Trends and patterns of antibiotic using from 2014 to 2018 in stomatology hospitals of China.

OBJECTIVE: To analyze trends of antibiotic consumption and expenditure in Chinese stomatology hospitals between 2014 and 2018 with a longitudinal study design, and show the impacts of the comprehensive policy on dental antibiotic use in China. SUBJECT AND METHODS: Consumption was quantified as the number of daily defined doses (DDDs) and expenditure as the procurement costs, using medical institutions' drug procurement data from the Chinese Monitoring Network for Rational Use of Drugs. Descriptive statistics was employed and the compound annual growth rate (CAGR) was calculated to show the average annual growth rate. RESULTS: Between 2014 and 2018, overall antibiotic consumption increased from 842.6 thousand DDDs to 1376.7 thousand DDDs (p < 0.001) and expenditure increased from 11.6 million RMB to 20.9 million RMB (p < 0.001), where other ß-lactam antibacterials accounted for the largest proportion of total consumption (37.1%-50.1%) and expenditure (52.9%-66.6%), and also increase the largest (CAGR = 18.4%, p < 0.001). The proportion of oral antibiotics was nearly 9 times of parenteral antibiotics in consumption (CAGR = 0.3%, p = 0.023) and only 2 times in expenditure (CAGR = -1.7%, p = 0.112). The non-restricted group accounted for more than 90% of consumption (CAGR = 0.6%, p < 0.001). In 2018, oral first-generation cephalosporins (22.8%), oral imidazole derivatives (22.3%), and oral second-generation cephalosporins (19.2%) were the most frequently used antibiotic classification, while parenteral second-generation cephalosporins were top one (19.8%) for expenditure. At chemical substance levels, the consumption of oral cefradine ranked top one (21.4%) and parenteral cefuroxime accounted for the largest proportion of expenditure (14.5%) in 2018. Oral cefradine, oral metronidazole, and oral cefaclor were the top three frequently consumed antibiotics throughout the five years. CONCLUSIONS: Despite the potential antibiotic overuse, the comprehensive antibiotic stewardship regulations of China got a satisfactory and better performance in dental practices. More effort is needed to establish more explicit guidelines to improve antibiotic stewardship, such as priority recommending amoxicillin and its derivatives for endodontic infections.

Polystyrene nanoplastics aggravated dibutyl phthalate-induced blood-testis barrier dysfunction via suppressing autophagy in male mice.

Nanoplastics (NPs) frequently cause adverse health effects by transporting organic pollutants such as dibutyl phthalate (DBP) into organisms by utilizing their large specific surface area, large surface charge, and increased hydrophobicity. However, the effects of NPs combined with DBP on the reproductive systems of mammals are still unclear. The present investigation involved the administration of polystyrene NPs (PS-NPs) to BALB/c mice via gavage, with a size of 100 nm and at doses of 5 mg/kg/day or 50 mg/kg/day, along with DBP at a dose of 0.5 mg/kg/day, or a combination of PS-NPs and DBP, for 30 days, to assess their potential for reproductive toxicity. The co-exposure of mice to PS-NPs and DBP resulted in a significant increase in reproductive toxicities compared to exposure to PS-NPs or DBP alone. This was demonstrated by a marked decrease in sperm quality, significant impairment of spermatogenesis, and increased disruption of the blood-testis barrier (BTB). Furthermore, a combination of in vivo and in vitro investigations were conducted to determine that the co-exposure of DBP and PS-NPs resulted in a noteworthy reduction in the expressions of tight junction proteins (ZO-1 and occludin). Moreover, the in vitro findings revealed that monobutyl phthalate (MBP, the active metabolite of DBP, 0.5 µg/mL) and PS-NPs (30 µg/mL or 300 µg/mL) inhibited autophagy in Sertoli cells, thereby increasing the expression of matrix metalloproteinases (MMPs). The study found that PS-NPs and DBP co-exposure caused harmful effects in male reproductive organs by disrupting BTB, which may be alleviated by reactivating autophagy. The paper's conclusions provided innovative perspectives on the collective toxicities of PS-NPs and other emerging pollutants.

Engineering stem cell therapeutics for cardiac repair.

Cardiovascular disease is the leading cause of death in the world. Stem cell-based therapies have been widely investigated for cardiac regeneration in patients with heart failure or myocardial infarction (MI) and surged ahead on multiple fronts over the past two decades. To enhance cellular therapy for cardiac regeneration, numerous engineering techniques have been explored to engineer cells, develop novel scaffolds, make constructs, and deliver cells or their derivatives. This review summarizes the state-of-art stem cell-based therapeutics for cardiac regeneration and discusses the emerged bioengineering approaches toward the enhancement of therapeutic efficacy of stem cell therapies in cardiac repair. We cover the topics in stem cell source and engineering, followed by stem cell-based therapies such as cell aggregates and cell sheets, and biomaterial-mediated stem cell therapies such as stem cell delivery with injectable hydrogel, three-dimensional scaffolds, and microneedle patches. Finally, we discuss future directions and challenges of engineering stem cell therapies for clinical translation.

Stepwise-Enhanced Tumor Targeting of Near-Infrared Emissive Au Nanoclusters with High Quantum Yields and Long-Term Stability.

We developed an in situ coordination-driven spatially confined strategy for preparing near-infrared emissive gold nanoclusters encapsulated by fluorinated polymers (AuNCs@PF, λmax = 810 nm) with good stability and high quantum yields (27.7%), far higher than those previously reported for NIR AuNCs (>800 nm). Based on the stepwise enhancements including long blood circulation-induced passive tumor targeting, fluoro-enhanced tumor permeation, and tumor microenvironment (weak acid)-induced aggregation retention in cells, these AuNCs demonstrated bright and stable NIR fluorescence imaging ability in tumors. Additionally, the AuNCs@PF were capable of fluorine magnetic resonance imaging and computed tomographic imaging. The multimodal imaging of tumor-bearing mice clearly implied the potential of AuNCs@PF in biomedical fields.

Pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor in children with acute leukaemia.

AIMS: This open-label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for the treatment of chemotherapy-induced neutropenia in children with acute leukaemia. METHODS: PEG-rhG-CSF was administered as a single 100 mcg/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG-rhG-CSF. PEG-rhG-CSF serum concentrations were determined by an enzyme-linked immunosorbent assay. Population pharmacokinetic (PPK) analysis was implemented using the nonlinear mixed-effects model. Short-term safety was evaluated through adverse events collection (registered at clinicaltrials.gov identifier: 03844360). RESULTS: A total of 16 acute leukaemia patients (1.8-13.6 years) were included, of whom two (12.5%) had grade 3 neutropenia, six (37.5%) had grade 4 neutropenia, and eight (50.0%) had severe neutropenia. For PPK modelling, 64 PEG-rhG-CSF serum concentrations were obtainable. A one-compartment model with first-order elimination was used for pharmacokinetic data modelling. The current weight was a significant covariate. The median (range) of clearance (CL) and area under the serum concentration-time curve (AUC) were 5.65 (1.49-14.45) mL/h/kg and 16514.75 (6632.45-54423.30) ng·h/mL, respectively. Bone pain, pyrexia, anaphylaxis and nephrotoxicity were not observed. One patient died 13 days after administration, and the objective assessment of causality was that an association with PEG-rhG-CSF was "possible". CONCLUSIONS: The AUC of PEG-rhG-CSF (100 mcg/kg, 3 mg maximum dose) in paediatric patients with acute leukaemia were similar to those of PEG-rhG-CSF (100 mcg/kg) in children with sarcoma. PEG-rhG-CSF is safe, representing an important therapeutic option for chemotherapy-induced neutropenia in paediatric patients with acute leukaemia.

Down-regulated IL36RN expression based on peripheral blood mononuclear cells and plasma of periodontitis patients and its clinical significance.

BACKGROUND: The role of IL-36 receptor antagonist (IL36RN), a mutated gene expression of IL-36 in periodontitis patients with peripheral blood mononuclear cells (PBMC) and plasma remains to be undetermined. MATERIALS AND METHODS: Our study discovered the IL36RN expression through GEO public databases and further validated by PBMC and plasma of periodontitis patients and healthy participants. A total of 194 participants of public datasets, consisting of 97 cases of periodontitis and 97 cases of healthy control were retrospectively evaluated and explored the gene enrichment pathways and clinical significance of IL36RN expression accompanied by three different cytokines. Furthermore, the clinical significance of IL36RN was evaluated in mild-to-severe patients of periodontitis by the receiver operating curve (ROC) using the area under the curve (AUC). RESULTS: IL36RN expressions were notably down-regulated in PBMC and plasma of periodontitis patients. Further, a positive correlation of IL36RN expression was significantly observed between PBMC and plasma of periodontitis patients while IL36RN expression was negatively correlated to serum-based three different cytokines of periodontitis patients. Meanwhile, the ROC-AUCs achieved a significantly higher range from 0.80 to 0.87 with PBMC of mild-to-severe and moderate-to-severe periodontitis patients whereas similar patients with plasma obtained a significant AUC range from 0.73 to 0.83. CONCLUSION: IL36RN can distinctively be detectable in periodontitis patients with PBMC and plasma, which can act as a down-regulated mutated gene that might play an effective role in causing periodontitis. IL36RN may involve by other inflammatory cytokines in the pathogenesis of periodontitis.

Parenchymal and stromal tissue regeneration of tooth organ by pivotal signals reinstated in decellularized matrix.

Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and vascular endothelial growth factor. In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signalling, but also parenchymal dentin via the Wnt/ß-catenin pathway. In an orthotopic large-animal model following parenchyma and stroma ablation, Wnt3a-recruited endogenous cells regenerated neurovascular stroma and differentiated into parenchymal odontoblast-like cells that extended the processes into newly formed dentin with a structure-mechanical equivalency to native dentin. Thus, the Alx3-Wnt3a axis enables postnatal progenitors with a modest innate regenerative capacity to regenerate adult tissues. Depleted signals in the decellularized matrix may be reinstated by a developmentally pivotal gene or corresponding protein.

A Metabolic Gene Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that emanates from the lips, mouth, paranasal sinuses, oropharynx, larynx, nasopharynx, and from other pharyngeal cancers. The availability of high-throughput expression data has made it possible to use global gene expression data to analyze the relationship between metabolic-related gene expression and clinical outcomes in HNSCC patients. METHOD: In this study, we used RNA sequencing (RNA-seq) data from the cancer genome atlas (TCGA), with validation in the GEO dataset to profile the metabolic microenvironment and define potential biomarkers for metabolic therapy. RESULTS: We extracted data for 529 patients and 327 metabolic genes (198 upregulated and 129 downregulated genes) in the TCGA database. Carbonic anhydrase 9 (CA9) and CA6 had the largest logFCs in the upregulated and downregulated genes, respectively. Our Cox regression model data showed 51 prognostic-related genes with lysocardiolipin acyltransferase 1 (LCLAT1) and choline dehydrogenase (CHDH) being associated with the highest risk (HR = 1.144, 95% CI = 1.044 ~ 1.251) and the lowest risk (HR = 0.580, 95% CI = 0.400 ~ 0.839) in HNSCC, respectively. We next used the ROC curve to evaluate whether the differentially expressed metabolic-related genes could serve as early predictors of HNSCC. The findings showed an AUC of 0.745 and 0.618 in the TCGA and GEO analysis, respectively. Besides, the ability for the genes to predict clinicopathological HNSCC status was analyzed and the data showed that the AUC for age, gender, grade, stage, T, M, and N was 0.520, 0.495, 0.568, 0.606, 0.577, 0.476, and 0.673, respectively, in the TCGA dataset. On the other hand, the AUC for age, gender, stage, T, M, N, smoking, and HPV16-pos was 0.599, 0.531, 0.622, 0.606, 0.616, 0.550, 0.614, 0.519, and 0.397, respectively, in the GEO dataset. CONCLUSION: Taken together, our study unearths a novel metabolic gene signature for the prediction of HNSCC prognosis based on the TCGA dataset. Our signature might point out the metabolic microenvironment disorders and provides potential treatment targets and prognostic biomarkers.

Traumatic Facial Fractures in Children and Adolescents.

This study showed a retrospective analysis of the incidence and pattern of traumatic facial fractures in a pediatric and adolescent population (≤18 years old) in China. The authors retrospectively reviewed 154 children and adolescent who had traumatic facial fractures and who were admitted to our university-affiliated hospitals from 2005 to 2010. This study enrolled 109 males and 45 females aged 11.9 ±â€Š5.2 years old. The incidence peaked around the periods of 12 to 18 years in the male, ≤6 and 16 to 18 years in the female. The most common etiologies were motor vehicle collisions (MVCs) (60, 39.0%), followed by high fall (40, 26.0%), low fall (32, 20.8%). The most common fracture sites were mandible (78, 50.6%) and nose (33, 21.4%), followed by orbit (31, 20.1%). A total of 35 (22.7%) patients suffered neurological deficit. The patients in the 12 to 18 age range group accounted for the largest proportion of 54.5%. Fracture incidence showed peaks between the hours of 12:00 to 16:00 PM (33.7%), during the autumn season (30.5%) and on Friday to Sunday (50.0%). The most common etiology and fracture site were MVCs and mandible, respectively. Etiologies and patterns of traumatic facial fractures vary with age. Continued efforts toward injury prevention of traumatic facial fracture among the children and adolescents are warranted.

Effects of low-temperature pretreatment on enhancing properties of refuse-derived fuel via microwave irradiation.

The present study focuses on pretreatment of enhancing the properties of refuse-derived fuel (RDF) via low-temperature microwave irradiation. These improved properties include lower chlorine content, a more porous surface structure and better combustion characteristics. In this study, low-temperature microwave irradiation was carried out in a modified microwave apparatus and the range of temperature was set to be 220-300℃. We found that the microwave absorbability of RDF was enhanced after being partly carbonized. Moreover, with the increasing of the final temperature, the organochlorine removal ratio was greatly increased to 80% and the content of chlorine was dramatically decreased to an extremely low level. It was also interesting to find that the chlorine of RDF was mainly released as HCl rather than organic chloride volatiles. The finding is just the same as the polyvinyl chloride pyrolysis process. In addition, pores and channels emerged during the modifying operation and the modified RDF has better combustibility and combustion stability than traditional RDF. This work revealed that low-temperature modification of RDF via microwave irradiation is significant for enhancing the quality of RDF and avoiding HCl erosion of equipment substantially.

Zn(2+)-Triggered Drug Release from Biocompatible Zirconium MOFs Equipped with Supramolecular Gates.

A new theranostic nanoplatform, comprising of monodisperse zirconium metal-organic frameworks (MOFs) as drug carriers and carboxylatopillar[5]arene-based supramolecular switches as gating entities, is constructed, and controlled drug release triggered by bio-friendly Zn(2+) ions (abundant in synaptic vesicles) and auxiliary thermal stimulus is realized. This on-command drug delivery system exhibits large pore sizes for drug encapsulation, excellent biodegradability and biocompatibility, extremely low cytotoxicity and premature drug release, and superior dual-stimuli responsiveness, opening a new avenue in targeted drug delivery and controlled release of therapeutic agents, especially in the treatment of central nervous system diseases.

Vertebroplasty versus kyphoplasty in osteoporotic vertebral compression fracture: a meta-analysis of prospective comparative studies.

PURPOSE: The goal of this article is to evaluate the efficacy and the safety of the percutaneous vertebroplasty (PVP) versus percutaneous kyphoplasty (PKP) in dealing with the osteoporotic vertebral compression fracture (OVCF). METHODS: In July 2014, a comprehensive systematic computer-based online search was performed by using the databases of PubMed, EMBASE, Cochrane Library, Web of Science, Wan Fang, and the China Biological Medicine. Only prospective comparative trials (PCT) and randomized controlled trials (RCT) that compared PVP with PKP were included. Trials were screened based on the inclusion and exclusion criteria previously formed. The Cochrane collaboration guidelines were also used to assess the quality of these included studies. The primary data of these studies [volume of the cement, postoperative vertebral height, visual analog scale (VAS) score and Oswestry Disability Index (ODI) score after the surgery, and so on] were carefully abstracted and processed by Revman 5.2.0 software The publication bias of the main results (cement leakage and adjacent-level fracture) were examined by Stata 12.0 (Begg and Egger test). Furthermore, the stability of the main results were also detected by sensitivity and cumulative analyses. RESULTS: Six RCT and 14 PCT studies involving 1,429 patients met our criteria and were included finally. Comparing these two methods, the PKP group took more operation time [SMD = 0.66, 95 % CI (0.28, 1.03), p = 0.0006] with higher anterior vertebral body height [SMD = 1.40, 95 % CI (0.49, 2.32), p = 0.003], greatly reduced Cobb angle in the long run [SMD = -0.61, 95 % CI (-1.04, -0.19), p = 0.005] and had lower risk of cement leakage. However, in VAS scores and ODI scores after the surgery whether for the short-term efficacy (no more than 1 week after the surgery) or long-term efficacy (more than six months), Cobb angle in the short run and new fracture in the adjacent level, no statistically differences were found between the two groups. CONCLUSIONS: Based on current evidence, PVP takes less time in the operation, while it has greater risk of cement leakage, was inferior in reducing Cobb angle in the long term and results in lower anterior vertebral body height after the surgery. For pain relief, which is the main desire of the patients, both procedures provide significant improvement in VAS and ODI pain scores. PVP is still an effective procedure.

Acetylcholine-triggered cargo release from supramolecular nanovalves based on different macrocyclic receptors.

Acetylcholine (ACh), a neurotransmitter located in cholinergic synapses, can trigger cargo release from mesoporous silica nanoparticles equipped with calixarene- or pillarene-based nanovalves by removing macrocycles from the stalk components. The amount and speed of cargo release can be controlled by varying the concentration of ACh in solution or changing the type of gating macrocycle. Although this proof-of-concept study is far from a real-life application, it provides a possible route to treat diseases related to the central nervous system.

Core-shell PLGA/collagen nanofibers loaded with recombinant FN/CDHs as bone tissue engineering scaffolds.

Poly(lactic-co-glycolic acid) (PLGA)/collagen nanofibrous scaffolds have been utilized in the tissue engineering field. It has been shown that both fibronectin (FN) and cadherin 11 (CDH) play important roles in the progress of osteogenesis and cell adhesion. The aim of this study was to fabricate recombinant FN/CDHs (rFN/CDHs)-loaded PLGA/collagen nanofibrous scaffolds and evaluate their effects on the adhesion and differentiation of human bone marrow mesenchymal stem cells (hMSCs). PLGA/collagen nanofibers were made by coaxial electrospinning. The morphology and mechanical properties of PLGA/collagen nanofibrous mats were analyzed by scanning electron microscopy and mechanical testing, respectively. The performance of scaffolds was evaluated in terms of the viability, morphology, and osteogenic gene expression levels of hMSCs. rFN/CDHs was successfully incorporated into the PLGA/collagen nanofibers. The release of rFN/CDHs from PLGA nanofibers was investigated by liquid chromatography-mass spectrometry. rFN/CDHs improved the mechanical properties of the PLGA/collagen nanofibers. The controlled release of rFN/CDHs can enhance the proliferation of hMSCs and induce osteogenic gene expression (alkaline phosphatase, RUNX2, and osteocalcin). Our data imply that rFN/CDHs may induce hMSCs differentiation into osteoblasts and PLGA/collagen nanofibers loaded with rFN/CDHs have potential in bone tissue engineering.

Influence of fluoride treatment on surface properties, biodegradation and cytocompatibility of Mg-Nd-Zn-Zr alloy.

Fluoride treatment is a commonly used technique or pre-treatment to optimize the degradation kinetic and improve the biocompatibility of magnesium-based implant. The influence of changed surface properties and degradation kinetics on subsequent protein adsorption and cytocompatibility is critical to understand the biocompatibility of the implant. In this study, a patent magnesium alloy Mg-Nd-Zn-Zr alloy (JDBM) designed for cardiovascular stent application was treated by immersion in hydrofluoric acid. A 1.5 µm thick MgF2 layer was prepared. The surface roughness was increased slightly while the surface zeta potential was changed to a much more negative value after the treatment. Static contact angle test was performed, showing an increase in hydrophilicity and surface energy after the treatment. The MgF2 layer slowed down in vitro degradation rate, but lost the protection effect after 10 days. The treatment enhanced human albumin adsorption while no difference of human fibrinogen adsorption amount was observed. Direct cell adhesion test showed many more live HUVECs retained than bare magnesium alloy. Both treated and untreated JDBM showed no adverse effect on HUVEC viability and spreading morphology. The relationship between changed surface characteristics, degradation rate and protein adsorption, cytocompatibility was also discussed.

Advancing the performance characteristics of rubber asphalt mixtures through the integration of Basic Oxygen Furnace (BOF) slag: A focus on static and dynamic mechanical enhancements.

To investigate the advantageous effects of incorporating industrial solid waste basic oxygen furnace (BOF) slag on the mechanical characteristics of warm-mixed rubber asphalt (WMRA) and hot-mixed rubber asphalt (HMRA) mixture, varying proportions of BOF slag were substituted for limestone coarse aggregates (0%, 25%, 50%, and 75%). Additionally, a 1.5% dosage of Sasobit warm-mixed modifier was introduced to prepare the rubber asphalt. Subsequent to preparation, both static mechanical tests (including Marshall and indirect tensile tests) and dynamic mechanical tests (including dynamic creep and elastic modulus tests) were conducted to evaluate the influence of BOF slag on the mechanical behavior of WMRA and HMRA mixtures across different substitution levels. Following testing, a two-way analysis of variance (ANOVA) was employed to dissect the impact of BOF slag content and Sasobit warm-mixed modifier on the static and dynamic mechanical properties of the rubber asphalt mixtures. The findings reveal that BOF slag exhibits commendable engineering aggregate properties, enabling substantial substitution of coarse aggregates in both HMRA and WMRA mixtures. As the proportion of BOF slag increases, it enhances the resistance of asphalt mixtures to permanent deformation and cracking under static and dynamic loading conditions, while broadening the range of elastic deformation for both WMRA and HMRA mixtures subjected to repeated loading. Moreover, a synergistic enhancement in the resistance of rubber asphalt mixtures to dynamic load-induced deformation is observed when employing both BOF slag and Sasobit warm-mixed modifier. The findings offer valuable insights for enhancing the performance of WMRA and HMRA mixtures, as well as broadening the utilization of BOF slag and waste rubber.

Design and in vitro evaluation of 223Ra/99mTc-loaded spherical nano-hydroxyapatite in bone tumor therapy.

Aim: Nano-hydroxyapatite (nHA) is a good nanocarrier to load 223Ra, but the low specific activity (sp.act.) of 223Ra@nHA limits its application in medicine. Methods: We proposed a method for preparing nHA using PEG as a template, which significantly increases the sp.act of 223Ra@nHA and a new method to loaded 99mTc for in vivo tracking. Results: The nHA synthesized using PEG as a template was associated with higher sp.act for 223Ra in comparison to nHA with identical particle size and without PEG. The nHA load 99mTc-MDP was associated with higher labeling rate and stability in comparison to 99mTc. Conclusion: All these findings suggest that using PEG as a template and 99mTc-MDP could be the most effective of synthetic 223Ra/99mTc@nHA.

[Box: see text].

Surface-associated residues in subtilisins contribute to poly-L-lactic acid depolymerization via enzyme adsorption.

Poly-L-lactic acid (PLLA) is currently the most abundant bioplastic; however, limited environmental biodegradability and few recycling options diminish its value as a biodegradable commodity. Enzymatic recycling is one strategy for ensuring circularity of PLLA, but this approach requires a thorough understanding of enzymatic mechanisms and protein engineering strategies to enhance activity. In this study, we engineer PLLA depolymerizing subtilisin enzymes originating from Bacillus species to elucidate the molecular mechanisms dictating their PLLA depolymerization activity and to improve their function. The surface-associated amino acids of two closely related subtilisin homologues originating from Bacillus subtilis (BsAprE) and Bacillus pumilus (BpAprE) were compared, as they were previously engineered to have nearly identical active sites, but still varied greatly in PLLA depolymerizing activity. Further analysis identified several surface-associated amino acids in BpAprE that lead to enhanced PLLA depolymerization activity when engineered into BsAprE. In silico protein modelling demonstrated increased enzyme surface hydrophobicity in engineered BsAprE variants and revealed a structural motif favoured for PLLA depolymerization. Experimental evidence suggests that increases in activity are associated with enhanced polymer binding as opposed to substrate specificity. These data highlight enzyme adsorption as a key factor in PLLA depolymerization by subtilisins.

Aged fragmented-polypropylene microplastics induced ageing statues-dependent bioenergetic imbalance and reductive stress: In vivo and liver organoids-based in vitro study.

Ageing is a nature process of microplastics that occurrs daily, and human beings are inevitably exposed to aged microplastics. However, a systematic understanding of ageing status and its toxic effect is currently still lacking. In this study, plastic cup lids-originated polypropylene (PP) microplastics were UV-photoaged until the carbonyl index (CI), a canonical indicator for plastic ageing, achieved 0.08, 0.17, 0.22 and 0.28. The adverse hepatic effect of these aged PPs (aPPs) was evaluated in Balb/c mice (75 ng/mL water, about 200 particles/day) and human-originated liver organoids (LOs, 50 particles/mL, ranged from 5.94 to 13.15 ng/mL) at low-dose equivalent to human exposure level. Low-dose of aged PP could induce hepatic reductive stress both in vitro and in vivo, by elevating the NADH/NAD+ratio in a CI-dependent manner, together with hepatoxicity (indicated by increased AST secretion and cytotoxicity), and disrupted the genes encoding the nutrients transporters and NADH subunits accompanied by the restricted ATP supply, declined mitochondrial membrane potential and mitochondrial complexI/IV activities, without significant increase in MDA levels in the liver. These changes in the liver disrupted systematic metabolism, representing a circulatory panel of increases in the lactate, triglyceride, Fgf21 levels, and decreases in the pyruvate level, linked the reductive stress to the declined body weight gain but elevated hepatic NADH contents following aPPs exposure. Additionally, assessing by the LOs, it was found that digestion drastically accelerated the ageing of aPPs and worsen the energy supply upon mitochondria, representing a "scattergun effect" induced by the formation of micro- and nano-plastics mixture toward NADH/NAD+imbalance.

Biomaterials-assisted cancer vaccine delivery: preclinical landscape, challenges, and opportunities.

INTRODUCTION: Cancer vaccines (protein and peptide, DNA, mRNA, and tumor cell) have achieved remarkable success in the treatment of cancer. In particular, advances in the design and manufacture of biomaterials have made it possible to control the presentation and delivery of vaccine components to immune cells. AREAS COVERED: This review summarizes findings from major databases, including PubMed, Scopus, and Web of Science, focusing on articles published between 2005 and 2024 that discuss biomaterials in cancer vaccine delivery. EXPERT OPINION: The development of cancer vaccines is hindered by several bottlenecks, including low immunogenicity, instability of vaccine components, and challenges in evaluating their clinical efficacy. To transform preclinical successes into viable treatments, it is essential to pursue continued innovation, collaborative research, and address issues related to scalability, regulatory pathways, and clinical validation, ultimately improving outcomes against cancer.