected strong nonrandom signals of convergent amino acid substitutions in aquatic insects. Collectively, our comparative genomic analysis revealed the evidence of molecular convergences in aquatic insects during both gene family evolution and convergent amino acid substitutions., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Clec1A, a member of C-type lectin receptor family, has a carbohydrate recognition domain in its extracellular region, but no known signaling motif in the cytoplasmic domain. Clec1a is highly expressed in endothelial cells and weakly in dendritic cells. Although this molecule was reported to play an important role in the host defense against Aspergillus fumigatus by recognizing 1,8-dihydroxynaphthalene-melanin on the fungal surface, the roles of this molecule in un-infected animals remain to be elucidated. In this study, we found that Clec1a -/- mice develop milder symptoms upon induction of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. The maximum disease score was significantly lower, and demyelination and inflammation of the spinal cord were much milder in Clec1a -/- mice compared to wild-type mice. No abnormality was detected in the immune cell composition in the draining lymph nodes and spleen on day 10 and 16 after EAE induction. Recall memory T cell proliferation after restimulation with myelin oligodendrocyte glycoprotein peptide (MOG 35-55 ) in vitro was decreased in Clec1a -/- mice, and antigen presenting ability of Clec1a -/- dendritic cells was impaired. Interestingly, RNA-Seq and RT-qPCR analyses clearly showed that the expression of inflammatory cytokines including Il17a, Il6 and Il1b was greatly decreased in Clec1a -/- mice after induction of EAE, suggesting that this reduced cytokine production is responsible for the amelioration of EAE in Clec1a -/- mice. These observations suggest a novel function of Clec1A in the immune system.

Dendritic cell immunoreceptor (DCIR; Clec4a2), a member of the C-type lectin receptor family, plays important roles in homeostasis of the immune and bone systems. However, the intestinal role of this molecule is unclear. Here, we show that dextran sodium sulfate (DSS)-induced colitis and azoxymethane-DSS-induced intestinal tumors are reduced in Clec4a2 -/- mice independently of intestinal microbiota. STAT5 phosphorylation and expression of Csf2 and tight junction genes are enhanced, while Il17a and Cxcl2 are suppressed in the Clec4a2 -/- mouse colon, which exhibits reduced infiltration of neutrophils and myeloid-derived suppressor cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) administration ameliorates DSS colitis associated with reduced Il17a and enhanced tight junction gene expression, whereas anti-GM-CSF exacerbates symptoms. Furthermore, anti-NA2, a ligand for DCIR, ameliorates colitis and prevents colorectal tumors. These observations indicate that blocking DCIR signaling ameliorates colitis and suppresses colonic tumors, suggesting DCIR as a possible target for the treatment of these diseases., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Proanthocyanidins (PAs) are considered to be effective natural byproduct and bioactive antioxidants. However, few studies have focused on their mode of action pathways. In this study, reactive oxygen species (ROS), oxidative stress indices, real-time PCR, Western blotting, confocal microscopy, and molecular docking were used to investigate the protective effect of purified kiwi leaves PAs (PKLPs) on Caco-2 cells’ oxidative stress mechanisms. The results confirmed that pre-treatment with PKLPs significantly reduced H2O2-induced oxidative damage, accompanied by declining ROS levels and malondialdehyde (MDA) accumulation in the Caco-2 cells. The PKLPs upregulated the expression of antioxidative enzymes (GSH-px, CAT, T-SOD) and the relative mRNA (Nrf, HO-1, SOD-1, CAT) of the nuclear factor erythroid 2-related factor (Nrf2) signaling pathway. The protein-expressing level of the Nrf2 and its relative protein (NQO-1, HO-1, SOD-1) were significantly increased (p < 0.05) in the PKLPs pre-treatment group compared to the model group. In conclusion, the novelty of this study is that it explains how PKLPs’ efficacy on the Nrf2-ARE signaling pathway, in protecting vital cells from oxidative stress, could be used for cleaner production.

Background: The past decade has witnessed a dramatic increase in the number of patients with inflammatory bowel disease (IBD) in China. The nationwide burden of hospitalization remains unclear, however. We aimed to address this gap by conducting analysis using a nationwide database., Methods: Population-based hospitalization rates from 2013 to 2018 were calculated by extrapolating the number of patients in the database to the national level. Surgical rates, annual hospital charges, and length of stay were also used for quantification of hospitalization burden. The Poisson regression analysis and the Cochran-Armitage trend test were conducted to analyze temporal trends as expressed as annual percentage of change (APC) with 95% confidential intervals (CIs)., Results: From 2013 to 2018, the hospitalization rates for Crohn's disease (CD) and ulcerative colitis (UC) in China increased from 2.20 (95% CI = 2.17-2.22) to 3.62 (3.59-3.65) per 100,000 inhabitants ( p  < 0.0001) with an APC of 10.68% (6.00-15.36%) and from 6.24 (6.20-6.28) to 8.29 (8.23-8.33) per 100,000 inhabitants ( p  < 0.0001) with an APC of 5.73% (2.32-9.15%), respectively. Surgical rates decreased from 7.96% (7.29-8.63%) to 5.56% (5.11-6.00%) for CD patients ( p  < 0.0001) with APC of -6.30% (-11.33 to -1.27%) and from 3.54% (3.26-3.82%) to 2.52% (2.32-2.72%) for UC patients ( p  < 0.0001) with APC of -6.35% (-16.21 to 3.51). In 2018, there were estimated 166,000 IBD patients hospitalized costing a total of $426.37 million ($149.91 + $276.46 million) across the entire China., Conclusion: The population-based hospitalization rate of IBD increased, whereas the surgical rate decreased from 2013 to 2018 in China., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Flower is an essential element in the human lifestyle but its role in disseminating antimicrobial resistance (AMR) between the environment and humans is unclear. In this study, we screened fresh flowers (Lilium spp.) collected from planting bases, market and florists in Guangzhou China aiming to investigate the prevalence of AMR genes, particularly cfr, optrA and poxtA mediating resistance to linezolid, a first-line drug for the treatment of different Gram-positive bacterial infections. We found 223 Enterococcus isolates consisting of Enterococcus faecalis, Enterococcus faecium and Enterococcus mundtii, and >50% of these isolates exhibited multiple-drug resistance. Additionally, 31 optrA-positive Enterococcus including 22 E. faecalis and 9 E. mundtii strains were recovered, however cfr and poxtA were not detected. The 22 E. faecalis strains were belonged to 7 Multilocus sequence types in which ST202 and ST376 were predominant and 9 E. mundtii strains from the same plantation bases were divided into three PFGE groups. Genetically, the majority of optrA were located on the chromosome and shared similar insertion sites and transpositions mediated by Tn554 family members. Plasmid-bearing optrA were identified in 6 E. faecalis strains where IS1216 family played key roles in horizontal transfer of optrA. These findings emphasize that the prevalence of drug resistant Enterococcus in fresh flowers is a latent danger and increases the risk of AMR dissemination to humans from the environment., 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 © 2021 Elsevier B.V. All rights reserved.)

The knowledge of high-pressure behavior of LiH is significant for the validation of fundamental theoretical models and applications in thermonuclear materials and potential energy supplies. The compressibility of 7 LiH under isentropic compression at high pressure was investigated experimentally and theoretically. The experimental technique for quasi-isentropic compression with low-density materials was developed using the magnetocumulative generator CJ-100 and x-ray flash radiography. The x-ray images and extracted interface of the sample target in dynamic flash radiography experiments were obtained. According to each interface size of the target both before and after compression, the compression ratio of 7 LiH and reference material aluminum was obtained. The density of the reference and using its known isentropic curve provide the pressure in the reference. The pressure in 7 LiH was deduced from the pressure in the reference and using the calculated gradient correction factor. The quasi-isentropic data point at 438 GPa was obtained experimentally. A semiempirical three-term complete equation of state was constructed and validated for 7 LiH using the theory of Mie-Grüneisen-Debye with experimental data from the literature. The quasi-isentrope data point is reasonably consistent with the theoretical results. The quasi-isentropic experimental techniques and results broaden the existing research scope and are practical and helpful to further validate theoretical models in the future.

RNA interference pathways mediated by different types of small non-coding RNAs (siRNAs, miRNAs and piRNAs) are conserved biological responses to exotic stresses, including viral infection. Aside from the well-established siRNA pathway, the miRNA pathway and the piRNA pathway process viral sequences, exogenously or endogenously, into miRNAs and piRNAs, respectively. During the host-virus interaction, viral sequences, including both coding and non-coding sequences, can be integrated as endogenous viral elements (EVEs) and thereby become present within the germline of a non-viral organism. In recent years, significant progress has been made in characterizing the biogenesis and function of viruses and EVEs associated with snRNAs. Overall, the siRNA pathway acts as the primarily antiviral defense against a wide range of exogenous viruses; the miRNA pathways associated with viruses or EVEs function in antiviral response and host gene regulation; EVE derived piRNAs with a ping-pong signature have the potential to limit cognate viral infection., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Polydnaviruses (PDVs) are obligatory symbionts of parasitoid wasps and play an important role in suppressing host immune defenses. Although PDV genes that inhibit host melanization are known in Microplitis bracovirus, the functional homologs in Cotesia bracoviruses remain unknown. Here, we find that Cotesia vestalis bracovirus (CvBV) can inhibit hemolymph melanization of its host, Plutella xylostella larvae, during the early stages of parasitization, and that overexpression of highly expressed CvBV genes reduced host phenoloxidase activity. Furthermore, CvBV-7-1 in particular reduced host phenoloxidase activity within 12 h, and the injection of anti-CvBV-7-1 antibody increased the melanization of parasitized host larvae. Further analyses showed that CvBV-7-1 and three homologs from other Cotesia bracoviruses possessed a C-terminal leucine/isoleucine-rich region and had a similar function in inhibiting melanization. Therefore, a new family of bracovirus genes was proposed and named as C-terminal Leucine/isoleucine-rich Protein (CLP). Ectopic expression of CvBV-7-1 in Drosophila hemocytes increased susceptibility to bacterial repression of melanization and reduced the melanotic encapsulation of parasitized D. melanogaster by the parasitoid Leptopilina boulardi. The formation rate of wasp pupae and the eclosion rate of C. vestalis were affected when the function of CvBV-7-1 was blocked. Our findings suggest that CLP genes from Cotesia bracoviruses encoded proteins that contain a C-terminal leucine/isoleucine-rich region and function as melanization inhibitors during the early stage of parasitization, which is important for successful parasitization., (© 2020 Institute of Zoology, Chinese Academy of Sciences.)

The interleukin-17 (IL-17) family consists of six family members (IL-17A-IL-17F) and all the corresponding receptors have been identified recently. This family is mainly involved in the host defense mechanisms against bacteria, fungi and helminth infection by inducing cytokines and chemokines, recruiting neutrophils, inducing anti-microbial proteins and modifying T-helper cell differentiation. IL-17A and some other family cytokines are also involved in the development of psoriasis, psoriatic arthritis and ankylosing spondylitis by inducing inflammatory cytokines and chemokines, and antibodies against IL-17A as well as the receptor IL-17RA are being successfully used for the treatment of these diseases. Involvement in the development of inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis and tumors has also been suggested in animal disease models. In this review, we will briefly review the mechanisms by which IL-17 cytokines are involved in the development of these diseases and discuss possible treatment of inflammatory diseases by targeting IL-17 family members., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Society for Immunology.)

Objective: To investigate the prevalence and associated factors of hyperkalemia in dialysis patients. Methods: Patients underwent hemodialysis (HD) and peritoneal dialysis (PD) from multi-center databases were recruited from January 2017 to December 2019, and those aged ≥18 years and with dialysis duration ≥3 months were included to analyze the prevalence and related factors of hyperkalemia. Results: A total of 12 364 patients were enrolled in the study, and 6 836 cases were men. The average age of the patients was (51±15) years. Among these patients, 4 230 cases underwent HD while 8 134 received PD. Hyperkalemia was detected in 20.7% (2 554/12 364) of the patients while hypokalemia was found in 17.0%(2 102/12 364) of the patients. Multivariate logistic regression showed that HD ( OR =2.25, 95% CI : 1.54-3.30), diabetes mellitus (DM) ( OR =1.65, 95% CI : 1.17-2.32), high body mass index (BMI) ( OR =1.06, 95% CI : 1.03-1.09), high levels of serum albumin ( OR =1.04, 95% CI : 1.01-1.07) and phosphorus ( OR =3.12, 95% CI : 2.44-4.00), low levels of serum bicarbonate ( OR =0.89, 95% CI : 0.87-0.92), triglycerides ( OR =0.76, 95% CI : 0.68-0.85) and creatinine ( OR =0.95, 95% CI : 0.90-0.99), usage of angiotensin converting enzyme inhibitor/Angiotensin Ⅱ receptor antagonist (ACEI/ARB, OR =1.38, 95% CI : 1.11-1.72) and beta-blocker ( OR =1.32, 95% CI : 1.07-1.64) were associated with hyperkalemia. Conclusions: Hyperkalemia occurred in 20.7% of the dialysis patients. HD, DM, high BMI, high levels of serum albumin and phosphorus, low levels of serum bicarbonate, triglycerides and creatinine, use of ACEI/ARB were associated with hyperkalemia.

Serine proteinase inhibitor B9 (serpin B9) is a member of the serine protease inhibitor superfamily, which is widely found in animals, plants and microorganisms. Serpin B9 has been reported to protect cells from the immune‑killing effect of granzyme B (GrB) released by lymphocytes. In recent years, an increasing number of studies have indicated that serpin B9 is involved in tumour apoptosis, immune evasion, tumorigenesis, progression, metastasis, drug resistance and even in maintaining the stemness of cancer stem cells (CSCs). Moreover, according to clinical studies, serpin B9 has been demonstrated to be significantly associated with the development of precancerous lesions, a poor prognosis and ineffective therapies, suggesting that serpin B9 may be a potential target for cancer treatment and an indicator of cancer diagnosis; thus, it has begun to attract increased attention from scholars. The present review concisely described the structure and biological functions of the serpin superfamily and serpin B9. In addition, related research on serpins in cancer is discussed in order to provide a comprehensive understanding of the role of serpin B9 in cancer, as well as its clinical significance for cancer diagnosis and prognosis.

Using ultrasound (US) in proanthocyanidin (PA) extraction has become one of the important emerging technologies. It could be the next generation for studying the US mechnophore impact on the bioactive compound's functionality. The objective of this study was to demonstrate the potential of US treatment on PAs extracted from kiwifruit ( Actinidia chinensis ) leaves, and to provide a comprehensive chemical composition and bioactivity relationship of the purified kiwifruit leaves PAs (PKLPs). Several methods like single-factor experiments and response surface methodology (RSM) for the four affected factors on US extraction efficiency were constructed. HPLC-QTOF-MS/MS, cytotoxicity analysis, and antioxidant activity were also demonstrated. In the results, the modeling of PA affected factors showed that 40% US-amplitude, 30 mL/g dry weight (DW) solvent to solid ration (S/S), and 70 °C for 15 min were the optimum conditions for the extraction of PAs. Furthermore, PKLPs exhibited significant radical scavenging and cellular antioxidant activity ( p < 0.05). In conclusion, this study's novelty comes from the broad prospects of using US in PKLP green extraction that could play an important role in maximizing this phytochemical functionality in drug discovery and food science fields.

Xiyanping (XYP) is a Chinese herbal medicine used in the clinic to treat respiratory infection and pneumonia. Recent evidence identified XYP as a potential inhibitor of severe acute respiratory syndrome coronavirus 2, implying XYP as a possible treatment for the coronavirus disease 2019 (COVID-19). Here, we conducted a prospective, multicenter, open-label and randomized controlled trial to evaluate the safety and effectiveness of XYP injection in patients with mild to moderate COVID-19. We consecutively recruited 130 COVID-19 patients with mild to moderate symptoms from five study sites, and randomized them in 1:1 ratio to receive XYP injection in combination with standard therapy or receive standard supportive therapy alone. We found that XYP injection significantly reduced the time to cough relief, fever resolution and virus clearance. Less patients receiving XYP injection experienced disease progression to the severe stage during the treatment process. No severe adverse events were reported during the study. Taken together, XYP injection is safe and effective in improving the recovery of patients with mild to moderate COVID-19. However, further studies are warranted to evaluate the efficacy of XYP in an expanded cohort comprising COVID-19 patients at different disease stages., (© 2021 John Wiley & Sons Ltd.)

Purpose: Calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are new agents approved by the US Food and Drug Administration for preventive treatment of chronic migraine. Comparison between CGRPmAbs and previously approved Botulinum neurotoxin A (BoNT-A) will inform optimal preventive treatment of chronic migraine, but head-to-head trials are lacking. We therefore aimed to perform adjusted indirect comparison between CGRPmAbs and BoNT-A through a meta-analysis. Methods: OVID MEDLINE, EMBASE and the Cochrane central register of controlled trials, clinical registries, and government websites were searched from inception to September 2019. Randomized controlled trials comparing CGRPmAbs or BoNT-A with placebo in the preventive treatment of chronic migraine were included. The primary outcomes were headache days and migraine days measured at week 12. Data were synthesized by using a frequentist approach; and the treatments were ranked by P-score. Results: We included 10 trials ( n = 4,678) after screening 1049 candidates. Six trials were with low risk of bias. Fremanezumab had an effect similar to BoNT-A in the reduction of headache days at week 12 (standard mean difference [SMD] 0.08, 95%CI -0.55 to -0.7). Galcanezumab reduced more migraine days than BoNT-A at week 12 (SMD, -0.94, 95%CI -1.24 to -0.63); fremanezumab showed similar findings (SMD, -0.55, 95%CI -0.85 to -0.24). Galcanezumab and fremanezumab had better effect in mitigating headache impact at week 12. CGRPmAbs and BoNT-A had similar adverse event rate. Conclusion: CGRPmAbs and BoNT-A had similar effect in the preventive treatment of chronic migraine. BoNT-A might be preferentially selected owing to its cost-effectiveness profiles. Further studies with direct comparison of the two treatments are warranted., 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 Chen, Ye, Tang, She, Chen and Zheng.)

Hypoxia is a common phenomenon during tumorigenesis and tumour development. In recent years, studies have found that hypoxia‑inducible factor (HIF)‑2α, also referred to as endothelial PAS domain protein‑1, plays an important role in tumours. HIF‑2α is an important oncogene and a critical prognostic indicator in non‑small cell lung cancer. However, no unified conclusion can be drawn concerning HIF‑2α and small cell lung cancer, since few studies to date have focused on their association. An increasing number of studies have confirmed that HIF‑2α is involved in tumorigenesis, cell proliferation, angiogenesis, metastasis, drug resistance and radiotherapy failure in lung cancer. Of note, HIF‑2α plays a crucial role in lung cancer to maintain cancer cell stemness. Based on the importance of HIF‑2α in lung cancer, HIF‑2α‑targeted therapy has been attracting increasing attention. Although this strategy currently appears to be promising in vitro , it has never been assessed as a therapy for lung cancer. The aim of the present review was to summarize the contribution of HIF‑2α to various aspects of lung cancer, as well as its potential as targeted therapy.

Background: Pregnancy and childbirth are the main causes of pelvic floor dysfunction (PFD). Although pelvic floor muscle tension is typically measured at 42 days postpartum to assess the severity of PFD and provide timely rehabilitation, it is still impossible to predict PFD and take targeted preventive measures in clinical practice. A PFD prediction model based on big data obtained in prenatal check-ups was established in this study to allow the formulation of personalized preventive strategies to reduce the incidence of PFD., Methods: A total of 1,500 women who underwent regular prenatal checkups and examinations for PFD at 42 days postpartum at the Zhuji Maternal and Child Health Hospital between May 2015 and May 2020 were selected. The data from 1,000 of them were selected as the training cohort, and the data from 500 of them were used as the validation cohort. The women were divided into a PFD group and a non-PFD group according to whether PFD was diagnosed at 42 days postpartum. A nomogram prediction model was created using the influencing factors that lead to PFD, and the discrimination and calibration of the nomogram were evaluated through internal and external validation., Results: A total of 389 cases (38.9%) of PFD were included in the training cohort. Multivariate analysis showed that age (odds ratio (OR) =1.896, P<0.001), history of childbirth (OR =4.531, P<0.001), history of constipation (OR =2.475, P<0.001), urinary incontinence during pregnancy (OR =4.416, P<0.001), and biparietal diameter at 32 weeks of gestation (OR =51.672, P=0.012) were independent influencing factors of PFD at 42 days postpartum. These factors were used to establish a nomogram prediction model. This prediction model maintained good discrimination between the training cohort and the external validation cohort (the area under the curve was 0.893 and 0.842 for the training and validation cohorts, respectively)., Conclusions: The study validated that the nomogram prediction model based on the factors influencing PFD can be used to predict PFD at 32 weeks of gestation for timely intervention and prevention of PFD.

Polydnaviruses (PDVs), classified into two genera, bracoviruses (BVs) and ichnoviruses (IVs), are large, double-stranded DNA viruses, which are beneficial symbionts of parasitoid wasps. PDVs do not replicate in their infected lepidopteran hosts. BV circles have been demonstrated to be integrated into host genomic DNA after natural parasitization. However, the integrations of IV circles in vivo remain largely unknown. Here, we analyzed the integration of Diadegma semiclausum ichnovirus (DsIV) in the genomic DNA of parasitized Plutella xylostella hemocytes. We found that DsIV circles are present in host hemocytes with non-integrated and integrated forms. Moreover, DsIV integrates its DNA circles into the host genome by two distinct strategies, conservatively, and randomly. We also found that four conserved-broken circles share similar motifs containing two reverse complementary repeats at their breaking sites, which were host integration motifs (HIMs). We also predicted HIMs of eight circles from other ichnoviruses, indicating that a HIM-mediated specific mechanism was conserved in IV integrations. Investigation of DsIV circle insertion sites of the host genome revealed the enrichment of microhomologies between the host genome and the DsIV circles at integration breakpoints. These findings will deepen our understanding of the infections of PDVs, especially IVs., 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 Wang, Zhou, Yang, Ye, Shi, Huang and Chen.)

An efficient and practical benzylic aerobic oxidation catalyzed by cheap and simple N -hydroxyimide organocatalyst has been achieved with high yields and broad substrate scope. The organocatalyst used can be recycled and reused by simple workup and only minute amount (1 mol% in most cases) of simple iron salt is used as promoter. Phenyl substrates with mild and strong electron-withdrawing group could also be oxygenated in high yields as well as other benzylic methylenes. Influence of substituents, gram-scale application, catalysts decay and general mechanism of this methodology has also been discussed., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background and Aims: Microvascular invasion (MVI) is a key pathological factor that severely affects the postoperative prognosis of patients with hepatocellular carcinoma (HCC). However, no MVI classification schemes based on standardized gross sampling protocols of HCC are available at present., Methods: 119 HCC specimens were sampled at multiple sites (3-, 7-, and 13 points) for the optimum MVI detection rate. 16,144 resected HCCs were graded as M0, M1 or M2 by adopting three-tiered MVI grading (MVI-TTG) scheme based on the seven-point sampling protocol (SPSP). Survival analyses were performed on 2573 patients to explore the advantages of MVI-TTG., Results: The MVI detection rate determined by SPSP was significantly higher than that determined by the 3-point sampling method (34.5% vs. 47.1%, p = 0.048), but was similar to that determined by the 13-point sampling method (47.1% vs. 51.3%, p = 0.517). Among 16,144 resected HCCs, the proportions of M0, M1 and M2 specimens according to SPSP were 53.4%, 26.2% and 20.4%, respectively. Postoperative survival analysis in 2573 HCC patients showed that the 3-year recurrence rates in M0, M1 and M2 MVI groups were 62.5%, 71.6% and 86.1%, respectively (p < 0.001), and the corresponding 3-year overall survival (OS) rates were 94.1%, 87.5% and 67.0%, respectively (p < 0.001). M1 grade was associated with early recurrence, while M2 grade was associated with both early and late recurrence. MVI-TTG had a larger area under the curve and net benefit rate than the two-tiered MVI grading scheme for predicting time to recurrence and OS., Conclusions: SPSP is a practical method to balance the efficacy of sampling numbers and MVI detection rates. MVI-TTG based on SPSP is a better prognostic predictor than the two-tiered MVI scheme. The combined use of SPSP and MVI-TTG is recommended for the routine pathological diagnosis of HCC.

Background: Infliximab (IFX) is effective at inducing and maintaining clinical remission and mucosal healing in patients with Crohn's disease (CD); however, 9%-40% of patients do not respond to primary IFX treatment. This study aimed to construct and validate nomograms to predict IFX response in CD patients., Methods: A total of 343 patients diagnosed with CD who had received IFX induction from four tertiary centers between September 2008 and September 2019 were enrolled in this study and randomly classified into a training cohort ( n  = 240) and a validation cohort ( n  = 103). The primary outcome was primary non-response (PNR) and the secondary outcome was mucosal healing (MH). Nomograms were constructed from the training cohort using multivariate logistic regression. Performance of nomograms was evaluated by area under the receiver-operating characteristic curve (AUC) and calibration curve. The clinical usefulness of nomograms was evaluated by decision-curve analysis., Results: The nomogram for PNR was developed based on four independent predictors: age, C-reactive protein (CRP) at week 2, body mass index, and non-stricturing, non-penetrating behavior (B1). AUC was 0.77 in the training cohort and 0.76 in the validation cohort. The nomogram for MH included four independent factors: baseline Crohn's Disease Endoscopic Index of Severity, CRP at week 2, B1, and disease duration. AUC was 0.79 and 0.72 in the training and validation cohorts, respectively. The two nomograms showed good calibration in both cohorts and were superior to single factors and an existing matrix model. The decision curve indicated the clinical usefulness of the PNR nomogram., Conclusions: We established and validated nomograms for the prediction of PNR to IFX and MH in CD patients. This graphical tool is easy to use and will assist physicians in therapeutic decision-making., (© The Author(s) 2020. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Blastomere loss is a common issue during frozen-thawed embryo transfer (FET). Our previous study showed that blastomere loss was associated with an increased risk of small-for-gestational-age (SGA) neonates. The present study assessed the impact of blastomere loss during cryopreservation by comparing the mRNA profiles of umbilical cord blood of FET offspring from the prospective cohort study. Umbilical cord blood samples were collected from 48 neonates, including 12 from the loss group, 11 from the intact group, and 25 from the matched spontaneous pregnancy group. RNA-seq technology was used to compare the global gene expression profiles of the lymphocytes. Then, we used TopHat software to map the reads and quantitative real-time PCR to validate some important differentially expressed genes (DEGs). We identified 92 DEGs between the loss group and the spontaneous pregnancy group, including IGF2 and H19. Ingenuity Pathway Analysis (IPA) showed that the DEGs were most affected in the blastomere loss group. Downstream analysis also predicted the activation of organismal death pathways. In conclusions, our pilot study sheds light on the mechanism underlying how human blastomere loss may affect offspring at the gene expression level. These conclusions are, however, only suggestive, as the current study is based on a very limited sample size and type or nature of biological samples. Additional studies with larger sample sizes and independent experiments with placental samples should be conducted to verify these findings.

The chemotherapeutic options for methicillin-resistant Staphylococcus aureus (MRSA) infections are limited. Due to the multiple resistant MRSA, therapeutic failure has occurred frequently, even using antibiotics belonging to different categories in clinical scenarios, very recently. This study aimed to investigate the interactions between 11 antibiotics representing different mechanisms of action against MRSA strains and provide therapeutic strategies for clinical infections. Susceptibilities for MRSA strains were determined by broth microdilution or agar dilution according to CLSI guideline. By grouping with each other, a total of 55 combinations were evaluated. The potential synergism was detected through drug interaction assays and further investigated for time-killing curves and an in vivo neutropenic mouse infection model. A total of six combinations (vancomycin with rifampicin, vancomycin with oxacillin, levofloxacin with oxacillin, gentamycin with oxacillin, clindamycin with oxacillin, and clindamycin with levofloxacin) showed synergistic activity against the MRSA ATCC 43300 strain. However, antibacterial activity against clinical isolate #161402 was only observed when vancomycin combined with oxacillin or rifampicin in time-killing assays. Next, therapeutic effectiveness of vancomycin/oxacillin and vancomycin/rifampicin was verified by an in vivo mouse infection model inoculated with #161402. Further investigations on antimicrobial synergism of vancomycin plus oxacillin and vancomycin plus rifampicin against 113 wild-type MRSA strains were evidenced by combined antibiotic MICs and bacterial growth inhibition and in vitro dynamic killing profiles. In summary, vancomycin/rifampicin and vancomycin/oxacillin are the most potential combinations for clinical MRSA infection upon both in vitro and in vivo tests. Other synergetic combinations of levofloxacin/oxacillin, gentamycin/oxacillin, clindamycin/oxacillin, and clindamycin/fosfomycin are also selected but may need more assessment for further application., (Copyright © 2020 Yu, Huang, Ye, Cai, Fang, Sun, Liao and Liu.)

MYB Proto-Oncogene Like 2 (MYBL2) is a highly conserved member of the Myb family of transcription factors and plays a critical role in regulating cell proliferation and survival. Here we show that overexpression of MYBL2 is frequently observed in lung adenocarcinoma (LUAD) and significantly correlates with advanced stage and poor patient survival. Knockdown of MYBL2 induced apoptosis in lung cancer cells and resulted in significant inhibition of cell proliferation, migration, and invasion. Notably, we identified Non-SMC Condensin I Complex Subunit H (NCAPH) gene as a direct target of MYBL2. NCAPH expression is highly correlated with that of MYBL2 in LUAD cases and is tightly affected by MYBL2 knockdown or overexpression in vitro. Chromatin immunoprecipitation (ChIP) assays also showed that MYBL2 directly binds to the transcription start site (TSS) of NCAPH. Moreover, we provided evidence that NCAPH functions as an oncogene in lung cancer and overexpression of NCAPH could partially rescue cell death and migration blockage induced by MYBL2 knockdown. Together, these results suggest that overexpression of MYBL2 promotes proliferation and migration of lung cancer cells via upregulating NCAPH, establishing their roles as novel prognostic biomarkers as well as potential therapeutic targets for the disease.

Objective: To observe the efficacy of early treatment of suspension moxibustion for Bell's palsy and its influence on the prognosis, and to explore whether the early treatment of suspension moxibustion has non-inferiority effect to hormone treatment and whether suspension moxibustion combined with hormone treatment has the synergistic effect., Methods: A total of 132 patients with acute-stage Bell's palsy were divided into a hormone group (94 cases) and a moxibustion group (38 cases) by non-random method, and the hormone group was further randomly divided into a hormone with moxibustion group (48 cases) and a hormone without moxibustion group (46 cases). The acupuncture and oral administration of mecobalamin capsule were used as basic treatment. Acupuncture was applied at Yangbai (GB 14), Sibai (ST 2), Quanliao (SI 18), Dicang (ST 4), Jiache (ST 6), Yifeng (TE 17), etc., with the needles retained for 30 min, once a day, 5 consecutive days per week; there was an interval of 2 days between two weeks, and a total of 4-week treatment was given. The oral administration of mecobalamin capsule was given 0.5 mg each time, 3 times a day for 4 weeks. The patients in the moxibustion group, on the basis of basic treatment, were treated with the suspension moxibustion at Yangbai (GB 14), Sibai (ST 2), Dicang (ST 4), Jiache (ST 6), Wangu (GB 12), Yifeng (TE 17) of affected side, 5 min per acupoint, once a day, 5 consecutive days per week; there was an interval of 2 days between two weeks, and a total of 4-week treatment was given. The patients in the hormone without moxibustion group, on the basis of basic treatment, were treated with prednisone acetate tablets. The patients in the hormone with moxibustion group, on the basis of basic treatment, were treated with suspension moxibustion and prednisone acetate tablets. All the treatment was given for 4 weeks. The House-Brcackmann facial nerve grading (H-B) global score and facial disability index (FDI) scale were used to evaluate the curative effect in the three groups before treatment, 2 weeks and 4 weeks into treatment and 4 weeks after treatment; the efficacy was compared among the three groups., Results: Compared before treatment, the H-B grading and FDI scores were significantly improved 2 weeks and 4 weeks into treatment and 4 weeks after treatment ( P <0.05). The various indexs of each group 2 weeks into treatment were not statistically significant in the three groups ( P >0.05); the H-B grading and FDI scores in the hormone with moxibustion group were superior to those in the moxibustion group and the hormone without moxibustion group 4 weeks into treatment and 4 weeks after treatment ( P <0.05), while there was no significant difference between the moxibustion group and the hormone without moxibustion group ( P >0.05). At the end of follow-up, the cured rate in the hormone with moxibustion group was 81.3% (39/48), which was superior to 68.4% (26/38) in the moxibustion group and 60.9% (28/46) in the hormone without moxibustion group ( P <0.05). However, there was no significant difference between the moxibustion group and the hormone without moxibustion group ( P >0.05)., Conclusion: The three treatment methods are all safe and effective for acute-stage Bell's palsy. The suspension moxibustion combined with hormone therapy are superior to suspension moxibustion or hormone therapy alone. Early treatment of suspension moxibustion is safe and effective for Bell's palsy, and has obvious synergistic effect with hormone. For the patients who cannot use hormone, suspension moxibustion could replace hormone, which is non-inferior to hormone.

The effect of blood pump flow rate on the cardiac functions of hemodialysis patients with arteriovenous fistula (AVF) is largely unknown. This study aimed to investigate if blood pump flow rate (Qb) and AVF access flow rate (Qa) can affect the cardiac function of Chinese hemodialysis patients. A total of 72 patients undergoing AVF hemodialysis were included from March 2010 to June 2014 and dichotomized into the high- and low-flow groups using the medians of Qb (220 mL/min) and Qa (1000 mL/min) as the cutoffs. The cardiac function parameters were measured by ultrasound dilution technique within the first (t + 30) and the last (t - 30) 30 min of dialysis. At t + 30, Qb-high group had significantly higher systolic blood pressure (SBP) and mean arterial pressure (MAP) than Qb-low group. At t - 30, Qb-high group had higher SBP, diastolic blood pressure (DBP), and MAP than Qb-low group. Qa-high group had higher SBP, MAP, cardiac output (CO), cardiac index (CI), central blood volume (CBV), and lower peripheral resistance than Qa-low group. Multiple linear regression showed that at t - 30, Qb was positively correlated with SBP and MAP. Qa was positively correlated with CO, CI, CBV, and PR but negatively correlated with heart rate. Although Qb > 220 mL/min and Qa >1000 mL/min would elevate some parameters, the means of SBP, DBP, MAP remain within the normal range, indicating that appropriate increase in blood pump flow rate has little effect on the cardiac function of hemodialysis patients., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Introduction: Spasticity is the most common complication after stroke, which is the main obstacle in the recovery of motor function. Spasticity seriously affects the quality of life and brings a heavy burden to families and society. Acupuncture is an effective method for stroke. However, whether acupuncture is effective for poststroke spasticity is still unknown. The purpose of this systematic review (SR) is to evaluate the effectiveness and safety of acupuncture for poststroke spasticity., Methods and Analysis: We will search the following databases from inception to July 2019: China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wan Fang Data, the Chinese Science and Technology Periodical Database (VIP), PubMed, Embase, The Cochrane Library, and Web of Science. All relevant randomized controlled trials (RCTs) utilizing acupuncture for poststroke spasticity will be included. The primary outcome is the modified Ashworth scale. Secondary outcomes include composite spasticity scale, clinic spasticity index, electromyographic activity, Hoffmann reflex activity, or other spasticity-related outcomes. Study selection, data extraction, and quality assessment will be performed independently by 2 reviewers. Assessment of risk of bias and data synthesis will be conducted using Review Manager V5.3 software., Ethics and Dissemination: The ethical approval is not required since SR is based on published studies. The results of this SR will be published in a peer-reviewed scientific journal according to the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) guidelines., Prospero Registration Number: CRD42019129779.

Objective: To explore the feasibility of 7, 12-dimethylbenz[a] anthracene (DMBA) induced tree shrew breast cancer model, and compare the effects of two administration modes by gavage and mammary gland injection. Methods: A total of 40 tree shrews were randomly divided into two groups (20 animals per group): DMBA gavage group and mammary gland injection group. DMBA was dissolved in edible vegetable oil. For gavage group, tree shrews were administered with DMBA solutions (15 mg/kg) by gavage once a day. For mammary gland injection group, DMBA solution (10 mg/kg) was injected into the mammary fat pad of tree shrews, and the injection was performed for a total of 3 times. From the first administration of DMBA, medroxyprogesterone acetate (MPA, 100 mg/kg) was intramuscularly injected into the muscles of the lateral thighs of tree shrews at the same time, for a total of 5 times. The tumorigenesis and survival of tree shrews were monitored. The tumor histological morphology was observed by HE staining. The expression of estrogen receptor (ER), progesterone receptor (PR), cytokeratin5/6 (CK5/6) and human epidermal factor receptor-2 (HER-2) was detected by immunohistochemical staining. Results: In the gavage group, there were 10 deaths, and 4 tree shrews developed mammary tumors with 20.0% (4/20) tumor formation rate. The success rate of mammary cancer modeling was 10.0% (2/20), and the tumor formation time was 197.3±15.1 days. In the mammary gland injection group, there were 8 tree shrews died, and 9 tree shrews formed tumors with 45.0% (9/20) tumor formation rate. The success rate of mammary cancer modeling was 40.0% (8/20), and the tumor formation time was 71.8±19.0 days. There was no significant difference in mortality and tumor formation rate ( P >0.05) between the two groups (all P >0.05). However, in the mammary gland injection group, the success rate of mammary cancer modeling was significantly higher than that in the gavage group ( P <0.05), whereas the tumor formation time was markedly shorter than that in the gavage group ( P <0.01). The pathological types in the gavage group included ductal hyperplasia, intraductal papilloma and ductal carcinoma in situ, while those in the breast injection group included intraductal papilloma and ductal carcinoma in situ. In both groups, immunohistochemical staining showed the negative expression of HER-2 but positive expression of ER, PR and CK5/6 with varying degrees. Conclusion: Both the DMBA gavage and mammary gland injection can successfully establish the tree shrew breast cancer model, and the modeling effect of mammary gland injection is better than gavage.

The effects of different cooking methods, including autoclaving, microwaving, sous vide, and stewing, on the nutritional quality of mushroom ( Hypsizygus marmoreus ) soup were investigated. The results showed that all four cooking methods increased the polysaccharide, polyphenol, and amino acid levels compared to uncooked soup. Stewing increased protein content with the other cooking methods showing no change when compared with uncooked soup. Sous vide increased nucleotide content with the other methods decreasing nucleotide levels, and this method was also the best for increasing polyphenol and flavor compounds. Autoclaving generated the highest levels of polysaccharides. In summary, each method had a characteristic effect on mushroom soup properties, and cooking improved the nutritional value of mushrooms by the increase in releasing macro- and micronutrients., Competing Interests: The authors declare that they do not have any conflict of interest.