Modified Dautrey's Procedure for Recurrent Temporomandibular Joint Dislocation.

This study introduced and analyzed the clinical effects of a modified Dautrey's procedure, involving down-fracture of the zygomatic arch and articular tubercle augmentation, for the treatment of recurrent TMJ dislocation. Recurrent TMJ dislocation patients were treated using the modified Dautrey's procedure. The recurrence of joint dislocation, maximal mouth opening (MMO), and pain were evaluated postoperatively. A total of 7 patients were treated using the modified procedure, with no instances of facial nerve injury. No recurrences occurred during the follow-up period of 0.5 to 5 years. The average MMO was 35.4 mm and 35.7 mm before the operation and during follow-up, respectively. The modified Dautrey's procedure was effective and particularly suitable for elderly patients with abnormal muscle control, resulting in low recurrence.

Immunochromatographic assays based on three kinds of nanoparticles for the rapid and highly sensitive detection of tylosin and tilmicosin in eggs.

Three kinds of immunochromatographic assays (ICAs) are proposed for the highly sensitive and rapid determination  of tylosin (TYL) and tilmicosin (TIM) in eggs based on colloidal gold (CG), latex microsphere (LM), and time-resolved fluorescent microsphere (TRFM). Three types of ICAs could tolerate the egg matrix via simple sample pretreatment and demonstrated high sensitivity for TYL and TIM with cut-off values of 6/6/3 µg/kg and 14/14/6 µg/kg, respectively. Furthermore, in a single-blind parallel study 20 egg samples were analyzed  by the three developed ICAs and confirmed by LC-MS/MS. The  results showed good consistency, and there were no false positive and false negative results in our three ICAs. Consequently, the proposed three ICAs offered rapid, highly sensitive, reliable, and selectable testing platforms for screening veterinary medicine or other small molecule contaminants.

Morphologies Transformation of BODIPY-Based Main Chain Supramolecular Polymers Amphiphiles: From Helical Nanowires to Nanosheets.

The aggregate morphologies of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) main chain supramolecular polymer amphiphiles (SPA) are tunable by a fine balance of different non-covalent interactions. When the BODIPY segments and sodium cholate are mixed in aqueous solution, they form SPA by electrostatic attraction and hydrogen-bonds. This SPA displays helical nanowires' morphology. After the third component dimeric ß-cyclodextrin (ß-CD-C) is added, the hydrogen bonds between the cholate are substituted by the host-guest interaction between cholate and ß-CD-C. Therefore, these SPA transform their aggregate morphologies into nanosheets' architecture. Therefore, a simple and effective way to regulate self-assembly by non-covalent forces is developed. This supramolecular method may provide an effective way to prepare various nanostructures in aqueous solution and show promising application in the future.

Risk factors for developing osteonecrosis of jaw in advanced cancer patients underwent zoledronic acid treatment.

Aim: To investigate the risk factors for developing osteonecrosis of jaw (ONJ) in advanced cancer patients with bone metastases underwent zoledronic acid (ZA) treatment. Materials & methods: Univariate and multivariate logistic regression analyses were performed to investigate factors associated with developing ONJ in advanced cancer patients. Results: A total of 2214 advanced cancer patients were included. Univariate and multivariate logistic regression analyses for risk factors associated with ONJ were older age (≥66 years, hazards ratio [HR]: 3.21; p = 0.007), anemia (HR: 3.29; p = 0.006) and duration of ZA exposure (between 1 and 2 years, HR: 3.91, p = 0.01; ≥2 years, HR: 8.07, p < 0.001), respectively. Conclusion: Patients with older age, anemia and/or more than 1 year of ZA treatment are at high risk of developing ONJ.

Preparation and Pharmacokinetics Evaluation of Solid Self-Microemulsifying Drug Delivery System (S-SMEDDS) of Osthole.

The study was performed aiming to enhance the solubility and oral bioavailability of poorly water-soluble drug osthole by formulating solid self-microemulsifying drug delivery system (S-SMEDDS) via spherical crystallization technique. Firstly, the liquid self-microemulsifying drug delivery system (L-SMEDDS) of osthole was formulated with castor oil, Cremophor RH40, and 1,2-propylene glycol after screening various lipids and emulsifiers. The type and amount of polymeric materials, good solvents, bridging agents, and poor solvents in S-SMEDDS formulations were further determined by single-factor study. The optimal formulation contained 1:2 of ethyl cellulose (EC) and Eudragit S100, which served as matrix forming and enteric coating polymers respectively. Anhydrous ethanol and dichloromethane with a ratio of 5:3 are required to perform as good solvent and bridging agent, respectively, with the addition of 0.08% SDS aqueous solution as poor solvent. The optimized osthole S-SMEDDS had a high yield (83.91 ± 3.31%) and encapsulation efficiency (78.39 ± 2.25%). Secondly, osthole L-SMEDDS was solidified to osthole S-SMEDDS with no significant changes in terms of morphology, particle size, and zeta potential. In vitro release study demonstrated a sustained release of the drug from osthole S-SMEDDS. Moreover, in vivo pharmacokinetic study showed that the Tmax and mean residence time (MRT(0-t)) of osthole were significantly prolonged and further confirmed that osthole S-SMEDDS exhibited sustained release effect in rabbits. Comparing with osthole aqueous suspension and L-SMEDDS, osthole S-SMEDDS increased bioavailability by 205 and 152%, respectively. The results suggested that S-SMEDDS was an effective oral solid dosage form, which can improve the solubility and oral bioavailability of poorly water-soluble drug osthole.

Transdermal Delivery of Recombinant Human Growth Hormone by Liposomal Gel for Skin Photoaging Therapy.

Human growth hormone (hGH) has emerged as a promising therapeutic agent to prevent and treat skin photoaging. However, the success of hGH therapy largely lies in the availability of an optimal delivery system that enables the efficient delivery of hGH to the dermal layer of the skin. Here, we report a delivery system of hyaluronic acid/liposome-gel-encapsulated hGH (HA/HL-Gel) that can transdermally deliver hGH into the skin for hGH-based photoaging therapy through the upregulation of collagen type I (collagen-I). Specifically, hGH-liposomes were prepared by ethanol injection and then modified with HA to achieve specific targeting. The best formulation of HA/hGH-liposomes (HA/HL) had a high encapsulation efficiency (about 20%), with a size of 180 ± 1.2 nm. The optimized HA/HL was further incorporated into the carbomer gel to form an HA/HL-Gel. The biological activity of HA/HL on human dermal fibroblasts (HDFs) was confirmed by the elevated expression level of collagen-I through the enhanced local formation of insulin-like growth factor-1 (IGF-1) in the photoaging model. Moreover, HA/HL-Gel reduced ultraviolet (UV)-induced erythema and wrinkle formation. Meanwhile, immunohistochemical staining further showed higher levels of collagen-I in the HA/HL-Gel group compared to other groups tested. Taken together, these results demonstrate that HA/HL-Gel treatment could significantly ameliorate skin photoaging and thus may be used as a clinical potential for antiaging therapy.

Recent advances and clinical translation of liposomal delivery systems in cancer therapy.

The limitations of conventional cancer treatment are driving the emergence and development of nanomedicines. Research in liposomal nanomedicine for cancer therapy is rapidly increasing, opening up new horizons for cancer treatment. Liposomal nanomedicine, which focuses on targeted drug delivery to improve the therapeutic effect of cancer while reducing damage to normal tissues and cells, has great potential in the field of cancer therapy. This review aims to clarify the advantages of liposomal delivery systems in cancer therapy. We describe the recent understanding of spatiotemporal fate of liposomes in the organism after different routes of drug administration. Meanwhile, various types of liposome-based drug delivery systems that exert their respective advantages in cancer therapy while reducing side effects were discussed. Moreover, the combination of liposomal agents with other therapies (such as photodynamic therapy and photothermal therapy) has demonstrated enhanced tumor-targeting efficiency and therapeutic efficacy. Finally, the opportunities and challenges faced by the field of liposome nanoformulations for entering the clinical treatment of cancer are highlighted.

Mechanism Underlying Bacillus subtilis BS-Z15 Metabolite-Induced Prevention of Grain Contamination by Aspergillus flavus.

Aspergillus flavus can cause mildew in corn, peanuts, and other foods as well as animal feed, which seriously endangers human and livestock health; thus, preventing A. flavus contamination is imperative. Previous studies have found that the secondary metabolites of Bacillus subtilis BS-Z15 have broad-spectrum-inhibiting fungal activity, further confirming that the main active inhibiting fungal substance is Mycosubtilin (Myco). In this paper, corn and peanuts were treated with 0, 100, and 200 µg/mL BS-Z15 secondary metabolites (BS-Z15-SMA) for 7 days, and the aflatoxin contamination prevention effect was examined. The results showed that with increasing BS-Z15-SMA concentration, the aflatoxin contamination prevention effect was significantly enhanced. The above toxicity phenomena became more significant with extended BS-Z15-SMA treatment time. Scanning electron microscopy showed that 4 µg/mL Myco treatment resulted in a dented A. flavus surface and breakage of both the conidial stem and the mycelium. Transcriptome results showed that Myco significantly affected gene expression in A. flavus spores. The downregulated genes were significantly enriched in cell wall synthesis, transcription and translation, transmembrane transport pathways, and pathways related to key enzymes for aflatoxin synthesis. These results suggest that Myco could be used as a new bioactive material to prevent aflatoxin synthesis and contamination.

An enhanced immunochromatography assay based on colloidal gold-decorated polydopamine for rapid and sensitive determination of gentamicin in animal-derived food.

In this study, an enhancing immunochromatography assay (ICA) based on colloidal gold-decorated polydopamine (CG@PDA) was firstly developed for gentamicin in milk, muscle, liver and kidney simultaneously. CG@PDA was synthesized by one-pot method with better signal intensity, colloidal stability, and antibody coupling efficiency than traditional colloidal gold. The detection limit of the developed ICA was about 1.50 µg/kg for the four animal-derived food, which was up to 92-fold more sensitive than the reported ICA based on colloidal gold. The recovery rates were ranged from 86.0% to 114.0% with coefficient of variation between 1.6% and 13.1%. Parallel analysis of 40 samples by commercial ELISA kits was confirmed the reliability. Our research indicated that polydopamine decorated can chemically modify the surface of colloidal gold and can thus remarkably improve the detection performances of ICA.

Rainbow latex microspheres lateral flow immunoassay with smartphone-based device for simultaneous detection of three mycotoxins in cereals.

The coexistent pollution of multiple mycotoxins displays a synergistic toxicity effect that significantly threatens human health. Therefore, it is essential to establish a rapid detection method for multi-mycotoxins in food. In this study, red, green, and blue latex microspheres (LMs) were applied as the aflatoxin B1 (AFB1), T-2 toxins (T-2), and zearalenone (ZEN) antibodies labeled tracer, respectively. Based on the principle of spatial resolution, a rainbow "traffic light" pattern latex microspheres lateral flow immunoassay (LMs-LFIA) integrated with a portable and user-friendly smartphone-based device was first developed to detect three kinds of mycotoxins simultaneously. The cut-off values of the method for AFB1/T-2/ZEN in cereals were 1/15/40 µg kg-1, the limits of detection were 0.04/0.40/1.21 µg kg-1, respectively. The recoveries ranged from 82.1% to 107.5%, with the coefficient of variation from 3.0% to 8.1%. A parallel analysis in 26 naturally contaminated cereal samples was confirmed by commercial ELISA kits; the results showed a good correlation (R2＞0.99), indicating the practical reliability of the rainbow LMs-LFIA. This method provided a visually enjoyable, portable, and sensitive detection mode for multi-target detection of mycotoxins or other small molecule hazard factors in food.

Enterovirus A71 utilizes host cell lipid ß-oxidation to promote its replication.

Enterovirus A71 (EV-A71) is a major pathogen that causes severe and fatal cases of hand-foot-and-mouth disease (HFMD), which is an infectious disease that endangers children's health. However, the pathogenic mechanisms underlying these severe clinical and pathological features remain incompletely understood. Metabolism and stress are known to play critical roles in multiple stages of the replication of viruses. Lipid metabolism and ER stress is an important characterization post viral infection. EV-A71 infection alters the perturbations of intracellular lipid homeostasis and induces ER stress. The characterizations induced by viral infections are essential for optimal virus replication and may be potential antiviral targets. In this study, we found that the addition of the chemical drug of ER stress, PKR IN, an inhibitor, or Tunicamycin, an activator, could significantly reduce viral replication with the decrease of lipid. The replication of viruses was reduced by Chemical reagent TOFA, an inhibitor of acetyl-CoA carboxylase (ACC) or C75, an inhibitor of fatty acid synthase (FASN), while enhanced by oleic acid (OA), which is a kind of exogenous supplement of triacylglycerol. The pharmacochemical reagent of carnitine palmitoyltransferase 1 (CPT1) called Etomoxir could knock down CPT1 to induce EV-A71 replication to decrease. This suggests that lipid, rather than ER stress, is the main factor affecting EV-A71 replication. In conclusion, this study revealed that it is the ß-oxidation of lipid that plays a core role, not ER stress, which is only a concomitant change without restrictive effect, on virus replication.

A multiple environment-sensitive prodrug nanomicelle strategy based on chitosan graftomer for enhanced tumor therapy of gambogic acid.

A novel multiple environment-sensitive polymeric prodrug of gambogic acid (GA) based on chitosan graftomer was fabricated for cancer treatment. Folic acid-chitosan conjugates was complexed with thermosensitive amine terminated poly-N-isopropylacrylamide (NH2-PNIPAM) to develop FA-CSPN. Gambogic acid was conjugated with the graftomer via esterification to achieve high drug-loading capacity and controlled drug release. The resulting amphiphilic prodrug, O-(gambogic acid)-N-(folic acid)-N'-(NH2-PNIPAM) chitosan graftomer (GFCP), could self-assemble into micelles. As expected, the micelles were stable and biocompatible, featuring pH-, esterase- and temperature-dependent manner of drug release. Moreover, the anticancer effect studies of GFCP micelles were performed using a tumor-bearing mouse model and cellular assays (tumor cell uptake assay, cytotoxicity and tumor-sphere penetration). Collectively, GFCP micelles show both potential in vivo and in vitro in improving the anticancer effectiveness of GA owing to high loading capacity, targeted tumor accumulation, and multiple tumor microenvironmental responsiveness.

α-tubulin tail modifications regulate microtubule stability through selective effector recruitment, not changes in intrinsic polymer dynamics.

Microtubules are non-covalent polymers of αß-tubulin dimers. Posttranslational processing of the intrinsically disordered C-terminal α-tubulin tail produces detyrosinated and Δ2-tubulin. Although these are widely employed as proxies for stable cellular microtubules, their effect (and of the α-tail) on microtubule dynamics remains uncharacterized. Using recombinant, engineered human tubulins, we now find that neither detyrosinated nor Δ2-tubulin affect microtubule dynamics, while the α-tubulin tail is an inhibitor of microtubule growth. Consistent with the latter, molecular dynamics simulations show the α-tubulin tail transiently occluding the longitudinal microtubule polymerization interface. The marked differential in vivo stabilities of the modified microtubule subpopulations, therefore, must result exclusively from selective effector recruitment. We find that tyrosination quantitatively tunes CLIP-170 density at the growing plus end and that CLIP170 and EB1 synergize to selectively upregulate the dynamicity of tyrosinated microtubules. Modification-dependent recruitment of regulators thereby results in microtubule subpopulations with distinct dynamics, a tenet of the tubulin code hypothesis.

Cell Membrane-Inspired Polymeric Vesicles for Combined Photothermal and Photodynamic Prostate Cancer Therapy.

Photothermal therapy (PTT) and photodynamic therapy (PDT) have emerged as highly prospective therapeutic modalities in cancer therapy. Notwithstanding, a critical challenge still remains in the exploration of an effective strategy to maximize the synergistic efficacy of PTT and PDT due to low photoconversion efficiency. Herein, inspired by the phospholipid bimolecular structure of the cell membrane, bionic cell membrane polymeric vesicles with photothermal/photodynamic synergy for prostate cancer therapy at one wavelength's excitation are constructed in one step by the coordination of hexadecyl trimethyl ammonium bromide (CTAB) from the surface of hydrophobic gold nanorods (AuNRs) with indocyanine green (ICG) and polycaprolactone (PCL), achieving their self-assembly in aqueous solutions. Importantly, the aggregation of the assembly improves the stability of the vesicles, realizing the synergistic effect of PTT and PDT for prostate cancer therapy. After being assembled within polymeric vesicles, bifunctional photosensitizer ICG can generate reactive oxygen species (ROS) and photothermal effect under light treatment. Their ROS not only induce PDT efficacy but also destroy the integrity of the lysosomal membrane, promoting the translocation of ICG and another photosensitizer called gold nanorods (AuNRs) into the cytosol. Moreover, their photothermal effects produced by both photosensitizers are able to engender greater damage to the tumor cells because of the close distance with organelles. This structure manifests good cellular uptake, highly effective tumor accumulation, high photothermal conversion efficiency, and excellent properties of enhanced photobleaching resistance, which are beneficial to ICG-based fluorescence tumor imaging. Using the same near-infrared (NIR) wavelength for excitation, the AuNR/ICG vesicles can reduce the side effect rate of photodamage on the skin. In addition, by generating reactive oxygen species (ROS) and double photothermal effect, the vesicles under NIR excitation can promote the apoptosis of PC3 tumor cells. Taken together, the spontaneous self-assembled AuNR/ICG vesicles exhibit huge potential in advanced-stage prostate cancer therapy, especially for the prostate-specific membrane antigen (PSMA)-negative castration-resistant subtype.

The application of polyetheretherketone (PEEK) implants in cranioplasty.

Cranioplasty is a challenge to neurosurgeons, especially considering protection of intracranial contents. In recent years, material choice for cranioplasty is still controversial, which brings complexity to this seemingly straightforward procedure. PEEK, a tough, rigid, biocompatible material, has been used more recently in cranioplasty to provide better protection. The aim of this review is to summarize the outcome of research conducted on the material for cranioplasty applications. We also reviewed the comparison of PEEK with several common materials in previous articles. This is also the most complete data review article at present. In addition, the combination of nano-materials and PEEK is also a hotspot of research, so we have made a careful review of this aspect. We also summarized our own experience, telling about the future prospects of PEEK in the field of clinical cranioplasty should be highlighted. Improving the bioactivity, porosity, thinning, biocompatibility, antibacterial ability, integration and cost reduction of PEEK implants without affecting their mechanical properties is a major challenge.

A Phase II Study of Methotrexate, Etoposide, Dexamethasone and Pegaspargase Sandwiched with Radiotherapy in the Treatment of Newly Diagnosed, Stage IE to IIE Extranodal Natural-Killer/T-Cell Lymphoma, Nasal-Type.

BACKGROUND: A phase II study of methotrexate, etoposide, dexamethasone, and pegaspargase (MESA) sandwiched with radiotherapy for newly diagnosed, stage IE-IIE extranodal natural-killer/T-cell lymphoma, nasal-type (ENKTL) was conducted to explore its clinical efficacy and safety, as well as novel serum biomarkers upon anti-metabolic treatment. METHODS: Four cycles of MESA sandwiched with radiotherapy were administered. The primary end point was the overall response rate (ORR). Serum metabolomic profiles were assessed by liquid chromatography-mass spectrometry, with specific metabolites quantified by targeted metabolic analysis. FINDINGS: Forty patients were enrolled and the ORR was 92.1% (95%CI, 83.1%-100.0%). The 2-year progression-free survival (PFS) rate was 89.1% and overall survival (OS) rate was 92.0%. Grade 3/4 non-hematologic and hematologic toxicities were observed in 17 (42.5%) and 26 patients (65·0%) during chemotherapy, and in 9 (22.5%) and 0 (0.0%) patients during radiotherapy, respectively. Fifty-six significantly decreased and 59 increased metabolites were identified in ENKTL, as compared to healthy volunteers. A predictive principal components analysis model of asparaginase-associated metabolites, asparaginase-associated metabolic score (AspM), was established, including alanine, aspartate, glutamate, and succinic acid. Patients with high AspM score displayed superior survival and prognostic significance of AspM was validated in a historical cohort of early and advanced-stage ENKTL treated with asparaginase-based regimens. Multivariate analysis confirmed AspM as a prognostic score independent of PINK and PINK combined with Epstein-Barr virus DNA. INTERPRETATION: MESA sandwiched with radiotherapy is an effective and safe regimen for early-stage ENKTL. AspM score may be a promising prognostic index of serum metabolites in addition to clinical prognostic index in ENKTL.

Cotton fabric with plasma pretreatment and ZnO/Carboxymethyl chitosan composite finishing for durable UV resistance and antibacterial property.

ZnO/carboxymethyl chitosan (ZnO/CMCS) composite was prepared and confirmed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Ultraviolet-visible (UV-vis) spectroscopy, Scanning electron microscope (SEM), Transmission electron microscope (TEM). The combination of plasma pretreatment and ZnO/CMCS composite finishing was applied to provide durable UV resistance and antibacterial activity for cotton fabric. Cotton fabric was pretreated by cold oxygen plasma and the ZnO/CMCS composite finishing was carried out by pad-dry-cure. Cotton fabric was characterized by SEM, FTIR, UV resistance, antibacterial activity and Thermogravimetry (TG). SEM and FTIR analysis demonstrated the presence of ZnO/CMCS composite on cotton fabric and the increasing loading efficiency of ZnO/CMCS composite owing to plasma treatment. UV resistance and antibacterial activity of the finished cotton fabric were greatly improved, which increased with the increasing concentration of ZnO/CMCS composite. TG analysis indicated that the combined finishing of cotton fabric with plasma pretreatment and ZnO/CMCS composite could improve its thermal property. The finished cotton fabric exhibited an excellent laundering durability in UV resistance and antibacterial activity.

Highly Sensitive Colorimetric Detection of Ochratoxin A by a Label-Free Aptamer and Gold Nanoparticles.

A label-free aptamer-based assay for the highly sensitive and specific detection of Ochratoxin A (OTA) was developed using a cationic polymer and gold nanoparticles (AuNPs). The OTA aptamer was used as a recognition element for the colorimetric detection of OTA based on the aggregation of AuNPs by the cationic polymer. By spectroscopic quantitative analysis, the colorimetric assay could detect OTA down to 0.009 ng/mL with high selectivity in the presence of other interfering toxins. This study offers a new alternative in visual detection methods that is rapid and sensitive for OTA detection.