Impact on sulfadiazine bio-accessibility in soils through organic diffusive gradients in thin films (o-DGT): Differentiation based on microplastic polymers, aging, and soil properties.

Due to the similar sources of swage irrigation, organic fertilizer, and sludge application, microplastics (MPs) and antibiotics coexist inevitably in the agriculture soils. However, the impacts of MPs with different polymer types and aging status on the bio-accessibility of co-existing antibiotics in soils remained unclear. Therefore, we using the diffusive gradients films for organic compounds devices (o-DGT) to evaluated the distribution of sulfadiazine (SDZ) in both paddy soil and saline soil amended with 0.5 % (w/w) MPs. Four polymer types (polyethylene: PE, polypropylene: PP, polyamide: PA, and polyethylene terephthalate: PET) and two aging statuses (aged PE and aged PP) of MPs were used in this study. Results showed that soil properties significantly influence the partition of SDZ in soil and soil solution, and SDZ gained a lower degradation rate but higher mobility in saline soil. MPs pose different impacts on partition of SDZ between paddy soil and saline soil. Notably, PP reduced the labile solid phase-solution phase partition coefficient (Kdl) by 17.7 % in paddy soil, while PE, PP, and aPE increased the Kdl value by 2.00, 1.62, and 2.81 times in saline soil. Besides, in saline soil, all the MPs reduced the SDZ concentration in the soil solution, while significantly increased the SDZ in o-DGT phase. Conversely, MPs did not impact the SDZ's o-DGT concentration in paddy soil. Additionally, MPs increased the R value of SDZ in two soils, especially in saline soil. It suggested that MPs could potentially enhance the resupply of SDZ from soil to plants, particularly under saline conditions. Furthermore, aged MPs had a more pronounced effect on these indicators compared to virgin MPs in saline soil. Therefore, MPs in soil poses a potential risk for biota's uptake of SDZ, particularly in fragile environment. Moreover, the risk intensifies with aged MPs.

Analysis the molecular similarity of least common amino acid sites in ACE2 receptor to predict the potential susceptible species for SARS-CoV-2.

SARS-CoV-2 infections in animals have been reported globally. However, the understanding of the complete spectrum of animals susceptible to SARS-CoV-2 remains limited. The virus's dynamic nature and its potential to infect a wide range of animals are crucial considerations for a One Health approach that integrates both human and animal health. This study introduces a bioinformatic approach to predict potential susceptibility to SARS-CoV-2 in both domestic and wild animals. By examining genomic sequencing, we establish phylogenetic relationships between the virus and its potential hosts. We focus on the interaction between the SARS-CoV-2 genome sequence and specific regions of the host species' ACE2 receptor. We analyzed and compared ACE2 receptor sequences from 29 species known to be infected, selecting 10 least common amino acid sites (LCAS) from key binding domains based on similarity patterns. Our analysis included 49 species across primates, carnivores, rodents, and artiodactyls, revealing complete consistency in the LCAS and identifying them as potentially susceptible. We employed the LCAS similarity pattern to predict the likelihood of SARS-CoV-2 infection in unexamined species. This method serves as a valuable screening tool for assessing infection risks in domestic and wild animals, aiding in the prevention of disease outbreaks.

Development and validation of a nomogram to predict postoperative delirium in older patients after major abdominal surgery: a retrospective case-control study.

BACKGROUND: Postoperative delirium is a common complication in older patients, with poor long-term outcomes. This study aimed to investigate risk factors and develop a predictive model for postoperative delirium in older patients after major abdominal surgery. METHODS: This study retrospectively recruited 7577 patients aged ≥ 65 years who underwent major abdominal surgery between January 2014 and December 2018 in a single hospital in Beijing, China. Patients were divided into a training cohort (n = 5303) and a validation cohort (n = 2224) for univariate and multivariate logistic regression analyses and to build a nomogram. Data were collected for 43 perioperative variables, including demographics, medical history, preoperative laboratory results, imaging, and anesthesia information. RESULTS: Age, chronic obstructive pulmonary disease, white blood cell count, glucose, total protein, creatinine, emergency surgery, and anesthesia time were associated with postoperative delirium in multivariate analysis. We developed a nomogram based on the above 8 variables. The nomogram achieved areas under the curve of 0.731 and 0.735 for the training and validation cohorts, respectively. The discriminatory ability of the nomogram was further assessed by dividing the cases into three risk groups (low-risk, nomogram score < 175; medium-risk, nomogram score 175~199; high-risk, nomogram score > 199; P < 0.001). Decision curve analysis revealed that the nomogram provided a good net clinical benefit. CONCLUSIONS: We developed a nomogram that could predict postoperative delirium with high accuracy and stability in older patients after major abdominal surgery.

Distinct neural activities of the cortical layer 2/3 across isoflurane anesthesia: A large-scale simultaneous observation of neurons.

Anesthesia inhibits neural activity in the brain, causing patients to lose consciousness and sensation during the surgery. Layers 2/3 of the cortex are important structures for the integration of information and consciousness, which are closely related to normal cognitive function. However, the dynamics of the large-scale population of neurons across multiple regions in layer 2/3 during anesthesia and recovery processes remains unclear. We conducted simultaneous observations and analysis of large-scale calcium signaling dynamics across multiple cortical regions within cortical layer 2/3 during isoflurane anesthesia and recovery in vivo by high-resolution wide-field microscopy. Under isoflurane-induced anesthesia, there is an overall decrease in neuronal activity across multiple regions in the cortical layer 2/3. Notably, some neurons display a paradoxical increase in activity during anesthesia. Additionally, the activity among multiple cortical regions under anesthesia was homogeneous. It is only during the recovery phase that variability emerges in the extent of increased neural activity across different cortical regions. Within the same duration of anesthesia, neural activity did not return to preanesthetic levels. To sum up, anesthesia as a dynamic alteration of brain functional networks, encompassing shifts in patterns of neural activity, homogeneousness among cortical neurons and regions, and changes in functional connectivity. Recovery from anesthesia does not entail a reversal of these effects within the same timeframe.

Deep learning from latent spatiotemporal information of the heart: Identifying advanced bioimaging markers from echocardiograms.

A key strength of echocardiography lies in its integration of comprehensive spatiotemporal cardiac imaging data in real-time, to aid frontline or bedside patient risk stratification and management. Nonetheless, its acquisition, processing, and interpretation are known to all be subject to heterogeneity from its reliance on manual and subjective human tracings, which challenges workflow and protocol standardization and final interpretation accuracy. In the era of advanced computational power, utilization of machine learning algorithms for big data analytics in echocardiography promises reduction in cost, cognitive errors, and intra- and inter-observer variability. Novel spatiotemporal deep learning (DL) models allow the integration of temporal arm information based on unlabeled pixel echocardiographic data for convolution of an adaptive semantic spatiotemporal calibration to construct personalized 4D heart meshes, assess global and regional cardiac function, detect early valve pathology, and differentiate uncommon cardiovascular disorders. Meanwhile, data visualization on spatiotemporal DL prediction models helps extract latent temporal imaging features to develop advanced imaging biomarkers in early disease stages and advance our understanding of pathophysiology to support the development of personalized prevention or treatment strategies. Since portable echocardiograms have been increasingly used as point-of-care imaging tools to aid rural care delivery, the application of these new spatiotemporal DL techniques show the potentials in streamlining echocardiographic acquisition, processing, and data analysis to improve workflow standardization and efficiencies, and provide risk stratification and decision supporting tools in real-time, to prompt the building of new imaging diagnostic networks to enhance rural healthcare engagement.

Spatial distribution, source, and fate of per- and polyfluoroalkyl substances in the surrounding environment of closed and converted fluorochemical factories in Fujian, China.

Following the closure of perfluorooctanesulfonic acid (PFOS) production to comply with the Stockholm Convention regulations or restrictions, manufacturers have shifted to developing short-chain alternatives like perfluorobutane sulfonic acid (PFBS). However, limited research has been conducted to evaluate the impact of this transition on the surrounding environment. This study focused on the spatial distribution, source, and fate of 18 per- and polyfluoroalkyl substances (PFAS) in the surrounding environment of the closure and transformation of two PFAS manufacturing plants in Fujian, China. The total concentrations of PFAS in surface water, sediment, and fish were within the range of 48.9-72,400 ng/L, 0.930-57.6 ng/g dw, and 3.33-1245 ng/g dw, respectively. The predominant compounds were PFBS, PFOS, and perfluorooctanoic acid (PFOA) among the three matrices. Principal component analysis highlighted significant differences in PFAS profiles across different regions of the Futun River, suggesting diverse sources of PFAS. Source apportionment indicated that despite being closed or converted for almost three years, the two factories still significantly impacted the surrounding environment. The shutdown factory mainly released PFAS characterized by perfluoroalkyl sulfonic acids. In contrast, the PFAS were released from conversion plant with the fingerprint being PFBS and perfluoroalkyl carboxylic acids. The conversion of the factories has resulted in the coexistence of long-chain and short-chain PFAS, which has complicated the composition of PFAS in the environment. As sewage treatment plant could not effectively remove PFBS and perfluorobutanoic acid (PFBA) in wastewater, and due to their strong migration ability, these chemicals had a wider impact range, increasing the difficulty of environmental restoration and management. Risk assessment showed that PFAS downstream of the two factories posed high or moderate ecological risks. Specifically, PFBS, PFOS, and PFOA displayed the highest risk quotients and should be paid further attention.

Isolation and Identification of Salinity-Tolerant Rhizobia and Nodulation Phenotype Analysis in Different Soybean Germplasms.

Increasing the soybean-planting area and increasing the soybean yield per unit area are two effective solutions to improve the overall soybean yield. Northeast China has a large saline soil area, and if soybeans could be grown there with the help of isolated saline-tolerant rhizobia, the soybean cultivation area in China could be effectively expanded. In this study, soybeans were planted in soils at different latitudes in China, and four strains of rhizobia were isolated and identified from the soybean nodules. According to the latitudes of the soil-sampling sites from high to low, the four isolated strains were identified as HLNEAU1, HLNEAU2, HLNEAU3, and HLNEAU4. In this study, the isolated strains were identified for their resistances, and their acid and saline tolerances and nitrogen fixation capacities were preliminarily identified. Ten representative soybean germplasm resources in Northeast China were inoculated with these four strains, and the compatibilities of these four rhizobium strains with the soybean germplasm resources were analyzed. All four isolates were able to establish different extents of compatibility with 10 soybean resources. Hefeng 50 had good compatibility with the four isolated strains, while Suinong 14 showed the best compatibility with HLNEAU2. The isolated rhizobacteria could successfully establish symbiosis with the soybeans, but host specificity was also present. This study was a preliminary exploration of the use of salinity-tolerant rhizobacteria to help the soybean nitrogen fixation in saline soils in order to increase the soybean acreage, and it provides a valuable theoretical basis for the application of saline-tolerant rhizobia.

Deep learning from atrioventricular plane displacement in patients with Takotsubo syndrome: lighting up the black-box.

Aims: The spatiotemporal deep convolutional neural network (DCNN) helps reduce echocardiographic readers' erroneous 'judgement calls' on Takotsubo syndrome (TTS). The aim of this study was to improve the interpretability of the spatiotemporal DCNN to discover latent imaging features associated with causative TTS pathophysiology. Methods and results: We applied gradient-weighted class activation mapping analysis to visualize an established spatiotemporal DCNN based on the echocardiographic videos to differentiate TTS (150 patients) from anterior wall ST-segment elevation myocardial infarction (STEMI, 150 patients). Forty-eight human expert readers interpreted the same echocardiographic videos and prioritized the regions of interest on myocardium for the differentiation. Based on visualization results, we completed optical flow measurement, myocardial strain, and Doppler/tissue Doppler echocardiography studies to investigate regional myocardial temporal dynamics and diastology. While human readers' visualization predominantly focused on the apex of the heart in TTS patients, the DCNN temporal arm's saliency visualization was attentive on the base of the heart, particularly at the atrioventricular (AV) plane. Compared with STEMI patients, TTS patients consistently showed weaker peak longitudinal displacement (in pixels) in the basal inferoseptal (systolic: 2.15 ± 1.41 vs. 3.10 ± 1.66, P < 0.001; diastolic: 2.36 ± 1.71 vs. 2.97 ± 1.69, P = 0.004) and basal anterolateral (systolic: 2.70 ± 1.96 vs. 3.44 ± 2.13, P = 0.003; diastolic: 2.73 ± 1.70 vs. 3.45 ± 2.20, P = 0.002) segments, and worse longitudinal myocardial strain in the basal inferoseptal (-8.5 ± 3.8% vs. -9.9 ± 4.1%, P = 0.013) and basal anterolateral (-8.6 ± 4.2% vs. -10.4 ± 4.1%, P = 0.006) segments. Meanwhile, TTS patients showed worse diastolic mechanics than STEMI patients (E'/septal: 5.1 ± 1.2 cm/s vs. 6.3 ± 1.5 cm/s, P < 0.001; S'/septal: 5.8 ± 1.3 cm/s vs. 6.8 ± 1.4 cm/s, P < 0.001; E'/lateral: 6.0 ± 1.4 cm/s vs. 7.9 ± 1.6 cm/s, P < 0.001; S'/lateral: 6.3 ± 1.4 cm/s vs. 7.3 ± 1.5 cm/s, P < 0.001; E/E': 15.5 ± 5.6 vs. 12.5 ± 3.5, P < 0.001). Conclusion: The spatiotemporal DCNN saliency visualization helps identify the pattern of myocardial temporal dynamics and navigates the quantification of regional myocardial mechanics. Reduced AV plane displacement in TTS patients likely correlates with impaired diastolic mechanics.

The Spatial Niche and Influencing Factors of Desert Rodents.

Resource partitioning may allow species coexistence. Sand dunes in the typical steppe of Alxa Desert Inner Mongolia, China, consisting of desert, shrub, and grass habitats, provide an appropriate system for studies of spatial niche partitioning among small mammals. In this study, the spatial niche characteristics of four rodents, Orientallactaga sibirica, Meriones meridianus, Dipus sagitta, and Phodopus roborovskii, and their responses to environmental changes in the Alxa Desert were studied from 2017 to 2021. Using the capture-mark-recapture method, we tested if desert rodents with different biological characteristics and life history strategies under heterogeneous environmental conditions allocate resources in spatial niches to achieve sympatric coexistence. We investigated the influence of environmental factors on the spatial niche breadth of rodents using random forest and redundancy analyses. We observed that the spatial niche overlap between O. sibirica and other rodents is extremely low (overlap index ≤ 0.14). P. roborovskii had the smallest spatial niche breadth. Spatial niche overlap was observed in two distinct species pairs, M. meridianus and D. sagitta, and P. roborovskii and D. sagitta. The Pielou evenness index of rodent communities is closely related to the spatial distribution of rodents, and the concealment of habitats is a key factor affecting the spatial occupation of rodents.

Diagnostic strategy of metagenomic next-generation sequencing for gram negative bacteria in respiratory infections.

OBJECTIVE: This study aims to identify the most effective diagnostic method for distinguishing pathogenic and non-pathogenic Gram-negative bacteria (GNB) in suspected pneumonia cases using metagenomic next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) samples. METHODS: The effectiveness of mNGS was assessed on BALF samples collected from 583 patients, and the results were compared with those from microbiological culture and final clinical diagnosis. Three interpretational approaches were evaluated for diagnostic accuracy. RESULTS: mNGS outperformed culture significantly. Among the interpretational approaches, Clinical Interpretation (CI) demonstrated the best diagnostic performance with a sensitivity of 87.3%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 98.3%. CI's specificity was significantly higher than Simple Interpretation (SI) at 37.9%. Additionally, CI excluded some microorganisms identified as putative pathogens by SI, including Haemophilus parainfluenzae, Haemophilus parahaemolyticus, and Klebsiella aerogenes. CONCLUSION: Proper interpretation of mNGS data is crucial for accurately diagnosing respiratory infections caused by GNB. CI is recommended for this purpose.

Evaluation of therapeutic effect and prognostic value of 18F-FDG PET/CT in different treatment nodes of DLBCL patients.

BACKGROUND: In the present study, we aimed to investigate the role of baseline (B), interim (I) and end-of-treatment (Eot) 18F-FDG PET/CT in assessing the prognosis of diffuse large B cell lymphoma (DLBCL), so as to identify patients who need intensive treatment at an early stage. METHODS: A total of 127 DLBCL patients (62 men; 65 women; median age 62 years) were retrospectively analyzed in this study. Baseline (n = 127), interim (n = 127, after 3-4 cycles) and end-of-treatment (n = 53, after 6-8 cycles) PET/CT images were re-evaluated; semi-quantitative parameters such as maximum standardized uptake value of lesion-to-liver ratio (SUVmax(LLR)) and lesion-to-mediastinum ratio (SUVmax(LMR)), total metabolic tumor volume (TMTV) and total metabolic tumor volume (TLG) were recorded. ΔTLG1 was the change of interim relative to baseline TLG (I to B), ΔTLG2 (Eot to B). ΔSUVmax and ΔTMTV were the same algorithm. The visual Deauville 5-point scale (D-5PS) has been adopted as the major criterion for PET evaluation. Visual analysis (VA) and semi-quantitative parameters were assessed for the ability to predict progression-free survival (PFS) and overall survival (OS) by using Kaplan-Meier method, cox regression and logistic regression analysis. When visual and semi-quantitative analysis are combined, the result is only positive if both are positive. RESULTS: At a median follow-up of 34 months, the median PFS and OS were 20 and 32 months. The survival curve analysis showed that advanced stage and IPI score with poor prognosis, ΔSUVmax(LLR)1 < 89.2%, ΔTMTV1 < 91.8% and ΔTLG1 < 98.8%, ΔSUVmax(LLR)2 < 86.4% were significantly related to the shortening of PFS in patient (p < 0.05). ΔSUVmax(LLR)1 < 83.2% and ΔTLG1 < 97.6% were significantly correlated with the shortening of OS in patients (p < 0.05). Visual analysis showed that incomplete metabolic remission at I-PET and Eot-PET increased the risk of progress and death. In terms of predicting recurrence by I-PET, the combination of visual and semi-quantitative parameters showed higher positive predictive value (PPV) and specificity than a single index. CONCLUSION: Three to four cycles of R-CHOP treatment may be a time point for early prediction of early recurrence/refractory (R/R) patients and active preemptive treatment. Combined visual analysis with semi-quantitative parameters of 18F-FDG PET/CT at interim can improve prognostic accuracy and may allow for more precise screening of patients requiring early intensive therapy.

Regulating Cholesterol in Tumorigenesis: A Novel Paradigm for Tumor Nanotherapeutics.

During the past decade, "membrane lipid therapy", which involves the regulation of the structure and function of tumor cell plasma membranes, has emerged as a new strategy for cancer treatment. Cholesterol is an important component of the tumor plasma membrane and serves an essential role in tumor initiation and progression. This review elucidates the role of cholesterol in tumorigenesis (including tumor cell proliferation, invasion/metastasis, drug resistance, and immunosuppressive microenvironment) and elaborates on the potential therapeutic targets for tumor treatment by regulating cholesterol. More meaningfully, this review provides an overview of cholesterol-integrated membrane lipid nanotherapeutics for cancer therapy through cholesterol regulation. These strategies include cholesterol biosynthesis interference, cholesterol uptake disruption, cholesterol metabolism regulation, cholesterol depletion, and cholesterol-based combination treatments. In summary, this review demonstrates the tumor nanotherapeutics based on cholesterol regulation, which will provide a reference for the further development of "membrane lipid therapy" for tumors.

Effects of overgrazing on the functional diversity of rodents in desert areas.

Environmental stressors and disturbances can cause changes in an ecosystem's community structure, which can be reflected in its functional diversity. As grazing intensity increases, this causes changes in the environment that inevitably lead to changes in the community structure, which can especially affect rodents due to their sensitivity to the environment. The effects of grazing prohibition and overgrazing on the functional diversity of desert rodent communities in Alxa were studied in April, July, and October of 2018-2020. The trap-day method was used to study rodent communities in disturbed habitats. Five functional traits were selected and quantified: nutrition, life history, physiology, morphology, and activity rhythm. The results showed that: (1) The species composition of rodent communities in the Alxa Desert in spring and autumn was significantly correlated with the functional traits of the hibernation, reproductive cycle, and feeding habits. The species composition in the summer was only significantly correlated with the functional traits of reproductive cycle and diet. (2) The effects of overgrazing on the functional diversity of rodents in desert areas have significant temporal and spatial characteristics. (3) In spring and summer, overgrazing made the Functional Richness index of the rodent community lower than that of areas where grazing is prohibited, but the Functional Evenness index was higher than that of grazing-prohibition areas. In autumn, overgrazing increased the Functional Richness index of the rodent community and decreased the Functional Evenness index. The Functional Divergence index was higher in overgrazing areas than in grazing-prohibited ones. These results suggest that, in spring and summer, overgrazing reduced the ecological space utilization ability of rodent communities; however, the impact on the degree of utilization of community resources is more comprehensive. In autumn, overgrazing increases the ability of rodent communities to use ecological space but reduces resource efficiency. Overgrazing makes the niche differentiation of rodent communities higher, the degree of overlap lower, and the competition between species weaker. Therefore, overgrazing will affect the functional diversity of the community through the utilization of ecological space, resource utilization, interspecific competition, and niche.

Excellent Polymerized Ionic-Liquid-Based Gel Polymer Electrolytes Enabled by Molecular Structure Design and Anion-Derived Interfacial Layer.

Polymerized ionic liquid (PIL)-based gel polymer electrolytes (GPEs) are well known as highly safe and stable electrolytes but with low ambient ionic conductivity. Herein, we first designed and synthesized an IL monomer with a long and flexible side chain and then mixed it with LiTFSI and MEMPTFSI to construct a PIL-based GPE (denoted as GM-GPE). The special molecular structure of the monomer greatly improves the ionic transport through the PIL chain, and the introduction of MEMPTFSI plasticizer further improves the ionic conductivity, promoting a TFSI--anion-derived SEI formation to suppress Li dendrite growth and forming an electrostatic shielding effect of MEMP+ cations to promote the uniform deposition of Li+. Consequently, the as-prepared GM-GPE exhibits high ambient ionic conductivity (4.3 × 10-4 S cm-1, 30 °C), robust electrochemical stability, excellent thermal stability, nonflammability, and superior ability to inhibit Li dendrite growth. The resultant LiFePO4|GM-GPE|Li cell exhibits a high discharge capacity of 150 mA h g-1 at 0.2 C along with a good cycling stability and rate capability. This work brings about new guidance for the development of high-quality GPEs with high ionic conductivity, high stability, and safety for long cycling and dendrite-free lithium metal batteries.

Gut microbiota and cognitive performance: A bidirectional two-sample Mendelian randomization.

PURPOSE: Previous studies have suggested a potential association between gut microbiota and neurological and psychiatric disorders. However, the causal relationship between gut microbiota and cognitive performance remains uncertain. METHODS: A two-sample Mendelian randomization (MR) study used SNPs linked to gut microbiota (n = 18,340) and cognitive performance (n = 257,841) from recent GWAS data. Inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were employed. Heterogeneity was assessed via Cochran's Q test for IVW. Results were shown with funnel plots. Outliers were detected through leave-one-out method. MR-PRESSO and MR-Egger intercept tests were conducted to address horizontal pleiotropy influence. LIMITATIONS: Limited to European populations, generic level, and potential confounding factors. RESULTS: IVW analysis revealed detrimental effects on cognitive perfmance associated with the presence of genus Blautia (P = 0.013, 0.966[0.940-0.993]), Catenibacterium (P = 0.035, 0.977[0.956-0.998]), Oxalobacter (P = 0.043, 0.979[0.960-0.999]). Roseburia (P < 0.001, 0.935[0.906-0.965]), in particular, remained strongly negatively associated with cognitive performance after Bonferroni correction. Conversely, families including Bacteroidaceae (P = 0.043, 1.040[1.001-1.081]), Rikenellaceae (P = 0.047, 1.026[1.000-1.053]), along with genera including Paraprevotella (P = 0.044, 1.020[1.001-1.039]), Ruminococcus torques group (P = 0.016, 1.062[1.011-1.115]), Bacteroides (P = 0.043, 1.040[1.001-1.081]), Dialister (P = 0.027, 1.039[1.004-1.074]), Paraprevotella (P = 0.044, 1.020[1.001-1.039]) and Ruminococcaceae UCG003 (P = 0.007, 1.040[1.011-1.070]) had a protective effect on cognitive performance. CONCLUSIONS: Our results suggest that interventions targeting specific gut microbiota may offer a promising avenue for improving cognitive function in diseased populations. The practical application of these findings has the potential to enhance cognitive performance, thereby improving overall quality of life.

Metformin-grafted polycaprolactone nanoscaffold targeting sensory nerve controlled fibroblasts reprograming to alleviate epidural fibrosis.

Epidural fibrosis (EF), associated with various biological factors, is still a major troublesome clinical problem after laminectomy. In the present study, we initially demonstrate that sensory nerves can attenuate fibrogenic progression in EF animal models via the secretion of calcitonin gene-related peptide (CGRP), suggesting a new potential therapeutic target. Further studies showed that CGRP could inhibit the reprograming activation of fibroblasts through PI3K/AKT signal pathway. We subsequently identified metformin (MET), the most widely prescribed medication for obesity-associated type 2 diabetes, as a potent stimulator of sensory neurons to release more CGRP via activating CREB signal way. We copolymerized MET with innovative polycaprolactone (PCL) nanofibers to develop a metformin-grafted PCL nanoscaffold (METG-PCLN), which could ensure stable long-term drug release and serve as favorable physical barriers. In vivo results demonstrated that local implantation of METG-PCLN could penetrate into dorsal root ganglion cells (DRGs) to promote the CGRP synthesis, thus continuously inhibit the fibroblast activation and EF progress for 8 weeks after laminectomy, significantly better than conventional drug loading method. In conclusion, this study reveals the unprecedented potential of sensory neurons to counteract EF through CGRP signaling and introduces a novel strategy employing METG-PCLN to obstruct EF by fine-tuning sensory nerve-regulated fibrogenesis.

Practice Patterns of Spatially Fractionated Radiation Therapy: A Clinical Practice Survey.

Purpose: Spatially fractionated radiation therapy (SFRT) is increasingly used for bulky advanced tumors, but specifics of clinical SFRT practice remain elusive. This study aimed to determine practice patterns of GRID and Lattice radiation therapy (LRT)-based SFRT. Methods and Materials: A survey was designed to identify radiation oncologists' practice patterns of patient selection for SFRT, dosing/planning, dosimetric parameter use, SFRT platforms/techniques, combinations of SFRT with conventional external beam radiation therapy (cERT) and multimodality therapies, and physicists' technical implementation, delivery, and quality procedures. Data were summarized using descriptive statistics. Group comparisons were analyzed with permutation tests. Results: The majority of practicing radiation oncologists (United States, 100%; global, 72.7%) considered SFRT an accepted standard-of-care radiation therapy option for bulky/advanced tumors. Treatment of metastases/recurrences and nonmetastatic primary tumors, predominantly head and neck, lung cancer and sarcoma, was commonly practiced. In palliative SFRT, regimens of 15 to 18 Gy/1 fraction predominated (51.3%), and in curative-intent treatment of nonmetastatic tumors, 15 Gy/1 fraction (28.0%) and fractionated SFRT (24.0%) were most common. SFRT was combined with cERT commonly but not always in palliative (78.6%) and curative-intent (85.7%) treatment. SFRT-cERT time sequencing and cERT dose adjustments were variable. In curative-intent treatment, concurrent chemotherapy and immunotherapy were found acceptable by 54.5% and 28.6%, respectively. Use of SFRT dosimetric parameters was highly variable and differed between GRID and LRT. SFRT heterogeneity dosimetric parameters were more commonly used (P = .008) and more commonly thought to influence local control (peak dose, P = .008) in LRT than in GRID therapy. Conclusions: SFRT has already evolved as a clinical practice pattern for advanced/bulky tumors. Major treatment approaches are consistent and follow the literature, but SFRT-cERT combination/sequencing and clinical utilization of dosimetric parameters are variable. These areas may benefit from targeted education and standardization, and knowledge gaps may be filled by incorporating identified inconsistencies into future clinical research.

Would future climate warming cause zoonotic diseases to spread over long distances?

Dipus sagitta is a major rodent found in arid environments and desert areas. They feed on plant seeds, young branches and some small insects, and have hibernating habits. Peak Dipus sagitta numbers impact the construction of the plant community in the environment, but also have a human impact as these rodents carry a variety of parasitic fleas capable of spreading serious diseases to humans. Based on 216 present distribution records of Dipus sagitta and seven environmental variables, this article simulates the potential distribution of Dipus sagitta during the Last Glacial Maximum, the mid-Holocene, the present and the future (2070s, RCP4.5, RCP8.5). This study also analyzes the geographic changes of the population distribution and evaluates the importance of climate factors by integrating contribution rate, replacement importance value and the jackknife test using the MaxEnt model. In this study, we opted to assess the predictive capabilities of our model using the receiver operating characteristic (ROC) and partial receiver operating characteristic (pROC) metrics. The findings indicate that the AUC value exceeds 0.9 and the AUC ratio is greater than 1, indicating superior predictive performance by the model. The results showed that the main climatic factors affecting the distribution of the three-toed jerboa were precipitation in the coldest quarter, temperature seasonality (standard deviation), and mean annual temperature. Under the two warming scenarios of the mid-Holocene and the future, there were differences in the changes in the distribution area of the three-toed jerboa. During the mid-Holocene, the suitable distribution area of the three-toed jerboa expanded, with a 93.91% increase in the rate of change compared to the Last Glacial Maximum. The size of the three-toed jerboa's habitat decreases under both future climate scenarios. Compared to the current period, under the RCP4.5 emission scenario, the change rate is -2.96%, and under the RCP8.5 emission scenario, the change rate is -7.41%. This indicates a trend of contraction in the south and expansion in the north. It is important to assess changes in the geographic population of Dipus sagitta due to climate change to formulate population control strategies of these harmful rodents and to prevent and control the long-distance transmission of zoonotic diseases.

Effects of Freeze-Drying Processes on the Acoustic Absorption Performance of Sustainable Cellulose Nanocrystal Aerogels.

Cellulose aerogels have great prospects for noise reduction applications due to their sustainable value and superior 3D interconnected porous structures. The drying principle is a crucial factor in the preparation process for developing high-performance aerogels, particularly with respect to achieving high acoustic absorption properties. In this study, multifunctional cellulose nanocrystal (CNC) aerogels were conveniently prepared using two distinct freeze-drying principles: refrigerator conventional freezing (RCF) and liquid nitrogen unidirectional freezing (LnUF). The results indicate that the rapid RCF process resulted in a denser CNC aerogel structure with disordered larger pores, causing a stronger compressive performance (Young's modulus of 40 kPa). On the contrary, the LnUF process constructed ordered structures of CNC aerogels with a lower bulk density (0.03 g/cm3) and smaller apertures, resulting in better thermal stability, higher diffuse reflection across visible light, and especially increased acoustic absorption performance at low-mid frequencies (600-3000 Hz). Moreover, the dissipation mechanism of sound energy in the fabricated CNC aerogels is predicted by a designed porous media model. This work not only paves the way for optimizing the performance of aerogels through structure control, but also provides a new perspective for developing sustainable and efficient acoustic absorptive materials for a wide range of applications.