Vancomycin-Loaded Sol-Gel System for In Situ Coating of Artificial Bone to Prevent Surgical Site Infections.

Surgical site infections (SSIs) related to implants have always been a major challenge for clinical doctors and patients. Clinically, doctors may directly apply antibiotics into the wound to prevent SSIs. However, this strategy is strongly associated with experience of doctors on the amount and the location of antibiotics. Herein, an in situ constructable sol-gel system is developed containing antibiotics during surgical process and validated the efficacy against SSIs in beagles. The system involves chitosan (CS), ß-glycerophosphate (ß-GP) and vancomycin (VAN), which can be adsorbed onto porous hydroxyapatite (HA) and form VAN-CS/ß-GP@HA hydrogel in a short time. The VAN concentration from VAN-CS/ß-GP@HA hydrogel is higher than minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) at the 21st day in vitro. In an in vivo canine model for the prevention of SSIs in the femoral condyle, VAN-CS/ß-GP@HA exhibits excellent biocompatibility, antimicrobial properties, and promotion of bone healing. In all, the CS/ß-GP instant sol-gel system is able to in situ encapsulate antibiotics and adhere on artificial bone implants during the surgery, effectively preventing SSIs related to implants.

Surface-Activated Ti3C2Tx Adsorption of Acetylene Black Coupled with Polyaniline as a Signal Tag for the Detection of the ESAT-6 Antigen of Mycobacterium tuberculosis.

Early secretory antigenic target-6 (ESAT-6) is regarded as the most immunogenic protein produced by Mycobacterium tuberculosis, whose detection is of great clinical significance for tuberculosis diagnosis. However, the detection of the ESAT-6 antigen has been hampered by the expensive cost and complex experimental procedures, resulting in low sensitivity. Herein, we developed a titanium carbide (Ti3C2Tx)-based aptasensor for ESAT-6 detection utilizing a triple-signal amplification strategy. First, acetylene black (AB) was immobilized on Ti3C2Tx through a cross-linking reaction to form the Ti3C2Tx-AB-PAn nanocomposite. Meanwhile, AB served as a conductive bridge, and Ti3C2Tx can synergistically promote the electron transfer of PAn. Ti3C2Tx-AB-PAn exhibited outstanding conductivity, high electrochemical signals, and abundant sites for the loading of ESAT-6 binding aptamer II (EBA II) to form a novel signal tag. Second, N-CNTs were adsorbed on NiMn layered double hydride (NiMn LDH) nanoflowers to obtain NiMn LDH/N-CNTs, exhibiting excellent conductivity and preeminent stability to be used as electrode modification materials. Third, the biotinylated EBA (EBA I) was immobilized onto a streptavidin-coated sensing interface, forming an amplification platform for further signal enhancement. More importantly, as a result of the synergistic effect of the triple-signal amplification platform, the aptasensor exhibited a wide detection linear range from 10 fg mL-1 to 100 ng mL-1 and a detection limit of 4.07 fg mL-1 for ESAT-6. We envision that our aptasensor provides a way for the detection of ESAT-6 to assist in the diagnosis of tuberculosis.

A self-assembling peptide inhibits the growth and function of fungi via a wrapping strategy.

Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC50 = 3.5 µM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 µM, better than fluconazole (17.2% at 1 µM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.

[Application characteristics and modern research progress of "bone-approaching" acupuncture].

The paper explores the evolution of "bone-approaching" acupuncture, its effect target and mechanism. The concrete operation procedure of "bone-approaching" method is recorded originally in Huangdi Neijing (Inner Canon of Yellow Emperor) as short needling and Shu needling (referring to the category of the five needling technique). The periosteum is the most effective stimulation target of "bone-approaching" acupuncture for analgesia, regaining consciousness and regulating spirit. The "bone-approaching" acupuncture is not only prominently effective on bone bi syndrome, but also has the unique effect on painful, encephalogenic and emotional diseases. The paper summarizes and improves "bone-approaching" acupuncture, i.e. "touching bone surface" with needle tip by slow insertion, "touching bone surface" without pain by swift insertion and "touching bone" with needle body by oblique insertion. It contributes to the inheritance, development and supplementation to the bone needling techniques in Huangdi Neijing and is significant for broadening the clinical application range of acupuncture.

Entangling of Peptide Nanofibers Reduces the Invasiveness of SARS-CoV-2.

The viral spike (S) protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells, facilitating its entry and infection. Here, functionalized nanofibers targeting the S protein with peptide sequences of IRQFFKK, WVHFYHK and NSGGSVH, which are screened from a high-throughput one-bead one-compound screening strategy, are designed and prepared. The flexible nanofibers support multiple binding sites and efficiently entangle SARS-CoV-2, forming a nanofibrous network that blocks the interaction between the S protein of SARS-CoV-2 and the ACE2 on host cells, and efficiently reduce the invasiveness of SARS-CoV-2. In summary, nanofibers entangling represents a smart nanomedicine for the prevention of SARS-CoV-2.

Ophthalmic Solution of Smart Supramolecular Peptides to Capture Semaphorin 4D against Diabetic Retinopathy.

Diabetic retinopathy (DR) is the leading cause of vision loss in working age population. Intravitreal injection of anti-VEGF antibody is widely used in clinical practice. However, about 27% of patients show poor response to anti-VEGF therapy and about 50% of these patients continue to have macular thickening. Frequent intravitreal injections of antibody may increase the chance of endophthalmitis and cause visual loss or even blindness once happened. Therefore, there is a greatly urgent need for novel noninvasive target to treat DR clinically. Here, the formulation of a smart supramolecular peptide (SSP) eye drop for DR treatment that is effective via specifically identifying and capturing soluble semaphorin 4D (sSema4D), a strongly pro-angiogenesis and exudates factor, is reported. The SSP nanostructures encapsulate sSema4D so that all biological effects mediated by three receptors of sSema4D are inhibited, thereby significantly alleviating pathological retinal angiogenesis and exudates in DR. Moreover, it is found that combination of SSPs eye drop and anti-VEGF injection shows better therapeutic effect over anti-VEGF treatment alone. Overall, SSP eye drop provide an alternative and effective method for noninvasive treatment for DR.

Light-Triggered Self-Assembly of Peptide Nanoparticles into Nanofibers in Living Cells through Molecular Conformation Changes and H-Bond Interactions.

Controlled self-assembly has attracted extensive interest in biological and nanotechnological applications. Enzymatic or biocatalytic triggered self-assembly is widely used for the diagnostic and prognostic marker in different pathologies because of their nanostructures and biological effects. However, it remains a great challenge to control the self-assembly of peptides in living cells with a high degree of spatial and temporal precision. Here we demonstrate a light-triggered platform that enables spatiotemporal control of self-assembly from nanoparticles into nanofibers in living cells through subtle molecular conformational changes and internal H-bonding interactions. The platform contained 3-methylene-2-(quinolin-8-yl) isoindolin-1-one, which acts as the light-controlled unit to disrupt the hydrophilic/lipophilic balance through the change of molecular conformation, and a peptide that can be a faster recombinant to assemble via H-bonding interactions. The process has good biocompatibility because it does not involve waste generation or oxygen consumption; moreover, the assembly rate constant was fast and up to 0.17 min-1. It is applied to the regulation of molecular assembly in living cells. As such, our findings demonstrate that light-triggered controllable assembly can be applied for initiative regulating cellular behaviors in living systems.

Potential of Forsythoside I as a therapeutic approach for acute lung injury: Involvement of TXNIP/NLRP3 inflammasome.

OBJECTIVE: To explore the role of Forsythoside I (FI) in acute lung injury (ALI) mouse and its underling mechanism. METHODS: The cell models of ALI are constructed by LPS induction. After pretreatment with different concentrations of FI, the lung injury is assessed by pathological changes of lung tissues and cell apoptosis. The cell viability, levels of pro-inflammatory cytokines, and the activation of TXNIP/NLRP3 pathway are inspected to investigate whether the effect of FI on inflammatory response is exerted by regulating the TXNIP/NLRP3 pathway. RESULTS: LPS induces inflammatory cell infiltration, tissue necrosis and pulmonary interstitial edema of mouse tissues, and LPS increases the protein concentration and levels of pro-inflammatory factors in mouse BALF. Additionally, enhanced cell apoptotic level, increased W/D ratio and MPO activity, as well as suppressed SOD activity are observed in LPS-induced mouse models. Those inflammation response, oxidative stress and lung injury can be attenuated by FI (12.5 mg/kg, 25 mg/kg, 50 mg/kg) in a dose-dependent manner. Meanwhile, both in vitro and in vivo studies reveal that FI can lead to suppressed TXNIP expression and inactivated NLRP3 inflammasomes. TXNIP is an upstream target of NLRP3, and FI mitigates ALI by decreasing TXNIP to block NLRP3 inflammasomes. CONCLUSION: FI protects against ALI through the mediation of TXNIP/NLRP3 inflammasome axis and therefore has a certain potential for ALI treatment.

Atom-Economic Silver-Catalyzed Difunctionalization of the Isocyano Group with Cyclic Oximes: Towards Pyrimidinediones.

An unprecedented silver-catalyzed difunctionalization of the isocyano group with cyclic oximes is described. This method allows efficient and atom-economic assembly of a vast array of structurally novel and interesting pyrimidinediones, and tolerates a range of functionalities. The resulting products can be easily converted into some useful compounds. Furthermore, the method can also be applied for the late-stage modification of a few biologically active molecules.

Spirocyclic Sultam and Heterobiaryl Synthesis through Rh-Catalyzed Cross-Dehydrogenative Coupling of N-Sulfonyl Ketimines and Thiophenes or Furans.

A useful approach is developed for the synthesis of various structurally interesting spirocyclic sultams and heterobiaryls using a cross-dehydrogenative coupling strategy that features high atom and step economy. This method employs [Cp*RhCl2]2 as a catalyst and N-sulfonylimine, a weak coordinating group, as an efficient directing group to assist C-H activation. A number of the coupled products were converted into interesting molecules through further synthetic transformations.

Selective remote C-H sulfonylation of aminoquinolines with arylsulfonyl chlorides via copper catalysis.

Copper-catalysed direct C-H bond sulfonylation of aminoquinolines using commercially available and inexpensive arylsulfonyl chlorides as the sulfonylation reagents is described. The reactions took place exclusively at the C5-H position of the quinoline rings and tolerated a wide spectrum of functional groups. Moreover, synthetic transformations of the sulfonylated products led to useful compounds.

Effects of Successive Rotation Regimes on Carbon Stocks in Eucalyptus Plantations in Subtropical China Measured over a Full Rotation.

Plantations play an important role in carbon sequestration and the global carbon cycle. However, there is a dilemma in that most plantations are managed on short rotations, and the carbon sequestration capacities of these short-rotation plantations remain understudied. Eucalyptus has been widely planted in the tropics and subtropics due to its rapid growth, high adaptability, and large economic return. Eucalyptus plantations are primarily planted in successive rotations with a short rotation length of 6~8 years. In order to estimate the carbon-stock potential of eucalyptus plantations over successive rotations, we chose a first rotation (FR) and a second rotation (SR) stand and monitored the carbon stock dynamics over a full rotation from 1998 to 2005. Our results showed that carbon stock in eucalyptus trees (TC) did not significantly differ between rotations, while understory vegetation (UC) and soil organic matter (SOC) stored less carbon in the SR (1.01 vs. 2.76 Mg.ha(-1) and 70.68 vs. 81.08 Mg. ha(-1), respectively) and forest floor carbon (FFC) conversely stored more (2.80 vs. 2.34 Mg. ha(-1)). The lower UC and SOC stocks in the SR stand resulted in 1.13 times lower overall ecosystem carbon stock. Mineral soils and overstory trees were the two dominant carbon pools in eucalyptus plantations, accounting for 73.77%~75.06% and 20.50%~22.39%, respectively, of the ecosystem carbon pool. However, the relative contribution (to the ecosystem pool) of FFC stocks increased 1.38 times and that of UC decreased 2.30 times in the SR versus FR stand. These carbon pool changes over successive rotations were attributed to intensive successive rotation regimes of eucalyptus plantations. Our eight year study suggests that for the sustainable development of short-rotation plantations, a sound silvicultural strategy is required to achieve the best combination of high wood yield and carbon stock potential.

Redox-neutral palladium-catalyzed C-H functionalization to form isoindolinones with carboxylic acids or anhydrides as readily available starting materials.

An operationally simple, Pd-catalyzed C-H functionalization is described for the synthesis of important and useful isoindolinones from readily available carboxamides and carboxylic acids or anhydrides. The reactions proceed efficiently with a broad range of substrates under redox-neutral reaction conditions and tolerate a diversity of functional groups. The mechanistic investigation suggests that the reactions involve C-H activation, nucleophilic addition, ß-O elimination, and dehydration steps.

[Understory vegetation composition and main woody population niche of artificial masson pine forest in south subtropical area].

This paper studied the characteristics of the natural understory vegetation in the artificial masson pine forest replanted after Chinese fir cut for 13 years. The results indicated that there were 100 species of understory vegetation, including 74 species of shrub or small arbor, accounting for 74.0% of the total species, belonging to 41 faculties and 63 categories, and 26 herbs belonging to 14 faculties and 23 categories. The tropical and subtropical elements were dominant in the vegetation, while the temperate ones were scare. The species diversity and richness were decreased after masson pine regenerated from Chinese fir. The analysis of important value showed that the main species of shrub or small arbor were Tinomiscium tonkinensis, Mycetia longiflora, Evodia lepta, Paederia scandens, Mussaenda pubuscens, Actinodaphne pilosa and Quercus glauca, and those of herb were Cyrtococcum patens, Blechnunm orientale, Dicranopteris dichotoma, Adiantum flabellulatum, Adiantum edgeworthii and Pteris semipinnata. The biomass of the vegetation in different slope positions was decreased in order of upside> downside > middle part. There was a significantly positive correlation between the niche breath and the important value of main woody population. The important values of woody populations were higher than those of the others, and their niche breadths were also larger, which meant that they were more adaptable to the habitat. The niche overlaps of six population counterparts Tinomiscium tonkinensis-Mycetia longiflora, Tinomiscium tonkinensis-Evodia lepta, Mussaenda pubuscens-Maesa japonica, Quercus glauca-Aphananthe aspera, Actinodaphne pilosa-Saraca chinensis and Evodia lepta-Quercus glaucathese were very large, which could offer information for the restoration and reconstruction in selecting natural vegetation. The large niche overlaps of major woody population counterparts suggested their similar utilization of natural resources.