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Abstract Objective The present study aimed to identify various distinguishing features for use in the accurate classification of stereoelectroencephalography (SEEG) channels based on high‐frequency oscillations (HFOs) inside and outside the epileptogenic zone (EZ). Methods HFOs were detected in patients with focal epilepsy who underwent SEEG. Subsequently, HFOs within the seizure‐onset and early spread zones were defined as pathological HFOs, whereas others were defined as physiological. Three features of HFOs were identified at the channel level, namely, morphological repetition, rhythmicity, and phase–amplitude coupling (PAC). A machine‐learning (ML) classifier was then built to distinguish two HFO types at the channel level by application of the above‐mentioned features, and the contributions were quantified. Further verification of the characteristics and classifier performance was performed in relation to various conscious states, imaging results, EZ location, and surgical outcomes. Results Thirty‐five patients were included in this study, from whom 166 104 pathological HFOs in 255 channels and 53 374 physiological HFOs in 282 channels were entered into the analysis pipeline. The results revealed that the morphological repetitions of pathological HFOs were markedly higher than those of the physiological HFOs; this was also observed for rhythmicity and PAC. The classifier exhibited high accuracy in differentiating between the two forms of HFOs, as indicated by an area under the curve (AUC) of 0.89. Both PAC and rhythmicity contributed significantly to this distinction. The subgroup analyses supported these findings. Significance The suggested HFO features can accurately distinguish between pathological and physiological channels substantially improving its usefulness in clinical localization. Plain Language Summary In this study, we computed three quantitative features associated with HFOs in each SEEG channel and then constructed a machine learning‐based classifier for the classification of pathological and physiological channels. The classifier performed well in distinguishing the two channel types under different levels of consciousness as well as in terms of imaging results, EZ location, and patient surgical outcomes.

Objective Although the advantages of postoperative braces have been verified in many fields, it is not clear whether postoperative braces can help reduce patients' adverse psychological emotions such as kinesiophobia, anxiety, and depression. This study aims to analyze whether the use of a postoperative brace helps reduce adverse psychological emotions in adolescent idiopathic scoliosis (AIS) patients undergoing spinal deformity surgeries. Methods All consecutive patients who underwent spinal corrective surgeries at our institution between April 2023 and July 2023 formed the prospective cohort. Outcome measures were collected in the preoperative period, 3 months after surgery, and 6 months after surgery. All patients were assessed using the Tampa scale for kinesiophobia (TSK), the hospital anxiety and depression scale (HADS), and the numerical rating scale (NRS). A statistical model of propensity score matching was used to eliminate potential selection bias and maintain comparability. Multivariate linear regression models were used to determine the relationship between postoperative brace and adverse psychological emotions. Results After propensity score matching, this study ultimately enrolled 150 patients. There were no significant differences between the two groups in terms of demographic and perioperative variables. The fully adjusted model showed that the TSK scores of the non‐brace group at the 3‐month (ꞵ = 2.50, 95% CI 0.80–4.20, p = 0.005) and 6‐month follow‐up (ꞵ = 2.75, 95% CI 0.75–4.74, p = 0.007) were significantly higher than those of the brace group. The HADS score of the non‐brace group at the 3‐month follow‐up was significantly higher than that of the brace group (ꞵ = 1.75, 95% CI 0.28–3.22, p = 0.019). The NRS score of the non‐brace group at the 3‐month follow‐up was significantly higher than that of the brace group (ꞵ = 0.69, 95% CI 0.05–1.33, p = 0.034). At the 6‐month follow‐up, there were no significant difference for HADS score or NRS score between the two groups. Conclusion In the early postoperative period, the postoperative brace could provide AIS patients with psychological supports and help them reduce the frequency of adverse psychological emotions. The postoperative brace could continuously improve the fear of movement within 6 months after surgery, and help reduce anxiety, depression, and pain within 3 months after surgery.

Objective The orthopedic surgical treatment strategies for patients with tumor‐induced osteomalacia (TIO) require improvement, especially for patients where the causative tumors are located in surgically challenging areas, requiring a greater degree of in‐depth investigation. This work aims to summarize and investigate clinical features and orthopedic surgical treatment effects of patients with tumor‐induced osteomalacia (TIO), whose causative tumors are located in the hip bones. Methods A retrospective analysis was conducted on the clinical data of all patients diagnosed with culprit tumors located in the hip bones who underwent surgical treatment at the orthopedic bone and soft tissue tumor sub‐professional group of Peking Union Medical College Hospital from January 2013 to January 2023. This retrospective study summarized the clinical data, preoperative laboratory test results, imaging findings, surgery‐related data, perioperative changes in blood phosphorus levels, and postoperative follow‐up data of all patients who met the inclusion criteria. Normally distributed data are presented as mean and standard deviation, while non‐normally distributed data are shown as the means and 25th and 75th interquartile ranges. Results The clinical diagnostic criteria for TIO were met by all 16 patients, as confirmed by pathology after surgery. Among the 16 patients, we obtained varying degrees of bone pain and limited mobility (16/16), often accompanied by difficulties in sitting up, walking, and fatigue. An estimated 62.5% (10/16) of patients had significantly shorter heights during the disease stages. All 16 patients underwent surgical treatment for tumors in the hip bones, totaling 21 surgeries. In the pathogenic tumor, there were 16 cases of skeletal involvement and none of pure soft tissue involvement. Out of the 16 patients, 13 cases had a gradual increase in blood phosphorus levels following the latest orthopedic surgery, which was followed up for 12 months to 10 years. Due to unresolved conditions after the original surgery, four patients received reoperation intervention. Two cases of refractory TIO did not improve in their disease course. Conclusion In summary, the location of the causative tumor in the hip bone is hidden and diverse, and there is no defined orthopedic surgical intervention method for this case in clinical practice. For patients with TIO where the tumors are located in the hip bones, surgical treatment is difficult and the risk of postoperative recurrence is high. Careful identification of the tumor edge using precise preoperative positioning and qualitative diagnosis is crucial to ensure adequate boundaries for surgical resection to reduce the likelihood of disease recurrence and improve prognosis.

Abstract Small extracellular vesicles (sEV) derived from diverse natural killer (NK) cell lines have proven their exceptional antitumor activities. However, sEV from human primary NK cells, especially memory-like NK cells, are rarely utilized for cancer treatment. In this study, we obtained sEV from IL-12, IL-15 and IL-18 cultured human memory-like NK cells (mNK-sEV) that showed strong cytokine-secretory ability. It was uncovered that mNK-sEV entered cancer cells via macropinocytosis and induced cell apoptosis via caspase-dependent pathway. Compared to sEV from conventionally cultured NK cells (conNK-sEV), mNK-sEV inhibited tumor growth to a greater extent. Concomitantly, pharmacokinetics and biodistribution results validated a higher accumulation of mNK-sEV than conNK-sEV in tumors of xenografted murine models. Notably, elevated containment of granulysin (GNLY) within mNK-sEV, at least in part, may contribute to the enhanced therapeutic effect. Herein our results present that mNK-sEV can be a novel class of therapeutic reagent for effective cancer treatment. Graphical Abstract

Abstract While numerous single nucleotide variants and small indels have been identified in Parkinson’s disease (PD), the contribution of structural variants (SVs), copy number variants (CNVs), and short tandem repeats (STRs) remains poorly understood. Here we investigated the association using the high-depth whole-genome sequencing data from 466 Chinese PD patients and 513 controls. Totally, we identified 29,561 SVs, 32,153 CNVs, and 174,905 STRs, and found that CNV deletions were significantly enriched in the end-proportion of autosomal chromosomes in PD. After genome-wide association analysis and replication in an external cohort of 352 cases and 547 controls, we validated that the 1.6 kb-deletion neighboring MUC19, 12.4kb-deletion near RXFP1 and GGGAAA repeats in SLC2A13 were significantly associated with PD. Moreover, the MUC19 deletion and the SLC2A13 5-copy repeat reduced the penetrance of the LRRK2 G2385R variant. Moreover, genes with these variants were dosage-sensitive. These data provided novel insights into the genetic architecture of PD.

Background: Cold damage of maize during germination is a global problem; it occurs frequently in northeast China, and leads to a large-scale reduction in yield. Low temperature tolerance of maize in germination is a complex quantitative trait controlled by multigenes, and no major QTLs or key genes have been identified. Results: An F2 isolation population with S319 and R144 as parents was constructed. The bulked segregant analysis (BSA) and specific-locus amplified fragment-sequencing (SLAF-seq) methods were applied to locate the chromosomal association regions related to low-temperature tolerance of maize during germination. Sequencing obtained 221.72 Gbp clean data, with an average sequencing depth of 25.96X. Four candidate regions associated with low-temperature tolerance trait of maize in germination were obtained, with a total length of 25.71 Mb and 1513 annotated genes, including 456 nonsynonymous mutant genes and 111 frameshift mutant genes. Conclusions: This study aimed to lay the foundation for the mining of candidate genes of low-temperature tolerance in maize during germination, and accelerate the process of targeted improvement of maize low-temperature tolerance molecular marker-assisted breeding.How to cite: Yu T, Zhang J, Cao J, et al. QTL analysis of low temperature tolerance in maize germination by SLAF-seq and BSA technique. Electron J Biotechnol 2024;70. https://doi.org/10.1016/j.ejbt.2024.04.003.

Abstract In carbonate reservoirs characterized by the fracture‐cavity system as storage spaces, the drilling process is highly prone to the loss of drilling fluid. This not only affects drilling efficiency but can also lead to severe accidents, such as blowouts. Therefore, it is crucial to understand the distribution pattern of these fractures. However, the formation of carbonate rock fracture‐cavity system systems, being controlled by various factors, is difficult to precisely identify. This limitation hampers the efficient development of such types of oil and gas fields. This paper presents a case study of the M55 sub‐section carbonate gas reservoir in the Sulige gasfield, proposing an improved You Only Look Once v5s (YOLOv5s) deep learning algorithm. It utilizes enhanced training with conventional logging data to identify response characteristics of fractures in the carbonate reservoirs. And its identification results have been confirmed to be accurate by various fracture data obtained through different means, such as the core samples, cast thin section photographs, imaging logging data, and seismic attributes. This method incorporates the Ghost convolution module to replace the Conv module in the backbone network of the YOLOv5s model, and modifies the C3 module into a Ghost Bottleneck module, effectively making the model more lightweight. Additionally, a Convolutional Block Attention Module is integrated into the Neck network, enhancing the model's feature extraction capabilities. Finally, the method employs the Efficient Intersection over Union Loss function instead of the Complete Intersection over Union Loss, reducing the network's regression loss. The validation results using actual data demonstrate that this method achieves an average recognition accuracy of 87.3% for the fracture‐cavity system, which is a 3% improvement over the baseline model (YOLOv5s). This enhancement is beneficial for precisely locating the drilling fluid loss positions in carbonate reservoirs.

Olea dioica Roxb, 1820 is a very important ethnomedicinal tree because of its medicinal properties and it belongs to the Oleaceae family. It is mainly distributed in evergreen and semi-evergreen forests. However, the chloroplast genome of O. dioica has not yet been reported. In this study, the chloroplast genome sequence of O. dioica was sequenced using next-generation sequencing technologies. The complete chloroplast genome of O. dioica was 155,138 bp in length (GenBank accession no. PP048999), comprising a large single-copy (LSC) region of 86,048 bp, a small single-copy (SSC) region of 17,816 bp, and two inverted repeat (IR) regions 25,637 bp each. The overall GC content was 37.8%. The complete chloroplast genome of O. dioica contains 131 complete genes, which are 88 protein-coding genes, 35 transfer RNA genes, and eight ribosomal RNA genes. A maximum-likelihood (ML) tree of O. dioica and 14 other species in the family Oleaceae suggested that O. dioica showed a close relationship with Olea brachiata.

Abstract The development and aging of the brain constitute a lifelong dynamic process, marked by structural and functional changes that entail highly coordinated cellular differentiation and epigenetic regulatory mechanisms. Chromatin accessibility serves as the foundational basis for genetic activity. However, the holistic and dynamic chromatin landscape that spans various brain regions throughout development and ageing remains predominantly unexplored. In this study, we employed single-nucleus ATAC-seq to generate comprehensive chromatin accessibility maps, incorporating data from 69,178 cells obtained from four distinct brain regions – namely, the olfactory bulb (OB), cerebellum (CB), prefrontal cortex (PFC), and hippocampus (HP) – across key developmental time points at 7 P, 3 M, 12 M, and 18 M. We delineated the distribution of cell types across different age stages and brain regions, providing insight into chromatin accessible regions and key transcription factors specific to different cell types. Our data contribute to understanding the epigenetic basis of the formation of different brain regions, providing a dynamic landscape and comprehensive resource for revealing gene regulatory programs during brain development and aging.

Abstract Approximately 90% of Parkinson’s patients (PD) suffer from dysarthria. However, there is currently a lack of research on acoustic measurements and speech impairment patterns among Mandarin-speaking individuals with PD. This study aims to assess the diagnosis and disease monitoring possibility in Mandarin-speaking PD patients through the recommended speech paradigm for non-tonal languages, and to explore the anatomical and functional substrates. We examined total of 160 native Mandarin-speaking Chinese participants consisting of 80 PD patients, 40 healthy controls (HC), and 40 MRI controls. We screened the optimal acoustic metric combination for PD diagnosis. Finally, we used the objective metrics to predict the patient’s motor status using the Naïve Bayes model and analyzed the correlations between cortical thickness, subcortical volumes, functional connectivity, and network properties. Comprehensive acoustic screening based on prosodic, articulation, and phonation abnormalities allows differentiation between HC and PD with an area under the curve of 0.931. Patients with slowed reading exhibited atrophy of the fusiform gyrus (FDR p = 0.010, R = 0.391), reduced functional connectivity between the fusiform gyrus and motor cortex, and increased nodal local efficiency (NLE) and nodal efficiency (NE) in bilateral pallidum. Patients with prolonged pauses demonstrated atrophy in the left hippocampus, along with decreased NLE and NE. The acoustic assessment in Mandarin proves effective in diagnosis and disease monitoring for Mandarin-speaking PD patients, generalizing standardized acoustic guidelines beyond non-tonal languages. The speech impairment in Mandarin-speaking PD patients not only involves motor aspects of speech but also encompasses the cognitive processes underlying language generation.

Abstract Mine water inrush is a serious threat to mine safety production. It is very important to identify water inrush source types quickly to prevent and control water damage. In this study, the aqueous chemical components Na+ + K+, Ca2+, Mg2+, Cl−, SO4 2− and HCO3− of different aquifers in Pingdingshan coalfield were selected as the characteristic values, and the Surface water, Quaternary pore water, Carboniferous limestone karst water, Permian sandstone water, and Cambrian limestone karst water were used as the labels. An intelligent water source discrimination model is proposed by combining data mining, classification models, and reinforcement learning. As outlier data in the samples may interfere with the model recognition ability, the data distribution range was analyzed using box plots, and 20 groups of abnormal samples were excluded. The processed water chemistry data were divided into 80% learning samples and 20% test samples, and the learning samples were fed into a light gradient boosting machine (LightGBM) for training. The tree-structured parson estimator (TPE) obtains the optimal values of the main parameters of LightGBM in a very short time. Substituting the hyperparameters back into the model yields a 13.9% improvement in the accuracy of the model, proving the effectiveness of the TPE algorithm. To further validate the performance of the model, TPE-LightGBM is compared and analyzed with a Random Search-Multi Layer Perceptron Machine (RS-MLP) and Genetic Algorithm-Extreme Gradient Boosting Tree (GA-SVM). The accuracy of TPE-LightGBM, RS-MLP, and GA-SVM is 0.931, 0.759, 0.724 in that order, and the generalization error RMSE is 0.415, 1.05, and 1.313 in that order. The results show that TPE-LightGBM is more advantageous in water source identification and is more resistant to overfitting. By calculating and comparing the information gain of each variable, the contribution of Ca2+ is the highest, so it is necessary to pay attention to the change in Ca2+ concentration. TPE-LightGBM’s high accuracy and generalization ability have a good prospect for the identification of sudden water source types.

Abstract Background Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. Methods This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). Conclusions DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

Abstract Background The Ehlers-Danlos syndromes (EDS) are a group of rare hereditary connective tissue disorders. EDS is clinically and genetically heterogeneous and usually involves multiple systems. There are 14 subtypes of EDS with hallmark features including joint hypermobility, skin hyperextensibility, and tissue fragility. The clinical manifestations and their severity differ among the subtypes, encompassing recurrent joint dislocations, scoliosis, arterial aneurysm and dissection, and organ rupture. Challenges in diagnosis and management arise from the complexity of the disease, which is further complicated by its rarity. The development of clinical guidelines and implementation of coordinated multi-disciplinary team (MDT) approaches have emerged as global priorities. Main body Chinese Multi-Disciplinary Working Group on the Ehlers-Danlos Syndromes was therefore established. Healthcare professionals were recruited from 25 top hospitals across China. The experts are specialized in 24 fields, including genetics, vascular surgery, dermatology, and orthopedics, as well as nursing care, rehabilitation, psychology, and nutrition. Based on GRADE methodology, the Guidelines were written by the Group supervised by methodologists, following a systemic review of all 4453 articles in PubMed published before August 9, 2023, using the search term “Ehlers Danlos”. A coordinated MDT approach for the diagnosis and management of EDS is highly recommended by the Group, along with 29 specific recommendations addressing key clinical questions. In addition to the treatment plan, the Guidelines also emphasize integrating support from nursing care, rehabilitation, psychology, and nutrition. This integration not only facilitates recovery in hospital settings, but most importantly, the transition from an illness-defined life to a more “normalized” life. Conclusion The first guidelines on EDS will shorten the diagnostic odyssey and solve the unmet medical needs of the patients. This article is a synopsis of the full guidelines.

Abstract Sleep disturbances profoundly affect the quality of life in individuals with neurological disorders. Closed-loop deep brain stimulation (DBS) holds promise for alleviating sleep symptoms, however, this technique necessitates automated sleep stage decoding from intracranial signals. We leveraged overnight data from 121 patients with movement disorders (Parkinson’s disease, Essential Tremor, Dystonia, Essential Tremor, Huntington’s disease, and Tourette’s syndrome) in whom synchronized polysomnograms and basal ganglia local field potentials were recorded, to develop a generalized, multi-class, sleep specific decoder – BGOOSE. This generalized model achieved 85% average accuracy across patients and across disease conditions, even in the presence of recordings from different basal ganglia targets. Furthermore, we also investigated the role of electrocorticography on decoding performances and proposed an optimal decoding map, which was shown to facilitate channel selection for optimal model performances. BGOOSE emerges as a powerful tool for generalized sleep decoding, offering exciting potentials for the precision stimulation delivery of DBS and better management of sleep disturbances in movement disorders.

Abstract Background The role of isocitrate dehydrogenase (IDH) mutation status for glioma stratification and prognosis is established. While structural magnetic resonance image (MRI) is a promising biomarker, it may not be sufficient for non-invasive characterisation of IDH mutation status. We investigated the diagnostic value of combined diffusion tensor imaging (DTI) and structural MRI enhanced by a deep radiomics approach based on convolutional neural networks (CNNs) and support vector machine (SVM), to determine the IDH mutation status in Central Nervous System World Health Organization (CNS WHO) grade 2–4 gliomas. Methods This retrospective study analyzed the DTI-derived fractional anisotropy (FA) and mean diffusivity (MD) images and structural images including fluid attenuated inversion recovery (FLAIR), non-enhanced T1-, and T2-weighted images of 206 treatment-naïve gliomas, including 146 IDH mutant and 60 IDH-wildtype ones. The lesions were manually segmented by experienced neuroradiologists and the masks were applied to the FA and MD maps. Deep radiomics features were extracted from each subject by applying a pre-trained CNN and statistical description. An SVM classifier was applied to predict IDH status using imaging features in combination with demographic data. Results We comparatively assessed the CNN-SVM classifier performance in predicting IDH mutation status using standalone and combined structural and DTI-based imaging features. Combined imaging features surpassed stand-alone modalities for the prediction of IDH mutation status [area under the curve (AUC) = 0.846; sensitivity = 0.925; and specificity = 0.567]. Importantly, optimal model performance was noted following the addition of demographic data (patients’ age) to structural and DTI imaging features [area under the curve (AUC) = 0.847; sensitivity = 0.911; and specificity = 0.617]. Conclusions Imaging features derived from DTI-based FA and MD maps combined with structural MRI, have superior diagnostic value to that provided by standalone structural or DTI sequences. In combination with demographic information, this CNN-SVM model offers a further enhanced non-invasive prediction of IDH mutation status in gliomas.

In order to improve the production of coalbed methane vertical wells in the central and northern Zhengzhuang block, southern Qinshui Basin, Shanxi, China, this paper analyzes the reasons for the poor stimulation effect of medium-deep coalbed methane vertical wells, based on the ground stress test data and fracturing monitoring data of these evaluation wells in the study area, proposes targeted stimulation techniques, designs and carries out field comparative pilot studies and analyzes their results. The results show that there are three main reasons for the low production of these vertical wells in the study area. Firstly, the vertical fracture is dominant, resulting in the shorter length of hydraulic fractures. With the increase of burial depth, the length and width of fractures decreases at the same fracturing scale. Secondly, with the increase of burial depth, the embedment depth of proppants into coal rock increases and the closure of hydraulic fractures speeds up. As a result, the stable production time is short, and the main form of gas production curve is “single peak” type. Thirdly, after the initial fracturing, the coal body structure is much more broken, and new fractures are easy to enter the initial fractures, which increases the difficulty of creating new fractures, resulting in poor stimulation effect. In view of the above reasons, the paper proposes an innovative technology of pre-plug, large-scale and remote-support re-fracturing. Pre-plug means that relatively low displacement, sand ratio and scale are first used to fill initial fractures, and then large-scale re-fracturing is carried out to create new fractures. Large-scale fracturing refers to the fracturing with large displacement, large fluid volume and high sand ratio. In order to improve the stimulation effect of middle-deep reservoirs, the fracturing fluid volume is increased from 600−800 m3 to more than 1 300−2 000 m3, the displacement is increased from 6−8 m3/min to more than 10−14 m3/min, and a low viscosity fracturing fluid system combined with low density proppants is used to increase the sand ratio from 7%−8% to more than 10%−15%. Remote-support is a combination of self-suspended proppants and large displacement to increase proppants migration distance and increase the proportion of the propped fractures. The average daily production of a single well reached 1 380 m3, which was 1 190 m3 higher than that before, and nearly 1 000 m3 higher than the stable gas production of adjacent wells, realizing the production breakthrough of vertical wells in the low-production area of the middle-deep reservoir in the north of Zhengzhuang block. Results of the comparative pilot studies showed that the average net construction pressure increased by 3.3 MPa after pre-plug, compared with the initial fracturing, which means that new fractures were formed and resulted in the production increase by 1 000 m3 compared with that of the wells without the Pre-plug. The pilot results show that, in general, the larger the technical parameters of pre-plug, large-scale and remote-support re-fracturing, the better the production performance.

Abstract Purpose The purpose of the study was to describe a novel growth guidance system, which can avoid metal debris and reduce the sliding friction forces, and test the durability and glidability of the system by in vitro test. Method Two major modifications were made to the traditional Shilla system, including the use of ultra-high molecular weight polyethylene (UHMWPE) gaskets to avoid direct contact between the screw and rod, and polishing the surface of the sliding part of the rod. We tested the durability of the system by a fatigue test, which the samples were test on the MTS system for a 10 million cycle of a constant displacement. Pre and post-testing involved weighing the UHMWPE gaskets and observing the wear conditions. The sliding ability were measured by a sliding displacement test. The maximum sliding displacement of the system was measured after a 300 cycles of dynamic compressive loads in a sinusoidal waveform. Results After the fatigue test, all the UHMWPE gaskets samples showed some of the fretting on the edge of the inner sides, but its still isolated and avoided the friction between the screws and rods. There was no production of metallic fretting around the sliding screws and rods. The average wear mass of the UHMWPE gaskets was 0.002 ± 0.001 g, less than 1.7% of the original mass. In the sliding test, the novel growth guidance system demonstrated the best sliding ability, with an average maximum sliding distance(AMSD) of 35.75 ± 5.73 mm, significantly better than the group of the traditional Shilla technique(AMSD 3.65 ± 0.46 mm, P

Abstract As a new technology to mitigate the high outburst risk of the low permeability coal seam, it is essential to delve deeper into the law and mechanism of pressure relief associated with the diamond beaded rope saw slotting. The paper presents a numerical calculation model under small size that is based on the superimposed beam theory and the contact surface model. The model is compared with the experimental results of similar models in the laboratory to verify its applicability for simulating the numerical calculation of stress distribution in coal seam cut by diamond beaded rope saw. The study then goes on to investigate the influence of coal seam inclination, working face length, coal seam hardness, and seam advancing distance on the pressure relief effect of diamond beaded rope saw cutting seam under engineering scale. The mechanism of the diamond beaded rope saw cutting seam is also analyzed. The results indicate that the diamond beaded rope saw effectively reduces pressure in low permeability coal seams, with the impact range extending to the slit area. Additionally, stress concentration was observed at the front of the slit. Increasing the inclination of the coal seam, working face length, and advancing distance of the cutting seam enhances the pressure relief effect of the diamond beaded rope saw. The latter two factors’ influence is reflected in the direction along the working face and the direction of mining advance, respectively. The efficacy of pressure relief through this particular method is comparatively better in soft coal than in hard coal. This research is significant in promoting the widespread application of diamond beaded rope saws in the pressure relief of coal seam cutting.

Abstract Background As an endemic shrub of the Qinghai-Tibetan Plateau (QTP), the distribution of Hippophae tibetana Schlecht. ranges between 2800 and 5200 m above sea level. As the most basal branch of the Hippophae genus, H. tibetana has an extensive evolutionary history. The H. tibetana is a valuable tree for studying the ecological evolution of species under extreme conditions. Results Here, we generated a high-quality chromosome-level genome of H. tibetana. The total size of the assembly genome is 917 Mb. The phylogenomic analysis of 1064 single-copy genes showed a divergence between 3.4 and 12.8 Mya for H. tibetana. Multiple gene families associated with DNA repair and disease resistance were significantly expanded in H. tibetana. We also identified many genes related to DNA repair with signs of positive selection. These results showed expansion and positive selection likely play important roles in H. tibetana’s adaptation to comprehensive extreme environments in the QTP. A comprehensive genomic and transcriptomic analysis identified 49 genes involved in the flavonoid biosynthesis pathway in H. tibetana. We generated transgenic sea buckthorn hairy root producing high levels of flavonoid. Conclusions Taken together, this H. tibetana high-quality genome provides insights into the plant adaptation mechanisms of plant under extreme environments and lay foundation for the functional genomic research and molecular breeding of H. tibetana.

Abstract Subthalamic nucleus deep brain stimulation (STN-DBS) has the potential to delay Parkinson’s disease (PD) progression. Whether oxidative stress participates in the neuroprotective effects of DBS and related signaling pathways remains unknown. To address this, we applied STN-DBS to mice and monkey models of PD and collected brain tissue to evaluate mitophagy, oxidative stress, and related pathway. To confirm findings in animal experiments, a cohort of PD patients was recruited and oxidative stress was evaluated in cerebrospinal fluid. When PD mice received STN stimulation, the mTOR pathway was suppressed, accompanied by elevated LC3 II expression, increased mitophagosomes, and a decrease in p62 expression. The increase in mitophagy and balance of mitochondrial fission/fusion dynamics in the substantia nigra caused a marked enhancement of the antioxidant enzymes superoxide dismutase and glutathione levels. Subsequently, fewer mitochondrial apoptogenic factors were released to the cytoplasm, which resulted in a suppression of caspase activation and reservation of dopaminergic neurons. While interfaced with an mTOR activator, oxidative stress was no longer regulated by STN-DBS, with no neuroprotective effect. Similar results to those found in the rodent experiments were obtained in monkeys treated with chronic STN stimulation. Moreover, antioxidant enzymes in PD patients were increased after the operation, however, there was no relation between changes in antioxidant enzymes and motor impairment. Collectively, our study found that STN-DBS was able to increase mitophagy via an mTOR-dependent pathway, and oxidative stress was suppressed due to removal of damaged mitochondria, which was attributed to the dopaminergic neuroprotection of STN-DBS in PD.

Abstract Methylation of the promoters of SHOX2 and RASSF1A (LungMe®) exhibits promise as a potential molecular biomarker for diagnosing lung cancer. This study sought to assess the aberrant methylation of SHOX2 and RASSF1A in broncho-exfoliated cells (BEC) and compare it with conventional cytology, histology examination, immunohistochemistry, and serum tumor markers to evaluate the overall diagnostic efficiency for lung cancer. This study recruited 240 patients, including 185 malignant cases and 55 benign cases. In our observation, we noted a slight reduction in the detection sensitivity, however, the ΔCt method exhibited a significant enhancement in specificity when compared to Ct judgment. Consequently, the ΔCt method proves to be a more appropriate approach for interpreting methylation results. The diagnostic sensitivity of cytology and histology was in ranged from 20.0%-35.1% and 42.9%-80%, respectively, while the positive detection rate of LungMe® methylation ranged from 70.0% to 100%. Additionally, our findings indicate a higher prevalence of SHOX2( +) among patients exhibiting medium and high expression of Ki67 (P

Abstract Background Aeromonas hydrophila infections can cause gastrointestinal symptoms such as diarrhea; however, deep infections are rarely reported. Outbreaks of A. hydrophila are reported more frequently in fish, poultry, and snakes than in humans. This study aimed to track clonal relatedness of deep infections caused by A. hydrophila using whole genome sequencing (WGS). Methods We collected three isolates of A. hydrophila in July 19 to August 29, 2019, from patients that underwent spine surgery. Accurate species identification was performed using whole-genome average nucleotide identity (ANI). Antimicrobial susceptibility testing was performed using a VITEK 2 automated AST-N334 Gram-negative susceptibility card system. Antimicrobial resistance and virulence genes were identified using the Comprehensive Antibiotic Resistance Database and Virulence Factor Database VFanalyzer. Results All three isolates were identified as A. hydrophila based on ANI and multilocus sequence typing analysis revealed that A. hydrophila belonged to a novel sequence type (ST1172). All three isolates were susceptible to amikacin and levofloxacin; however, they were resistant to piperacillin/tazobactam, ceftriaxone, cefuroxime, cefoxitin, and imipenem. Isolate 19W05620 (patient 3) showed increased ceftazidime resistance (minimum inhibitory concentration ≥ 64 µg/mL). All three isolates possessed the same chromosomally encoded β-lactamases, including bla OXA-724 (β-lactamase), imiH (metallo-β-lactamase), and bla MOX-13 (AmpC) in plasmids. Conclusions Our study validated the transmission of a novel carbapenem-resistant A. hydrophila sequence type (ST1172) in patients that underwent spine surgery. Control measures should be developed to prevent dissemination of A. hydrophila in the hospital setting.

Background: The glycolytic pathway and immune response play pivotal roles in the intervertebral disc degeneration (IDD) progression. This study aimed to develop a glycolysis-related diagnostic model and analyze its relationship with the immune response to IDD. Methods: GSE70362, GSE23130, and GSE15227 datasets were collected and merged from the Gene Expression Omnibus, and differential expression analysis was performed. Glycolysis-related differentially expressed genes (GLRDEGs) were identified, and a machine learning-based diagnostic model was constructed and validated, followed by Gene Set Enrichment Analysis (GSEA). Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed, and mRNA-miRNA and mRNA-transcription factor (TF) interaction networks were constructed. Immune infiltration was analyzed using single-sample GSEA (ssGSEA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm between high- and low-risk groups. Results: In the combined dataset, samples from 31 patients with IDD and 55 normal controls were analyzed, revealing differential expression of 16 GLRDEGs between the two groups. Using advanced machine learning techniques (LASSO, support vector machine, and random forest algorithms), we identified eight common GLRDEGs (PXK, EIF3D, WSB1, ZNF185, IGFBP3, CKAP4, RPL15, and, SSR1) and developed a diagnostic model, which demonstrated high accuracy in distinguishing IDD from control samples (area under the curve, 0.935). We identified 42 mRNA-miRNA and 33 mRNA-TF interaction pairs. Using the RiskScore from the diagnostic model, the combined dataset was stratified into high- and low-risk groups. SsGSEA revealed significant differences in the infiltration abundances of the four immune cell types between the groups. The CIBERSORT algorithm revealed the strongest correlation between resting natural killer (NK) cells and ZNF185 in the low-risk group and between CD8+ T cells and SSR1 in the high-risk group. Conclusions: Our study reveals a potential interplay between glycolysis-associated genes and immune infiltration in IDD pathogenesis. These findings contribute to our understanding of IDD and may guide development of novel diagnostic markers and therapeutic interventions.

ABSTRACT Understanding changes in the distribution patterns and diversity of soil microbial communities from the perspectives of age-related changes, seasonal variations, and the interaction between the two factors can facilitate the management of plantations. In Chinese fir plantations, we collected soils from different depths in over-mature forests, mature forests, near-mature forests, middle-aged forests, and young forests in summer, autumn, and winter in China’s subtropical regions. As the forests developed, bacterial and fungal communities’ diversity changed, reached a minimum value at near-mature forests, and then increased in mature forests or over-mature forests. Near-mature forests had the lowest topological properties. The Shannon index of microbial communities varied with seasonal changes (P < 0.05). Bacterial and fungal community composition at genus level was more closely related to temperature indicators (including daily average temperature, daily maximum temperature, and daily minimum temperature) (P < 0.01, 0.5554 < R2 0.05, 0.0321 < R2

Disulfidptosis, a newly discovered mode of cell death caused by excessive accumulation of intracellular disulfide compounds, is closely associated with tumor development. This study focused on the relationship between disulfidptosis and clear cell renal cell carcinoma (ccRCC). Firstly, the characterizations of disulfidptosis-related genes (DRGs) in ccRCC were showed, which included number variation (CNV), single nucleotide variation (SNV), DNA methylation, mRNA expression and gene mutation. Then, the ccRCC samples were classified into three clusters through unsupervised clustering based on DRGs. Survival and pathway enrichment differences were evaluated among the three clusters. Subsequently, the differentially expressed genes (DEGs) among the three clusters were screened by univariate Cox, LASSO, and multivariate Cox analysis, and five key DEGs were obtained. Based on the five key DEGs, the ccRCC samples were reclassified into two geneclusters and the survival differences and immune cell infiltration between two geneclusters was investigated. In next step, ccRCC samples were divided into two groups according to PCA scores of five key DEGs, namely high PCA score group (HPSG) and low PCA score group (LPSG). On this basis, differences in survival prognosis, immune cell infiltration and correlation with immune checkpoint, as well as differences in sensitivity to targeted drugs were compared between HPSG and LPSG. The expression levels of four immune checkpoints were higher in HPSG than in LPSG, whereas the LPSG was more sensitive to targeted drug therapy than the HPSG. Finally, validation experiments on HDAC4 indicated that HDAC4 could increase the proliferation and colony formation ability of ccRCC cells.

Biomass and carbon allocation among plant organs are influenced by the individual tree's development and climate conditions. Chinese fir forests play an important role in the carbon cycle and climate change mitigation in China. Understanding how forest age, tree size, and climate factors affect biomass and carbon allocation in Chinese fir forests is crucial to fully utilize the carbon sequestration potential. We analyzed the response of Chinese fir biomass allocation fractions (BAFs) and carbon stock allocation fractions (CAFs) to forest age, tree size, and climate factors, utilizing field survey data on biomass of 93 trees in Fujian, Sichuan, Guangxi, and Jiangxi provinces and carbon storage of 40 trees in Fujian, Sichuan, and Guangxi provinces in China. Our results showed that BAFs depend on individual development. In young and middle-aged forests, BAFs were unaffected by diameter at breast height (DBH), whereas branch and root biomass fractions displayed a significant positive correlation with DBH, and stem biomass fraction displayed a negative correlation with DBH in mature forests. Carbon concentration exhibited substantial variation among distinct components and regions. Overall, the carbon concentration of each organ ranked as Guangxi > Sichuan > Fujian. BAFs of dominant trees are almost independent of climatic factors, while suppressed trees will alter their strategies for biomass allocation in response to climate change. Stem biomass fraction exhibited a significant positive correlation with maximum growing season temperature, mean summer temperature, and maximum summer temperature, whereas leaf biomass fraction showed the opposite trend. Under future climate warming, Chinese fir will allocate more biomass to the stem, at the expense of leaf biomass. These findings support the idea that biomass allocation patterns serve as adaptive patterns to address fluctuations in internal and external conditions. The interaction between climate factors and tree size shows promise for predicting trends in forest biomass and carbon accumulation in the context of future climate change.

Abstract Congenital vertebral malformation, affecting 0.13–0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.

Abstract Acute lung injury (ALI) is a complex disease with numerous causes. This review begins with a discussion of disease development from direct or indirect pulmonary insults, as well as varied pathogenesis. The heterogeneous nature of ALI is then elaborated upon, including its epidemiology, clinical manifestations, potential biomarkers, and genetic contributions. Although no medication is currently approved for this devastating illness, supportive care and pharmacological intervention for ALI treatment are summarized, followed by an assessment of the pathophysiological gap between human ALI and animal models. Lastly, current research progress on advanced nanomedicines for ALI therapeutics in preclinical and clinical settings is reviewed, demonstrating new opportunities towards developing an effective treatment for ALI.

The high energy coordination compounds Cu(TZCA)2(ClO4)2 (ECCs-1) was prepared by 1H-tetrazole-5-carbohydrazide (TZCA) with a high energy skeleton and a strong coordination ability group. At the same time, the reaction activity of the ligand was explored, and the single crystal structure of it and intermediate were obtained. The structures of all substances were characterized by IR and EA. And the structure and composition of ECCs-1 are confirmed by ESP, AC, SEM and ICP-OES. Physical and chemical properties tests show that ECCs-1 has an acceptable thermal stability (Td = 177°C) and extremely sensitive mechanical stimulation (IS = 1 J, FS = 5 N). The comprehensive performance test results show that ECCs-1 has excellent initiation ability. In addition, the decomposition mechanism of ECCs-1 is explored from two aspects of experiment and theoretical calculation.

Abstract The carbonate rock formations have obvious dual media characteristics, fracture development and good physical conditions, which are the main seepage channels and storage spaces for gas after the reconstruction of underground gas storage. The carbonate strata of the Ordovician system are important natural gas reservoirs in the eastern area of Sulige Gas Field in the Ordos Basin, and the identification and characterization of their fractures are of great significance for the modeling of fractures in the later stage and the improvement of the operation scheme of the gas storage. At present, there is little research on fractures, which restricts exploration and development. Therefore, taking the 39–61 gas storage reservoir in the eastern area of Sulige Gas Field in the Ordos Basin as the research object, this paper identifies and studies the characteristics of the fractures by core, microscopic, conventional logging curves, and imaging logging identification. The results show that the fracture length ranges from 5 to 15 cm and the width ranges from 0.1 to 3 mm. The fracture angles are mostly between 75° and 90° and the main direction is NW–SE. In conventional logging curves, porosity logging has a good response to fractures, while resistivity logging has a general response to fractures; In layers with more developed fractures, natural gamma values are mostly higher than 40API, rock volume density is less than 2.8 g/cm3, neutron porosity is greater than 12.5%, and acoustic time difference is greater than 160 μ s/m. This study is of great significance for improving the identification of carbonate fractures, enriching the relevant theories, and providing guidance for the construction of carbonate gas storage.

In the process of deep mining, the geological type of the mine is complicated. Under the condition of “three heights and one disturbance”, it is easy to cause coal and gas outburst and other coal and rock dynamic disasters near the hidden structure. In order to clarify the mechanism of dynamic disasters induced by hidden structures, taking No.8 Mine in Pingdingshan as the engineering background, the stress-strain evolution characteristics and disaster causing law of normal and reverse faults in different mining directions and their simultaneous existence are studied by numerical simulation, and the influence of different hidden structures on driving face is analyzed. The results show that when driving encounters a single fault, the stress-strain is concentrated in front of the work and inside the fault. Normal faults are more likely to produce stress concentration, and the range of stress concentration is larger. At the same driving distance, the principal strain of the reverse fault is slightly larger than that of the normal fault. With the driving distance increases, when the driving distance increases to 15 m, the stress-strain concentration area gradually coincides, and finally a stress-strain superposition area is formed in the fault area. When driving encounters multiple faults, the stress is concentrated on the structural coal in front of the working face and between the two faults. The superimposed stress-strain distribution is different in the case of normal-reverse faults and reverse-normal faults. In the case of normal-reverse faults, the superimposed stress-strain is mainly distributed near the normal faults. In the case of reverse-normal faults, the stress-strain in structural coal between the two faults also increases significantly. Near the multiple hidden structures dominated by reverse faults and reverse faults, the increase rate of strain energy is larger, which is more conducive to the accumulation of strain energy, and the risk of coal and gas outburst increases. Under the combined action of mining stress, fault structural stress and static stress in the coal rock mass, coal and gas outburst and other coal and rock dynamic disasters are eventually triggered. Multiple hidden structures are more likely to produce stress concentration than single structures, and the risk of coal and rock dynamic disaster increases.

Dynamic orthoses have a significant effect on the treatment of elbow capsular contracture. Because of the lack of quantitative research on traction forces, determining the appropriate traction force to help stretch soft tissues and maintain the joint's range of motion is a challenge in the rehabilitation process. We developed a human elbow finite element (FE) model incorporating the activity behavior of the muscles and considering different capsular contracture locations, including total, anterior and posterior capsular contractures, to analyze the internal biomechanical responses of different capsular contracture models during flexion (30 to 80 degrees). Traction loads of 10, 20, 30 and 40 N were applied to the ulna and radius at the maximum flexion angle (80 degrees) to explore the appropriate traction loads at week 4 after a joint capsule injury. We observed a significant increase in posterior capsule stress with anterior capsular contracture (ACC), and the maximum peak stress was 1.3 times higher than that in the healthy model. During the fourth week after elbow capsule injury, the appropriate traction forces for total capsule contracture (TCC), ACC and posterior capsule contracture (PCC) were 20, 10 and 20 N, respectively; these forces maintained a stable biomechanical environment for the elbow joint and achieved a soft tissue pulling effect, thus increasing elbow mobility. The results can be used as a quantitative guide for the rehabilitation physicians to determine the traction load for a specific patient.

Objective To compare the radiological outcomes in Lenke 5C type patients whose lowest instrumented vertebra (LIV) was L3 or L4 in a case-match study. Methods We conducted a retrospective case-match study and included 82 patients in the study. Radiological results before surgery, after surgery, and at last follow-up were recorded and analyzed in the L3 and L4 groups. Results After matching the age, Risser’s sign, sex, and main Cobb, 41 pairs of patients were enrolled in our study. The total fusion segments in the L3 group (median [interquartile range]: 5.0 [6.0–5.0]) were shorter than those in the L4 group (6.0 [6.5–6.0]). The main curve was significantly corrected after surgery in both groups, and was comparable at the last follow-up between groups. In addition, according to the results of Fisher precision probability test, there was no significant difference of coronal or sagittal imbalance between the 2 groups at the 2-year follow-up. Conclusion The correction in coronal and sagittal planes in L3 group and L4 group remains similar. On account of more motion segments, L3 could be an ideal choice as LIV in moderate Lenke 5C type AIS. Long-term follow-up is needed to evaluate the effect of larger compensatory lumbar-sacral curve when stopping at L3.

Background: Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) and subthalamic nucleus (STN) is employed for the treatment of dystonia. Pallidal low-frequency oscillations have been proposed as a pathophysiological marker for dystonia. However, the role of subthalamic oscillations and STN-GPi coupling in relation to dystonia remains unclear. Objective: We aimed to explore oscillatory activities within the STN-GPi circuit and their correlation with the severity of dystonia and efficacy achieved by DBS treatment. Methods: Local field potentials were recorded simultaneously from the STN and GPi from 13 dystonia patients. Spectral power analysis was conducted for selected frequency bands from both nuclei, while power correlation and the weighted phase lag index were used to evaluate power and phase couplings between these two nuclei, respectively. These features were incorporated into generalized linear models to assess their associations with dystonia severity and DBS efficacy. Results: The results revealed that pallidal theta power, subthalamic beta power and subthalamic-pallidal theta phase coupling and beta power coupling all correlated with clinical severity. The model incorporating all selected features predicts empirical clinical scores and DBS-induced improvements, whereas the model relying solely on pallidal theta power failed to demonstrate significant correlations. Conclusions: Beyond pallidal theta power, subthalamic beta power, STN-GPi couplings in theta and beta bands, play a crucial role in understanding the pathophysiological mechanism of dystonia and developing optimal strategies for DBS.

BackgroundHereditary neurodevelopmental disorders (NDDs) are prevalent in poorly prognostic pediatric diseases, but the pathogenesis of NDDs is still unclear. Irregular myelination could be one of the possible causes of NDDs.Case presentationHere, whole exome sequencing was carried out for a consanguineous Pakistani family with NDDs to identify disease-associated variants. The co-segregation of candidate variants in the family was validated using Sanger sequencing. The potential impact of the gene on NDDs has been supported by conservation analysis, protein prediction, and expression analysis. A novel homozygous variant DOP1A(NM_001385863.1):c.2561A>G was identified. It was concluded that the missense variant might affect the protein-protein binding sites of the critical MEC interaction region of DOP1A, and DOP1A-MON2 may cause stability deficits in Golgi-endosome protein traffic. Proteolipid protein (PLP) and myelin-associate glycoprotein (MAG) could be targets of the DOP1A-MON2 Golgi-endosome traffic complex, especially during the fetal stage and the early developmental stages. This further supports the perspective that disorganized myelinogenesis due to congenital DOP1A deficiency might cause neurodevelopmental disorders (NDDs).ConclusionOur case study revealed the potential pathway of myelinogenesis-relevant NDDs and identified DOP1A as a potential NDDs-relevant gene in humans.

PurposeThis study aimed to investigate the factors associated with pathologic node-negativity (ypN0) in patients who received neoadjuvant chemotherapy (NAC) to develop and validate an accurate prediction nomogram.MethodsThe CSBrS-012 study (2010–2020) included female patients with primary breast cancer treated with NAC followed by breast and axillary surgery in 20 hospitals across China. In the present study, 7,711 eligible patients were included, comprising 6,428 patients in the primary cohort from 15 hospitals and 1,283 patients in the external validation cohort from five hospitals. The hospitals were randomly assigned. The primary cohort was randomized at a 3:1 ratio and divided into a training set and an internal validation set. Univariate and multivariate logistic regression analyses were performed on the training set, after which a nomogram was constructed and validated both internally and externally.ResultsIn total, 3,560 patients (46.2%) achieved ypN0, and 1,558 patients (20.3%) achieved pathologic complete response in the breast (bpCR). A nomogram was constructed based on the clinical nodal stage before NAC (cN), ER, PR, HER2, Ki67, NAC treatment cycle, and bpCR, which were independently associated with ypN0. The area under the receiver operating characteristic curve (AUC) for the training set was 0.80. The internal and external validation demonstrated good discrimination, with AUCs of 0.79 and 0.76, respectively.ConclusionWe present a real-world study based on nationwide large-sample data that can be used to effectively screen for ypN0 to provide better advice for the management of residual axillary disease in breast cancer patients undergoing NAC.

Chitin is the second most abundant natural polysaccharide after cellulose, the lower molecular weight oligomers of its alkaline deacetylation product, chitooligosaccharides (COS), have a wide range of biological activities and important application prospects in the food, pharmaceutical and other industries. COS can be produced by physical, chemical, or enzymatic methods, each with its own advantages and disadvantages. The biological activities of COS are influenced by their physicochemical properties, but the mechanisms of are incompletely understood. Thus, this review discusses the synthesis of COS, biological activities such as antimicrobial activity, antioxidant activity, hypocholesterolemic activity and enhancement of calcium absorption and their mechanisms in the context of different molecular weights and degree of polymerization, as well as their applications in the food industry. Finally, the need of comprehensive characterization of COS and elucidation of its molecular mechanisms were highlighted, to further promote the commercialization and application of COS in the food industry.

Temporal interference (TI) stimulation, a novel non-invasive stimulation strategy, has recently been shown to modulate neural activity in deep brain regions of living mice. Yet, it is uncertain if this method is applicable to larger brains and whether the electric field produced under traditional safety currents can penetrate deep regions as observed in mice. Despite recent model-based simulation studies offering positive evidence at both macro- and micro-scale levels, the absence of electrophysiological data from actual brains hinders comprehensive understanding and potential application of TI. This study aims to directly measure the spatiotemporal properties of the interfered electric field in the rhesus monkey brain and to validate the effects of TI on the human brain. Two monkeys were involved in the measurement, with implantation of several stereo-electroencephalography (SEEG) depth electrodes. TI stimulation was applied to anesthetized monkeys using two pairs of surface electrodes at differing stimulation parameters. Model-based simulations were also conducted and subsequently compared with actual recordings. Additionally, TI stimulation was administered to patients with motor disorders to validate its effects on motor symptoms.Through the integration of computational electric field simulation with empirical measurements, it was determined that the temporally interfering electric fields in the deep central regions are capable of attaining a magnitude sufficient to induce a subthreshold modulation effect on neural signals. Additionally, an improvement in movement disorders was observed as a result of TI stimulation. This study is the first to systematically measure the TI electric field in living non-human primates, offering empirical evidence that TI holds promise as a more focal and precise method for modulating neural activities in deep regions of a large brain. This advancement paves the way for future applications of TI in treating neuropsychiatric disorders.

BackgroundPreeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors.MethodsWe retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24–45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher’s exact test and Mann–Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors.ResultsBy using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively.ConclusionIncorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.

Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is very rare, with about 1000 reported cases globally. Removing most TIO culprit tumors requires the evaluation and intervention of orthopedic doctors. However, orthopedic doctors often have a poor understanding of the optical treatment of TIO due to its rarity. In addition, most TIO patients lack specific clinical manifestations. Also, the clinical localization and qualitative diagnosis of TIO are difficult and thus can easily be misdiagnosed and mistreated. Furthermore, the true incidence rate of TIO may be underestimated. Although many breakthroughs have been made in exploring the pathogenesis, clinical diagnosis, and treatment of TIO, rational and standardized orthopedic surgical treatment experience summary and sorting for TIO patients are lacking. In this article, the recent experience and progress in the field of orthopedic surgical treatment for TIO globally have been summarized, providing a theoretical basis and new clinical practice guidance for the rational treatment of TIO patients.

Whole-crop wheat (Triticum aestivum, WCW) has a high nutritional value and digestibility. No-tillage (NT) can reduces energy and labor inputs in the agricultural production process, thus decreasing production costs. There are many studies on planting techniques of WCW at present, few being on no-tillage planting. This study aimed to compare the effects of different tillage methods and maturity stages on the yield, nutritive value, and silage fermentation quality of WCW. The experiment included two tillage methods (NT; conventional tillage, CT), two maturity stages (flowering stage; milk stage), and three years (2016-2017; 2017-2018; 2018-2019). Years had a strong influence on the yield and nutritional composition of WCW. This was mainly related to the amount of rainfall, as it affects the seedling emergence rate of wheat. Although tillage methods showed no significant effects on the yield, plant height, and stem number per plant of WCW (P > 0.05), compared to CT, the dry matter (DM) and crude protein (CP) yields of NT decreased by 0.74 t/ha and 0.13 t/ha. Tillage methods showed no significant effects on the nutritive composition of WCW (P > 0.05). The WCW at the milk stage had greater DM (5.25 t/ha) and CP (0.60 t/ha) yields than that at the flowering stage (3.19 t/ha and 0.39 t/ha) (P< 0.05). The acid detergent fiber concentration of WCW decreased by 34.5% from the flowering to the milk stage, whereas water-soluble carbohydrates concentration increased by 50.6%. The CP concentration at the milk stage was lower than that at the flowering stage (P< 0.05). The lactic acid concentration of NT (17.1 g/kg DM) silage was lower than that of CT (26.6 g/kg DM) silage (P< 0.05). The WCW silage at the milk stage had a lower NH3-N concentration (125 g/kg TN) than that at the flowering stage (169 g/kg TN) (P< 0.05). Wheat sown by NT and CT was of similar yield and nutritional value, irrespective of harvest stages. WCW harvested at the milk stage had greater yield and better nutritional composition and silage fermentation quality than that at the flowering stage. Based upon the results of the membership function analysis, no-tillage sowing of wheat was feasible and harvesting at milk stage was recommended.

Background: Globus pallidus internus (GPi) and subthalamic nucleus (STN) are two common deep brain stimulation (DBS) targets. This meta-analysis was to compared the efficacy and safety of these two DBS targets for the treatment of Meige syndrome (MS). Methods: A systematic search was performed using EMBASE, MEDLINE, the Cochrane Library, and ClinicalTrials.gov to identify DBS trials for MS. Review Manager 5.3 was used to perform meta-analysis and the mean difference (MD) was analyzed and calculated with a random effect model. Pearson's correlation coefficients and meta-regression analyses were utilized to identify relevant predictive markers. Results: Twenty trials involving 188 participants with GPi-DBS and 110 individuals with STN-DBS were eligible. Both groups showed improvement of the Burke-Fahn-Marsden Dystonia Rating Scale-Movement (BFMDRS-M) and Disability (BFMDRS-D) scores (BFMDRS-M: MD = 10.57 [7.74–13.41] for GPi-DBS, and MD = 8.59 [4.08–13.11] for STN-DBS; BFMDRS-D: MD = 5.96 [3.15–8.77] for GPi-DBS, and MD = 4.71 [1.38–8.04] for STN-DBS; all P