Preliminary study on AI-assisted diagnosis of bone remodeling in chronic maxillary sinusitis.

OBJECTIVE: To construct the deep learning convolution neural network (CNN) model and machine learning support vector machine (SVM) model of bone remodeling of chronic maxillary sinusitis (CMS) based on CT image data to improve the accuracy of image diagnosis. METHODS: Maxillary sinus CT data of 1000 samples in 500 patients from January 2018 to December 2021 in our hospital was collected. The first part is the establishment and testing of chronic maxillary sinusitis detection model by 461 images. The second part is the establishment and testing of the detection model of chronic maxillary sinusitis with bone remodeling by 802 images. The sensitivity, specificity and accuracy and area under the curve (AUC) value of the test set were recorded, respectively. RESULTS: Preliminary application results of CT based AI in the diagnosis of chronic maxillary sinusitis and bone remodeling. The sensitivity, specificity and accuracy of the test set of 93 samples of CMS, were 0.9796, 0.8636 and 0.9247, respectively. Simultaneously, the value of AUC was 0.94. And the sensitivity, specificity and accuracy of the test set of 161 samples of CMS with bone remodeling were 0.7353, 0.9685 and 0.9193, respectively. Simultaneously, the value of AUC was 0.89. CONCLUSION: It is feasible to use artificial intelligence research methods such as deep learning and machine learning to automatically identify CMS and bone remodeling in MSCT images of paranasal sinuses, which is helpful to standardize imaging diagnosis and meet the needs of clinical application.

Radical Homopolymerization of Linear α-Olefins Enabled by 1,4-Cyano Group Migration.

α-Olefins are valued and abundant building blocks from fossil resources. They are widely used to provide small-molecule or polymeric products. Despite numerous advantages of radical polymerization, it has been well-documented as textbook knowledge that α-olefins and their functionalized derivatives cannot be radically homopolymerized because of the degradative chain transfer side reactions. Herein, we report our studies on the homopolymerization of thiocyanate functionalized α-olefins enabled by 1,4-cyano group migration under radical conditions. By this approach, a library of ABC sequence-controlled polymers with high molecular weights can be prepared. We can also extend this strategy to the homopolymerization of α-substituted styrenic and acylate monomers which are known to be challenging to achieve. Overall, the demonstrated functional group migration radical polymerization could provide new possibilities to synthesize polymers with unprecedented main chain sequences and structures. These polymers are promising candidates for novel polymeric materials.

Gut bacteria exacerbates TNBS-induced colitis and kidney injury through oxidative stress.

Gut microbiota has been implicated in the initiation and progression of various diseases; however, the underlying mechanisms remain elusive and effective therapeutic strategies are scarce. In this study, we investigated the role and mechanisms of gut microbiota in TNBS-induced colitis and its associated kidney injury while evaluating the potential of dietary protein as a therapeutic intervention. The intrarectal administration of TNBS induced colitis in mice, concurrently with kidney damage. Interestingly, this effect was absent when TNBS was administered intraperitoneally, indicating a potential role of gut microbiota. Depletion of gut bacteria with antibiotics significantly attenuated the severity of TNBS-induced inflammation, oxidative damage, and tissue injury in the colon and kidneys. Mechanistic investigations using cultured colon epithelial cells and bone-marrow macrophages unveiled that TNBS induced cell oxidation, inflammation and injury, which was amplified by the bacterial component LPS and mitigated by thiol antioxidants. Importantly, in vivo administration of thiol-rich whey protein entirely prevented TNBS-induced colonic and kidney injury. Our findings suggest that gut bacteria significantly contribute to the initiation and progression of colitis and associated kidney injury, potentially through mechanisms involving LPS-induced exaggeration of oxidative cellular damage. Furthermore, our research highlights the potential of dietary thiol antioxidants as preventive and therapeutic interventions.

Comparison of the applicability of seven calculation equations of glomerular filtration rate among elderly people in China.

BACKGROUND: At present, estimated glomerular filtration rate (eGFR) remains the most frequently utilized parameter in the evaluation of kidney injury severity. Numerous equations have been formulated based on serum creatinine (Scr) or serum cystatin C (Cysc) levels. However, there is a lack of consensus regarding the efficacy of these equations in assessing eGFR, particularly for elderly individuals in China. This study aimed to evaluate the applicability of the MDRD, MDRDc, CKD-EPI series, BIS1, and FAS equations within the Chinese elderly population. METHODS: A cohort of 298 elderly patients with measured GFR (mGFR) was enrolled. The patients were categorized into three subgroups based on their mGFR levels. The eGFR performance was examined, taking into account bias, interquartile range (IQR), accuracy P30, and root-mean-square error (RMSE). Bland-Altman plots were employed to verify the validity of eGFR. RESULTS: The participants had a median age of 71 years, with 167 (56.0%) being male. Overall, no significant differences in bias were observed among the seven equations (P > 0.05). In terms of IQR, P30, and RMSE, the BIS1 equation demonstrated superior accuracy (14.61, 72.1%, and 13.53, respectively). When mGFR < 30 ml/min/1.73 m2, all equations underestimated the true GFR, with the highest accuracy reaching only 59%. Bland-Altman plots indicated that the BIS1 equation exhibited the highest accuracy, featuring a 95% confidence interval (CI) width of 52.37. CONCLUSIONS: This study suggested that the BIS1 equation stands out as the most applicable for estimating GFR in Chinese elderly patients with normal renal function or only moderate decline. 2020NL-085-03, 2020.08.10, retrospectively registered.

Single-cell RNA sequencing analysis of the retina under acute high intraocular pressure.

JOURNAL/nrgr/04.03/01300535-202419110-00032/figure1/v/2024-03-08T184507Z/r/image-tiff High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases, yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown. Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel (Healaflow®). Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure. Our results identified a total of 12 cell types, namely retinal pigment epithelial cells, rod-photoreceptor cells, bipolar cells, Müller cells, microglia, cone-photoreceptor cells, retinal ganglion cells, endothelial cells, retinal progenitor cells, oligodendrocytes, pericytes, and fibroblasts. The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells, with ganglion cells decreased by 23%. Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure. We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression. We found upregulation of the B3gat2 gene, which is associated with neuronal migration and adhesion, and downregulation of the Tsc22d gene, which participates in inhibition of inflammation. This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure. These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.

Monoethanolamine enhanced iohexol degradation in the Co(II)/sulfite system: Nonnegligible role of complexation in accelerating cobalt redox cycling.

Generation of sulfate radicals (SO4•-) from sulfite activation has emerged as a promising method for abatement of organic pollutants in the water and wastewater treatment. Co(II) has garnered attention due to its high catalytic activity in the sulfite activation, which is compromised by the slow Co(II)/Co(III) redox cycling. Regarding the regulation of Co(II) electronic structure via the complexation effect, monoethanolamine (MEA), a common chelator, is introduced into the Co(II)/sulfite system. MEA addition results in a significant improvement in iohexol abatement efficiency, increasing from 40% to 92%. The superior iohexol abatement relies on the involvement of SO4•-, hydroxyl radicals (HO•) and Co(IV). Hydrogen radical (•H) is unexpectedly detected, acting as a strong reducing agent, contributing to the reduction of Co(III). This enhancement of sulfite activation by MEA is due to the formation of the Co(II)-MEA complex, in which the complexation ratio of Co(II) and MEA is critical. Electrochemical characterization and theoretical calculations demonstrate that the complexation can facilitate the Co(II)/Co(III) redox cycling with the concomitant enhancement of sulfite activation. This work provides a new insight into the Co(II)/sulfite system in the presence of organic ligands.

Novel insights into the effects of 5-hydroxymethfurural on genomic instability and phenotypic evolution using a yeast model.

5-Hydroxymethfurural (5-HMF) is naturally found in a variety of foods and beverages and represents a main inhibitor in the lignocellulosic hydrolysates used for fermentation. This study investigated the impact of 5-HMF on the genomic stability and phenotypic plasticity of the yeast Saccharomyces cerevisiae. Using next-generation sequencing technology, we examined the genomic alterations of diploid S. cerevisiae isolates that were subcultured on a medium containing 1.2 g/L 5-HMF. We found that in 5-HMF-treated cells, the rates of chromosome aneuploidy, large deletions/duplications, and loss of heterozygosity were elevated compared with that in untreated cells. 5-HMF exposure had a mild impact on the rate of point mutations but altered the mutation spectrum. Contrary to what was observed in untreated cells, more monosomy than trisomy occurred in 5-HMF-treated cells. The aneuploidy mutant with monosomic chromosome IX was more resistant to 5-HMF than the diploid parent strain because of the enhanced activity of alcohol dehydrogenase. Finally, we found that overexpression of ADH6 and ZWF1 effectively stabilized the yeast genome under 5-HMF stress. Our findings not only elucidated the global effect of 5-HMF on the genomic integrity of yeast but also provided novel insights into how chromosomal instability drives the environmental adaptability of eukaryotic cells.IMPORTANCESingle-cell microorganisms are exposed to a range of stressors in both natural and industrial settings. This study investigated the effects of 5-hydroxymethfurural (5-HMF), a major inhibitor found in baked foods and lignocellulosic hydrolysates, on the chromosomal instability of yeast. We examined the mechanisms leading to the distinct patterns of 5-HMF-induced genomic alterations and discovered that chromosomal loss, typically viewed as detrimental to cell growth under most conditions, can contribute to yeast tolerance to 5-HMF. Our results increased the understanding of how specific stressors stimulate genomic plasticity and environmental adaptation in yeast.

Radical chemistry in polymer science: an overview and recent advances.

Radical chemistry is one of the most important methods used in modern polymer science and industry. Over the past century, new knowledge on radical chemistry has both promoted and been generated from the emergence of polymer synthesis and modification techniques. In this review, we discuss radical chemistry in polymer science from four interconnected aspects. We begin with radical polymerization, the most employed technique for industrial production of polymeric materials, and other polymer synthesis involving a radical process. Post-polymerization modification, including polymer crosslinking and polymer surface modification, is the key process that introduces functionality and practicality to polymeric materials. Radical depolymerization, an efficient approach to destroy polymers, finds applications in two distinct fields, semiconductor industry and environmental protection. Polymer chemistry has largely diverged from organic chemistry with the fine division of modern science but polymer chemists constantly acquire new inspirations from organic chemists. Dialogues on radical chemistry between the two communities will deepen the understanding of the two fields and benefit the humanity.

Population Pharmacokinetic Analysis of Follicle-Stimulating Hormone During Ovarian Stimulation: Relation with Weight, Prolactin and Gene Polymorphism in THADA and ADIPOQ.

BACKGROUND: Personalisation strategies of ovarian stimulation for in vitro fertilisation (IVF)/ intracytoplasmic sperm injection (ICSI) treatments using exogenous follicle-stimulating hormone (FSH) have been extensively studied over the past 20 years. This research aimed to develop a FSH population pharmacokinetic (PPK) model taking into account the contribution of gene polymorphisms in Chinese reproductive-age women. METHODS: Data from 173 patients undergoing GnRH agonist down-regulation long protocols of IVF/ICSI treatment were collected. PPK analysis was subsequently conducted using the nonlinear mixed-effect model (NONMEM) software. Several covariates, including 18 single nucleotide polymorphisms, demographic factors and biological characteristics, were evaluated. The final PPK model was extensively validated using bootstrapping and normalised prediction error distribution, as well as external validation on an independent group of 35 patients. RESULTS: FSH PPK was accurately described by a one-compartment model with first-order absorption. The typical population value of apparent clearance was estimated to be 0.81 L/h [relative standard errors (RSE) 5.3%] with an inter-individual variability (IIV) of 16.0%. The typical apparent distribution volume was 8.36 L (RSE 9.7%, 59.7% IIV), and the absorption rate constant was estimated to be 0.0444 h-1 (RSE 9.1%). Body weight, basal prolactin concentration and the gene ADIPOQ (rs1501299) showed a significant covariate effect on the FSH clearance rate and exposure concentration. Genotypes of THADA (rs12478601) significantly influenced the distribution volume. Simulation results indicated that patients with the TT genotype of THADA (rs12478601) required a longer time to reach steady state and had less fluctuation in FSH levels. Model evaluations showed that the final model accurately and precisely described the observed data and demonstrated effective prediction performance. CONCLUSION: PPK models of FSH have been developed, which could potentially be used for FSH dosage individualisation in the clinical setting. CLINICAL TRIAL REGISTRATION: This study has been registered with the Chinese Clinical Trials Registry (ChiCTR2100049142).

Exploring thyroxine binding globulin structural changes and its release from human hepatoblastoma cells upon interaction with silica particles: A prelude to unrevealing the mechanism of thyroid hormone dysregulation.

Endocrine dysregulation in the presence of environmental chemical risk factors is a global adverse health concern. The aim of this investigation was to explore the structural changes and binding affinity of thyroxine (T4) binding protein (TBG) upon interaction with SiO2 particles as the second largest mineral in the Earth's crust and one of the most important constituents of rock, soil, and dust. Therefore, the interaction of TBG with SiO2 particles was assessed by fluorescence quenching, molecular docking, ANS and synchronous fluorescence, and far-UV CD analyses. Also, the release of TBG from human hepatoblastoma cell line, Hep G2, was assessed by ELISA assay. The results displayed that the value of stoichiometry of binding site (n) of TBG for T4 was approximately equal to one, which was reduced to 0.36 in the presence of SiO2 particles. Also, the binding affinity (Kb) values revealed that the binding affinity between T4 and TBG was strong (97.90 × 105 L/mol), while the presence of SiO2 particles resulted in the calculation of a Kb around 0.00159 × 105 L/mol, which was significantly lower than that of the absence of SiO2 particles. This data was also verified by molecular docking analyses which indicated that SiO2 particles interacted with the T4 binding pocket of TBG. Moreover, further studies exhibited that although the equimolar concentration of T4 to TBG resulted in the superior stability of TBG-T4 complex relative to free TBG, the presence of SiO2 particles with the same concentration led to denaturation of the secondary structure of TBG. Furthermore, it was seen that the amount of released TBG in the cell culture medium of Hep G2 was about 2.21 ng/mL protein, whereas this amount in SiO2 particles-treated cell group was significantly reduced to 1.71 ng/mL protein (*P < 0.05). In conclusion, this study implies that SiO2 particles show the potential to result in inhibition of TBG release, TBG denaturation, and interfere with TBG binding affinity which may lead to dysregulation of the thyroid hormone transport and associated signaling pathways.

Nonlethal Furfural Exposure Causes Genomic Alterations and Adaptability Evolution in Saccharomyces cerevisiae.

Furfural is a major inhibitor found in lignocellulosic hydrolysate, a promising feedstock for the biofermentation industry. In this study, we aimed to investigate the potential impact of this furan-derived chemical on yeast genome integrity and phenotypic evolution by using genetic screening systems and high-throughput analyses. Our results showed that the rates of aneuploidy, chromosomal rearrangements (including large deletions and duplications), and loss of heterozygosity (LOH) increased by 50-fold, 23-fold, and 4-fold, respectively, when yeast cells were cultured in medium containing a nonlethal dose of furfural (0.6 g/L). We observed significantly different ratios of genetic events between untreated and furfural-exposed cells, indicating that furfural exposure induced a unique pattern of genomic instability. Furfural exposure also increased the proportion of CG-to-TA and CG-to-AT base substitutions among point mutations, which was correlated with DNA oxidative damage. Interestingly, although monosomy of chromosomes often results in the slower growth of yeast under spontaneous conditions, we found that monosomic chromosome IX contributed to the enhanced furfural tolerance. Additionally, terminal LOH events on the right arm of chromosome IV, which led to homozygosity of the SSD1 allele, were associated with furfural resistance. This study sheds light on the mechanisms underlying the influence of furfural on yeast genome integrity and adaptability evolution. IMPORTANCE Industrial microorganisms are often exposed to multiple environmental stressors and inhibitors during their application. This study demonstrates that nonlethal concentrations of furfural in the culture medium can significantly induce genome instability in the yeast Saccharomyces cerevisiae. Notably, furfural-exposed yeast cells displayed frequent chromosome aberrations, indicating the potent teratogenicity of this inhibitor. We identified specific genomic alterations, including monosomic chromosome IX and loss of heterozygosity of the right arm of chromosome IV, that confer furfural tolerance to a diploid S. cerevisiae strain. These findings enhance our understanding of how microorganisms evolve and adapt to stressful environments and offer insights for developing strategies to improve their performance in industrial applications.

Nanoscale effects of TiO2 nanoparticles on the rheological behaviors of ultra-high molecular weight polyethylene (UHMWPE).

Considering the molar mass between entanglements to be an intrinsic property of ultra-high molecular weight polyethylene (UHMWPE), the number of entanglements per chain increases with increasing molar mass, correspondingly making the UHMWPE intractable. Herein, we dispersed TiO2 nanoparticles with different characteristics into UHMWPE solutions to disentangle the molecular chains. Compared with the UHMWPE pure solution, the viscosity of the mixture solution declines by 91.22%, and the critical overlap concentration increases from 1 wt% to 1.4 wt%. A rapid precipitation method was utilized to obtain UHMWPE and UHMWPE/TiO2 composites from the solutions. The melting index of UHMWPE/TiO2 is 68.85 mg, which is in sharp contrast to that of UHMWPE which is 0 mg. We characterized the microstructures of UHMWPE/TiO2 nanocomposites using TEM, SAXS, DMA, and DSC. Accordingly, this significant improvement in processability contributed to the reduction of entanglements and a schematic model was proposed to explain the mechanism by which nanoparticles disentangle molecular chains. Simultaneously, the composite demonstrated better mechanical properties than UHMWPE. In summary, we provide a strategy to promote the processability of UHMWPE without sacrificing its outstanding mechanical properties.

Comparative study and multi-parameter analysis to optimize device structure of triboelectric nanogenerators.

Triboelectric nanogenerator is becoming one of the most efficient energy harvesting device among all mechanical energy harvesters. This device consists of dielectric friction layers and metal electrode which generates electrical charges using electrostatic induction effect. There are several factors influencing the performance of this generator which needs to be evaluated prior to experiment. The absence of a universal technique for TENG simulation makes the device design and optimization hard before practical fabrication, which also lengthens the exploration and advancement cycle and hinders the arrival of practical applications. In order to deepen the understanding the core physic behind the working process of this device, this work will provide comparative analysis on different modes of TENG. Systematic investigation on different material combination, effect of material thickness, dielectric constant and impact of surface patterning is evaluated to shortlist the best material combination. COMSOL Multiphysics simulating environment is used to design, model and analyze factor affecting the overall output performance of TENG. The stationary study in this simulator is performed using 2D geometry structure with higher mesh density. During this study short circuit and open circuit condition were applied to observe the behavior of charge and electric potential produced. This observation is analyzed by plotting charge transfer/electric potential against various displacement distances of dielectric friction layers. The ouput is then provided to load ciruitary to measure the maximum output power of the models. Overall, this study provides an excellent understanding and multi-parameter analysis on basic theoretical and simulation modeling of TENG device.

Rationalizing the Dependence of Poly (Vinylidene Difluoride) (PVDF) Rheological Performance on the Nano-Silica.

Research on the rheological performance and mechanism of polymer nanocomposites (PNCs), mainly focuses on non-polar polymer matrices, but rarely on strongly polar ones. To fill this gap, this paper explores the influence of nanofillers on the rheological properties of poly (vinylidene difluoride) (PVDF). The effects of particle diameter and content on the microstructure, rheology, crystallization, and mechanical properties of PVDF/SiO2 were analyzed, by TEM, DLS, DMA, and DSC. The results show that nanoparticles can greatly reduce the entanglement degree and viscosity of PVDF (up to 76%), without affecting the hydrogen bonds of the matrix, which can be explained by selective adsorption theory. Moreover, uniformly dispersed nanoparticles can promote the crystallization and mechanical properties of PVDF. In summary, the viscosity regulation mechanism of nanoparticles for non-polar polymers, is also applicable to PVDF, with strong polarity, which is of great value for exploring the rheological behavior of PNCs and guiding the process of polymers.

The Combined Administration of Vitamin C and Copper Induces a Systemic Oxidative Stress and Kidney Injury.

Vitamin C (ascorbic acid; AA) and copper (Cu2+) are well used supplements with many health-promoting actions. However, when they are used in combination, the Fenton reaction occurs, leading to the formation of highly reactive hydroxyl radicals. Given that kidney is vulnerable to many toxicants including free radicals, we speculated that the in vivo administration of AA plus Cu2+ may cause oxidative kidney injury. The purpose of this study was to address this possibility. Mice were administered with AA and Cu2+, alone or in combination, via oral gavage once a day for various periods. Changes in the systemic oxidative status, as well renal structure and functions, were examined. The administration of AA plus Cu2+ elevated protein oxidation in serum, intestine, bladder, and kidney, as evidenced by the increased sulfenic acid formation and decreased level of free sulfhydryl groups (-SH). The systemic oxidative stress induced by AA plus Cu2+ was associated with a significant loss of renal function and structure, as indicated by the increased blood urea nitrogen (BUN), creatinine and urinary proteins, as well as glomerular and tubular cell injury. These effects of AA and Cu2+ were only observed when used in combination, and could be entirely prevented by thiol antioxidant NAC. Further analysis using cultured renal tubular epithelial cells revealed that AA plus Cu2+ caused cellular protein oxidation and cell death, which could be abolished by NAC and catalase. Moreover, coincubation of AA and Cu2+ led to H2O2 production. Collectively, our study revealed that a combined administration of AA and Cu2+ resulted in systemic oxidative stress and renal cell injury. As health-promoting supplements, AA and Cu2+ should not be used together.

Development of Dietary Thiol Antioxidant via Reductive Modification of Whey Protein and Its Application in the Treatment of Ischemic Kidney Injury.

Thiol antioxidants play important roles in cell and body defense against oxidative stress. In body fluid, albumin is the richest source of thiol antioxidants. One recent study showed that the reductive modification of thiol residues in albumin potentiated its antioxidative activity. Given that whey protein (WP) contains albumin and other thiol-active proteins, this property of WP could be exploited to develop novel thiol antioxidants. The aim of this study was to address this possibility. WP was reductively modified with dithiothreitol (DTT). The modified protein exhibited significantly elevated free sulfhydryl groups (-SH) and thiol antioxidative activity. It detoxified H2O2 and prevented H2O2-initiated protein oxidation and cell death in a -SH group-dependent way in vitro. In addition, it reacted with GSH/GSSG and altered the GSH/GSSG ratio via thiol-disulfide exchange. In vivo, oral administration of the reductively modified WP prevented oxidative stress and renal damage in a mouse model of renal injury caused by ischemia reperfusion. It significantly improved renal function, oxidation, inflammation, and cell injury. These protective effects were not observed in the WP control and were lost after blocking the -SH groups with maleimide. Furthermore, albumin, one of the ingredients of WP, also exhibited similar protective effects when reductively modified. In conclusion, the reductive modification of thiol residues in WP transformed it into a potent thiol antioxidant that protected kidneys from ischemia reperfusion injury. Given that oxidative stress underlies many life-threatening diseases, the reductively modified dietary protein could be used for the prevention and treatment of many oxidative-stress-related conditions, such as cardiovascular diseases, cancer, and aging.

Shuffling the yeast genome using CRISPR/Cas9-generated DSBs that target the transposable Ty1 elements.

Although homologous recombination between transposable elements can drive genomic evolution in yeast by facilitating chromosomal rearrangements, the details of the underlying mechanisms are not fully clarified. In the genome of the yeast Saccharomyces cerevisiae, the most common class of transposon is the retrotransposon Ty1. Here, we explored how Cas9-induced double-strand breaks (DSBs) directed to Ty1 elements produce genomic alterations in this yeast species. Following Cas9 induction, we observed a significant elevation of chromosome rearrangements such as deletions, duplications and translocations. In addition, we found elevated rates of mitotic recombination, resulting in loss of heterozygosity. Using Southern analysis coupled with short- and long-read DNA sequencing, we revealed important features of recombination induced in retrotransposons. Almost all of the chromosomal rearrangements reflect the repair of DSBs at Ty1 elements by non-allelic homologous recombination; clustered Ty elements were hotspots for chromosome rearrangements. In contrast, a large proportion (about three-fourths) of the allelic mitotic recombination events have breakpoints in unique sequences. Our analysis suggests that some of the latter events reflect extensive processing of the broken ends produced in the Ty element that extend into unique sequences resulting in break-induced replication. Finally, we found that haploid and diploid strain have different preferences for the pathways used to repair double-stranded DNA breaks. Our findings demonstrate the importance of DNA lesions in retrotransposons in driving genome evolution.

Multi-objective parameter optimization of CNC plane milling for sustainable manufacturing.

Energy modeling and cutting parameter optimization of the machining process have been recognized as powerful and effective ways to save energy. However, in the actual machining process, technologists often use empirical methods to determine the final cutting parameters. Due to the lack of theoretical support and optimization tools, this method is difficult to fully consider the constraints of machine tool capability, cutting tool performance, and workpiece material, which affects the overall performance of the machine tool to give full play. To address this problem, a multi-objective parameter optimization method of computer numerical control (CNC) plane milling for sustainable manufacturing was proposed in this paper. More specifically, three tasks were carried out: (1) an accurate milling energy model considering transient processes such as spindle acceleration was established; (2) a multi-objective parameter optimization model of CNC plane milling was established with cutting parameters as optimization variables and considering various complex constraints; (3) by drawing 3D surface maps, the internal relationship between the cutting parameters and the optimization index was presented in detail and intuitively. Finally, a case study was carried out in the XHK-714F vertical machining center. The results showed that the processing efficiency is improved by 21.0%, the energy consumption is reduced by 15.3%, and the surface roughness is reduced by 5.5% through the optimization of cutting parameters, which verified the effectiveness and feasibility of the proposed model and method.

AIoT enabled resampling filter for temperature extraction of the Brillouin gain spectrum.

The Artificial Intelligence of Things (AIoT) turns passive fiber sensors into learning machines. It can be used to integrate intelligent nodes into a multi-dimensional sensing system. In this study, the temperature measurement system based on Brillouin Gain Spectrum (BGS) test setup is creatively implemented with the AIoT architecture; the training and testing stages of the neural network are divided into different layers of equipment to improve performance and reduce the network traffic. To enable the lightweight and low-power consumption edge computing device to extract accurate temperature from the BGS during testing, we have integrated the post-processing method inspired by curve fitting into the machine learning and proposed the efficient digital resampling filter. The resampling filter approach is achieved by the peak range algorithm with Gauss differential operator and digital band-pass filter. The evaluation results for different methods on the BGS datasets show the superior performance of our approach. Notably, the approach can increase temperature extraction accuracy and compress the sampling data. The RMSEA of the extraction temperature is 0.5635, which can bring an almost 21% accuracy increase over the classic method. Compared with the classic method of processing the original data on the same hardware platform, the amount of data post-processed by the filter is reduced by 75%; the time consumption is reduced by 22%.

Dual-responsive nanovaccine for cytosolic delivery of antigens to boost cellular immune responses and cancer immunotherapy.

Cancer vaccine contributing to the success of the treatment and prevention of tumors has attracted a huge attention as a strategy for tumor immunotherapy in recent years. A major challenge of cancer vaccine is to target cytosols of dendritic cells (DCs) in the lymph nodes (LNs) to enhance efficiency of antigen cross-presentation, which elicits high levels of cytotoxic T-lymphocytes to destruct tumor cells. Here, we address this issue by conjugating ovalbumin (OVA) to PEG-PCL using disulfide bond (-ss-), and the degradable pH-responsive polymer-PEI-PCL as delivery carrier. In addition, the mol ratio of PEG-PCL to PEI-PCL in the mixed micelles was tailored to deliver the OVA to LNs. Subsequently, CpG ODN1826, a TLR-9 agonist, was further introduced into a mixed micelle of 30 nm or less as a unique tumor vaccine. Importantly, the results demonstrated the mixed micelles with 1:1 mol of PCL-PEG and PCL-PEI can effectively migrate to distal LNs where antigen were efficiently captured by DCs, meanwhile, OVA was modified to the surface of mixed micelles via disulfide bonds (-ss-) for promotion efficiency of antigen cross-presentation. More surprisingly, combination of tumor vaccine with anti-PD-1, the therapy of ectopic melanoma (B16-OVA) and lung metastasis melanoma (B16-OVA) is excellent therapeutic effect. Taken together, our works offers a novel strategy for the cytosol delivery of antigens to achieve potent cancer immunotherapy.