Phage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine model.

Bacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of the immune response on clinical effectiveness. Here, we develop a mouse model to assess phage treatment using a cocktail of five phages from the Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage treatment significantly reduces fecal bacterial loads of Vancomycin-Resistant Enterococcus. We also characterize immune responses elicited following administration of the phage cocktail. While minimal innate responses are observed after phage administration, two rounds of treatment induces phage-specific neutralizing antibodies and accelerate phage clearance from tissues. Interestingly, the myophages in our cocktail induce a more robust neutralizing antibody response than the siphophages. This anti-phage immunity reduces the effectiveness of the phage cocktail in our murine model. Collectively, this study shows phage-specific immune responses may be an important consideration in the development of phage cocktails for therapeutic use.

Efficacy of anti-interleukin-17A biological agents for palmoplantar psoriasis and palmoplantar pustulosis: A network meta-analysis.

BACKGROUND: The comparative efficacy of anti-IL (interleukin)-17A biological agents in palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) are not well established. OBJECTIVE: To investigate the efficacy of different dosage regimens of anti-IL-17A biological agents compared with placebo in PP and PPP. METHODS: A literature search was conducted in PubMed, clinicaltrials.gov, and Embase. Meta-analysis was performed for all outcomes of randomized controlled trials, while network meta-analysis was only performed for the primary outcome. RESULTS: In total, 21 articles exploring the efficacy of 5 treatment options were included, 4 cohort studies were also reviewed. Meta-analysis demonstrated a statistically significant difference favoring anti-IL-17A biological agents versus placebo (OR = 6.84, 95 %[CI] [5.34, 8.76]). On-label secukinumab was identified as the most effective treatment option for patients with PP (OR = 33.50, 95 %[CI] [4.37,256.86]). PPP treated with secukinumab 300 mg showed benefit in terms of PPPASI 75 responses over 52 weeks. CONCLUSION: IL-17A biological agents had better PP disease clearance compared with placebo and on-label secukinumab was identified as the most effective treatment option for PP patients. Secukinumab 300 mg showed benefit for PPP patients.

Streptococcus sciuri sp. nov., Staphylococcus marylandisciuri sp. nov. and Staphylococcus americanisciuri sp. nov., isolated from faeces of eastern grey squirrel (Sciurus carolinensis).

One novel Streptococcus strain (SQ9-PEAT) and two novel Staphylococcus strains (SQ8-PEAT and GRT3T) were isolated from faeces of a wild eastern grey squirrel. The strains were non-spore-forming, non-motile Gram-positive cocci, facultative anaerobes. The genomes for these strains were sequenced. The 16S rRNA gene and core-genome-based phylogenetic analyses showed that strain SQ9-PEAT was closely related to Streptococcus hyointestinalis, strain SQ8-PEAT to Staphylococcus pettenkoferi and Staphylococcus argensis, and strain GRT3T to Staphylococcus rostri, Staphylococcus muscae and Staphylococcus microti. Average nucleotide identity and pairwise digital DNA-DNA hybridization values calculated for these novel strains compared to type strain genomes of phylogenetically related species within the genera Streptococcus and Staphylococcus clearly revealed that strain SQ9-PEAT represents a novel species of the genus Streptococcus and strains SQ8-PEAT and GRT3T represent two novel species of the genus Staphylococcus. Phenotypical features of these novel type strains differed from the features of the type strains of other phylogenetically related species. MALDI-TOF mass spectrometry supported identification of these novel species. Based on these data, we propose one novel species of the genus Streptococcus, for which the name Streptococcus sciuri sp. nov. with the type strain SQ9-PEAT (=DSM 114656T=CCUG 76426T=NCTC 14727T) is proposed, and two novel species of the genus Staphylococcus, for which the names Staphylococcus marylandisciuri sp. nov. with the type strain SQ8-PEAT (=DSM 114685T=CCUG 76423T=NCTC 14723T) and Staphylococcus americanisciuri sp. nov. with the type strain GRT3T (=DSM 114696T=CCUG 76427T=NCTC 14722T) are proposed. The genome G+C contents are 38.29, 36.49 and 37.26 mol% and complete draft genome sizes are 1 692 266, 2 371 088 and 2 237 001 bp for strains SQ9-PEAT, SQ8-PEAT and GRT3T, respectively.

Local injection of micro-dose anti-interleukin-17A antibody for palmoplantar pustulosis: A real-world study.

Palmoplantar pustulosis (PPP), a chronic and stubborn skin disease, is mainly confined to the palms or/and soles, making it possible for localized use of therapeutic antibodies. In this real-world prospective cohort study, 8 patients with PPP received palms/soles injections of ixekizumab (0.8 mg in 0.1 ml) every 2 to 8 weeks due to the COVID-19 pandemic. The treatment endpoint was a 75% improvement from baseline in Palmoplantar Pustulosis/Psoriasis Area and Severity Index (PPPASI 75). At week 8, 75%, 50% and 12.5% of 8 patients reached PPPASI 50, PPPASI 75 and PPPASI 90. At week 12, 100%, 75% and 25% of 8 patients reached PPPASI 50, PPPASI 75 and PPPASI 90. This is the first study to evaluate the efficacy and safety of local injection of micro-dose ixekizumab for PPP in real clinical practice. A high proportion of patients rapidly achieved PPPASI 75, and maintained long-term efficacy with satisfactory safety.

Paracholeplasma manati sp. nov. isolated from Florida manatees (Trichechus manatus latirostris).

Four novel strains of a member of the genus Paracholeplasma (OakleyT, Holly, Lorelei and Ariel) were isolated from skin of Florida manatees (Trichechus manatus latirostris). These strains were phenotypically and genetically characterized and compared with the known species of the genera Acholeplasma (A.), Alteracholeplasma (Al.), Haploplasma (H.), Paracholeplasma (P.) and Mariniplasma (M.). All the strains produced acid from glucose but did not hydrolyze arginine or urea. All were propagated in ambient air supplemented with 5±1 % CO2 at 35-37 °C using SP4-Z, Columbia and brain-heart infusion medium. Colonies on solid medium showed a typical fried-egg appearance and transmission electron microscopy revealed a typical mycoplasma-like cellular morphology. The results of phylogenetic analyses based on partial 16S rRNA, rpoB, gyrB and parE gene sequences and the whole proteome data indicated that the novel species is a unique species but phylogenetically closely related to Paracholeplasma vituli, Paracholeplasma morum and 'Paracholeplasma brassicae'. The average nucleotide identity and digital DNA-DNA hybridization values between strain OakleyT and the closely related species were significantly lower than the accepted thresholds for describing novel prokaryotic species at the genomic level. On the basis of the genomic, phenotypic and phylogenetic properties, the novel strains represent a novel species of the genus Paracholeplasma, for which the name Paracholeplasma manati sp. nov. with the type strain OakleyT (=NCTC 14352T =DSM 110686T) is proposed. The genomic DNA G+C content and complete draft genome size for the type strain are 38.35 % and 1 873 856 bp, respectively.

Neisseria montereyensis sp. nov., Isolated from Oropharynx of California Sea Lion (Zalophus californianus): Genomic, Phylogenetic, and Phenotypic Study.

A novel Neisseria strain, designated CSL10203-ORH2T, was isolated from the oropharynx of a wild California sea lion (Zalophus californianus) that was admitted to The Marine Mammal Center in California, USA. The strain was originally cultured from an oropharyngeal swab on BD Phenylethyl Alcohol (PEA) agar with 5% sheep blood under aerobic conditions. Phylogenetic analyses based on 16S rRNA, rplF, and rpoB gene sequences and the core genome sequences indicated that the strain was most closely related to only N. zalophi CSL 7565T. The average nucleotide identity and digital DNA-DNA hybridization values between strain CSL10203-ORH2T and the closely related species N. zalophi CSL 7565T were 89.84 and 39.70%, respectively, which were significantly lower than the accepted species-defined thresholds for describing novel prokaryotic species at the genomic level. Both type strains were phenotypically similar but can be easily and unambiguously distinguished between each other by the analysis of their housekeeping genes, e.g., rpoB, gyrB, or argF. The major fatty acids in both type strains were C12:0, C16:0, C16:1-c9, and C18:1-c11. Based on the genomic, phenotypic, and phylogenetic properties, the novel strain represents a novel species of the genus Neisseria, for which the name Neisseria montereyensis sp. nov. with the type strain CSL10203-ORH2T (= DSM 114706T = CCUG 76428T = NCTC 14721T) is proposed. The genome G + C content is 45.84% and the complete draft genome size is 2,310,535 bp.

[Rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by diagnostic bronchoscopy].

OBJECTIVE: To explore the rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by bedside diagnostic bronchoscopy, so as to start effective anti-infection treatment before the results of macrogenome next generation sequencing (mNGS) test. METHODS: The clinical data of three patients with severe Chlamydophila psittaci pneumonia who were successfully treated in the First Affiliated Hospital of Xinjiang Medical University, the First People's Hospital of Aksu District, and the First Division Hospital of Xinjiang Production and Construction Corps from October 2020 to June 2021 were retrospectively analyzed, including the rapid assessment of early pathogens by bedside diagnostic bronchoscopy and the use of antibiotics to start anti-infection treatment. These patients were successfully treated. RESULTS: The three patients were male, aged 63, 45 and 58 years old, respectively. Before the onset of the penumonia, they had a clear medical history of bird exposure. The clinical manifestations mainly included fever, dry cough, shortness of breath and dyspnea. One case had abdominal pain and lethargy. The results of laboratory examination indicated that the peripheral blood white blood cell count (WBC) of two patients were high [(10.2-11.9)×109/L], the percentage of neutrophils increased (85.2%-94.6%) and the percentage of lymphocytes decreased (3.2%-7.7%) in all 3 patients after admission to hospital and entering into intensive care unit (ICU). The procalcitonin (PCT) of 3 patients increased after admission, and still increased when entering ICU (0.3-4.8 ng/L), so did C-reactive protein (CRP, 58.0-162.0 mg/L) and erythrocyte sedimentation rate (ESR, 36.0-90.0 mm/1 h). After admission, serum alanine transaminase (ALT) increased in 2 cases (136.7 U/L, 220.5 U/L), so did aspartate transaminase (AST) in 2 cases (249.6 U/L, 164.2 U/L). ALT (162.2-267.9 U/L) and AST (189.8-223.2 U/L) increased in 3 patients when they entered ICU. The level of serum creatinine (SCr) of 3 patients were normal after admission and entering ICU. The chest computed tomography (CT) findings of 3 patients were acute interstitial pneumonia, bronchopneumonia and lung consolidation, of which 2 cases were accompanied by a small amount of pleural effusion, and 1 case was accompanied by more regular small air sacs. Multiple lung lobes were involved, but mainly one lung lobe. The oxygenation index (PaO2/FiO2) of the 3 patients admitting to ICU were 100.0, 57.5 and 105.4 mmHg (1 mmHg ≈ 0.133 kPa), respectively, which met with the diagnostic criteria of moderate and severe acute respiratory distress syndrome (ARDS). All three patients received endotracheal intubation and mechanical ventilation. Under the bedside bronchoscope, the bronchial mucosa of 3 patients were obviously congested and edematous, without purulent secretion, and there was 1 case with mucosal hemorrhage. Three patients underwent bedside diagnostic bronchoscopy, and the evaluation result of the pathogen was that it might be atypical pathogen infection, so they were given moxifloxacin, cisromet and doxycycline intravenously, respectively, and combined with carbapenem antibiotics intravenously. After 3 days, the detection results of mNGS in bronchoalveolar lavage fluid (BALF) showed that only Chlamydia psittaci was infected. At this time, the condition was significantly improved, and PaO2/FiO2 was significantly increased. Therefore, the antibiotic treatment scheme remained unchanged, and mNGS only served to verify the initial diagnosis. Two patients were extubated on the 7th and 12th day of admission to the ICU, respectively, while one patient was extubated on the 16th day of admission to the ICU due to nosocomial infection. All 3 patients were transferred to the respiratory ward after the condition was stable. CONCLUSIONS: The bedside diagnostic bronchoscopy based on clinical characteristics is conducive to not only the rapid assessment of the early pathogens of severe Chlamydia psittaci pneumonia, but also effective anti-infection treatment before the returning of mNGS test results, which can make up for the lag and uncertainty of the mNGS test results.

Minimal Antigenic Evolution after a Decade of Norovirus GII.4 Sydney_2012 Circulation in Humans.

Norovirus is a major human pathogen that can cause severe gastroenteritis in vulnerable populations. The extensive viral diversity presented by human noroviruses constitutes a major roadblock for the development of effective vaccines. In addition to the large number of genotypes, antigenically distinct variants of GII.4 noroviruses have chronologically emerged over the last 3 decades. The last variant to emerge, Sydney_2012, has been circulating at high incidence worldwide for over a decade. We analyzed 1449 capsid sequences from GII.4 Sydney_2012 viruses to determine genetic changes indicative of antigenic diversification. Phylogenetic analyses show that Sydney_2012 viruses scattered within the tree topology with no single cluster dominating during a given year or geographical location. Fourteen residues presented high variability, 7 of which mapped to 4 antigenic sites. Notably, ~52% of viruses presented mutations at 2 or more antigenic sites. Mutational patterns showed that residues 297 and 372, which map to antigenic site A, changed over time. Virus-like particles (VLPs) developed from wild-type Sydney_2012 viruses and engineered to display all mutations detected at antigenic sites were tested against polyclonal sera and monoclonal antibodies raised against Sydney_2012 and Farmington_Hills_2002 VLPs. Minimal changes in reactivity were detected with polyclonal sera and only 4 MAbs lost binding, with all mapping to antigenic site A. Notably, reversion of residues from Sydney_2012 reconstituted epitopes from ancestral GII.4 variants. Overall, this study demonstrates that, despite circulating for over a decade, Sydney_2012 viruses present minimal antigenic diversification and provides novel insights on the diversification of GII.4 noroviruses that could inform vaccine design. IMPORTANCE GII.4 noroviruses are the major cause of acute gastroenteritis in all age groups. This predominance has been attributed to the continued emergence of phylogenetically discrete variants that escape immune responses to previous infections. The last GII.4 variant to emerge, Sydney_2012, has been circulating at high incidence for over a decade, raising the question of whether this variant is undergoing antigenic diversification without presenting a major distinction at the phylogenetic level. Sequence analyses that include >1400 capsid sequences from GII.4 Sydney_2012 showed changes in 4 out of the 6 major antigenic sites. Notably, while changes were detected in one of the most immunodominant sites over time, these resulted in minimal changes in the antigenic profile of these viruses. This study provides new insights on the mechanism governing the antigenic diversification of GII.4 norovirus that could help in the development of cross-protective vaccines to human noroviruses.

Genome-wide analysis of the CML gene family and its response to melatonin in common bean (Phaseolus vulgaris L.).

Calmodulin-like proteins (CML) are important calcium signal transduction proteins in plants. CML genes have been analyzed in several plants. However, little information on CML in Phaseolus vulgare is available. In this study, we identified 111 PvCMLs distributed on eleven chromosomes. Phylogenetic analysis classified them into seven subfamilies. Cis-acting element prediction showed that PvCML contained elements related to growth and development, response to abiotic stress and hormones. Moreover, the majority of PvCMLs showed different expression patterns in most of the nine tissues and developmental stages which indicated the role of PvCML in the growth and development of common bean. Additionally, the common bean was treated with melatonin by seed soaking, and root transcriptome at the 5th day and qRT-PCR of different tissue at several stages were performed to reveal the response of PvCML to the hormone. Interestingly, 9 PvCML genes of subfamily VI were detected responsive to exogenous melatonin, and the expression dynamics of nine melatonin response PvCML genes after seed soaking with melatonin were revealed. Finally, the protein interaction network analysis of nine melatonin responsive PvCMLs was constructed. The systematic analysis of the PvCML gene family provides theoretical support for the further elucidation of their functions, and melatonin response molecular mechanism of the CML family in P. vulgaris.

Determining critical overlap concentration of polyethylene oxide to support excipient safety assessment of opioid products.

Intravenous administration of abuse-deterrent opioid products poses high safety risks, in part due to the presence of high molecular weight polymeric excipients. Previous in vivo studies in animal models have shown that the higher molecular weight (Mw) polymeric excipients like polyethylene oxide (PEO) were directly linked to such adverse responses as intravenous hemolysis and kidney damage. PEO polymers have been widely used in abuse-deterrent formulations (ADF) of opioid products, adding to concerns over the general safety of the opioid category due to the unknown safety risk from abuse via unintended routes. The current study focused on the determination of the critical overlap concentration (c*) at various PEO molecular weights to aid in explaining differences in observed adverse responses from previous animal studies on the intravenous administration of PEO solutions. Adverse in vivo responses may be related to the viscoelastic regime of the polymer solution, which depends not only on Mw but also on concentration. Having a localized polymer concentration in the blood above the c*, i.e., the transition from the dilute to semi-dilute entangled viscoelastic regime, may influence the flow behavior and interactions of cells in the blood. The relationship of c* to this combination of physical, chemical, and rheological effects is a possible driving force behind adverse in vivo responses.

Community structure of endophytic fungi in roots and leaves of Fagopyrum mill and Avena sativa in a Chinese northern cold region

In order to explore the endophytic fungi of Fagopyrum Mill and Avena sativa, Illumina Miseq high-throughput sequencing was used to analyze the community structure and diversity of endophytic fungi in leaves and roots of buckwheat and oat at the mature stage. The results of community structure showed that there were 205 operational taxonomic units (OTUs) in buckwheat roots and 181 OTUs in buckwheat leaves based on 97% sequence similarity level. There were 152 OTUs and 127 OTUs in the root and the leaf of oat, respectively. At the phylum level, Ascomycota and Basidiomycota were the dominant endophytic fungi in buckwheat roots and leaves, while Ascomycota was the dominant endophytic fungus in oat roots and leaves. Alpha diversity analysis showed that the Ace index, Chao index and Shannon index of buckwheat roots were higher than that of buckwheat leaves, and the three indices of oat roots were also higher than that of oat leaves, indicating that the richness and diversity of endophytic fungi community in roots were higher than that in leaves. Biomarkers were found by significant difference analysis in buckwheat and oat. The endophytic functional groups of buckwheat and oat were mainly distributed in Pathotroph and Saprotroph. The results of this study laid a foundation for fully exploiting the dominant endophytic fungal resources of buckwheat and oat and further developing microbial fertilizers.

CUR5g, a novel autophagy inhibitor, exhibits potent synergistic anticancer effects with cisplatin against non-small-cell lung cancer.

Autophagy, a highly conserved degradation process of eukaryotic cells, has been proven to be closely related to chemoresistance and metastasis of non-small-cell lung cancer (NSCLC). Autophagy inhibitors, such as chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), has been shown to mediate anticancer effects in preclinical models, especially when combined with chemotherapy. However, the vast majority of autophagy inhibitors, including CQ and HCQ, actually disrupt lysosomal or/and possibly non-lysosomal processes other than autophagy. It is therefore of great significance to discover more specific autophagy inhibitors. In this study, after screening a series of curcumin derivatives synthesized in our laboratory, we found that (3E,5E)-1-methyl-3-(4-hydroxybenzylidene)-5-(3-indolymethylene)-piperidine-4-one (CUR5g) selectively inhibited autophagosome degradation in cancer cells by blocking autophagosome-lysosome fusion. CUR5g did not affect the lysosomal pH and proteolytic function, nor did it disturb cytoskeleton. CUR5g blocked the recruitment of STX17, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, to autophagosomes via a UVRAG-dependent mechanism, resulting in the inability of autophagosomes to fuse with lysosomes. CUR5g alone did not induce apoptosis and necrosis of A549 cells, but significantly inhibited the mobility and colony formation of A549 cells. More excitingly, CUR5g showed no obvious toxicity to normal HUVECs in vitro or mice in vivo. CUR5g enhances the cisplatin sensitivity of A549 cells and effectively inhibited autophagy in tumor tissues in vivo. Collectively, our study identified a new late-stage autophagy inhibitor and provided a novel option for NSCLC treatment, particular when combined with cisplatin.

A Salt-Tolerant Streptomyces paradoxus D2-8 from Rhizosphere Soil of Phragmites communis Augments Soybean Tolerance to Soda Saline-Alkali Stress.

Soil salinity and alkalization limit plant growth and agricultural productivity worldwide. The application of salt-tolerant plant growth-promoting rhizobacteria (PGPR) effectively improved plant tolerance to saline-alkali stress. To obtain the beneficial actinomyces resources with salt tolerance, thirteen isolates were isolated from rhizosphere saline and alkaline soil of Phragmites communis. Among these isolates, D2-8 was moderately halophilic to NaCl and showed 120 mmol soda saline-alkali solution tolerance. Moreover, the plant growth-promoting test demonstrated that D2-8 produced siderophore, IAA, 1-aminocyclopropane-1-carboxylate deaminase (ACCD), and organic acids. D2-8 showed 99.4% homology with the type strain Streptomyces paradoxus NBRC 14887T and shared the same branch, and, therefore, it was designated S. paradoxus D2-8. Its genome was sequenced to gain insight into the mechanism of growth-promoting and saline-alkali tolerance of D2-8. IAA and siderophore biosynthesis pathway, genes encoding ACC deaminase, together with six antibiotics biosynthesis gene clusters with antifungal or antibacterial activity, were identified. The compatible solute ectoine biosynthesis gene cluster, production, and uptake of choline and glycine betaine cluster in the D2-8 genome may contribute to the saline-alkali tolerance of the strain. Furthermore, D2-8 significantly promoted the seedling growth even under soda saline-alkali stress, and seed coating with D2-8 isolate increased by 5.88% of the soybean yield in the field. These results imply its significant potential to improve soybean soda saline-alkali tolerance and promote crop health in alkaline soil.

ZOOMICS: Comparative Metabolomics of Red Blood Cells From Guinea Pigs, Humans, and Non-human Primates During Refrigerated Storage for Up to 42 Days.

Unlike other rodents, guinea pigs (Cavia porcellus) have evolutionarily lost their capacity to synthesize vitamin C (ascorbate) de novo and, like several non-human primates and humans, rely on dietary intake and glutathione-dependent recycling to cope with oxidant stress. This is particularly relevant in red blood cell physiology, and especially when modeling blood storage, which exacerbates erythrocyte oxidant stress. Herein we provide a comprehensive metabolomics analysis of fresh and stored guinea pig red blood cell concentrates (n = 20), with weekly sampling from storage day 0 through 42. Results were compared to previously published ZOOMICS studies on red blood cells from three additional species with genetic loss of L-gulonolactone oxidase function, including humans (n = 21), olive baboons (n = 20), and rhesus macaques (n = 20). While metabolic trends were comparable across all species, guinea pig red blood cells demonstrated accelerated alterations of the metabolic markers of the storage lesion that are consistent with oxidative stress. Compared to the other species, guinea pig red blood cells showed aberrant glycolysis, pentose phosphate pathway end product metabolites, purine breakdown products, methylation, glutaminolysis, and markers of membrane lipid remodeling. Consistently, guinea pig red blood cells demonstrated higher end storage hemolysis, and scanning electron microscopy confirmed a higher degree of morphological alterations of their red blood cells, as compared to the other species. Despite a genetic inability to produce ascorbate that is common to the species evaluated, guinea pig red blood cells demonstrate accelerated oxidant stress under standard storage conditions. These data may offer relevant insights into the basal and cold storage metabolism of red blood cells from species that cannot synthesize endogenous ascorbate.

A gentamicin-thioctic acid multifunctional hydrogel for accelerating infected wound healing.

Bacterial infections remain a major concern during wound healing and tissue bonding. The excessive proliferation of bacteria will seriously hinder the repair of the wound and even lead to death. Generally, surgical sutures might cause damage to the surrounding tissues and inevitable infection due to the unfixed shape of the wound. Thus, it is urgent to develop novel antibacterial skin dressing with self-healing and strong adhesion properties. Herein, we prepared an antibacterial and self-healable hydrogel with strong adhesion activity through natural small molecules, including thioctic acid TA and gentamicin (GM). The rapid ring-opening-polymerization of the TA (PTA) forms the backbone of macromolecules, and the functional hydrogel was constructed with the crosslinking of GM, termed as G-PTA, which offers hydrogen bonding interactions between the amino and hydroxyl groups of GM and carboxylic group side chains of poly(TA). The synthesized hydrogel exhibited rapid self-healing ability and strong tissue adhesion due to the internal dynamic disulfide bonds and multiple hydrogen bonds. Importantly, the introduction of GM enabled the G-PTA hydrogel to sustainably release antibiotics and exhibit a durative antibacterial effect with the degradation of PTA, which further shorten the therapeutic time and enhance tissue regeneration in a wound infection model. The in vitro and in vivo experiments demonstrate that the G-PTA hydrogel has potential as a surgical antibacterial biological adhesive, especially for bacterial wound infections.

Gut Microbiota Alteration Influences Colorectal Cancer Metastasis to the Liver by Remodeling the Liver Immune Microenvironment.

Background/Aims: This study aimed to explore the effect of gut microbiota-regulated Kupffer cells (KCs) on colorectal cancer (CRC) liver metastasis. Methods: A series of in vivo and in vitro researches were showed to demonstrate the gut microbiota and its possible mechanism in CRC liver metastasis. Results: Fewer liver metastases were identified in the ampicillin-streptomycin-colistin and colistin groups. Increased proportions of Parabacteroides goldsteinii, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides uniformis were observed in the colistin group. The significant expansion of KCs was identified in the ampicillin-streptomycin-colistin and colistin groups. B. vulgatus levels were positively correlated with KC levels. More liver metastases were observed in the vancomycin group. An increased abundance of Parabacteroides distasonis and Proteus mirabilis and an obvious reduction of KCs were noted in the vancomycin group. P. mirabilis levels were negatively related to KC levels. The number of liver metastatic nodules was increased in the P. mirabilis group and decreased in the B. vulgatus group. The number of KCs decreased in the P. mirabilis group and increased in the B. vulgatus group. In vitro, as P. mirabilis or B. vulgatus doses increased, there was an opposite effect on KC proliferation in dose- and time-dependent manners. P. mirabilis induced CT26 cell migration by controlling KC proliferation, whereas B. vulgatus prevented this migration. Conclusions: An increased abundance of P. mirabilis and decreased amount of B. vulgatus play key roles in CRC liver metastasis, which might be related to KC reductions in the liver.

Analysis of Epidemic Characteristics and Related Pathogenic Factors of 2726 Cases of Pityriasis Alba.

PURPOSE: To understand the distribution characteristics of onset time, onset age and gender of pityriasis alba (PA) patients in the dermatology clinic of our hospital and to further explore the pathogenesis of the disease to provide a scientific basis for the prevention and treatment of this disease. PATIENTS AND METHODS: The clinical data of 2726 outpatients with PA diagnosed for the first time from January 2016 to December 2020 were collected and descriptively analyzed. RESULTS: The number of patients with PA was less from January to March. The peak was reached in July and August. The number of cases affected by the COVID-19 epidemic in 2020 was significantly lower than that in previous years. Furthermore, the onset age of the patients ranged from 0 to 64 years old, and the median age of the total population was 7 (3, 13) years old, including 1566 males (57.45%) and 1160 females (42.55%). The ratio of male to female was 1.35:1. The number of male patients before 18 years old was higher than that of female patients, especially in the high paroxysmal age group. CONCLUSION: PA can be seen all the year round, and the onset peak of the disease is from July to August every year. It occurs frequently at the age of 1 to 14 before puberty. In the season of high incidence of PA, the protection from sun and moisture retention should be strengthened for infants and adolescents.

Mycoplasma miroungirhinis sp. nov. and Mycoplasma miroungigenitalium sp. nov., isolated from northern elephant seals (Mirounga angustirostris), Mycoplasma phocoenae sp. nov., isolated from harbour porpoise (Phocoena phocoena), and Mycoplasma phocoeninasale sp. nov., isolated from harbour porpoise and California sea lions (Zalophus californianus).

Seven novel independent strains of Mycoplasma species were isolated from northern elephant seals (ES2806-NAST, ES2806-GENT, ES3157-GEN-MYC and ES3225-GEN-MYC), a harbour porpoise (C264-GENT and C264-NAST), and a California sea lion (CSL7498). These strains were phenotypically and genetically characterized and compared to the known Mycoplasma species. Four strains (C264-GENT, C264-NAST, CSL7498 and ES2806-NAST) hydrolysed arginine but not urea and did not produce acid from carbohydrates. Strains ES2806-GENT, ES3157-GEN-MYC and ES3225-GEN-MYC did not produced acid from carbohydrates and did not hydrolyse arginine or urea; hence, it is assumed that organic acids are used as the energy source for them. All were isolated and propagated in ambient air supplemented with 5±1 % CO2 at +35-37 °C using either SP4 or PPLO medium. Colonies on solid medium showed a typical fried-egg appearance and transmission electron microscopy revealed a typical mycoplasma cellular morphology. The complete genomes were sequenced for all type strains. Average nucleotide and amino acid identity analyses showed that these novel strains were distant from the phylogenetically closely related Mycoplasma species. Based on these data, we propose four novel species of the genus Mycoplasma, for which the name Mycoplasma miroungirhinis sp. nov. is proposed with the type strain ES2806-NAST (=NCTC 14430T=DSM 110945T), Mycoplasma miroungigenitalium sp. nov. is proposed with the type strain ES2806-GENT (=NCTC 14429T=DSM 110944T) and representative strains ES3157-GEN-MYC and ES3225-GEN-MYC, Mycoplasma phocoenae sp. nov. is proposed with the type strain C264-GENT (=NCTC 14344T=DSM 110687T) and Mycoplasma phocoeninasale sp. nov. is proposed with the type strain C264-NAST (=NCTC 14343T=DSM 110688T) and representative strain CSL7498. The genome G+C contents are 24.06, 30.09, 28.49 and 29.05% and the complete genome sizes are 779 550, 815 486, 693 115, and 776 009 bp for strains ES2806-NAST, ES2806-GENT, C264-GENT and C264-NAST, respectively.

Modulation of HIV Replication in Monocyte-Derived Macrophages (MDM) by Host Antiviral Factors Secretory Leukocyte Protease Inhibitor and Serpin Family C Member 1 Induced by Steroid Hormones.

The impact of steroid hormones estrogen and progesterone on human immunodeficiency virus type 1 (HIV-1) replication is well documented. However, the exact mechanism involved in the regulation of HIV-1 replication by estrogen and progesterone is still unclear. In the present study, we wanted to elucidate the molecular mechanisms underlying the modulation of HIV-1 replication by estrogen and progesterone. To achieve this goal, we used real-time quantitative PCR arrays (PCR arrays) to identify differentially expressed host genes in response to hormone treatments that are involved in antiviral responses. Our in vitro results suggest that treatment with high doses of estrogen and progesterone promotes the expression of host antiviral factors Secretory leukocyte protease inhibitor (SLPI) and Serpin family C member 1 (SERPIN C1) among others produced in response to HIV-1 infection. SLPI is an enzyme that inhibits human leukocyte elastase, human cathepsin G, human trypsin, neutrophil elastase, and mast cell chymase. SERPIN C1 is a plasma protease inhibitor that regulates the blood coagulation cascade by the inhibition of thrombin and other activated serine proteases of the coagulation system. A dose dependent downmodulation of HIV-1 replication was observed in monocyte-derived macrophages (MDMs) pre-treated with the two proteins SLPI and SERPIN C1. Further investigations suggests that the host antiviral factors, SLPI and SERPIN C1 act at the pre-integration stage, inhibiting HIV-1 viral entry and leading to the observed downmodulation of HIV-1 replication. Our studies would help identify molecular mechanisms and pathways involved in HIV-1 pathogenesis.

The molecular events underpinning cultivar differences in melatonin counteracting salt damage in Phaseolus vulgaris.

Melatonin (N -acetyl-5-methoxytryptamine) plays important roles in multiple stress responses, especially under salt stress. However, cultivar differences in melatonin mediated salt stress tolerance are unclear. Phaseolus vulgaris L. (common bean) cultivars Jiyin 1 (JY, salt-tolerant) and Xuliyabai (XL, salt-sensitive) were used in this study. Exogenous melatonin significantly improved root growth under salt stress in JY, but had little effect on XL. Physiology analysis showed significant differences in activities of antioxidant enzymes (superoxide, SOD; and catalase, CAT) and malondialdehyde content between JY and XL. Meanwhile, the change of ABA content in JY and XL root was opposite in salt plus melatonin treatment. Comparative root transcriptomes of JY and XL revealed 3505 and 668 differentially expressed genes (DEGs) regulated by salt stress and melatonin. The most enriched melatonin-responsive genes under salt stress are mainly involved in regulation of transcription, oxidation-reduction process, transcription factor activity, oxidoreductase activity. In addition, melatonin induced more obvious changes of DEGs in JY than that in XL under salt condition. Melatonin also significantly induced 41 DEGs only in JY, including signal transduction genes, transcription factors, ubiquitin protein ligases, ion homeostasis and osmotic adjustment genes etc. This study uncovered the molecular mechanism of cultivar difference of melatonin response under salt stress in common bean.