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Abstract Background Current research lacks comprehensive investigation into the biomechanical changes in the spinal cord and nerve roots during scoliosis correction. This study employs finite element analysis to extensively explore these biomechanical variations across different Cobb angles, providing valuable insights for clinical treatment. Methods A personalized finite element model, incorporating vertebrae, ligaments, spinal cord, and nerve roots, was constructed using engineering software. Forces and displacements were applied to achieve Cobb angle improvements, designating T1/2-T4/5 as the upper segment, T5/6-T8/9 as the middle segment, and T9/10-L1/2 as the lower segment. Simulations under traction, pushing, and traction + torsion conditions were conducted, and biomechanical changes in each spinal cord segment and nerve roots were analyzed. Results Throughout the scoliosis correction process, the middle spinal cord segment consistently exhibited a risk of injury under various conditions and displacements. The lower spinal cord segment showed no significant injury changes under traction + torsion conditions. In the early correction phase, the upper spinal cord segment demonstrated a risk of injury under all conditions, and the lower spinal cord segment presented a risk of injury under pushing conditions. Traction conditions posed a risk of nerve injury on both sides in the middle and lower segments. Under pushing conditions, there was a risk of nerve injury on both sides in all segments. Traction + torsion conditions implicated a risk of injury to the right nerves in the upper segment, both sides in the middle segment, and the left side in the lower segment. In the later correction stage, there was a risk of injury to the upper spinal cord segment under traction + torsion conditions, the left nerves in the middle segment under traction conditions, and the right nerves in the upper segment under pushing conditions. Conclusion When the correction rate reaches 61–68%, particular attention should be given to the upper-mid spinal cord. Pushing conditions also warrant attention to the lower spinal cord and the nerve roots on both sides of the main thoracic curve. Traction conditions require attention to nerve roots bilaterally in the middle and lower segments, while traction combined with torsion conditions necessitate focus on the right-side nerve roots in the upper segment, both sides in the middle segment, and the left-side nerve roots in the lower segment.

Abstract The chloroplast genomes of wild loquat can help to determine their place in the history of evolution. Here, we sequenced and assembled two novel wild loquat’s chloroplast genomes, one is Eriobotrya elliptica, and the other is an unidentified wild loquat, which we named “YN-1”. Their sizes are 159,471 bp and 159,399 bp, respectively. We also assembled a cultivated loquat named ‘JFZ’, its chloroplast genome size is 159,156 bp. A comparative study was conducted with six distinct species of loquats, including five wild loquats and one cultivated loquat. The results showed that both E. elliptica and “YN-1” have 127 genes, one gene more than E. fragrans, which is psbK. Regions trnF-GAA-ndhJ, petG-trnP-UGG, and rpl32-trnL-UAG were found to exhibit high variability. It was discovered that there was a positive selection on rpl22 and rps12. RNA editing analysis found several chilling stress-specific RNA editing sites, especially in rpl2 gene. Phylogenetic analysis results showed that “YN-1” is closely related to E. elliptica, E. obovata and E. henryi.

BackgroundDilated cardiomyopathy (DCM) is a cardiac disease with a poor prognosis of unclear etiology. Previous studies have shown that metabolism is associated with DCM. This study investigates the causal relationship between 1400 metabolites and DCM using a two-sample Mendelian randomization (MR) approach.MethodsThe study utilized data from the OpenGWAS database, comprising 355,381 Europeans, including 1,444 DCM cases. A total of 1,400 metabolites were evaluated for their causal association with DCM. Instrumental variables (IVs) were selected based on genetic variation and used in the MR analysis. The primary analysis method was inverse variance weighting (IVW), supplemented by weighted median-based estimation and sensitivity analyses.ResultsOf the 1,400 metabolites analyzed, 52 were identified as causally associated with DCM. The analysis revealed both positively and negatively correlated metabolites with DCM risk. Notable findings include the positive correlation of Tryptophan betaine and 5-methyluridine (ribothymidine) levels, and an inverse association of Myristoleate and Erythronate levels with DCM.ConclusionsThe study provides significant insights into the metabolites potentially involved in the pathogenesis of DCM. These findings could pave the way for new therapeutic strategies and biomarker identification in DCM management.

The contribution of plant hormones and energy-rich compounds and their metabolites (ECMs) in alleviating aluminum (Al) toxicity by elevated pH remains to be clarified. For the first time, a targeted metabolome was applied to identify Al-pH-interaction-responsive hormones and ECMs in Citrus sinensis leaves. More Al-toxicity-responsive hormones and ECMs were identified at pH 4.0 [4 (10) upregulated and 7 (17) downregulated hormones (ECMs)] than those at pH 3.0 [1 (9) upregulated and 4 (14) downregulated hormones (ECMs)], suggesting that the elevated pH improved the adaptation of hormones and ECMs to Al toxicity in leaves. The roles of hormones and ECMs in reducing leaf Al toxicity mediated by elevated pH might include the following aspects: (a) improved leaf growth by upregulating the levels of jasmonoyl-L-isoleucine (JA-ILE), 6-benzyladenosine (BAPR), N6-isopentenyladenosine (IPR), cis-zeatin-O-glucoside riboside (cZROG), and auxins (AUXs), preventing Al toxicity-induced reduction of gibberellin (GA) biosynthesis, and avoiding jasmonic acid (JA)-mediated defense; (b) enhanced biosynthesis and accumulation of tryptophan (TRP), as well as the resulting increase in biosynthesis of auxin, melatonin and secondary metabolites (SMs); (c) improved ability to maintain the homeostasis of ATP and other phosphorus (P)-containing ECMs; and (d) enhanced internal detoxification of Al due to increased organic acid (OA) and SM accumulation and elevated ability to detoxify reactive oxygen species (ROS) due to enhanced SM accumulation. To conclude, the current results corroborate the hypotheses that elevated pH reduces Al toxicity by upregulating the ability to maintain the homeostasis of ATP and other P-containing ECMs in leaves under Al toxicity and (b) hormones participate in the elevated pH-mediated alleviation of Al toxicity by positively regulating growth, the ability to detoxify ROS, and the internal detoxification of Al in leaves under Al toxicity. Our findings provide novel insights into the roles of hormones and ECMs in mitigating Al toxicity mediated by the elevated pH.

Abstract Objective To study the biomechanical characteristics of each tissue structure when using different 3D printing Cage in osteoporotic patients undergoing interbody fusion. Methods A finite element model of the lumbar spine was reconstructed and validated with regarding a range of motion and intervertebral disc pressure from previous in vitro studies. Cage and pedicle screws were implanted and part of the lamina, spinous process, and facet joints were removed in the L4/5 segment of the validated mode to simulate interbody fusion. A 280 N follower load and 7.5 N·m moment were applied to different postoperative models and intact osteoporotic model to simulate lumbar motion. The biomechanical characteristics of different models were evaluated by calculating and analyzing the range of motion of the fixed and cephalic adjacent segment, the stress of the screw-rod system, the stress at the interface between cage and L5 endplate, and intervertebral disc pressure of the adjacent segment. Results After rigid fixation, the range of motion of the fixed segment of model A-C decreased significantly, which was much smaller than that of the osteoporotic model. And with the increase of the axial area of the interbody fusion cages, the fixed segment of model A-C tended to be more stable. The range of motion and intradiscal pressure of the spinal models with different interbody fusion cages were higher than those of the complete osteoporosis model, but there was no significant difference between the postoperative models. On the other hand, the L5 upper endplate stress and screw-rod system stress of model A-C show a decreasing trend in different directions of motion. The stress of the endplate is the highest during flexion, which can reach 40.5 MPa (model A). The difference in endplate stress between models A-C was the largest during lateral bending. The endplate stress of models A and B was 150.5% and 140.9% of that of model C, respectively. The stress of the screw-rod system was the highest during lateral bending (model A, 102.0 MPa), which was 108.4%, 102.4%, 110.4%, 114.2% of model B and 158.5%, 110.1%, 115.8%, 125.4% of model C in flexion, extension, lateral bending, and rotation, respectively. Conclusions For people with osteoporosis, no matter what type of cage is used, good immediate stability can be achieved after surgery. Larger cage sizes provide better fixation without significantly increasing ROM and IDP in adjacent segments, which may contribute to the development of ASD. In addition, larger cage sizes can disperse endplate stress and reduce stress concentration, which is of positive significance in preventing cage subsidence after operation. The cage and screw rod system establish a stress conduction pathway on the spine, and a larger cage greatly enhances the stress-bearing capacity of the front column, which can better distribute the stress of the posterior spine structure and the stress borne by the posterior screw rod system, reduce the stress concentration phenomenon of the nail rod system, and avoid exceeding the yield strength of the material, resulting in the risk of future instrument failure.

Abstract Objective This study aimed to compare the biomechanical properties of lumbar interbody fusion involving two types of cages. The study evaluated the effectiveness of the cage spanning the ring apophysis, regardless of the endplate's integrity. Methods A finite element model of the normal spine was established and validated in this study. The validated model was then utilized to simulate Lateral Lumbar Interbody Fusion (LLIF) with posterior pedicle screw fixation without posterior osteotomy. Two models of interbody fusion cage were placed at the L4/5 level, and the destruction of the bony endplate caused by curetting the cartilaginous endplate during surgery was simulated. Four models were established, including Model 1 with an intact endplate and long cage spanning the ring apophysis, Model 2 with endplate decortication and long cage spanning the ring apophysis, Model 3 with an intact endplate and short cage, and Model 4 with endplate decortication and short cage. Analyzed were the ROM of the fixed and adjacent segments, screw rod system stress, interface stress between cage and L5 endplate, trabecular bone stress on the upper surface of L5, and intervertebral disc pressure (IDP) of adjacent segments. Results There were no significant differences in ROM and IDP between adjacent segments in each postoperative model. In the short cage model, the range of motion (ROM), contact pressure between the cage and endplate, stress in L5 cancellous bone, and stress in the screw-rod system all exhibited an increase ranging from 0.4% to 79.9%, 252.9% to 526.9%, 27.3% to 133.3%, and 11.4% to 107%, respectively. This trend was further amplified when the endplate was damaged, resulting in a maximum increase of 88.6%, 676.1%, 516.6%, and 109.3%, respectively. Regardless of the integrity of the endplate, the long cage provided greater support strength compared to the short cage. Conclusions Caution should be exercised during endplate preparation and cage placement to maintain the endplate's integrity. Based on preoperative X-ray evaluation, the selection of a cage that exceeds the width of the pedicle by at least 5 mm (ensuring complete coverage of the vertebral ring) has demonstrated remarkable biomechanical performance in lateral lumbar interbody fusion procedures. By opting for such a cage, we expect a reduced occurrence of complications, including cage subsidence, internal fixation system failure, and rod fracture.

Abstract Background Pelvic parameters have been taken into consideration for the evaluation of the outcomes of bracing in AIS. To discuss the stress required to correct the pelvic deformity related to Lenke5 adolescent idiopathic scoliosis (AIS) by finite element analysis, and provide a reference for the shaping of the pelvic region of the brace. Methods An three-dimensional (3D) corrective force on the pelvic area was defined. Computed tomography images were used to reconstruct a 3D model of Lenke5 AIS. Computer-aided engineering software Abaqus was used to implement finite element analysis. By adjusting the magnitude and position of corrective forces, coronal pelvic coronal plane rotation (PCPR) and Cobb angle (CA) of lumbar curve in the coronal plane, horizontal pelvic axial plane rotation, and apical vertebra rotation (AVR) were minimized to achieve the best effect on the spine and pelvic deformity correction. The proposed corrective conditions were divided into three groups: (1) forces applied on X-axis; (2) forces applied both in the X- and Y-axis; and (3) forces applied along the X-, Y-, and Z-axis at the same time. Results In three groups, CA correction reduced by 31.5%, 42.5%, and 59.8%, and the PCPR changed to 12°, 13°, and 1° from 6.5°, respectively. The best groups of correction forces should simultaneously locate on the sagittal, transverse, and coronal planes of the pelvis. Conclusions For Lenke5 AIS, 3D correction forces can sufficiently reduce scoliosis and pelvic asymmetrical state. Force applied along the Z-axis is vital to correct the pelvic coronal pelvic tilt associated with Lenke5 AIS.

Abstract Objective To study the biomechanical characteristics of various tissue structures of different sizes of 3D printed Cage in lumbar interbody fusion. Methods A finite element model of normal spine was reconstructed and verified. Pedicle screws and Cage of different sizes were implanted in the L4/5 segment to simulate lumbar interbody fusion. The range of motion of the fixed and cephalic adjacent segment, the stress of the screw-rod system, the stress at the interface between cage and L5 endplate, and intervertebral disc pressure of the adjacent segment were calculated and analyzed. Results The range of motion and intervertebral disc pressure of the adjacent segment of each postoperative model were larger than those of the intact model, but there was not much difference between them. The stress of cage-endplate interface was also larger than that of the intact model. However, the difference is that the stress of the endplate and the screw-rod system has a tendency to decrease with the increase of the axial area of cage. Conclusions Cage with larger axial area in lumbar interbody fusion can reduce the stress of internal fixation system and endplate, but will not increase the range of motion and intervertebral disc pressure of adjacent segment. It has a certain effect in preventing the cage subsidence, internal fixation system failure and screw rod fracture.

Abstract Background At present, research on spinal shortening is mainly focused on the safe distance of spinal shortening and the mechanism of spinal cord injury, but there is no research on the biomechanical characteristics of different shortening distances. The purpose of this study was to study the biomechanical characteristics of spine and internal fixation instruments at different shortening distances by the finite element (FE) method. Methods An FE model of lumbar L1-S was established and referred to the previous in vitro experiments to verify the rationality of the model by verifying the Intradiscal pressure (IDP) and the range of motion (ROM) of the motion segment. Five element models of spinal shortening were designed under the safe distance of spinal shortening, and the entire L3 vertebra and both the upper and lower intervertebral discs were resected. Model A was not shortened, while models B-E were shortened by 10%, 20%, 30% and 50% of the vertebral body, respectively. Constraining the ROM of the sacrum in all directions, a 7.5 N ·m moment and 280 N follower load were applied on the L1 vertebra to simulate the motion of the lumbar vertebrae in three planes. The ROM of the operated segments, the Von Mises stress (VMS) of the screw-rod system, the VMS of the upper endplate at the interface between the titanium cage and the L4 vertebral body, and the ROM and the IDP of the adjacent segment (L5/S) were recorded and analysed. Results All surgical models showed good stability at the operated segments (L1-5), with the greatest constraint in posterior extension (99.3-99.7%), followed by left-right bending (97.9-98.7%), and the least constraint in left-right rotation (84.9-86.3%) compared with the intact model. The VMS of the screw-rod system and the ROM and IDP of the distal adjacent segments of models A-E showed an increasing trend, in which the VMS of the screw-rod system of model E was the highest under flexion (172.5 MPa). The VMS of the endplate at the interface between the cage and L4 upper endplate of models A-E decreased gradually, and these trend were the most obvious in flexion, which were 3.03, 2.95, 2.83, 2.78, and 2.61 times that of the intact model, respectively. Conclusion When performing total vertebrae resection and correcting the spinal deformity, if the corrected spine has met our needs, the distance of spinal shortening should be minimized to prevent spinal cord injury, fracture of internal fixations and adjacent segment disease (ASD).

Abstract Background Advancements in medicine and the popularity of lumbar fusion surgery have made lumbar adjacent segment disease (ASDz) increasingly common, but there is no mature plan for guiding its surgical treatment. Therefore, in this study, four different finite element (FE) ASDz models were designed and their biomechanical characteristics were analysed to provide a theoretical basis for clinical workers to choose the most appropriate revision scheme for ASDz. Methods According to whether internal fixation was retained, different FE models were created to simulate ASDz revision surgery, and flexion, extension, axial rotation and lateral bending were simulated by loading. The biomechanical characteristics of the adjacent segments of the intervertebral disc and the internal fixation system and the range of motion (ROM) of the lumbar vertebrae were analysed. Results The difference in the ROM of the fixed segment between FE models that did or did not retain the original internal fixation was less than 0.1°, and the difference was not significant. However, the stress of the screw–rod system when the original internal fixation was retained and prolonged fixation was performed with dual-trajectory screws was less than that when the original internal fixation was removed and prolonged fixation was performed with a long bar. Especially in axial rotation, the difference between models A and B is the largest, and the difference in peak stress reached 30 MPa. However, for the ASDz revision surgery segment, the endplate stress between the two models was the lowest, and the intradiscal pressure (IDP) of the adjacent segment was not significantly different between different models. Conclusion Although ASDz revision surgery by retaining the original internal fixation and prolonging fixation with dual-trajectory screws led to an increase in stress in the fusion segment endplate, it provides stability similar to ASDz revision surgery by removing the original internal fixation and prolonging fixation with a long bar and does not lead to a significant change in the IDP of the adjacent segment while avoiding a greater risk of rod fracture.

Abstract Objective To investigate and evaluate the biomechanical behaviour of tension-band-reconstruction (TBR) and ordinary titanium plates in open-door laminoplasty by finite element (FE) analysis. Methods TBR titanium plate and ordinary titanium plate were implanted into a validated finite element model of healthy adult cervical vertebrae. Among them, 5 ordinary titanium plate were used in model A, 2 TBR titanium plates and 3 ordinary titanium plates were used in model B, and 5 TBR titanium plates were used in model C. The same loading conditions was applied identically to all models. Range of motion (ROM) of the vertebral body, stress distribution of the titanium plate and intradiscal pressure (IDP) were compared in flexion, extension, lateral bending and rotation. Results The ROM of model B and C was similar in flexion and extension, and both were smaller than that of model A. The highest von Mises stress in the titanium plate appears is in model C. The IDP in C2/3 was significantly higher than that in other segments in flexion. There was no significant difference in IDP among three models in left lateral bending and left axial rotation. Conclusion Application of TBR titanium plate in open-door laminoplasty can reduced ROM in flexion, extension and axial rotation of the cervical vertebrae. But the increase of stress in TBR titanium plate could lead to higher risk of adverse events such as titanium plate deformation. Moreover, compared with complete TBR titanium plate, the combination of TBR titanium plate for C3 and C7 with ordinary titanium plate for the other vertebrae largely reduce the stress of the titanium plates by ensuring stability. The proposed FE model (C2-T1) exhibits a great potential in evaluating biomechanical behaviour of TBR titanium plate for open-door laminoplasty.

abstract: Background: Exposure to Migraine may be one of the risk factors for the onset of rheumatoid arthritis (RA), while the relationship between the two is debatable. In this study, the connection between migraine and the risk of RA was investigated using a systematic review and meta-analysis of the pertinent literature. Methods: Up to July 2022, the PubMed, EMBASE, Web of Science (WOS), and scopus databases were employed to search for observational studies on the risk of RA in migraineurs. The effect sizes were pooled using a random-effects model or a fixed-effects model. Results: Out of 2345 records, 5 studies (3 case and control studies and 2 cohort studies) were identified and included in the meta-analysis. According to a pooled analysis, migraine sufferers had a higher chance of developing RA (pooled adjusted effect estimate: 1.94, 95% confidence interval: 1.74–2.17; p

With the global service of the BeiDou Navigation Satellite System (BDS), the Galileo Navigation Satellite System (Galileo), and the modernization of the Global Positioning System (GPS), achieving high-precision positioning through triple-frequency-only observations in medium baseline real-time kinematics (RTK) is anticipated. This study investigates the impacts of double-difference (DD) troposphere delay and ionosphere delay on ambiguity resolution (AR) based on six medium baselines at a latitude of 30°. Additionally, it evaluates positioning accuracy, fixing rate, convergence time, and computational time using triple-frequency-only (B1I/B2a/B3I, E1/E5a/E5b, L1/L2/L5) data, comparing these results to those obtained from dual-frequency (B1I/B2a, E1/E5a, L1/L2) and combined dual-frequency and triple-frequency data. The experimental findings suggest that, for geometry-based wide-lane (WL) AR, the DD troposphere delay and ionosphere delay can be disregarded. However, they cannot be overlooked when aiming to resolve the raw ambiguity. Triple-frequency-only RTK exhibits comparable positioning accuracy to dual-frequency RTK, with its primary advantage lying in faster convergence. The probability of achieving convergence within 180 s is approximately 8.0% higher for triple-frequency-only RTK compared to dual-frequency RTK. In terms of computational time, the use of triple-frequency-only data reduces the required time by 8.26 s compared to the approach that simultaneously employs both dual-frequency and triple-frequency data, resulting in a computational time reduction of approximately 20%. Therefore, when conducting medium baseline RTK positioning, it is recommended to adopt the ambiguity resolution method proposed in this paper based on triple-frequency-only observations.

The hydrogenation of methyl formate to methanol is considered one of the most effective methods for recycling methyl formate products. We recently developed a highly efficient and cost-effective Cu-SiO2 catalyst using the ammonia-evaporation (AE) method. The Cu-SiO2-AE catalyst demonstrated superior performance, achieving a methyl formate conversion of 94.2% and a methanol selectivity of 99.9% in the liquid product. The catalyst also displayed excellent stability over a durability test of 250 h. Compared to the commonly used Cu-Cr catalyst in the industry, the Cu-SiO2-AE catalyst exhibited higher conversion of methyl formate and methanol yield under the same reaction conditions. Characterization results revealed a significant presence of Si-OH groups in the Cu-SiO2-AE catalyst. These groups enhanced the hydrogen spillover effect and improved hydrogenation efficiency by preventing sintering during the reaction to stabilize the Cu species. The strategy employed in this study is applicable to the rational design of highly efficient catalysts for industrial applications.

Grassland resilience is influenced by climate change and human activities. However, little is known about how grassland resilience has changed, driven by climate change and human activities, on the Mongolian Plateau. We calculated grassland resilience on the Mongolian Plateau from 2000 to 2021 using the kernel normalized difference vegetation index (kNDVI), quantified the trends of grassland resilience using a newly proposed “critical slowing down” indicator with a machine learning algorithm, and compared the driving forces for these changes between Inner Mongolia and Mongolia. The findings of this study demonstrate that heightened levels of precipitation and reduced temperature contribute to the enhanced resilience of grassland ecosystems on the Mongolian Plateau. Conversely, the presence of grazing activities exhibits a detrimental effect on such resilience. In semi-arid regions, approximately 43% of grassland areas are undergoing a discernible decline in resilience. This decline is particularly pronounced in regions characterized by heightened levels of grazing intensity. In addition, resilience declined in 54% of areas with population growth compared with 32% in areas with population decline. Inner Mongolia, with its higher intensity of human activities, has a more serious decline in ecological resilience than Mongolia, indicating that further ecological restoration measures are needed.

Abstract Background This study compared the biomechanics of artificial pedicle fixation in spine reconstruction with a 3-dimensional (3D)-printed prosthesis after total en bloc spondylectomy (TES) by finite element analysis. Methods A thoracolumbar (T10–L2) finite element model was developed and validated. Two models of T12 TES were established in combination with different fixation methods: Model A consisted of long-segment posterior fixation (T10/11, L1/2) + 3D-printed prosthesis; and Model B consisted of Model A + two artificial pedicle fixation screws. The models were evaluated with an applied of 7.5 N·m and axial force of 200 N. We recorded and analyzed the following: (1) stiffness of the two fixation systems, (2) hardware stress in the two fixation systems, and (3) stress on the endplate adjacent to the 3D-printed prosthesis. Results The fixation strength of Model B was enhanced by the screws in the artificial pedicle, which was mainly manifested as an improvement in rotational stability. The stress transmission of the artificial pedicle fixation screws reduced the stress on the posterior rods and endplate adjacent to the 3D-printed prosthesis in all directions of motion, especially in rotation. Conclusions After TES, the posterior long-segment fixation combined with the anterior 3D printed prosthesis could maintain postoperative spinal stability, but adding artificial pedicle fixation increased the stability of the fixation system and reduced the risk of prosthesis subsidence and instrumentation failure.

Abstract Background Regarding the repair of vertebral compression fractures, there is a lack of adequate biomechanical verification as to whether only half of the vertebral body and the upper and lower intervertebral discs affect spinal biomechanics; there also remains debate as to the appropriate length of fixation. Methods A model of old vertebral compression fractures with kyphosis was established based on CT data. Vertebral column resection (VCR) and posterior unilateral vertebral resection and reconstruction (PUVCR) were performed at T12; long- and short-segment fixation methods were applied, and we analyzed biomechanical changes after surgery. Results Range of motion (ROM) decreased in all fixed models, with lumbar VCR decreasing the most and short posterior unilateral vertebral resection and reconstruction (SPUVCR) decreasing the least; in the long posterior unilateral vertebral resection and reconstruction (LPUVCR) model, the internal fixation system produced the maximum VMS stress of 213.25 mPa in a lateral bending motion and minimum stress of 40.22 mPa in a lateral bending motion in the SVCR. Conclusion There was little difference in thoracolumbar ROM between PUVCR and VCR models, while thoracolumbar ROM was smaller in long-segment fixation than in short-segment fixation. In all models, the VMS was most significant at the screw-rod junction and greatest at the ribcage–vertebral body interface, partly explaining the high probability of internal fixation failure and prosthesis migration in these two positions.

Understanding the tumor microenviroment is important before it can be exploited therapeutically. Here, the authors use single cell sequencing to study stromal cells in mouse tumors and identify a subset of interferon-licensed cancer associated fibroblasts that appear after anti-TGFβ treatment.

Signaling of IL-33 via its receptor, ST2, has been implicated in macrophage function in tissue repair. Here the authors show, using genetic mouse models and single-cell transcriptomic data, that the IL-33/ST2 axis regulates both ILC2-derived IL-13 and macrophage differentiation/reparative function required for club cell regeneration.

Some members of the Rosaceae family, particularly pear, contain stone cells in their fruits. Although stone cells in pear fruits are well studied, relatively little attention has been given to loquat stone cells. Only a few reports have suggested a relationship between stone cell traits and storage and transport tolerance of loquat fruits. Previously, we generated the variety JT8 from the interspecific hybrid of the loquat cultivar Jiefangzhong (JFZ; Eriobotrya japonica Lindl. cv. Jiefangzhong, female parent) and wild Taiwanese loquat (TL; E. deflexa Nakai, male parent). The JT8 fruits had a granular feel, similar to that of pear fruits, due to the presence of stone cells. In this study, the shape, size, development, and distribution dynamics of stone cells of Eriobotrya plants were thoroughly investigated. The results showed that loquat stone cells are brachysclereids and often contain typical branching pits. Loquat stone cells were distributed as both single stone cells and in stone cell clusters (SCCs), and the density of the stone cells near the core was higher than that near the peel. Stone cell density first increased and then decreased during fruit development. These traits noted in Eriobotrya were very similar to those observed in pear, indicating a close relationship between loquat and pear. Moreover, the contents, density dynamics, and aggregation traits of stone cells of the interspecific hybrid JT8 were derived from the male parent (TL). Transgressive segregation was likely exhibited in the content of stone cells and the size of the SCCs. More specifically, the content of stone cells reached 1.61% (w/w). In extreme cases, SCCs of JT8 exceeded 1,000 μm in length and 500 μm in width. This demonstrated that stone cell traits could be transmitted from parent to progeny through interspecific hybridization. The density dynamics of stone cells in two loquat cultivars with different storage and transport tolerances were also investigated, which indicated that the cultivar with more stone cells was more tolerant to storage and transport. We suggest that wild loquat genetic resources containing stone cells in Eriobotrya plants can be used to gradually improve the storage and transport tolerance of loquat fruits.

Abstract Background Loquat (Eriobotrya japonica) is a subtropical tree bearing fruit that ripens during late spring and early summer, which is the off-season for fruit production. The specific flowering habit of loquat, which starts in fall and ends in winter, has attracted an increasing number of researchers who believe that it may represent an ideal model for studying flowering shift adaptations to climate change in Rosaceae. These studies require an understanding of gene expression patterns within the fruit and other tissues of this plant. Although ACTINs (ACTs) have previously been used as reference genes (RGs) for gene expression studies in loquats, a comprehensive analysis of whether these RGs are optimal for normalizing RT-qPCR data has not been performed. Results In this study, 11 candidate RGs (RIBOSOMAL-LIKE PROTEIN4 (RPL4), RIBOSOMAL-LIKE PROTEIN18 (RPL18), Histone H3.3 (HIS3), Alpha-tubulin-3 (TUA3), S-Adenosyl Methionine Decarboxylase (SAMDC), TIP41-like Family Protein (TIP41), (UDP)-glucose Pyrophosphorylase (UGPase), 18S ribosomal RNA (18S), Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH), Plasma Intrinsic Protein 2 (PIP2) and ACTIN(ACT)) were assessed to determine their expression stability in 23 samples from different tissues or organs of loquat. Integrated expression stability evaluations using five computational statistical methods (GeNorm, NormFinder, ΔCt, BestKeeper, and RefFinder) suggested that a RG set, including RPL4, RPL18, HIS3 and TUA3, was the most stable one across all of the tested loquat samples. The expression pattern of EjCDKB1;2 in the tested loquat tissues normalized to the selected RG set demonstrated its reliability. Conclusions This study reveals the reliable RGs for accurate normalization of gene expression in loquat. In addition, our findings demonstrate an efficient system for identifying the most effective RGs for different organs, which may be applied to related rosaceous crops.

Zirconia exhibits excellent biocompatibility and is widely used as dental implant materials in prosthodontics. Over the past years, research and development of dental implant biomaterials has focused on osseointegration, but few reports exist regarding the role of the immune environment on cellular responses to these materials. The present study investigates the effect of different nanostructured zirconia surface topographies on macrophage phenotypes and their influence on gingival fibroblast behavior. Three different nanostructured zirconia surfaces are characterized using scanning electron microscopy, atomic force microscopy, and water contact angle. Blank-machined zirconia (BMZ) surfaces were superior to RAW264.7 cell proliferation and adhesion. RAW264.7 seeded on all nanostructured zirconia surfaces polarized toward both inflammatory M1 and anti-inflammatory M2 macrophages with more M2 macrophage phenotype on BMZ surfaces. Meanwhile, conditioned media (CM) from RAW264.7 culture on three nanostructured zirconia surfaces inhibited cell apoptosis to human gingival fibroblasts (HGFs) but promoted HGF proliferation and secretion. Under modulation of RAW264.7 culture, HGFs cultured on BMZ surfaces significantly secreted more extracellular matrix with a higher expression of collagen-I (COL-I), vinculin (VCL), and fibronectin (FN) than those coated on self-glazed zirconia (CSGZ) and self-glazed zirconia (SGZ) surfaces. After being coated with a nano zirconia film, CSGZ surfaces showed certain changes in cell proliferation, adhesion, and protein production compared with SGZ surfaces. These findings will provide an overview of manipulating surface topography to modulate macrophage phenotypes in order to create an effective macrophage immune response and reinforce soft tissue integration.

A facile, green, and high-output hydrothermal synthesis was proposed for the fabrication of highly fluorescent nitrogen-doped carbon quantum dots (N-doped CDs). The nitrogen content in N-doped CDs reached 19.2% and demonstrated strong blue fluorescence emission was obtained with fluorescence quantum yield (QY) of up to 32.9%, which exhibit high fluorescence quantum yield, high photostability, and excellent biocompatibility. The N-doped CDs possess high photostability, low toxicity, and excellent biocompatibility, based on which the N-doped CDs were successfully applied as a fluorescence probe for cell imaging. Moreover, it was then successfully demonstrated for sensitive and selective detection of Fe3+ in serum.

Stirred-suspension bioreactors are a promising modality for large-scale culture of 3D aggregates of pluripotent stem cells and their progeny. Yet, cells within these clusters experience limitations in the transfer of factors and particularly O2 which is characterized by low solubility in aqueous media. Cultured stem cells under different O2 levels may exhibit significantly different proliferation, viability and differentiation potential. Here, a transient diffusion-reaction model was built encompassing the size distribution and ultrastructural characteristics of embryonic stem cell (ESC) aggregates. The model was coupled to experimental data from bioreactor and static cultures for extracting the effective diffusivity and kinetics of consumption of O2 within mouse (mESC) and human ESC (hESC) clusters. Under agitation, mESC aggregates exhibited a higher maximum consumption rate than hESC aggregates. Moreover, the reaction-diffusion model was integrated with a population balance equation (PBE) for the temporal distribution of ESC clusters changing due to aggregation and cell proliferation. Hypoxia was found to be negligible for ESCs with a smaller radius than 100 µm but became appreciable for aggregates larger than 300 µm. The integrated model not only captured the O2 profile both in the bioreactor bulk and inside ESC aggregates but also led to the calculation of the duration that fractions of cells experience a certain range of O2 concentrations. The approach described in this study can be employed for gaining a deeper understanding of the effects of O2 on the physiology of stem cells organized in 3D structures. Such frameworks can be extended to encompass the spatial and temporal availability of nutrients and differentiation factors and facilitate the design and control of relevant bioprocesses for the production of stem cell therapeutics.

Nanog is a principal pluripotency regulator exhibiting a disperse distribution within stem cell populations in vivo and in vitro. Increasing evidence points to a functional role of Nanog heterogeneity on stem cell fate decisions. Allelic control of Nanog gene expression was reported recently in mouse embryonic stem cells. To better understand how this mode of regulation influences the observed heterogeneity of NANOG in stem cell populations, we assembled a multiscale stochastic population balance equation framework. In addition to allelic control, gene expression noise and random partitioning at cell division were considered. As a result of allelic Nanog expression, the distribution of Nanog exhibited three distinct states but when combined with transcriptional noise the profile became bimodal. Regardless of their allelic expression pattern, initially uniform populations of stem cells gave rise to the same Nanog heterogeneity within ten cell cycles. Depletion of NANOG content in cells switching off both gene alleles was slower than the accumulation of intracellular NANOG after cells turned on at least one of their Nanog gene copies pointing to Nanog state-dependent dynamics. Allelic transcription of Nanog also raises issues regarding the use of stem cell lines with reporter genes knocked in a single allelic locus. Indeed, significant divergence was observed in the reporter and native protein profiles depending on the difference in their half-lives and insertion of the reporter gene in one or both alleles. In stem cell populations with restricted Nanog expression, allelic regulation facilitates the maintenance of fractions of self-renewing cells with sufficient Nanog content to prevent aberrant loss of pluripotency. Our findings underline the role of allelic control of Nanog expression as a prime determinant of stem cell population heterogeneity and warrant further investigation in the contexts of stem cell specification and cell reprogramming.

Heterogeneity is an often unappreciated characteristic of stem cell populations yet its importance in fate determination is becoming increasingly evident. Although gene expression noise has received greater attention as a source of non-genetic heterogeneity, the effects of stochastic partitioning of cellular material during mitosis on population variability have not been researched to date. We examined self-renewing human embryonic stem cells (hESCs), which typically exhibit a dispersed distribution of the pluripotency marker NANOG. In conjunction with our experiments, a multiscale cell population balance equation (PBE) model was constructed accounting for transcriptional noise and stochastic partitioning at division as sources of population heterogeneity. Cultured hESCs maintained time-invariant profiles of size and NANOG expression and the data were utilized for parameter estimation. Contributions from both sources considered in this study were significant on the NANOG profile, although elimination of the gene expression noise resulted in greater changes in the dispersion of the NANOG distribution. Moreover, blocking of division by treating hESCs with nocodazole or colcemid led to a 39% increase in the average NANOG content and over 68% of the cells had higher NANOG level than the mean NANOG expression of untreated cells. Model predictions, which were in excellent agreement with these findings, revealed that stochastic partitioning accounted for 17% of the total noise in the NANOG profile of self-renewing hESCs. The computational framework developed in this study will aid in gaining a deeper understanding of how pluripotent stem/progenitor cells orchestrate processes such as gene expression and proliferation for maintaining their pluripotency or differentiating along particular lineages. Such models will be essential in designing and optimizing efficient differentiation strategies and bioprocesses for the production of therapeutically suitable stem cell progeny.