PEGylation renders carnosine resistant to hydrolysis by serum carnosinase and increases renal carnosine levels.

Carnosine's protective effect in rodent models of glycoxidative stress have provided a rational for translation of these findings in therapeutic concepts in patient with diabetic kidney disease. In contrast to rodents however, carnosine is rapidly degraded by the carnosinase-1 enzyme. To overcome this hurdle, we sought to protect hydrolysis of carnosine by conjugation to Methoxypolyethylene glycol amine (mPEG-NH2). PEGylated carnosine (PEG-car) was used to study the hydrolysis of carnosine by human serum as well as to compare the pharmacokinetics of PEG-car and L-carnosine in mice after intravenous (IV) injection. While L-carnosine was rapidly hydrolyzed in human serum, PEG-car was highly resistant to hydrolysis. Addition of unconjugated PEG to carnosine or PEG-car did not influence hydrolysis of carnosine in serum. In mice PEG-car and L-carnosine exhibited similar pharmacokinetics in serum but differed in half-life time (t1/2) in kidney, with PEG-car showing a significantly higher t1/2 compared to L-carnosine. Hence, PEGylation of carnosine is an effective approach to prevent carnosine degradations and to achieve higher renal carnosine levels. However, further studies are warranted to test if the protective properties of carnosine are preserved after PEGylation.

Nanocellulose-Based Hybrid Scaffolds for Skin and Bone Tissue Engineering: A 10-Year Overview.

Cellulose, the most abundant polymer on Earth, has been widely utilized in its nanoform due to its excellent properties, finding applications across various scientific fields. As the demand for nanocellulose continues to rise and its ease of use becomes apparent, there has been a significant increase in research publications centered on this biomaterial. Nanocellulose, in its different forms, has shown tremendous promise as a tissue engineered scaffold for regeneration and repair. Particularly, nanocellulose-based composites and scaffolds have emerged as highly demanding materials for both soft and hard tissue engineering. Medical practitioners have traditionally relied on collagen and its analogue, gelatin, for treating tissue damage. However, the limited mechanical strength of these biopolymers restricts their direct use in various applications. This issue can be overcome by making hybrids of these biopolymers with nanocellulose. This review presents a comprehensive analysis of the recent and most relevant publications focusing on hybrid composites of collagen and gelatin with a specific emphasis on their combination with nanocellulose. While bone and skin tissue engineering represents two areas where a majority of researchers are concentrating their efforts, this review highlights the use of nanocellulose-based hybrids in these contexts.

A review of flow field characteristics in submerged hollow fiber membrane bioreactor: Micro-interface, module and reactor.

As an important part of the membrane field, hollow fiber membranes (HFM) have been widely concerned by scholars. HFM fouling in the industrial application results in a reduction in its lifespan and an increase in cost. In recent years, various explorations on the HFM fouling control strategies have been carried out. In the current work, we critically review the influence of flow field characteristics in HFM-based bioreactor on membrane fouling control. The flow field characteristics mainly refer to the spatial and temporal variation of the related physical parameters. In the HFM field, the physical parameter mainly refers to the variation characteristics of the shear force, flow velocity and turbulence caused by hydraulics. The factors affecting the flow field characteristics will be discussed from three levels: the micro-flow field near the interface of membrane (micro-interface), the flow field around the membrane module and the reactor design related to flow field, which involves surface morphology, crossflow, aeration, fiber packing density, membrane vibration, structural design and other related parameters. The study of flow field characteristics and influencing factors in the HFM separation process will help to improve the performance of HFM in full-scale water treatment plants.

Factorial structure and measurement invariance of the Chinese version of the Oral Health Impact Profile-14 among clinical populations and non-clinical populations: an evidence for public oral investigations.

OBJECTIVE: Oral health-related quality of life (OHRQoL) is a multidimensional concept that is commonly used to examine the impact of oral health status on quality of life. The purpose of this study was to examine the optimal factor model of the Chinese version of the Oral Health Impact Profile (OHIP-14) questionnaire in clinical populations, measurement invariance across clinical status and gender cohorts. This would ensure equal validity of the Chinese version of OHIP-14 in different populations and further support public oral investigations. METHODS: The Chinese version of OHIP-14 was used to investigate 490 dental patients and 919 college students. Confirmatory factor analysis (CFA), item analysis and reliability, measurement invariance, and the t-test were used for data analyses. RESULTS: We found that the 7-factor structure had the best-fit index in the sample (CFI = 0.970, TLI = 0.952; SRMR = 0.029, RMSEA = 0.052(0.040,0.063)). The reliability of the scales was satisfactory (Cronbach's α = 0.942). The error variance invariance fitted the data adequately in measurement invariance, indicating that measurement invariance is acceptable both across the clinical and non-clinical populations (∆CFI=-0.017, ∆RMSEA = 0.010) and across genders in the clinical population (∆CFI = 0.000, ∆RMSEA=-0.003). T-test for scores showed that the clinical populations scored significantly higher than the non-clinical populations, as did the overall score (t = 7.046, p < 0.001, d = 0.396), in terms of functional limitation (t = 2.178, p = 0.030, d = 0.125), physical pain (t = 7.880, p < 0.001,d = 0.436), psychological discomfort (t = 8.993, p < 0.001, d = 0.514), physical disability (t = 6.343, p < 0.001, d = 0.358), psychological disability (t = 5.592, p < 0.001, d = 0.315), social disability (t = 5.301, p < 0.001,d = 0.304), social handicap (t = 4.452, p < 0.001, d = 0.253), and that in the non-clinical populations, females scored significantly higher than males, as did in terms of physical pain (t = 3.055, p = 0.002, d = 0.280), psychological discomfort (t = 2.478, p = 0.014, d = 0.222), and psychological disability (t = 2.067, p = 0.039, d = 0.188). CONCLUSION: This study found that the Chinese version of OHIP-14 has measurement invariance between the clinical and non-clinical populations and across genders in the clinical populations, and can be widely used in OHRQoL assessment for public oral investigations.

Reversible Controlling the Supramolecular Chirality of Side Chain Azobenzene Polymers: Chiral Induction and Modulation.

Chirality represents a fundamental structure in nature and the induction and reversible modulation of supramolecular chirality with feasible techniques is of great value in the design of new chiroptical smart materials. Herein, two kinds of azobenzene side-chain polymers (without spacer: Azo-PMA0; with 6 spacers: Azo-PMA6) are synthesized, the length of spacer and azobenzene chromophores play a vital role in chirality transfer and modulation. The supramolecular chiral arrangement of Azo-PMA0 (amorphous phase) can be completely controlled and reversibly modulated over multiple cycles by 450 nm circularly polarized light driven by the supramolecular interaction between azo groups of polymer chains, with an absorption dissymmetry factor (g) value of 0.0019. The chiroptical properties of Azo-PMA6 (liquid crystal state) can also be reversibly modulated by UV light and thermal annealing treatment during trans-cis isomerization of azo chromophore, with the g-value changes from 0-0.038. The successful construction of reversible chiral induction and modulation based on side chain azobenzene polymers may pave the way for designing photo-switchable functional materials.

Preparation of fluorescein-modified polymer dots and their application in chiral discrimination of lysine enantiomers.

Fluorescein-functionalized fluorescent polymer dots (F-PDs) were prepared by a facile one-pot method by magnetic stirring under mild conditions based on carboxymethylcellulose (CMC) and fluorescein as the precursors. The obtained F-PDs exhibited a nanoscale size of 3.2 ± 1.1 nm, excellent water solubility, and bright yellow fluorescence emission with a fluorescence quantum yield of 12.0%. The fluorescent probe displays rapid and sensitive chiral discrimination for lysine focused on different complexation abilities between lysine enantiomers and Cu2+. The concentration of L-lysine in the range 4 to 14 mM (R2 = 0.997) was measured by the fluorescence intensity ratio (I513/I429); the exitation wavelength was set to λex = 365 nm. The detection limit was 0.28 mM (3σ/slope). Importantly, this sensor accurately predicted the enantiomeric excess (ee) of lysine enantiomers at the designed concentration (lysine: 20 mM; Cu2+: 10 mM) ranges. The proposed sensor was successfully applied to determine L-lys (recovery: 95.8-101%; RSD: 0.465-3.34%) and ee values (recovery: 98.5-102%; RSD: 2.61-3.21%) in human urine samples using the standard addition method.

Exploring the Circular Polarization Capacity from Chiral Cellulose Nanocrystal Films for a Photo-Controlled Chiral Helix of Supramolecular Polymers.

Circularly polarized light (CPL) is key to asymmetric photochemistry as it could impart the chiral organization information into chemical products. Here, we demonstrate the circular polarization capacity of chiral cellulose nanocrystal (CNC) films to trigger photo-alignment of achiral supramolecular polymers into helical structures. Right-handed transmitted (T-) CPL was generated from self-assembled CNC films, which induced amorphous azobenzene (Azo) supramolecular polymers into chiral structures. The chiral induction effect of T-CPL is enhanced on Azo polymers with longer spacers. The absorptive dissymmetry factor (gabs ) values of liquid-crystal supramolecular polymers can be amplified significantly (over 10 times) after T-CPL irradiation. Moreover, by integrating carbon dots into CNC films, CPL emission with a considerable luminescence dissymmetry factor (glum ) up to -0.66 was achieved, and it could be used for the photo-alignment of Azo polymers with high chiroptical properties. This work provides new insight for the photo modulation of supramolecular polymers by CPL-active materials.

[Mechanical Design and Research of Wearable Exoskeleton Assisted Robot for Upper Limb Rehabilitation].

Based on the biomechanical mechanism of human upper limb, the disadvantages of traditional rehabilitation training and the current status of upper limb rehabilitation robot, a six degree of freedom, flexible adjustment, wearable upper limb rehabilitation exoskeleton design scheme is proposed. Firstly, the mechanics of each joint of the upper limb is analyzed, and the virtual prototype design of the whole mechanical structure of the upper limb rehabilitation wearable exoskeleton is carried out by using CATIA three-dimensional software. The tooth transmission of the forearm and the upper arm single row four point contact ball bearing with internal/external rotation and the shoulder flexible passive adjustment mechanism (viscoelastic damper) are innovatively designed. Then, the joints of the upper limb rehabilitation exoskeleton are analyzed, theoretical analysis and calculation of the driving torque, the selection of the motor and gearbox of each driving joint are carried out. Finally, the whole finite element analysis of the upper limb exoskeleton is carried out. The research and experimental results showed that the design scheme of the upper limb exoskeleton assist structure is highly feasible, which can help the patients with upper limb paralysis and motor dysfunction self-rehabilitation.

Molecular Evolution of Tooth-Related Genes Provides New Insights into Dietary Adaptations of Mammals.

Mammals have evolved different tooth phenotypes that are hypothesized to be associated with feeding habits. However, the genetic basis for the linkage has not been well explored. In this study, we investigated 13 tooth-related genes, including seven enamel-related genes (AMELX, AMBN, ENAM, AMTN, ODAM, KLK4 and MMP20) and six dentin-related genes (DSPP, COL1A1, DMP1, IBSP, MEPE and SPP1), from 63 mammals to determine their evolutionary history. Our results showed that different evolutionary histories have evolved among divergent feeding habits in mammals. There was stronger positive selection for eight genes (ENAM, AMTN, ODAM, KLK4, DSPP, DMP1, COL1A1, MEPE) in herbivore lineages. In addition, AMELX, AMBN, ENAM, AMTN, MMP20 and COL1A1 underwent accelerated evolution in herbivores. While relatively strong positive selection was detected in IBSP, SPP1, and DSPP, accelerated evolution was only detected for MEPE and SPP1 genes among the carnivorous lineages. We found positive selection on AMBN and ENAM genes for omnivorous primates in the catarrhini clade. Interestingly, a significantly positive association between the evolutionary rate of ENAM, ODAM, KLK4, MMP20 and the average enamel thickness was found in primates. Additionally, we found molecular convergence in some amino acid sites of tooth-related genes among the lineages whose feeding habit are similar. The positive selection of related genes might promote the formation and bio-mineralization of tooth enamel and dentin, which would make the tooth structure stronger. Our results revealed that mammalian tooth-related genes have experienced variable evolutionary histories, which provide some new insights into the molecular basis of dietary adaptation in mammals.

NIR-II Absorbing Semiconducting Polymer-Triggered Gene-Directed Enzyme Prodrug Therapy for Cancer Treatment.

Exploration of facile strategies for precise regulation of target gene expression remains highly challenging in the development of gene therapies. Especially, a stimuli-responsive nanocarrier integrated with ability of noninvasive remote control for treating wide types of cancers is rarely developed. Herein, a NIR-II absorbing semiconducting polymer (PBDTQ) is employed to remotely activate the heat-inducible heat-shock protein 70 (HSP70) promoter under laser irradiation, further realizing regulation of gene-directed enzyme prodrug therapy (GDEPT) for cancer treatment in mild hyperthermia. In this multifunctional nanocomposite, the PBDTQ and double suicide gene plasmid (pSG) based on HSP70 promoter are incorporated into a lipid complex. Upon NIR-II laser excitation, the mild photothermal effect (≈43 °C) generated from PBDTQ can cause the release of pSG and activation of HSP70 promoter, and then upregulate suicide gene expression triggered by the HSP70 promoter which can further convert the nontoxic prodrug into its cytotoxic metabolites. Therefore, this work demonstrates a universal NIR-II laser-triggered GDEPT using semiconducting polymers as the photothermal generator for cancer treatment with minimized collateral damage and nontargeted side effects.

Recent Advances on Fabrication of Polymeric Composites Based on Multicomponent Reactions for Bioimaging and Environmental Pollutant Removal.

As the core of polymer chemistry, manufacture of functional polymers is one of research hotspots over the past several decades. Various polymers are developed for diverse applications due to their tunable structures and unique properties. However, traditional step-by-step preparation strategies inevitably involve some problems, such as separation, purification, and time-consuming. The multicomponent reactions (MCRs) are emerging as environmentally benign synthetic strategies to construct multifunctional polymers or composites with pendant groups and designed structures because of their features, such as efficient, fast, green, and atom economy. This mini review summarizes the latest advances about fabrication of multifunctional fluorescent polymers or adsorptive polymeric composites through different MCRs, including Kabachnik-Fields reaction, Biginelli reaction, mercaptoacetic acid locking imine reaction, Debus-Radziszewski reaction, and Mannich reaction. The potential applications of these polymeric composites in biomedical and environmental remediation are also highlighted. It is expected that this mini-review will promote the development preparation and applications of functional polymers through MCRs.

Preparation of boronic acid-modified polymer dots under mild conditions and their applications in pH and glucose detection.

For the first time, boronic acid-modified polymer dots (B-PDs) were fabricated by a "synthesis-modification integration" route using polyethylenimine (PEI) and phenylboronic acid as precursors. Under optimized preparation conditions, the B-PDs exhibited an average size of 2.2 nm, good water solubility, and high fluorescence quantum yield of 8.69%. The B-PDs showed reversible fluorescence response in acid solutions (blue emissions) and alkaline solutions (green emissions). The fluorescence emissions of B-PDs demonstrated an obvious red shift with varying the pH value from 1 - 13. Moreover, glucose could assemble on the surface of B-PDs due to the reversible reaction between boronic acid and cis-diols, which resulted in a blue shift of emission wavelength and an obvious increase of FL intensity at λex = 380 nm based on the aggregation-induced enhancement effect. The glucose sensing method was thus developed in the range 0.0001 - 1.0 mol L-1. Applications to real human blood and glucose injection samples demonstrated satisfactory results. The B-PDs based on the analytical method display good selectivity, wide detection range, and simplicity in preparation and detection, implying promising applications as a practical platform for biosensing.

Liposomes with Water as a pH-Responsive Functionality for Targeting of Acidic Tumor and Infection Sites.

A lipid named DCPA was synthesized under microwave-assisted heating. DCPA possesses a pyridine betaine, hydrophilic group that can be complexed with water through hydrogen bonding (DCPA-H2 O). DCPA-H2 O liposomes became protonated relatively fast already at pH<6.8, due to the high HOMO binding energy of DCPA-H2 O. In murine models, DCPA-H2 O liposomes had longer blood circulation times than natural DPPC or cationic DCPM liposomes, while after tail-vein injection DCPA-H2 O liposomes targeted faster to solid tumors and intra-abdominal infectious biofilms. Therapeutic efficacy in a murine, infected wound-healing model of tail-vein injected ciprofloxacin-loaded DCPA-H2 O liposomes exceeded the ones of clinically applied ciprofloxacin as well as of ciprofloxacin-loaded DPPC or DCPM liposomes.

[Advances in Research of Chitosan-based Composites for Implanted Medical Devices].

It is well known that chitosan-based composites are widely used in implantable medical devices. The development of chitosan-based composite materials with different types was summarized in this paper, such as inorganic, organic and composite phases. Then, combined with the research focus, the development of 3D printing technology and chitosan-based composites was summarized. It was also pointed out that the existing problems in our research, which need to be solved urgently. At last, the development direction and broad application prospect of chitosan-based composites were prospected. And we look forward to providing reference for relevant research.

Multi-Stimuli-Triggered Shape Transformation of Polymeric Filaments Derived from Dynamic Covalent Block Copolymers.

Using dynamic polymers to achieve the morphology transformation of polymeric assemblies under different conditions is challenging. Herein, we reported diversiform shape transformation of multi-responsive polymer filaments, which were self-assembled by a new kind of amphiphilic block copolymer (PVEG-PVEA) possessing dynamic and reversible acylhydrazone bonds through reacting benzaldehyde-containing block copolymers poly(vinylbenzaldehyde)-b-poly(N-(4-vinylbenzyl)-N,N-diethylamine) (PVBA-PVEA) with acylhydrazine-modified oligoethylene glycol. It was found that the resulting amphiphilic and dynamic PVEG-PVEA was capable of hierarchically self-assembling into intriguing core-branched filaments in aqueous solution. Notably, the features of acylhydrazone bonds and PVEA block endow the filaments with multi-responsiveness including acid, base, and temperature, leading to the multiple morphological transformations under such stimuli. Moreover, the core-branched filaments would further transform into polymeric braided bundles driven by hydrogen-bonding interactions of amide bonds. It is noteworthy that both core-branched filaments and braided bundles made from polymers are quite rare. These diversiform polymeric assemblies and their morphological evolution were characterized by TEM, Cryo-TEM, SEM, and DLS. Finally, we used PVBA-PVEA as a platform to facilely prepare functional polymers, such as glycopolymers via the reaction of amino-containing sugars and aldehyde groups. The obtained glycopolymers self-assembled into glycofibers for the biomimicry of glycans via binding with lectins. These findings not only are conducive to understanding of the stimulated shape change process of dynamic polymeric assemblies in water but also provide a new method for the facile fabrication of smart and functional polymeric assemblies for different potential applications, such as biomimicry and targeted drug nanocarriers or delivery vehicles.

Modulating Morphologies and Surface Properties of Nanoparticles from Cellulose-Grafted Bottlebrush Copolymers Using Complementary Hydrogen-Bonding between Nucleobases.

Herein we report the synthesis of a cellulose-grafted bottlebrush copolymer with nucleobases as hydrophobic moieties. Well-defined spherical micelles from this bottlebrush copolymer were fabricated via a solvent switch method. A morphological transition from spheres to worms was only observed to occur when a diblock copolymer with a complementary nucleobase functionality was introduced. Hydrophobic interaction is not capable of triggering the morphological transformation, and the diblock copolymer with the heterogeneous acrylamide nucleobase monomer can induce the morphological transition at higher A:T molar ratios, which might be caused by the weak H-bonding interaction. This supramolecular "grafting to" method enables the preparation of a series of nanoparticles with similar shapes and dimensions but distinct surface properties such as zeta potentials. Moreover, reversible morphological transitions between worm-like micelles and spheres can be achieved using a reversible collapsing and swelling of a thermoresponsive polymer. This work highlights that a supramolecular "grafting to" approach between complementary nucleobases can be utilized to tune morphologies and surface properties of nanoparticles.

Somatosensory changes in Chinese patients after coronectomy vs. total extraction of mandibular third molar: a prospective study.

OBJECTIVES: This study aimed to quantitatively compare the somatosensory function changes of inferior alveolar nerve (IAN) after mandibular third molar extraction with a surgery protocol of coronectomy, as opposed to the conventional method. MATERIALS AND METHODS: Patients with a lower third molar directly contacting IAN were recruited and assigned either to a test group (coronectomy group) or a control group (conventional extraction). A standardized quantitative sensory testing (QST) battery was performed for four times: one week before surgery and the second, seventh, and 28th days after surgery. Z-scores and the loss/gain coding system were applied for each participant. RESULTS: A total of 140 molars (test group: n = 91, control group: n = 49) were enrolled. The sensitivity of the mechanical detection threshold (MDT) and pressure pain threshold (PPT) significantly increased after surgery more than before surgery in both groups (P ≤ 0.001). After the surgery, the sensitivities of the cold detection threshold (CDT), cold pain threshold (CPT), and heat pain threshold (HPT) were significantly higher in the test group than in the control group (P ≤ 0.027). The risk of IANI was significantly larger (P = 0.041) in the test group than in the control group. CONCLUSIONS: QST was a sensitive way to detect somatosensory abnormalities even with no subjective complaint caused by surgery. Coronectomy had less influence on IAN function than conventional total extraction. CLINICAL RELEVANCE: The somatosensory function changes after mandibular third molar extraction were quantitatively studied, and coronectomy was proved a reliable alternation to reduce IAN injury rate.

Biopolymer-Based Microcarriers for Three-Dimensional Cell Culture and Engineered Tissue Formation.

The concept of three-dimensional (3D) cell culture has been proposed to maintain cellular morphology and function as in vivo. Among different approaches for 3D cell culture, microcarrier technology provides a promising tool for cell adhesion, proliferation, and cellular interactions in 3D space mimicking the in vivo microenvironment. In particular, microcarriers based on biopolymers have been widely investigated because of their superior biocompatibility and biodegradability. Moreover, through bottom-up assembly, microcarriers have opened a bright door for fabricating engineered tissues, which is one of the cutting-edge topics in tissue engineering and regeneration medicine. This review takes an in-depth look into the recent advancements of microcarriers based on biopolymers-especially polysaccharides such as chitosan, chitin, cellulose, hyaluronic acid, alginate, and laminarin-for 3D cell culture and the fabrication of engineered tissues based on them. The current limitations and potential strategies were also discussed to shed some light on future directions.

[Blepharoptosis and dysarthria in a boy aged 2 years].

A boy, aged 2 years and 4 months, had a sudden onset of blepharoptosis of the right eyelid, accompanied by the mouth deviated to the right side, drinking cough, nystagmus, and developmental regression. Cranial MRI showed softening lesions formed after infarction of the right dorsolateral medulla oblongata, while head CT angiography showed no imaging of the proximal part of the V4 segment of the right vertebral artery. The child was diagnosed with dorsolateral medulla oblongata syndrome and was treated with gamma globulin to regulate immune function, with mannitol to reduce neuronal edema, with low-molecular-weight heparin sodium to improve local hypercoagulation of occluded blood vessels, with hyperbaric oxygen to improve local ischemia and hypoxia and promote the recovery of brain function, and with neuromuscular electrical stimulation to promote the recovery of neuromuscular function. Before discharge, only mild right ataxia and Horner syndrome remained. This article reports the first case of infantile dorsolateral medulla oblongata syndrome and provides experience for the diagnosis and treatment of the disease.