Transcriptome Analysis in Response to Infection of Xanthomonas oryzae pv. oryzicola Strains with Different Pathogenicity.

Bacterial leaf streak (BLS) caused by Xanthomonas oryzae pv. oryzicola (Xoc) is one of the most important quarantine diseases in the world. Breeding disease-resistant varieties can solve the problem of prevention and treatment of BLS from the source. The discovery of the molecular mechanism of resistance is an important driving force for breeding resistant varieties. In this study, a BLS-resistant near isogenic line NIL-bls2 was used as the material. Guangxi Xoc strain gx01 (abbreviated as WT) and its mutant strain (abbreviated as MT) with a knockout type III effectors (T3Es) gene were used to infect rice material NIL-bls2. The molecular interaction mechanism of rice resist near isogenic lines in response to infection by different pathogenic strains was analyzed by transcriptome sequencing. The results showed that there were 415, 134 and 150 differentially expressed genes (DEGs) between the WT group and the MT group at 12, 24 and 48 h of post inoculation (hpi). Through GO and KEGG enrichment analysis, it was found that, compared with non-pathogenic strains, the T3Es secreted by pathogenic strains inhibited the signal transduction pathway mediated by ethylene (ET), jasmonic acid (JA) and salicylic acid (SA), and the MAPKK (MAPK kinase) and MAPKKK (MAPK kinase kinase) in the MAPK (mitogen-activated protein kinase) cascade reaction, which prevented plants from sensing extracellular stimuli in time and starting the intracellular immune defense mechanism; and inhibited the synthesis of lignin and diterpenoid phytochemicals to prevent plants from establishing their own physical barriers to resist the invasion of pathogenic bacteria. The inhibitory effect was the strongest at 12 h, and gradually weakened at 24 h and 48 h. To cope with the invasion of pathogenic bacteria, rice NIL-bls2 material can promote wound healing by promoting the synthesis of traumatic acid at 12 h; at 24 h, hydrogen peroxide was degraded by dioxygenase, which reduced and eliminated the attack of reactive oxygen species on plant membrane lipids; and at 48 h, rice NIL-bls2 material can resist the invasion of pathogenic bacteria by promoting the synthesis of lignin, disease-resistant proteins, monoterpene antibacterial substances, indole alkaloids and other substances. Through transcriptome sequencing analysis, the molecular interaction mechanism of rice resistance near isogenic lines in response to infection by different pathogenic strains was expounded, and 5 genes, Os01g0719300, Os02g0513100, Os03g0122300, Os04g0301500, and Os10g0575100 closely related to BLS, were screened. Our work provides new data resources and a theoretical basis for exploring the infection mechanism of Xoc strain gx01 and the resistance mechanism of resistance gene bls2.

Oldest colobine calcaneus from East Asia (Zhaotong, Yunnan, China).

Apart from a juvenile hominoid, the locality of Shuitangba (southwestern China, 6.5-6.0 Ma) has yielded a mandible and proximal femur attributed to the colobine genus Mesopithecus. A complete colobine calcaneus also accompanies this material, but its association with the other Mesopithecus material remains to be confirmed. These fossil elements are very important as they represent the oldest known colobines from East Asia, extend the dispersal of Mesopithecus to southwestern China, and underscore its close affinities and potential ancestry to the odd-nosed colobines. The present article focuses on the functional morphology of this complete calcaneus to reconstruct the positional habits, infer the paleocology, and understand the dispersal patterns of this fossil colobine. The studied characters corroborate the attribution of this element to colobines and support potential affinities with the Mesopithecus remains of the same locality. Functionally, characters such as the long and narrow tuber calcanei, the short proximal calcaneal region, and the relatively extended and long and narrow proximal calcaneoastragalar facet appear to enable habitual pedal flexion with conjunct inversion that accommodate the foot on diversely oriented and differently sized arboreal substrates. On the other hand, the relatively short distal calcaneal region is functionally related to (mainly terrestrial) quadrupedal activities, wherein thrust and rapid flexion are required. This combination of characters suggests that the Shuitangba colobine could move at ease on arboreal substrates and was also able to occasionally use terrestrial substrates. The potential affinities of this calcaneus to Mesopithecus and its positional profile most likely imply an eastward migration via forested corridors. In Shuitangba, this fossil colobine could trophically and positionally exploit a wide range of habitats successfully coexisting with resident hominoids.

Prediction Model of Cardiac Risk for Dental Extraction in Elderly Patients with Cardiovascular Diseases.

BACKGROUND: With the rapidly increasing population of elderly people, dental extraction in elderly individuals with cardiovascular diseases (CVDs) has become quite common. The issue of how to assure the safety of elderly patients with CVDs undergoing dental extraction has perplexed dentists and internists for many years. And it is important to derive an appropriate risk prediction tool for this population. OBJECTIVES: The aim of this retrospective, observational study was to establish and validate a prediction model based on the random forest (RF) algorithm for the risk of cardiac complications of dental extraction in elderly patients with CVDs. METHODS: Between August 2017 and May 2018, a total of 603 patients who fulfilled the inclusion criteria were used to create a training set. An independent test set contained 230 patients between June 2018 and July 2018. Data regarding clinical parameters, laboratory tests, clinical examinations before dental extraction, and 1-week follow-up were retrieved. Predictors were identified by using logistic regression (LR) with penalized LASSO (least absolute shrinkage and selection operator) variable selection. Then, a prediction model was constructed based on the RF algorithm by using a 5-fold cross-validation method. RESULTS: The training set, based on 603 participants, including 282 men and 321 women, had an average participant age of 72.38 ± 8.31 years. Using feature selection methods, 11 predictors for risk of cardiac complications were screened out. When the RF model was constructed, its overall classification accuracy was 0.82 at the optimal cutoff value of 18.5%. In comparison to the LR model, the RF model showed a superior predictive performance. The AUROC (area under the receiver operating characteristic curve) scores of the RF and LR models were 0.83 and 0.80, respectively, in the independent test set. The AUPRC (area under the precision-recall curve) scores of the RF and LR models were 0.56 and 0.35, respectively, in the independent test set. CONCLUSION: The RF-based prediction model is expected to be applicable for preoperative clinical assessment for preventing cardiac complications in elderly patients with CVDs undergoing dental extraction. The findings may aid physicians and dentists in making more informed recommendations to prevent cardiac complications in this patient population.

Improvement of sulfamethoxazole (SMX) elimination and inhibition of formations of hydroxylamine-SMX and N4-acetyl-SMX by membrane bioreactor systems.

Sulfamethoxazole (SMX) has frequently been detected in aquatic environments. In natural environment, not only individual microorganism but also microbial consortia are involved in some biotransformation of pollutants. The competition for space under consortia causing cell-cell contact inhibition changes the cellular behaviors. Herein, the membrane bioreactor system (MBRS) was applied to improve SMX elimination thorough exchanging the cell-free broths (CFB). The removal efficiency of SMX was increased by more than 24% whether under the pure culture of A. faecalis or under the co-culture of A. faecalis and P. denitrificans with MBRS. Meanwhile, MBRS significantly inhibited the formation of HA-SMX, and Ac-SMX from parent compound. Additionally, the cellular growth under MBRS was obviously enhanced, indicating that the increases in the cellular growth under MBRS are possibly related to the decreases in the levels of HA-SMX and Ac-SMX compared to that without MBRS. The intracellular NADH/NAD+ ratios of A. faecalis under MBRS were increased whether thorough itself-recycle of CFB or exchanging CFB between the pure cultures of A. faecalis and P. denitrificans, suggesting that the enhancement in the bioremoval efficiencies of SMX under MBRS by A. faecalis is likely related to the increases in the NADH/NAD+ ratio. Taken together, the regulation of cell-to-cell communication is preferable strategy to improve the bioremoval efficiency of SMX.

Autogenous Metallic Pipe Leak Repair in Potable Water Systems.

Copper and iron pipes have a remarkable capability for autogenous repair (self-repair) of leaks in potable water systems. Field studies revealed exemplars that metallic pipe leaks caused by nails, rocks, and erosion corrosion autogenously repaired, as confirmed in the laboratory experiments. This work demonstrated that 100% (N = 26) of 150 µm leaks contacting representative bulk potable water in copper pipes sealed autogenously via formation of corrosion precipitates at 20-40 psi, pH 3.0-11.0, and with upward and downward leak orientations. Similar leaks in carbon steel pipes at 20 psi self-repaired at pH 5.5 and 8.5, but two leaks did not self-repair permanently at pH 11.0 suggesting that water chemistry may control the durability of materials that seal the leaks and therefore the permanence of repair. Larger 400 µm holes in copper pipes had much lower (0-33%) success of self-repair at pH 3.0-11.0, whereas all 400 µm holes in carbon steel pipes at 20 psi self-repaired at pH 4.0-11.0. Pressure tests indicated that some of the repairs created at 20-40 psi ambient pressure could withstand more than 100 psi without failure. Autogenous repair has implications for understanding patterns of pipe failures, extending the lifetime of decaying infrastructure, and developing new plumbing materials.

Bacterial cellulose nanopaper as reinforcement for polylactide composites: renewable thermoplastic NanoPaPreg.

Bacterial cellulose (BC) is often regarded as a prime candidate nano-reinforcement for the production of renewable nanocomposites. However, the mechanical performance of most BC nanocomposites is often inferior compared with commercially available polylactide (PLLA). Here, the manufacturing concept of paper-based laminates is used, i.e., "PaPreg," to produce BC nanopaper reinforced PLLA, which has been called "nanoPaPreg" by the authors. It is demon-strated that high-performance nanoPaPreg (vf = 65 vol%) with a tensile modulus and strength of 6.9 ± 0.5 GPa and 125 ± 10 MPa, respectively, can be fabricated. It is also shown that the tensile properties of nanoPaPreg are predominantly governed by the mechanical performance of BC nanopaper instead of the individual BC nanofibers, due to difficulties impregnating the dense nanofibrous BC network.

Accurate movement of jaw segment in virtual 3D orthognathic surgery.

In traditional virtual 3D orthognathic surgery, after repositioning the maxillary segment to the desired position, surgeons usually roughly rotate or adjust the mandibular segment to obtain a relatively good relationship with maxillary dentition to calculate the virtual terminal occlusion splint. However, surgeons are not easy to avoid penetrability, overlap, or an overly large space existing between the maxillary and mandibular dentitions during this process. The present report offered a new method to obtain a suitable virtual terminal occlusal splint that could avoid penetrability, overlap, or an overly large space between the maxillary and mandibular dentitions, and simultaneously accurately moving the maxillary or mandibular segment to the desired position utilizing the planned terminal occlusion plaster models in virtual orthognathic surgery. For double jaw surgery, after aligning the planned plaster models to the 3D maxilla and mandible, we could simultaneously move the maxillary and mandibular segment as a whole that maintain the planned terminal occlusion to the desired position. This present method may enhance the accuracy of 3D virtual orthognathic surgery and save plenty of time spend on virtual surgery simulation, which also offers a useful educational method for training junior surgeons and students.

Polyethyleneimine surface-modified silver-selenium nanocomposites for anti-infective treatment of wounds by disrupting biofilms.

Bacterial biofilm formation is associated with the pathogenicity of pathogens and poses a serious threat to human health and clinical therapy. Complex biofilm structures provide physical barriers that inhibit antibiotic penetration and inactivate antibiotics via enzymatic breakdown. The development of biofilm-disrupting nanoparticles offers a promising strategy for combating biofilm infections. Hence, polyethyleneimine surface-modified silver-selenium nanocomposites, Ag@Se@PEI (ASP NCs), were designed for synergistic antibacterial effects by destroying bacterial biofilms to promote wound healing. The results ofin vitroantimicrobial experiments showed that, ASP NCs achieved efficient antibacterial effects againstStaphylococcus aureus (S. aureus)andEscherichia coli (E. coli)by disrupting the formation of the bacterial biofilm, stimulating the outbreak of reactive oxygen species and destroying the integrity of bacterial cell membranes. Thein-vivobacterial infection in mice model showed that, ASP NCs further promoted wound healing and new tissue formation by reducing inflammatory factors and promoting collagen fiber formation which efficiently enhanced the antibacterial effect. Overall, ASP NCs possess low toxicity and minimal side effects, coupled with biocompatibility and efficient antibacterial properties. By disrupting biofilms and bacterial cell membranes, ASP NCs reduced inflammatory responses and accelerated the healing of infected wounds. This nanocomposite-based study offers new insights into antibacterial therapeutic strategies as potential alternatives to antibiotics for wound healing.

Machine Learning Algorithms for the Diagnosis of Class III Malocclusions in Children.

Artificial intelligence has been applied to medical diagnosis and decision-making but it has not been used for classification of Class III malocclusions in children. OBJECTIVE: This study aims to propose an innovative machine learning (ML)-based diagnostic model for automatically classifies dental, skeletal and functional Class III malocclusions. METHODS: The collected data related to 46 cephalometric feature measurements from 4-14-year-old children (n = 666). The data set was divided into a training set and a test set in a 7:3 ratio. Initially, we employed the Recursive Feature Elimination (RFE) algorithm to filter the 46 input parameters, selecting 14 significant features. Subsequently, we constructed 10 ML models and trained these models using the 14 significant features from the training set through ten-fold cross-validation, and evaluated the models' average accuracy in test set. Finally, we conducted an interpretability analysis of the optimal model using the ML model interpretability tool SHapley Additive exPlanations (SHAP). RESULTS: The top five models ranked by their area under the curve (AUC) values were: GPR (0.879), RBF SVM (0.876), QDA (0.876), Linear SVM (0.875) and L2 logistic (0.869). The DeLong test showed no statistical difference between GPR and the other models (p > 0.05). Therefore GPR was selected as the optimal model. The SHAP feature importance plot revealed that he top five features were SN-GoMe (the ratio of the length of the anterior skull base SN to that of the mandibular base GoMe), U1-NA (maxillary incisor angulation to NA plane), Overjet (the distance between two lines perpendicular to the functional occlusal plane from U1 and L), ANB (the difference between angles SNA and SNB), and AB-NPo (the angle between the AB and N-Pog line). CONCLUSIONS: Our findings suggest that ML models based on cephalometric data could effectively assist dentists to classify dental, functional and skeletal Class III malocclusions in children. In addition, features such as SN_GoMe, U1_NA and Overjet can as important indicators for predicting the severity of Class III malocclusions.

Effects of soil microplastic heterogeneity on plant growth vary with species and microplastic types.

Microplastics are heterogeneously distributed in soils. However, it is unknown whether soil microplastic heterogeneity affects plant growth and root foraging responses and whether such effects vary with plant species and microplastic types. We grew each of seven herbaceous species (Platycodon grandiflorus, Trifolium repens, Portulaca oleracea, Medicago sativa, Taraxacum mongolicum, Perilla frutescenst, and Paspalum notatum) in heterogeneous soil (patches without microplastics and patches with 0.2 % microplastics) and homogeneous soil (patches with 0.1 % microplastics). Three microplastic types were tested: polypropylene (PP), polyacrylonitrile (PAN), and polyester (PET). P. frutescens showed no response to soil microplastic heterogeneity. For P. grandiflora, microplastic heterogeneity tended to decrease its biomass (total, shoot and root) when the microplastic was PAN and also shoot biomass when it was PET, but had no effect when it was PP. For T. repens, microplastic heterogeneity promoted biomass when PAN was used, decreased total and root biomass when PET was used, but showed no effect when PP was used. Microplastic heterogeneity increased biomass of P. oleracea and decreased that of M. sativa when PET was used, but had no effect when PP or PAN was used. For T. mongolicum, microplastic heterogeneity reduced biomass when the microplastic was PAN, tended to increase total and root biomass when it was PP, but showed no effect when it was PET. For P. notatum, microplastic heterogeneity increased biomass when the microplastic was PP, decreased it when PET was used, but had no effect when PAN was used. However, biomass of none of the seven species showed root foraging responses at the patch level. Therefore, soil microplastic heterogeneity can influence plant growth, but such effects depend on species and microplastic types and are not associated with root foraging. Our findings highlight the roles of soil microplastic heterogeneity, which may influence species interactions and community structure and productivity.

Effect of PEG anchor in PEGylation of folate-modified cationic liposomes with PEG-derivatives on systemic siRNA delivery into the Tumor.

In this study, we prepared small interfering RNA (siRNA)/cationic liposome complexes (lipoplexes) modified with folate (FA)-polyethylene glycol (PEG, MW 2000, 3400 or 5000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) to facilitate their uptake into tumor cells via folate receptor (FR), and with PEG1600-cholesterol (PEG1600-Chol) or PEG2000-chondroitin sulfate conjugate (PEG2000-CS), to enhance their systemic stability. Among the FA-PEG-modified siRNA lipoplexes, 0.5 mol% FA-PEG5000-DSPE-modified lipoplexes with 2.5 mol% PEG2000-CS or PEG1600-Chol (LP-0.5F5/2.5P2-CS and LP-0.5F5/2.5P1.6-CL, respectively) exhibited selective growth inhibition of human nasopharyngeal carcinoma KB cells through transduction with polo-like kinase 1 (PLK1) siRNA. Furthermore, the LP-0.5F5/2.5P2-CS and LP-0.5F5/2.5P1.6-CL lipoplexes exhibited decreased agglutination with erythrocytes through PEGylation, and markedly decreased the accumulation of siRNA in murine lungs after systemic injection. Finally, systemic injection of LP-0.5F5/2.5P2-CS and LP-0.5F5/2.5P1.6-CL lipoplexes resulted in accumulation of siRNA in KB tumor xenografts. These findings suggest that PEGylation of FA-PEG5000-DSPE-modified siRNA lipoplexes with PEG2000-CS or PEG1600-Chol might improve their systemic stability without the loss of selective transfection activity in tumor cells.

Comparison of micro-radiofrequency therapy and tolterodine for the treatment of newly diagnosed overactive bladder: A retrospective cohort study.

Purpose: This study aimed to retrospectively compare the efficacy and safety of micro-radiofrequency (RF) therapy through the urethra vs. oral tolterodine tartrate in the treatment of newly diagnosed overactive bladder (OAB). Materials and methods: In this study, 46 patients who were newly diagnosed with moderate-to-severe OAB were included; 23 of them underwent the micro-RF treatment procedure, and the other 23 patients took tolterodine. Bladder diaries were recorded 3 days before treatment and during the follow-up period on 1, 3, and 7 weeks after micro-RF therapy or oral tolterodine. Micturition parameters including daily voiding times, daily urge urinary incontinence (UI) episodes, daily urgency episodes, mean volume per micturition, post-void residual volume (PVR), maximum urine flow rate (Qmax), overactive bladder symptom score (OABSS), and quality of life (QoL) score were analyzed. Results: All 46 patients underwent either micro-RF or oral tolterodine treatment, as well as a complete follow-up. The incidence of adverse events in the micro-RF group was 8.7% (2/23), and that in the tolterodine group was 43.5% (10/23). The following two adverse events happened in the micro-RF group: an injury to the urethra during catheterization in a man and a urinary tract infection in a woman, both of which were relieved or disappeared after day 3. The adverse effects in the tolterodine group were mainly dry mouth (4/23), dysuria (5/23), and constipation (8/23), but none of the patients withdrew from the drug therapy. Compared to pre-therapy, all parameters of both groups, including daily voiding times, daily urgency episodes, mean volume per micturition, OABSS, and QoL score, demonstrated significant improvements during follow-up in 7 weeks after therapy, except for daily UI episodes in the tolterodine group, while the above parameters showed bigger improvements in the micro-RF group than in the tolterodine group. Besides, the general treatment efficacy of micro-RF was 73.9% (17/23), which was significantly better than tolterodine (10/23, 43.5%), and the difference was 30.4% [95% CI: 3.4-57.5%, p = 0.036]. Conclusion: In this retrospective study, we found that micro-RF therapy is safe and more effective than oral tolterodine for newly diagnosed moderate-to-severe OAB in a short-term follow-up. Stronger evidence would be provided through a well-designed, prospective, randomized controlled trial.

Effect of the combination of cationic lipid and phospholipid on gene-knockdown using siRNA lipoplexes in breast tumor cells and mouse lungs.

Previously, using three types of cationic lipids, the effect of phospholipids in liposomal formulations on gene-knockdown efficacy was determined after in vitro and in vivo transfection with small interfering RNA (siRNA)/cationic liposome complexes (siRNA lipoplexes) containing various cationic lipids and phospholipids. In the present study, six other types of cationic lipids, namely N,N-dimethyl-N-tetradecyltetradecan-1-aminium bromide, N-hexadecyl-N,N-dimethylhexadecan-1-aminium bromide (DC-1-16), 2-[bis{2-(tetradecanoyloxy)ethyl}amino]-N,N,N-trimethyl-2-oxoethan-1-aminium chloride (DC-6-14), 1,2-di-O-octadecenyl-3-trimethylammonium propane chloride (DOTMA), 1,2-distearoyl-3-trimethylammonium-propane chloride (DSTAP) and 1,2-dioleoyl-3-dimethylammonium-propane were selected, and the effect of phospholipids in liposomal formulations containing each cationic lipid on gene-knockdown was evaluated. A total of 30 types of cationic liposomes composed of each cationic lipid with phosphatidylethanolamine containing unsaturated or saturated diacyl chains (C14, C16 or C18) were prepared. Regardless of the type of cationic lipid, the inclusion of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in the liposomal formulations resulted in injectable size of siRNA lipoplexes after mixing of siRNA and cationic liposomes. Transfection of their lipoplexes with luciferase (Luc) siRNA into human breast cancer MCF-7-Luc cells stably expressing Luc led to a strong knockdown of Luc. Furthermore, the systemic injection of siRNA lipoplexes composed of DC-1-16, DC-6-14, DOTMA or DSTAP with DOPE resulted in siRNA accumulation in the lungs. Significant gene-knockdown was observed in the lungs of mice following the systemic injection of siRNA lipoplexes containing DC-1-16 and DOPE. Cationic liposomes composed of DC-1-16 and DOPE serve as potential carriers for in vitro and in vivo siRNA transfection.

Automated Sagittal Skeletal Classification of Children Based on Deep Learning.

Malocclusions are a type of cranio-maxillofacial growth and developmental deformity that occur with high incidence in children. Therefore, a simple and rapid diagnosis of malocclusions would be of great benefit to our future generation. However, the application of deep learning algorithms to the automatic detection of malocclusions in children has not been reported. Therefore, the aim of this study was to develop a deep learning-based method for automatic classification of the sagittal skeletal pattern in children and to validate its performance. This would be the first step in establishing a decision support system for early orthodontic treatment. In this study, four different state-of-the-art (SOTA) models were trained and compared by using 1613 lateral cephalograms, and the best performance model, Densenet-121, was selected was further subsequent validation. Lateral cephalograms and profile photographs were used as the input for the Densenet-121 model, respectively. The models were optimized using transfer learning and data augmentation techniques, and label distribution learning was introduced during model training to address the inevitable label ambiguity between adjacent classes. Five-fold cross-validation was conducted for a comprehensive evaluation of our method. The sensitivity, specificity, and accuracy of the CNN model based on lateral cephalometric radiographs were 83.99, 92.44, and 90.33%, respectively. The accuracy of the model with profile photographs was 83.39%. The accuracy of both CNN models was improved to 91.28 and 83.98%, respectively, while the overfitting decreased after addition of label distribution learning. Previous studies have been based on adult lateral cephalograms. Therefore, our study is novel in using deep learning network architecture with lateral cephalograms and profile photographs obtained from children in order to obtain a high-precision automatic classification of the sagittal skeletal pattern in children.

CBCT combining with plaster models: application in virtual three-dimensional subapical segmental osteotomy to obtain more precise occlusal splint.

Anterior subapical segmental osteotomy is considered to be an important surgical technique to obtain functional occlusion and improve the facial profile for patients with maxillary and mandibular protrusion or retrusion, and some complications, such as ischemic necrosis of the distal segment, devitalization of the teeth adjacent to the osteotomy site, and inadequate movement space of segment for obtaining a good occlusion or facial profile, usually exist during surgery. Imprecise measurement of root length, interradicular distance, and intertooth distance based on traditional panoramic radiography that demonstrated existing horizontal distortion and vertical distortion may play an important role in resulting in these problems. In addition, the root is invisible for surgical simulation in traditional plaster models. The recently developed cone-beam computed tomography (CBCT) presents a higher spatial resolution with a lower radiation dose, simultaneously with excellent accuracy and without magnification of images. The presented technique was used to obtain a precise occlusal splint in virtual 3D subapical segmental osteotomy by combining CBCT with plaster models that could guarantee the measurement accuracy of root length, interradicular distance, and intertooth distance, followed by the result of fewer tooth root damage and more precise forecasting of available movement space of jaw segment. Combining with other advantages of virtual 3D surgery, such as precise teeth surface of plaster models, soft tissue simulation, genoplasty simulation, and zygoma plasty simulation, this presented technique may offer a preferable method to patients who need subapical segmental osteotomy.

Optimal combination of cationic lipid and phospholipid in cationic liposomes for gene knockdown in breast cancer cells and mouse lung using siRNA lipoplexes.

Formulation of cationic liposomes is a key factor that determine the gene knockdown efficiency by cationic liposomes/siRNA complexes (siRNA lipoplexes). Here, to determine the optimal combination of cationic lipid and phospholipid in cationic liposomes for in vitro and in vivo gene knockdown using siRNA lipoplexes, three types of cationic lipid were used, namely 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), dimethyldioctadecylammonium bromide (DDAB) and 11-[(1,3-bis(dodecanoyloxy)-2-((dodecanoyloxy)methyl)propan-2-yl)amino]-N,N,N-trimethyl-11-oxoundecan-1-aminium bromide (TC-1-12). Thereafter, 30 types of cationic liposome composed of each cationic lipid with phosphatidylcholine or phosphatidylethanolamine containing saturated or unsaturated dialkyl chains (C14, C16, or C18) were prepared. The inclusion of phosphatidylethanolamine containing unsaturated and long dialkyl chains with DOTAP- or DDAB-based cationic liposomes induced strong luciferase gene knockdown in human breast cancer MCF-7-Luc cells stably expressing luciferase gene. Furthermore, the inclusion of phosphatidylcholine or phosphatidylethanolamine containing saturated and short dialkyl chains or unsaturated and long dialkyl chains into TC-1-12-based cationic liposomes resulted in high gene knockdown efficacy. When cationic liposomes composed of DDAB/1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), TC-1-12/DOPE and TC-1-12/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine were used, significant gene knockdown occurred in the lungs of mice following systemic injection of siRNA lipoplexes. Overall, the present findings indicated that optimal phospholipids in cationic liposome for in vitro and in vivo siRNA transfection were affected by the types of cationic lipid used.

Biomaterials and 3D Bioprinting Strategies to Model Glioblastoma and the Blood-Brain Barrier.

Glioblastoma (GBM) is the most prevalent and lethal adult primary central nervous system cancer. An immunosuppresive and highly heterogeneous tumor microenvironment, restricted delivery of chemotherapy or immunotherapy through the blood-brain barrier (BBB), together with the brain's unique biochemical and anatomical features result in its universal recurrence and poor prognosis. As conventional models fail to predict therapeutic efficacy in GBM, in vitro 3D models of GBM and BBB leveraging patient- or healthy-individual-derived cells and biomaterials through 3D bioprinting technologies potentially mimic essential physiological and pathological features of GBM and BBB. 3D-bioprinted constructs enable investigation of cellular and cell-extracellular matrix interactions in a species-matched, high-throughput, and reproducible manner, serving as screening or drug delivery platforms. Here, an overview of current 3D-bioprinted GBM and BBB models is provided, elaborating on the microenvironmental compositions of GBM and BBB, relevant biomaterials to mimic the native tissues, and bioprinting strategies to implement the model fabrication. Collectively, 3D-bioprinted GBM and BBB models are promising systems and biomimetic alternatives to traditional models for more reliable mechanistic studies and preclinical drug screenings that may eventually accelerate the drug development process for GBM.

Compensating the cell-induced light scattering effect in light-based bioprinting using deep learning.

Digital light processing (DLP)-based three-dimensional (3D) printing technology has the advantages of speed and precision comparing with other 3D printing technologies like extrusion-based 3D printing. Therefore, it is a promising biomaterial fabrication technique for tissue engineering and regenerative medicine. When printing cell-laden biomaterials, one challenge of DLP-based bioprinting is the light scattering effect of the cells in the bioink, and therefore induce unpredictable effects on the photopolymerization process. In consequence, the DLP-based bioprinting requires extra trial-and-error efforts for parameters optimization for each specific printable structure to compensate the scattering effects induced by cells, which is often difficult and time-consuming for a machine operator. Such trial-and-error style optimization for each different structure is also very wasteful for those expensive biomaterials and cell lines. Here, we use machine learning to learn from a few trial sample printings and automatically provide printer the optimal parameters to compensate the cell-induced scattering effects. We employ a deep learning method with a learning-based data augmentation which only requires a small amount of training data. After learning from the data, the algorithm can automatically generate the printer parameters to compensate the scattering effects. Our method shows strong improvement in the intra-layer printing resolution for bioprinting, which can be further extended to solve the light scattering problems in multilayer 3D bioprinting processes.

The findings of 18F-fluorodeoxyglucose positron emission tomography-computed tomography scan in patients with hidradenitis suppurativa in Malaysia: A multicenter study.

Hidradenitis suppurativa (HS) is known to have association with systemic diseases with chronic inflammation such as psoriasis. We aim to describe the concomitant systemic inflammation in patients with HS using 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) scan. This was a case-control study conducted in three tertiary hospitals in Northern Malaysia from January to December 2017, involving HS patients aged 18 years and above. Thirty-two HS patients with age- and sex-matched controls were recruited with a mean age of 31.4 years (range: 18-56). Numerous cutaneous inflammatory foci were detected on FDG-PET/CT scan in clinically unapparent sites (27/32, 84.4%). Approximately 90.6%, 93.8%, and 50.0% of the patients had significantly higher cutaneous uptake over nasal, mandibular, and scalp regions, respectively (P < 0.0001). PET/CT scan did not detect any systemic inflammation unlike those found in psoriasis. Three (9.4%) patients had thyroid nodules with high uptake (maximum standard uptake values ranging from 2.9 to 11.3). Two of them were confirmed to have papillary thyroid carcinoma, while the third patient has inconclusive finding. 18F-FDG PET/CT scan may be useful to map disease burden of HS. Nonlesional inflammatory foci on the skin of the nose, mandibular, and scalp are probably significant. The association of thyroid carcinoma in HS warrants further evaluation.

Effect of pre­freezing and saccharide types in freeze­drying of siRNA lipoplexes on gene­silencing effects in the cells by reverse transfection.

Our previous study reported that reverse (Rev)­transfection with small interfering RNA (siRNA)/cationic liposome complexes (siRNA lipoplexes) freeze­dried in trehalose or sucrose solution resulted in high gene­silencing activity in cells. The current study investigated whether pre­freezing or saccharide types present during the freeze­drying of siRNA lipoplexes affected gene­silencing in cells after Rev­transfection. Three types of cationic cholesterol derivatives and three types of dialkyl or trialkyl cationic lipids were used for the preparation of cationic liposomes. Additionally, six types of siRNA lipoplexes were vacuum­dried in trehalose or sucrose solution without a pre-freezing process in multi­well plates. A strong gene­silencing activity after Rev­transfection was observed regardless of the cationic lipid types in the cationic liposomes. It was also investigated whether saccharide types in the freeze­drying of siRNA lipoplexes affected gene­silencing after Rev­transfection. siRNA lipoplexes freeze­dried in monosaccharides (glucose, fructose, galactose or mannose), disaccharides (maltose, lactose, lactulose or cellobiose) and trisaccharide solution (raffinose or melezitose) demonstrated high gene­silencing activity. However, following Rev­transfection with siRNA lipoplexes freeze­dried in monosaccharides or trisaccharides, certain saccharides induced cytotoxicity and/or off­target effects. The results of the current study indicated that disaccharides may be suitable for the preparation of vacuum­dried or freeze­dried siRNA lipoplexes for Rev­transfection.