Alzheimer's disease early screening and staged detection with plasma proteome using machine learning and convolutional neural network.

Alzheimer's disease (AD) stands as the prevalent progressive neurodegenerative disease, precipitating cognitive impairment and even memory loss. Amyloid biomarkers have been extensively used in the diagnosis of AD. However, amyloid proteins offer limited information about the disease process and accurate diagnosis depends on the presence of a substantial accumulation of amyloid deposition which significantly impedes the early screening of AD. In this study, we have combined plasma proteomics with an ensemble learning model (CatBoost) to develop a cost-effective and non-invasive diagnostic method for AD. A longitudinal panel has been identified that can serve as reliable biomarkers across the entire progression of AD. Simultaneously, we have developed a neural network algorithm that utilizes plasma proteins to detect stages of Alzheimer's disease. Based on the developed longitudinal panel, the CatBoost model achieved an area under the operating curve of at least 0.90 in distinguishing mild cognitive impairment from cognitively normal. The neural network model was utilized for the detection of three stages of AD, and the results demonstrated that the neural network model exhibited an accuracy as high as 0.83, surpassing that of the traditional machine learning model.

[Design and practice of biological reaction engineering flipped classroom in applied undergraduate colleges].

This study aims to explore and refine the teaching aspects of a flipped classroom approach for biological reaction engineering. The study encompasses three iterations of teaching practice, focusing on key elements such as theme content selection, implementation process, evaluation and effectiveness. By integrating relevant industry and societal topics with course's professional knowledge, students are encouraged to independently collect data, analyze and discuss findings, and present their work in group. Comprehensive literacy of students is assessed through discussion reports, defense reports, utilization of new tools, and team cooperation. Analysis of student performance reveals that the design and implementation of the flipped classroom approach significantly enhances student motivation to learn, improves scores, and supports the achievement of course objectives. Therefore, the methodology presented in this study may serve as a reference for implementing teaching reforms in core courses in applied undergraduate colleges, thereby fostering well-round individuals with strong theoretical foundation, innovative analytical skills, and excellent teamwork abilities.

Molecular mechanism of the one-component regulator RccR on bacterial metabolism and virulence.

The regulation of carbon metabolism and virulence is critical for the rapid adaptation of pathogenic bacteria to host conditions. In Pseudomonas aeruginosa, RccR is a transcriptional regulator of genes involved in primary carbon metabolism and is associated with bacterial resistance and virulence, although the exact mechanism is unclear. Our study demonstrates that PaRccR is a direct repressor of the transcriptional regulator genes mvaU and algU. Biochemical and structural analyses reveal that PaRccR can switch its DNA recognition mode through conformational changes triggered by KDPG binding or release. Mutagenesis and functional analysis underscore the significance of allosteric communication between the SIS domain and the DBD domain. Our findings suggest that, despite its overall structural similarity to other bacterial RpiR-type regulators, RccR displays a more complex regulatory element binding mode induced by ligands and a unique regulatory mechanism.

Direct and Continuous Monitoring of Multicomponent Antibiotic Gentamicin in Blood at Single-Molecule Resolution.

Point-of-care monitoring of small molecules in biofluids is crucial for clinical diagnosis and treatment. However, the inherent low degree of recognition of small molecules and the complex composition of biofluids present significant obstacles for current detection technologies. Although nanopore sensing excels in the analysis of small molecules, the direct detection of small molecules in complex biofluids remains a challenge. In this study, we present a method for sensing the small molecule drug gentamicin in whole blood based on the mechanosensitive channel of small conductance in Pseudomonas aeruginosa (PaMscS) nanopore. PaMscS can directly detect gentamicin and distinguish its main components with only a monomethyl difference. The 'molecular sieve' structure of PaMscS enables the direct measurement of gentamicin in human whole blood within 10 min. Furthermore, a continuous monitoring device constructed based on PaMscS achieved continuous monitoring of gentamicin in live rats for approximately 2.5 h without blood consumption, while the drug components can be analyzed in situ. This approach enables rapid and convenient drug monitoring with single-molecule level resolution, which can significantly lower the threshold for drug concentration monitoring and promote more efficient drug use. Moreover, this work also lays the foundation for the future development of continuous monitoring technology with single-molecule level resolution in the living body.

Bedside electrical impedance tomography to assist the management of pulmonary embolism: A case report.

Background: Pulmonary embolism (PE) is a common worldwide disease with high mortality. Timely diagnosis and management of PE could significantly improve clinical outcomes. Electrical impedance tomography (EIT) is a novel noninvasive technique to monitor lung perfusion and help detect PE at the bedside. Here we present a case of clinical management of subsegmental PE with the help of the bilateral ventilation and perfusion(V/Q) asymmetry EIT image. Case presentation: A 72-year-old cancer patient with respiratory failure and acute kidney injury in the intensive care unit was suspected of PE based on his clinical manifestation. The contraindication of computed tomography pulmonary angiography (CTPA) for PE diagnosis prevented escalating anticoagulation therapy. Besides EIT ventilation and perfusion monitoring showed an abnormal asymmetry V/Q match between the bilateral lungs which promoted our decision to start systemic continuous anticoagulation therapy and improved the patient clinically. The following CTPA which clarified the diagnosis of PE suggests that the patient has benefited from our decision. Conclusion: For critically ill patients with suspected PE, the asymmetry of the EIT V/Q image may provide crucial objective information for clinical management.

Optimal Selection of Sampling Points within Sewer Networks for Wastewater-Based Epidemiology Applications.

Wastewater-based epidemiology (WBE) has great potential to monitor community public health, especially during pandemics. However, it faces substantial hurdles in pathogen surveillance through WBE, encompassing data representativeness, spatiotemporal variability, population estimates, pathogen decay, and environmental factors. This paper aims to enhance the reliability of WBE data, especially for early outbreak detection and improved sampling strategies within sewer networks. The tool implemented in this paper combines a monitoring model and an optimization model to facilitate the optimal selection of sampling points within sewer networks. The monitoring model utilizes parameters such as feces density and average water consumption to define the detectability of the virus that needs to be monitored. This allows for standardization and simplicity in the process of moving from the analysis of wastewater samples to the identification of infection in the source area. The entropy-based model can select optimal sampling points in a sewer network to obtain the most specific information at a minimum cost. The practicality of our tool is validated using data from Hildesheim, Germany, employing SARS-CoV-2 as a pilot pathogen. It is important to note that the tool's versatility empowers its extension to monitor other pathogens in the future.

Pseudomonas aeruginosa regulator PvrA binds simultaneously to multiple pseudo-palindromic sites for efficient transcription activation.

Tetracycline repressor (TetR) family regulators (TFRs) are the largest group of DNA-binding transcription factors and are widely distributed in bacteria and archaea. TFRs play vital roles in controlling the expression of various genes and regulating diverse physiological processes. Recently, a TFR protein Pseudomonas virulence regulator A (PvrA), was identified from Pseudomonas aeruginosa as the transcriptional activator of genes involved in fatty acid utilization and bacterial virulence. Here, we show that PvrA can simultaneously bind to multiple pseudo-palindromic sites and upregulate the expression levels of target genes. Cryo-electron microscopy (cryo-EM) analysis indicates the simultaneous DNA recognition mechanism of PvrA and suggests that the bound DNA fragments consist of a distorted B-DNA double helix. The crystal structure and functional analysis of PvrA reveal a hinge region that secures the correct domain motion for recognition of the promiscuous promoter. Additionally, our results showed that mutations disrupting the regulatory hinge region have differential effects on biofilm formation and pyocyanin biosynthesis, resulting in attenuated bacterial virulence. Collectively, these findings will improve the understanding of the relationship between the structure and function of the TetR family and provide new insights into the mechanism of regulation of P. aeruginosa virulence.

The impact of blood MCP-1 levels on Alzheimer's disease with genetic variation of UNC5C and NAV3 loci.

Background: Previous study shows that monocyte chemoattractant protein-1 (MCP-1), which is implicated in the peripheral proinflammatory cascade and blood-brain barrier (BBB) disruption, modulates the genetic risks of AD in established AD loci. Methods: In this study, we hypothesized that blood MCP-1 impacts the AD risk of genetic variants beyond known AD loci. We thus performed a genome-wide association study (GWAS) using the logistic regression via generalized estimating equations (GEE) and the Cox proportional-hazards models to examine the interactive effects between single nucleotide polymorphisms (SNPs) and blood MCP-1 level on AD in three cohorts: the Framingham Heart Study (FHS), Alzheimer's Disease Neuroimaging Initiative (ADNI) and Religious Orders Study/Memory and Aging Project (ROSMAP). Results: We identified SNPs in two genes, neuron navigator 3 (NAV3, also named Unc-53 Homolog 3, rs696468) (p < 7.55×10- 9) and Unc-5 Netrin Receptor C (UNC5C rs72659964) (p < 1.07×10- 8) that showed an association between increasing levels of blood MCP-1 and AD. Elevating blood MCP-1 concentrations increased AD risk and AD pathology in genotypes of NAV3 (rs696468-CC) and UNC5C (rs72659964-AT + TT), but did not influence the other counterpart genotypes of these variants. Conclusions: NAV3 and UNC5C are homologs and may increase AD risk through dysregulating the functions of neurite outgrowth and guidance. Overall, the association of risk alleles of NAV3 and UNC5C with AD is enhanced by peripheral MCP-1 level, suggesting that lowering the level of blood MCP-1 may reduce the risk of developing AD for people with these genotypes.

Advances in the adenylation domain: discovery of diverse non-ribosomal peptides.

Non-ribosomal peptide synthetases are mega-enzyme assembly lines that synthesize many clinically useful compounds. As a gatekeeper, they have an adenylation (A)-domain that controls substrate specificity and plays an important role in product structural diversity. This review summarizes the natural distribution, catalytic mechanism, substrate prediction methods, and in vitro biochemical analysis of the A-domain. Taking genome mining of polyamino acid synthetases as an example, we introduce research on mining non-ribosomal peptides based on A-domains. We discuss how non-ribosomal peptide synthetases can be engineered based on the A-domain to obtain novel non-ribosomal peptides. This work provides guidance for screening non-ribosomal peptide-producing strains, offers a method to discover and identify A-domain functions, and will accelerate the engineering and genome mining of non-ribosomal peptide synthetases. KEY POINTS: • Introducing adenylation domain structure, substrate prediction, and biochemical analysis methods • Advances in mining homo polyamino acids based on adenylation domain analysis • Creating new non-ribosomal peptides by engineering adenylation domains.

SP-GNN: Learning structure and position information from graphs.

Graph neural network (GNN) is a powerful model for learning from graph data. However, existing GNNs may have limited expressive power, especially in terms of capturing adequate structural and positional information of input graphs. Structure properties and node position information are unique to graph-structured data, but few GNNs are capable of capturing them. This paper proposes Structure- and Position-aware Graph Neural Networks (SP-GNN), a new class of GNNs offering generic and expressive power of graph data. SP-GNN enhances the expressive power of GNN architectures by incorporating a near-isometric proximity-aware position encoder and a scalable structure encoder. Further, given a GNN learning task, SP-GNN can be used to analyze positional and structural awareness of GNN tasks using the corresponding embeddings computed by the encoders. The awareness scores can guide fusion strategies of the extracted positional and structural information with raw features for better performance of GNNs on downstream tasks. We conduct extensive experiments using SP-GNN on various graph datasets and observe significant improvement in classification over existing GNN models.

Circulating Endothelial Progenitor Cells Reduce the Risk of Alzheimer's Disease.

Cerebrovascular damage coexists with Alzheimer's disease (AD) pathology and increases AD risk. However, it is unclear whether endothelial progenitor cells reduce AD risk via cerebrovascular repair. By using the Framingham Heart Study (FHS) offspring cohort, which includes data on different progenitor cells, the incidence of AD dementia, peripheral and cerebrovascular pathologies, and genetic data (n = 1,566), we found that elevated numbers of circulating endothelial progenitor cells with CD34+CD133+ co-expressions had a dose-dependent association with decreased AD risk (HR = 0.67, 95% CI: 0.46-0.96, p = 0.03) after adjusting for age, sex, years of education, and APOE ε4. With stratification, this relationship was only significant among those individuals who had vascular pathologies, especially hypertension (HTN) and cerebral microbleeds (CMB), but not among those individuals who had neither peripheral nor central vascular pathologies. We applied a genome-wide association study (GWAS) and found that the number of CD34+CD133+ cells impacted AD risk depending on the homozygous genotypes of two genes: KIRREL3 rs580382 CC carriers (HR = 0.31, 95% CI: 0.17-0.57, p<0.001), KIRREL3 rs4144611 TT carriers (HR = 0.29, 95% CI: 0.15-0.57, p<0.001), and EXOC6B rs61619102 CC carriers (HR = 0.49, 95% CI: 0.31-0.75, p<0.001) after adjusting for confounders. In contrast, the relationship did not exist in their counterpart genotypes, e.g. KIRREL3 TT/CT or GG/GT carriers and EXOC6B GG/GC carriers. Our findings suggest that circulating CD34+CD133+ endothelial progenitor cells can be therapeutic in reducing AD risk in the presence of cerebrovascular pathology, especially in KIRREL3 and EXOC6B genotype carriers.

Nucleotide binding as an allosteric regulatory mechanism for Akkermansia muciniphila ß-N-acetylhexosaminidase Am2136.

ß-N-acetylhexosaminidases (EC3.2.1.52), which belong to the glycosyl hydrolase family GH20, are important enzymes for oligosaccharides modification. Numerous microbial ß-N-acetylhexosaminidases have been investigated for applications in biology, biomedicine and biotechnology. Akkermansia muciniphila is an anaerobic intestinal commensal bacterium which possesses specific ß-N-acetylhexosaminidases for gut mucosal layer colonization and mucin degradation. In this study, we assessed the in vitro mucin glycan cleavage activity of the A. muciniphila ß-N-acetylhexosaminidase Am2136 and demonstrated its ability that hydrolyzing the ß-linkages joining N-acetylglucosamine to a wide variety of aglycone residues, which indicated that Am2136 may be a generalist ß-N-acetylhexosaminidase. Structural and enzyme activity assay experiments allowed us to probe the essential function of the inter-domain interactions in ß23-ß33. Importantly, we revealed that the hydrolysis activity of Am2136 was enhanced by nucleotides. We further speculated that this activation mechanism might be associated with the conformational motions between domain III and IV. To our knowledge, this is the first report of nucleotide effector regulated ß-N-acetylhexosaminidase, to reveal its novel biological functions. These findings contribute to understanding the distinct properties within the GH20 family and lay a certain foundation to develop controllable glycan hydrolyzing catalysts.Abbreviations: OD600 - optical cell densities at 600 nm; LB - Luria-Bertani; IPTG - isopropyl ß-D-1-thiogalactopyranoside; PMSF - phenylmethanesulfonyl fluoride; rmsd - root mean square deviation; GlcNAc - N-acetyl-ß-D-glucosamine; GalNAc - N-acetyl-ß-D-galactosamine; Gal - galactose.

Ion selectivity and gating behavior of the CorA-type channel Bpss1228.

Magnesium is an essential element to sustain all forms of life. Total intracellular magnesium content is determined by the balance of magnesium influx and efflux. CorA is a divalent selective channel in the metal ion transport superfamily and is the major Mg2+ uptake pathway in prokaryotes and eukaryotic mitochondria. Previous studies have demonstrated that CorA showed distinct magnesium bound closed conformation and Mg2+-free states. In addition, CorA is regulated by cytoplasmic magnesium ions and its gating mechanism has been investigated by electron paramagnetic resonance technique and molecular dynamic simulations. Here, we report a study of the putative CorA-type channel Bpss1228 from Burkholderia pseudomallei, which has been shown to be significantly associated with pseudomallei infection. We expressed and purified the Bpss1228 in full-length. Subsequently, electrophysiological experiments further investigated the electrical characteristics of Bpss1228 and revealed that it was a strictly cation-selective channel. We also proved that Bpss1228 not only possessed magnesium-mediated regulatory property a remarkable ability to be modulated by magnesium ions. Finally, we observed the three-step gating behavior of Bpss1228 on planar lipid bilayer, and further proposed a synergistic gating mechanism by which CorA family channels control intracellular magnesium homeostasis.

Hexavalent Chromium Exposure Induces Intestinal Barrier Damage via Activation of the NF-κB Signaling Pathway and NLRP3 Inflammasome in Ducks.

Hexavalent chromium [Cr(VI)] is a dangerous heavy metal which can impair the gastrointestinal system in various species; however, the processes behind Cr(VI)-induced intestinal barrier damage are unknown. Forty-eight healthy 1-day-old ducks were stochastically assigned to four groups and fed a basal ration containing various Cr(VI) dosages for 49 days. Results of the study suggested that Cr(VI) exposure could significantly increase the content of Cr(VI) in the jejunum, increase the level of diamine oxidase (DAO) in serum, affect the production performance, cause histological abnormalities (shortening of the intestinal villi, deepening of the crypt depth, reduction and fragmentation of microvilli) and significantly reduced the mRNA levels of intestinal barrier-related genes (ZO-1, occludin, claudin-1, and MUC2) and protein levels of ZO-1, occludin, cand laudin-1, resulting in intestinal barrier damage. Furthermore, Cr(VI) intake could increase the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) but decrease the activities of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione reductase (GR), as well as up-regulate the mRNA levels of TLR4, MyD88, NF-κB, TNFα, IL-6, NLRP3, caspase-1, ASC, IL-1ß, and IL-18 and protein levels of TLR4, MyD88, NF-κB, NLRP3, caspase-1, ASC, IL-1ß, and IL-18 in the jejunum. In conclusion, Cr(VI) could cause intestinal oxidative damage and inflammation in duck jejunum by activating the NF-κB signaling pathway and the NLRP3 inflammasome.

Molecular cloning, characterization, and expression analysis of TIPE1 in chicken (Gallus gallus): Its applications in fatty liver hemorrhagic syndrome.

Tumor necrosis factor-α-induced protein eight like 1 (TIPE1) plays important role in autophagy, immunity, and lipid metabolism. The potential role of TIPE1 in fatty liver hemorrhage syndrome (FLHS) is elusory. In the present study, the full-length coding sequence of TIPE1 was cloned, and the polyclonal antibody of TIPE1 was produced by the recombinant TIPE1 protein. The bioinformatic analysis showed that the chicken TIPE1 protein, which was predicted to be a hydrophobic and non-transmembrane protein without signal peptide was highly different from that of mammals. Furthermore, proceeded by using TIPE1 polyclonal antibody, the tissue distribution analysis showed that TIPE1 protein is ubiquitously expressed in various tissues in adult hens and chicks, with its level being higher in the liver and, spleen, moderate in intestinal, brain, and heart. Besides, immunohistochemistry and immunofluorescence observation demonstrated that TIPE1 mainly existed in the cytoplasm in liver, duodenum, and cecum cell. Notably, the TIPE1 expressions were significantly decreased in laying hens suffering from FLHS. Collectively, these results showed that the chicken TIPE1 polyclonal antibody was successfully prepared and further used to analyze the expression profiles of chicken. And the expression of TIPE1 was reduced in FLHS which provided the foundation for further investigation in FLHS.

High-fidelity biosensing of dNTPs and nucleic acids by controllable subnanometer channel PaMscS.

Current tools for dNTP analysis mainly rely on expensive fluorescent labeling, mass spectrometry or electrochemistry. Single-molecule assay by protein nanopores with an internal diameter of ca. 1-3.6 nm provides a useful tool for dNTP sensing. However, the most commonly used protein nanopores require additional modifications to enable dNTP detection. In this study, the PaMscS channel (mechanosensitive channel of small conductance from Pseudomonas aeruginosa) embedded in the bilayer lipid membrane (BLM) of E. coli polar lipid extract was applied as a nanopore for single molecular sensing. Two mutants of PaMscS nanopores on the side portal region (PaMscS W130A and PaMscS K180R) were selected for direct dNTP or pyrophosphoric acid (PPi) detection without aptamer or protein modification. Notably, the PaMscS mutant pore can be adjusted by regulation of osmolarity differences, which is crucial for the optimal detection of specific molecules. In addition, we established a PaMscS-based diagnosis method for the rapid sensing of disease-associated nucleic acids by monitoring the consumption of dNTPs, with 86% specificity and 100% sensitivity among 22 clinical samples. This protein nanopore, without aptamer or modification, paves a new way for dNTPs, PPi direct sensing and nucleic acid detection with low cost but high versatility.

Antioxidant Effects of Resveratrol in Intervertebral Disk.

Intervertebral disk (IVD) degeneration (IVDD) can cause various spinal degenerative diseases. Cumulative evidence has indicated that IVDD can result from inflammation, apoptosis, autophagy, biomechanical changes and other factors. Currently, lack of conservative treatment for degenerative spinal diseases leads to an urgent demand for clinically applicable medication to ameliorate the progression of IVDD. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol compound extracted from red wine or grapes, has shown protective effects on IVD, alleviating the progression of IVDD. Resveratrol has been demonstrated as a scavenger of free radicals both in vivo and in vitro. The antioxidant effects of resveratrol are likely attributed to its regulation on mitochondrial dysfunction or the elimination of reactive oxygen species. This review will summarize the mechanisms of the reactive oxygen species production and elaborate the mechanisms of resveratrol in retarding IVDD progression, providing a comprehensive understanding of the antioxidant effects of resveratrol in IVD.

Evaluating the efficiency of three methods to clean and disinfect screw- and cement-retained prostheses.

STATEMENT OF PROBLEM: Screw- and cement-retained prostheses (SCRPs) may be contaminated during fabrication in a dental laboratory, leading to mechanical and biological complications related to the implant treatment. Studies that explored methods to efficiently and conveniently clean and disinfect SCRPs are sparse. PURPOSE: The purpose of this clinical study was to compare the efficiency of 3 methods to remove contaminants and microorganisms present on the surface of an SCRP. MATERIAL AND METHODS: Forty-eight 1-unit SCRPs fabricated in a dental laboratory were randomly divided into 3 groups: wiping, soaking, or ultrasonic cleaning. The presence of contaminants was determined by scanning electron microscopy, and microbial cells were cultured before and after treatment. Bacterial colony-forming units (CFUs) on the surface of the SCRPs and contamination density at the implant-abutment interface and emergence profile area were assessed. Statistical tests including ANCOVA were used to compare the efficiency of different methods before and after treatment (α=.05). RESULTS: Significant differences in contamination density were noted during the treatment at the implant-abutment interface and at the emergence profile area in the 3 groups (P<.05), but no significant differences were observed in the number of CFUs (P>.05). There were significant differences among the 3 methods for cleaning efficiency both at the implant-abutment interface (P=.023) and the emergence profile area (P=.038). At the implant-abutment interface, the contamination density after treatment was lower in the ultrasonic cleaning group than that in the soaking group (P=.007), whereas at the emergence profile area, the contamination density after treatment was lower in the ultrasonic cleaning group than that in the wiping group (P=.019) and the soaking group (P=.048). CONCLUSIONS: All 3 treatment methods reduced contaminants on the SCRP surface, but ultrasonic cleaning yielded the most favorable results. However, none of the methods provided additional disinfection for SCRPs previously disinfected by ozone and UV in a dental laboratory.

Bone augmentation with autologous tooth shell in the esthetic zone for dental implant restoration: a pilot study.

OBJECTIVES: To investigate the outcome and short-term follow-up of autogenous tooth shell (TS) grafting for bone augmentation in the esthetic zone, as well as stability and esthetics of implant-supported restoration. MATERIALS AND METHODS: A total of 8 patients with 11 implants in 11 sites were enrolled in this study. All the horizontal and/or vertical bone defects in the esthetic zone were augmented by tooth shells, which were fixed laterally to the residual bone with osteosynthesis screws. The gap between the shell and residual bone was filled with Bio-Oss® granules. Four months after bone augmentation, dimensionally sufficient dental implants were inserted and implants-supported prostheses were made 3 months later. The esthetic outcome was evaluated by pink esthetic score (PES) and white esthetic score (WES) one year after prosthetic restoration. Horizontal ridge width (HRW) was assessed before and immediately after bone augmentation, as well as 4 and 19 months post-augmentation by radiography. The stability and absorption of TS grafts were evaluated at the 4th and 19th months post-augmentation. RESULTS: Though wound dehiscences occurred in 3 cases, secondary healings were obtained after TS modification and irrigation. The other 5 cases went through uneventful healing during the whole observation period. Radiographic examination showed that HRW was 8.01 ± 0.93 mm (median: 7.80, 95% CI 7.38, 8.64) 4 months after TS augmentation, which was statistically different compared to HRW (2.72 ± 1.73 mm) at the baseline. Mean HRW gain was 5.29 ± 2.03 mm (median: 4.60, 95% CI 3.92, 6.66). Three-dimensional bone volume in all the augmented sites was sufficient for dental implants insertion and prosthetic restoration. Follow-up of one year showed stable marginal bone around dental implants. The implant survival rate was 100%. HRW losses were 0.65 ± 0.43 mm (the 4th month) and 1.05 ± 0.54 mm (the 19th month) compared to HRW immediately after augmentation. The PES and WES of final prosthetic restorations were 8.09 ± 0.70 and 8.91 ± 0.54, respectively. CONCLUSIONS: Autogenous tooth shell grafting is a reliable approach for bone augmentation in the esthetic zone for dental implant treatment, allowing for favorable stability and esthetic outcome of implant-supported prosthesis within the one-year follow-up period.

[Construction of the curriculum for developing the ability to solving complex engineering problems in the field of biotechnology industry].

Accurately understanding the features and connotations of complex engineering problems is an important prerequisite for setting graduation requirements, constructing curriculum and designing teaching contents. By discussing the characteristics of complex engineering problems in the biological industry, this paper explored the demands for undergraduates in Yangtze river delta region, summarized the typical jobs and their requirements, and expounded the connotation of complex engineering problems contained in various typical tasks. On this basis, a gradual curriculum system was constructed, which included multiple stages of conceiving, formation and application, to cultivate the ability to solve complex engineering problems in the major of bioengineering. The curriculum coordinated the implementation of deep integration of industry and education, research feed back course construction, course team and advanced courses building up, professional associations covered all crews and students, supporting the ability training of solving complex engineering problems.