ABSTRACT
Failure of central nervous system projection neurons to spontaneously regenerate long-distance axons underlies irreversibility of white matter pathologies. A barrier to axonal regenerative research is that the axons regenerating in response to experimental treatments stall growth before reaching post-synaptic targets. Here, we test the hypothesis that the interaction of regenerating axons with live oligodendrocytes, which were absent during developmental axon growth, contributes to stalling axonal growth. To test this hypothesis, first, we used single cell RNA-seq (scRNA-seq) and immunohistology to investigate whether post-injury born oligodendrocytes incorporate into the glial scar after optic nerve injury. Then, we administered demyelination-inducing cuprizone and stimulated axon regeneration by Pten knockdown (KD) after optic nerve crush. We found that post-injury born oligodendrocyte lineage cells incorporate into the glial scar, where they are susceptible to the demyelination diet, which reduced their presence in the glial scar. We further found that the demyelination diet enhanced Pten KD-stimulated axon regeneration and that localized cuprizone injection promoted axon regeneration. We also present a resource for comparing the gene expression of scRNA-seq-profiled normal and injured optic nerve oligodendrocyte lineage cells.
Subject(s)
Axons , Demyelinating Diseases , Humans , Axons/physiology , Gliosis/metabolism , Gliosis/pathology , Cuprizone , Nerve Regeneration/physiology , Retinal Ganglion Cells/metabolism , Oligodendroglia , Demyelinating Diseases/chemically induced , Demyelinating Diseases/metabolismABSTRACT
Central nervous system projection neurons fail to spontaneously regenerate injured axons. Targeting developmentally regulated genes in order to reactivate embryonic intrinsic axon growth capacity or targeting pro-growth tumor suppressor genes such as Pten promotes long-distance axon regeneration in only a small subset of injured retinal ganglion cells (RGCs), despite many RGCs regenerating short-distance axons. A recent study identified αRGCs as the primary type that regenerates short-distance axons in response to Pten inhibition, but the rare types which regenerate long-distance axons, and cellular features that enable such response, remained unknown. Here, we used a new method for capturing specifically the rare long-distance axon-regenerating RGCs, and also compared their transcriptomes with embryonic RGCs, in order to answer these questions. We found the existence of adult non-α intrinsically photosensitive M1 RGC subtypes that retained features of embryonic cell state, and showed that these subtypes partially dedifferentiated towards an embryonic state and regenerated long-distance axons in response to Pten inhibition. We also identified Pten inhibition-upregulated mitochondria-associated genes, Dynlt1a and Lars2, which promote axon regeneration on their own, and thus present novel therapeutic targets.
Subject(s)
Amino Acyl-tRNA Synthetases , Optic Nerve Injuries , Amino Acyl-tRNA Synthetases/metabolism , Axons/physiology , Mitochondria , Nerve Regeneration/physiology , Optic Nerve Injuries/genetics , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Retinal Ganglion Cells/metabolismABSTRACT
A novel methodology for the synthesis of indanone derivates has been developed. The palladium-catalyzed annulation reaction of o-bromobenzaldehydes with norbornene derivatives is achieved through extremely concise reaction processes. The indanone skeleton was established directly via C-H activation of the aldehyde group under a mild reaction condition. This method is simple and practical, which simplified the traditional synthesis method for the rapid construction of indanone.
ABSTRACT
A novel methodology for the synthesis of nitrones via palladium-catalyzed redox cross-coupling of nitro compounds and alcohols is established. The protocol is a mild, convenient, ligand-free, and scalable synthesis method that can be compatible with various nitro compounds and alcohols. Nitrone is a significant multifunctional platform synthon which can be synthesized directly and efficiently via this tactic from commercially available and cheap raw materials.
ABSTRACT
Cracks provide the earliest and most immediate visual response to structural deterioration of asphalt pavements. Most of the current methods for crack detection are based on visible light sensors and convolutional neural networks. However, such an approach obviously limits the detection to daytime and good lighting conditions. Therefore, this paper proposes a crack detection technique cross-modal feature alignment of YOLOV5 based on visible and infrared images. The infrared spectrum characteristics of silicate concrete can be an important supplement. The adaptive illumination-aware weight generation module is introduced to compute illumination probability to guide the training of the fusion network. In order to alleviate the problem of weak alignment of the multi-scale feature map, the FA-BIFPN feature pyramid module is proposed. The parallel structure of a dual backbone network takes 40% less time to train than a single backbone network. As determined through validation on FLIR, LLVIP, and VEDAI bimodal datasets, the fused images have more stable performance compared to the visible images. In addition, the detector proposed in this paper surpasses the current advanced YOLOV5 unimodal detector and CFT cross-modal fusion module. In the publicly available bimodal road crack dataset, our method is able to detect cracks of 5 pixels with 98.3% accuracy under weak illumination.
ABSTRACT
It is urgent to develop a polyamide (PA) thin-film composite (TFC) membrane with a new method in this study by designing and constructing a new nanomaterial support layer instead of the conventional support layer. Polydopamine-wrapped single-walled carbon nanotubes (PDA@MWCNTs) as the place of the polymerization reaction can optimize the PA film structure and performance. The resulting composite membrane presents a higher water flux of 15.8 L·m-2·h-1·bar-1 and a rejection rate of 97% to Na2SO4, simultaneously maintaining this high separation performance in 300 min. It is a new ideal to construct novel support layer by using inorganic nanoparticles and organic polymer nanofiber membranes.
ABSTRACT
Most traditional synthetic dyes and functional reagents used in silk fabrics are not biodegradable and lack green environmental protection. Natural dyes have attracted more and more attention because of their coloring, functionalization effects, and environmental benefits. In this study, natural dyes were extracted from lac and used for coloring and functionalization in silk fabrics without any other harmful dyes. The extraction conditions were studied and analyzed by the univariate method. The optimal extraction process was that the volume ratio of ethanol to water was 60:40 with a solid-liquid ratio of 1:10, and reacting under the neutrality condition for 1 h at 70 °C. Silk fabric can be dyed dark owing to the certain lifting property of lac. After being dyed by Al3+ post-medium, the levels of the washing fastness, light fastness, and friction fastness of silk fabric are all above four with excellent fastness. The results show that the dyed silk fabrics have good UV protection, antioxidation, and antibacterial properties. The UV protection coefficient UPF is 42.68, the antioxidant property is 98.57%, and the antibacterial property can reach more than 80%. Therefore, the dyeing and functionalization of silk fabrics by utilizing naturally lac dyes show broad prospects in terms of the application of green sustainable dyeing and functionalization.
Subject(s)
Coloring Agents , Silk , Textiles , Coloring Agents/chemistry , Silk/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antioxidants/chemistryABSTRACT
Podocyte injury is a characteristic pathological hallmark of diabetic nephropathy (DN). However, the exact mechanism of podocyte injury in DN is incompletely understood. This study was conducted using db/db mice and immortalized mouse podocytes. High-throughput sequencing was used to identify the differentially expressed long noncoding RNAs in kidney of db/db mice. The lentiviral shRNA directed against long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) or microRNA-26a-5p (miR-26a-5p) agomir was used to treat db/db mice to regulate the SNHG5/miR-26a-5p pathway. Here, we found that the expression of transient receptor potential canonical type 6 (TRPC6) was significantly increased in injured podocytes under the condition of DN, which was associated with markedly decreased miR-26a-5p. We determined that miR-26a-5p overexpression ameliorated podocyte injury in DN via binding to 3'-UTR of Trpc6, as evidenced by the markedly reduced activity of luciferase reporters by miR-26a-5p mimic. Then, the upregulated SNHG5 in podocytes and kidney in DN was identified, and it was proved to sponge to miR-26a-5p directly using luciferase activity, RNA immunoprecipitation, and RNA pull-down assay. Knockdown of SNHG5 attenuated podocyte injury in vitro, accompanied by an increased expression of miR-26a-5p and decreased expression of TRPC6, demonstrating that SNHG5 promoted podocyte injury by controlling the miR-26a-5p/TRPC6 pathway. Moreover, knockdown of SNHG5 protects against podocyte injury and progression of DN in vivo. In conclusion, SNHG5 promotes podocyte injury via the miR-26a-5p/TRPC6 pathway in DN. Our findings provide novel insights into the pathophysiology of podocyte injury and a potential new therapeutic strategy for DN.
Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , MicroRNAs , Podocytes , RNA, Long Noncoding , Mice , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Diabetic Nephropathies/metabolism , TRPC6 Cation Channel/genetics , TRPC6 Cation Channel/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Podocytes/metabolism , Apoptosis/genetics , Diabetes Mellitus/metabolismABSTRACT
The multispectral radiometric temperature measurement technique is affected by the unknown emissivity, and there is no multispectral radiometric temperature inversion algorithm applicable to any scene or target. To address the above problems, this paper converts the multispectral radiometric temperature inversion problem into an image recognition problem containing the temperature information to be measured, and proposes a graphical multispectral radiometric temperature adaptive inversion algorithm. In this paper, we use the difference between spectral channels to convert the one-dimensional radiation data into a two-dimensional radiation map; use the generalized inverse to obtain the spectral emissivity distribution features, fuse them with the two-dimensional radiation map, and use an improved deep learning network to achieve adaptive temperature inversion. It is experimentally verified that the algorithm proposed in this paper can achieve simultaneous inversion of temperature and emissivity for any scene or target with sufficient data set.
ABSTRACT
Neural networks are the most promising tool to solve the problem that an assumed emissivity model is needed in the field of multispectral radiometric temperature measurement. Existing neural network multispectral radiometric temperature measurement algorithms have been investigating the problems of network selection, network porting, and parameter optimization. The inversion accuracy and adaptability of the algorithms have been unsatisfactory. In view of the great success of deep learning in the field of image processing, this Letter proposes the idea of converting one-dimensional multispectral radiometric temperature data into two-dimensional image data for data processing to improve the accuracy and adaptability of multispectral radiometric temperature measurement by deep learning algorithms. Simulation and experimental validation are carried out. In the simulation, the error is less than 0.71% without noise and 1.80% with 5% random noise, which improves the accuracy by more than 1.55% and 2.66% compared with the classical BP (backpropagation) algorithm, and 0.94% and 0.96% compared with the GIM-LSTM (generalized inverse matrix-long short-term memory) algorithm. In the experiment, the error is less than 0.83%. This indicates that the method has high research value and is expected to lead multispectral radiometric temperature measurement technology to a new level.
ABSTRACT
Cell death is a fundamental physiological process in all living organisms. Processes such as embryonic development, organ formation, tissue growth, organismal immunity, and drug response are accompanied by cell death. In recent years with the development of electron microscopy as well as biological techniques, especially the discovery of novel death modes such as ferroptosis, cuprotosis, alkaliptosis, oxeiptosis, and disulfidptosis, researchers have been promoted to have a deeper understanding of cell death modes. In this systematic review, we examined the current understanding of modes of cell death, including the recently discovered novel death modes. Our analysis highlights the common and unique pathways of these death modes, as well as their impact on surrounding cells and the organism as a whole. Our aim was to provide a comprehensive overview of the current state of research on cell death, with a focus on identifying gaps in our knowledge and opportunities for future investigation. We also presented a new insight for macroscopic intracellular survival patterns, namely that intracellular molecular homeostasis is central to the balance of different cell death modes, and this viewpoint can be well justified by the signaling crosstalk of different death modes. These concepts can facilitate the future research about cell death in clinical diagnosis, drug development, and therapeutic modalities.
ABSTRACT
A concise and highly efficient synthesis method of direct esterification of aldehydes via Pd-catalyzed C-H bond activation of aldehyde group has been developed. The strategy avoids the preoxidation step of aldehyde or use of condensing agents in ester synthesis, which is not only applicable to various alcohols but also suitable for the esterification of phenolics which are usually difficult to be esterified. The methodology has the significant advantages of broad substrate scope, mild reaction conditions, and nonrequirement of additional oxidants.
Subject(s)
Aldehydes , Palladium , Aldehydes/chemistry , Palladium/chemistry , Esterification , Alcohols/chemistry , CatalysisABSTRACT
In this paper, we present the discovery of a novel salicylic acid derivative, moldavica acid A (1), and a new natural dibenzo[b,f]oxepin, moldavica acid B (2), together with four known phenylpropionic acids (3-6) and protocatechuic acid (7) that were isolated from Dracocephalum moldavica L. Their structures were elucidated by comprehensive spectroscopic methods, including infrared and nuclear magnetic resonance. Compound 1 is the first example of salicylic acid linking a carboxylated α-pyrone via an ethyl bridge. Beyond expanding the knowledge of the chemical diversity of D. moldavica, both compounds 1 and 2 were shown to upregulate the expression of Kruppel-like factor 2, which could serve as a prospective therapeutic target for the treatment of atherosclerosis.
ABSTRACT
Due to its poor toughness and hydrophilicity, the application of polylactic acid (PLA) in the field of absorbent sanitary materials is restricted. A butenediol vinyl alcohol copolymer (BVOH) was used to improve PLA via melt blending. The morphology, molecular structure, crystallization, thermal stability, tensile property, and hydrophilicity of PLA/BVOH composites with different mass ratios were investigated. The results show that the PLA/BVOH composites possessed a two-phase structure with good interfacial adhesion. The BVOH could effectively blend into PLA without a chemical reaction. The addition of the BVOH promoted the crystallization of PLA, improved the perfection of the crystalline region, and increased the glass transition temperature and melting temperature of PLA in the heating process. Moreover, the thermal stability of PLA was markedly improved by adding the BVOH. The addition of the BVOH also had a significant effect on the tensile property of the PLA/BVOH composites. When the content of the BVOH was 5 wt.%, the elongation at the break of the PLA/BVOH composites could reach 9.06% (increased by 76.3%). In addition, the hydrophilicity of PLA was also significantly improved, and the water contact angles decreased with the increase in the BVOH content and time. When the content of the BVOH was 10 wt.%, the water contact angle could reach 37.3° at 60 s, suggesting good hydrophilicity.
ABSTRACT
Objective To evaluate extrathyroidal extension (ETE) in papillary thyroid microcarcinoma (PTMC) with three-dimensional tomographic ultrasound imaging (3D-TUI). Methods A total of 97 thyroid nodules of 79 patients with PTMC treated in PUMC Hospital from February 2016 to January 2018 were included in this study.Two ultrasound experts performed independent blinded assessment of the relationship between thyroid nodules and thyroid capsule by two-dimensional ultrasound (2D-US) and 3D-TUI.The results of 2D-US and 3D-TUI in evaluating ETE were compared with intraoperative findings and postoperative histological and pathological results. Results Among the 97 nodules,54 (55.7%) nodules had ETE.The diagnostic sensitivity (68.5% vs.37.0%;χ2=10.737,P=0.002),accuracy (74.5% vs.56.7%;χ2=6.686,P=0.015),and area under the receiver operating characteristic curve[0.761 (95%CI=0.677-0.845) vs.0.592 (95%CI=0.504-0.680);Z=3.500,P<0.001] of 3D-TUI were higher than those of 2D-US.However,3D-TUI and 2D-US showed no significant difference in the specificity (84.1% vs.81.4%;χ2=0.081,P=0.776),negative predictive value (67.9% vs.50.7%;χ2=3.645,P=0.066),or positive predictive value (84.1% vs.71.4%;χ2=1.663,P=0.240). Conclusion Compared with 2D-US,3D-TUI demonstrates increased diagnostic efficiency for ETE of PTMC.
Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Thyroid Nodule , Humans , Thyroid Neoplasms/diagnosis , Carcinoma, Papillary/pathology , Ultrasonography/methods , Retrospective StudiesABSTRACT
Persons with isolated antibody to hepatits B virus (HBV) core antigen (IAHBc) may have occult HBV infection (OBI), which is associated with reactivation and potential risk for hepatocellular carcinoma and HBV transmission. We used National Health and Nutrition Examination Survey data to estimate US IAHBc prevalence and published studies of IAHBc-associated OBI prevalence to estimate OBI burden. During 2001-2018, the prevalence of IAHBc was 0.8% (approximately 2.1 million persons), and the OBI burden range was 35 500-83 600 persons. These data support the need for more robust estimates of IAHBc-associated OBI prevalence in the general US population.
Subject(s)
Hepatitis B , Liver Neoplasms , DNA, Viral , Hepatitis B Antibodies , Hepatitis B Core Antigens , Hepatitis B Surface Antigens , Hepatitis B virus , Humans , Nutrition Surveys , Prevalence , United States/epidemiologyABSTRACT
Hepatitis B virus (HBV) infection causes hepatocellular carcinoma but its association with other cancers is not well established. We compared age-adjusted incidence of primary cancers among 5773 HBV-infected persons with US cancer registries during 2006-2018. Compared with the US population, substantially higher incidence among HBV-infected persons was observed for hepatocellular carcinoma (standardized rate ratio [SRR], 30.79), gastric (SRR, 7.95), neuroendocrine (SRR, 5.88), cholangiocarcinoma (SRR, 4.62), and ovarian (SRR, 3.72) cancers, and non-Hodgkin lymphoma (SRR, 2.52). Clinicians should be aware of a heightened potential for certain nonhepatic malignancies among hepatitis B patients, as earlier diagnosis favors improved survival.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis B, Chronic , Hepatitis B , Liver Neoplasms , Carcinoma, Hepatocellular/epidemiology , Delivery of Health Care , Hepatitis B/complications , Hepatitis B virus , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/epidemiology , Humans , Incidence , Liver Neoplasms/epidemiologyABSTRACT
BACKGROUND AND AIMS: During 2016-2020, the United States experienced person-to-person hepatitis A outbreaks that are unprecedented in the vaccine era, during which case-fatality ratios reported by some jurisdictions exceeded those historically associated with hepatitis A. APPROACH AND RESULTS: To identify factors associated with hepatitis A-related mortality, we performed a matched case-control study (matched on age [±5 years] and county of residence in a 1:4 ratio) using data collected from health department and hospital medical records of outbreak-associated patients in Kentucky, Michigan, and West Virginia. Controls were hepatitis A outbreak-associated patients who did not die. There were 110 cases (mean age 53.6 years) and 414 matched controls (mean age 51.9 years); most cases (68.2%) and controls (63.8%) were male. Significantly (P < 0.05) higher odds of mortality were associated with preexisting nonviral liver disease (adjusted odds ratio [aOR], 5.2), history of hepatitis B (aOR, 2.4), diabetes (aOR, 2.2), and cardiovascular disease (aOR, 2.2), as well as initial Model for End-Stage Liver Disease (MELD) score ≥ 30 (aOR, 10.0), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio > 2 (aOR, 10.3), and platelet count < 150,000/µL (aOR, 3.7) among hepatitis A outbreak-associated patients in the independent multivariable conditional logistic regression analyses (each model adjusted for sex). CONCLUSIONS: Preexisting liver disease, diabetes, cardiovascular disease, and initial MELD score ≥ 30, AST/ALT ratio ≥ 1, and platelet count < 150,000/µL among hepatitis A patients were independently associated with higher odds of mortality. Providers should be vigilant for such features and have a low threshold to escalate care and consider consultation for liver transplantation. Our findings support the recommendation of the Advisory Committee on Immunization Practices to vaccinate persons with chronic liver disease, though future recommendations to include adults with diabetes and cardiovascular disease should be considered.
Subject(s)
Disease Outbreaks/statistics & numerical data , End Stage Liver Disease/epidemiology , Hepatitis A/mortality , Adult , Aged , Aged, 80 and over , Case-Control Studies , End Stage Liver Disease/diagnosis , End Stage Liver Disease/virology , Female , Hepatitis A/prevention & control , Hepatitis A/transmission , Hepatitis A/virology , Hepatitis A Vaccines/administration & dosage , Humans , Male , Middle Aged , Risk Assessment/statistics & numerical data , Risk Factors , Severity of Illness Index , United States/epidemiology , Young AdultABSTRACT
The data processing of multi-wavelength pyrometry (MWP) is faced with the problem of solving N equations and N+1 unknown underdetermined equations. The traditional iterative optimization methods are difficult to meet the actual measurement requirements in terms of accuracy and efficiency. With the development of artificial intelligence technology in the field of data processing, it is expected to solve this problem. A generalized inverse matrix (GIM) is combined with a long short-term memory (LSTM) neural network algorithm for data processing of MWP is proposed, which emissivity influence is dispensed completely. Firstly, GIM is used for classification of the emissivity. Furthermore, inputting to the LSTM network not only ensures the accuracy of temperature measurement but also greatly improves the efficiency. The simulation results demonstrated that the accuracy of the GIM-LSTM algorithm was superior to that of the GIM-EPF and BP methods. After random noise was added, the relative error was still less than that for the GIM-EPF and BP methods, and the algorithm exhibited excellent anti-noise performance. Publicly available temperature data for the exhaust plume of a rocket engine were processed by the GIM-LSTM method, and the average relative error was less than the traditional method. Especially, in terms of inversion speed, the operational time of the GIM-LSTM algorithm was at the millisecond level, which is of great significance for the real-time monitoring of rocket exhaust plumes. The proposed GIM-LSTM data processing algorithm affords high accuracy and speed and is suitable for practical measurement of high-emissivity objects in real-time via MWP.
ABSTRACT
BACKGROUND: After decades of decline, US acute hepatitis B incidence flattened since 2011. In persons aged ≥40 years and in jurisdictions affected by the opioid crisis, there is an increase in new cases. Data suggest new infections are occurring among US-born persons. METHODS: We used National Health and Nutrition Examination Survey data during 2001-2018 to examine changes in total antibody to hepatitis B virus core antigen (anti-HBc) prevalence in US-born persons. During 2013-2018, the distribution of characteristics was examined. RESULTS: During 2001-2006, 2007-2012, and 2013-2018, anti-HBc prevalence was 3.5%, 2.5%, and 2.6% among US-born persons, respectively. This corresponded to 5.7 (range, 4.8-6.6) million US-born persons with resolved or current HBV infection during 2013-2018, including 344 600 persons aged 6-29 years. The largest increase and highest prevalence was among persons who reported injection drug use (IDU), which increased from 35.3% during 2001-2006 to 58.4% during 2013-2018 (Pâ =â .07). CONCLUSIONS: Anti-HBc prevalence among US-born persons remained flat during the most recent period, coinciding with a doubling of prevalence among persons reporting IDU. These data are consistent with acute hepatitis B surveillance trends, showing increasing incidence in subpopulations where prevention could be strengthened.Anti-HBc prevalence among US-born persons decreased from 2001-2006 to 2007-2012 and remained flat during 2013-2018, coinciding with a near doubling of prevalence among US-born persons reporting a history of injection drug use.