Radiotherapy is a preferred treatment for brain metastases, which kills cancer cells via high doses of radiation meanwhile hardly avoiding damage to surrounding healthy cells. Therefore, the delineation of organs-at-risk (OARs) is vital in treatment planning to minimize radiation-induced toxicity. However, the following aspects make OAR delineation a challenging task: extremely imbalanced organ sizes, ambiguous boundaries, and complex anatomical structures. To alleviate these challenges, we imitate how specialized clinicians delineate OARs and present a novel cascaded multi-OAR segmentation framework, called OAR-SegNet. OAR-SegNet comprises two distinct levels of segmentation networks: an Anatomical-Prior-Guided network (APG-Net) and a Point-Cloud-Guided network (PCG-Net). Specifically, APG-Net handles segmentation for all organs, where multi-view segmentation modules and a deep prior loss are designed under the guidance of prior knowledge. After APG-Net, PCG-Net refines small organs through the mini-segmentation and the point-cloud alignment heads. The mini-segmentation head is further equipped with the deep prior feature. Extensive experiments were conducted to demonstrate the superior performance of the proposed method compared to other state-of-the-art medical segmentation methods.
The molecular weight (MW) of an enzyme is a critical parameter in enzyme-constrained models (ecModels). It is determined by two factors: the presence of subunits and the abundance of each subunit. Although the number of subunits (NS) can potentially be obtained from UniProt, this information is not readily available for most proteins. In this study, we addressed this gap by extracting and curating subunit information from the UniProt database to establish a robust benchmark dataset. Subsequently, we propose a novel model named DeepSub, which leverages the protein language model and Bi-directional Gated Recurrent Unit (GRU), to predict NS in homo-oligomers solely based on protein sequences. DeepSub demonstrates remarkable accuracy, achieving an accuracy rate as high as 0.967, surpassing the performance of QUEEN. To validate the effectiveness of DeepSub, we performed predictions for protein homo-oligomers that have been reported in the literature but are not documented in the UniProt database. Examples include homoserine dehydrogenase from Corynebacterium glutamicum, Matrilin-4 from Mus musculus and Homo sapiens, and the Multimerins protein family from M. musculus and H. sapiens. The predicted results align closely with the reported findings in the literature, underscoring the reliability and utility of DeepSub.
Databases, Protein , Deep Learning , Protein Subunits , Protein Subunits/chemistry , Protein Subunits/metabolism , Animals , Humans , Protein Multimerization , Mice , Computational Biology/methods
How plants find a way to thrive in alpine habitats remains largely unknown. Here we present a chromosome-level genome assembly for an alpine medicinal herb, Triplostegia glandulifera (Caprifoliaceae), and 13 transcriptomes from other species of Dipsacales. We detected a whole-genome duplication event in T. glandulifera that occurred prior to the diversification of Dipsacales. Preferential gene retention after whole-genome duplication was found to contribute to increasing cold-related genes in T. glandulifera. A series of genes putatively associated with alpine adaptation (e.g. CBFs, ERF-VIIs, and RAD51C) exhibited higher expression levels in T. glandulifera than in its low-elevation relative, Lonicera japonica. Comparative genomic analysis among five pairs of high- vs low-elevation species, including a comparison of T. glandulifera and L. japonica, indicated that the gene families related to disease resistance experienced a significantly convergent contraction in alpine plants compared with their lowland relatives. The reduction in gene repertory size was largely concentrated in clades of genes for pathogen recognition (e.g. CNLs, prRLPs, and XII RLKs), while the clades for signal transduction and development remained nearly unchanged. This finding reflects an energy-saving strategy for survival in hostile alpine areas, where there is a tradeoff with less challenge from pathogens and limited resources for growth. We also identified candidate genes for alpine adaptation (e.g. RAD1, DMC1, and MSH3) that were under convergent positive selection or that exhibited a convergent acceleration in evolutionary rate in the investigated alpine plants. Overall, our study provides novel insights into the high-elevation adaptation strategies of this and other alpine plants.
BACKGROUND: The purpose of this study is to examine and evaluate the existing clinical practice guidelines and consensus statements regarding tracheostomy care for non-mechanically ventilated patients. METHODS: A systematic search of databases, and professional organisations was conducted from inception to 19 March 2023. Two appraisers evaluated each guideline using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) and the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Text and Opinion Papers. RESULTS: No specific clinical guidelines exist on airway management in non-mechanically ventilated patients. Of 6318 articles identified, we included 12 clinical practice guidelines, and 9 consensus statements, which were from China, the US, the UK, South Korea, Australia, France and Belgium. The AGREE II scores in six domains are (1) the scope and purpose, 70.30%; (2) stakeholder involvement, 37.61%; (3) rigor of development, 33.97%; (4) clarity of presentation, 68.16%; (5) applicability, 44.23% and (6) editorial independence, 40.06%. The overall quality of evidence was level B. The summarised recommendations for clinical practice encompass the following six areas: airway humidification, management of the trach cuff, management of inner cannula, tracheostoma care, tracheostomy suctioning and management and prevention of common post-operative complications. CONCLUSIONS: The overall quality of the clinical guidelines on non-ventilated tracheostomy care was moderate, and further improvements are needed in domains of stakeholder involvement, applicability, clarity of presentation and editorial independence. Recommendations on non-ventilated tracheostomy care are often embedded in the guidelines on ventilated tracheostomy. Specific clinical guidelines are needed to provide a standardised approach to tracheostomy care for non-ventilated patients. RELEVANCE TO CLINICAL PRACTICE: Patients with non-ventilated tracheostomy need specialised airway management. Improving patient outcomes requires standardised protocols, patient involvement, quality evaluation, and interdisciplinary approaches. NO PATIENT OR PUBLIC CONTRIBUTION: The study reviewed clinical practice guidelines and consensus statements, therefore patient or public input was not needed.
Ratio-scaled VO2 is the widely used method for quantifying running economy (RE). However, this method should be criticized due to its theoretical defect and curvilinear relationship indicated by the allometric scaling, although no consensus has been achieved on the generally accepted exponent b value of body weight. Therefore, this study aimed to provide a quantitative synthesis of the reported exponents used to scale VO2 to body weight. Six electronic databases were searched based on related terms. Inclusion criteria involved human cardiopulmonary testing data, derived exponents, and reported precision statistics. The random-effects model was applied to statistically analyze exponent b. Subgroup and meta-regression analyses were conducted to explore the potential factors contributing to variation in b values. The probability of the true exponent being below 1 in future studies was calculated. The estimated b values were all below 1 and aligned with the 3/4 power law, except for the 95 % prediction interval of the estimated fat-free body weight exponent b. A publication bias and a slightly greater I2 and τ statistic were also observed in the fat-free body weight study cohort. The estimated probabilities of the true body weight exponent, full body weight exponent, and fat-free body weight exponent being lower than 1 were 93.8 % (likely), 95.1 % (very likely), and 94.5 % (likely) respectively. 'Sex difference', 'age category', 'sporting background', and 'testing modality' were four potential but critical variables that impacted exponent b. Overall, allometric-scaled RE should be measured by full body weight with exponent b raised to 3/4.
Adsorption and activation of C-H bonds by photocatalysts are crucial for the efficient conversion of C-H bonds to produce high-value chemicals. Nevertheless, the delivery of surface-active oxygen species for C-H bond oxygenation inevitably needs to overcome obstacles due to the separated active centers, which suppresses the catalytic efficiency. Herein, Ni dopants are introduced into a monolayer Bi2WO6 to create cascaded active units consisting of unsaturated W atoms and Bi/O frustrated Lewis pairs. Experimental characterizations and density functional theory calculations reveal that these special sites can establish an efficient and controllable C-H bond oxidation process. The activated oxygen species on unsaturated W are readily transferred to the Bi/O sites for C-H bond oxygenation. The catalyst with a Ni mass fraction of 1.8% exhibits excellent toluene conversion rates and high selectivity towards benzaldehyde. This study presents a fascinating strategy for toluene oxidation through the design of efficient cascaded active units.
BACKGROUND: Previous studies have found that psychological interventions have a positive effect on improving physical and psychological problems in colorectal cancer survivors. However, there is still a lack of high-quality evidence reviews that summarize and compare the impact of different psychological interventions. The aim of this study was to synthesize existing psychological interventions and use network meta-analysis to explore whether psychological interventions improve anxiety, depression, fatigue and quality of life in colorectal cancer (CRC) survivors. METHODS: We will extract relevant randomized controlled trials of psychological interventions for CRC survivors from eight electronic databases, including PubMed, Embase, The Cochrane Library, Web of Science, CINAHL, PsycInFO, CNKI, and Wanfang database. Two reviewers will independently screen the literature and extract data. The risk of bias of the included studies will be assessed using the RoB2: Revised Cochrane Risk of Bias Tool. We will then conduct paired meta-analyses and network meta-analyses of the extracted data, using a frequency-based framework and random effects models. DISCUSSION: To the best of our knowledge, this study is the first proposed qualitative and quantitative integration of existing evidence using systematic evaluation and network meta-analysis. This study will inform health policy makers, healthcare providers' clinical intervention choices and guideline revisions, and will help to reduce depression and anxiety in CRC survivors, reduce fatigue, improve quality of life.
Colorectal Neoplasms , Quality of Life , Humans , Network Meta-Analysis , Psychosocial Intervention , Depression/therapy , Anxiety/therapy , Survivors/psychology , Fatigue/therapy , Colorectal Neoplasms/therapy , Meta-Analysis as Topic , Systematic Reviews as Topic
Epoxy resin thermosets (ERTs) are an important class of polymeric materials. However, owing to their highly cross-linked nature, they suffer from poor recyclability, which contributes to an unacceptable level of environmental pollution. There is a clear need for the design of inherently recyclable ERTs that are based on renewable resources. We present the synthesis and closed-loop recycling of a fully lignocellulose-derivable epoxy resin (DGF/MBCA), prepared from dimethyl ester of 2,5-furandicarboxylic acid (DMFD), 4,4'-methylenebis(cyclohexylamine) (MBCA), and glycidol, which displays excellent thermomechanical properties (a glass transition temperature of 170°C, and a storage modulus at 25°C of 1.2 gigapascals). Notably, the material undergoes methanolysis in the absence of any catalyst, regenerating 90% of the original DMFD. The diamine MBCA and glycidol can subsequently be reformed by acetolysis. Application and recycling of DGF/MBCA in glass and plant fiber composites are demonstrated.
BACKGROUND: Ventricular septal rupture (VSR) is a mechanical issue that can occur following an acute myocardial infarction (AMI) and has a high mortality rate. It requires a comprehensive, team-based approach for prompt diagnosis and maintaining stable blood flow. While the occurrence of VSR has lessened over the past hundred years and advancements have been made in treatment techniques, the mortality rate within 30 days can still surpass 40 percent. Surgery is the primary treatment method. For patients with stable blood flow, it's generally considered safer to perform surgery 4-6 weeks after the AMI to repair the VSR. However, the timing of surgery for patients with early instability in their blood flow is still a topic of debate. SUMMARY: There's a lack of set criteria and standards to determine the best time for surgery in patients with VSR following an infarction who have unstable blood flow, especially when considering the use of blood circulation support devices and other techniques for maintaining blood flow that are used in clinical settings. KEY MESSAGES: This review outlines the features of different mechanical circulatory support devices utilized in treating VSR, along with the current scoring system designed to direct the treatment approach for VSR patients.
Genome-scale metabolic models (GEMs) have been widely employed to predict microorganism behaviors. However, GEMs only consider stoichiometric constraints, leading to a linear increase in simulated growth and product yields as substrate uptake rates rise. This divergence from experimental measurements prompted the creation of enzyme-constrained models (ecModels) for various species, successfully enhancing chemical production. Building upon studies that allocate macromolecule resources, we developed a Python-based workflow (ECMpy) that constructs an enzyme-constrained model. This involves directly imposing an enzyme amount constraint in GEM and accounting for protein subunit composition in reactions. However, this procedure demands manual collection of enzyme kinetic parameter information and subunit composition details, making it rather user-unfriendly. In this work, we've enhanced the ECMpy toolbox to version 2.0, broadening its scope to automatically generate ecGEMs for a wider array of organisms. ECMpy 2.0 automates the retrieval of enzyme kinetic parameters and employs machine learning for predicting these parameters, which significantly enhances parameter coverage. Additionally, ECMpy 2.0 introduces common analytical and visualization features for ecModels, rendering computational results more user accessible. Furthermore, ECMpy 2.0 seamlessly integrates three published algorithms that exploit ecModels to uncover potential targets for metabolic engineering. ECMpy 2.0 is available at https://github.com/tibbdc/ECMpy or as a pip package (https://pypi.org/project/ECMpy/).
Formaldehyde (FALD) has gained prominence as an essential C1 building block in the synthesis of valuable chemicals. However, there are still challenges in converting FALD into commodities. Recently, cell-free biocatalysis has emerged as a popular approach for producing such commodities. Acetoin, also known as 3-hydroxy-2-butanone, has been widely used in food, cosmetic, agricultural and the chemical industry. It is valuable to develop a process to produce acetoin from FALD. In this study, a cell-free multi-enzyme catalytic system for the production of acetoin using FALD as the substrate was designed and constructed. It included three scales: FALD utilization pathway, glycolysis pathway and acetoin synthesis pathway. After the optimization of the reaction system, 20.17â¯mM acetoin was produced from 122â¯mM FALD, with a yield of 0.165â¯mol/mol, reaching 99.0% of the theoretical yield. The pathway provides a new approach for high-yield acetoin production from FALD, which consolidates the foundation for the production of high value-added chemicals using cheap one-carbon compounds.
Acetoin , Biocatalysis , Formaldehyde , Acetoin/metabolism , Formaldehyde/metabolism , Cell-Free System
Proper transcription orchestrated by RNA polymerase II (RNPII) is crucial for cellular development, which is rely on the phosphorylation state of RNPII's carboxyl-terminal domain (CTD). Sporangia, developed from mycelia, are essential for the destructive oomycetes Phytophthora, remarkable transcriptional changes are observed during the morphological transition. However, how these changes are rapidly triggered and their relationship with the versatile RNPII-CTD phosphorylation remain enigmatic. Herein, we found that Phytophthora capsici undergone an elevation of Ser5-phosphorylation in its uncanonical heptapeptide repeats of RNPII-CTD during sporangia development, which subsequently changed the chromosomal occupation of RNPII and primarily activated transcription of certain genes. A cyclin-dependent kinase, PcCDK7, was highly induced and phosphorylated RNPII-CTD during this morphological transition. Mechanistically, a novel DCL1-dependent microRNA, pcamiR1, was found to be a feedback modulator for the precise phosphorylation of RNPII-CTD by complexing with PcAGO1 and regulating the accumulation of PcCDK7. Moreover, this study revealed that the pcamiR1-CDK7-RNPII regulatory module is evolutionarily conserved and the impairment of the balance between pcamiR1 and PcCDK7 could efficiently reduce growth and virulence of P. capsici. Collectively, this study uncovers a novel and evolutionary conserved mechanism of transcription regulation which could facilitate correct development and identifies pcamiR1 as a promising target for disease control.
MicroRNAs , Phytophthora , RNA Polymerase II , Transcription, Genetic , RNA Polymerase II/metabolism , RNA Polymerase II/genetics , Phosphorylation , MicroRNAs/metabolism , MicroRNAs/genetics , Phytophthora/pathogenicity , Phytophthora/genetics , Phytophthora/metabolism , Cyclin-Dependent Kinases/metabolism , Cyclin-Dependent Kinases/genetics
We established a normal embryonic development table for the Anji salamander Hynobius amjiensis, a critically endangered tailed amphibian of the family Hynobiidae with a very limited distribution in East China, following the standards set by the early developmental table of vertebrates. Put together 32 embryonic stages for the Anji salamander was defined. The total embryonic period from oviposition to hatching is approximately 30 days at 9 °C. Stages 1-16 represent early development from cleavage to neurulation. Stages 17-32 represent organogenesis documenting later developmental events such as tail, gill, and limb formation, and hatching (Stage 32). We provided a detailed description of the external morphology and color changes of the head, trunk, limbs, tail, external gills, and balancers at various stages from egg-laying to hatching. We also described several cases of abnormal embryonic development. The establishment of the embryonic development table in H. amjiensis contributes to better understanding of the ontogeny in tailed amphibians, distinguishing closely related species, and identifying abnormal embryonic amphibians.
Embryo, Nonmammalian , Embryonic Development , Urodela , Animals , Urodela/embryology , Embryonic Development/physiology , Embryo, Nonmammalian/embryology , Female , Organogenesis/physiology , Tail/embryology , China
Background: Psychological capital, an intrinsic personal asset, enhances junior nurses' ability to navigate transition and sustain superior job performance. This study aimed to classify junior nurses into distinct psychological capital profiles and examine their associations with burnout and perceived stress levels. Methods: A cross-sectional study involving 480 junior nurses from three hospitals in Beijing assessed psychological capital, stress, and burnout using e-questionnaires, from July 2021 to August 2022. We employed exploratory latent profile analysis for psychological capital profiling and logistic regression with the best subset method to identify the influential factors. Results: The results of the latent profile analysis supported the models of two latent profiles, which were defined as low psychological capital (224, 46.5%) and high psychological capital (256, 53.5%). Logistic regression revealed that introverted nurses and those experiencing moderate to high levels of burnout and stress were more likely to exhibit low psychological capital. Conclusion: Nursing management should proactively identify and support junior nurses with low psychological capital, with a focus on introverted individuals, to mitigate the impact of stress and burnout.
Burnout, Professional , Nursing Staff, Hospital , Humans , Burnout, Professional/psychology , Cross-Sectional Studies , Female , Male , Adult , Nursing Staff, Hospital/psychology , Nursing Staff, Hospital/statistics & numerical data , Surveys and Questionnaires , China , Stress, Psychological/psychology , Young Adult
Vibrio harveyi causes high mortality and severely limits grouper culture. The gut microbiota is an important biological barrier against pathogen invasion. In this study, we investigated dynamic changes in the intestinal microbial community, gene transcription and immune responses signatures of pearl gentian grouper (Epinephelus fuscoguttatusâ × Epinephelus lanceolatusâ) at 0, 3 and 7 days (referred to as d0, d3 and d7 groups, respectively) after infection with V. harveyi. The results demonstrated that the d7 treatment reduced the gut microbial diversity and increased the proportion of Proteobacteria and Cyanobacteria. Notably, several putative pathogenic genera (Sphingomonas and Bacteroides) proliferated, while putative probiotic genera (Rhodococcus and Lactobacillus) reduced, and these changes in intestinal bacteria might be correlated to the alterations of host immune-related molecules. The d3 and d7 treatments also altered the histomorphology and gene transcription profiles mainly associated with immune function in intestine, such as 'MAPK signaling pathway', 'Apoptosis' and 'Toll-like receptor (TLR) signaling pathway'. Furthermore, d3 group induced a homeostatic dysregulation of the antioxidant system, cytokines and TLR signaling, with a tendency to gradually return to a normal state in d7 group, along with the apoptosis process. The pathogenic infection suppressed the expression of JNK pathway and enhanced the ERK pathway. In conclusion, the dysbiosis of the intestinal bacterial communities caused by the immune changes that occurred during V. harveyi infection disrupted the intestine health in the pearl gentian grouper. These results provided a comprehensive understandings of the immune defense mechanisms in fish and valuable references to develop disease control strategies in grouper aquaculture.
Bass , Fish Diseases , Gastrointestinal Microbiome , Vibrio Infections , Vibrio , Animals , Vibrio/physiology , Fish Diseases/immunology , Fish Diseases/microbiology , Bass/immunology , Bass/genetics , Vibrio Infections/veterinary , Vibrio Infections/immunology , Immunity, Innate/genetics , Transcription, Genetic
Tissue engineering envisions functional substitute creation for damaged tissues. Insulin-like growth factor-1 (IGF-1) plays roles in bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation (OD), and we investigated its specific mechanism. BMSCs were cultured and OD was induced. Surface antigens (CD105, CD90, CD44, CD45, CD34) were identified by flow cytometry. Adipogenic, chondrogenic, and osteogenic differentiation abilities of BMSCs were observed. BMSCs were cultured in osteogenic medium containing 80 ng/mL IGF-1 for 3 weeks. Alkaline phosphatase activity, calcification level, osteogenic factor (runt related protein 2 [RUNX2], osteocalcin [OCN], osterix [OSX]), total (t-) ERK1/2 and phosphorylated- (p-) ERK1/2 levels, and SRY-related high-mobility-group box 4 (SOX4) levels were assessed by alkaline phosphatase staining and Alizarin Red staining, Western blot, and reverse transcription-quantitative polymerase chain reaction. The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway inhibitor (PD98059) was used to inhibit the MAPK/ERK pathway in IGF-1-treated BMSCs. Small interfering-SOX4 was transfected into BMSCs to down-regulate SOX4. IGF-1 increased alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels in BMSCs, indicating that IGF-1 induced rat BMSC OD. SOX4, and p-ERK1/2 and t-ERK1/2 levels were elevated in IGF-1-induced BMSCs, which were annulled by PD98059. PD98059 partly averted IGF-1-induced rat BMSC OD. SOX4 levels, alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels were reduced after SOX4 down-regulation, showing that downregulation of SOX4 averted the effect of IGF-1 on inducing rat BMSC OD. IGF-1 induced rat BMSC OD by stimulating SOX4 via the MAPK/ERK pathway.
BACKGROUND: The development of antiretroviral therapy broadly extends the life expectancy of persons living with HIV (PLHIV). However, stigma and discrimination are still great threat to these individuals and the world's public health care system. Accurate and reproducible measures are prerequisites for robust results. Therefore, it is essential to choose an acceptable measure with satisfactory psychometric properties to assess stigma and discrimination. There has been no systematic review of different stigma and discrimination tools in the field of HIV care. Researchers and clinical practitioners do not have a solid reference for selecting stigma and discrimination measurement tools. METHODS: We systematically searched English and Chinese databases, including PubMed, EMBASE, CINAHL, Web of Science, PsycINFO, ProQuest Dissertations and Theses, The Cochrane Library, CNKI,, and Wanfang, to obtain literature about stigma and discrimination measurement tools that have been developed and applied in the field of HIV. The search period was from 1st January, 1996 to 22nd November 2021. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline (2018 version) was applied to assess the risk of bias for each involved study and summarize the psychometric properties of each tool. The modified version of the Grading of Recommendations Assessment, Development, and, Evaluation (GRADE) method was used to grade the evidence and develop recommendations. RESULTS: We included 45 studies and 19 PROMs for HIV/AIDS-related stigma and discrimination among PLHIV. All studies had sufficient methodological quality in content validity, structural validity, internal consistency, and the hypothesis testing of structural validity. Limited evidence was found for cross-cultural validity, stability, and criterion validity. No relevant evidence was found concerning measurement error and responsiveness. The Internalized AIDS-related Stigma Scale (IARSS), Internalized HIV Stigma Scale (IHSS), and Wright's HIV stigma scale (WHSS) are recommended for use. CONCLUSIONS: This study recommends three PROMs for different stigma and discrimination scenarios, including IARSS for its good quality and convenience, IHSS for its broader range of items, higher sensitivity, and greater precision, and WHSS for its comprehensive and quick screening. Researchers should also consider the relevance and feasibility of the measurements before putting them into practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022308579.
HIV Infections , Psychometrics , Social Stigma , Humans , HIV Infections/psychology
Cardiovascular thrombotic events have long been a perplexing factor in clinical settings, influencing patient prognoses significantly. Ultrasound-mediated acoustic therapy, an innovative thrombolytic treatment method known for its high efficiency, non-invasiveness, safety, and convenience, has demonstrated promising potential for clinical applications and has gradually become a focal point in cardiovascular thrombotic disease research. The current challenge lies in the technical complexities of preparing ultrasound-responsive carriers with thrombus-targeting capabilities and high thrombolytic efficiency. Additionally, optimizing the corresponding acoustic treatment mode is crucial to markedly enhance the thrombolytic effectiveness of ultrasound-mediated acoustic therapy. In light of the current status, this article provides a comprehensive review of the research progress in innovative ultrasound-mediated acoustic therapy for cardiovascular thrombotic diseases. It explores the impact of technical methods, therapeutic mechanisms, and influencing factors on the thrombolytic efficiency and clinical potential of ultrasound-mediated acoustic therapy. The review places particular emphasis on identifying solutions and key considerations in addressing the challenges associated with this cutting-edge therapeutic approach.
Heme, an iron-containing porphyrin derivative, holds great promise in fields like medicine, food production and chemicals. Here, we developed an engineered Corynebacterium glutamicum strain for efficient heme production by combining modular engineering and RBS engineering. The whole heme biosynthetic pathway was methodically divided into 5-ALA synthetic module, uroporphyrinogen III (UPG III) synthetic module and heme synthetic module for further construction and optimization. Three heme synthetic modules were compared and the siroheme-dependent (SHD) pathway was identified to be optimal in C. glutamicum for the first time. To further improve heme production, the expression of genes in UPG III synthetic module and heme synthetic module was coordinated optimized through RBS engineering, respectively. Subsequently, heme oxygenase was knocked out to reduce heme degradation. The engineered strain HS12 showed a maximum iron-containing porphyrin derivatives titer of 1592 mg/L with the extracellular secretion rate of 45.5% in fed-batch fermentation. Our study constructed a C. glutamicum chassis strain for efficient heme accumulation, which was beneficial for the advancement of efficient heme and other porphyrins production.
Cancer reprogramming is an important facilitator of cancer development and survival, with tumor cells exhibiting a preference for aerobic glycolysis beyond oxidative phosphorylation, even under sufficient oxygen supply condition. This metabolic alteration, known as the Warburg effect, serves as a significant indicator of malignant tumor transformation. The Warburg effect primarily impacts cancer occurrence by influencing the aerobic glycolysis pathway in cancer cells. Key enzymes involved in this process include glucose transporters (GLUTs), HKs, PFKs, LDHs, and PKM2. Moreover, the expression of transcriptional regulatory factors and proteins, such as FOXM1, p53, NF-κB, HIF1α, and c-Myc, can also influence cancer progression. Furthermore, lncRNAs, miRNAs, and circular RNAs play a vital role in directly regulating the Warburg effect. Additionally, gene mutations, tumor microenvironment remodeling, and immune system interactions are closely associated with the Warburg effect. Notably, the development of drugs targeting the Warburg effect has exhibited promising potential in tumor treatment. This comprehensive review presents novel directions and approaches for the early diagnosis and treatment of cancer patients by conducting in-depth research and summarizing the bright prospects of targeting the Warburg effect in cancer.
