Potassium ameliorates cotton (Gossypium hirsutum L.) fiber length by regulating osmotic and K+ /Na+ homeostasis under salt stress.

Potassium (K) application can alleviate cotton salt stress, but the regulatory mechanisms affecting cotton fiber elongation and ion homeostasis are still unclear. A two-year field experiment was conducted to explore the effects of K on the osmolyte contents (soluble sugar, K+ content, and malate) and related enzyme activities during the fiber elongation of two cotton cultivars with contrasting salt sensitivity (CCRI-79; salt tolerant cultivar, and Simian 3; salt-sensitive cultivar). Three K application treatments (0, 150, and 300 kg K2 O ha-1 ) were applied at three soil salinity levels (low salinity, EC = 1.73 ± 0.05 dS m-1 ; medium salinity, EC = 6.32 ± 0.10 dS m-1 ; high salinity, EC = 10.84 ± 0.24 dS m-1 ). K application improved fiber length and alleviated salt stress by increasing the maximum velocity of fiber elongation (Vmax ). The increase rate of K on fiber length decreased with elevating salt stress, and the increase rate of K on Vmax of CCRI-79 was greater than that of Simian3. K application can increase the enzyme activities (phosphoenolpyruvate carboxylase, PEPC, E.C. 4.1.1.31; pyrophosphatase, PPase, E.C. 3.6.1.1; and plasma membrane H+ -ATPase, PM H+ -ATPase, E.C. 3.6.3.14) as well as the content of osmolytes associated with the enzymes mentioned above. K increased the osmolyte contents under salt stress, and the increase in the K+ content of the fibers was much higher than that of soluble sugar and malate. The results of this study indicated K fertilizer application rates regulate the metabolism of osmolytes in cotton fiber development under salt stress, K+ is more critical to fiber elongation.

A Review of Finite Element Models of Ligaments in the Foot and Considerations for Practical Application.

Finite element (FE) modeling has been used as a research tool for investigating underlying ligaments biomechanics and orthopedic applications. However, FE models of the ligament in the foot have been developed with various configurations, mainly due to their complex three-dimensional geometry, material properties, and boundary conditions. Therefore, the purpose of this review was to summarize the current state of finite element modeling approaches that have been used in the field of ligament biomechanics, to discuss their applicability to foot ligament modeling in a practical setting, and also to acknowledge current limitations and challenges. A comprehensive literature search was performed. Each article was analyzed in terms of the methods used for: (a) ligament geometry, (b) material property, (c) boundary and loading condition related to its application, and (d) model verification and validation. Of the reviewed studies, 79.8% of the studies used simplified representations of ligament geometry, the nonlinear mechanical behavior of ligaments was taken into account in only 19.2% of the studies, 33.6% of included studies did not include any kind of validation of the FE model. Further refinement in the functional modeling of ligaments, the microstructure level characteristics, nonlinearity, and time-dependent response, may be warranted to ensure the predictive ability of the models.

ACL graft with extra-cortical fixation rotates around the femoral tunnel aperture during knee flexion.

PURPOSE: An understanding of the behavior of a new ACL graft in the femoral tunnel during knee motion and external loading can provide information pertinent to graft healing, tunnel enlargement, and graft failure. The purpose of the study was to measure the percentage of the tunnel filled by the graft and determine the amount and location of the graft-tunnel contact with knee motion and under external knee loads. METHODS: Single bundle anatomical ACL reconstruction was performed on six cadaveric knees. Specimens were positioned with a robotic testing system under: (1) passive flexion-extension, (2) 89-N anterior and posterior tibial loads, (3) 5-N m internal and external torques, and (4) 7-N m valgus moment. The knees were then dissected, repositioned by the robot and the geometry of the femoral tunnel and graft were digitized by laser scanning. The percentage of tunnel filled and the contact region between graft and tunnel at the femoral tunnel aperture were calculated. RESULTS: The graft occupies approximately 70% of the femoral tunnel aperture and anterior tibial loading tended to reduce this value. The graft contacted about 60% of the tunnel circumference and the location of the graft-tunnel contact changed significantly with knee flexion. CONCLUSION: This study found that the graft tends to rotate around the tunnel circumference during knee flexion-extension and contract under knee loading. The "windshield-wiper" and "bungee cord" effect may contribute to femoral tunnel enlargement, affect graft healing, and lead to graft failure. There can be a considerable motion of the graft in the tunnel after surgery and appropriate rehabilitation time should be allowed for graft-tunnel healing to occur. To reduce graft motion, consideration should be given to interference screw fixation or a graft with bone blocks, which may allow an earlier return to activity.

Detoxification of lignocellulosic prehydrolyzate by lignin nanoparticles prepared from biorefinery biowaste to improve the ethanol production.

This study proposed a recyclable p-toluenesulfonic acid (p-TsOH) fractionation process for co-producing lignin nanoparticles (LNPs) and fermentable sugars from lignocellulosic biorefinery biowaste (enzymatic hydrolysis residue (EHR)). The prepared LNPs were used to detoxify the inhibitors in the xylose-rich prehydrolyzate for improving ethanol production. Results showed that the EHR was fractionated into a cellulose-rich water-insoluble solid (WIS) fraction and a lignin-rich spent liquor (SL) fraction. Cellulase hydrolysis of WIS produced 97.7% of glucose yield, while the LNPs of an average particle size of 98.0 nm with 76.3 % yield (based on the untreated EHR) were obtained from the diluted SL. LNPs demonstrated higher detoxification ability than EHR at the same dosage. Moreover, the fermentability of the detoxified xylose-rich prehydrolyzate was significantly improved. The sugar utilization ratio was 94.8%, and the ethanol yield reached its peak value of 85.4% after 36 h of fermenting the detoxified xylose-rich prehydrolyzate.

Topical delivery of pluronic F127/TPGS mixed micelles-based hydrogel loaded with glycyrrhizic acid for atopic dermatitis treatment.

OBJECTIVE: The purpose of this study was to develop pluronic F127/d-a-tocopheryl polyethylene glycol 1000 succinate mixed micelles-based hydrogel (MMs-gel) for topical delivery of glycyrrhizic acid (GL) to improve its skin permeability and atopic dermatitis (AD) treatment. SIGNIFICANCE: GL loaded MMs-gel (GL-MMs-gel) could be potentially used as a promising nanocarrier for the treatment of AD. METHODS: GL-MMs were prepared by thin film hydration method and then loaded into carbopol gel. The formulation of GL-MMs-gel was optimized by full factorial design and systematically characterized for drug content, pH, spreadability, in vitro drug release and percutaneous permeation, etc. The therapeutic effect of GL-MMs-gel was also investigated in AD-like skin lesion model in BALB/c mice and compared with GL solution-based gel (GL-sol-gel). RESULTS: Spherical GL-MMs with particle size of ∼30 nm were successfully incorporated into carbopol gel to form GL-MMs-gel with drug content of (98.80 ± 1.30) %, pH of 6.0 ± 0.08, and spreadability of (7.1 ± 0.2) cm. In vitro drug release profile of GL-MMs-gel exhibited a sustained-release behavior. The permeation flux for GL-MMs-gel (5.15 ± 0.33 µg/cm2/h) was significantly higher than that of GL-sol-gel (3.08 ± 0.34 µg/cm2/h) and GL-MMs-gel increased the accumulative amounts of GL in rats' skin 8.41 times than GL-sol-gel. The GL-MMs-gel was more effective than GL-sol-gel in suppressions of various AD symptoms including skin lesions, edema, high IgE levels, epidermal hyperplasia, and mast cell infiltration. CONCLUSION: All results revealed that MMs-gel could be a promising carrier for topical delivery of GL for the treatment of AD.

Glycyrrhizic acid-based self-assembled micelles for improving oral bioavailability of paeoniflorin.

BACKGROUND: Paeoniflorin (Pae), a water-soluble monoterpene glucoside, has high potential clinical value in autoimmune and inflammatory diseases. However, the extremely low oral bioavailability of Pae (approximately 3%-4%) limits its formulation development and clinical application. This study aimed to develop micelles using the glycyrrhizic acid (GL) as the carrier to improve the oral absorption of Pae. METHODS: Pae-loaded GL micelles were prepared by the ultrasonic dispersion method and its formulation was optimized by single-factor tests. Characterizations of Pae-loaded GL micelles including particle size, zeta potential, entrapment efficiency (EE), drug loading (DL), morphology, and drug release in vitro were carried out. The single-pass intestinal perfusion and pharmacokinetic studies of Pae-loaded GL micelles were also evaluated in rats and compared with Pae solution and the mixed solution of Pae and GL. RESULTS: The optimized Pae-loaded GL micelles had EE of (42.21 ± 0.89)%, particle size of (58.89 ± 4.24) nm with PDI of (0.194 ± 0.010), zeta potential of (-24.40 ± 1.90) mV. Pae-loaded GL micelles showed a nearly spherical shape under TEM. Drug release of micelles demonstrated a delayed drug release compared to Pae solution. The single-pass intestinal perfusion study showed a significantly higher permeability of Pae in duodenum (p < 0.05), jejunum (p < 0.05), ileum (p < 0.01) and colon (p < 0.01) intestine after perfusion of Pae-loaded GL micelles as compared to Pae solution. The in vivo pharmacokinetics demonstrated that the Cmax and AUC0-t values of Pae-loaded GL micelles were approximately 2.18- and 3.64-fold superior than the Pae solution. CONCLUSION: These results suggested GL could be a potential carrier for the oral delivery of Pae.

[Advances in formation and application of self-assembled nanoparticles from traditional Chinese medicine].

Due to the diverse sources and unique structures, the chemical components of Chinese medicinal materials are easy to self-assemble to form nanoparticles. The formation of self-assembled nanoparticles(SAN) can not only affect the absorption and distribution of the effective ingredients in Chinese medicinal materials but also may improve the biological activity of the effective ingredients or their simple mixtures, which is of great significance for revealing the compatibility mechanism of Chinese medicine prescription, developing new Chinese medicine products, and producing new nanomaterials. This paper reviews the formation, isolation, characterization, and application of SAN of Chinese medicines, and discusses the problems and development trends of the relevant research, which can provide reference for the further study and promote the innovation and application of such SAN.

[Effect of self-assembled nanoparticles from Shaoyao Gancao Decoction on release and absorption of main components of Baishao].

To study the effect of self-assembled nanoparticles from Shaoyao Gancao Decoction(SGD-SAN) on the encapsulation, in vitro release and intestinal absorption of the main components of Baishao. Particle size analysis and morphological observation were used to verify the formation of SGD-SAN in the decoction. The entrapment efficiency(EE) of SGD-SAN on the main components of Baishao was determined by ultrafiltration centrifugation. The dialysis bag method was used to study the in vitro release of the main components of Baishao with pH 6.8 phosphate buffer solution as the release media. Single-pass intestinal perfusion study was performed to investigate the effect of SGD-SAN on the absorption of the main components of Baishao. The results showed that there were nanoparticles in the SGD, and the particle sizes and PDI of SGD-SAN were about 200 nm and 0.38, respectively. SGD-SAN was irregularly spherical under transmission electron microscope(TEM). The EEs of albiflorin, paeoniflorin and benzoylpaeoniflorin in SGD-SAN were 33.78%±1.03%,33.61%±0.90%,88.53%±0.58%, respectively. The release characteristics of albiflorin, paeoniflorin and benzoylpaeoniflorin from SGD-SAN showed a slow-release effect on pH 6.8 phosphate buffer solution media. SGD-SAN could significantly enhance the absorption of albiflorin, paeoniflorin and benzoylpaeoniflorin in the ileum. The results of this study indicated that SAN could be formed during the mixed decoction of Baishao and Gancao, and SGD-SAN could encapsulate the components of Baishao, with a certain slow-release effect, and the formation of SAN facilitated the absorption of drugs in the ileum.

Single-bundle MCL reconstruction with anatomic single-bundle ACL reconstruction does not restore knee kinematics.

PURPOSE: The purpose of this study was to evaluate and compare knee kinematics and kinetics following either single bundle, modified triangular or double-bundle reconstruction of the superficial medial collateral ligament (sMCL) with single bundle anatomic ACL reconstruction. METHODS: Using a cadaveric model (n = 10), the knee kinematics and kinetics following three MCL reconstructions (single-bundle (SB), double-bundle (DB), modified triangular) with single bundle anatomic ACL reconstruction were compared with the intact and deficient knee state. The knees were tested under (1) an 89-N anterior tibial load, (2) 5 N-m internal and external rotational tibial torques, and (3) a 7 N-m valgus torque. RESULTS: Anatomic ACL reconstruction with SB MCL reconstruction was able to restore anterior tibial translation and external rotation to intact knee values but failed to the internal and valgus rotatory stability. Anatomical DB MCL reconstruction (with SB ACL reconstruction) and the modified triangular MCL reconstruction (with SB ACL reconstruction) restored all knee kinematics to the intact value. CONCLUSION: This study shows that clinical presentation with combined ACL and severe sMCL injury, single-bundle MCL with single-bundle ACL reconstruction does not restore knee kinematics. Anatomical double-bundle MCL reconstruction may produce slightly better biomechanical stability than the modified triangular MCL reconstruction, but the modified triangular reconstruction might be more clinically practical with the advantages of being less invasive and technically simpler while at the same time can restore a nearly normal knee joint.

The femoral posterior fan-like extension of the ACL insertion increases the failure load.

PURPOSE: To examine the role of the posterior fan-like extension of the ACL's femoral footprint on the ACL failure load. METHODS: Sixteen (n = 16) fresh frozen, mature porcine knees were used in this study and randomized into two groups (n = 8): intact femoral ACL insertion (ACL intact group) and cut posterior fan-like extension of the ACL (ACL cut group). In the ACL cut group, flexing the knees to 90°, created a folded border between the posterior fan-like extension and the midsubstance insertion of the femoral ACL footprint and the posterior fan-like extension was dissected and both areas were measured. Specimens were placed in a testing machine at 30° of flexion and subjected to anterior tibial loading (60 mm/min) until ACL failure. RESULTS: The intact ACL group had a femoral insertion area of 182.1 ± 17.1 mm2. In the ACL cut group, the midsubstance insertion area was 113.3 ± 16.6 mm2, and the cut posterior fan-like extension portion area was 67.1 ± 8.3 mm2. The failure load of the ACL intact group was 3599 ± 457 N and was significantly higher (p < 0.001) than the failure load of the ACL cut group 392 ± 83 N. CONCLUSION: Transection of the posterior fan-like extension of the ACL femoral footprint has a significant effect on the failure load of the ligament during anterior loading at full extension. Regarding clinical relevance, this study suggests the importance of the posterior fan-like extension of the ACL footprint which potentially may be retained with remnant preservation during ACL reconstruction. Femoral insertion remnant preservation may allow incorporation of the fan-like structure into the graft increasing graft strength.

Partial meniscectomy does not affect the biomechanics of anterior cruciate ligament reconstructed knee with a lateral posterior meniscal root tear.

PURPOSE: The purpose of this study was to determine the effects of a lateral meniscus posterior root tear, partial meniscectomy, and total meniscectomy on knee biomechanics in the setting of anterior cruciate ligament (ACL) reconstruction. METHODS: Thirteen fresh-frozen cadaver knees were tested with a robotic testing system under an 89.0-N anterior tibial load at full extension (FE), 15°, 30°, 60° and 90° of knee flexion and a simulated pivot-shift loading (7.0 Nm valgus and 5.0 Nm internal tibial rotation) at FE, 15° and 30° of knee flexion. Anterior tibial translation (ATT) and the in-situ force of ACL graft under the different loadings were measured in four knee states: (1) ACL reconstruction with intact lateral meniscus (Intact meniscus), (2) ACL reconstruction with lateral meniscal posterior root tear (Root tear), (3) ACL reconstruction with lateral posterior partial meniscectomy (Partial meniscectomy) and (4) ACL reconstruction with total lateral meniscectomy (Total meniscectomy). RESULTS: Under anterior tibial loading, compared with an intact meniscus, root tear significantly increased ATT at 15° and 30° of knee flexion (p < 0.05) and partial meniscectomy had almost same increased ATT as with root tear at any knee flexion between FE and 90°. Under simulated pivot-shift loading, total meniscectomy increased ATT compared with intact meniscus, root tear, partial meniscectomy at FE (p < 0.05). CONCLUSION: Under anterior tibial and simulated pivot-shift loading, partial meniscectomy has no significant effect on the stability of ACL-reconstructed knee with lateral meniscal posterior root tear, while total meniscectomy increased laxity at less than 30° of knee flexion. Clinically, in cases of irreparable meniscal root tears or persistent pain a partial meniscectomy can be considered in the setting of ACL reconstruction.

Formulation of pluronic F127/TPGS mixed micelles to improve the oral absorption of glycyrrhizic acid.

Background: Glycyrrhizic acid (GL), a pentacyclic triterpenoid glycoside, has been used as a hepatoprotective agent for the treatment of acute and chronic hepatitis. However, its poor solubility and permeability across the gastrointestinal mucosa limit its clinical efficacy. This study aimed to develop mixed micelles based on pluronic F127 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) to improve the oral bioavailability of GL.Methods: GL loaded pluronic F127/TPGS mixed micelles (GL-F127/TPGS-MMs) were prepared by thin film hydration method, and their physicochemical properties including particle size, zeta potential, entrapment efficiency (EE), drug loading (DL), X-ray diffraction (XRD) analysis, differential scanning calorimetry (DSC), and drug release were characterized. Furthermore, the pharmacokinetic and biodistribution studies of GL-F127/TPGS-MMs were evaluated in rats and compared with GL solution.Results: GL-F127/TPGS-MMs were found to be of spherical shape with particle size of (27.41 ± 4.90) nm, EE% of 95.38% and DL% of 12.99%. The results of XRD and DSC indicated that GL was encapsulated in the micelles. Drug release of GL-F127/TPGS-MMs demonstrated a sustained release behavior as compared to GL solution. The pharmacokinetic and biodistribution studies showed a significantly higher oral absorption and liver accumulation of glycyrrhetinic acid (GA) after oral administration of GL-F127/TPGS-MMs as compared to GL solution.Conclusion: These results suggested F127/TPGS-MMs might be a potential nanocarrier for oral delivery of GL.

[Preparation and in vitro release of ginkgolide B nanosuspension].

To prepare ginkgolide B nanosuspension(GB-NS), and investigate its dissolution behaviors in vitro. The miniaturized media milling method was used to prepare nanosuspensions, with average particle size and polydispersity index as the evaluation indexes. The formulation and process of GB-NS were optimized by single factor experiment and Box-Behnken design-response surface method. The morphology was observed by scanning electron microscope(SEM), and thecrystallinity of GB-NS was investigated by X-rays diffraction(XRD). The paddle method was used to study the dissolution of GB-NS in vitro. The mean particle size of optimized GB-NS was(180±7) nm, with a polydispersity index of 0.196±0.036. SEM showed that GB-NS was rod-like or irregular granular. XRD showed that the crystallinity of GB-NS was significantly reduced compared with GB raw material. The cumulative dissolution rate of GB-NS reached 90% in 30 min, which was higher than that of GB raw material. The findings suggested that the miniaturized media milling method was simple, efficient and feasible to prepare GB-NS. And the dissolution rate of GB was significantly improved by nanosuspension technology.

[Preparation and in vitro quality evaluation of self-microemulsion co-loaded with tenuifolin and ß-asarone].

To prepare and optimize the self-microemulsion co-loaded with tenuifolin and ß-asarone(TF/ASA-SMEDDS) and evaluate its quality. The prescription compositions of TF/ASA-SMEDDS were screened by solubility test, single factor test and pseudo-tern-ary phase diagram, and the prescriptions were further optimized by Box-Behnken response surface method, with the drug loading and particle size as the evaluation indexes. Then the optimized TF/ASA-SMEDDS was evaluated for emulsified appearance, particle size, morphology and drug release in vitro. The optimized prescription for TF/ASA-SMEDDS was as follows: caprylic citrate triglyceride polyoxyethylene castor oil-glycerol(10.8∶39.2∶50), drug loading of(5.563±0.065) mg·g~(-1) for tenuifolin and(5.526±0.022) mg·g~(-1) for ß-asarone; uniform and transparent pan-blue nanoemulsion can be formed after emulsification, with particle size of(28.84±0.44) nm. TEM showed that TF/ASA-SMEDDS can form spherical droplets with a uniform particle size after emulsification; In vitro release test results showed that the drug release rate and cumulative release of tenuifolin and ß-asarone were significantly improved. The preparation process of TF/ASA-SMEDDS was simple and can effectively improve in vitro release of tenuifolin and ß-asarone.

Transcriptome and metabolome analysis of Pichia stipitis to three representative lignocellulosic inhibitors.

During the bioconversion of xylose to ethanol, Pichia stipitis cells are often inhibited by substances generated in the lignocellulosic hydrolysate. However, the response mechanism of P. stipitis to inhibitors has not been completely understood till date. With this aim, integrated transcriptomic and metabolomic analyses were performed on P. stipitis to investigate the interactive effects of three representative inhibitors [vanillin, 5-hydroxymethylfurfural (5-HMF), and acetic acid] present in lignocellulosic hydrolysates. The genes involved in carbohydrate metabolism were observed to significantly down-regulated in the presence of the three combined inhibitors in both lag and middle exponential phases. In addition, inhibitor addition induced amino acid metabolism (e.g., glutamine and asparagine syntheses), since the yeast cells required more amino acids in stressful conditions. The metabolomic analysis yielded similar results, particularly those related with the analysis of metabolic biomarkers including fatty acids, amino acids, and sugars. 70 intracellular metabolites were detected by gas chromatography coupled with mass spectrometry (GC-MS), and samples from different phases were clearly separated by principal component analysis (PCA). The large amount of specific responsive genes and metabolites highlighted the complex regulatory mechanisms involved in the fermentation process in the presence of the three combined inhibitors.

Curcumin suppresses epithelial-to-mesenchymal transition of peritoneal mesothelial cells (HMrSV5) through regulation of transforming growth factor-activated kinase 1 (TAK1).

OBJECTIVE: Peritoneal fibrosis remains a serious complication of long-term peritoneal dialysis (PD) leading to peritoneal membrane ultrafiltration failure. Epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is a key process of peritoneal fibrosis. Curcumin has been previously shown to inhibit EMT of renal tubular epithelial cells and prevent renal fibrosis. There are only limited reports on inhibition of PMCs-EMT by curcumin. This study aimed to investigate the effect of curcumin on the regulation of EMT and related pathway in PMCs treated with glucose-based PD. METHODS: EMT of human peritoneal mesothelial cells (HMrSV5) was induced with glucose-based peritoneal dialysis solutions (PDS). Cells were divided into a control group, PDS group, and PDS group receiving varied concentrations of curcumin. Cell Counting Kit-8 (CCK-8) assay was used to measure cell viability, and a transwell migration assay was used to verify the capacity of curcumin to inhibit EMT in HMrSV5 cells. Real-time quantitative PCR and western blot were used to detect the expression of genes and proteins associated with the EMT. RESULTS: High glucose PDS decreased cell viability and increased migratory capacity. Curcumin reversed growth inhibition and migration capability of human peritoneal mesothelial cells (HPMCs). In HMrSV5 cells, high glucose PDS also decreased expression of epithelial markers, and increased expression of mesenchymal markers, a characteristic of EMT. Real-time RT-PCR and western blot revealed that, compared to the 4.25% Dianeal treated cells, curcumin treatment resulted in increased expression of E-cadherin (epithelial marker), and decreased expression of α-SMA (mesenchymal markers) (P < 0.05). Furthermore, curcumin reduced mRNA expression of two extracellular matrix protein, collagen I and fibronectin. Curcumin also reduced TGF-ß1 mRNA and supernatant TGF-ß1 protein content in the PDS-treated HMrSV5 cells (P < 0.05). Furthermore, it significantly reduced protein expression of p-TAK1, p-JNK and p-p38 in PDS-treated HMrSV5 cells. CONCLUSIONS: Our results demonstrate that curcumin showed an obvious protective effect on PDS-induced EMT of HMrSV5 cells and suggest implication of the TAK1, p38 and JNK pathway in mediating the effects of curcumin in EMT of MCs.

Structural and mechanistic insights into regulation of HBO1 histone acetyltransferase activity by BRPF2.

HBO1, a member of the MYST family of histone acetyltransferases (HATs), is required for global acetylation of histone H3K14 and embryonic development. It functions as a catalytic subunit in multisubunit complexes comprising a BRPF1/2/3 or JADE1/2/3 scaffold protein, and two accessory proteins. BRPF2 has been shown to be important for the HAT activity of HBO1 toward H3K14. Here we demonstrated that BRPF2 can regulate the HAT activity of HBO1 toward free H3 and H4, and nucleosomal H3. Particularly, a short N-terminal region of BRPF2 is sufficient for binding to HBO1 and can potentiate its activity toward H3K14. The crystal structure of the HBO1 MYST domain in complex with this segment of BRPF2 together with the biochemical and cell biological data revealed the key residues responsible for the HBO1-BRPF2 interaction. Our structural and functional data together indicate that the N-terminal region of BRPF2 plays an important role in the binding of HBO1 and a minor role in the binding of nucleosomes, which provide new mechanistic insights into the regulation of the HAT activity of HBO1 by BRPF2.

Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis.

BACKGROUND: Peritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD). The goal of this study was to investigate the anti-fibrotic effects of curcumin on the PF response to PD and its' mechanism. METHODS: Male Sprague-Dawley rats were infused with 20 mL of 4.25% glucose-based standard PD fluid for 8 consecutive weeks to establish PF model and then divided into five groups: Control, received sham operation and 0.9% physiological saline; PD, received 4.25% standard PD fluid; Curcumin, PD rats injected intraperitoeally with curcumin for 8 weeks at doses of 10, 20 or 40 mg/kg. Masson's staining was performed to evaluate the extent of PF. Peritoneal Equilibration Test (PET) was conducted to assess ultrafiltration volume (UFV) and mass transfer of glucose (MTG), quantitative RT-PCR, and immunohistochemistry or western blotting were performed to measure the expression levels of inflammation and fibrosis-associated factors. We also detected the TGF-ß1 in peritoneal fluid by ELISA. RESULTS: Compared with the control group, the PD rats showed decreased UFV (2.54 ± 0.48 to 9.87 ± 0.78 mL, p < 0.05] and increased MTG (18.99 ± 0.86 to 10.85 ± 0.65 mmol/kg, p < 0.05) as well as obvious fibroproliferative response, with markedly increased peritoneal thickness (178.33 ± 4.42 to 25.26 ± 0.32um, p < 0.05) and higher expression of a-SMA, collagen I and TGF-ß1. Treatment with curcumin significantly increased UFV, reduced MTG and peritoneal thickness of PD rats. The elevated TGF-ß1 in peritoneal fluid of PD rats was significantly decreased by curcumin. It attenuated the increase in protein and mRNA of TGF-ß1, α-SMA and collagen I in peritoneum of PD rats. The mRNA expressions of TAK1, JNK and p38, as well as the protein expressions of p-TAK1, p-JNK and p-p38 in peritoneum of PD rats were reduced by curcumin. CONCLUSIONS: Present results demonstrate that curcumin showed a protective effect on PD-related PF and suggest an implication of TAK1, p38 and JNK pathway in mediating the benefical effects of curcumin.

Quantitative lipidomic insights in the inhibitory response of Pichia stipitis to vanillin, 5-hydroxymethylfurfural, and acetic acid.

To obtain a global view of the dynamic phospholipids in Pichia stipitis during the ethanol fermentation in the presence of three representative inhibitors (vanillin, 5-hydroxymethylfurfural, and acetic acid). Considerable efforts have been expended to elucidate the biochemical mechanisms of inhibitors interaction with phospholipids. In this study, a comparative lipidomic analysis was performed using liquid chromatography-mass/mass spectrometry (LC-MS/MS) on P. stipitis. Partial least squares-discriminate analysis (PLS-DA) was used to deal with the large quantity of data generated using the systematic methods. PLS-DA revealed that phosphatidylinositol (PI) (PI34:1, PI34:2 and PI34:6), phosphatidylserine (PS) (PS34:1 and PS34:2), phosphatidylethanolamine (PE) (PE34:1 and PE34:2), and phosphatidylcholine (PC) (PC34:1, PC34:2, and PC34:3) were the predominant biomarkers. Further analysis of different classes of phospholipids indicated that: (a) the samples from three combined inhibitors condition during the lag phase possessed the lowest PI/PS value 1.4%, (b) alterations in PC/PE ratios with changes in inhibitors were coincident with the changes in xylose utilization rates, and (c) the levels of unsaturated and the relatively long chain phospholipids increased in the inhibitor-plus condition. These findings suggest that regulation of membrane properties with inhibitors might offer a way of self-protection of yeast to inhibitors stress.

Medial collateral ligament reconstruction is necessary to restore anterior stability with anterior cruciate and medial collateral ligament injury.

PURPOSE: The purpose of this study was to compare knee kinematics and graft forces in anterior cruciate ligament (ACL) reconstruction combined with one of two superficial medial collateral ligament (sMCL) reconstruction techniques (parallel or triangular vector sMCL reconstruction). METHODS: Twenty porcine knees were divided into two groups (n = 20), parallel or triangular vector sMCL reconstruction, with both groups having anatomic single-bundle ACL reconstruction. The knees were tested under (1) an 89-N anterior tibial load, (2) 4 Nm internal and external rotational tibial torques, and (3) a 7 Nm valgus torque. RESULTS: With ACL/sMCL co-injuries, single-bundle ACL reconstruction alone does not restore anterior, valgus, and internal stability. Triangular vector sMCL reconstruction better restored anterior stability, and parallel sMCL reconstruction better restored valgus stability. CONCLUSION: This study showed that single-bundle ACL reconstruction alone was not able to restore anterior tibial translation, valgus rotation, and external rotation of the intact knee with combined ACL and sMCL injuries and sMCL reconstruction was also required. The combined ACL and parallel sMCL reconstruction better restored valgus and external rotation stability, while the combined ACL and triangular vector method better restored anterior tibial translation. With combined ACL and severe sMCL injury, both ligaments should be reconstructed. The two sMCL reconstruction techniques exhibited slightly different kinematics and graft force; however, there was not enough difference to recommend one over the other.