[Determination of 25 disinfection by-products in drinking water using liquid-liquid extraction and gas chromatography].

OBJECTIVE: To establish a liquid-liquid extraction and gas chromatography method for the determination of 7 kinds of haloacetaldehydes, 7 kinds of haloacetonitriles, 7 kinds of halonitromethanes and 4 kinds of haloacetamides in drinking water. METHODS: A liquid-liquid extraction gas chromatography technique was employed. Experimental parameters, such as capillary column type, inlet temperature, concentration of salting out reagent and sample pH were optimized to develop an analytical method, and then method validation was conducted. RESULTS: HP-5 MS UI column(30 m×0.25 mm, 0.25 µm), inlet temperature at 180 ℃, addition of 8 g sodium chloride in 50 mL water sample and pH 4-5 were chosen as the final parameters. Good correlation coefficients were obtained in the linear range of 0.20-15 µg/L, with r greater than 0.999.Methods detection limits were between 0.008-0.088 µg/L. When spiked concentration was 1.0 µg/L for pure water and tap water, the recoveries were 81%-106% and 75%-117%, respectively, and relative standard deviations were both less than 4%. When spiked concentration was 12 µg/L for pure water and tap water, the recoveries were 92%-101% and 86%-106%, respectively, and relative standard deviations were less than 4% and 2%, respectively. CONCLUSION: This method is simple, sensitive, and effective. It is suitable for simultaneous determination of 25 disinfection byproducts in drinking water.

Knockdown of fibronectin extra domain B suppresses TGF-ß1-mediated cell proliferation and collagen deposition in keloid fibroblasts via AKT/ERK signaling pathway.

Keloids represent a dermal fibrotic disease characterized by excess collagen deposition and invasion of normal skin beyond the wound boundary, similar to malignant tumor features. Fibronectin extra domain B (EDB) is highly expressed in many tumors but has not been studied in keloids. The present study aimed to investigate the expression and the influence of EDB on keloid and elucidate the putative signaling pathway. We examined expression of EDB and the effects of EDB on fibroblast proliferation, apoptosis and the expression of the related proteins and genes. The level of phosphorylation of Smad, ERK, and AKT was estimated to elucidate the signaling pathways. The results showed that EDB in human keloid tissues and fibroblasts was overexpressed. EDB knockdown suppressed the cell proliferation of keloid fibroblasts (KFs) treated by transforming growth factor-ß1 (TGF-ß1). Also, the phosphorylation of Smad, ERK, and AKT in TGF-ß1-induced KFs was inhibited In addition, the low expression of pro-collagen-I (Col-I) and Col-III protein and mRNA level was observed in the siEDB group. EDB knockdown inhibited cell proliferation and suppressed collagen deposition in TGF-1-induced KFs. The underlying mechanism is the activation of TGF-ß1/Smad, ERK, and AKT signaling pathways. Together, the results suggested that EDB is a promising therapeutic target for keloid clinical treatment.

Functional insights into the Streptococcus pneumoniae HicBA toxin-antitoxin system based on a structural study.

Streptococcus pneumonia has attracted increasing attention due to its resistance to existing antibiotics. TA systems are essential for bacterial persistence under stressful conditions such as nutrient deprivation, antibiotic treatment, and immune system attacks. In particular, S. pneumoniae expresses the HicBA TA gene, which encodes the stable HicA toxin and the labile HicB antitoxin. These proteins interact to form a non-toxic TA complex under normal conditions, but the toxin is activated by release from the antitoxin in response to unfavorable growth conditions. Here, we present the first crystal structure showing the complete conformation of the HicBA complex from S. pneumonia. The structure reveals that the HicA toxin contains a double-stranded RNA-binding domain that is essential for RNA recognition and that the C-terminus of the HicB antitoxin folds into a ribbon-helix-helix DNA-binding motif. The active site of HicA is sterically blocked by the N-terminal region of HicB. RNase activity assays show that His36 is essential for the ribonuclease activity of HicA, and nuclear magnetic resonance (NMR) spectra show that several residues of HicB participate in binding to the promoter DNA of the HicBA operon. A toxin-mimicking peptide that inhibits TA complex formation and thereby increases toxin activity was designed, providing a novel approach to the development of new antibiotics.

Dietary supplementation with pioglitazone hydrochloride improves intramuscular fat, fatty acid profile, and antioxidant ability of thigh muscle in yellow-feathered chickens.

BACKGROUND: Muscle fat content and fatty acid composition play an important role in poultry flavor and taste. To investigate the effects of pioglitazone hydrochloride (PGZ) on growth performance and thigh muscle quality in yellow-feathered chickens, 360 female chickens were randomly divided into three groups and treated with three doses of PGZ (0, 7.5, and 15 mg kg-1 ) for 28 days. Each group had six replicates of 20 chickens. RESULTS: The results showed that dietary supplementation with 15 mg kg-1 PGZ increased average daily feed intake (ADFI) and the average daily gain (ADG) from 0 to 14 days. Furthermore, the triglyceride (TG) level was decreased by 15 mg kg-1 PGZ, whereas the eviscerated yield was increased. The relative weight of the heart and kidneys showed a linear increase with dietary PGZ supplementation, and the drip loss of the thigh muscle was significantly decreased by 15 mg kg-1 PGZ supplementation. Moreover, a* value, intramuscular fat (IMF), and polyunsaturated fatty acids (PUFAs) showed a linear increase, and pH24 h and drip loss showed a quadratic influence with the levels of PGZ supplementation. In particular, the PUFA proportion was increased by 7.63% and 9.14% in the 7.5 mg kg-1 PGZ and 15 mg kg-1 PGZ groups, respectively. Additionally, 15 mg kg-1 of PGZ increased the total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX ) activity. CONCLUSION: In summary, 15 mg kg-1 PGZ has substantial effects on growth performance and meat quality, particularly by decreasing drip loss and increasing IMF content, PUFA proportions, and antioxidant ability. © 2019 Society of Chemical Industry.

Dietary supplementation with pioglitazone hydrochloride and chromium methionine manipulates lipid metabolism with related genes to improve the intramuscular fat and fatty acid profile of yellow-feathered chickens.

BACKGROUND: Intramuscular fat (IMF) and polyunsaturated fatty acids (PUFAs) have been thought to play a crucial role in improving meat quality. Considering the ability of pioglitazone hydrochloride (PGZ) to deposit fat, and the anti-stress capability of chromium methionine (CrMet), we combined these compounds to produce higher quality meat in poultry. A total of 3000 female chickens were divided into four groups (five replicates, each with 150 chickens): control, control plus15 mg·kg-1 PGZ, control plus 200 µg·kg-1 CrMet, and control plus15 mg·kg-1 PGZ plus 200 µg·kg-1 CrMet. The experiment lasted for 28 days. RESULTS: Compared to the control group and the PGZ group, the average daily gain (ADG) was significantly increased in the PGZ plus CrMet group, whereas the feed-to-gain ratio (F/G) was decreased from 0 to 14 days. Meanwhile, the redness value of breast muscle and IMF of thigh muscle increased in the PGZ plus CrMet group compared with the control group and these detections in the PGZ plus CrMet group exhibited highest value among the four groups. The cooking loss decreased in the breast muscle and thigh muscle after PGZ combined with CrMet in diets. The percentages of C16:1, C18:2n-6 and PUFAs increased in the PGZ plus CrMet group. The mRNA abundance of peroxisome proliferator activated receptor (PPAR) γ, PPAR coactivator 1 α, and fatty acid binding protein 3 was significantly enhanced with PGZ plus CrMet supplementation. CONCLUSION: Collectively, dietary supplementation with PGZ plus CrMet improved growth performance and meat quality by decreasing the cooking loss and increasing the IMF and PUFA levels. © 2019 Society of Chemical Industry.

Cecropin A Modulates Tight Junction-Related Protein Expression and Enhances the Barrier Function of Porcine Intestinal Epithelial Cells by Suppressing the MEK/ERK Pathway.

Inflammatory bowel disease (IBD) in humans and animals is associated with bacterial infection and intestinal barrier dysfunction. Cecropin A, an antimicrobial peptide, has antibacterial activity against pathogenic bacteria. However, the effect of cecropin A on intestinal barrier function and its related mechanisms is still unclear. Here, we used porcine jejunum epithelial cells (IPEC-J2) as a model to investigate the effect and mechanism of cecropin A on intestinal barrier function. We found that cecropin A reduced Escherichia coli (E. coli) adherence to IPEC-J2 cells and downregulated mRNA expression of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). Furthermore, cecropin A elevated the transepithelial electrical resistance (TER) value while reducing the paracellular permeability of the IPEC-J2 cell monolayer barrier. Finally, by using Western blotting, immunofluorescence and pathway-specific antagonists, we demonstrated that cecropin A increased ZO-1, claudin-1 and occludin protein expression and regulated membrane distribution and F-actin polymerization by increasing CDX2 expression. We conclude that cecropin A enhances porcine intestinal epithelial cell barrier function by downregulating the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. We suggest that cecropin A has the potential to replace antibiotics in the treatment of IBD due to its antibacterial activity on gram-negative bacteria and its enhancement effect on intestinal barrier function.

Downregulation of miR-493 promoted melanoma proliferation by suppressing IRS4 expression.

Accumulating evidence indicated that aberrantly expressed microRNAs play critical roles in the initiation and progression of human cancers. However, the underlying functions of miR-493 in human melanoma remains unknown. Here, our study found that miR-493 expression was downregulated in human melanoma tissues and cells. Overexpression of miR-493 suppressed cell proliferation and cell cycle in human melanoma cell line A375. IRS4 was defined as a target for downregulation by miR-493 and was confirmed by luciferase assay. We also found that knockdown of IRS4 counteracted the proliferation promotion by miR-493 inhibitor. In summary, these results demonstrated that miR-493 acts as a tumor suppressor and inhibits cell proliferation and cell cycle in human melanoma by directly targeting IRS4.

Analysis of the efficacy of blunt separation combined with uncrosslinked sodium hyaluronate composite solution for the treatment of tear trough deformity in Asians.

BACKGROUND: Filling therapy is becoming increasingly popular for correcting tear trough deformities (TTD). However, its therapeutic effect and retention time are limited. AIMS: To improve the clinical efficacy and safety of TTD treatment in Asians, we used a blunt separation technique to break the adhesion site of periorbital subcutaneous tissue, and while repairing skin dermis after injury, it was combined with uncrosslinked hyaluronic acid compound solution to promote collagen regeneration and treat TTDs. PATIENTS/METHODS: Twenty-six Chinese patients (21 women and 5 men) with TTD, with a mean age of 34.54 ± 9.21 (range, 20-56) years, were enrolled. Symptom improvement, recurrence rates, treatment safety, and patient satisfaction were evaluated. RESULTS: All patients' tear trough rating scale (TTRS) scores decreased significantly immediately after treatment. The TTRS scores at 1, 3, and 6 months, and 1 year after treatment demonstrated significant differences from those before treatment (all p < 0.05). All patients' experienced mild pain, erythema, and swelling during the treatment. Three patients developed postinjection bruising after treatment, which lasted for 6-7 days and subsequently disappeared. No other adverse reactions were observed during the follow-up. There were no recurrent cases, and patient satisfaction was very high. CONCLUSIONS: Blunt separation combined with an uncrosslinked sodium hyaluronate composite solution is safe and effective for treating TTDs in Asians with few side effects and has good clinical application prospects.

Discovery of Antimicrobial Agents Based on Structural and Functional Study of the Klebsiella pneumoniae MazEF Toxin-Antitoxin System.

Klebsiella pneumoniae causes severe human diseases, but its resistance to current antibiotics is increasing. Therefore, new antibiotics to eradicate K. pneumoniae are urgently needed. Bacterial toxin-antitoxin (TA) systems are strongly correlated with physiological processes in pathogenic bacteria, such as growth arrest, survival, and apoptosis. By using structural information, we could design the peptides and small-molecule compounds that can disrupt the binding between K. pneumoniae MazE and MazF, which release free MazF toxin. Because the MazEF system is closely implicated in programmed cell death, artificial activation of MazF can promote cell death of K. pneumoniae. The effectiveness of a discovered small-molecule compound in bacterial cell killing was confirmed through flow cytometry analysis. Our findings can contribute to understanding the bacterial MazEF TA system and developing antimicrobial agents for treating drug-resistant K. pneumoniae.

Rosacea treatment with mussel adhesive protein delivered via microneedling: In vivo and clinical studies.

BACKGROUND: Rosacea is a prevalent chronic dermatological condition marked by facial inflammation and erythema, significantly compromising the quality of life for affected individuals. Current treatment methods for rosacea are not considered ideal because of the complex etiology of the disease. Mussel adhesive protein (MAP) is a glycoprotein derived from the foot gland of mussels. The protein exhibits anti-inflammatory properties, relieves skin itching, and promotes wound healing. AIMS: We aimed to explore the feasibility of using MAP administered via microneedle delivery for treating rosacea and the potential molecular mechanism involved. MATERIALS AND METHODS: The therapeutic effect and mechanism of MAP microneedle delivery in an LL-37-induced rosacea-like mouse model were observed using morphological and histological methods. Twenty-seven patients with erythematotelangiectatic rosacea (ETR) underwent treatment once every 1 month, with three treatments constituting one treatment course. The therapeutic effect was evaluated by comparing the clinical images taken at baseline, after the first treatment course, and after the second treatment course. The red value, CEA, and GFSS score were also calculated. RESULTS: In response to the microneedle delivery of MAP, innate immunity, inflammatory infiltration, and abnormal neurovascular regulation improved significantly in rosacea-like mice. In the clinical experiments, the microneedle delivery of MAP significantly improved the symptoms of erythema, flushing, and telangiectasia in patients with ETR, and no obvious adverse reactions were observed. CONCLUSIONS: MAP delivered by microneedling is effective and safe for treating ETR.

Lysine Distinctively Manipulates Myogenic Regulatory Factors and Wnt/Ca2+ Pathway in Slow and Fast Muscles, and Their Satellite Cells of Postnatal Piglets.

Muscle regeneration, representing an essential homeostatic process, relies mainly on the myogenic progress of resident satellite cells, and it is modulated by multiple physical and nutritional factors. Here, we investigated how myogenic differentiation-related factors and pathways respond to the first limiting amino acid lysine (Lys) in the fast and slow muscles, and their satellite cells (SCs), of swine. Thirty 28-day-old weaned piglets with similar body weights were subjected to three diet regimens: control group (d 0-28: 1.31% Lys, n = 12), Lys-deficient group (d 0-28: 0.83% Lys, n = 12), and Lys rescue group (d 0-14: 0.83% Lys; d 15-28: 1.31% Lys, n = 6). Pigs on d 15 and 29 were selectively slaughtered for muscular parameters evaluation. Satellite cells isolated from fast (semimembranosus) and slow (semitendinosus) muscles were also selected to investigate differentiation ability variations. We found Lys deficiency significantly hindered muscle development in both fast and slow muscles via the distinct manipulation of myogenic regulatory factors and the Wnt/Ca2+ pathway. In the SC model, Lys deficiency suppressed the Wnt/Ca2+ pathways and myosin heavy chain, myogenin, and myogenic regulatory factor 4 in slow muscle SCs but stimulated them in fast muscle SCs. When sufficient Lys was attained, the fast muscle-derived SCs Wnt/Ca2+ pathway (protein kinase C, calcineurin, calcium/calmodulin-dependent protein kinase II, and nuclear factor of activated T cells 1) was repressed, while the Wnt/Ca2+ pathway of its counterpart was stimulated to further the myogenic differentiation. Lys potentially manipulates the differentiation of porcine slow and fast muscle myofibers via the Wnt/Ca2+ pathway in opposite trends.

Mussel adhesive protein treatment delivered by microneedling for sensitive skin: A clinical study.

BACKGROUND: Mussel adhesive protein (MAP) is extracted from the mycelial glands of marine mussels. It has anti-inflammatory properties and may relieve skin itching and other symptoms. AIMS: Based on the anti-inflammatory effect of MAP, this study was designed to treat sensitive skin (SS) using MAP delivered by skin microneedling. PATIENTS/METHODS: Twenty-three Chinese female patients with SS were enrolled. Treatments were delivered three times at one-month intervals. Symptom improvement and recurrence rates, treatment safety, and patient satisfaction levels were evaluated. RESULTS: After one course of treatment, 20 patients had a Symptom Score Reducing Index (SSRI) of >20%, with an effectiveness rate of 87%. At the end of treatment, all patients had an SSRI of >20%, and the effectiveness rate was 100%. Dryness, tightness, desquamation, flushing, burning, itching, and tingling improved. After treatment, the Clinical Erythema Assessment and Lesion Severity Index of Facial Telangiectasia scores were significantly decreased. Clinical photographs following treatment revealed improved erythema reaction and decreased capillary density. During treatment, the patients experienced mild pain and erythema and swelling reaction without exudation. Complications, such as pigmentation changes or scarring, were absent. Additionally, there were no cases of recurrence, and patient satisfaction levels were high. CONCLUSION: MAP combined with microneedling can help treat SS, showing satisfactory safety outcomes and high patient satisfaction.

Domain swapping of the C-terminal helix promotes the dimerization of a novel ribonuclease protein from Mycobacterium tuberculosis.

Polyketide metabolism-associated proteins in Mycobacterium tuberculosis play an essential role in the survival of the bacterium, which makes them potential drug targets for the treatment of tuberculosis (TB). The novel ribonuclease protein Rv1546 is predicted to be a member of the steroidogenic acute regulatory protein-related lipid-transfer (START) domain superfamily, which comprises bacterial polyketide aromatase/cyclases (ARO/CYCs). Here, we determined the crystal structure of Rv1546 in a V-shaped dimer. The Rv1546 monomer consists of four α-helices and seven antiparallel ß-strands. Interestingly, in the dimeric state, Rv1546 forms a helix-grip fold, which is present in START domain proteins, via three-dimensional domain swapping. Structural analysis revealed that the conformational change of the C-terminal α-helix of Rv1546 might contribute to the unique dimer structure. Site-directed mutagenesis followed by in vitro ribonuclease activity assays was performed to identify catalytic sites of the protein. This experiment suggested that surface residues R63, K84, K88, and R113 are important in the ribonuclease function of Rv1546. In summary, this study presents the structural and functional characterization of Rv1546 and supplies new perspectives for exploiting Rv1546 as a novel drug target for TB treatment.

Chemical composition of pigeon crop milk and factors affecting its production: a review.

Pigeons are important commercial poultry in addition to being ornamental birds. In 2021, more than 111 million pairs of breeding pigeons were kept in stock and 1.6 billion squabs were slaughtered for meat in China. However, in many countries, pigeons are not domestic birds; thus, it is necessary to elucidate the factors involved in their growth and feeding strategy due to their economic importance. Pigeons are altricial birds, so feedstuffs cannot be digested by squabs, which instead are fed a mediator named pigeon crop milk. During lactation, breeding pigeons (both female and male) ingest diets and generate crop milk to feed squabs. Thus, research on squab growth is more complex than that on chicken and other poultry. To date, research on the measurement of crop milk composition and estimation of the factors affecting its production has not ceased, and these results are worth reviewing to guide production. Moreover, some studies have focused on the formation mechanism of crop milk, reporting that the synthesis of crop milk is controlled by prolactin and insulin-activated pathways. Furthermore, the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) pathway, target of rapamycin (TOR) pathway and AMP-activated protein kinase (AMPK) pathway were also reported to be involved in crop milk synthesis. Therefore, this review focuses on the chemical composition of pigeon crop milk and factors affecting its production during lactation. This work explores novel mechanisms and provides a theoretical reference for improving production in the pigeon industry, including for racing, ornamental purposes, and production of meat products.

Iturin A Rescued STb-R-Induced Pork Skeletal Muscle Growth Restriction through the Hypothalamic-Pituitary-mTORC1 Growth Axis.

The engineered STb-Rosetta Escherichia coli (STb-R) was designed to investigate the effects of Iturin A on the skeletal muscle growth of weaned piglets. A total of 28 piglets were randomly divided into 4 groups (7 piglets per group): the control group (100 mL PBS), the Iturin A group (100 mL 320 mg/kg body weight (BW) Iturin A), the STb-R group (100 mL 1 × 1010 CFU/mL STb-R), and the Iturin A + STb-R group (100 mL 320 mg/kg BW Iturin A + 1 × 1010 CFU/mL STb-R). Compared with the control, STb-R-reduced body weight gain were rescued by Iturin A. The semimembranosus muscle weight recovered to normal level in the Iturin A + STb-R group. The level of relevant genes of the growth axis were elevated by Iturin A, including GHRH in the hypothalamus, GHRHR and GH in the pituitary, and GHR, IGF-1 and IGF-1R in the semimembranosus muscle. Moreover, Iturin A increased the mean fiber area and the number of proliferating cells in the semimembranosus muscle, which were decreased by STb-R. Additionally, the mTORC1 pathway was reactivated by Iturin A to relieve the suppression of STb-R. Collectively, the hypothalamic-pituitary growth axis-mediated Iturin A reactivated the mTORC1 pathway to rescue STb-R-restricted pork skeletal muscle growth.

Novel technique for rosacea treatment using optimal pulse technology: In vivo and clinical studies.

BACKGROUND: Rosacea is a chronic inflammatory skin disease affecting the face, and the current treatment effect is not satisfactory. Based on the photomodulation of optimal pulse technology (OPT), we developed a novel treatment mode, namely, advanced OPT with low energy, three pulses, and long pulse width (AOPT-LTL). AIMS: We aimed to explore the feasibility and underlying molecular mechanisms of AOPT-LTL treatment in a rosacea-like mouse model. Furthermore, we evaluated the safety and efficacy in patients with erythematotelangiectatic rosacea (ETR). MATERIALS AND METHODS: Morphological, histological, and immunohistochemical analyses were used to investigate the efficacy and mechanisms of AOPT-LTL treatment in the LL-37-induced rosacea-like mouse model. Moreover, 23 patients with ETR were included and received different times of treatment at intervals of 2 weeks depending on the severity of their condition. The treatment effect was assessed by comparing clinical photographs at baseline, 1 week, and 3 months after treatment, combined with the red value, GFSS, and CEA scores. RESULTS: After the AOPT-LTL treatment of the mice, we observed that the rosacea-like phenotype, inflammatory cell infiltration, and vascular abnormalities were significantly ameliorated, and the expression of the core molecules of rosacea was significantly inhibited. In the clinical study, the AOPT-LTL treatment exerted satisfactory therapeutic effects on erythema and flushing of ETR patients. No serious adverse events were observed. CONCLUSIONS: AOPT-LTL is a safe and effective method for the treatment of ETR.

Effective of a novel technique for sensitive skin treatment with optimal pulse technology: A clinical study.

BACKGROUND AND AIMS: Photomodulation is a non-photothermal effect that mobilizes energy and regulates cell activity at the mitochondrial level, and has been used to treat sensitive skin (SS) in recent years. Based on the photomodulated effect of optimal pulse technology (OPT), we developed a novel treatment mode (advanced OPT with low energy, three pulses, long pulse width, AOPT-LTL) for the treatment of facial SS and evaluated its effectiveness. METHODS: A total of thirty Chinese women with SS were included in this study. Patients were received different times of AOPT-LTL treatment with an interval of 2 to 4 weeks depending on the severity. Clinical improvement was evaluated by comparing baseline and post-treatment photographs. In addition, the skin objective signs and subjective symptoms, as well as adverse events and patient satisfaction were also analyzed and tabulated. RESULTS: All included patients completed the treatment and follow-up period. After one course of treatment, 76.7% of patients had a Symptom Score Reducing Index (SSRI) >20%, suggesting that the treatment was effective. Within two courses of treatment, all patients had SSRI >20%, demonstrating significant improvement in skin sensitivity. The analysis of clinical photographs showed that facial dryness, desquamation, flushing, and skin color significantly improved, capillary density decreased, the dilated capillaries were retracted. During the treatment period, no obvious adverse reactions occurred in any patients, and the patients' satisfaction was high. CONCLUSIONS: This novel technique of AOPT-LTL might be an effective and safe modality for the treatment of SS.

Lysine Interacts with Frizzled7 to Activate ß-Catenin in Satellite Cell-Participated Skeletal Muscle Growth.

This work provided an interesting finding of lysine (Lys) control on skeletal muscle growth besides protein synthesis. According to the isobaric tag for relative and absolute quantitation and molecular docking analyses, we found both in in vivo skeletal muscle and in vitro muscle satellite cells (MuSCs) that the frizzled7 (FZD7) expression level was positively correlated with Lys levels and this was consistent with the activation of the Wnt/ß-catenin pathway. On the other hand, FZD7 inhibition suppressed the Lys-rescued Wnt/ß-catenin pathway, FZD7 knockdown caused cell proliferation, and Wnt/ß-catenin pathway restrictions could not be compensated for by Lys or Wnt3a. Furthermore, the combination between Lys and recombinant pig frizzled7 (rpFZD7) protein was confirmed by isothermal titration calorimetry. This finding displayed concrete evidence that Lys is not only a molecular block of protein synthesis but is also a ligand for FZD7 to activate ß-catenin to stimulate MuSCs in promoting skeletal muscle growth.

Second intention healing of nasal ala and dorsum defects in Asians.

BACKGROUND: Reconstruction of defects of nasal ala and dorsum after surgical excision presents a substantial challenge to dermatologic surgeons. Second intention healing is a simple and extremely useful method to optimize cosmesis after skin cancer removal. OBJECTIVES: This study reported the cosmetic outcomes after second intention healing of nasal ala and dorsum defects in Asians, and estimated the time to epithelialization and complete healing. MATERIALS AND METHODS: Fifteen defects (<1 cm in diameter) of the nasal ala and dorsum in 10 patients were allowed to heal by secondary intention. Cosmetic results were evaluated and the time to epithelialization and complete healing were recorded. RESULTS: Cosmetic outcomes were good to excellent in 80% of the defects; defects of the dorsum showed poorer cosmetic results than defects of the ala. The wounds needed 5-17 days (mean 11.3; SD ± 4.18) to complete epithelialization and 10-24 days (mean 17.7; SD ± 4.85) to heal completely. CONCLUSIONS: Second intention healing of small nasal ala and dorsum defects (<1 cm in diameter) in Asians produces satisfactory cosmetic results with a low complication rate.

Structural and functional analysis of the Klebsiella pneumoniae MazEF toxin-antitoxin system.

Bacterial toxin-antitoxin (TA) systems correlate strongly with physiological processes in bacteria, such as growth arrest, survival and apoptosis. Here, the first crystal structure of a type II TA complex structure of Klebsiella pneumoniae at 2.3 Šresolution is presented. The K. pneumoniae MazEF complex consists of two MazEs and four MazFs in a heterohexameric assembly. It was estimated that MazEF forms a dodecamer with two heterohexameric MazEF complexes in solution, and a truncated complex exists in heterohexameric form. The MazE antitoxin interacts with the MazF toxin via two binding modes, namely, hydro-phobic and hydro-philic interactions. Compared with structural homologs, K. pneumoniae MazF shows distinct features in loops ß1-ß2, ß3-ß4 and ß4-ß5. It can be inferred that these three loops have the potential to represent the unique characteristics of MazF, especially various substrate recognition sites. In addition, K. pneumoniae MazF shows ribonuclease activity and the catalytic core of MazF lies in an RNA-binding pocket. Mutation experiments and cell-growth assays confirm Arg28 and Thr51 as critical residues for MazF ribonuclease activity. The findings shown here may contribute to the understanding of the bacterial MazEF TA system and the exploration of antimicrobial candidates to treat drug-resistant K. pneumoniae.