Effects of exotic Spartina alterniflora invasion on benthic environments in the Yellow Sea.

For four decades, cordgrass (Spartina alterniflora) has invaded salt marshes in the Yellow Sea, altering physical, biogeochemical, and biological processes. Here, we investigated the ecological effects of S. alterniflora invasion on benthic environments compared to native halophytes. S. alterniflora contributed to higher carbon accumulation rates compared with bare tidal flat in sediments (3.4 times), through greater primary production and root biomass, compared to Suaeda japonica (2.5 times) and Phragmites australis (2.4 times) over the given period. The results showed that S. alterniflora eradication treatments inhibited its growth but did not significantly affect the benthic communities. Compared to P. australis and bare tidal flats, S. alterniflora invasion resulted in lower greenhouse gas emission and higher contributions to macrobenthos nutrition, and increased sediment stability and carbon burial. Overall, these multiple lines of evidence provide new insights on S. alterniflora invasion, suggesting that the current eradication policy would be carefully reviewed.

Big Data Analysis of Facial Fracture Epidemiology in South Korea From 2015 to 2020: Impacts of Aging and Personal Mobility.

The epidemiology of facial fractures is continuously evolving due to various influencing factors, including social, economic, and technological advancements. Thus, an updated analysis of facial bone fractures is necessary. This study aimed to provide an updated epidemiological analysis of facial bone fractures and assess severity using multiple factors. We retrospectively reviewed patients who underwent facial bone fracture surgery at 3 teaching hospitals in South Korea between January 2015 and December 2020. Data collected included patient demographics (sex and age), trauma mechanism, alcohol intoxication status, and fracture types. Trauma mechanisms were categorized into 7 groups: assault, fall, sports, occupational injury, motor vehicle crash, bicycle, and personal mobility. Severity was assessed using the modified facial injury severity scale. A total of 5953 patients (4437 males and 1516 females) were included, with ages ranging from 1 to 92 years (mean age: 36.37±18.61 y). A steady decline in the number of patients was observed from 2015 to 2020. Falls were the most common cause of facial fractures (2300 cases, 39%), and nasal bone fractures were the most frequent type (3683 cases, 46%). The number of elderly patients (> 60 y) and injuries caused by personal mobility devices increased steadily. Male sex and alcohol intoxication were associated with higher severity scores. Motor vehicle crashes had the highest severity scores (2.246). While the incidence of facial bone fractures has decreased in recent years, the proportion of elderly patients and injuries caused by personal mobility devices is increasing, posing a significant burden on the health care system.

Rational Design of Pyrido[3,2-b]indolizine as a Tunable Fluorescent Scaffold for Fluorogenic Bioimaging.

Novel fluorescent scaffolds are highly demanding for a wide range of applications in biomedical investigation. To meet this demand, the pyrido[3,2-b]indolizine scaffold was designed as a versatile organic fluorophore. With the aid of computational modeling, fluorophores offering tunable emission colors (blue to red) were constructed. Notably, constructed fluorophores absorb lights in the visible range (>400 nm) despite their small sizes (<300 g/mol). Among the fluorophores was discovered a highly fluorogenic fluorophore with a unique turn-on property, 1, and it was developed into a washing-free bioprobe for visualizing cellular lipid droplets in living cells. Furthermore, motivated by the core's compact size and structural analogy to indole, unprecedented tryptophan-analogous fluorogenic unnatural amino acids were constructed and incorporated into fluorogenic peptide probes for monitoring peptide-protein interactions.

Unveiling the dynamics of B lymphocytes in systemic lupus erythematosus patients treated with belimumab through longitudinal single-cell RNA sequencing.

OBJECTIVES: Unraveling the mechanisms underlying treatment response for targeted therapeutics in systemic lupus erythematosus (SLE) patients is challenging due to the limited understanding of diverse responses of circulating immune cells, particularly B cells. We investigated B lymphocyte dynamics during anti-BAFF treatment, utilizing longitudinal single-cell transcriptome data. METHODS: We conducted single-cell RNA sequencing on PBMCs in four Korean SLE patients before and after belimumab treatment at the following time points: 2 weeks, 1, 3, 6, and 12 months. RESULTS: Analyzing over 73 000 PBMCs, we identified 8 distinct subsets of B cells and plasmablasts and analyzed dynamic changes within these cell subsets: initial declines in naive and transitional B cells followed by an increase at three months, contrasted by an initial increase and subsequent decrease in memory B cells by the third month. Meanwhile, plasmablasts exhibited a consistent decline throughout treatment. B cell activation pathways, specifically in naive and memory B cells, were downregulated during the third and sixth months. These findings were validated at the protein level throughout the first four weeks of treatment using flow cytometry. Comparative analysis with bulk transcriptome data from 22 Japanese SLE patients showed increased NR4A1 expression six months post-belimumab treatment, indicating its role in restricting self-reactive B cells, thereby contributing to the biological responses of anti-BAFF treatment. CONCLUSION: The observed B cell dynamics provided insights into the immunological mechanisms underlying the therapeutic effects of anti-BAFF in SLE patients. Furthermore, it underscores the need for research in predicting drug responses based on immune profiling.

Inhibition of BCAT1-mediated cytosolic leucine metabolism regulates Th17 responses via the mTORC1-HIF1α pathway.

Branched-chain amino acids (BCAAs), particularly leucine, are indispensable AAs for immune regulation through metabolic rewiring. However, the molecular mechanism underlying this phenomenon remains unclear. Our investigation revealed that T-cell receptor (TCR)-activated human CD4+ T cells increase the expression of BCAT1, a cytosolic enzyme responsible for BCAA catabolism, and SLC7A5, a major BCAA transporter. This upregulation facilitates increased leucine influx and catabolism, which are particularly crucial for Th17 responses. Activated CD4+ T cells induce an alternative pathway of cytosolic leucine catabolism, generating a pivotal metabolite, ß-hydroxy ß-methylbutyric acid (HMB), by acting on BCAT1 and 4-hydroxyphenylpyruvate dioxygenase (HPD)/HPD-like protein (HPDL). Inhibition of BCAT1-mediated cytosolic leucine metabolism, either with BCAT1 inhibitor 2 (Bi2) or through BCAT1, HPD, or HPDL silencing using shRNA, attenuates IL-17 production, whereas HMB supplementation abrogates this effect. Mechanistically, HMB contributes to the regulation of the mTORC1-HIF1α pathway, a major signaling pathway for IL-17 production, by increasing the mRNA expression of HIF1α. This finding was corroborated by the observation that treatment with L-ß-homoleucine (LßhL), a leucine analog and competitive inhibitor of BCAT1, decreased IL-17 production by TCR-activated CD4+ T cells. In an in vivo experimental autoimmune encephalomyelitis (EAE) model, blockade of BCAT1-mediated leucine catabolism, either through a BCAT1 inhibitor or LßhL treatment, mitigated EAE severity by decreasing HIF1α expression and IL-17 production in spinal cord mononuclear cells. Our findings elucidate the role of BCAT1-mediated cytoplasmic leucine catabolism in modulating IL-17 production via HMB-mediated regulation of mTORC1-HIF1α, providing insights into its relevance to inflammatory conditions.

General Treatments Promoting Independent Living in Parkinson's Patients and Physical Therapy Approaches for Improving Gait-A Comprehensive Review.

This study delves into the multifaceted approaches to treating Parkinson's disease (PD), a neurodegenerative disorder primarily affecting motor function but also manifesting in a variety of symptoms that vary greatly among individuals. The complexity of PD symptoms necessitates a comprehensive treatment strategy that integrates surgical interventions, pharmacotherapy, and physical therapy to tailor to the unique needs of each patient. Surgical options, such as deep brain stimulation (DBS), have been pivotal for patients not responding adequately to medication, offering significant symptom relief. Pharmacotherapy remains a cornerstone of PD management, utilizing drugs like levodopa, dopamine agonists, and others to manage symptoms and, in some cases, slow down disease progression. However, these treatments often lead to complications over time, such as motor fluctuations and dyskinesias, highlighting the need for precise dosage adjustments and sometimes combination therapies to optimize patient outcomes. Physical therapy plays a critical role in addressing the motor symptoms of PD, including bradykinesia, muscle rigidity, tremors, postural instability, and akinesia. PT techniques are tailored to improve mobility, balance, strength, and overall quality of life. Strategies such as gait and balance training, strengthening exercises, stretching, and functional training are employed to mitigate symptoms and enhance functional independence. Specialized approaches like proprioceptive neuromuscular facilitation (PNF), the Bobath concept, and the use of assistive devices are also integral to the rehabilitation process, aimed at improving patients' ability to perform daily activities and reducing the risk of falls. Innovations in technology have introduced robotic-assisted gait training (RAGT) and other assistive devices, offering new possibilities for patient care. These tools provide targeted support and feedback, allowing for more intensive and personalized rehabilitation sessions. Despite these advancements, high costs and accessibility issues remain challenges that need addressing. The inclusion of exercise and activity beyond structured PT sessions is encouraged, with evidence suggesting that regular physical activity can have neuroprotective effects, potentially slowing disease progression. Activities such as treadmill walking, cycling, and aquatic exercises not only improve physical symptoms but also contribute to emotional well-being and social interactions. In conclusion, treating PD requires a holistic approach that combines medical, surgical, and therapeutic strategies. While there is no cure, the goal is to maximize patients' functional abilities and quality of life through personalized treatment plans. This integrated approach, along with ongoing research and development of new therapies, offers hope for improving the management of PD and the lives of those affected by this challenging disease.

Quantification of steal flow on Doppler ultrasound in patients with arteriovenous graft for hemodialysis.

PURPOSE: Arteriovenous fistula (AVF) is the preferred treatment for long-term hemodialysis patients to allow reliable vascular access. Arteriovenous graft (AVG) is monitored using Doppler sonography to check a vessel's condition and predict complications such as steal syndrome. In this study, we developed an analysis algorithm and method to quantify steal syndrome using Doppler sonography. METHODS: Doppler sonography was used to determine the pattern of anterograde and retrograde flow. The ratio of blood volumes was calculated with a vision analysis software. First, performance of the developed algorithm was validated by comparing it with commercial Doppler sonography data. Doppler sonography was performed for an artificial vessel to analyze the steal flow. RESULTS: A total of 58 patients with steal flow were enrolled in this study. Of these patients, 23 did not have a difference in fingertip temperature between both sides. The median difference in temperature of 35 patients was 0.8°C (range, 0.3-1.9°C). The ratio of retrograde flow volume/antegrade flow volume in patients with the presence of temperature difference was significantly higher compared to that in patients without the temperature difference (p < .001). The ROC curve for the difference in flow volume had an AUC of 0.770. The optimal cutoff of difference in the flow volume between the two groups was 0.24 (sensitivity of 91.4 % and specificity of 52.2%). The flow volume difference was significantly positively correlated to temperature difference (r = 0.487, p < .003). CONCLUSION: Our algorithm could measure steal flow volume of a bidirectional waveform by antegrade arterial flow and retrograde reversal flow.

Detecting T-cell receptor clonality in patients with severe atopic dermatitis refractory to dupilumab.

BACKGROUND: Trials and real-life studies demonstrated clinically meaningful improvements of disease activity in the majority of patients with moderate to severe atopic dermatitis (AD) treated with the anti-IL-4RA-antibody dupilumab. However, misdiagnosis or confounding skin diseases in particular cutaneous T-cell lymphoma (CTCL) may lead to inadequate response. OBJECTIVE: To investigate the clinical and pathological features of patients with AD who showed insufficient response to dupilumab. METHODS: We reviewed the medical records of 371 patients treated with dupilumab for severe AD. Insufficient response was defined as failure to achieve an improvement of the eczema area severity index (EASI) of at least 50% (EASI-50) at Week 16 and of 75% (EASI-75) at Week 52. Among 46 patients with insufficient response, 35 patients consented to a re-evaluation including a full physical exam, biopsies and laboratory assessments including immunohistochemistry and T-cell receptor gene rearrangement analysis to differentiate CTCL. RESULTS: Of the 371 patients treated with dupilumab, 46 (12.3%) patients showed insufficient response to dupilumab. Of these, 35 underwent further evaluation, and 19 (54.2% of inadequate responders) were finally diagnosed with mycosis fungoides (MF). In these patients, transition to or addition of conventional MF treatment led to clinical improvements. CONCLUSIONS: Insufficient response to dupilumab treatment may help uncover early MF on an existing AD background.

Association between Atherosclerosis and High-Risk Colorectal Adenomas based on Cardio-Ankle Vascular Index and Ankle-Brachial Index.

Background/Aims: Colorectal adenomas are precancerous lesions that may lead to colorectal cancer. Recent studies have shown that colorectal adenomas are associated with atherosclerosis. The cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) are noninvasive methods for evaluating atherosclerosis. This study examined the association between atherosclerosis and high-risk colorectal adenomas based on the CAVI and ABI. Methods: The data of patients aged ≥50 years who had a colonoscopy and CAVI and ABI measurements from August 2015 to December 2021 at the Kangwon National University Hospital were analyzed retrospectively. After the colonoscopy, subjects were divided into no, overall, and high-risk (size ≥1 cm, high-grade dysplasia or villous adenoma, three or more adenomas) adenoma groups based on the pathology findings. The data were subjected to univariate and multivariate logistic regression analyses. Results: Among the 1,164 subjects, adenomas and high-risk adenomas were found in 613 (52.6%) and 118 (10.1%) patients, respectively. The rate of positive ABI (<0.9) and positive CAVI (≥9.0) were significantly higher in the high-risk adenoma group (22.0% and 55.9%) than in the no adenoma (12.3% and 39.6%) and the overall adenoma group (15.7% and 44.0%) (p=0.008 and p=0.006, respectively). Multivariate analysis revealed a positive CAVI and smoking status to be significantly associated with high-risk adenoma with an odds ratio of 1.595 (95% confidence interval 1.055-2.410, p=0.027) and 1.579 (1.072-2.324, p=0.021), respectively. Conclusions: In this study, a significant correlation between positive CAVI and high-risk adenomas was observed. Therefore, CAVI may be a significant predictor for high-risk colorectal adenoma.

Optimizing Rehabilitation Outcomes for Stroke Survivors: The Impact of Speed and Slope Adjustments in Anti-Gravity Treadmill Training.

Background and Objectives: This study explored the efficacy of customized anti-gravity treadmill (AGT) training, with adjustments in speed and incline, on rehabilitation outcomes for stroke patients, focusing on knee extensor muscle strength, joint angle, balance ability, and activities of daily living (ADLs). Materials and Methods: In this study, 30 individuals diagnosed with a stroke were divided into three groups. Experimental group 1 (EG1) underwent training without changes to speed and incline, experimental group 2 (EG2) received training with an increased incline, and experimental group 3 (EG3) underwent training with increased speed. Initially, all participants received AGT training under uniform conditions for two weeks. Subsequently, from the third to the sixth week, each group underwent their specified training intervention. Evaluations were conducted before the intervention and six weeks post-intervention using a manual muscle strength tester for knee strength, TETRAX for balance ability, Dartfish software for analyzing knee angle, and the Korean version of the Modified Barthel Index (K-MBI) for assessing activities of daily living. Results: Within-group comparisons revealed that AGT training led to enhancements in muscle strength, balance ability, joint angle, and ADLs across all participant groups. Between-group analyses indicated that EG2, which underwent increased incline training, demonstrated significant improvements in muscle strength and balance ability over EG1. EG3 not only showed significant enhancements in muscle strength, joint angle, and ADLs when compared to EG1 but also surpassed EG2 in terms of knee strength improvement. Conclusions: In conclusion, the application of customized AGT training positively impacts the rehabilitation of stroke patients, underscoring the importance of selecting a treatment method tailored to the specific needs of each patient.

A Comprehensive Review: Robot-Assisted Treatments for Gait Rehabilitation in Stroke Patients.

Robot-assisted gait training (RAGT) is at the cutting edge of stroke rehabilitation, offering a groundbreaking method to improve motor recovery and enhance the quality of life for stroke survivors. This review investigates the effectiveness and application of various RAGT systems, including both end-effector and exoskeleton robots, in facilitating gait enhancements. The selection process for this comprehensive analysis involved a meticulous review of the literature from databases such as PubMed, the Cochrane Library, and EMBASE, focusing on studies published between 2018 and 2023. Ultimately, 27 studies met the criteria and were included in the final analysis. The focus of these studies was on the various RAGT systems and their role in promoting gait and balance improvements. The results of these studies conclusively show that patients experience significant positive effects from RAGT, and when combined with other physiotherapy methods, the outcomes are notably superior in enhancing functional ambulation and motor skills. This review emphasizes RAGT's capability to deliver a more customized and effective rehabilitation experience, highlighting the importance of tailoring interventions to meet the specific needs of each patient.

Managing Vascular Pedicle Exposure in Free Tissue Transfer Using a Reprocessed Micronized Dermal Substitute in Lower Extremity Reconstructions.

Lower extremity reconstruction is challenging because of its intricate anatomy and dynamic biomechanics. Although microsurgical free tissue transfer offers pivotal solutions to limited local tissue availability, vascular pedicle exposure after free tissue transfer is common. We evaluated a novel method of managing pedicle exposure after free tissue transfer using a reprocessed micronized dermal substitute. Ten patients who underwent lower-extremity reconstruction using free tissue transfer and micronized dermal substitute between January and December 2023 were retrospectively reviewed. When native tissue could not be closed over the pedicle, reprocessed micronized artificial dermal matrix (rmADM) was cut and stacked to protect and stabilize it. Epithelialization was achieved by secondary skin grafting or healing by secondary intention. Flap dimensions, recipient artery and vein, ADM size, time required for granulation tissue maturation and complete epithelialization, and flap outcomes were analyzed. The mean age was 55.80 ± 20.70 years, and six patients (60%) were diabetic. The mean rmADM coverage area was 8.70 ± 8.41 cm2, and the average time required for complete epithelialization was 50.89 ± 14.21 days. Except for one total necrosis due to bypass graft failure, nine limbs were successfully salvaged. Application of rmADM offers numerous advantages, including vascular collapse prevention, moisture maintenance, granulation tissue growth promotion, and pedicle stabilization.

Evolutionary Spread of Distinct O-methyltransferases Guides the Discovery of Unique Isoaspartate-Containing Peptides, Pamtides.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a structurally diverse class of natural products with a distinct biosynthetic logic, the enzymatic modification of genetically encoded precursor peptides. Although their structural and biosynthetic diversity remains largely underexplored, the identification of novel subclasses with unique structural motifs and biosynthetic pathways is challenging. Here, it is reported that peptide/protein L-aspartyl O-methyltransferases (PAMTs) present in several RiPP subclasses are highly homologous. Importantly, it is discovered that the apparent evolutionary transmission of the PAMT gene to unrelated RiPP subclasses can serve as a basis to identify a novel RiPP subclass. Biochemical and structural analyses suggest that homologous PAMTs convert aspartate to isoaspartate via aspartyl-O-methyl ester and aspartimide intermediates, and often require cyclic or hairpin-like structures for modification. By conducting homology-based bioinformatic analysis of PAMTs, over 2,800 biosynthetic gene clusters (BGCs) are identified for known RiPP subclasses in which PAMTs install a secondary modification, and over 1,500 BGCs where PAMTs function as a primary modification enzyme, thereby defining a new RiPP subclass, named pamtides. The results suggest that the genome mining of proteins with secondary biosynthetic roles can be an effective strategy for discovering novel biosynthetic pathways of RiPPs through the principle of "guilt by association".

Determination of progressive stages of type 2 diabetes in a 45% high-fat diet-fed C57BL/6J mouse model is achieved by utilizing both fasting blood glucose levels and a 2-hour oral glucose tolerance test.

Type 2 diabetes is considered one of the top ten life-threatening diseases worldwide. Following economic growth, obesity and metabolic syndrome became the most common risk factor for type 2 diabetes. In this regard, high-fat diet-fed C57BL/6J mouse model is widely used for type 2 diabetes pathogenesis and novel therapeutics development. However, criteria for classifying type 2 diabetes progressive stages in this mouse model are yet to be determined, led to the difficulty in experimental end-point decision. In this study, we fed C57BL/6J male mice with 45% high-fat diet, which is physiologically close to human high-fat consumption, and evaluated the progression of type 2 diabetes. After consuming high-fat diet for 4 weeks, mice developed metabolic syndrome, including obesity, significant increase of fasting plasma cholesterol level, elevation of both C-peptide and fasting blood glucose levels. By combining both fasting blood glucose test and 2-hour-oral glucose tolerance test, our results illustrated clear progressive stages from metabolic syndrome into pre-diabetes before onset of type 2 diabetes in C57BL/6J mice given a 45% high-fat diet. Besides, among metabolic measurements, accumulating body weight gain > 16.23 g for 12 weeks could be utilized as a potential parameter to predict type 2 diabetes development in C57BL/6J mice. Thus, these results might support future investigations in term of selecting appropriate disease stage in high-fat diet-fed C57BL/6J mouse model for studying early prevention and treatment of type 2 diabetes.

Spatiotemporal estimation of nutrient data from the northwest pacific and east asian seas.

Nutrient data obtained from field observations have the potential to enhance our understanding of oceanic biogeochemical cycling and productivity changes. In particular, long-term nutrient data can provide valuable information on the links between climate change and biogeochemical changes. However, unlike other observational variables such as sea surface temperature, nutrient data are limited in terms of their broad-scale observations and automated sensor-based measurements. In this study, we analyzed nitrate and phosphate data obtained from coastal regions in Northeast Asia and the northwest Pacific from 1980 to 2019 using the spatiotemporal kriging technique and provide results in a spatiotemporal grid format. The data are available at monthly intervals and may be attractive to researchers in the fields of oceanography, marine ecology, and marine biogeochemistry at the climate change scale. Furthermore, sharing the source code of the data production process can contribute to better long-term data reproduction in the future.

A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage.

This study was conducted to investigate the effects of anti-gravity treadmill (AGT) training, which provides visual feedback and Biorescue training on proprioception, muscle strength, balance, and gait, in stroke patients. A total of 45 people diagnosed with post-stroke were included as study subjects; they were randomized to an AGT training group provided with visual feedback (Group A), a Biorescue training group provided with visual feedback (Group B), and an AGT/Biorescue group that subsequently received AGT training and Biorescue training (Group C). A muscle strength-measuring device was used to evaluate muscle strength. Timed Up and Go and Bug Balance Scale assessment sheets were used to evaluate balance ability. Dartfish software was used to evaluate gait ability. The results of the study showed that Groups A and C had a significant increase in muscle strength compared with Group B; in terms of balance and gait abilities, Group C showed a significant increase in balance ability and gait speed and a significant change in knee joint angle compared with Groups A and B. In conclusion, this study suggests that including a method that applies multiple therapeutic interventions is desirable in the rehabilitation of stroke patients to improve their independence.

Single-cell RNA sequencing identifies distinct transcriptomic signatures between PMA/ionomycin- and αCD3/αCD28-activated primary human T cells.

Immunologists have activated T cells in vitro using various stimulation methods, including phorbol myristate acetate (PMA)/ionomycin and αCD3/αCD28 agonistic antibodies. PMA stimulates protein kinase C, activating nuclear factor-κB, and ionomycin increases intracellular calcium levels, resulting in activation of nuclear factor of activated T cell. In contrast, αCD3/αCD28 agonistic antibodies activate T cells through ZAP-70, which phosphorylates linker for activation of T cell and SH2-domain-containing leukocyte protein of 76 kD. However, despite the use of these two different in vitro T cell activation methods for decades, the differential effects of chemical-based and antibody-based activation of primary human T cells have not yet been comprehensively described. Using single-cell RNA sequencing (scRNA-seq) technologies to analyze gene expression unbiasedly at the single-cell level, we compared the transcriptomic profiles of the non-physiological and physiological activation methods on human peripheral blood mononuclear cell-derived T cells from four independent donors. Remarkable transcriptomic differences in the expression of cytokines and their respective receptors were identified. We also identified activated CD4 T cell subsets (CD55+) enriched specifically by PMA/ionomycin activation. We believe this activated human T cell transcriptome atlas derived from two different activation methods will enhance our understanding, highlight the optimal use of these two in vitro T cell activation assays, and be applied as a reference standard when analyzing activated specific disease-originated T cells through scRNA-seq.