Co-delivery of Plinabulin and Tirapazamine boosts anti-tumor efficacy by simultaneously destroying tumor blood vessels and killing tumor cells.

It is imperative to optimize chemotherapy for heightened anti-tumor therapeutic efficacy. Unrestrained tumor cell proliferation and sustained angiogenesis are pivotal for cancer progression. Plinabulin, a vascular disrupting agent, selectively destroys tumor blood vessels. Tirapazamine (TPZ), a hypoxia-activated prodrug, intensifies cytotoxicity in diminishing oxygen levels within tumor cells. Despite completing Phase III clinical trials, both agents exhibited modest treatment efficiency due to dose-limiting toxicity. In this study, we employed methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-b-PDLLA) to co-deliver Plinabulin and TPZ to the tumor site, concurrently disrupting blood vessels and eliminating tumor cells, addressing both symptoms and the root cause of tumor progression. Plinabulin was converted into a prodrug with esterase response (PSM), and TPZ was synthesized into a hexyl chain-containing derivative (TPZHex) for effective co-delivery. PSM and TPZHex were co-encapsulated with mPEG-b-PDLLA, forming nanodrugs (PT-NPs). At the tumor site, PT-NPs responded to esterase overexpression, releasing Plinabulin, disrupting blood vessels, and causing nutritional and oxygen deficiency. TPZHex was activated in response to increased hypoxia, killing tumor cells. In treating 4T1 tumors, PT-NPs demonstrated enhanced therapeutic efficacy, achieving a 92.9 % tumor suppression rate and a 20 % cure rate. This research presented an innovative strategy to enhance synergistic efficacy and reduce toxicity in combination chemotherapy.

A polyetheretherketone framework removable partial denture for a 6-year-old child with nonsyndromic oligodontia made using glass-ceramic hemispheres to enhance retention: A clinical report.

A 6-year-old child with nonsyndromic oligodontia in the mixed dentition received a removable dental prosthesis with a polyetheretherketone framework and artificial gingiva, restoring esthetics and function. Computer-aided design and computer-aided manufacturing hemispherical glass-ceramic attachments were added to the teeth under the guidance of acid-etching and bonding guides to obtain an undercut area. The bonding and cementation of the attachments and the prosthesis delivery were completed in a single visit. This method offers a suitable prosthodontic treatment option for treating children with oligodontia in the mixed dentition.

C-type lectin 12B/4E of black rockfish (Sebastes schlegelii) macrophages as pattern recognition receptors in the antibacterial mechanism of exploration.

As lower vertebrates, fish have both innate and adaptive immune systems, but the role of the adaptive immune system is limited, and the innate immune system plays an important role in the resistance to pathogen infection. C-type lectins (CLRs) are one of the major pattern recognition receptors (PRRs) of the innate immune system. CLRs can combine with pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) to trigger NF-κB signaling pathway and exert immune efficacy. In this study, Ssclec12b and Ssclec4e of the C-type lectins, were found to be significantly up-regulated in the transcripts of Sebastes schlegelii macrophages stimulated by bacteria. The identification, expression and function of these lectins were studied. In addition, the recombinant proteins of the above two CLRs were obtained by prokaryotic expression. We found that rSsCLEC12B and rSsCLEC4E could bind to a variety of bacteria in a Ca2+-dependent manner, and promoted the agglutination of bacteria and blood cells. rSsCLEC12B and rSsCLEC4E assisted macrophages to recognize PAMPs and activate the NF-κB signaling pathway, thereby promoting the expression of inflammatory factors (TNF-α, IL-1ß, IL-6, IL-8) and regulating the early immune inflammation of macrophages. These results suggested that SsCLEC12B and SsCLEC4E could serve as PRRs in S. schlegelii macrophages to recognize pathogens and participate in the host antimicrobial immune process, and provided a valuable reference for the study of CLRs involved in fish innate immunity.

Immunometabolism in cancer: basic mechanisms and new targeting strategy.

Maturing immunometabolic research empowers immune regulation novel approaches. Progressive metabolic adaptation of tumor cells permits a thriving tumor microenvironment (TME) in which immune cells always lose the initial killing capacity, which remains an unsolved dilemma even with the development of immune checkpoint therapies. In recent years, many studies on tumor immunometabolism have been reported. The development of immunometabolism may facilitate anti-tumor immunotherapy from the recurrent crosstalk between metabolism and immunity. Here, we discuss clinical studies of the core signaling pathways of immunometabolism and their inhibitors or agonists, as well as the specific functions of these pathways in regulating immunity and metabolism, and discuss some of the identified immunometabolic checkpoints. Understanding the comprehensive advances in immunometabolism helps to revise the status quo of cancer treatment. An overview of the new landscape of immunometabolism. The PI3K pathway promotes anabolism and inhibits catabolism. The LKB1 pathway inhibits anabolism and promotes catabolism. Overactivation of PI3K/AKT/mTOR pathway and IDO, IL4I1, ACAT, Sirt2, and MTHFD2 promote immunosuppression of TME formation, as evidenced by increased Treg and decreased T-cell proliferation. The LKBI-AMPK pathway promotes the differentiation of naive T cells to effector T cells and memory T cells and promotes anti-tumor immunity in DCs.

[Analysis of imaging characteristics and effectiveness of cervical spondylotic myelopathy with cervical kyphosis].

Objective: To investigate the imaging characteristics of cervical kyphosis and spinal cord compression in cervical spondylotic myelopathy (CSM) with cervical kyphosis and the influence on effectiveness. Methods: The clinical data of 36 patients with single-segment CSM with cervical kyphosis who were admitted between January 2020 and December 2022 and met the selection criteria were retrospectively analyzed. The patients were divided into 3 groups according to the positional relationship between the kyphosis focal on cervical spine X-ray film and the spinal cord compression point on MRI: the same group (group A, 20 cases, both points were in the same position), the adjacent group (group B, 10 cases, both points were located adjacent to each other), and the separated group (group C, 6 cases, both points were located >1 vertebra away from each other). There was no significant difference between groups ( P>0.05) in baseline data such as gender, age, body mass index, lesion segment, disease duration, and preoperative C 2-7 angle, C 2-7 sagittal vertical axis (C 2-7 SVA), C 7 slope (C 7S), kyphotic Cobb angle, fusion segment height, and Japanese Orthopedic Association (JOA) score. The patients underwent single-segment anterior cervical discectomy with fusion (ACDF). The occurrence of postoperative complications was recorded; preoperatively and at last follow-up, the patients' neurological function was evaluated using the JOA score, and the sagittal parameters (C 2-7 angle, C 2-7 SVA, C 7S, kyphotic Cobb angle, and height of the fused segments) were measured on cervical spine X-ray films and MRI and the correction rate of the cervical kyphosis was calculated; the correlation between changes in cervical sagittal parameters before and after operation and the JOA score improvement rate was analyzed using Pearson correlation analysis. Results: In 36 patients, only 1 case of dysphagia occurred in group A, and the dysphagia symptoms disappeared at 3 days after operation, and the remaining patients had no surgery-related complications during the hospitalization. All patients were followed up 12-42 months, with a mean of 20.1 months; the difference in follow-up time between the groups was not significant ( P>0.05). At last follow-up, all the imaging indicators and JOA scores of patients in the 3 groups were significantly improved when compared with preoperative ones ( P<0.05). The correction rate of cervical kyphosis in group A was significantly better than that in group C, and the improvement rate of JOA score was significantly better than that in groups B and C, all showing significant differences ( P<0.05), and there was no significant difference between the other groups ( P>0.05). The correlation analysis showed that the improvement rate of JOA score was negatively correlated with C 2-7 angle and kyphotic Cobb angle at last follow-up ( r=-0.424, P=0.010; r=-0.573, P<0.001), and positively correlated with the C 7S and correction rate of cervical kyphosis at last follow-up ( r=0.336, P=0.045; r=0.587, P<0.001), and no correlation with the remaining indicators ( P>0.05). Conclusion: There are three main positional relationships between the cervical kyphosis focal and the spinal cord compression point on imaging, and they have different impacts on the effectiveness and sagittal parameters after ACDF, and those with the same position cervical kyphosis focal and spinal cord compression point have the best improvement in effectiveness and sagittal parameters.

Accuracy of the novel digital non-cross-arch surgical guides with integration of tooth undercut retention and screw-bone support for implant placement in mandibular free-end.

BACKGROUND: Large cross-arch free-end surgical guides can obscure the visual field, compromising surgical accuracy due to insufficient stability at the free-end. This in vitro study aims to evaluate the accuracy of novel digital non-cross-arch surgical guides designed for implant placement at the mandibular free-end, incorporating tooth undercut retention and screw-bone support. MATERIALS AND METHODS: A mandibular dental model lacking left molars was utilized to fabricate unilateral (cross-arch) tooth-supported surgical guides (GT I, n = 20). Subsequently, two additional types of surgical guides were fabricated: GT II (covering two teeth, n = 20) and GT III (covering three teeth, n = 20). These novel surgical guides were designed to utilize the undercut of the supporting teeth for retention and enhance stability with screw-bone support at the guide's free-end. Furthermore, 60 identical guiding blocks were assembled on the three types of surgical guides to facilitate the implants' insertion. On a phantom head, 120 implant replicas were placed at the Federal Dentaire Internationale (FDI) teeth positions #36 and #37 on the dental model, employing a combination of surgical guides and guiding blocks. To assess accuracy, planned and placed implant positions were compared using intraoral optical scanning. Discrepancies in angulation and linear deviations, including the coronal/apical 3D deviations, lateral deviation as well as depth deviation, were measured. Statistical analysis was performed using two-way ANOVA and Bonferroni test (α = 0.05). RESULTS: GT I exhibited significantly largest discrepancies, including angular and linear deviations at the crest and apex at every implant site. Especially in depth, at implant site #36, the mean deviation value of GT I (0.27 ± 0.13 mm) was twice as large as GT III (0.13 ± 0.07 mm), and almost twice as large as GT II (0.14 ± 0.08 mm). However, at implant site #37, this deviation increased to almost a five-fold relationship between GT I (0.63 ± 0.12 mm) and II (0.14 ± 0.09 mm), as well as between GT I and III (0.13 ± 0.09 mm). No significant discrepancies existed between the novel surgical guides at either implant site #36 or #37. CONCLUSION: This study provides a practical protocol for enhancing accuracy of implant placement and reducing the size of free-end surgical guides used at mandibular molar sites.

Effect of Polymer and Crosslinker Concentration on Static and Dynamic Gelation Behavior of Phenolic Resin Hydrogel.

The application results of profile control and water plugging technology are highly related to the gelation time and strength of phenolic resin hydrogel. In this work, a hydrogel solution was prepared by fully mixing the prepared polymer solution with a crosslinker. The static gelation process of PFR hydrogel in ampoule bottles and porous media was analyzed by changes in the viscosity and residual resistance coefficient. Then, the dynamic gelation of the PFR hydrogel in porous media was tested using a circulating flow device, and the changes in viscosity and injection pressure were analyzed during the dynamic gelation process. Finally, the effects of the polymer concentration and crosslinker concentration on dynamic gelation were analyzed. The initial gelation time and final gelation time in porous media were 1-1.5 times and 1.5-2 times those in ampoule bottles under static conditions, respectively. The initial dynamic gelation time in porous media was 2-2.5 times and 1.5-2 times the initial static gelation times in ampoule bottles and porous media, respectively. The final dynamic gelation time was four times and two times the initial static gelation times in ampoule bottles and porous media, respectively. The production after dynamic gelation in porous media comprised hydrogel aggregates and water fluid, leading to a high injection pressure and low viscosity of the produced liquid. As the concentration of polymer and crosslinker increased, the dynamic gelation time was shortened and the gel strength was increased. In the dynamic gelation process in porous media, the phenol resin hydrogel could migrate deeply, but it was limited by the concentrations of the polymer and crosslinker. The results of subsequent water flooding showed that the polymer hydrogel had a good plugging ability after dynamic gelation. The deep reservoir could only be blocked off in the subsequent water flooding process when the migration of hydrogel happened in the dynamic gelation process.

Hydrogen Embrittlement as a Conspicuous Material Challenge─Comprehensive Review and Future Directions.

Hydrogen is considered a clean and efficient energy carrier crucial for shaping the net-zero future. Large-scale production, transportation, storage, and use of green hydrogen are expected to be undertaken in the coming decades. As the smallest element in the universe, however, hydrogen can adsorb on, diffuse into, and interact with many metallic materials, degrading their mechanical properties. This multifaceted phenomenon is generically categorized as hydrogen embrittlement (HE). HE is one of the most complex material problems that arises as an outcome of the intricate interplay across specific spatial and temporal scales between the mechanical driving force and the material resistance fingerprinted by the microstructures and subsequently weakened by the presence of hydrogen. Based on recent developments in the field as well as our collective understanding, this Review is devoted to treating HE as a whole and providing a constructive and systematic discussion on hydrogen entry, diffusion, trapping, hydrogen-microstructure interaction mechanisms, and consequences of HE in steels, nickel alloys, and aluminum alloys used for energy transport and storage. HE in emerging material systems, such as high entropy alloys and additively manufactured materials, is also discussed. Priority has been particularly given to these less understood aspects. Combining perspectives of materials chemistry, materials science, mechanics, and artificial intelligence, this Review aspires to present a comprehensive and impartial viewpoint on the existing knowledge and conclude with our forecasts of various paths forward meant to fuel the exploration of future research regarding hydrogen-induced material challenges.

Three dimensionally printed template with an interproximal isolation design guide consecutive closure of multiple diastema with injectable resin composite.

OBJECTIVE: This article describes a novel 3D-printed template armed with interproximal matrices to isolate interproximal contact areas and guide injectable resin composite for consecutive closure of multiple diastema. CLINICAL CONSIDERATIONS: Among several treatment options proposed for diastema closure, direct resin composite is noninvasive and easy to repair. The "composite injection technique" has been introduced to improve time efficiency and reduce technique sensitivity for clinicians. However, in the case of multiple diastema, the overflow of excess resin materials onto the adjacent teeth during injection poses challenges for recontouring the interproximal anatomy. A 3D-printed template with special-designed gaps at interproximal areas was designed and fabricated based on a virtual diagnostic wax-up. Flowable resin composite was then consecutively injected through the template to close diastemata at multiple adjacent teeth. CONCLUSION: This technique using a 3D-printed template with interproximal isolation design contributed to an efficient and accurate operation for multiple anterior diastema closure. CLINICAL SIGNIFICANCE: Efficient and accurate freehand buildups of composite restoration for multiple diastema are challenging in operative dentistry. The described noninvasive full digital workflow provides a predictable method to accurately recontour the multiple target restorations and reduce the chair-side time and technical sensitivity.

Strigolactones shape the assembly of root-associated microbiota in response to phosphorus availability.

Plants rely on strigolactones (SLs) to regulate their development and form symbiotic relationships with microbes as part of the adaptive phosphorus (P) efficiency strategies. However, the impact of SLs on root-associated microbial communities in response to P availability remains unknown. Here, root microbiota of SL biosynthesis (max3-11) and perception (d14-1) were compared to wild-type Col-0 plants under different P concentrations. Using high-throughput sequencing, the relationship between SLs, P concentrations, and the root-associated microbiota was investigated to reveal the variation in microbial diversity, composition, and interaction. Plant genotypes and P availability played important but different roles in shaping the root-associated microbial community. Importantly, SLs were found to attract Acinetobacter in low P conditions, which included an isolated CP-2 (Acinetobacter soli) that could promote plant growth in cocultivation experiments. Moreover, SLs could change the topologic structure within co-occurrence networks and increase the number of keystone taxa (e.g., Rhizobiaceae and Acidobacteriaceae) to enhance microbial community stability. This study reveals the key role of SLs in mediating root-associated microbiota interactions.IMPORTANCEStrigolactones (SLs) play a crucial role in plant development and their symbiotic relationships with microbes, particularly in adapting to phosphorus levels. Using high-throughput sequencing, we compared the root microbiota of plants with SL biosynthesis and perception mutants to wild-type plants under different phosphorus concentrations. These results found that SLs can attract beneficial microbes in low phosphorus conditions to enhance plant growth. Additionally, SLs affect microbial network structures, increasing the stability of microbial communities. This study highlights the key role of SLs in shaping root-associated microbial interactions, especially in response to phosphorus availability.

NosZ I carrying microorganisms determine N2O emissions from the subtropical paddy field under elevated CO2 and strongly CO2-responsive cultivar.

Elevated CO2 (eCO2) decreases N2O emissions from subtropical paddy fields, but the underlying mechanisms remain to be investigated. Herein, the response of key microbial nitrogen cycling genes to eCO2 (ambient air +200 µmol CO2 mol-1) in four rice cultivars, including two weakly CO2-responsive (W27, H5) and two strongly CO2-responsive cultivars (Y1540, L1988), was investigated. Except for nosZ I, eCO2 did not significantly alter the abundance of the other genes. NosZ I was a crucial factor governing N2O emissions, especially under eCO2 and a strongly responsive cultivar. eCO2 affected the nosZ I gene abundance (p < 0.05), for instance, the nosZ I gene abundance of cultivar W27 increased from 1.53 × 107 to 2.86 × 107 copies g-1 dw soil (p < 0.05). In the nosZ I microbial community, the known taxa were mainly Pseudomonadota (phylum) (19.74-31.72 %) and Alphaproteobacteria (class) (0.56-13.12 %). In the nosZ I community assembly process, eCO2 enhanced the role of stochasticity, increasing from 35 % to 85 % (p < 0.05), thereby inducing diffusion limitations of weakly responsive cultivars to dominate (67 %). Taken together, the increase in nosZ I gene abundance is a potential reason for the alleviation of N2O emissions from subtropical paddy fields under eCO2.

Laser-Guided, Self-Confined Graphitization for High-Conductivity Embedded Electronics.

Facile fabrication of highly conductive and self-encapsulated graphene electronics is in urgent demand for carbon-based integrated circuits, field effect transistors, optoelectronic devices, and flexible sensors. The current fabrication of these electronic devices is mainly based on layer-by-layer techniques (separate circuit preparation and encapsulation procedures), which show multistep fabrication procedures, complicated renovation/repair procedures, and poor electrical property due to graphene oxidation and exfoliation. Here, we propose a laser-guided interfacial writing (LaserIW) technique based on self-confined, nickel-catalyzed graphitization to directly fabricate highly conductive, embedded graphene electronics inside multilayer structures. The doped nickel is used to induce chain carbonization, which firstly enhances the photothermal effect to increase the confined temperature for initial carbonization, and the generated carbon further increases the light-absorption capacity to fabricate high-quality graphene. Meanwhile, the nickel atoms contribute to the accelerated connection of carbon atoms. This interfacial carbonization inherently avoids the exfoliation and oxidation of the as-formed graphene, resulting in an 8-fold improvement in electrical conductivity (~20,000 S/m at 7,958 W/cm2 and 2 mm/s for 20% nickel content). The LaserIW technique shows excellent stability and reproducibility, with ±2.5% variations in the same batch and ±2% variations in different batches. Component-level wireless light sensors and flexible strain sensors exhibit excellent sensitivity (665 kHz/(W/cm2) for passive wireless light sensors) and self-encapsulation (<1% variations in terms of waterproof, antifriction, and antithermal shock). Additionally, the LaserIW technique allows for one-step renovation of in-service electronics and nondestructive repair of damaged circuits without the need to disassemble encapsulation layers. This technique reverses the layer-by-layer processing mode and provides a powerful manufacturing tool for the fabrication, modification, and repair of multilayer, multifunctional embedded electronics, especially demonstrating the immense potential for in-space manufacturing.

Dan-shen Yin promotes bile acid metabolism and excretion to prevent atherosclerosis via activating FXR/BSEP signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dan-shen Yin (DSY), a traditional prescription, has been demonstrated to be effective in decreasing hyperlipidemia and preventing atherosclerosis (AS), but its mechanism remains unknown. We hypothesized that DSY activates farnesoid X receptor (FXR) to promote bile acid metabolism and excretion, thereby alleviating AS. AIM OF THE STUDY: This study was designed to explore whether DSY reduces liver lipid accumulation and prevents AS by activating FXR and increasing cholesterol metabolism and bile acid excretion. MATERIALS AND METHODS: The comprehensive chemical characterization of DSY was analyzed by UHPLC-MS/MS. The AS models of ApoE-/- mice and SD rats was established by high-fat diet and high-fat diet combined with intraperitoneal injection of vitamin D3, respectively. The aortic plaque and pathological changes were used to evaluate AS. Lipid levels, H&E staining and oil red O staining were used to evaluate liver lipid accumulation. The cholesterol metabolism and bile acid excretion were evaluated by enzyme-linked immunosorbent assay, UPLC-QQQ/MS. In vitro, the lipid and FXR/bile salt export pump (BSEP) levels were evaluated by oil red O staining, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. RESULTS: A total of 36 ingredients in DSY were identified by UPLC-MS/MS analysis. In vivo, high-dose DSY significantly inhibited aortic intimal thickening, improved arrangement disorder, tortuosity, and rupture of elastic fibers, decreased lipid levels, and reduced the number of fat vacuoles and lipid droplets in liver tissue in SD rats and ApoE-/- mice. Further studies found that high-dose DSY significantly reduced liver lipid and total bile acids levels, increased liver ursodeoxycholic acid (UDCA) and other non-conjugated bile acids levels, increased fecal total cholesterol (TC) levels, and augmented FXR, BSEP, cholesterol 7-alpha hydroxylase (CYP7A1), ATP binding cassette subfamily G5/G8 (ABCG5/8) expression levels, while decreasing ASBT expression levels. In vitro studies showed that DSY significantly reduced TC and TG levels, as well as lipid droplets, while also increasing the expression of ABCG5/8, FXR, and BSEP in both HepG2 and Nr1h4 knockdown HepG2 cells. CONCLUSION: This study demonstrated that DSY promotes bile acid metabolism and excretion to prevent AS by activating FXR. For the prevent of AS and drug discovery provided experimental basis.

CK1δ/ε kinases regulate TDP-43 phosphorylation and are therapeutic targets for ALS-related TDP-43 hyperphosphorylation.

Hyperphosphorylated TAR DNA-binding protein 43 (TDP-43) aggregates in the cytoplasm of neurons is the neuropathological hallmark of amyotrophic lateral sclerosis (ALS) and a group of neurodegenerative diseases collectively referred to as TDP-43 proteinopathies that includes frontotemporal dementia, Alzheimer's disease, and limbic onset age-related TDP-43 encephalopathy. The mechanism of TDP-43 phosphorylation is poorly understood. Previously we reported casein kinase 1 epsilon gene (CSNK1E gene encoding CK1ε protein) as being tightly correlated with phosphorylated TDP-43 (pTDP-43) pathology. Here we pursued studies to investigate in cellular models and in vitro how CK1ε and CK1δ (a closely related family sub-member) mediate TDP-43 phosphorylation in disease. We first validated the binding interaction between TDP-43 and either CK1δ and CK1ε using kinase activity assays and predictive bioinformatic database. We utilized novel inducible cellular models that generated translocated phosphorylated TDP-43 (pTDP-43) and cytoplasmic aggregation. Reducing CK1 kinase activity with siRNA or small molecule chemical inhibitors resulted in significant reduction of pTDP-43, in both soluble and insoluble protein fractions. We also established CK1δ and CK1ε are the primary kinases that phosphorylate TDP-43 compared to CK2α, CDC7, ERK1/2, p38α/MAPK14, and TTBK1, other identified kinases that have been implicated in TDP-43 phosphorylation. Throughout our studies, we were careful to examine both the soluble and insoluble TDP-43 protein fractions, the critical protein fractions related to protein aggregation diseases. These results identify CK1s as critical kinases involved in TDP-43 hyperphosphorylation and aggregation in cellular models and in vitro, and in turn are potential therapeutic targets by way of CK1δ/ε inhibitors.

Diagnostic investigation of avian reovirus field variants circulating in broiler chickens in Pennsylvania of United States between 2017 and 2022.

Avian reovirus (ARV) has been continuously affecting the poultry industry in Pennsylvania (PA) in recent years. This report provides our diagnostic investigation on monitoring ARV field variants from broiler chickens in Pennsylvania. Genomic characterization findings of 72 ARV field isolates obtained from broiler cases during the last 6 years indicated that six distinct cluster variant strains (genotype I-VI), which were genetically diverse and distant from the vaccine and vaccine-related field strains, continuously circulated in PA poultry. Most of the variants clustered within genotype V (24/72, 33.3%), followed by genotype II (16/72, 22.2%), genotype IV (13/72, 18.1%), genotype III (13/72, 18.1%), genotype VI (05/72, 6.94%), and genotype I (1/72, 1.38%). The amino acid identity between 72 field variants and the vaccine strains (1133, 1733, 2408, 2177) varied from 45.3% to 99.7%, while the difference in amino acid counts ranged from 1-164. Among the field variants, the amino acid identity and count difference ranged from 43.3% to 100% and 0 to 170, respectively. Variants within genotype V had maximum amino acid identity (94.7-100%), whereas none of the variants within genotypes II and VI were alike. These findings indicate the continuing occurrence of multiple ARV genotypes in the environment.

Digital intraoperative evaluation of restorative space and nontemplate-guided tooth preparation when replacing failed anterior restorations: A dental technique.

Assessing the correlation between the current restorative space and the target restorative space is important in determining whether additional tooth preparation is required when replacing failed prostheses. However, existing techniques are not always accurate or efficient. This article describes a digital workflow for the accurate chairside evaluation of the current restorative space and nontemplate-guided tooth preparation. Reference data was obtained from an initial scan of the existing restoration with an intraoral scanner. After removing the existing restoration, a second scan of the tooth was made and compared with the reference data to evaluate the current restorative space. Subsequently, the abutment tooth was prepared and rescanned, with the restorative space being re-evaluated until it met the requirements. This workflow enables the immediate and accurate evaluation of the restorative space, facilitating accurate chairside tooth preparation without the need for silicone indices or other templates, thereby saving time and cost.

Bio-functional hydroxyapatite-coated 3D porous polyetherketoneketone scaffold for enhanced osteogenesis and osteointegration in orthopedic applications.

Polyetherketoneketone (PEKK), a high-performance thermoplastic special engineering material, maintains bone-like mechanical properties and has received considerable attention in the biomedical field. The 3D printing technique enables the production of porous scaffolds with a honeycomb structure featuring precisely controlled pore size, porosity and interconnectivity, which holds significant potential for applications in tissue engineering. The ideal pore architecture of porous PEKK scaffolds has yet to be elucidated. Porous PEKK scaffolds with five pore sizes P200 (225 ± 9.8 µm), P400 (411 ± 22.1 µm), P600 (596 ± 23.4 µm), P800 (786 ± 24.2 µm) and P1000 (993 ± 26.0 µm) were produced by a 3D printer. Subsequently, the optimum pore size, the P600, for mechanical properties and osteogenesis was selected based on in vitro experiments. To improve the interfacial bioactivity of porous PEKK scaffolds, hydroxyapatite (HAp) crystals were generated via in situ biomimetic mineralization induced by the phase-transited lysozyme coating. Herein, a micro/nanostructured surface showing HAp crystals on PEKK scaffold was developed. In vitro and in vivo experiments confirmed that the porous PEKK-HAp scaffolds exhibited highly interconnected pores and functional surface structures that were favorable for biocompatibility and osteoinductivity, which boosted bone regeneration. Therefore, this work not only demonstrates that the pore structure of the P600 scaffold is suitable for PEKK orthopedic implants but also sheds light on a synergistic approach involving 3D printing and biomimetic mineralization, which has the potential to yield customized 3D PEKK-HAp scaffolds with enhanced osteoinductivity and osteogenesis, offering a promising strategy for bone tissue engineering.

Classified diagnosis and treatment scheme of oral cosmetic restoration based on aesthetic analysis (part â ¡): Chinese aesthetic connotation and analysis scheme.

At present, the commonly used clinical protocols of oral cosmetic restoration are mostly based on the oral aesthetic indexes proposed by Western developed countries (referred to as Western aesthetics), which are different from the oral aesthetic indexes unique to Chinese people (referred to as Chinese aesthetics). In the design of restoration schemes and the evaluation of restoration effects, these differences have a large or small effect on the doctor-patient-technology triad. Improper handling could directly weaken the cooperation efficiency of the three parties, reduce patient satisfaction, and even lead to medical disputes in serious cases. From doing a good job of oral cosmetic restoration in China, the connotative characteristics of Chinese oral aesthetics are introduced in this paper, and the value of oral aesthetic analysis in diagnosis and treatment is discussed. The process and method of aesthetic analysis and assessment through the modified Chinese psychosocial impact of dental aesthetics questionnaire and the evaluation ruler of the expected value of oral cosmetic restoration are further introduced in detail.

Mendelian Randomization Validates the Immune Landscape Mediated by Aggrephagy in Esophageal Squamous Cell Carcinoma Patients from the Perspectives of Multi-omics.

Objective: To delineate the immune landscape of ESCC patients mediated by aggrephagy through bioinformatics and identify prognostic cell cluster genes with causal attributes to esophageal cancer through Mendelian randomization. Methods: Quality control, dimension reduction, and annotation were performed on the ESCC single-cell dataset. NMF clustering of various cell subgroups was carried out based on the expression of AGG-related genes, and AGG-related genes in each cluster were identified. Pseudo-temporal analysis was used to observe changes in the expression of AGG-related genes in each cluster. Cell communication analysis was employed to observe interactions between cell subgroups. Changes in classification, metabolism, or KEGG pathways in related subgroups were observed based on different cell characteristics. The AGG cluster attributes of TCGA and GEO samples were assessed based on GSVA, and the prognosis of each cluster was observed. The immune treatment situation and the relationship between mutation level and prognosis of AGG cluster-related samples were observed through the TIDE database and microsatellite instability. Finally, the eQTL of genes in each prognostic AGG cluster was used as an instrumental variable, with esophageal cancer as the outcome factor. Through Mendelian randomization analysis, AGG cluster-related genes with a causal relationship to esophageal cancer were established. Results: Dimension reduction clustering of single-cell transcriptome data identified 19 different cell subgroups. After re-annotation of the 19 cell subgroups, it was found that the CAF cells, B cells, T cells, NK cells, etc., of ESCA patients were all elevated compared to the control group. CAF cells had a high degree of communication with most cells. There were significant differences in macrophage metabolism and B-cell-mediated signal transduction pathways in different AGG clusters. The TUBA1B+Mac-C0 cluster, along with other clusters, exhibits predictive prognostic and immunotherapeutic potential at the transcriptional level. Mendelian randomization analysis revealed a causal relationship between genes such as CTSZ, CTSC, DAD, COLEC12, ATOX1, within the AGG cluster, and the onset of esophageal cancer. Conclusion: Aggrephagy mediates and influences the alterations and interactions of various immune cells in patients with ESCC. We elucidate the roles of AGG-related clusters, such as TUBA1B+Mac-C0, VIM+CD8+T_cells-C0, UBB+Mac-C2, in mediating prognosis and immune therapy in ESCC patients. Genes causally associated with the occurrence of esophageal cancer are identified within the AGG cluster, including CTSZ, CTSC, DAD, COLEC12, ATOX1, etc., offering new evidence for clinical immune therapy. These findings underscore the significance of these gene clusters in influencing both prognosis and immune responses in the context of esophageal cancer, shedding light on potential therapeutic targets and prognostic markers.

Analyses of hypoxia-related risk factors and clinical relevance in breast cancer.

Introduction: Hypoxia plays an important role in the heterogeneity, relapse, metastasis, and drug resistance of breast cancer. In this study, we explored the hypoxia-related biological signatures in different subtypes of breast cancer and identified the key prognostic factors by bioinformatics methods. Methods: Based on The Cancer Genome Atlas (TCGA) Breast Cancer datasets, we divided the samples into immune-activated/suppressed populations by single-sample gene set enrichment analysis (ssGSEA) and then used hierarchical clustering to further identify hypoxic/non-hypoxic populations from the immune-suppressed samples. A hypoxia related risk model of breast cancer was constructed. Results: Nuclear factor interleukin-3 regulated (NFIL3), serpin family E member 1 (SERPINE1), FOS, biglycan (BGN), epidermal growth factor receptor (EGFR), and sushi-repeat-containing protein, X-linked (SRPX) were identified as key hypoxia-related genes. Margin status, American Joint Committee on Cancer (AJCC) stage, hypoxia status, estrogen receptor/progesterone receptor (ER/PR) status, NFIL3, SERPINE1, EGFR, and risk score were identified as independent prognostic indicators for breast cancer patients. The 3- and 5-year survival curves of the model and immunohistochemical staining on the breast cancer microarray verified the statistical significance and feasibility of our model. Among the different molecular types of breast cancer, ER/PR+ and HER2+ patients might have higher hypoxia-related risk scores. ER/PR-negative samples demonstrated more activated immune-related pathways and better response to most anticancer agents. Discussion: Our study revealed a novel risk model and potential feasible prognostic factors for breast cancer and might provide new perspectives for individual breast cancer treatment.