Empagliflozin Attenuates Pulmonary Arterial Remodeling Through Peroxisome Proliferator-Activated Receptor Gamma Activation.

The loss of peroxisome proliferator-activated receptor gamma (PPARγ) exacerbates pulmonary arterial hypertension (PAH), while its upregulation reduces cell proliferation and vascular remodeling, thereby decreasing PAH severity. SGLT2 inhibitors, developed for type 2 diabetes, might also affect signal transduction in addition to modulating sodium-glucose cotransporters. Pulmonary arterial smooth muscle cells (PASMCs) isolated from patients with idiopathic pulmonary arterial hypertension (IPAH) were treated with three SGLT2 inhibitors, canagliflozin (Cana), dapagliflozin (Dapa), and empagliflozin (Empa), to investigate their antiproliferative effects. To assess the impact of Empa on PPARγ, luciferase reporter assays and siRNA-mediated PPARγ knockdown were employed to examine regulation of the γ-secretase complex and its downstream target Notch3. Therapy involving daily administration of Empa was initiated 21 days after inducing hypoxia-induced PAH in mice. Empa exhibited significant antiproliferative effects on fast-growing IPAH PASMCs. Empa activated PPARγ to prevent formation of the γ-secretase complex, with specific impacts on presenilin enhancer 2 (PEN2), which plays a crucial role in maintaining γ-secretase complex stability, thereby inhibiting Notch3. Similar results were obtained in lung tissue of chronically hypoxic mice. Empa attenuated pulmonary arterial remodeling and right ventricle hypertrophy in a hypoxic PAH mouse model. Moreover, PPARγ expression was significantly decreased and PEN2, and Notch3 levels were increased in lung tissue from PAH patients compared with non-PAH lung tissue. Empa reverses vascular remodeling by activating PPARγ to suppress the γ-secretase-Notch3 axis. We propose Empa as a PPARγ activator and potential therapeutic for PAH.

Initial Experience of Metabolic Imaging with Hyperpolarized [1-13C]pyruvate MRI in Kidney Transplant Patients.

BACKGROUND: Kidney transplant is the treatment of choice for patients with end-stage renal disease. Early detection of allograft injury is important to delay or prevent irreversible damage. PURPOSE: To investigate the feasibility of hyperpolarized (HP) [1-13C]pyruvate MRI for assessing kidney allograft metabolism. SUBJECTS: 6 participants (mean age, 45.2 +- 12.4 years, 2 females) scheduled for kidney allograft biopsy and 5 patients (mean age, 59.6 +- 10.4 years, 2 females) with renal cell carcinoma (RCC). ASSESSMENT: Five of the six kidney allograft participants underwent biopsy after MRI. Estimated glomerular filtration rate (eGFR) and urine protein-to-creatine ratio (uPCR) were collected within 4 weeks of MRI. Kidney metabolism was quantified from HP [1-13C]pyruvate MRI using the lactate-to-pyruvate ratio in allograft kidneys and non-tumor bearing kidneys from RCC patients. RESULTS: Biopsy was performed a mean of 9 days (range 5-19 days) after HP [1-13C]pyruvate MRI. Three biopsies were normal, one showed low-grade fibrosis and one showed moderate microvascular inflammation. All had stable functioning allografts with eGFR > 60 mL/min/1.73 m2 and normal uPCR. One participant who did not undergo biopsy had reduced eGFR of 49 mL/min/1.73 m2 and elevated uPCR. The mean lactate-to-pyruvate ratio was 0.373 in participants with normal findings (n = 3) and 0.552 in participants with abnormal findings (n = 2). The lactate-to-pyruvate ratio was highest (0.847) in the participant with reduced eGFR and elevated uPRC. Native non-tumor bearing kidneys had a mean lactate-to-pyruvate ratio of 0.309. DATA CONCLUSION: Stable allografts with normal findings at biopsy showed lactate-to-pyruvate ratios similar to native non-tumor bearing kidneys, whereas allografts with abnormal findings showed higher lactate-to-pyruvate ratios.

Spatial Transcriptomics Identifies Cellular and Molecular Characteristics of Scleroderma Skin Lesions: Pilot Study in Juvenile Scleroderma.

Juvenile localized and systemic scleroderma are rare autoimmune diseases which cause significant disability and morbidity in children. The mechanisms driving juvenile scleroderma remain unclear, necessitating further cellular and molecular level studies. The Visium CytAssist spatial transcriptomics (ST) platform, which preserves the spatial location of cells and simultaneously sequences the whole transcriptome, was employed to profile the histopathological slides from skin lesions of juvenile scleroderma patients. (1) Spatial domains were identified from ST data and exhibited strong concordance with the pathologist's annotations of anatomical structures. (2) The integration of paired ST data and single-cell RNA sequencing (scRNA-seq) from the same patients validated the comparable accuracy of the two platforms and facilitated the estimation of cell type composition in ST data. (3) The pathologist-annotated immune infiltrates, such as perivascular immune infiltrates, were clearly delineated by the ST analysis, underscoring the biological relevance of the findings. This is the first study utilizing spatial transcriptomics to investigate skin lesions in juvenile scleroderma patients. The validity of the ST data was corroborated by gene expression analyses and the pathologist's assessments. Integration with scRNA-seq data facilitated the cell type-level analysis and validation. Analyses of immune infiltrates through combined ST data and pathological review enhances our understanding of the pathogenesis of juvenile scleroderma.

A vexing case of a 73-year-old man with fevers, orbital cellulitis, and asymptomatic interstitial lung disease.

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a rare and recently identified disease resulting from a somatic mutation in the X-linked UBA1 gene in cells of myeloid lineage. It can present in a myriad of ways with the potential to affect various organ systems, including the lungs. VEXAS is usually steroid responsive, but no strong data exists for the use of a steroid-sparing agent. There is limited emerging evidence for haematopoietic stem cell transplantation in a select number of cases. Regardless, prognosis for this condition is poor and a treatment algorithm remains a priority. Herein, we present a case of VEXAS that came to attention with discovery of a relatively asymptomatic interstitial lung disease and led to recurrent febrile episodes with evolving multi-organ involvement.

Comparison of macular thickness in diabetic patients acquired from optical coherence tomography mode and optical coherence tomography angiography mode in Cirrus HD-OCT 5000.

PURPOSE: To compare macular thickness obtained using two different modes of image acquisitions with Cirrus HD-OCT 5000. METHODS: Patients with diabetes were recruited and macular thickness were obtained using optical coherence tomography (OCT) mode and optical coherence tomography angiography (OCTA) mode. The OCT mode involved a Macular Cube (512×128 pixels) centred on the fovea covering a 6 × 6 mm2 macular region. The OCTA acquisition involved scanning of a 6 × 6 mm² scan (350×350 pixels) centred on the fovea. Data was exported and compared according to the Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Fixation deviation was defined as the deviation of the foveal point from the grid center in the OCT scan and OCTA scan. RESULTS: Eighty-six diabetic patients were recruited had similar macular thickness in all ETDRS subfield except the superior outer sector. The 95 % limits of agreement between the two modes were within 9.7µm to -9.0µm. It took longer to complete each OCTA mode (median of 7.4 s) than the OCT mode (median time of 5.8 s) (Wilcoxon test, p < 0.001), but OCTA generated a smaller fixation deviation (median 68.8µm) than the OCT mode (median 103.0µm) (Wilcoxon test, p = 0.014). CONCLUSIONS: Improved fixation in OCTA compared with OCT was evident, likely because of the faster scanning speed and higher sampling density of OCTA. Macular thickness was found similar. There appears no requirement to obtain macular thickness measurements using a separate OCT mode. This approach can reduce patient chair time, improve patient comfort, and streamline the clinical workflow.

Initial Experience of Metabolic Imaging With Hyperpolarized [1-13C]pyruvate MRI in Kidney Transplant Patients.

BACKGROUND: Kidney transplant is the treatment of choice for patients with end-stage renal disease. Early detection of allograft injury is important to delay or prevent irreversible damage. PURPOSE: To investigate the feasibility of hyperpolarized (HP) [1-13C]pyruvate MRI for assessing kidney allograft metabolism. STUDY TYPE: Prospective. SUBJECTS: Six participants (mean age, 45.2 ± 12.4 years, two females) scheduled for kidney allograft biopsy and five patients (mean age, 59.6 ± 10.4 years, two females) with renal cell carcinoma (RCC). FIELD STRENGTH/SEQUENCE: Three Tesla, T2-weighted fast spin echo, multi-echo gradient echo, single shot diffusion-weighted echo-planar imaging, and time-resolved HP 13C metabolite-selective imaging. ASSESSMENT: Five of the six kidney allograft participants underwent biopsy after MRI. Estimated glomerular filtration rate (eGFR) and urine protein-to-creatine ratio (uPCR) were collected within 4 weeks of MRI. Kidney metabolism was quantified from HP [1-13C]pyruvate MRI using the lactate-to-pyruvate ratio in allograft kidneys and non-tumor bearing kidneys from RCC patients. STATISTICAL TESTS: Descriptive statistics (mean ± SD). RESULTS: Biopsy was performed a mean of 9 days (range 5-19 days) after HP [1-13C]pyruvate MRI. Three biopsies were normal, one showed low-grade fibrosis and one showed moderate microvascular inflammation. All had stable functioning allografts with eGFR >60 mL/min/1.73 m2 and normal uPCR. One participant who did not undergo biopsy had reduced eGFR of 49 mL/min/1.73 m2 and elevated uPCR. The mean lactate-to-pyruvate ratio was 0.373 in participants with normal findings (N = 3) and 0.552 in participants with abnormal findings (N = 2). The lactate-to-pyruvate ratio was highest (0.847) in the participant with reduced eGFR and elevated uPRC. Native non-tumor bearing kidneys had a mean lactate-to-pyruvate ratio of 0.309. DATA CONCLUSION: Stable allografts with normal findings at biopsy showed lactate-to-pyruvate ratios similar to native non-tumor bearing kidneys, whereas allografts with abnormal findings showed higher lactate-to-pyruvate ratios. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Duckweed-based optical biosensor for herbicide toxicity assessment.

In response to the pervasive issue of herbicide pollution in environmental water bodies, particularly from herbicides used extensively in agriculture, traditional chemical-based water quality analysis methods have proven costly and time-consuming, often failing to meet regulatory standards. To overcome these limitations, global environmental agencies have turned to rapidly-growing species like duckweed as bioindicators for herbicide and pesticide contamination. However, conventional biological assessment methods, such as the 168-h duckweed growth inhibition test, are slow and lack real-time monitoring capabilities. To address this challenge, we developed an innovative approach by integrating opto-mechanical technology with duckweed to create a cost-effective biosensor for herbicide detection, priced under $10 USD per system. This advancement allows for the rapid detection of herbicide impacts on duckweed growth within just 48 h, significantly improving upon traditional methods. Our biosensor achieves detection limits of 10 ppm (p < 0.05) for glyphosate and 1 ppm (p < 0.05) for glufosinate, both prominent herbicides globally. This mini-biosensing platform offers a practical alternative to the official method, which requires 168 h and higher thresholds (36.4 ppm for glyphosate and 34.0 ppm for glufosinate) for routine environmental analysis. Thus, these duckweed-based optical biosensors represent a promising advancement in environmental monitoring, enhancing accessibility and efficacy for widespread adoption globally.

Benefits of chest wall mobilization on respiratory efficiency and functional exercise capacity in people with severe chronic obstructive pulmonary disease (COPD): A randomized controlled trial.

BACKGROUND: Coexistence of chest wall hypomobility and lung hyperinflation compromises respiratory muscle function and respiratory efficiency in people with severe chronic obstructive pulmonary disease (COPD). This study aimed to investigate the effect of chest wall mobilization on functional exercise capacity, respiratory muscle activity and respiratory muscle tissue oxygen saturation for people with severe COPD. METHODS: Thirty male adults (age: 75 ± 6) diagnosed with severe COPD completed a 6-week programme (twice/week) according to intervention randomization (chest wall mobilization group, CWMG, n = 15; control group, CG, n = 15). Both groups received standardized education and walking exercise, while CWMG also received chest wall and thoracic spine mobilization. Electromyography of the essential and accessory respiratory muscles and tissue oxygen saturation of the intercostal muscle (StO2, measured by near-infrared spectroscopy) during incremental cycle exercise test were measured and compared between the two groups at pre-programme, post-programme and 3-month follow-up. RESULTS: Patients in CWMG demonstrated a significant increase in exercise tolerance from <3 METS to 4-6 METS (p = 0.000) after intervention. A significant decrease in activity of scalene, sternocleidomastoids and intercostal muscle during exercise test (p < 0.01) was found in CWMG, as compared to CG. A significant decrease in StO2 (p < 0.05) and greater decline in the slope of oxygenation dissociation (p = 0.000) were seen in CWMG during exercise test. These positive results were maintained at 3-month follow-up in CWMG. CONCLUSION: Improvements in exercise tolerance, respiratory muscle efficiency and oxygenation extraction ability in CWMG suggest a potential clinical benefit of integrating chest wall and thoracic spine mobilization for rehabilitation of people with severe COPD.

Efficient Permeable Monolithic Hybrid Tribo-Piezo-Electromagnetic Nanogenerator Based on Topological-Insulator-Composite.

Escalating energy demands of self-independent on-skin/wearable electronics impose challenges on corresponding power sources to offer greater power density, permeability, and stretchability. Here, a high-efficient breathable and stretchable monolithic hybrid triboelectric-piezoelectric-electromagnetic nanogenerator-based electronic skin (TPEG-skin) is reported via sandwiching a liquid metal mesh with two-layer topological insulator-piezoelectric polymer composite nanofibers. TPEG-skin concurrently extracts biomechanical energy (from body motions) and electromagnetic radiations (from adjacent appliances), operating as epidermal power sources and whole-body self-powered sensors. Topological insulators with conductive surface states supply notably enhanced triboelectric and piezoelectric effects, endowing TPEG-skin with a 288 V output voltage (10 N, 4 Hz), ∼3 times that of state-of-the-art devices. Liquid metal meshes serve as breathable electrodes and extract ambient electromagnetic pollution (±60 V, ±1.6 µA cm-2). TPEG-skin implements self-powered physiological and body motion monitoring and system-level human-machine interactions. This study provides compatible energy strategies for on-skin/wearable electronics with high power density, monolithic device integration, and multifunctionality.

Photoangiolysis with the 445-nm Blue Laser and the Potassium-Titanyl-Phosphate Laser: A Comparison.

OBJECTIVES: Photoangiolytic lasers have yielded significant innovation in laryngeal surgery in the last 25 years. After the discontinuation of the potassium titanyl phosphate (KTP) laser, a novel 445-nm blue laser was developed. The optimal balance between a laser's desired tissue effects and collateral tissue damage is a major determinant of laser selection in microlaryngeal surgery. The shell-less incubation system for the chick chorioallantoic membrane (CAM) simulates the microvasculature of the human vocal fold and is useful for testing effects of laser settings and in simulated surgery. The aim of this study is to compare the tissue effects of the KTP and blue lasers using the shell-less CAM model. METHODS: The shell-less incubation system contains: polymethylpentene film (used as a culture vessel), calcium lactate and distilled water supplementations. By using this system, the chick chorioallantoic membrane (CAM) can be fully exposed with a good field for surgery simulation. The effects of the 2 lasers (532 nm KTP and 445 nm blue) were quantified at clinically relevant energy settings and laser distances from target. Measures included imaging real-time vascular reactions in the CAM model, post-procedure histologic analysis of CAM tissue and temperature changes. RESULTS: Vessel coagulation and rupture rates were less common with the blue laser compared with the KTP laser. Histologic analysis demonstrated less tissue disruption with the blue laser. Temperature changes were less with the blue laser. CONCLUSION: In this CAM model with specific conditions, the blue laser reveals less tissue damage than the KTP laser. Suitable working distance and power setting of the laser are necessary for desired tissue effects.Level of Evidence: Level 3.

Relationship between genotype, phenotype, and refractive status in patients of inherited retinal degeneration.

BACKGROUND: To elucidate the relationship between inherited retinal disease, visual acuity and refractive error development in Asian patients. SUBJECTS: Five hundred phakic eyes with refractive data were analysed in this retrospective cohort. Diseases were categorized by clinical phenotypes, and the prevalent genotypes identified in the Taiwan Inherited Retinal Degeneration Project were analysed. Consecutive surveys in Taiwan have provided the rates of myopia in the general population. RESULTS: No differences were observed among the disease phenotypes with respect to myopia (P = 0.098) and high myopia rates (P = 0.037). The comparison of refractive error between retinitis pigmentosa and diseases mainly affecting the central retina showed no difference, and the refraction analyses in diseases of different onset ages yielded no significance. Moreover, there was no difference in the myopia rate between the diseases and general population. Among the genotypes, a higher spherical equivalent was seen in RPGR and PROM1-related patients and emmetropic trends were observed in patients with CRB1 and PRPF31 mutations. Furthermore, significantly poorer visual acuity was found in ABCA4, CRB1 and PROM1-related patients, and more preserved visual acuity was seen in patients with EYS, USH2A, and RDH12 mutations. CONCLUSIONS: No significant differences were observed in visual acuity, refractive state and myopia rate between patients with inherited retinal disease and the general population, and different subtypes of inherited retinal disease shared similar refractive state, except for higher cylindrical dioptres found in patients with Leber's congenital amaurosis. The heterogeneity of disease-causing genes in Asian patients may lead to variable refractive state.

Extraction Effects on Roselle Functionalities: Antioxidant, Antiglycation, and Antibacterial Capacities.

This study investigated the effects of certain roselle (Hibiscus sabdariffa Linnaeus) extraction methods on various functional properties, including the antioxidant and antiglycation capacities and bacterial growth inhibition. Roselle anthocyanins were extracted using water and ethanol solvents at different temperatures and concentrations. The results revealed that the extraction rate increased with higher temperatures and ethanol concentrations (p < 0.05). Ethanol extracts exhibited higher total organic acid and total anthocyanin contents compared to water extracts, while water extracts showed higher total saccharide, total polyphenol, and total flavonoid contents (p < 0.05). Furthermore, the water extracts demonstrated superior Trolox equivalent antioxidant capacity (TEAC) values, while the ethanol extracts exhibited better 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability, antiglycation capacity, and bacterial growth inhibition. A Pearson correlation analysis revealed strong associations between specific components and functional properties, such as a positive correlation between the total anthocyanin content and antiglycation capacity (R2 = 0.9862). A principal component analysis and agglomerative hierarchical clustering highlighted distinct clusters of water and ethanol extracts, indicating solvent-dependent variations in functional properties. This study assessed roselle extraction models for antioxidant, antiglycation, and antibacterial activities, which could be used for the development of functional alcoholic or non-alcoholic beverages.

Validity of the Chinese multimorbidity-weighted index in measuring disease burden using health check-ups data in primary care.

BACKGROUND: As multimorbidity becomes common that imposes a considerable burden to patients, but the extent to which widely-used multimorbidity indexes can be applied to quantify disease burden using primary care data in China is not clear. We applied the Chinese Multimorbidity-Weighted Index (CMWI) to health check-ups data routinely collected among older adults by primary care, to examine its validity in measuring multimorbidity associated risks of disability and mortality in annual follow-ups. METHODS: The study utilized data from annual health check-ups of older adults, which included information on individual age, sex, and 14 health conditions at primary care in a district of Guangzhou, Guangdong, China. The risk of CMWI for mortality was analysed in a total sample of 45,009 persons 65 years and older between 2014 and 2020 (average 2.70-year follow-up), and the risk for disability was in a subsample of 18,320 older adults free of physical impairment in 2019 and followed-up in 2020. Risk of death and disability were assessed with Cox proportional hazard regression and binary logistic regression, respectively, with both models adjusted for age and sex variables. The model fit was assessed by the Akaike information criterion (AIC), and C-statistic or the area under the receiver operating characteristic curve (AUC). RESULTS: One unit increase in baseline-CMWI (Median= 1.70, IQR: 1.30-3.00) was associated with higher risk in subsequent disability (OR = 1.12, 95%CI = 1.05,1.20) and mortality (OR = 1.18, 95%CI = 1.14, 1.22). Participants in the top tertile of CMWI had 99% and 152% increased risks of disability and mortality than their counterparts in the bottom tertile. Model fit was satisfied with adequate AUC (0.84) or C-statistic (0.76) for both outcomes. CONCLUSIONS: CMWI, calculated based on primary care's routine health check-ups data, provides valid estimates of disability and mortality risks in older adults. This validated tool can be used to quantity and monitor older patients' health risks in primary care.

Diets of white-headed langurs (Trachypithecus leucocephalus) inhabiting limestone forests: The effects of habitat fragmentation and implication for conservation.

Information about wildlife diets is crucial for comprehending how species adapt to varying environments in fragmented habitats and for developing effective conservation strategies. White-headed langurs (Trachypithecus leucocephalus) are exclusively found in fragmented limestone forests in southwestern China. To investigate the effects of habitat fragmentation on langurs' diets, we collected published dietary data and relevant environmental factors spanning from 1996 to 2021 at two regions with different degrees of fragmentation (Banli > Bapen), from 10 studies (three of Banli and seven of Bapen). The results demonstrated that the diets of white-headed langurs were significantly influenced by environmental factors, including habitat fragmentation, annual rainfall, and mean annual temperature. Food item diversity index was significantly and positively affected by the fragmentation index, the higher fragmentation the langurs suffered, the more diverse food items they consumed. Besides, fruit consumption was negatively influenced by annual rainfall and the consumption of other items was influenced by mean annual temperature. Notably, although there are no significant differences in the feeding proportions of food items or food item diversity indices were observed between the Banli and Bapen groups, the Banli groups extensively consumed ground-supported kudzu (Pueraria montana var. lobata), a plant rarely recorded in the dietary preferences of the Bapen groups, implying that the large plants likely lacking in the fragmented limestone forests. Our findings provide evidence of the major impact of habitat fragmentation on the dietary composition of white-headed langurs, highlighting the need of considering the possibility that the habitats of the white-headed langurs have all undergone extreme fragmentation, inferring the conservation efforts should prioritize protecting native vegetation and reducing human disturbance.

Evolutionary analysis of genes from WOX family and their expression profile in grape (Vitis vinifera) under different stresses.

The WUSCHEL-related homeobox (WOX) transcription factor family plays critical roles in plant growth, development, and stress adaptation, but the biological functions in response to various stress of the WOX gene family have not been extensively researched in grapevine (Vitis vinifera ). In this study, 12 grapevine WOXs were identified from the grapevine genome. Quantitative PCR and microarray expression profiling found that the expression of WOXs had an obvious tissue-specific pattern. Conjoint analysis between various tissues and treated materials indicated VvWUS1 expression is associated with expression of genes from grapevine rupestris stem pitting-associated virus; and VvWOX3 with grapevine fanleaf virus. The gene expression patterns of the WOXs in grape were different under salt stress, with VvWOX8/9 , VvWUS1 , and VvWOX3 responding more strongly to salt stress than control by 18.20-, 9.50-, and 9.19-fold. This study further improves understanding of the evolution and function of the WOX gene family, and offers a theoretical framework and reference for breeding grapevine to better tolerate adversity and permit cultivation of seedlings free of viruses.

Increased oxygen stimulation promotes chemoresistance and phenotype shifting through PLCB1 in gliomas.

Gliomas, the most common CNS (central nerve system) tumors, face poor survival due to severe chemoresistance exacerbated by hypoxia. However, studies on whether altered hypoxic conditions benefit for chemo-sensitivity and how gliomas react to increased oxygen stimulation are limited. In this study, we demonstrated that increased oxygen stimulation promotes glioma growth and chemoresistance. Mechanically, increased oxygen stimulation upregulates miR-1290 levels. miR-1290, in turn, downregulates PLCB1, while PLCB1 facilitates the proteasomal degradation of ß-catenin and active-ß-catenin by increasing the proportion of ubiquitinated ß-catenin in a destruction complex-independent mechanism. This process inhibits PLCB1 expression, leads to the accumulation of active-ß-catenin, boosting Wnt signaling through an independent mechanism and ultimately promoting chemoresistance in glioma cells. Pharmacological inhibition of Wnt by WNT974 could partially inhibit glioma volume growth and prolong the shortened survival caused by increased oxygen stimulation in a glioma-bearing mouse model. Moreover, PLCB1, a key molecule regulated by increased oxygen stimulation, shows promising predictive power in survival analysis and has great potential to be a biomarker for grading and prognosis in glioma patients. These results provide preliminary insights into clinical scenarios associated with altered hypoxic conditions in gliomas, and introduce a novel perspective on the role of the hypoxic microenvironment in glioma progression. Furthermore, the outcomes reveal the potential risks of utilizing hyperbaric oxygen treatment (HBOT) in glioma patients, particularly when considering HBOT as a standalone option to ameliorate neuro-dysfunctions or when combining HBOT with a single chemotherapy agent without radiotherapy.

Reservoir-computing based associative memory and itinerancy for complex dynamical attractors.

Traditional neural network models of associative memories were used to store and retrieve static patterns. We develop reservoir-computing based memories for complex dynamical attractors, under two common recalling scenarios in neuropsychology: location-addressable with an index channel and content-addressable without such a channel. We demonstrate that, for location-addressable retrieval, a single reservoir computing machine can memorize a large number of periodic and chaotic attractors, each retrievable with a specific index value. We articulate control strategies to achieve successful switching among the attractors, unveil the mechanism behind failed switching, and uncover various scaling behaviors between the number of stored attractors and the reservoir network size. For content-addressable retrieval, we exploit multistability with cue signals, where the stored attractors coexist in the high-dimensional phase space of the reservoir network. As the length of the cue signal increases through a critical value, a high success rate can be achieved. The work provides foundational insights into developing long-term memories and itinerancy for complex dynamical patterns.

Early Arthrocentesis for Temporomandibular Joint Arthralgia: A Superiority Trial.

OBJECTIVES: The aim of this superiority trial was to investigate the clinical outcomes of arthrocentesis as an early treatment supported by use of an occlusal splint vs use of an occlusal splint only in the management of temporomandibular joint (TMJ) arthralgia. METHODS: Ninety-five adults presenting with TMJ arthralgia were recruited into the study and randomised into 2 groups: Group 1 received arthrocentesis as an early treatment supported by use of an occlusal splint, whereas group 2 received treatment with an occlusal splint only. Seventy-four patients (group 1: n = 37; group 2: n = 37) completed the 1-year follow-up schedule and were included in the final analysis. Reduction of pain intensity measured by a numeric rating scale and increase in mouth opening distance (unassisted maximal, assisted maximal, and pain-free) was seen in both treatment groups. RESULTS: In group 1, pain intensity significantly decreased at 6 weeks and all subsequent time points compared with group 2. In terms of mouth opening distance, a significant improvement was observed in both groups during the course of treatment, but statistical significance was not seen between the 2 treatment groups. CONCLUSIONS: Early arthrocentesis supported by use of an occlusal splint is superior to use of an occlusal splint alone in the treatment of TMJ arthralgia. Arthrocentesis with occlusal splint support could be discussed as first-line treatment for arthralgia of the TMJ, which may co-occur with various painful and nonpainful conditions of TMJ disorders.

Impact of exogenous melatonin foliar application on physiology and fruit quality of wine grapes (Vitis vinifera) under salt stress.

Soil salinisation is an important abiotic stress faced in grape cultivating, leading to weakened plant vigour and reduced fruit quality. Melatonin as a novel hormone has shown positive exogenous application value. Therefore, this study used wine grape (Vitis vinifera ) 'Pinot Noir' as a test material to investigate the changes of foliar spraying with different concentrations of melatonin on the physiology and fruit quality of wine grapes in a field under simulated salt stress (200mmolL-1 NaCl). The results showed that foliar spraying of melatonin significantly increased the intercellular CO2 concentration, maximum photochemical quantum yield of PSII, relative chlorophyll and ascorbic acid content of the leaves, as well as the single spike weight, 100-grain weight, transverse and longitudinal diameters, malic acid, α-amino nitrogen and ammonia content of fruits, and decreased the initial fluorescence value of leaves, ascorbate peroxidase activity, glutathione content, fruit transverse to longitudinal ratio and tartaric acid content of plants under salt stress. Results of the comprehensive evaluation of the affiliation function indicated that 100µmolL-1 melatonin treatment had the best effect on reducing salt stress in grapes. In summary, melatonin application could enhance the salt tolerance of grapes by improving the photosynthetic capacity of grape plants under salt stress and promoting fruit development and quality formation, and these results provide new insights into the involvement of melatonin in the improvement of salt tolerance in crop, as well as some theoretical basis for the development and industrialisation of stress-resistant cultivation techniques for wine grapes.