Circadian rhythm disruption upregulating Per1 in mandibular condylar chondrocytes mediating temporomandibular joint osteoarthritis via GSK3ß/ß-CATENIN pathway.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) has a high incidence rate, but its pathogenesis remains unclear. Circadian rhythm is an important oscillation in the human body and influences various biological activities. However, it is still unclear whether circadian rhythm affects the onset and development of TMJOA. METHODS: We disrupted the normal rhythm of rats and examined the expression of core clock genes in the mandibular condylar cartilage of the jaw and histological changes in condyles. After isolating rat mandibular condylar chondrocytes, we upregulated or downregulated the clock gene Per1, examined the expression of cartilage matrix-degrading enzymes, tested the activation of the GSK3ß/ß-CATENIN pathway and verified it using agonists and inhibitors. Finally, after downregulating the expression of Per1 in the mandibular condylar cartilage of rats with jet lag, we examined the expression of cartilage matrix-degrading enzymes and histological changes in condyles. RESULTS: Jet lag led to TMJOA-like lesions in the rat mandibular condyles, and the expression of the clock gene Per1 and cartilage matrix-degrading enzymes increased in the condylar cartilage of rats. When Per1 was downregulated or upregulated in mandibular condylar chondrocytes, the GSK3ß/ß-CATENIN pathway was inhibited or activated, and the expression of cartilage matrix-degrading enzymes decreased or increased, which can be rescued by activator and inhibitor of the GSK3ß/ß-CATENIN pathway. Moreover, after down-regulation of Per1 in mandibular condylar cartilage in vivo, significant alleviation of cartilage degradation, cartilage loss, subchondral bone loss induced by jet lag, and inhibition of the GSK3ß/ß-CATENIN signaling pathway were observed. Circadian rhythm disruption can lead to TMJOA. The clock gene Per1 can promote the occurrence of TMJOA by activating the GSK3ß/ß-CATENIN pathway and promoting the expression of cartilage matrix-degrading enzymes. The clock gene Per1 is a target for the prevention and treatment of TMJOA.

Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents.

Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bth allele differs from the wild-type allele at only a single base pair. Injection of Cas9-guide RNA-lipid complexes targeting the Tmc1Bth allele into the cochlea of neonatal Tmc1Bth/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears than in uninjected ears or ears injected with control complexes that targeted an unrelated gene. Enhanced acoustic startle responses were observed among injected compared to uninjected Tmc1Bth/+ mice. These findings suggest that protein-RNA complex delivery of target gene-disrupting agents in vivo is a potential strategy for the treatment of some types of autosomal-dominant hearing loss.

Changes of Temporomandibular Joint Morphology and Symptoms in Class II Malocclusion Patients With Bilateral Sagittal Split Ramous Osteotomy.

This study included 46 patients with class II malocclusion ranging in age from 19 to 39 years old treated with bilateral sagittal split ramous osteotomy (BSSRO). Left and right temporomandibular joints (TMJs) of each subject were evaluated independently with cone-beam computed tomography (CBCT) before operation (T1), 1 week after operation (T2), and 1 year after operation (T3) and assessed the effects of orthognathic surgery (OGS) on the temporomandibular joint disease (TMD) symptoms. Temporomandibular joint morphology evaluation included condylar volume, condylar area, cortical bone thickness, depth of the mandibular fossa, fossa thickness, joint nodule angle, joint space, and condyle-fossa relationship, which were calculated by using the Mimics software and 3-matic software. Data were statistically analyzed with SPSS software (P <0.05 means statistically significant). In our study, bilateral TMJs have no difference in T3. Bilateral sagittal split ramous osteotomy had no significant effect on the articular fossa. The condyle volume and surface area decreased from T1 to T3, but the cortical thickness of the bone did not change significantly. More anterior condyle positions in T1 and more posterior in T3.21 patients had at least 1 sign or symptom of TMD in T1 and 27 patients in T3. Four patients who were asymptomatic in T1 developed pain after surgery, 10 developed noises, 12 showed limited mouth opening, and 8 had abnormal opening patterns. It is concluded that more condylar posterior position after BSSRO and the reduction of condyle may be related to the enlargement of anterior space. The number of patients with joint symptoms increased postoperative, and the impact of BSSRO on TMD may be negative.

Mycobacteriaceae Mineralizes Micropolyethylene in Riverine Ecosystems.

Microplastic (MP) contamination is a serious global environmental problem. Plastic contamination has attracted extensive attention during the past decades. While physiochemical weathering may influence the properties of MPs, biodegradation by microorganisms could ultimately mineralize plastics into CO2. Compared to the well-studied marine ecosystems, the MP biodegradation process in riverine ecosystems, however, is less understood. The current study focuses on the MP biodegradation in one of the world's most plastic contaminated rivers, Pearl River, using micropolyethylene (mPE) as a model substrate. Mineralization of 13C-labeled mPE into 13CO2 provided direct evidence of mPE biodegradation by indigenous microorganisms. Several Actinobacteriota genera were identified as putative mPE degraders. Furthermore, two Mycobacteriaceae isolates related to the putative mPE degraders, Mycobacterium sp. mPE3 and Nocardia sp. mPE12, were retrieved, and their ability to mineralize 13C-mPE into 13CO2 was confirmed. Pangenomic analysis reveals that the genes related to the proposed mPE biodegradation pathway are shared by members of Mycobacteriaceae. While both Mycobacterium and Nocardia are known for their pathogenicity, these populations on the plastisphere in this study were likely nonpathogenic as they lacked virulence factors. The current study provided direct evidence for MP mineralization by indigenous biodegraders and predicted their biodegradation pathway, which may be harnessed to improve bioremediation of MPs in urban rivers.

Sulphur dioxide and fluoride co-exposure induce incisor hypomineralization and amelogenin upregulation via YAP/RUNX2 signaling pathway.

Sulphur dioxide (SO2) and fluoride are among the most common environmental pollutants affecting human health, and both co-exist in areas predominantly consuming coal. It is vital to analyse the combined toxicity of SO2 and fluoride, and their effects on health and the underlying mechanisms of their co-exposure have not yet been adequately assessed. In the present study, we used ICR mice and LS8 cells to investigate the toxicity of SO2 and fluoride exposure to the enamel, alone or in combination. Factorial design analysis was used to reveal the combined toxicity in vitro and in vivo. Co-exposure to SO2 and fluoride exacerbated enamel injury, resulting in more severe hypomineralization of incisor, and enamel structure disorders in mice, and could induce the accumulation of protein residue in the matrix of the enamel. Amelogenin expression was increased upon exposure to SO2 and fluoride, but enamel matrix proteases were not affected. Consistent with our in vivo results, co-exposure of SO2 and fluoride aggravated amelogenin expression in LS8 cells, and increased the YAP and RUNX2 levels. Co-exposure to SO2 and fluoride resulted in greater toxicity than individual exposure, both in vitro and in vivo, indicating that residents of areas exposed to SO2 and fluoride may have an increased risk of developing enamel damage.

A Modified Procedure for Anterior Maxillary Osteotomy.

ABSTRACT: Anterior maxillary osteotomy is a traditional operation in the treatment of maxillary protrusion. Varies fields about operation have been changed or improved in those years to avoid different kinds of complications. In our study, the authors would present 1 kind of improved anterior maxillary osteotomy surgical method. The study was conducted at the Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Guangzhou, Guangdong province. Patients are divided into improved group and general group. Patients after surgery were claimed to have regular return visits. Occlusion, tooth vitalities, postoperative complications would be well evaluated. The operative time, blood losses, complications showed no different at maxillary operation. Our procedure could give much better and direct sight of anterior maxillary bone, and the simplified osteotomy lines could help maxilla move, reduce the times spent on hard tissue cut off or grind. The modified procedure can meet clinical command, improve dentofacial deformities, and gives convenience to surgeon.

Enabling Oxygen-Sulfur Exchange Reaction to Produce Semicrystalline Copolymers from Carbon Disulfide and Ethylene Oxide.

This work describes the first example of semicrystalline poly(thiocarbonate)s from carbon disulfide (CS2 ) and ethylene oxide (EO), two mass producible low-cost monomers. Lewis acid/base pairs (LPs) exhibit high activity (EO conversion up to >99%, 8 h) in catalyzing the copolymerization under low Lewis pair/monomer ratio of 1:1500. Oxygen-sulfur exchange reaction (O-S ER) during the copolymerization of CS2 and EO, the generation and mutual copolymerization with COS, CO2 , and episulfide, is harnessed to introduce crystallizable segments [SC(O)O and SC(S)S] in the copolymer. The type of Lewis base is found to have a great impact on the chain microstructure and the crystalline properties. The formed copolymers with melting point from 117.7 to 245.3 °C are obtained. The maximum crystallinity is estimated to be 78% based on the powder wide-angle X-ray diffraction pattern. This work provides a general method to prepare semicrystalline sulfur-containing polymers.

Treatment of a mandibular functional shift in an adolescent boy with temporomandibular disorder and crossbites.

A mandibular functional shift usually poses a challenge for orthodontists, especially when it is accompanied by a temporomandibular disorder (TMD). Accurate diagnosis and complete elimination of the etiologic factors are the keys to an esthetic and stable outcome. This article describes the treatment of a teenager with a mandibular functional shift, TMD symptoms, and facial asymmetry resulting from an asymmetric maxillary arch form and multiple crossbites as occlusal interferences. The treatment alternatives and effective orthodontic techniques are described. To optimize the treatment results and prevent the recurrence of the TMD after treatment, the displaced mandible was repositioned by full-time wearing of a splint for 10 months. Adhesive bite-blocks were used to maintain the newly acquired mandibular position during fixed appliance treatment. A series of nickel-titanium and stainless steel rectangular archwires was placed in the maxillary arch to reshape it for 8 months after alignment. Finally, the displaced mandible was steadily seated into its physiologic position with fine occlusion. The TMD symptoms disappeared and never relapsed after treatment. At 2 years 3 months of retention, there was good stability. The combined splint and fixed appliance approach resolved an intractable clinical problem and avoided using additional appliances. An esthetic, functional, and stable outcome was achieved that satisfied both the patient and his parents.

Transport and retention of sinking microplastics in a well-mixed estuary.

Estuaries have been shown to be potential hotspots of microplastic accumulation, but the hydrodynamic conditions and particle properties that control this process need further investigation. We have designed a series of numerical particle-tracking experiments to examine the sensitivity of retention in estuaries to particle size, particle density and varying tides and freshwater flow. At the end of the simulation, over 90 % of sinking particles are retained in the estuary, and the retention rate is further increased by high river runoff. In contrast, increased river discharge increases the number of marginally-buoyant (i.e. density close to estuarine water) particles that escape the estuary. Larger particle size tends to limit the downstream transport of sinking particles but can facilitate the transport of marginally-buoyant particles. Tidal asymmetry, vertical turbulent mixing and the vertical structure of the subtidal circulation are proposed as the underlying mechanisms controlling the fate of particles.

Changes in carbohydrate metabolism and soil microorganisms under the stress of polyamide and polyethylene nanoplastics during rice (Oryza sativa L.) growth.

Nanoplastics (NPs) presence in agricultural soils can affect plant growth and impact the quality of agricultural products. To investigate the effect of polyamide (PA) NPs and polyethylene (PE) NPs on carbohydrate metabolism and soil microorganisms during rice growth, rice seedlings were exposed to soil containing 2 g/kg of 100 nm PA or 100 nm PE powder for 33 d. The results revealed that 100 nm PE reduced shoot length and dry weight of rice by 4.14 % and 15.68 %, respectively. Analyzing the expression of hexokinase-2 (HXK), phosphofructokinase-1 (PFK), pyruvate kinase (PK) and isocitrate dehydrogenase (IDH), which are four genes related to carbohydrate metabolism, 100 nm PA decreased the expression of PFK and increased the expression of PK and IDH. 100 nm PE increased the expression of HXK, PFK, PK, and IDH. The results of soil microorganisms showed that 100 nm PA significantly effects on 3 bacterial phyla (Bacteroidota, Deinococcota, and Desulfobacterota), whereas 100 nm PE significantly effects on phylum Rozellomycota, class Umbelopsidomycetes, and an unclassified Firmicutes. Our study provides direct evidence of the negative effects of PA and PE on rice, which may be important for assessing the risk of NPs on agroecosystems.

Machine learning-assisted assessment of key meteorological and crop factors affecting historical mulch pollution in China.

Degraded mulch pollution is of a great concern for agricultural soils. Although numerous studies have examined this issue from an environmental perspective, there is a lack of research focusing on crop-specific factors such as crop type. This study aimed to explore the correlation between meteorological and crop factors and mulch contamination. The first step was to estimate the amounts of mulch-derived microplastics (MPs) and phthalic acid esters (PAEs) during the rapid expansion period (1993-2012) of mulch usage in China. Subsequently, the Elastic Net (EN) and Random Forest (RF) models were employed to process a dataset that included meteorological, crop, and estimation data. At the national level, the RF model suggested that coldness in fall was crucial for MPs generation, while vegetables acted as a key factor for PAEs release. On a regional scale, the EN results showed that crops like vegetables, cotton, and peanuts remained significantly involved in PAEs contamination. As for MPs generation, coldness prevailed over all regions. Aridity became more critical for southern regions compared to northern regions due to solar radiation. Lastly, each region possessed specific crop types that could potentially influence its MPs contamination levels and provide guidance for developing sustainable ways to manage mulch contamination.

Impact of Invisalign® first system on molar width and incisor torque in malocclusion during the mixed dentition period.

In orthodontic treatment of patients during the mixed dentition period, arch expansion and opening deep overbite are one of the objectives to achieve proper alignment of the teeth and correction of sagittal and vertical discrepancies. However, the expected outcomes of most therapeutic regimens are not clear, making it impossible to standardize early treatment effects. Therefore, this study was designed to evaluate the impact of the Invisalign® First System on the dental arch circumference and incisor inclination in patients during the mixed dentition period. A total of 21 children during the mixed dentition period (10 females and 11 males, with an average age of 8.76 years) were included in this study. The patients received non-extraction treatment through Invisalign® First System clear aligners, and no other auxiliary devices were used except Invisalign® accessories. Subsequently, the cooperation degree of patients during treatment and the oral measurement parameters at the beginning (T1) and the end (T2) of treatment were collected. All patients showed moderate/good cooperation degree during treatment. Besides, horizontal width of the maxillary first molar increased significantly; the designed arch expansion was 4.1 mm (±1.4 mm), while the actual arch expansion was 3.0 mm (±1.7 mm). Furthermore, the torque expression rate of upper anterior teeth reached 56.53%. Invisalign® First System clear aligners can effectively correct the teeth of patients during the mixed dentition period, widen the circumference of dental arch, and control the torque of incisors.

Amyloid-ß peptide treatment reverses bone loss in the mandibular condyle via Wnt signalling pathway.

Objective: To explore the effect of amyloid-ß peptide (Aß) on mandibular condyle to develop a new treatment for postmenopausal women with Temporomandibular joint osteoarthritis. Methods: A murine bone loss model was established by ovariectomy. Microstructure parameters of the condyle were measured by microcomputed tomography before and after intraperitoneal injection with Aß. Flow cytometry, Alizarin red staining, RT-qPCR assays, FITC/PI staining, Oil Red O staining and western blotting were used to evaluate the effect of Aß on the osteogenic differentiation of mouse bone marrow stromal stem cells (mBMSCs). Results: In vivo, condylar microstructure parameters increased. Serum osteoprotegerin and procollagen type 1 N propeptide increased in a dose-dependent manner after the injection of Aß, which were opposite the changes observed in c-terminal telopeptides of type I collagen, tumor necrosis factor-α and the high serum level of leptin. In vitro, Aß promoted calcium nodule formation in the cells. The expression of ALP, Runx2, osteorix and osteocalcin increased significantly. The expression of mRNAs related to the Wnt signaling pathway was significantly upregulated, which could be blocked by DKK1. Conclusion: Aß can reverse bone loss in the mandibular condyle in ovariectomized mice through promoting the osteogenic differentiation of mBMSCs via the Wnt pathway.

pH-responsive CuS/DSF/EL/PVP nanoplatform alleviates inflammatory bowel disease in mice via regulating gut immunity and microbiota.

The clinical treatment of inflammatory bowel disease (IBD) is challenging. We developed copper sulfate (CuS)/disulfiram (DSF)/methacrylic acid-ethyl acrylate copolymer (EL)/polyvinylpyrrolidone (PVP) nanoplatform (CuS/DSF/EL/PVP) and evaluated its efficiency for treating IBD. After oral administration, the pH-sensitive EL protected the CuS/DSF/EL/PVP against degradation by acidic gastric juices. Once the colon was reached, EL was dissolved, releasing DSF and Cu2+. Further, the main in vivo metabolite of DSF can bind to Cu2+ and form copper (II) N, N-diethyldithiocarbamate (CuET), which significantly alleviated acute colitis in mice. Notably, CuS/DSF/EL/PVP outperformed CuS/EL/PVP and DSF/EL/PVP nanoplatforms in reducing colonic pathology and improving the secretion of inflammation-related cytokines (such as IL-4 and IL-10) in the colonic mucosa. RNA-seq analysis revealed that the nanoplatform reduced colonic inflammation and promoted intestinal mucosal repair by upregulating C-type lectin receptor (CLR)-related genes and signaling pathways. Furthermore, CuS/DSF/EL/PVP showed potential for improving colitis Th1/Th17 cells through innate immunity stimulation, down-regulation of inflammatory cytokines, and upregulation of anti-inflammatory cytokines. Additionally, the intervention with CuS/DSF/EL/PVP led to increased intestinal flora diversity, decreased Escherichia-Shigella abundance, and elevated levels of short-chain fatty acid (SCFA)-producing bacteria Prevotella, Lactobacillus, and Bifidobacterium, indicating their potential to modulate the dysregulated intestinal flora and suppress inflammation. STATEMENT OF SIGNIFICANCE: Our study introduces the CuS/DSF/EL/PVP nanoplatform as a therapeutic strategy for treating inflammatory bowel disease (IBD). This approach demonstrates significant efficacy in targeting the colon and alleviating acute colitis in mice. It uniquely modulates gut immunity and microbiota, exhibiting a notable impact on inflammation-related cytokines and promoting intestinal mucosal repair. The nanoplatform's ability to regulate gut flora diversity, combined with its cost-effective and scalable production, positions it as a potentially transformative treatment for IBD, offering new avenues for personalized medical interventions.

Micro- and nano-plastics in the atmosphere: A review of occurrence, properties and human health risks.

The ubiquitous occurrence of micro/nano plastics (MNPs) poses potential threats to ecosystem and human health that have attracted broad concerns in recent decades. Detection of MNPs in several remote regions has implicated atmospheric transport as an important pathway for global dissemination of MNPs and hence as a global health risk. In this review, the latest research progress on (1) sampling and detection; (2) origin and characteristics; and (3) transport and fate of atmospheric MNPs was summarized. Further, the current status of exposure risks and toxicological effects from inhaled atmospheric MNPs on human health is examined. Due to limitations in sampling and identification methodologies, the study of atmospheric nanoplastics is very limited today. The large spatial variation of atmospheric MNP concentrations reported worldwide makes it difficult to compare the overall indoor and outdoor exposure risks. Several in vitro, in vivo, and epidemiological studies demonstrate adverse effects of immune response, apoptosis and oxidative stress caused by MNP inhalation that may induce cardiovascular diseases and reproductive and developmental abnormalities. Given the emerging importance of atmospheric MNPs, the establishment of standardized sampling-pretreatment-detection protocols and comprehensive toxicological studies are critical to advance environmental and health risk assessments of atmospheric MNPs.

Dopamine promotes osteogenic differentiation of PDLSCs by activating DRD1 and DRD2 during orthodontic tooth movement via ERK1/2 signaling pathway.

Introduction: Orthodontic tooth movement (OTM) involves complex interactions between mechanical forces and periodontal tissue adaptation, mainly mediated by periodontal ligament cells, including periodontal ligament stem cells (PDLSCs), osteoblasts, and osteoclasts. Dopamine (DA), a neurotransmitter known for its critical role in bone metabolism, is investigated in this study for its potential to enhance osteogenic differentiation in PDLSCs, which are pivotal in OTM. This study examined the potential of DA to facilitate OTM by binding to DA receptors (D1R and D2R) and activating the ERK1/2 signaling pathway. We propose that DA's interaction with these receptors on PDLSCs could enhance osteogenic differentiation, thereby accelerating bone remodeling and reducing the duration of orthodontic treatments, which offering a novel approach to improve clinical outcomes in orthodontic care. Methods: This study utilized a rat OTM model, micro-CT, histological analyses, and in vitro assays to investigate dopamine's effect on osteogenesis. PDLSCs were cultured and treated with DA, and cytotoxicity, osteogenic differentiation, gene and protein expression assessed. Results: Dopamine administration significantly increased trabecular bone density and osteogenic marker expression in an OTM rat model. In vitro, DA at 10 nM optimally promoted human PDLSCs osteogenesis without affecting proliferation. Blocking DA receptors or inhibiting the ERK1/2 pathway attenuated these effects, underscoring the importance of dopaminergic signaling in tension-induced osteogenesis during OTM. Conclusion: Taken together, our study reveals that local dopamine administration at a concentration of 10 nM not only enhances tension-induced osteogenesis in vivo but also significantly promotes osteogenic differentiation of PDLSCs in vitro through D1 and D2 receptor-mediated ERK1/2 signaling pathway activation.

Alendronate sodium induces G1 phase arrest and apoptosis in human umbilical vein endothelial cells by inhibiting ROS-mediated ERK1/2 signaling.

Bisphosphonates are potent bone resorption inhibitors, among which alendronate sodium (ALN) is commonly prescribed for most osteoporosis patients, but long-term application of ALN can cause bisphosphonate-related osteonecrosis of jaw (BRONJ), the pathogenesis of which remains unclear. Previous studies have suggested that bisphosphonates cause jaw ischemia by affecting the biological behavior of vascular endothelial cells, leading to BRONJ. However, the impacts of ALN on vascular endothelial cells and its mechanism remain unclear. The purpose of this work is to assess the influence of ALN on human umbilical vein endothelial cells (HUVECs) and clarify the molecular pathways involved. We found that high concentration of ALN induced G1 phase arrest in HUVECs, demonstrated by downregulation of Cyclin D1 and Cyclin D3. Moreover, high concentration of ALN treatment showed pro-apoptotic effect on HUVECs, demonstrated by increased levels of the cleaved caspase-3, the cleaved PARP and Bax, along with decreased levels of anti-apoptotic protein Bcl-2. Further experiments showed that ERK1/2 phosphorylation was decreased. Additionally, ALN provoked the build-up of reactive oxygen species (ROS) in HUVECs, leading to ERK1/2 pathway suppression. N-acetyl-L-cysteine (NAC), a ROS scavenger, efficiently promoted the ERK1/2 phosphorylation and mitigated the G1 phase arrest and apoptosis triggered by ALN in HUVECs. PD0325901, an inhibitor of ERK1/2 that diminishes the ERK1/2 phosphorylation enhanced the ALN-induced G1 phase arrest and apoptosis in HUVECs. These findings show that ALN induces G1 phase arrest and apoptosis through ROS-mediated ERK1/2 pathway inhibition in HUVECs, providing novel insights into the pathogenic process, prevention and treatment of BRONJ in individuals receiving extended use of ALN.

Retention of buoyant plastic in a well-mixed estuary due to tides, river discharge and winds.

Estuaries can act as plastic retention hotspots, but the hydrodynamic controls on retention are not well understood. This study investigates the retention of river-sourced buoyant plastics in a well-mixed estuary, the Waitemata Estuary, using validated numerical simulations of floats with different tides, winds, and freshwater discharge. The proportion of floats grounded on the shore in all seven simulations is higher than 60 % and over 90 % in five simulations after ten days. <20 % of the floats leave the estuarine mouth in any of the simulations. An increase of two orders of magnitude in freshwater discharge doubles the likelihood for floats to reach the lower estuary. However, we find increased freshwater discharge doubles the lateral circulation towards the shore and results in similar proportions of grounding (90 %) as the low discharge cases. These findings challenge the conventional view that plastics preferentially enter the open ocean after high river discharge.

Structural design of gradient porous dental implant based on orthogonal test.

OBJECTIVES: To solve the current problems of loosening and dislodging caused by the high elastic modulus of solid implants, we attempted to study a gradient porous dental implant that can lower the stress concentration and reduce the elastic modulus. METHODS: SolidWorks software was utilized to design the abutment and mechanical structure of the gradient porous implant. The mechanical properties of the gradient porous implant were evaluated by an orthogonal experimental design from four aspects: pore shape, pore diameter, porous layer height, and circumferential distribution. ANSYS software was used to evaluate the distribution of Von-Mises stress in the implant and its surrounding bone tissues under different structural combination parameters to derive the optimal combination of gradient porous implant parameters. RESULTS: The effects of the four factors, namely, pore shape, pore diameter, porous layer height and pore distribution, on the maximum Von-Mises stress on the implant were as follows. As the pore shape became smaller and the circumferential distribution decreased, the Von-Mises stress decreased significantly. The pore diameter went from 500 µm to 600 µm and then to 700 µm. The Von-Mises stress decreased and then increased. It increased with the increase in the height of the porous layer. CONCLUSIONS: The final optimal combination of parameters for the gradient porous implant was as follows: square pore shape, pore diameter of 600 µm, porous layer height of 3 mm, and quadratic step in pore distribution.

Glucose oxidase-loaded colloidal stable WS2 nanobowls for combined starvation/photothermal therapy of colorectal tumors.

Glucose is used as an important nutrient to support cell growth. The glucose oxidase (GOx) can transform glucose into gluconic acid and toxic H2O2, which can be used for tumor starvation therapy. However, the leakage of GOx may cause severe side effects to the normal tissue. To prevent the accidental leakage of GOx, this study proposes the chemical modification of GOx on the photothermal transducing agent surface, to realize the safe and combined starvation and photothermal therapy of colorectal tumors. Polyvinylpyrrolidone (PVP)-modified WS2 nanobowls (WS2-PVP) as a photothermal transducing agent were produced using a one-pot preparation method. Then, α-lipoic acid (LA) molecules were immobilized at the sulfur-deficient sites on the surface of WS2 nanobowls to afford the chemical loading of GOx through amide bonds. Under the irradiation of a near-infrared laser (808 nm), thermal energy is generated by WS2 to kill colorectal cancer cells locally. The photothermal conversion efficiency of WS2-PVP-LA was 27.2%. This study is anticipated to open up an alternative avenue for the rational design of multifunctional nanotherapeutics for tumor therapy.