Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease.

OBJECTIVE: Despite the increasing number of genes associated with Charcot-Marie-Tooth (CMT) disease, many patients currently still lack appropriate genetic diagnosis for this disease. Autosomal dominant mutations in aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT. Here, we describe causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) for 3 families affected with CMT. METHODS: Whole-exome sequencing was performed in 16 patients and 14 unaffected members of 3 unrelated families. The functional impact of the genetic variants identified was investigated using bioinformatic prediction tools and confirmed using cellular and biochemical assays. RESULTS: Combined linkage analysis for the 3 families revealed significant linkage (Zmax LOD = 6.9) between the genomic co-ordinates on chromosome 1: 108681600-110300504. Within the linkage region, heterozygous SerRS missense variants segregated with the clinical phenotype in the 3 families. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation. INTERPRETATION: Our findings suggest the heterozygous SerRS variants identified represent a novel cause for autosomal dominant CMT. Mutant SerRS proteins are known to impact various molecular and cellular functions. Our findings provide significant advances on the current understanding of the molecular mechanisms associated with ARS-related CMT. ANN NEUROL 2023;93:244-256.

Construction of cellulose-based highly sensitive extended-gate field effect chiral sensor.

Chiral recognition is an emerging field of modern chemical analysis, and the development of health-related fields depends on the production of enantiomers. Cellulose is a kind of natural polymer material with certain chiral recognition ability. Limited by the chiral recognition ability of natural cellulose itself, more cellulose derivatives have been gradually developed for chiral recognition and separation. Based on the difference in action between cellulose derivatives and enantiomers, this work synthesized cellulose-tris(4-methylphenylcarbamate) (CMPC) chiral recognition mediators and a CMPC-functionalized extended-gate organic field effect transistor (EG-OFET) was constructed for the first time. Three chiral molecules were selected as model analytes to evaluate the enantiomeric recognition ability of the platform, including threonine (Thr), 2-chloromandelic acid (CA), and 1,2-diphenylethylenediamine (DPEA). The detection limit for 1,2-diphenylethylenediamine (DPEA) is down to 10-13 M. Through the amplification effect of the EG-OFET platform, the difference in the interaction between CMPC and three chiral molecules with different structures is converted into a current signal output. At the same time, the enantiomer discrimination mechanism of CMPC was further studied by means of spectroscopy and nuclear magnetic resonance.

Alcohol Pretreatment to Eliminate the Interference of Micro Additive Particles in the Identification of Microplastics Using Raman Spectroscopy.

Raman spectroscopy is an indispensable tool in the analysis of microplastics smaller than 20 µm. However, due to its limitation, Raman spectroscopy may be incapable of effectively distinguishing microplastics from micro additive particles. To validate this hypothesis, we characterized and compared the Raman spectra of six typical slip additives with polyethylene and found that their hit quality index values (0.93-0.96) are much higher than the accepted threshold value (0.70) used to identify microplastics. To prevent this interference, a new protocol involving an alcohol treatment step was introduced to successfully eliminate additive particles and accurately identify microplastics. Tests using the new protocol showed that three typical plastic products (polyethylene pellets, polyethylene bottle caps, and polypropylene food containers) can simultaneously release microplastic-like additive particles and microplastics regardless of the plastic type, daily-use scenario, or service duration. Micro additive particles can also adsorb onto and modify the surfaces of microplastics in a manner that may potentially increase their health risks. This study not only reveals the hidden problem associated with the substantial interference of additive particles in microplastic detection but also provides a cost-effective method to eliminate this interference and a rigorous basis to quantify the risks associated with microplastic exposure.

Signal on-off ratiometric electrochemical sensor coupled with a molecularly imprinted polymer for the detection of carbendazim.

A stable ratiometric electrochemical sensor is introduced for the selective detection of carbendazim (CBD). Specifically, the proposed sensor employs a Co@Mo2C bimetallic nanomaterial as the glassy carbon electrode substrate and a layer of molecularly imprinted polymer (MIP) was in situ fabricated on glassy carbon electrode by electropolymerization, with o-aminophenol as the functional monomer and CBD acting as template. A ratiometric MIP sensor was constructed by adding ferrocene (Fc) internal reference directly to the sample solution. The bimetallic nanomaterials provide a large loading platform for the MIP layer through synergistic effects, amplifying the signal. Excellent CBD binding selectivity is achieved by the templating effect of the three-dimensional (3D) MIP layer. The internal standard is added directly to the electrolyte solution to be tested, allowing the new type of ratiometric electrochemical sensor to avoid the cumbersome steps of other methods and reducing the difficulty and human error of the experimental procedure. Combining a ratiometric strategy with a 3D MIP structure realises the dual-signal detection of CBD. The optimised sensor showed an excellent linear relationship between 0.01 and 1 000 µM, with a correlation coefficient of 0.997 and a detection limit of 3.4 nM (S/N = 3).

Effect of Molar Substitution on the Properties of γ-Hydroxypropyl Starch.

A new type of hydroxyalkyl starch, γ-hydroxypropyl starch (γ-HPS), was prepared by etherification of alkali-activated starch with 3-chloropropanol. The reaction efficiency, morphological change, thermodynamic and apparent viscosity properties, and other physicochemical characteristics were described. The molar substitution (MS) of modified whole starch was determined to be 0.008, 0.017, 0.053, 0.106, and 0.178, with a ratio of 5%, 15%, 25%, 35%, and 45% 3-chloropropanol to starch (v/w), respectively. Compared to native starch, the granular size and shape and the X-ray diffraction pattern of γ-HPS are not very different. For low-substituted γ-HPS, the implications may be less evident. Thermal stability measurements by means of thermogravimetric analyses and differential scanning calorimetry (TGA-DSC) proved that thermal stability was reduced and water retaining capacity was increased after hydroxypropylation. Furthermore, the findings also showed that the solubility, light transmittance, and retrogradation of γ-HPS pastes could be improved by etherification. The greater the MS of the γ-HPS, the more its freeze-thaw stability and acid resistivity increased. In this study, we provide relevant information for the application of γ-HPS in food and non-food industries.

The Larix kaempferi genome reveals new insights into wood properties.

Here, through single-molecule real-time sequencing, we present a high-quality genome sequence of the Japanese larch (Larix kaempferi), a conifer species with great value for wood production and ecological afforestation. The assembled genome is 10.97 Gb in size, harboring 45,828 protein-coding genes. Of the genome, 66.8% consists of repeat sequences, of which long terminal repeat retrotransposons are dominant and make up 69.86%. We find that tandem duplications have been responsible for the expansion of genes involved in transcriptional regulation and stress responses, unveiling their crucial roles in adaptive evolution. Population transcriptome analysis reveals that lignin content in L. kaempferi is mainly determined by the process of monolignol polymerization. The expression values of six genes (LkCOMT7, LkCOMT8, LkLAC23, LkLAC102, LkPRX148, and LkPRX166) have significantly positive correlations with lignin content. These results indicated that the increased expression of these six genes might be responsible for the high lignin content of the larches' wood. Overall, this study provides new genome resources for investigating the evolution and biological function of conifer trees, and also offers new insights into wood properties of larches.

Relationship between the Height of Alveolar Bone Resorption and Sex and Age in Adolescents.

OBJECTIVES: To explore the relationship between the height of alveolar bone resorption and sex and age in the adolescent dentition. METHODS: Multi-slice computed tomography (MSCT) was used to measure the height of alveolar bone resorption at labial, lingual, mesial and distal sites of teeth in 149 adolescents aged from 10 to 20 years. SPSS 25.0 software was used to analyze the relationship between the height of alveolar bone resorption and sex and age. RESULTS: There was no significant difference in the height of alveolar bone resorption between sex (P>0.05). The height of alveolar bone resorption was positively correlated with age in all types of teeth. The model constructed by combining the alveolar bone resorption height data of four sites (y=2.569x1+3.106x2+4.108x3+1.451x4-0.082, R2max=0.756)had a better ability to infer age than that of combining two sites (y=5.942x1+4.489x2+0.612, R2max=0.706) and a single site (R2max=0.638). CONCLUSIONS: The height of alveolar bone resorption is positively correlated with the age of adolescents. The combination of four sites has a stronger ability to infer the relationship between the height of alveolar bone resorption and age in adolescents and has higher accuracy in practical application.

[Recent Advance of Stainless Steel Used In Non-active Surgical Implantable Medical Device and Regulatory Perspective].

Stainless steel has been widely used in non-active surgical implantable medical device of cardiovascular, orthopedics, dental and ophthalmology. In this paper, we mainly focused on development of stainless steel, as well as the material-related standard evolution. We further summarized the recent advancement of stainless steel use in surgical implantable medical device. Insight and regulatory perspective has been further demonstrated.

Prognostic value of quantitative flow ratio measured immediately after drug-coated balloon angioplasty for in-stent restenosis.

OBJECTIVES: This study aimed to evaluate prognostic value of quantitative flow ratio (QFR) in drug-coated balloon (DCB) angioplasty for in-stent restenosis (ISR). BACKGROUND: There is a high incidence of recurrent ISR after DCB angioplasty. QFR is a novel method for fast computation of fractional flow reserve for the target vessel based on quantitative coronary angiography (QCA) and fluid dynamics algorithms. METHODS: Patients participating in the RESTORE ISR China randomized trial were enrolled and classified into the recurrent restenosis group and the non-recurrent restenosis group. The binary classifications followed the QCA standards of ISR. Clinical and angiographic characteristics of the groups were analyzed, and the QFRs before and after lesion preparation and after final DCB angioplasty were measured and compared. RESULTS: A total of 208 patients who underwent follow-up angiography were enrolled in the study, with 226 lesions measured in total. QFR value after DCB angioplasty (odds ratio [OR] 0.88; 95% confidence interval [CI] 0.83-0.93; p < .0001 for 1 mm increase), lesion length (OR: 1.08; 95% CI: 1.01-1.15; p = .017), and vessel caliber lumen diameter (OR: 0.35; 95% CI 0.13-0.89; p = .027) were independently associated with recurrent restenosis after DCB angioplasty. The optimal QFR cut-off value was determined to be 0.90 with a sensitivity of 0.94, specificity of 0.56, and accuracy of 0.79 in predicting recurrent restenosis. CONCLUSIONS: The QFR value after DCB angioplasty is a promising predictor of DES ISR.

Novel 2,3-Dialdehyde Cellulose-Based Films with Photodynamic Inactivation Potency by Incorporating the ß-Cyclodextrin/Curcumin Inclusion Complex.

Antibacterial packaging film mediated by photodynamic inactivation (PDI) is a new concept in food industry. The objective of this study was to fabricate a green 2,3-dialdehyde cellulose (DAC)-based antimicrobial film with PDI potency by incorporating the ß-cyclodextrin/curcumin (ß-CD/Cur) complex as a photosensitizer. The PDI-mediated films were characterized by evaluating the surface morphology, chemical structure, light transmittance, mechanical properties, photochemical and thermal stability, and water solubility. The results showed that the DAC-CD/Cur films were soluble in water and mechanically strong with a tensile strength of 63.87 MPa and an elongation break of 1.32%, which was attributed to the formation of hydrogen bonds between DAC and ß-CD/Cur molecules. Meanwhile, the composite films possessed a good light transmittance but impeded the penetration of ultraviolet light and efficiently delayed the degradation of curcumin. More importantly, the PDI-mediated films exhibited a broad-spectrum ability to kill Listeria monocytogenes, Vibrio parahaemolyticus, and Shewanella putrefaciens in pure culture. Notably, they also potently inactivated these harmful bacteria on ready-to-eat salmon with a maximum of ∼4 Log CFU/g (99.99%) reduction after 60 min irradiation (13.68 J/cm2). Therefore, the PDI-mediated DAC-CD/Cur films are novel and promising antimicrobial food packaging films in food industry.

Polydopamine nanodots-based cost-effective nanoprobe for glucose detection and intracellular imaging.

The cellular glucose detection remains a vital topic, which could provide some essential information about the glucose-based pathological and physiological processes. In this study, a smart polydopamine nanodots-based cost-effective fluorescence turn-on nanoprobe (denoted as PDA-Ag-GOx) for intracellular glucose detection is established. Silver nanoparticles (AgNPs) are directly formed in one step by the reduction of fluorescent polydopamine nanodots (PDADs) which have much phenolic hydroxyls on the surface. The fluorescence of PDADs could be quenched by AgNPs through surface plasmon-enhanced energy transfer (SPEET) from donor PDADs to acceptor AgNPs. Glucose oxidase (GOx) is modified on the PDA-Ag NPs by covalent bond. In the presence of glucose, GOx could catalyze glucose to produce H2O2 and gluconic acid. The generated acid and H2O2 would degrade AgNPs into Ag+, the PDADs release and restore its fluorescence. The proposed nanoprobe has some advantages, such as cost-effective, easy preparation, and excellent selectivity toward glucose, which could be successfully utilized to intracellular glucose imaging.

Chitosan oligosaccharide modified liposomes enhance lung cancer delivery of paclitaxel.

Lung cancer is one of the leading causes of cancer-related death worldwide. Various therapeutic failed in the effective treatment of the lung cancer due to their limited accumulation and exposure in tumors. In order to promote the chemotherapeutics delivery to lung tumor, we introduced chitosan oligosaccharide (CSO) modification on the liposomes. CSO conjugated Pluronic P123 polymers with different CSO grafting amounts, called as CP50 and CP20, were synthesized and used to prepare CSO modified liposomes (CP50-LSs and CP20-LSs). CP50-LSs and CP20-LSs displayed significantly enhanced cellular uptake in A549 cells in vitro as well as superior tumor accumulation in vivo compared with non-CSO modified liposomes (P-LSs). This phenomenon was related to the increased affinity between CSO modified liposomes and tumor cells following massive adsorption of collagen, which was highly expressed in lung tumors. In the A549 tumor-bearing mouse model, intravenous injection of paclitaxel (PTX)-loaded CP50-LSs every 3 days for 21 days resulted in optimal antitumor therapeutic performance with an inhibition rate of 86.4%. These results reveal that CSO modification provides promising applicability for nanomedicine design in the lung cancer treatment.

Lipid/PAA-coated mesoporous silica nanoparticles for dual-pH-responsive codelivery of arsenic trioxide/paclitaxel against breast cancer cells.

Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy. In particular, the distinction of tumor microenvironment and normal tissues is often used in stimulus-responsive drug delivery systems for controlled release of therapeutic agents at target sites. In this study, we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA), and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PTX/ATO). Tumor-targeting peptide F56 was used to modify MSNs, which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis. PAA- and PSL-coated nanoparticles were characterized by TGA, TEM, FT-IR, and DLS. The drug-loaded nanoparticles displayed a dual-pH-responsive (pHe = 6.5, pHendo = 5.0) and sequential drug release profile. PTX within PSL was preferentially released at pH = 6.5, whereas ATO was mainly released at pH = 5.0. Drug-free carriers showed low cytotoxicity toward MCF-7 cells, but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells, showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs. Furthermore, the extracellular release of PTX caused an expansion of the interstitial space, allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect. As a result, FPL-PMSN-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy.

Enhanced antitumour efficacy of functionalized doxorubicin plus schisandrin B co-delivery liposomes via inhibiting epithelial-mesenchymal transition.

Non-small cell lung cancer (NSCLC) is a malignant cancer characterized by easy invasion, metastasis and poor prognosis, so that conventional chemotherapy cannot inhibit its invasion and metastasis. Doxorubicin (DOX), as a broad-spectrum antitumour drug, cannot be widely used in clinic because of its poor targeting, short half-life, strong toxicity and side effects. Therefore, the aim of our study is to construct a kind of PFV modified DOX plus schisandrin B liposomes to solve the above problems, and to explore its potential mechanism of inhibiting NSCLC invasion and metastasis. The antitumour efficiency of the targeting liposomes was carried out by cytotoxicity, heating ablation, wound healing, transwell, vasculogenic mimicry channels formation and metastasis-related protein tests in vitro. Pharmacodynamics were evaluated by tumour inhibition rate, HE staining and TUNEL test in vivo. The enhanced anti-metastatic mechanism of the targeting liposomes was attributed to the downregulation of vimentin, vascular endothelial growth factor, matrix metalloproteinase 9 and upregulation of E-cadherin. In conclusion, the PFV modified DOX plus schisandrin B liposomes prepared in this study provided a treatment strategy with high efficiency for NSCLC.

[Purification and component identification of total proanthocyanidins in Choerospondias axillaris pericarp].

The present study determined the quantitative markers of total proanthocyanidins in the purification of the industrial waste Choerospondias axillaris pericarp based on the comparison results of high-performance liquid chromatography(HPLC) and mass spectrometry(MS) and optimized the purification process with two stable procyanidins as markers. The adsorption and desorption of five different macroporous adsorption resins, the static adsorption kinetics curve of NKA-Ⅱ resin, the maximum sample load, and the gradient elution were investigated. The UPLC-Q-TOF-MS/MS was employed for qualitative analysis of the newly-prepared total proanthocyanidins of C. axillaris pericarp. As revealed by the results, NKA-Ⅱ resin displayed strong adsorption and desorption toward total proanthocyanidins. The sample solution(50 mg·mL~(-1)) was prepared from 70% ethanol crude extract of C. axillaris pericarp dissolved in water and 7-fold BV of the sample solution was loaded, followed by static adsorption for 12 h. After 8-fold BV of distilled water and 6-fold BV of 10% ethanol were employed to remove impurities, the solution was eluted with 8-fold BV of 50% ethanol, concentrated, and dried under reduced pressure, and purified total proanthocyanidin powder was therefore obtained. Measured by vanillin-hydrochloric acid method, the purity and transfer rate of total proanthocyanidins were 47.67% and 59.92%, respectively, indicating the feasibi-lity of the optimized process. UPLC-Q-TOF-MS/MS qualitative analysis identified 16 procyanidins in C. axillaris total proanthocyanidins. The optimized purification process is simple in operation and accurate in component identification, and it can be applied to the process investigation of a class of components that are difficult to be separated and purified. It can also provide technical support and research ideas for the comprehensive utilization of industrial waste.

RPV-modified epirubicin and dioscin co-delivery liposomes suppress non-small cell lung cancer growth by limiting nutrition supply.

Chemotherapy for non-small cell lung cancer (NSCLC) is far from satisfactory, mainly due to poor targeting of antitumor drugs and self-adaptations of the tumors. Angiogenesis, vasculogenic mimicry (VM) channels, migration, and invasion are the main ways for tumors to obtain nutrition. Herein, RPV-modified epirubicin and dioscin co-delivery liposomes were successfully prepared. These liposomes showed ideal physicochemical properties, enhanced tumor targeting and accumulation in tumor sites, and inhibited VM channel formation, tumor angiogenesis, migration and invasion. The liposomes also downregulated VM-related and angiogenesis-related proteins in vitro. Furthermore, when tested in vivo, the targeted co-delivery liposomes increased selective accumulation of drugs in tumor sites and showed extended stability in blood circulation. In conclusion, RPV-modified epirubicin and dioscin co-delivery liposomes showed strong antitumor efficacy in vivo and could thus be considered a promising strategy for NSCLC treatment.

Ameloblastoma with mucous cells: A clinicopathological, BRAF mutation, and MAML2 rearrangement study.

OBJECTIVES: To investigate the clinicopathological features, BRAF V600E mutation, and MAML2 rearrangement of ameloblastoma with mucous cell differentiation. MATERIALS AND METHODS: Five cases of ameloblastoma with mucous cell differentiation were retrospectively studied. Clinicopathological features, BRAF V600E mutation, and MAML2 rearrangement were analyzed. Follow-up information was available for all cases. RESULTS: Of five cases, two cases were male and three were female, aged 18-55 years. Four cases were located in the mandible and one case in the maxilla. Histologically, four of the five cases (80%) presented with cystic features and three of the five cases (60%) with varying degrees of squamous metaplasia. The mucous cells were located in the epithelial islands or the luminal aspect of the cystic cavities. The BRAF V600E mutation was found in three of five cases (60%). All the cases showed no MAML2 rearrangement. Two cases were recurrent lesions, and one case had a local recurrence during the follow-up. CONCLUSIONS: Ameloblastoma with mucous cell differentiation is closely related to the cystic features, squamous metaplasia, and shows a high prevalence of BRAF V600E mutation. The absence of MAML2 rearrangement reveals that ameloblastoma with mucous cell differentiation and central mucoepidermoid carcinoma (MEC) are two distinct tumor entities.

Plastic bronchitis associated with adenovirus serotype 7 in children.

BACKGROUND: Plastic bronchitis is an uncommon but severe respiratory disease characterized by formation of casts in tracheobronchial tree. It can lead to airway obstruction and even respiratory failure. CASE PRESENTATION: Plastic bronchitis is mostly seen in both post-cardiac surgery patients, especially Fontan procedure, and infections including those caused by influenza viruses, Mycoplasma pneumoniae or tuberculosis. But it has rarely been reported to be associated with adenovirus infection. We report 2 cases of plastic bronchitis arising from adenovirus serotype 7 infection, manifested in repeated high fever, cough, and progressive dyspnea, and were diagnosed and eventually cured by bronchoscopy. CONCLUSIONS: Plastic bronchitis is a rare, variable and potentially fatal disease. In the cases we described, the cause was associated with adenovirus serotype 7 and its treatment required intervention with bronchoscopy and adequate control of the underlying disease.

Enhanced antitumor efficacy using epirubicin and schisandrin B co-delivery liposomes modified with PFV via inhibiting tumor metastasis.

As a malignant tumor, breast cancer is very prone to metastasis. Chemotherapy is one of the most common means for treating breast cancer. However, due to the serious metastasis and the poor targeting effect of traditional chemotherapeutic drugs, even after years of efforts, the therapeutic effect is still unsatisfied. Therefore, in this study, we constructed a kind of PFV modified epirubicin plus schisandrin B liposomes to solve the above disadvantages. In vitro experiments showed that the targeting liposomes with ideal physicochemical property could increase the cytotoxicity of MDA-MB-435S cells, destroy the formation of vasculogenic mimicry (VM), and inhibit tumor invasion and migration. Action mechanisms indicated that the inhibition of targeting liposomes on tumor metastasis was attributed to the regulation of the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), vimentin (VIM), and E-cadherin (E-cad). In vivo pharmacodynamic experiments showed that the targeting liposomes could significantly improve the antitumor effect in mice. H&E staining and TUNEL results showed that the targeting liposomes could promote the apoptosis of tumor cells. Hence, the PFV modified epirubicin plus schisandrin B liposomes constructed in this study provided a new therapeutic strategy for breast cancer.

GGP modified daunorubicin plus dioscin liposomes inhibit breast cancer by suppressing epithelial-mesenchymal transition.

Tumor invasion and metastasis are the nodus of anti-tumor. Epithelial cell-mesenchymal transition is widely regarded as one of the key steps in the invasion and metastasis of breast cancer. In this study, GGP modified daunorubicin plus dioscin liposomes are constructed and characterized. GGP modified daunorubicin plus dioscin liposome has suitable particle size, narrow PDI, zeta potential of about -5 mV, long cycle effect, and enhanced cell uptake due to surface modification of GGP making the liposome could enter the inside of the tumor to fully exert its anti-tumor effect. The results of in vitro experiments show that the liposome has superior killing effect on tumor cells and invasion. In vivo results indicate that the liposome prolongs the drug's prolonged time in the body and accumulates at the tumor site with little systemic toxicity. In short, the targeted liposome can effectively inhibit tumor invasion and may provide a new strategy for the treatment of invasive breast cancer.