Demystifying COVID-19 mortality causes with interpretable data mining.

While COVID-19 becomes periodical, old individuals remain vulnerable to severe disease with high mortality. Although there have been some studies on revealing different risk factors affecting the death of COVID-19 patients, researchers rarely provide a comprehensive analysis to reveal the relationships and interactive effects of the risk factors of COVID-19 mortality, especially in the elderly. Through retrospectively including 1917 COVID-19 patients (102 were dead) admitted to Xiangya Hospital from December 2022 to March 2023, we used the association rule mining method to identify the risk factors leading causes of death among the elderly. Firstly, we used the Affinity Propagation clustering to extract key features from the dataset. Then, we applied the Apriori Algorithm to obtain 6 groups of abnormal feature combinations with significant increments in mortality rate. The results showed a relationship between the number of abnormal feature combinations and mortality rates within different groups. Patients with "C-reactive protein > 8 mg/L", "neutrophils percentage > 75.0 %", "lymphocytes percentage < 20%", and "albumin < 40 g/L" have a 2 × mortality rate than the basic one. When the characteristics of "D-dimer > 0.5 mg/L" and "WBC > 9.5 × 10 9 /L" are continuously included in this foundation, the mortality rate can be increased to 3 × or 4 × . In addition, we also found that liver and kidney diseases significantly affect patient mortality, and the mortality rate can be as high as 100%. These findings can support auxiliary diagnosis and treatment to facilitate early intervention in patients, thereby reducing patient mortality.

Cell-based tissue engineered flexor tendon allograft: A canine in vivo study.

This study aimed to compare the clinically established autologous extrasynovial tendon graft to a newly developed tissue-engineered allograft (Eng-allograft) in terms of functional outcomes following flexor tendon reconstruction in a canine model. The second and fifth flexor digitorum profundus (FDP) tendons from 16 dogs were transected and repaired in Zone II. After 6 weeks of cage activity, the repaired tendons were intentionally ruptured, creating a clinically relevant model for reconstruction. The re-ruptured FDP tendons were then reconstructed using either the clinically standard autologous extrasynovial tendon graft or the Eng-allograft, which had been revitalized with autologous bone marrow-derived mesenchymal stem cells (BMSCs) and synovialized using carbodiimide derivatized synovial fluid (cd-SYN). Following 12 weeks of postoperative rehabilitation, the functional outcomes of the surgical digits were evaluated. The Eng-allograft group exhibited improved digital function, including lower digit work of flexion and reduced adhesion status, while maintaining similar tendon gliding resistance compared to the autograft group. However, the failure load of both the distal and proximal host/graft conjunctions in the Eng-allograft group was significantly lower than that of the autograft group with higher graft rupture at the host-graft junction. In conclusion, the decellularized allogenic intrasynovial tendon, when revitalized BMSCs and synovialized with cd-SYN, demonstrates positive effects on digital function improvement and adhesion reduction. However, the healing at both proximal and distal graft/host junctions is far lower than the autograft. Further research is needed to enhance the healing capacity of allograft conjunctions, aiming to achieve a comparable level of healing seen with autografts.

Electrostatic force on a spherical particle confined between two planar surfaces.

A charge-free particle in a uniform electric field experiences no net force in an unbounded domain. A boundary, however, breaks the symmetry and the particle can be attracted or repelled to it, depending on the applied field direction [Z. Wang et al., Phys. Rev. E, 2022, 106, 034607]. Here, we investigate the effect of a second boundary because of its common occurrence in practical applications. We consider a spherical particle suspended between two parallel walls and subjected to a uniform electric field, applied in a direction either normal or tangential to the surfaces. All media are modeled as leaky dielectrics, thus allowing for the accumulation of free charge at interfaces, while bulk media remain charge-free. The Laplace equation for the electric potential is solved using a multipole expansion and the boundaries are accounted for by a set of images. The results show that in the case of a normal electric field, which corresponds to a particle between two electrodes, the force is always attractive to the nearer boundary and, in general, weaker that the case of only one wall. Intriguingly, for a given particle-wall separation we find that the force may vary nonmonotonically with confinement and its magnitude may exceed the one-wall value. In the case of tangential electric field, which corresponds to a particle between insulating boundaries, the force follows the same trends but it is always repulsive.

Decoding molecular signature on heart of septic mice with distinct left ventricular ejection fraction.

Dysregulated cardiac function after sepsis in intensive care unit is known to predict poor long-term outcome and increase mortality. Their pathological feature and molecular mechanism remain unclear. We observed that septic patients with depressed left ventricular ejection fraction (LVEF) have the highest in-hospital and 28 days mortality comparing to patients with hyperdynamic LVEF or with heart failure with preserved LVEF. Echocardiograms reveal that survivors post cecum ligation and puncture (CLP) on rodents have stable LVEF and non-survivors have fluctuated LVEF at CLP early phase. CLP-induced mice fall into three groups based on LVEF 24 h post-surgery: high-, low-, and normal-LVEF. Transcriptomic and proteomic analyses identify jointly and distinctively changed genes, proteins and biologically essential pathways in left ventricles from three CLP groups. Notably, transmission electron microscopy shows different mitochondrial and sarcomere defects associated with LVEF variances. Together, this study systematically characterizes the molecular, morphological, and functional alterations in CLP-induced cardiac injury.

Characterizing distinct profiles of immune and inflammatory response with age to Omicron infection.

Background: Understanding inflammatory and immune responses to Omicron infection based on age is crucial when addressing this global health threat. However, the lacking of comprehensive elucidation hinders the development of distinct treatments tailored to different age populations. Methods: 1299 cases of Omicron infection in Shanghai were enrolled between April 10, 2022 and June 3, 2022, dividing into three groups by ages: Adult group (18-59 years), Old group (60-79 years), and Elder group (≥ 80 years). Laboratory data including inflammatory cytokines, cellular, and humoral immunity were collected and analyzed. Results: The mean age of Adult, Old, and Elder groups were 44.14, 69.98, and 89.35 years, respectively, with 40.9% being men. The Elder group patients exhibited higher white blood cell (WBC) counts and elevated levels of inflammatory cytokines, but their lymphocyte counts were relatively lower. In comparison to the Old group patients, the Elder group patients demonstrated significantly lower CD3+ T-cell counts, CD3+ T-cell proportion, CD4+ T-cell counts, CD8+ T-cell counts, and CD19+ B-cell counts, while the NK-cell counts were higher. Omicron negative patients displayed a higher proportion of CD19+ B-cells and higher levels of Complement-3 and IL-17 compared to the positive patients in the Old group. Omicron negative patients had lower WBC counts, CD3+CD8+ T-cells proportion, and the levels of serum amyloid A and IgA in the Elder group, but the CD4+/CD8+ ratio was higher. Conclusions: Our study identified the distinct profiles of inflammatory and immune responses to Omicron infection varying with age and highlighted the diverse correlations between the levels of various biomarkers and Omicron infected/convalescent patients.

Chinese experts' consensus on the application of intensive care big data.

The development of intensive care medicine is inseparable from the diversified monitoring data. Intensive care medicine has been closely integrated with data since its birth. Critical care research requires an integrative approach that embraces the complexity of critical illness and the computational technology and algorithms that can make it possible. Considering the need of standardization of application of big data in intensive care, Intensive Care Medicine Branch of China Health Information and Health Care Big Data Society, Standard Committee has convened expert group, secretary group and the external audit expert group to formulate Chinese Experts' Consensus on the Application of Intensive Care Big Data (2022). This consensus makes 29 recommendations on the following five parts: Concept of intensive care big data, Important scientific issues, Standards and principles of database, Methodology in solving big data problems, Clinical application and safety consideration of intensive care big data. The consensus group believes this consensus is the starting step of application big data in the field of intensive care. More explorations and big data based retrospective research should be carried out in order to enhance safety and reliability of big data based models of critical care field.

Particle-surface interactions in a uniform electric field.

The electrostatic force on a spherical particle near a planar surface is calculated for the cases of a uniform electric field applied in either normal or tangential direction to the surface. The particle and suspending media are assumed to be weakly conducting, so that that the leaky dielectric model applies. The Laplace equation for the electric potential is solved in bipolar coordinate system and the potential is obtained in terms of a series expansion of Legendre polynomials. The force on the particle is calculated using the Maxwell tensor. We find that in the case of normal electric field, which corresponds to a particle near an electrode, the force is always attractive but at a given separation it varies nontrivially with particle-suspending medium conductivity ratio; the force on a particle that is more conducting than the suspending medium is much larger compared to the force on a particle less conducing than the suspending medium. In the case of tangential electric field, which corresponds to a particle near an insulating boundary, the force is always repulsive.

20S-ginsenoside Rg3 inhibits the biofilm formation and haemolytic activity of Staphylococcus aureus by inhibiting the SaeR/SaeS two-component system.

Introduction. Staphylococcus aureus is a major cause of chronic diseases and biofilm formation is a contributing factor. 20S-ginsenoside Rg3 (Rg3) is a natural product extracted from the traditional Chinese medicine red ginseng.Gap statement. The effects of Rg3 on biofilm formation and haemolytic activity as well as its antibacterial mechanism against S. aureus have not been reported.Aim. This study aimed to investigate the effects of Rg3 on biofilm formation and haemolytic activity as well as its antibacterial action against clinical S. aureus isolates.Methodology. The effect of Rg3 on biofilm formation of clinical S. aureus isolates was studied by crystal violet staining. Haemolytic activity analysis was carried out. Furthermore, the influence of Rg3 on the proteome profile of S. aureus was studied by quantitative proteomics to clarify the mechanism underlying its antibacterial action and further verified by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR).Results. Rg3 significantly inhibited biofilm formation and haemolytic activity in clinical S. aureus isolates. A total of 63 with >1.5-fold changes in expression were identified, including 34 upregulated proteins and 29 downregulated proteins. Based on bioinformatics analysis, the expression of several virulence factors and biofilm-related proteins, containing CopZ, CspA, SasG, SaeR/SaeS two-component system and SaeR/SaeS-regulated proteins, including leukocidin-like protein 2, immunoglobulin-binding protein G (Sbi) and fibrinogen-binding protein, in the S. aureus of the Rg3-treated group was downregulated. RT-qPCR confirmed that Rg3 inhibited the regulation of SaeR/SaeS and decreased the transcriptional levels of the biofilm-related genes CopZ, CspA and SasG.Conclusions. Rg3 reduces the formation of biofilm by reducing cell adhesion and aggregation. Further, Rg3 can inhibit the SaeR/SaeS two-component system, which acts as a crucial signal transduction system for the anti-virulence activity of Rg3 against clinical S. aureus isolates.

Comparison of antibacterial activities and resistance mechanisms of omadacycline and tigecycline against Enterococcus faecium.

This study aims to compare the antimicrobial activity of omadacycline with tigecycline against clinical isolates of Enterococcus faecium and investigate their resistance mechanisms. Non-duplicate clinical E. faecium isolates (n = 224) were collected and the minimal inhibitory concentrations (MICs) of omadacycline and tigecycline were determined by broth microdilution method. The tet genes and the genetic mutations in 16 S rRNA genes and 30 S ribosomal protein S10 were determined by PCR and sequence alignment. The global protein abundances of the omadacycline-induced and parent isolates were determined by a Q Exactive plus mass spectrometer. The MIC50/MIC90 of omadacycline and tigecycline against the 224 E. faecium isolates were 0.25/0.5 mg l-1 and 0.125/0.25 mg l-1, respectively. Among these E. faecium isolates, the frequency of the isolates with omadacycline MICs ≥ 0.25 mg l-1 were significantly higher than that with tigecycline MICs ≥ 0.25 mg l-1. Moreover, the T1473C and/or G1468A mutations in the 16 S rRNA and Lys98Glu mutation in the 30 S ribosomal protein S10 were identified in the 3 series of tigecycline or omadacycline- nonsusceptible isolates selected in vitro. The abundances of 32 proteins changed in the omadacycline-induced isolate, of which 10 increased and 22 decreased. The abundance of tet(M) increased significantly in the omadacycline-induced isolate, and the abundance of proteins included in cellular process and metabolic process decreased. In conclusion, Omadacycline and tigecycline exhibits excellent activities against clinical isolates of E. faecium and exposure to omadacycline and tigecycline can result in significant cross-resistance to both antibiotics. The high-level expression of tet(M) in E. faecium may confer resistance to omadacycline.

Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers.

Rotator cuff (RC) attaches to humerus across a triphasic yet continuous tissue zones (bone-fibrocartilage-tendon), termed "enthesis". Regrettably, rapid and functional enthesis regeneration is challenging after RC tear. The existing grafts bioengineered for RC repair are insufficient, as they were engineered by a scaffold that did not mimic normal enthesis in morphology, composition, and tensile property, meanwhile cannot simultaneously stimulate the formation of bone-fibrocartilage-tendon tissues. Herein, an optimized decellularization approach based on a vacuum aspiration device (VAD) was developed to fabricate a book-shaped decellularized enthesis matrix (O-BDEM). Then, three recombinant growth factors (CBP-GFs) capable of binding collagen were synthesized by fusing a collagen-binding peptide (CBP) into the N-terminal of BMP-2, TGF-ß3, or GDF-7, and zone-specifically tethered to the collagen of O-BDEM to fabricate a novel scaffold (CBP-GFs/O-BDEM) satisfying the above-mentioned requirements. After ensuring the low immunogenicity of CBP-GFs/O-BDEM by a novel single-cell mass cytometry in a mouse model, we interleaved urine-derived stem cell-sheets into this CBP-GFs/O-BDEM to bioengineer an enthesis-like graft. Its high-performance on regenerating enthesis was determined in a canine model. These findings indicate this CBP-GFs/O-BDEM may be an excellent scaffold for constructing enthesis-like graft to patch large/massive RC tears, and provide breakthroughs in fabricating graded interfacial tissue.

Lapatinib Acts against Biofilm Formation and the Hemolytic Activity of Staphylococcus aureus.

Biofilm formation and hemolytic activity are closely related to the pathogenesis of Staphylococcus aureus infections. Herein, we show that lapatinib (12.5 µM) significantly inhibits biofilm formation and hemolytic activity of both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates. Using quantitative reverse transcription PCR, we found that the RNA levels of transcriptional regulatory genes (RNAIII, agrA, agrC, saeR, and saeS), biofilm-formation-related genes (atl, cidA, clfA, clfB, and icaA), and virulence-related genes (cap5A, hla, hld, hlg, lukDE, lukpvl-S, staphopain B, alpha-3 PSM, beta PSM, and delta PSM) of S. aureus decreased after 6 h treatment with lapatinib. Wild-type S. aureus isolates were continuously cultured in vitro in the presence of increasing concentrations of lapatinib for about 140 days. Subsequently, S. aureus isolates with reduced susceptibility to lapatinib (the inhibitory effect of lapatinib on the biofilm formation of these S. aureus isolates was significantly weakened) were selected. Mutations in the genomes of S. aureus isolates with reduced susceptibility to lapatinib were detected by whole-genome sequencing. We identified four genes with mutations: three genes with known functions (membrane protein, pyrrolidone-carboxylate peptidase, and sensor histidine kinase LytS, respectively) and one gene with unknown function (hypothetical protein). In conclusion, this study indicates that lapatinib significantly inhibits biofilm formation and the hemolytic activity of S. aureus.

Inhibition of Staphylococcus aureus and biofilm formation by the anthelminthic drug, triclabendazole.

Triclabendazole (TBD) has been widely used in the treatment of helminthic infection. The anti-biofilm activity and antibacterial mechanism of TBD against Staphylococcus aureus were not known. Here, the anti-biofilm activity of TBD against clinical S. aureus isolates from China was systematically evaluated. Under TBD pressure, TBD-induced tolerant S. aureus with elevated TBD minimum inhibitory concentration (MIC) was selected in vitro and the genetic mutations between the parental isolates and TBD-induced tolerant derivatives were determined by whole-genome sequencing. TBD could significantly inhibit biofilm formation at sub-inhibitory concentration and disperse mature biofilm of clinical S. aureus isolates. In addition, TBD displayed bactericidal activity against the bacterial cells embedded in the biofilm and showed anti-persisters activity. Proteomic analysis showed that KEGG pathways of ABC transporters and beta-lactam resistance were significantly changed after TBD exposure. Moreover, SAUSA300_RS08395 (molecular chaperone DnaK), SAUSA300_RS11200 (sensor histidine kinase KdpD), SAUSA300_RS06325 (DNA translocase FtsK) were identified as candidate targets of TBD in S. aureus. Overexpression experiments further demonstrated that the elevated transcriptional level of DnaK resulted in S. aureus growth delay after exposure to a sub-MIC concentration of 1/2× MIC TBD. In conclusion, TBD exhibits antibacterial and anti-biofilm activity against S. aureus possibly by targeting the DnaK chaperone system.

Loratadine inhibits Staphylococcus aureus virulence and biofilm formation.

There are no anti-virulence and anti-biofilm treatments for Staphylococcus aureus infection. We found that 25 µM loratadine inhibits S. aureus biofilm formation under static or flow-based conditions. Testing of loratadine effects on 255 clinical S. aureus strains with varying biofilm robustness showed inhibition of biofilm formation in medium and strong, but not weak, biofilm-producing strains. At 25 µM, loratadine reduced pigmentation and hemolysis of the bacteria without affecting growth. Loratadine (5 mg/kg) reduced mortality in S. aureus pulmonary infection model mice and acted synergistically with vancomycin to reduce pulmonary bacterial load and levels of inflammatory cytokines in bronchoalveolar lavage fluid. Loratadine analogues (side-chain carbamate moiety changed) inhibited biofilm formation, pigmentation, and hemolysis of S. aureus. Regarding mechanism, loratadine exposure reduced RNA levels of virulence-related S. aureus genes, and loratadine-induced mutations in MgrA reduced loratadine-MgrA binding. Overexpression of mutated mgrA in wild-type S. aureus decreased the biofilm formation inhibition effect of loratadine.

Application of Transumbilical Laparoscopic Surgery on Low/Ultralow Rectal Cancer for Anal Sphincter Preservation.

Background: Rectal cancer is a common malignant tumor in the gastrointestinal tract. This work compares the effects of transumbilical laparoscopic surgery (TULS) and laparoscopic-assisted surgery on the anus-preserving effect of low/ultralow rectal cancer. Materials and Methods: Eighty patients with rectal cancer admitted to our hospital from February 2011 to July 2016 were randomly selected and divided into the laparoscopic group and TULS group, 40 cases in each group, all underwent radical anorectal cancer radical surgery. Statistical analysis was performed on surgical-related indicators in the two groups. Results: Two patients converted to open surgery were excluded. Five patients were excluded because of radical abdomen perineal resection for rectal cancer. Six patients were converted to TULS from laparoscopic surgery. Sixty-seven patients in the experimental group successfully completed anus-sparing surgery, and none died during the operation. The compliance rate of the distance between the lower edge of the tumor and the incision edge of the specimen in the TULS group was better than that in the laparoscopic group (P < .05). There were no significant differences between the two groups in terms of surgical time, blood loss, number of lymph node dissections, functional time of voluntary defecation and postoperative complications, tumor-free recurrence rate at 3 years, and 3-year survival rate after surgery (P > .05). Conclusions: The TULS method is safe and feasible in low and ultralow rectal cancer surgery. It has more advantages than laparoscopic-assisted surgery for anus preservation.

Age-related cellular and microstructural changes in the rotator cuff enthesis.

Rotator cuff injuries increase with age. The enthesis is the most frequent site of rotator cuff injury and degeneration. Understanding age-related changes of the enthesis are essential to determine the mechanism of rotator cuff injuries, degeneration, and to guide mechanistically driven therapies. In this study, we explored age-related cellular changes of the rotator cuff enthesis in young, mature, and aged rats. Here we found that the aged enthesis is typified by an increased mineralized zone and decreased nonmineralized zone. Proliferation, migration, and colony-forming potential of rotator cuff derived cells (RCECs) was attenuated with aging. The tenogenic and chondrogenic potential were significantly reduced, while the osteogenic potential increased in aged RCECs. The adipogenic potential increased in RCECs with age. This study explores the cellular differences found between young, mature, and aged rotator cuff enthesis cells and highlights the importance of using age-appropriate models, as well as provides a basis for further delineation of mechanisms and potential therapeutics for rotator cuff injuries.

Early treadmill running delays rotator cuff healing via Neuropeptide Y mediated inactivation of the Wnt/ß-catenin signaling.

BACKGROUND: Defining the optimal rehabilitation programs for rotator cuff healing remains a challenge. Early treadmill running may have negative effects on tendon-bone interface (TBI) healing with increased expression of Neuropeptide Y (NPY). However, the underlying mechanism is still unknown. METHODS: The mice were randomly assigned to four groups: control group, treadmill group, treadmill â€‹+ â€‹BIBO3304 group and BIBO3304 group alone. Specifically, the control group was allowed free cage activity without any treatment after surgery. The treadmill group received early treadmill running initiated from postoperative day 2. The treadmill â€‹+ â€‹BIBO3304 group received treadmill running combined with intra-articular injection of BIBO3304 postoperatively. The BIBO3304 group only received type 1 NPY receptor (Y1 receptor, Y1R) antagonist BIBO3304 postoperatively. Healing outcomes of the rotator cuff were evaluated by histological analysis, synchrotron radiation micro-computed tomography (SR-µCT) scanning, and biomechanical testing at 4 and 8 weeks after surgery. The expression of NPY and its Y1 receptor during the treadmill running were tested by immunofluorescence. In addition, the related signaling pathway of Neuropeptide Y among all groups was detected by immunohistochemistry and western-blot. RESULTS: Immunofluorescence results show that early treadmill training could lead to a significant increase in the expression of NPY at the healing site, and Y1R was widely expressed in both normal or injured rotator cuff without statistical difference. At the same time, early treadmill running delayed the healing of rotator cuff, as indicated with unsatisfactory outcomes, including a significantly lower histological score, decreased bone formation and inferior biomechanical properties at postoperative week 4 and 8. Moreover, the use of BIBO3304 could partly alleviate the negative effects of early treadmill running on the healing of rotator cuff and promote the natural healing process of rotator cuff, as evidenced by significant differences observed between the treadmill and treadmill â€‹+ â€‹BIBO3304 groups, as well as observed between the control and BIBO3304 groups. On the other hand, the expressions of Wnt3a and ß-catenin in the treadmill group were significantly lower compared with the other groups, while the expression in the BIBO3304 group was the highest, as evaluated by immunohistochemistry and western-blot. CONCLUSIONS: Early treadmill running increased the expression of NPY at the RC healing site, which might burden the expression of Wnt3a/ß-catenin and delay the healing process, inhibition of Y1 receptor with BIBO3304 could promote bone-tendon healing through the Wnt/ß-catenin signaling.The translational potential of this article: This is the first study to evaluate the specific role of the NPY-Y1R axis and its underlying mechanism by which early treadmill running delays bone-tendon healing. Further, our study may provide references of precise and individualized exercise-based rehabilitation strategies for TBI healing in clinic. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This is the first study to evaluate the specific role of the NPY-Y1R axis and its underlying mechanism by which early treadmill running delays bone-tendon healing. Further, our study may provide references of precise and individualized exercise-based rehabilitation strategies for TBI healing in clinic.

The antiviral drug efavirenz reduces biofilm formation and hemolysis by Staphylococcus aureus.

Introduction. Biofilm formation and hemolysis are closely related to the pathogenicity of Staphylococcus aureus.Hypothesis/Gap Statement. Strategies that reduce the mortality of S. aureus infections may involve novel antimicrobials and/or drugs that decrease S. aureus virulence, such as biofilm formation. The antiviral drug efavirenz is a non-nucleoside reverse transcriptase inhibitor, which also has shown antibacterial effect on Bacillus subtilis and Escherichia coli. Its effect on pathogen virulence has not yet been explored.Aim. This study investigates the antimicrobial and anti-virulence effect of efavirenz on S. aureus.Methodology. Biofilm biomasses were detected by crystal violet staining. Hemolysis activities of S. aureus were determined by rabbit erythrocytes lysis assay. RNA levels of transcriptional regulatory genes, biofilm-related genes, and virulence-related genes of S. aureus were determined by RT-qPCR.Results. Efavirenz showed an inhibitory effect on the growth of S. aureus, Enterococcus faecalis and Streptococcus agalactiae at 50 µM. Efavirenz significantly inhibited biofilm formation of both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) at 25 µM, but did not affect the growth of planktonic S. aureus cells. Moreover, hemolysis by S. aureus was inhibited by efavirenz at 25 µM. The expression levels of RNA transcriptional regulatory genes (agrA, agrC, sigB, saeR and saeS), biofilm-related genes (cidA, clfA, clfB, fnbA, fnbB), and virulence-related genes (hla, hld, staphopain B, alpha-3 PSM, beta PSM, delta PSM) of S. aureus decreased significantly at 25 µM efavirenz.Conclusion. Efavirenz inhibits S. aureus biofilm formation and virulence in vitro.

Antibacterial and anti-biofilm activities of histidine kinase YycG inhibitors against Streptococcus agalactiae.

This study aims to investigate the antibacterial and anti-biofilm activities of YycG inhibitors H2-60 and H2-81 against Streptococcus agalactiae. A total of 118 nonduplicate S. agalactiae clinical isolates were collected, and the minimal inhibitory concentrations (MICs) of H2-60 and H2-81 were determined. H2-60 and H2-81 inhibit biofilm formation of S. agalactiae were detected by crystal violet staining, and against established biofilms of S. agalactiae were observed by confocal laser scanning microscope. Inhibitory effect of H2-60 and H2-81 on the phosphorylation activity of the HisKA domain of YycG' protein was measured. The MIC50/MIC90 was 3.13/6.25 µM for H2-60 and 6.25/12.5 µM for H2-81 against S. agalactiae, respectively. S. agalactiae planktonic cells can be decreased by H2-60 or H2-81 for more than 3 × log10 CFU ml-1 after 24 h treatment. Biofilm formation of 8 S. agalactiae strains (strong biofilm producers) was significantly reduced after treated with 1/4 × MIC of H2-60 or H2-81 for 24 h. H2-60 and H2-81 could reduce 45.79% and 29.56% of the adherent cells in the established biofilm of S. agalactiae after 72 h treatment, respectively. H2-60 combined with daptomycin reduced 83.63% of the adherent cells in the established biofilm of S. agalactiae, which was significantly better than that of H2-60 (45.79%) or daptomycin (55.07%) alone. The half maximal inhibitory concentrations (IC50) were 35.6 µM for H2-60 and 46.3 µM for H2-81 against the HisKA domain of YycG' protein. In conclusion, YycG inhibitors H2-60 and H2-81 exhibit excellent antibacterial and anti-biofilm activities against S. agalactiae.

Enhanced Impact Properties of Hybrid Composites Reinforced by Carbon Fiber and Polyimide Fiber.

A series of hybrid fiber-reinforced composites were prepared with polyimide fiber and carbon fiber as the reinforcement and epoxy resin as the matrix. The influence of stacking sequence on the Charpy impact and flexural properties of the composites as well as the failure modes were studied. The results showed that hybrid fiber-reinforced composites yielded nearly 50% increment in Charpy impact strength compared with the ones reinforced by carbon fiber. The flexural performance was significantly improved compared with those reinforced solely by polyimide fibers and was greatly affected by the stacking sequence. The specimens with compressive sides distributed with carbon fiber possessed higher flexural strength, while those holding a sandwich-like structure with carbon fiber filling between the outer layers displayed a higher flexural modulus.

Calcitonin Gene-Related Peptide Influences Bone-Tendon Interface Healing Through Osteogenesis: Investigation in a Rabbit Partial Patellectomy Model.

BACKGROUND: Calcitonin gene-related peptide (CGRP), which has been shown to play an important role in osteogenesis during fracture repair, is also widely distributed throughout the tendon and ligament. Few studies have focused on the role of CGRP in repair of the bone-tendon interface (BTI). PURPOSE: To explore the effect of CGRP expression on BTI healing in a rabbit partial patellectomy model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 60 mature rabbits were subjected to a partial patellectomy and then randomly assigned to CGRP, CGRP-antagonist, and control groups. In the CGRP-antagonist group, the CGRP receptor antagonist BIBN4096BS was administered to block CGRP receptors. The patella-patellar tendon complex was harvested at 8 and 16 weeks postoperatively and subjected to radiographic, microlaser Raman spectroscopy, histologic, and biomechanical evaluation. RESULTS: Radiographic data showed that local CGRP expression improved the growth parameters of newly formed bone, including area and volumetric bone mineral density (P < .05 for both). Raman spectroscopy revealed that the relative bone mineral composition increased in the CGRP group compared with in the control group and the CGRP-antagonist group (P < .05 for both). Histologic testing revealed that the CGRP group demonstrated better integration, characterized by well-developed trabecular bone expansion from the residual patella and marrow cavity formation, at the 8- and 16-week time points. Mechanical testing demonstrated that the failure load, ultimate strength, and stiffness in the CGRP group were significantly higher than those in the control group (P < .05 for all), whereas these parameters in the CGRP-antagonist group were significantly lower compared with those in the control group at 16 weeks after surgery (P < .05 for all). CONCLUSION: Increasing the local concentration of CGRP in the early stages of BTI healing enhanced osteogenesis in a rabbit partial patellectomy model and promoted healing of the BTI injury, whereas treatment using a CGRP antagonist had the opposite effect. However, exogenous CGRP expression did not induce novel bone remolding. CLINICAL RELEVANCE: CGRP may have potential as a new therapy for BTI injuries or may be added to postoperative regimens to facilitate healing.