A Systematic Review of Cognitive Impairment in Individuals With Colorectal Cancer.

PROBLEM IDENTIFICATION: Patients with colorectal cancer (CRC) encounter varying degrees of objective and subjective cognitive impairment. The prevalence of objective and subjective cognitive impairment, factors affecting cognitive impairment, and interventions are presented in this review. LITERATURE SEARCH: The CINAHL Plus®, Cochrane Library, Embase®, PsycINFO®, PubMed®, and CNKI databases were systematically searched from the time of the database's establishment to May 2023. Manual searches for the relevant articles in the literature's references were also conducted. DATA EVALUATION: The results were independently assessed by two reviewers. SYNTHESIS: 25 studies were included. The prevalence of cognitive impairment in individuals with CRC was measured differently according to study designs. A model of factors contributing to cognitive impairment guided the integration of factors, including cancer treatments, psychosocial factors, and physical and emotional health conditions. Incorporated intervention programs could be integrated between objective and subjective aspects. Interventions relieved cognitive impairment in individuals with CRC. IMPLICATIONS FOR NURSING: The results of this review supported enhanced assessment and monitoring of cognitive impairment, particularly subjective cognitive impairment.

Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids.

Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to adult spinal cord tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here, we found that early developmental spinal cord had higher levels of ECM proteins associated with neural development and axon growth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs) and facilitated axonal outgrowth and regeneration of spinal cord organoids more effectively than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior performance as a delivery vehicle for NPCs and organoids in spinal cord injury (SCI) models. This suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.

Responsive regularity of neurons in the hindlimb region of primary somatosensory cortex to different temperature thermal needle stimulation of "Zusanli"(ST36) in mice. / å°é¼ åˆçº§ä½“æ„Ÿçš®å±‚åŽè‚¢åŒºç¥žç»å ƒå¯¹"足三里"不同温度热刺激的响应规律.

OBJECTIVES: To study the regularity of central response to thermal needle stimulation of "Zusanli" (ST36) at different temperature, and to analyze the temperature difference of central responses. METHODS: Six male C57BL/6j adult mice were used in the present study. For observing activities of neurons in the hindlimb region of left primary somatosensory cortex (S1HL, A/P=0.46 mm, M/L=1.32 mm, D/V=-0.14 mm) by using a fast high-resolution miniature two-photon microscopy (FHIRM-TPM), the mice were anesthetized with 3% isoflurane (inhalation), with its head fixed in a stereotaxic apparatus, then, adeno-associated virus (AAV-hSyn-GCaMP6f-WPRE-hGHpA, for showing intracellular calcium transients in neurons transfected) was injected into the left S1HL region using a micro-syringe after scalp surgical operation. The mice's right ST36 were stimulated using internal thermal needles with the temperature being 43 ℃, or 45 ℃, or 47 ℃, separately. Image J software and MATLAB 2020b software were used to process the image data of neuronal calcium activity (Ca2+ signaling) in the left S1HL region, including the instant maximum calcium peak value (ΔF/F) in 2 s, instant calcium spike frequency in 2 s, short-term calcium peak value (ΔF/F) in 3.5 min, short-term calcium spike frequency in 3.5 min, calcium peak duration in 3.5 min, maximum calcium peak value (ΔF/F) at the 1st , 2nd and 3rd min, and calcium spike frequency at the 1st, 2nd and 3rd min after thermal needle stimulation. RESULTS: In comparison with the normal temperature needle stimulation, the instant intracellular maximum calcium peak value, instant calcium spike frequency, short-term maximum calcium peak value, short-term calcium spike frequency, and calcium peak duration of S1HL neurons in response to 43 ℃, 45 ℃ and 47 ℃ internal thermal needle stimulation of ST36 were significantly increased (P<0.001, P<0.01). Comparison among the 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation showed that the 45 ℃ thermal needle stimulation was obviously superior to 43 ℃ and 47 ℃ thermal needle stimulation in increasing instant calcium spike frequency, short-term calcium spike frequency and calcium peak duration of S1HL neurons (P<0.001, P<0.01). The 47 ℃ thermal needle stimulation was stronger than 43 ℃ and 45 ℃ thermal needle stimulation in increasing the instant maximum calcium peak value (P<0.001). The maximum calcium peak value was apparently higher (P<0.001) at the 2nd min than that at the 1st and 3rd min after 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation. No significant differences were found in the short-term maximum calcium peak value among the 3 thermal needle stimulation and in the calcium spike frequency among the 3 time points after 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation. CONCLUSIONS: S1HL neurons respond to all 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation of ST36 in mice, while more actively to 45 ℃ thermal needle stimulation.

Moxibustion for declined cardiorespiratory fitness of apparently healthy older adults: A study protocol for a randomized controlled trial.

BACKGROUND: Aging and age-related declines lead to varying degrees of decreased cardiorespiratory fitness (CRF) in apparently healthy older adults. Exercise training, the primary approach for enhancing CRF, encounters several constraints when used with elderly individuals. Existing evidence implies that moxibustion might enhance the CRF of older adults. However, clinical research in this area still needs to be improved. METHODS: This study will employ a randomized, assessor-blinded, controlled trial design involving 126 eligible participants. These participants will be stratified and randomly assigned to one moxibustion group, one sham moxibustion group, and one blank control group. Acupoints of bilateral Zusanli (ST36), Shenque (CV8), and Guanyuan (CV4) are selected for both real and sham moxibustion groups. The treatment will last 60 min per session, 5 sessions a week for 12 weeks. The blank control group will not receive any intervention for CRF improvement. Primary outcomes will be the mean change in peak oxygen uptake (VO2peak), anaerobic threshold (AT), and serum central carbon metabolites (CCB) from the baseline to observation points. Secondary outcome measures involve the six-minute walk distance (6MWD), the Short Form 36 Health Survey (SF-36), and the Qi and Blood Status Questionnaire (QBSQ). Outcome assessments will be conducted at weeks 4, 8, 12, and 24 as part of the follow-up. Adverse events will be assessed at each visit. DISCUSSION: This trial can potentially ascertain moxibustion's effectiveness and safety in enhancing CRF among apparently healthy older adults. TRAIL REGISTRATION: ChiCTR, ChiCTR2300070303. Registered on April 08, 2023.

The Effect of Nutrient Deficiencies on the Annual Yield and Root Growth of Summer Corn in a Double-Cropping System.

The North China Plain has a typical winter wheat-summer corn double-cropping pattern. The effects of nutrient deficiency conditions on the root characteristics and yield of summer corn in the double-cropping system were studied for four years. Long-term monotonous fertilization patterns undermine crop rotation systems and are detrimental to the sustainability of agricultural production. To complement the development of rational fertilization strategies by exploring the response of crop rotation systems to nutrient deficiencies, an experiment was conducted in a randomized complete block design consisting of five treatments with three replicates for each treatment: (1) an adequate supply of nitrogen and phosphate fertilizers and potash-deficient treatment (T1); (2) an adequate supply of nitrogen and potash fertilizers and phosphorus-deficient treatment (T2); (3) an adequate supply of phosphorus and potash fertilizers and nitrogen-deficient treatment (T3); (4) nutrient-sufficient treatment for crop growth (T4); and (5) no-fertilizer treatment (CK). The results showed that different nutrient treatments had significant effects on the root length density (RLD), root surface area density (RSAD), and root dry weight density (RDWD) in summer corn. At the physiological maturity stage (R6), the root indexes of RLD, RSAD, and RDWD were significantly higher in the 0-20 cm soil layer in T4 compared to CK, with an increase of 86.2%, 131.4%, and 100.0%, respectively. Similarly, in the 20-40 cm soil layer, the root indexes of T4 were 85.7%, 61.3%, and 50.0% higher than CK, with varied differences observed in the other nutrient-deficient treatments. However, there was no significant difference among the treatments in the 40-60 cm layer except for T4, whose root index showed a difference. The root fresh weight and root dry matter in T4, T3, T2, and T1 were increased to different degrees compared with CK. In addition, these differences in root indexes affected the annual yield of crops, which increased by 20.96%, 21.95%, and 8.14% in T4, T2, and T1, respectively, compared to CK. The spike number and the number of grains per spike of T4 were 10.8% and 8.3% higher than those of CK, which led to the differences in summer corn yields. The 1000-kernel weight of T4, T2, and T1 were 9.5%, 8.8%, and 7.4% higher than that of CK, whereas the determining nutrient was nitrogen fertilizer, and phosphorus fertilizer had a higher effect on yield than potassium fertilizer. This provides a theoretical basis for the effect of nutrient deficiency conditions on yield stability in a double-cropping system.

Porcine reproductive and respiratory syndrome virus infection activates ADAM17 to induce inflammatory responses.

Porcine reproductive and respiratory syndrome (PRRS), which has posed substantial threats to the swine industry worldwide, is primarily characterized by interstitial pneumonia. A disintegrin and metalloproteinase 17 (ADAM17) is a multifunctional sheddase involved in various inflammatory diseases. Herein, our study showed that PRRS virus (PRRSV) infection elevated ADAM17 activity, as demonstrated in primary porcine alveolar macrophages (PAMs), an immortalized PAM cell line (IPAM cells), and the lung tissues of PRRSV-infected piglets. We found that PRRSV infection promoted ADAM17 translocation from the endoplasmic reticulum to the Golgi by enhancing its interaction with inactive rhomboid protein 2 (iRhom2), a newly identified ADAM17 regulator, which in turn elevated ADAM17 activity. By screening for PRRSV-encoded structural proteins, viral envelope (E) and nucleocapsid (N) proteins were identified as the predominant ADAM17 activators. E and N proteins bind with both ADAM17 and iRhom2 to form ternary protein complexes, ultimately strengthening their interactions. Additionally, we demonstrated, using an ADAM17-knockout cell line, that ADAM17 augmented the shedding of soluble TNF-α, a pivotal inflammatory mediator. We also discovered that ADAM17-mediated cleavage of porcine TNF-α occurred between Arg-78 and Ser-79. By constructing a precision mutant cell line with Arg-78-Glu/Ser-79-Glu substitution mutations in TNF-α, we further revealed that the ADAM17-mediated production of soluble TNF-α contributed to the induction of inflammatory responses by PRRSV and its E and N proteins. Taken together, our results elucidate the mechanism by which PRRSV infection activates the iRhom2/ADAM17/TNF-α axis to enhance inflammatory responses, providing valuable insights into the elucidation of PRRSV pathogenesis.

HDAC3 promotes Sertoli cell maturation and maintains the blood-testis barrier dynamics.

Germ cell development depends on the capacity of somatic Sertoli cells to undergo differentiation into a mature state and establish a germ cell-specific blood-testis barrier (BTB). The BTB structure confers an immunological barrier for meiotic and postmeiotic germ cells, and its dynamic permeability facilitates a transient movement of preleptotene spermatocytes through BTB to enter meiosis. However, the regulatory factors involved in Sertoli cell maturation and how BTB dynamics coordinate germ cell development remain unclear. Here, we found a histone deacetylase HDAC3 abundantly expresses in Sertoli cells and localizes in both cytoplasm and nucleus. Sertoli cell-specific Hdac3 knockout in mice causes infertility with compromised integrity of blood-testis barrier, leading to germ cells unable to traverse through BTB and an accumulation of preleptotene spermatocytes in juvenile testis. Mechanistically, nuclear HDAC3 regulates the expression program of Sertoli cell maturation genes, and cytoplasmic HDAC3 forms a complex with the gap junction protein Connexin 43 to modulate the BTB integrity and dynamics through regulating the distribution of tight junction proteins. Our findings identify HDAC3 as a critical regulator in promoting Sertoli cell maturation and maintaining the homeostasis of the blood-testis barrier.

Structural changes in spinal cord following optic neuritis: Insights from quantitative spinal MRI.

OBJECTIVES: Previous studies have demonstrated that optic neuritis (ON) affects brain plasticity. However, whether ON affects the spinal cord remains unclear. We aimed to investigate the spinal cord changes in ON and their associations with disability. METHODS: A total of 101 ON patients, and 41 healthy controls (HC) were retrospectively recruited. High-resolution imaging was conducted using a Magnetization Prepared Rapid Acquisition Gradient-Echo (MP-RAGE) sequence for T1-weighted images and an echo planar imaging (EPI) sequence for Diffusion Tensor Imaging (DTI) data collection. Additionally, patients' disability and cognitive impairment were evaluated using the Expanded Disability Status Scale (EDSS) and the Paced Auditory Serial Addition Test (PASAT), respectively. The quantitative spinal MRI was employed to examine the cross-sectional area (CSA) and diffusion indicators, with a specific focus on calculating the average values across the C2-C7 cervical spinal cord segments. CSA, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared between groups. Correlation analyses were performed between CSA, diffusion indicators, and clinical variables. RESULTS: No significant differences were found in CSA between ON patients and HCs. MD (p = 0.007) and RD (p = 0.018) were increased in ON patients compared with HCs, and AD was decreased in ON (p = 0.013). The AD values of the ON patients were significantly positively correlated with PASAT scores (r = 0.37, p < 0.001). CONCLUSIONS: This study provided imaging evidence for DTI abnormalities in patients with ON. Spinal cord DTI can improve our knowledge of the path physiology of ON, and clinical progression.

Single-Electron Reduction of "Push-Pull" C-C Single Bond and Decyanation Using Tertiary Amines as the Organic Electron Donor.

Using commercially available tertiary amines as an organic electron donor (OED), the reduction of "push-pull" C-C single bond and reductive decyanation of tetrahydroisoquinolines were realized. These reactions exhibited higher reaction efficiency and better functional group tolerance compared with those of metallic reductants, and the mechanistic study indicated that a radical intermediate was involved in the reduction of the C-C single bond, which provides a new way to the OED-enabled mild reduction.

Revealing the role of the gut microbiota in enhancing targeted therapy efficacy for lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death globally. Although the gut microbiota's role in the antitumor efficacy of many cancers has been revealed, its involvement in the response to gefitinib therapy for LUAD remains unclear. To fill this gap, we conducted a longitudinal study that profiled gut microbiota changes in PC-9 tumor-bearing mice under different treatments, including gefitinib monotherapy and combination therapies with probiotics, antibiotics, or Traditional Chinese Medicine (TCM). Our findings demonstrated that combining probiotics or TCM with gefitinib therapy outperformed gefitinib monotherapy, as evidenced by tumor volume, body weight, and tumor marker tests. By contrast, antibiotic intervention suppressed the antitumor efficacy of gefitinib. Notably, the temporal changes in gut microbiota were strongly correlated with the different treatments, prompting us to investigate whether there is a causal relationship between gut microbiota and the antitumor efficacy of gefitinib using Mediation Analysis (MA). Finally, our research revealed that thirteen mediators (Amplicon Sequence Variants, ASVs) regulate the antitumor effect of gefitinib, regardless of treatment. Our study provides robust evidence supporting the gut microbiota's significant and potentially causal role in mediating gefitinib treatment efficacy in mice. Our findings shed light on a novel strategy for antitumor drug development by targeting the gut microbiota.

A Motion-Aware DNN Model with Edge Focus Loss and Quality Control for Short-Axis Left Ventricle Segmentation of Cine MR Sequences.

Accurate segmentation of the left ventricle myocardium is the key step of automatic assessment of cardiac function. However, the current methods mainly focus on the end-diastolic and the end-systolic frames in cine MR sequences and lack the attention to myocardial motion in the cardiac cycle. Additionally, due to the lack of fine segmentation tools, the simplified approach, excluding papillary muscles and trabeculae from myocardium, is applied in clinical practice. To solve these problems, we propose a motion-aware DNN model with edge focus loss and quality control in this paper. Specifically, the bidirectional ConvLSTM layer and a new motion attention layer are proposed to encode motion-aware feature maps, and an edge focus loss function is proposed to train the model to generate the fine segmentation results. Additionally, a quality control method is proposed to filter out the abnormal segmentations before subsequent analyses. Compared with state-of-the-art segmentation models on the public dataset and the in-house dataset, the proposed method has obtained high segmentation accuracy. On the 17-segment model, the proposed method has obtained the highest Pearson correlation coefficient at 14 of 17 segments, and the mean PCC of 85%. The experimental results highlight the segmentation accuracy of the proposed method as well as its availability to substitute for the manually annotated boundaries for the automatic assessment of cardiac function.

Observation of transition from superfluorescence to polariton condensation in CsPbBr3 quantum dots film.

The superfluorescence effect has received extensive attention due to the many-body physics of quantum correlation in dipole gas and the optical applications of ultrafast bright radiation field based on the cooperative quantum state. Here, we demonstrate not only to observe the superfluorescence effect but also to control the cooperative state of the excitons ensemble by externally applying a regulatory dimension of coupling light fields. A new quasi-particle called cooperative exciton-polariton is revealed in a light-matter hybrid structure of a perovskite quantum dot thin film spin-coated on a Distributed Bragg Reflector. Above the nonlinear threshold, polaritonic condensation occurs at a nonzero momentum state on the lower polariton branch owning to the vital role of the synchronized excitons. The phase transition from superfluorescence to polariton condensation exhibits typical signatures of a decrease of the linewidth, an increase of the macroscopic coherence as well as an accelerated radiation decay rate. These findings are promising for opening new potential applications for super-brightness and unconventional coherent light sources and could enable the exploitation of cooperative effects for quantum optics.

Chemical Framework to Design Linear-like Relaxors toward Capacitive Energy Storage.

ABO3-type perovskite relaxor ferroelectrics (RFEs) have emerged as the preferred option for dielectric capacitive energy storage. However, the compositional design of RFEs with high energy density and efficiency poses significant challenges owing to the vast compositional space and the absence of general rules. Here, we present an atomic-level chemical framework that captures inherent characteristics in terms of radius and ferroelectric activity of ions. By categorizing A/B-site ions as host framework, rattling, ferroelectrically active, and blocking ions and assembling these four types of ions with specific criteria, linear-like relaxors with weak locally correlated and highly extendable unit-cell polarization vectors can be constructed. As example, we demonstrate two new compositions of Bi0.5K0.5TiO3-based and BaTiO3-based relaxors, showing extremely high recoverable energy densities of 17.3 and 12.1 J cm-3, respectively, both with a high efficiency of about 90%. Further, the role of different types of ions in forming heterogeneous polar structures is identified through element-specific local structure analysis using neutron total scattering combined with reverse Monte Carlo modeling. Our work not only opens up new avenues toward rational compositional design of high energy storage performance lead-free RFEs but also sheds light on atomic-level manipulation of functional properties in compositionally complex ferroelectrics.

Melatonin in cancer biology: pathways, derivatives, and the promise of targeted delivery.

Melatonin, historically recognized for its primary role in regulating circadian rhythms, has expanded its influence particularly due to its wide range of biological activities. It has firmly established itself in cancer research. To highlight its versatility, we delved into how melatonin interacts with key signaling pathways, such as the Wnt/ß-Catenin, PI3K, and NF-κB pathways, which play foundational roles in tumor development and progression. Notably, melatonin can intricately modulate these pathways, potentially affecting various cellular functions such as apoptosis, metastasis, and immunity. Additionally, a comprehensive review of current clinical studies provides a dual perspective. These studies confirm melatonin's potential in cancer management but also underscore its inherent limitations, particularly its limited bioavailability, which often relegates it to a supplementary role in treatments. Despite this limitation, there is an ongoing quest for innovative solutions and current advancements include the development of melatonin derivatives and cutting-edge delivery systems. By synthesizing the past, present, and future, this review provides a detailed overview of melatonin's evolving role in oncology, positioning it as a potential cornerstone in future cancer therapeutics.

A High-Performance Strain Sensor for the Detection of Human Motion and Subtle Strain Based on Liquid Metal Microwire.

Flexible strain sensors have a wide range of applications, such as human motion monitoring, wearable electronic devices, and human-computer interactions, due to their good conformability and sensitive deformation detection. To overcome the internal stress problem of solid sensing materials during deformation and prepare small-sized flexible strain sensors, it is necessary to choose a more suitable sensing material and preparation technology. We report a simple and high-performance flexible strain sensor based on liquid metal nanoparticles (LMNPs) on a polyimide substrate. The LMNPs were assembled using the femtosecond laser direct writing technology to form liquid metal microwires. A wearable strain sensor from the liquid metal microwire was fabricated with an excellent gauge factor of up to 76.18, a good linearity in a wide sensing range, and a fast response/recovery time of 159 ms/120 ms. Due to these extraordinary strain sensing performances, the strain sensor can monitor facial expressions in real time and detect vocal cord vibrations for speech recognition.

CO2 Storage Monitoring via Time-Lapse Full Waveform Inversion with Automatic Differentiation.

In the field of CO2 capture utilization and storage (CCUS), recent advancements in active-source monitoring have significantly enhanced the capabilities of time-lapse acoustical imaging, facilitating continuous capture of detailed physical parameter images from acoustic signals. Central to these advancements is time-lapse full waveform inversion (TLFWI), which is increasingly recognized for its ability to extract high-resolution images from active-source datasets. However, conventional TLFWI methodologies, which are reliant on gradient optimization, face a significant challenge due to the need for complex, explicit formulation of the physical model gradient relative to the misfit function between observed and predicted data over time. Addressing this limitation, our study introduces automatic differentiation (AD) into the TLFWI process, utilizing deep learning frameworks such as PyTorch to automate gradient calculation using the chain rule. This novel approach, AD-TLFWI, not only streamlines the inversion of time-lapse images for CO2 monitoring but also tackles the issue of local minima commonly encountered in deep learning optimizers. The effectiveness of AD-TLFWI was validated using a realistic model from the Frio-II CO2 injection site, where it successfully produced high-resolution images that demonstrate significant changes in velocity due to CO2 injection. This advancement in TLFWI methodology, underpinned by the integration of AD, represents a pivotal development in active-source monitoring systems, enhancing information extraction capabilities and providing potential solutions to complex multiphysics monitoring challenges.

DNA methylation remodeled amino acids biosynthesis regulates flower senescence in carnation (Dianthus caryophyllus).

Dynamic DNA methylation regulatory networks are involved in many biological processes. However, how DNA methylation patterns change during flower senescence and their relevance with gene expression and related molecular mechanism remain largely unknown. Here, we used whole genome bisulfite sequencing to reveal a significant increase of DNA methylation in the promoter region of genes during natural and ethylene-induced flower senescence in carnation (Dianthus caryophyllus L.), which was correlated with decreased expression of DNA demethylase gene DcROS1. Silencing of DcROS1 accelerated while overexpression of DcROS1 delayed carnation flower senescence. Moreover, among the hypermethylated differentially expressed genes during flower senescence, we identified two amino acid biosynthesis genes, DcCARA and DcDHAD, with increased DNA methylation and reduced expression in DcROS1 silenced petals, and decreased DNA methylation and increased expression in DcROS1 overexpression petals, accompanied by decreased or increased amino acids content. Silencing of DcCARA and DcDHAD accelerates carnation flower senescence. We further showed that adding corresponding amino acids could largely rescue the senescence phenotype of DcROS1, DcCARA and DcDHAD silenced plants. Our study not only demonstrates an essential role of DcROS1-mediated remodeling of DNA methylation in flower senescence but also unravels a novel epigenetic regulatory mechanism underlying DNA methylation and amino acid biosynthesis during flower senescence.

Associations of MRI-Derived Glymphatic System Impairment With Global White Matter Damage and Cognitive Impairment in Mild Traumatic Brain Injury: A DTI-ALPS Study.

BACKGROUND: Assessing the glymphatic function using diffusion tensor image analysis along the perivascular space (DTI-ALPS) may be helpful for mild traumatic brain injury (mTBI) management. PURPOSE: To assess glymphatic function using DTI-ALPS and its associations with global white matter damage and cognitive impairment in mTBI. STUDY TYPE: Prospective. POPULATION: Thirty-four controls (44.1% female, mean age 49.2 years) and 58 mTBI subjects (43.1% female, mean age 48.7 years), including uncomplicated mTBI (N = 32) and complicated mTBI (N = 26). FIELD STRENGTH/SEQUENCE: 3-T, single-shot echo-planar imaging sequence. ASSESSMENT: Magnetic resonance imaging (MRI) was done within 1 month since injury. DTI-ALPS was performed to assess glymphatic function, and peak width of skeletonized mean diffusivity (PSMD) was used to assess global white matter damage. Cognitive tests included Auditory Verbal Learning Test and Digit Span Test (forward and backward). STATISTICAL TESTS: Neuroimaging findings comparisons were done between mTBI and control groups. Partial correlation and multivariable linear regression assessed the associations between DTI-ALPS, PSMD, and cognitive impairment. Mediation effects of PSMD on the relationship between DTI-ALPS and cognitive impairment were explored. P-value <0.05 was considered statistically significant, except for cognitive correlational analyses with a Bonferroni-corrected P-value set at 0.05/3 ≈ 0.017. RESULTS: mTBI showed lower DTI-ALPS and higher PSMD, especially in complicated mTBI. DTI-ALPS was significantly correlated with verbal memory (r = 0.566), attention abilities (r = 0.792), executive function (r = 0.618), and PSMD (r = -0.533). DTI-ALPS was associated with verbal memory (ß = 8.77, 95% confidence interval [CI] 5.00, 12.54), attention abilities (ß = 5.67, 95% CI 4.56, 6.97), executive function (ß = 2.34, 95% CI 1.49, 3.20), and PSMD (ß = -0.79, 95% CI -1.15, -0.43). PSMD mediated 46.29%, 20.46%, and 24.36% of the effects for the relationship between DTI-ALPS and verbal memory, attention abilities, and executive function. DATA CONCLUSION: Glymphatic function may be impaired in mTBI reflected by DTI-ALPS. Glymphatic dysfunction may cause cognitive impairment related to global white matter damage after mTBI. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Synthetic biology in microalgae towards fucoxanthin production for pharmacy and nutraceuticals.

Synthetic biology has emerged as a powerful tool for engineering biological systems to produce valuable compounds, including pharmaceuticals and nutraceuticals. Microalgae, in particular, offer a promising platform for the production of bioactive compounds due to their high productivity, low land and water requirements, and ability to perform photosynthesis. Fucoxanthin, a carotenoid pigment found predominantly in brown seaweeds and certain microalgae, has gained significant attention in recent years due to its numerous health benefits, such as antioxidation, antitumor effect and precaution osteoporosis. This review provides an overview of the principles and applications of synthetic biology in the microbial engineering of microalgae for enhanced fucoxanthin production. Firstly, the fucoxanthin bioavailability and metabolism in vivo was introduced for the beneficial roles, followed by the biological functions of anti-oxidant activity, anti-inflammatory activity, antiapoptotic role antidiabetic and antilipemic effects. Secondly, the cultivation condition and strategy were summarized for fucoxanthin improvement with low production costs. Thirdly, the genetic engineering of microalgae, including gene overexpression, knockdown and knockout strategies were discussed for further improving the fucoxanthin production. Then, synthetic biology tools of CRISPR-Cas9 genome editing, transcription activator-like effector nucleases as well as modular assembly and chassis engineering were proposed to precise modification of microalgal genomes to improve fucoxanthin production. Finally, challenges and future perspectives were discussed to realize the industrial production and development of functional foods of fucoxanthin from microalgae.

Prediction and related genes of cancer distant metastasis based on deep learning.

Cancer metastasis is one of the main causes of cancer progression and difficulty in treatment. Genes play a key role in the process of cancer metastasis, as they can influence tumor cell invasiveness, migration ability and fitness. At the same time, there is heterogeneity in the organs of cancer metastasis. Breast cancer, prostate cancer, etc. tend to metastasize in the bone. Previous studies have pointed out that the occurrence of metastasis is closely related to which tissue is transferred to and genes. In this paper, we identified genes associated with cancer metastasis to different tissues based on LASSO and Pearson correlation coefficients. In total, we identified 45 genes associated with bone metastases, 89 genes associated with lung metastases, and 86 genes associated with liver metastases. Through the expression of these genes, we propose a CNN-based model to predict the occurrence of metastasis. We call this method MDCNN, which introduces a modulation mechanism that allows the weights of convolution kernels to be adjusted at different positions and feature maps, thereby adaptively changing the convolution operation at different positions. Experiments have proved that MDCNN has achieved satisfactory prediction accuracy in bone metastasis, lung metastasis and liver metastasis, and is better than other 4 methods of the same kind. We performed enrichment analysis and immune infiltration analysis on bone metastasis-related genes, and found multiple pathways and GO terms related to bone metastasis, and found that the abundance of macrophages and monocytes was the highest in patients with bone metastasis.