Ultrafine electro-optical frequency comb based on cascade phase modulation with cyclic frequency shifting.

An ultrafine electro-optical frequency comb (EOFC) with plentiful comb teeth is demonstrated. Adopting a single-frequency fiber laser as a light source, cascade phase modulation based on a sinusoidal signal and a frequency-time transformation (FTT) signal is executed to generate the EOFC with high fineness. Meanwhile, a cyclic fast frequency shifting strategy is introduced to boost the number of comb teeth and the bandwidth of the EOFC. As a result, an EOFC with 12600 comb lines covering a broad bandwidth from -6.3 GHz to 6.3 GHz is established, corresponding to an ultrafine comb space of 1 MHz. Moreover, the power fluctuation of a comb tooth is less than 0.5 dBm. This state-of-the-art EOFC has significant potential in the field of precision spectroscopy.

Widespread Occurrence and Transport of p-Phenylenediamines and Their Quinones in Sediments across Urban Rivers, Estuaries, Coasts, and Deep-Sea Regions.

p-Phenylenediamines (PPDs) are widely used as antioxidants in tire rubber, and their derived quinone transformation products (PPD-Qs) may pose a threat to marine ecosystems. A compelling example is N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD)-derived quinone, called 6PPD-Q, as the causal toxicant for stormwater-linked acute mortality toward coho salmon. However, the knowledge of the co-occurrences of PPDs and PPD-Qs and their transport from freshwater to oceanic waterbodies on a large geographical scale remains unknown. Herein, we performed the first large-scale survey of these chemicals in sediments across urban rivers, estuaries, coasts, and deep-sea regions. Our results demonstrated that seven PPDs and four PPD-Qs are ubiquitously present in riverine, estuarine, and coastal sediments, and most of them also occur in deep-sea sediments. The most dominant chemicals of concern were identified as 6PPD and 6PPD-Q. Total sedimentary concentrations of PPDs and PPD-Qs presented a clear spatial trend with decreasing levels from urban rivers (medians: 39.7 and 15.2 ng/g) to estuaries (14.0 and 5.85 ng/g) and then toward coasts (9.47 and 2.97 ng/g) and deep-sea regions (5.24 and 3.96 ng/g). Interestingly, spatial variation in the ratios of 6PPD to 6PPD-Q (R6PPD/6PPD-Q) also presented a clear decreasing trend. Our field measurements implied that riverine outflows of PPDs and PPD-Qs may be an important route to transport these tire rubber-derived chemicals to coastal and open oceans.

Glycopolymer Nanoparticles with On-Demand Glucose-Responsive Insulin Delivery and Low-Hypoglycemia Risks for Type 1 Diabetic Treatment.

Diabetic patients with type 1 or advanced type 2 stages need timely and precise insulin injection to regulate the daily blood glucose levels (BGLs). Otherwise, risks of serious or even deadly diabetes-associated complications occur. To achieve prolonged glucose regulation and low hypoglycemia risks, a novel on-demand glucose-responsive glycopolymer system was constructed for insulin delivery, which was self-assembled into nanoparticles by dynamic covalent bonds between two polymers: fluorophenylboronic acid-grafted polymer (poly-F) and polyol polymer (poly-G). Insulin was loaded during the assembly process. The nanoparticles showed excellent glucose responsiveness in vitro, with controlled insulin release at different glucose concentrations. In vivo treatment on type 1 diabetic mice showed prolonged BGL regulation and lower hypoglycemia risks. The mild preparation of the nanoparticles and outstanding glucose control shed light on the optional diabetic treatment for further clinical use.

NIR Activated Upper Critical Solution Temperature Polymeric Micelles for Trimodal Combinational Cancer Therapy.

The balance between drug efficiency and its side effects on normal tissues is still a challenging problem to be solved in current cancer therapies. Among different strategies, cancer therapeutic methods based on nanomedicine delivery systems have received extensive attention due to their unique advantages such as improved circulation and reduced toxicity of drugs in the body. Herein, we constructed dual-responsive polymeric micelles DOX&ALS@MFM based on an upper critical solution temperature (UCST) polymer to simultaneously combine chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT). Amphiphilic block copolymer P(AAm-co-AN)-b-PEI-ss-PEG-FA with a critical point of 42 °C was able to self-assemble into polymeric micelles under physiological conditions, which further encapsulated anticancer drug doxorubicin (DOX) and photosensitizer ALS to obtain drug-loaded micelles DOX&ALS@MFM. Micelles aggregated at tumor sites due to folate targeting and an enhanced permeability retention (EPR) effect. After that, the high intracellular concentration of glutathione (GSH) and near-infrared (NIR) light prompted disassembly of the polymer to release DOX and ALS. ALS not only plays a role in PTT but also produces singlet oxygen, therefore killing tumor cells by PDT. Both in vitro and in vivo studies demonstrated the photothermal conversion and reactive oxygen species generation ability of DOX&ALS@MFM micelles, at the same time as the excellent inhibitory effect on tumor growth with NIR light irradiation. Thus, our research substantiated a new strategy for the biomedical application of UCST polymers in the cited triple modal tumor therapy.

Cervical metastasis of gingival carcinoma misdiagnosed as branchiogenic carcinoma, a rare entity - report of a case and review of literature.

BACKGROUND: A cervical cystic mass is associated with a number of pathologies that present with similar symptoms. These conditions are difficult to differentiate using fine-needle aspiration (FNA), ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI). Another dilemma in the differential diagnosis of cervical cystic masses is due to the controversies associated with the existence of branchiogenic carcinoma (BC). BC is an extremely rare disease that must be differentiated from other conditions presenting with cervical cystic masses, especially cystic metastasis from occult primary lesions. CASE PRESENTATION: We present a case report of a right cervical cystic metastasis from a significantly small squamous cell carcinoma primary gingival lesion misdiagnosed as BC by histopathology. A 62-year-old female presented with a painless progressively enlarging cervical mass at the anterior edge of the sternocleidomastoid muscle in the right submandibular region. Preoperative MRI and US revealed a well-defined cystic round mass. Postoperative histological examination indicated BC. Positron emission tomography/computed tomography (PET/CT) revealed high 18F-FDG (18F 2-fluoro-2-deoxy-D-glucose) uptake in surgical regions with a SUV (standard uptake value) max 4.0 and ipsilateral nasopharynx with a SUVmax 4.4, without any distant metastasis. Pathologic results revealed nasopharyngeal lymphadenosis. Considering the low incidence of BC and the limitation of diagnosis in one institution, the patient was referred to another hospital. Physical examination detected a significantly small neoplasm (~3 mm diameter) in the right lower gingiva. Histopathological examination of the neoplasm revealed a well-differentiated squamous cell carcinoma. Surgery, including a partial mandibulectomy and modified neck dissection (neck level I-V and submental lymph nodes) were undertaken. Postoperative histopathological results revealed a well-differentiated squamous cell carcinoma of right lower gingiva and two metastatic lymph nodes in the 18 lymph nodes of level II. A month later, recurrence occurred in the right cervical level II. The patient was placed on postoperative concurrent chemo-radiotherapy and supportive care. The patient suffered from cachexia and survived for only six months after surgery. CONCLUSIONS: In cases of cervical cystic masses that appear after the age of 40, clinicians should bear in mind that occult primary lesions should be excluded and examination of the gingiva should be undertaken. PET/CT has a limited role in identifying small occult primary lesions and a comprehensive physical examination must be carefully performed.

Speech Acoustic Parameters for Predicting Presbyphagia: A Preliminary Study in the Elderly Shanghainese Population.

PURPOSE: Age is a high-risk factor for dysphagia. Speech and swallowing share the same anatomical and neurophysiological basis. Their functions are closely related; hence, speech assessment can predict the risk of dysphagia. This study aimed to investigate the factors influencing presbyphagia in a normal elderly Shanghainese population by analyzing speech acoustic parameters. METHODS: Relevant speech acoustic parameters were compared between 15 people with dysphagia and 15 without dysphagia. After extracting sensitive speech acoustic parameters related to swallowing, changes in sensitive parameters were compared at different ages to analyze the relevant factors influencing presbyphagia in the normal elderly population. RESULTS: Eight speech acoustic parameters related to swallowing, including maximum phonation time (MPT), max F0, /ʔʌ/Jitter, /ʔʌ/L-DDK, /hʌ/L-DDK, /pataka/DDK, F1/a/, and vowel space area, were extracted after comparing the relevant data between the two groups. Analyzing the changes in each of these parameters between different age groups (age 18-39, 40-64, and 65 and above), we discovered that three speech acoustic parameters, including MPT, /hʌ/L-DDK, and /pataka/DDK, had statistical differences, with a decreasing trend in their mean values with increasing age. CONCLUSIONS: The elderly group had significantly lower MPT, /hʌ/L-DDK, and /pataka/DDK than the young and middle-aged groups. We hypothesized that reduced respiratory support and control, decreased range of mouth movements and coordination, closed control of the vocal cords, and inadequate airflow control in vocal cord abduction are risk factors for presbyphagia in the elderly Shanghainese population.

Auricular reconstruction using Medpor combined with different hearing rehabilitation approaches for microtia.

BACKGROUND: Congenital microtia-atresia affects patients in two specific ways: severe conductive hearing loss and difficulty in integrating into social environments due to auricle malformation. AIMS/OBJECTIVES: To investigate the safety and efficacy of single-stage auricular reconstruction and hearing rehabilitation in children with microtia and external auditory canal atresia. MATERIAL AND METHODS: From January 2016 to December 2019, we included 32 patients with microtia and external canal atresia who received auricle reconstruction with high-density polyethylene (Medpor) framework and three different hearing rehabilitation approaches at the Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. Twenty patients underwent the traditional external auditory canal and middle ear repair (EACR), eight patients were implanted with Bonebridge (BB) devices, and four patients were implanted with bone-anchored hearing aid (BAHA) in one stage. Postoperative changes in auricle morphology and hearing and speech recognition and occurrence of complications were evaluated. RESULTS: After 6-24 months of follow-up, the auricle shape recovered well in all three groups, and the average score of 14 fine structures in the auricle was 9.43 (EACR), 10.67 (BB), and 9.75 (BAHA) points. The average score of auricle symmetry was 6.83 (EACR), 6.00 (BB), and 6.44 (BAHA) points. No significant differences in auricle shape were observed among the three groups (p > .05). After surgery, the average hearing improvement in the BB group was 43.33 dB, and the average speech recognition threshold declined to 42.28 dB. In the BAHA group, the average hearing improvement was 35 dB, and the average speech recognition threshold declined to 33.5 dB, similar to that of the BB group. However, in the EACR group, the average hearing improvement was only 4.13 dB, and the average speech recognition threshold declined to 11.36 dB. No vertigo, tinnitus, cerebrospinal fluid leakage, facial nerve paralysis, osseointegration failure, and other complications occurred in all the patients. In the EACR group, auricle stent fracture, ear canal restenosis, and canal atresia occurred in one patient each. In the BAHA group, two patients developed local ear infections. CONCLUSIONS AND SIGNIFICANCE: The procedure of single-stage auricular reconstruction and hearing rehabilitation for microtia is feasible and effective. The appropriate method of hearing reconstruction should be determined by evaluating the development of the inner and middle ear of the patients. For those patients with poor development of the mastoid and ossicular chain, hearing aid devices are recommended to achieve a stable and significant hearing effect.

In vitro and in vivo Evaluation of a Novel Estrogen-Targeted PEGylated Oxaliplatin Liposome for Gastric Cancer.

BACKGROUND: Chemotherapy is still the main first-line treatment for advanced metastatic gastric cancer, but it has the limitations of serious side effects and drug resistance. Conventional liposome has been substantially used as drug carriers, but they lack targeting character with lower drug bioavailability in tumor tissues. Based on the above problems, a novel estrogen-targeted PEGylated liposome loaded with oxaliplatin (ES-SSL-OXA) was prepared to further improve the metabolic behavior, the safety profile, and the anti-tumor efficacy of oxaliplatin. METHODS: Four kinds of oxaliplatin (OXA) liposomes were prepared by film hydration method. The obtained formulations were characterized in terms of entrapment efficiency (EE), particle size, and so on by HPLC and DLS (dynamic light scanning). The morphology of ES-SSL-OXA was detected by transmission electron microscope (TEM). The in vitro and in vivo targeting effect of ES-SSL-OXA was verified by fluorescence microscopy and in vivo imaging system in gastric cancer cells (SGC-7901) and tumor-bearing athymic mice. The in vitro and in vivo antitumor efficacies of ES-SSL-OXA were investigated on SGC-7901 cells and athymic tumor-bearing mice. Pharmacokinetic, biodistribution, and acute toxicity tests of ES-SSL-OXA were performed on ICR mice. RESULTS: The ES-SSL-OXA exhibited an average particle size of about 153.37 nm with an encapsulation efficiency of 46.20% and low leakage rates at 4°C and 25°C. In vivo and in vitro targeting study confirmed that ES-SSL-OXA could effectively target the tumor site. The antitumor activity demonstrated the strongest inhibition in tumor growth of ES-SSL-OXA. Pharmacokinetics and acute toxicity study showed that ES-SSL-OXA could significantly improve the metabolic behavior and toxicity profile of oxaliplatin. CONCLUSION: In this study, a novel estrogen-targeted long-acting liposomal formulation of OXA was successfully prepared. ES fragment effectively targeted the delivery system to tumor tissues which highly express estrogen receptor, providing a promising therapeutic method for gastric cancer in clinic.

Estrone-targeted liposomes for mitoxantrone delivery via estrogen receptor: In vivo targeting efficacy, antitumor activity, acute toxicity and pharmacokinetics.

Estrogen receptor (ER) is a potential target receptor for ER-positive cancer therapy including breast cancers, gastric cancers, and human acute myeloblastic leukaemia. In order to reduce the side-effects of mitoxantrone (MTO), estrone-targeted liposomes for MTO delivery via ER were designed for selectively targeting cancer cells. In previous studies, MTO-loaded estrogen receptor targeted and sterically stabilized liposome (ES-SSL-MTO; ES: estrone, is known to bind the ER) had been synthesized and showed a very high antiproliferative effect with IC50 value of 0.7 ng/mL. Based on these, further studies including in vivo targeting efficacy and antitumor activity, acute toxicity and pharmacokinetics of MTO liposomes were carried out. The results showed SSL (sterically stabilized liposome, PEGylated liposome, PEG: Polyethylene Glycol) could reduce drug metabolism, improve the stability of liposomes, prolong in vivo circulation time of drugs, reduce the toxicity of MTO. But SSL could not be enriched in tumor tissues. However, estrone (ES)-targeted liposomes could be delivered to tumor sites. ES-SSL could effectively enter into ER-expressing tumor cellsand be accumulated, prolong the circulation time in vivo, reduce side effects of drug. ES-SSL-MTO could provide higher bioavailability than MTO, enhance the anti-tumor effect and the safety of MTO, reduce the toxicity and side effects of MTO and improve the therapeutic effect of MTO. These facts proved ES-SSL is a useful tumor-targeting drug delivery system for MTO.

Preparation, Characterization, and Pharmacokinetic Study of a Novel Long-Acting Targeted Paclitaxel Liposome with Antitumor Activity.

BACKGROUND: Breast cancer is the leading cause of cancer death in women. Chemotherapy to inhibit the proliferation of cancer cells is considered to be the most important therapeutic strategy. The development of long-circulating PEG and targeting liposomes is a major advance in drug delivery. However, the techniques used in liposome preparation mainly involve conventional liposomes, which have a short half-life, high concentrations in the liver and spleen reticuloendothelial system, and no active targeting. METHODS: Four kinds of paclitaxel liposomes were prepared and characterized by various analytical techniques. The long-term targeting effect of liposomes was verified by fluorescence detection methods in vivo and in vitro. Pharmacokinetic and acute toxicity tests were conducted in ICR mice to evaluate the safety of different paclitaxel preparations. The antitumor activity of ES-SSL-PTX was investigated in detail using in vitro and in vivo human breast cancer MCF-7 cell models. RESULTS: ER-targeting liposomes had a particle size of 137.93±1.22 nm and an acceptable encapsulation efficiency of 88.07±1.25%. The liposome preparation is best stored at 4°C, and is stable for up to 48 hrs. Cytotoxicity test on MCF-7 cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. We used the near-infrared fluorescence imaging technique to confirm that ES-SSL-PTX was effectively targeted and could quickly and specifically identify the tumor site. Pharmacokinetics and acute toxicity in vivo experiments were carried out. The results showed that ES-SSL-PTX could significantly prolong the half-life of the drug, increase its circulation time in vivo, improve its bioavailability and reduce its toxicity and side effects. ES-SSL-PTX can significantly improve the pharmacokinetic properties of paclitaxel, avoid allergic reaction of the original solvent, increase antitumor efficacy and reduce drug toxicity and side effects. CONCLUSION: ES-SSL-PTX has great potential for improving the treatment of breast cancer, thereby improving patient prognosis and quality of life.

Plastic debris in marine birds from an island located in the South China Sea.

Plastic debris has become one of the most serious issues in the marine environment, but little information is available on the occurrence of plastic debris in marine birds from China. In this study, one seabird species and two shorebird species were collected from Yongxing Island of South China Sea to investigate the accumulation of plastic debris. A total of 56 items of plastic debris were observed in 4 of 9 birds, with size ranging from 0.67 to 8.64 mm. Microplastics (<5 mm, 52 items) accounted for 92.9% of the total items. The main color of plastic debris in marine birds was blue (91.1%), followed by dark (5.4%) and white (3.6%). The primary shape of plastic debris was thread (89.2%), followed by sheet (8.9%) and foam (1.8%). Plastic fragments were predominated by polypropylene-polyethylene copolymer (83.9%). This study highlighted that marine birds can mistake plastic debris as food items.

Sorption and desorption of phenanthrene on biodegradable poly(butylene adipate co-terephtalate) microplastics.

Biodegradable plastics, as alternatives to conventional plastics, are increasingly used, but their interactions with organic pollutants are still unknown. In this study, the sorption and desorption behaviors on a type of biodegradable plastic-poly(butylene adipate co-terephtalate) (PBAT) were investigated, and at the same time two types of conventional plastics-polyethylene (PEc and PEv) and polystyrene (PS) were used for comparison. Phenanthrene (PHEN) was chosen as one of representative organic pollutants. Results indicated that the sorption and desorption capacities of PBAT were not only higher than those of the other types of microplastics, but also higher than those of carbonaceous geosorbents. The surface area normalized results illustrated that sorption and desorption of the microplastics were positively correlated with their abundance of rubbery subfraction. The sorption kinetic results showed that the sorption rates of PBAT and PEc were higher than PEv and PS. The effects of water chemistry factors including salinity, dissolved organic matter and Cu2+ ion on the sorption process displayed the same trend, but the degrees of influence on the four microplastics differed. The degrees of influence were mainly dependent on the abundance of rubbery subfraction for microplastics. These findings indicate that the biodegradable poly(butylene adipate co-terephtalate) microplastics are actually stronger vectors than the conventional microplastics, and crystallization characteristics of the microplastics have great influences on the vector effect.

Comparing the osteoconductive potential between tubular and cylindrical beta-tricalcium phosphate scaffolds: An experimental study in rats.

Beta-tricalcium phosphate (ß-TCP) has been widely used for bone regeneration for many years. However, there are few studies on the osteoconduction ability of different shaped ß-TCP scaffolds. In this study, we compared the osteoconductive potential between the tubular and cylindrical ß-TCP scaffolds in long bone defect animal model. The results showed that more regenerated bone and a better healing property were observed in tubular group than that in cylindrical group. By hematoxylin-eosin staining, the central part of the callus was more compacted in tubular group. And moreover, the increased osteocalcin and osterix expression were found in tubular group, suggesting more vigorous regeneration of bone defect. These results demonstrated that tubular ß-TCP scaffold would be more benefit to promote bone regeneration, indicating that tubular ß-TCP scaffold has a good potential for long bone defect repair in clinical practice. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1934-1940, 2018.

Oestrone-targeted liposomes for mitoxantrone delivery via oestrogen receptor - synthesis, physicochemical characterization and in-vitro evaluation.

OBJECTIVES: Targeted delivery of mitoxantrone (MTO, an anthraquinone drug with high antitumour effect) may be achieved using a novel nanoparticulate delivery system via binding the oestrogen receptor (ER, highly expressed in a variety of human tumours). METHODS: A novel liposomal nanoparticle (NP) was developed using a conjugate derived from 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000] (DSPE-PEG2000 -NH2 ) and oestrone (ES, is known to bind the ER) to produce an ES-targeted PEGylated liposome (ES-SSL). The resulting targeted NP was loaded with MTO to produce a targeted liposome-MTO formulation (ES-SSL-MTO). KEY FINDINGS: The targeted formulation (~140 nm, 1.5 mV) achieved over 95% drug encapsulation efficiency and a favourable stability at 4, 25 and 37 °C up to 48 h. The flow cytometric data indicated that cellular uptake of ES-SSL into human leukaemia HL-60 cells was mediated via binding the oestrogen receptor. In addition, the ES-SSL-MTO significantly reduced the growth of HL-60 cells. CONCLUSIONS: Our results provide a proof of principle that ES-modified PEGylated liposomes can target the ER, thereby potentially improving the therapeutic benefits in ER-overexpressed tumours.

Treatment of phosphate-containing oily wastewater by coagulation and microfiltration.

The oily wastewater generated from pretreatment unit of electrocoating industry contains oils, phosphate, organic solvents, and surfactants. In order to improve the removal efficiencies of phosphate and oils, to mitigate the membrane fouling, coagulation for ceramic membrane microfiltration of oily wastewater was performed. The results of filtration tests show that the membrane fouling decreased and the permeate flux and quality increased with coagulation as pretreatment. At the coagulant Ca (OH)2 dosage of 900 mg/L, the removal efficiency of phosphate was increased from 46.4% without coagulation to 99.6%; the removal of COD and oils were 97.0% and 99.8%, respectively. And the permeate flux was about 70% greater than that when Ca(OH)2 was not used. The permeate obtained from coagulation and microfiltration can be reused as make-up water, and the recommended operation conditions for pilot and industrial application are transmembrane pressure of 0.10 MPa and cross-flow velocity of 5 m/s. The comparison results show that 0.2 microm ZrO2 microfilter with coagulation could be used to perform the filtration rather than conventional ultrafilter, with very substantial gain in flux and removal efficiency of phosphate.

Mechanically resilient, injectable, and bioadhesive supramolecular gelatin hydrogels crosslinked by weak host-guest interactions assist cell infiltration and in situ tissue regeneration.

Although considered promising materials for assisting organ regeneration, few hydrogels meet the stringent requirements of clinical translation on the preparation, application, mechanical property, bioadhesion, and biocompatibility of the hydrogels. Herein, we describe a facile supramolecular approach for preparing gelatin hydrogels with a wide array of desirable properties. Briefly, we first prepare a supramolecular gelatin macromer via the efficient host-guest complexation between the aromatic residues of gelatin and free diffusing photo-crosslinkable acrylated ß-cyclodextrin (ß-CD) monomers. The subsequent crosslinking of the macromers produces highly resilient supramolecular gelatin hydrogels that are solely crosslinked by the weak host-guest interactions between the gelatinous aromatic residues and ß-cyclodextrin (ß-CD). The obtained hydrogels are capable of sustaining excessive compressive and tensile strain, and they are capable of quick self healing after mechanical disruption. These hydrogels can be injected in the gelation state through surgical needles and re-molded to the targeted geometries while protecting the encapsulated cells. Moreover, the weak host-guest crosslinking likely facilitate the infiltration and migration of cells into the hydrogels. The excess ß-CDs in the hydrogels enable the hydrogel-tissue adhesion and enhance the loading and sustained delivery of hydrophobic drugs. The cell and animal studies show that such hydrogels support cell recruitment, differentiation, and bone regeneration, making them promising carrier biomaterials of therapeutic cells and drugs via minimally invasive procedures.