Failure evolution and instability prediction of fiber-reinforced polymer-confined cement mortar specimens under axial compression.

In geotechnical engineering, a large number of pillars are often left in underground space to support the overlying strata and protect the surface environment. To enhance pillar stability and prevent instability, this study proposes an innovative technology for pillar reinforcement. Specifically, local confinement of the pillar is achieved through fiber-reinforced polymer (FRP) strips, resulting in the formation of a more stable composite structure. In order to validate the effectiveness of this structural approach, acoustic emission characteristics and surface strain field characteristics were monitored during failure processes, while mathematical models were employed to predict specimen instability. The test results revealed that increasing FRP strip confinement width led to heightened activity in acoustic emission events during failure processes, accompanied by a decrease in shear cracks but an increase in tensile cracks. Moreover, ductility was improved and deformation resistance capacity was enhanced within specimens. Notably, initial crack generation occurred within unconfined regions of specimens during failures; however, both length and width as well as overall numbers of cracks significantly decreased due to implementation of FRP strips. Consequently, specimen failure speed was slowed down accordingly. Finally, the instability of the partial FRP-confined cement mortar could be more accurately predicted based on the model of FRP-confined concrete. It was verified by the test results.

Low-intensity focused ultrasound stimulation promotes stroke recovery via astrocytic HMGB1 and CAMK2N1 in mice.

BACKGROUND: Low-intensity focused ultrasound stimulation (LIFUS) has been developed to enhance neurological repair and remodelling during the late acute stage of ischaemic stroke in rodents. However, the cellular and molecular mechanisms of neurological repair and remodelling after LIFUS in ischaemic stroke are unclear. METHODS: Ultrasound stimulation was treated in adult male mice 7 days after transient middle cerebral artery occlusion. Angiogenesis was measured by laser speckle imaging and histological analyses. Electromyography and fibre photometry records were used for synaptogenesis. Brain atrophy volume and neurobehaviour were assessed 0-14 days after ischaemia. iTRAQ proteomic analysis was performed to explore the differentially expressed protein. scRNA-seq was used for subcluster analysis of astrocytes. Fluorescence in situ hybridisation and Western blot detected the expression of HMGB1 and CAMK2N1. RESULTS: Optimal ultrasound stimulation increased cerebral blood flow, and improved neurobehavioural outcomes in ischaemic mice (p<0.05). iTRAQ proteomic analysis revealed that the expression of HMGB1 increased and CAMK2N1 decreased in the ipsilateral hemisphere of the brain at 14 days after focal cerebral ischaemia with ultrasound treatment (p<0.05). scRNA-seq revealed that this expression pattern belonged to a subcluster of astrocytes after LIFUS in the ischaemic brain. LIFUS upregulated HMGB1 expression, accompanied by VEGFA elevation compared with the control group (p<0.05). Inhibition of HMGB1 expression in astrocytes decreased microvessels counts and cerebral blood flow (p<0.05). LIFUS reduced CAMK2N1 expression level, accompanied by increased extracellular calcium ions and glutamatergic synapses (p<0.05). CAMK2N1 overexpression in astrocytes decreased dendritic spines, and aggravated neurobehavioural outcomes (p<0.05). CONCLUSION: Our results demonstrated that LIFUS promoted angiogenesis and synaptogenesis after focal cerebral ischaemia by upregulating HMGB1 and downregulating CAMK2N1 in a subcluster of astrocytes, suggesting that LIFUS activated specific astrocyte subcluster could be a key target for ischaemic brain therapy.

On-Tissue Spatial Proteomics Integrating MALDI-MS Imaging with Shotgun Proteomics Reveals Soy Consumption-Induced Protein Changes in a Fragile X Syndrome Mouse Model.

Fragile X syndrome (FXS), the leading cause of inherited intellectual disability and autism, is caused by the transcriptional silencing of the FMR1 gene, which encodes the fragile X messenger ribonucleoprotein (FMRP). FMRP interacts with numerous brain mRNAs that are involved in synaptic plasticity and implicated in autism spectrum disorders. Our published studies indicate that single-source, soy-based diets are associated with increased seizures and autism. Thus, there is an acute need for an unbiased protein marker identification in FXS in response to soy consumption. Herein, we present a spatial proteomics approach integrating mass spectrometry imaging with label-free proteomics in the FXS mouse model to map the spatial distribution and quantify levels of proteins in the hippocampus and hypothalamus brain regions. In total, 1250 unique peptides were spatially resolved, demonstrating the diverse array of peptidomes present in the tissue slices and the broad coverage of the strategy. A group of proteins that are known to be involved in glycolysis, synaptic transmission, and coexpression network analysis suggest a significant association between soy proteins and metabolic and synaptic processes in the Fmr1KO brain. Ultimately, this spatial proteomics work represents a crucial step toward identifying potential candidate protein markers and novel therapeutic targets for FXS.

MXene-based anode materials for high performance sodium-ion batteries.

As an emerging class of layered transition metal carbides/nitrides/carbon-nitrides, MXenes have been one of the most investigated anode subcategories for sodium ion batteries (SIBs), due to their unique layered structure, metal-like conductivity, large specific surface area and tunable surface groups. In particular, different MAX precursors and synthetic routes will lead to MXenes with different structural and electrochemical properties, which actually gives MXenes unlimited scope for development. In this feature article, we systematically present the recent advances in the methods and synthetic routes of MXenes, together with their impact on the properties of MXenes and also the advantages and disadvantages. Subsequently, the sodium storage mechanisms of MXenes are summarized, as well as the recent research progress and strategies to improve the sodium storage performance. Finally, the main challenges currently facing MXenes and the opportunities in improving the performance of SIBs are pointed out.

The value of radiographic features in predicting postoperative facial nerve function in vestibular schwannoma patients: A retrospective study and nomogram analysis.

OBJECTIVE: The purpose of this study was to identify significant prognostic factors associated with facial paralysis after vestibular schwannoma (VS) surgery and develop a novel nomogram for predicting facial nerve (FN) outcomes. METHODS: Retrospective data were retrieved from 355 patients who underwent microsurgery via the retrosigmoid approach for VS between December 2017 and December 2022. Univariate and multivariate logistic regression analysis were used to construct a radiographic features-based nomogram to predict the risk of facial paralysis after surgery. RESULTS: Following a thorough screening process, a total of 185 participants were included. The univariate and multivariate logistic regression analysis revealed that tumor size (p = 0.005), fundal fluid cap (FFC) sign (p = 0.014), cerebrospinal fluid cleft (CSFC) sign (p < 0.001), and expansion of affected side of internal auditory canal (IAC) (p = 0.033) were independent factors. A nomogram model was constructed based on these indicators. When applied to the validation cohort, the nomogram demonstrated good discrimination and favorable calibration. Then we generated a web-based calculator to facilitate clinical application. CONCLUSION: Tumor size, FFC and CSFC sign, and the expansion of the IAC, serve as good predictors of postoperative FN outcomes. Based on these factors, the nomogram model demonstrates good predictive performance.

The effect of overweight or obesity on osteoporosis: A systematic review and meta-analysis.

BACKGROUND: Osteoporosis and obesity are closely related, and the relationships between different types of obesity and osteoporosis are inconsistent. OBJECTIVE: Our objective was to summarize earlier data concerning the association between osteoporosis and obesity (general and central), and to compare the impacts of these two obesity indicators on osteoporosis. METHODS: From inception to May 2021, a comprehensive search in electronic bibliographic databases was conducted, and the search was updated in December 2021, July 2022 and June 2023. The data were independently extracted and evaluated by two investigators from epidemiological studies that reported the impact of obesity on the odds of incident osteoporosis. RESULTS: There were 24 studies included in the final analysis when it came to general obesity measured by body mass index (BMI). Individuals with overweight and obesity had decreased odds of osteoporosis (odds ratio (OR), 0.451, 95% confidence intervals (CIs): 0.366-0.557). Sensitivity analyses showed that both overweight and obesity were decreased odds of osteoporosis, with reductions of 48.6% and 70.1%, respectively (OR, 0.514, 95% CI: 0.407-0.649; OR, 0.299, 95% CI: 0.207-0.433). Conversely, individuals classified as underweight were found to have higher odds of osteoporosis (OR, 2.540, 95% CI: 1.483-4.350). In term of central obesity, the final analysis consisted of 7 studies. No significant association was observed between central obesity and osteoporosis (OR, 0.913, 95% CI: 0.761-1.096). CONCLUSIONS: General overweight and obesity were associated with lower odds of developing osteoporosis, whereas underweight was associated with higher odds. However, central obesity did not show a significant association with osteoporosis. These findings underscore the importance of considering the impact of obesity on osteoporosis. Further research is necessary to reinforce the evidence and validate our findings.

Total body bone mineral density and various spinal disorders: a Mendelian randomization study.

Introduction: Observational studies have yielded inconsistent findings regarding the correlation between bone mineral density (BMD) and various spinal disorders. To explore the relationship between total-body BMD and various spinal disorders further, we conducted a Mendelian randomization analysis to assess this association. Methods: Two-sample bidirectional Mendelian randomization (MR) analysis was employed to investigate the association between total-body BMD and various spinal disorders. The inverse-variance weighted (IVW) method was used as the primary effect estimate, and additional methods, including weighted median, MR-Egger, simple mode, and weighted mode, were used to assess the reliability of the results. To examine the robustness of the data further, we conducted a sensitivity analysis using alternative bone-density databases, validating the outcome data. Results: MR revealed a significant positive association between total-body BMD and the prevalence of spondylosis and spinal stenosis. When total-body BMD was considered as the exposure factor, the analysis demonstrated an increased risk of spinal stenosis (IVW odds ratio [OR] 1.23; 95% confidence interval [CI], 1.14-1.32; P < 0.001) and spondylosis (IVW: OR 1.24; 95%CI, 1.16-1.33; P < 0.001). Similarly, when focusing solely on heel BMD as the exposure factor, we found a positive correlation with the development of both spinal stenosis (IVW OR 1.13, 95%CI, 1.05-1.21; P < 0.001) and spondylosis (IVW OR 1.10, 95%CI, 1.03-1.18; P = 0.0048). However, no significant associations were found between total-body BMD and other spinal disorders, including spinal instability, spondylolisthesis/spondylolysis, and scoliosis (P > 0.05). Conclusion: This study verified an association of total-body BMD with spinal stenosis and with spondylosis. Our results imply that when an increasing trend in BMD is detected during patient examinations and if the patient complains of numbness and pain, the potential occurrence of conditions such as spondylosis or spinal stenosis should be investigated and treated appropriately.

The Weight-loss Effect of GLP-1RAs Glucagon-Like Peptide-1 Receptor Agonists in Non-diabetic Individuals with Overweight or Obesity: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are new drugs for the treatment of obesity. OBJECTIVE: To assess the weight-loss effects of GLP-1RAs in the treatment of patients with overweight or obesity without diabetes. METHODS: This is a systematic review with meta-analysis and trial sequential analysis. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from their inception to January 1, 2022. Eligible trials report on outcomes including body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), or total body fat (TBF). Mean differences (MDs) and standardized mean differences (SMDs) were summarized using random-effects models. RESULTS: Forty-one trials involving 15,135 participants were included. Compared with controls, GLP-1RAs significantly reduced BW (MD -5.319 kg, 95% CI: -6.465, -4.174), BMI (MD -2.373 kg/m2, 95% CI: -2.821, -1.924), WC (MD -4.302 cm, CI:-5.185 to -3.419), WHR (MD -0.011, CI -0.015 to -0.007), but not TBF (MD -0.320%, CI -1.420 to -0.780). Trial sequential analysis (TSA) supported conclusive evidence of the effects of GLP-1RAs on BW, BMI, and WC for weight loss. GLP-1RAs had nonlinear dose-response relationships with weight loss. Extensive sensitivity analyses demonstrated the robustness of the results, though the GRADE certainty of the evidence ranged from high to very low. High to moderate GRADE certainty of evidence suggested semaglutide as the most effective GLP-1RA agent, with the best efficacy and low to moderate risk of adverse effects. CONCLUSIONS: The present study provides conclusive evidence for the effect of GLP-1RAs on weight loss in a nonlinear dose-response manner in patients with obesity or overweight without diabetes. In terms of changes in BW, BMI, and WC, there is firm evidence for the overall weight-loss effects of GLP-1RAs. Of the GLP-1RAs, semaglutide might be the most effective agent.

Preparation for mice spaceflight: Indications for training C57BL/6J mice to adapt to microgravity effect with three-dimensional clinostat on the ground.

Like astronauts, animals need to undergo training and screening before entering space. At present, pre-launch training for mice mainly focuses on adaptation to habitat system. Training for the weightless environment of space in mice has not received much attention. Three-dimensional (3D) clinostat is a method to simulate the effects of microgravity on Earth. However, few studies have used a 3D clinostat apparatus to simulate the effects of microgravity on animal models. Therefore, we conducted a study to evaluate the feasibility and effects of long-term treatment with three-dimensional clinostat in C57BL/6 J mice. Thirty 8-week-old male C57BL/6 J mice were randomly assigned to three groups: mice in individually ventilated cages (MC group, n = 6), mice in survival boxes (SB group, n = 12), and mice in survival boxes receiving 3D clinostat treatment (CS group, n = 12). The mice showed good tolerance after 12 weeks of alternate day training. To evaluate the biological effects of simulated microgravity, the changes in serum metabolites were monitored using untargeted metabolomics, whereas bone loss was assessed using microcomputed tomography of the left femur. Compared with the metabolome of the SB group, the metabolome of the CS group showed significant differences during the first three weeks and the last three weeks. The KEGG pathways in the late stages were mainly related to the nervous system, indicating the influence of long-term microgravity on the central nervous system. Besides, a marked reduction in the trabecular number (P < 0.05) and an increasing trend of trabecular spacing (P < 0.1) were observed to occur in a time-dependent manner in the CS group compared with the SB group. These results showed that mice tolerated well in a 3D clinostat and may provide a new strategy in pre-launch training for mice and conducting relevant ground-based modeling experiments.

Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging.

Single-cell (SC) analysis provides unique insight into individual cell dynamics and cell-to-cell heterogeneity. Here, we utilize trapped ion mobility separation coupled with dual-polarity ionization mass spectrometry imaging (MSI) to enable high-throughput in situ profiling of the SC lipidome. Multimodal SC imaging, in which dual-polarity-mode MSI is used to perform serial data acquisition runs on individual cells, significantly enhanced SC lipidome coverage. High-spatial resolution SC-MSI identifies both inter- and intracellular lipid heterogeneity; this heterogeneity is further explicated by Uniform Manifold Approximation and Projection and machine learning-driven classifications. We characterize SC lipidome alteration in response to stearoyl-CoA desaturase 1 inhibition and, additionally, identify cell-layer specific lipid distribution patterns in mouse cerebellar cortex. This integrated multimodal SC-MSI technology enables high-resolution spatial mapping of intercellular and cell-to-cell lipidome heterogeneity, SC lipidome remodeling induced by pharmacological intervention, and region-specific lipid diversity within tissue.

DiLeu Isobaric Labeling Coupled with Limited Proteolysis Mass Spectrometry for High-Throughput Profiling of Protein Structural Changes in Alzheimer's Disease.

High-throughput quantitative analysis of protein conformational changes has a profound impact on our understanding of the pathological mechanisms of Alzheimer's disease (AD). To establish an effective workflow enabling quantitative analysis of changes in protein conformation within multiple samples simultaneously, here we report the combination of N,N-dimethyl leucine (DiLeu) isobaric tag labeling with limited proteolysis mass spectrometry (DiLeu-LiP-MS) for high-throughput structural protein quantitation in serum samples collected from AD patients and control donors. Twenty-three proteins were discovered to undergo structural changes, mapping to 35 unique conformotypic peptides with significant changes between the AD group and the control group. Seven out of 23 proteins, including CO3, CO9, C4BPA, APOA1, APOA4, C1R, and APOA, exhibited a potential correlation with AD. Moreover, we found that complement proteins (e.g., CO3, CO9, and C4BPA) related to AD exhibited elevated levels in the AD group compared to those in the control group. These results provide evidence that the established DiLeu-LiP-MS method can be used for high-throughput structural protein quantitation, which also showed great potential in achieving large-scale and in-depth quantitative analysis of protein conformational changes in other biological systems.

ATP-Coated Dual-Functionalized Titanium(IV) IMAC Material for Simultaneous Enrichment and Separation of Glycopeptides and Phosphopeptides.

Protein glycosylation and phosphorylation are two of the most common post-translational modifications (PTMs), which play an important role in many biological processes. However, low abundance and poor ionization efficiency of phosphopeptides and glycopeptides make direct MS analysis challenging. In this study, we developed a hydrophilicity-enhanced bifunctional Ti-IMAC (IMAC: immobilized metal affinity chromatography) material with grafted adenosine triphosphate (denoted as epoxy-ATP-Ti4+) to enable simultaneous enrichment and separation of common N-glycopeptides, phosphopeptides, and M6P glycopeptides from tissue/cells. The enrichment was achieved through a dual-mode mechanism based on the electrostatic and hydrophilic properties of the material. The epoxy-ATP-Ti4+ IMAC material was prepared from epoxy-functionalized silica particles via a convenient two-step process. The ATP molecule provided strong and active phosphate sites for binding phosphopeptides in the conventional IMAC mode and also contributed significantly to the hydrophilicity, which permitted the enrichment of glycopeptides via hydrophilic interaction chromatography. The two modes could be implemented simultaneously, allowing glycopeptides and phosphopeptides to be collected sequentially in a single experiment from the same sample. In addition to standard protein samples, the material was further applied to glycopeptide and phosphopeptide enrichment and characterization from HeLa cell digests and mouse lung tissue samples. In total, 2928 glycopeptides and 3051 phosphopeptides were identified from the mouse lung tissue sample, supporting the utility of this material for large-scale PTM analysis of complex biological samples. Overall, the newly developed epoxy-ATP-Ti4+ IMAC material and associated fractionation method enable simple and effective enrichment and separation of glycopeptides and phosphopeptides, offering a useful tool to study potential crosstalk between these two important PTMs in biological systems. The MS data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD029775.

Fracturing Behaviors and Mechanism of Serial Coal Pillar Specimens with Different Strength.

The fracturing behaviors of serial coal pillars is significant for understanding their failure mechanism. To reveal this, the bearing stress, acoustic emission, electrical resistivity, local strain, force chain distribution, and cracks evolution of serial coal pillars under uniaxial compression were evaluated by experiment and numerical simulation. The results show that four bearing stages are observed during the fracturing process (i.e., nonlinear growth, linear growth, yielding growth, and weakening stages). The acoustic emission features, electrical resistivity responses, strain develops, force chain distributions, cracks evolutions, and local displacement are highly consistent to illustrate the fracturing behaviors. System fracturing of serial coal pillar specimens is appeared along with the collapse of lower uniaxial compressive strength coal pillar specimen. The limit bearing capacity of serial coal pillar specimens is almost equal to the strength of lower uniaxial compressive strength coal pillar specimen. The unbalanced deformation characteristics of serial coal pillar specimens are presented due to the strength differences. The evolution of the key deformation element is the rooted reason for the overall fracturing mechanism of serial coal pillar specimens. For serial coal pillar specimens with different strengths, the critical condition of system fracturing is that the sum of secant modulus of upper and bottom coal pillars is zero, which is expected to predict the system fracturing of serial pillars in the underground coal mining.

A conditional knockout rat resource of mitochondrial protein-coding genes via a DdCBE-induced premature stop codon.

Hundreds of pathogenic variants of mitochondrial DNA (mtDNA) have been reported to cause mitochondrial diseases, which still lack effective treatments. It is a huge challenge to install these mutations one by one. We repurposed the DddA-derived cytosine base editor to incorporate a premature stop codon in the mtProtein-coding genes to ablate mitochondrial proteins encoded in the mtDNA (mtProteins) instead of installing pathogenic variants and generated a library of both cell and rat resources with mtProtein depletion. In vitro, we depleted 12 of 13 mtProtein-coding genes with high efficiency and specificity, resulting in decreased mtProtein levels and impaired oxidative phosphorylation. Moreover, we generated six conditional knockout rat strains to ablate mtProteins using Cre/loxP system. Mitochondrially encoded ATP synthase membrane subunit 8 and NADH:ubiquinone oxidoreductase core subunit 1 were specifically depleted in heart cells or neurons, resulting in heart failure or abnormal brain development. Our work provides cell and rat resources for studying the function of mtProtein-coding genes and therapeutic strategies.

Gadolinium (III)-Chelated Deformable Mesoporous Organosilica Nanoparticles as Magnetic Resonance Imaging Contrast Agent.

Magnetic resonance imaging (MRI) contrast agents, such as Magnevist (Gd-DTPA), are routinely used for detecting tumors at an early stage. However, the rapid clearance by the kidney of Gd-DTPA leads to short blood circulation time, which limits further improvement of the contrast between tumorous and normal tissue. Inspired by the deformability of red blood cells, which improves their blood circulation, this work fabricates a novel MRI contrast agent by incorporating Gd-DTPA into deformable mesoporous organosilica nanoparticles (D-MON). In vivo distribution shows that the novel contrast agent is able to depress rapid clearance by the liver and spleen, and the mean residence time is 20 h longer than Gd-DTPA. Tumor MRI studies demonstrated that the D-MON-based contrast agent is highly enriched in the tumor tissue and achieves prolonged high-contrast imaging. D-MON significantly improves the performance of clinical contrast agent Gd-DTPA, exhibiting good potential in clinical applications.

Integrin ß1/FAK/SRC signal pathway is involved in autism spectrum disorder in Tspan7 knockout rats.

TSPAN7 is related to various neurological disorders including autism spectrum disorder (ASD). However, the underlying synaptic mechanism of TSPAN7 in ASD is still unclear. Here, we showed that Tspan7 knockout rats exhibited ASD-like and ID-like behavioral phenotypes, brain structure alterations including decreased hippocampal and cortical volume, and related pathological changes including reduced hippocampal neurons number, neuronal complexity, dendritic spines, and synapse-associated proteins. Then, we found that TSPAN7 deletion interrupted the integrin ß1/FAK/SRC signal pathway that was followed by the down-regulation of PSD95, SYN, and GluR1/2, which are key synaptic integrity-related proteins. Furthermore, reactivation of SRC restored the expression of synaptic integrity-related proteins in primary neurons of TSPAN7 knockout brains. Taken together, our results suggested that TSPAN7 knockout caused ASD-like and ID-like behaviors in rats and impaired neuronal synapses possibly through the down-regulation of the integrin ß1/FAK/SRC signal pathway, which might be a new mechanism on regulation of synaptic proteins expression and on ASD pathogenesis by mutated TSPAN7. These findings provide novel insights into the role of TSPAN7 in psychiatric diseases and highlight integrin ß1/FAK/SRC as a potential target for ASD therapy.

Enabling Global Analysis of Protein Citrullination via Biotin Thiol Tag-Assisted Mass Spectrometry.

Citrullination is a key post-translational modification (PTM) that affects protein structures and functions. Although it has been linked to various biological processes and disease pathogenesis, the underlying mechanism remains poorly understood due to a lack of effective tools to enrich, detect, and localize this PTM. Herein, we report the design and development of a biotin thiol tag that enables derivatization, enrichment, and confident identification of citrullination via mass spectrometry. We perform global mapping of the citrullination proteome of mouse tissues. In total, we identify 691 citrullination sites from 432 proteins which represents the largest data set to date. We discover novel distribution and functions of this PTM. This study depicts a landscape of protein citrullination and lays the foundation for further deciphering their physiological and pathological roles.

Signal Amplification Pretargeted PET/Fluorescence Imaging Based on Human Serum Albumin-Encapsulated GdF3 Nanoparticles for Diagnosis of Ovarian Cancer.

Different modal imaging techniques could be complementary in tumor diagnosis. Human serum albumin (HSA)-encapsulated GdF3 nanoparticles were developed as T1 magnetic resonance imaging (MRI) contrast agents. However, no significant T1 enhancement in the tumor site of the SKOV3 human ovarian cancer xenograft tumor model was observed within 3 h after injection of tetrazine-modified GdF3@HSA NPs through small-animal MRI. After intravenous injection of 18F (or Cy7)-labeled Reppe anhydride, pretargeted positron emission tomography (PET) (near-infrared (NIR) fluorescence) imaging was used to reveal the pharmacokinetics of GdF3@HSA NPs in the SKOV3 xenograft mouse model to locate the tumor. The probe based on Reppe anhydride achieved rapid ligation with tetrazine-modified GdF3@HSA nanoparticles (NPs), which accumulated in tumor through Reppe anhydride/tetrazine bioorthogonal chemistry. This pretargeting strategy enabled excellent tumor visualization and quantification at an early period after nanoparticle injection (3 h p.i.), while the MRI images with significant T1 enhancement could be obtained until 24 h after injection of Gd-based contrast agents only. In vivo pretargeted multimodal imaging based on the tetrazine/Reppe anhydride system using HSA-encapsulated GdF3 nanoparticles would be beneficial for amplification of the imaging signal in the disease site and enhancing diagnostic efficiency.

The effect of calcium supplementation in people under 35 years old: A systematic review and meta-analysis of randomized controlled trials.

Background: The effect of calcium supplementation on bone mineral accretion in people under 35 years old is inconclusive. To comprehensively summarize the evidence for the effect of calcium supplementation on bone mineral accretion in young populations (≤35 years). Methods: This is a systematic review and meta-analysis. The Pubmed, Embase, ProQuest, CENTRAL, WHO Global Index Medicus, Clinical Trials.gov, WHO ICTRP, China National Knowledge Infrastructure (CNKI), and Wanfang Data databases were systematically searched from database inception to April 25, 2021. Randomized clinical trials assessing the effects of calcium supplementation on bone mineral density (BMD) or bone mineral content (BMC) in people under 35 years old. Results: This systematic review and meta-analysis identified 43 studies involving 7,382 subjects. Moderate certainty of evidence showed that calcium supplementation was associated with the accretion of BMD and BMC, especially on femoral neck (standardized mean difference [SMD] 0.627, 95% confidence interval [CI] 0.338-0.915; SMD 0.364, 95% CI 0.134-0.595; respectively) and total body (SMD 0.330, 95% CI 0.163-0.496; SMD 0.149, 95% CI 0.006-0.291), also with a slight improvement effect on lumbar spine BMC (SMD 0.163, 95% CI 0.008-0.317), no effects on total hip BMD and BMC and lumbar spine BMD were observed. Very interestingly, subgroup analyses suggested that the improvement of bone at femoral neck was more pronounced in the peripeak bone mass (PBM) population (20-35 years) than the pre-PBM population (<20 years). Conclusions: Our findings provided novel insights and evidence in calcium supplementation, which showed that calcium supplementation significantly improves bone mass, implying that preventive calcium supplementation before or around achieving PBM may be a shift in the window of intervention for osteoporosis. Funding: This work was supported by Wenzhou Medical University grant [89219029].

Osteoporosis and bone fractures are common problems among older people, particularly older women. These conditions cause disability and reduce quality of life. Progressive loss of bone mineral density is usually the culprit. So far, strategies to prevent bone weakening with age have produced disappointing results. For example, taking calcium supplements in later life only slightly reduces the risk of osteoporosis or fracture. New approaches are needed. Bone mass increases gradually early in life and peaks and plateaus around 20-35 years of age. After that period, bone mass slowly declines. Some scientists suspect that increasing calcium intake during this period of peak bone mass may reduce osteoporosis or fracture risk later in life. A meta-analysis by Liu, Le et al. shows that boosting calcium intake in young adulthood strengthens bones. The researchers analyzed data from 43 randomized controlled trials that enrolled 7,382 participants. About half the studies looked at the effects of taking calcium supplements and the other half analyzed the effects of a high calcium diet. Boosting calcium intake in people younger than age 35 improved bone mineral density throughout the body. It also increased bone mineral density at the femoral neck, where most hip fractures occur. Calcium supplementation produced larger effects in individuals between the ages of 20 and 35 than in people younger than 20. Both high calcium diets and calcium supplements with doses less than 1000 mg/d boosted bone strength. Higher dose calcium supplements did not provide any extra benefits. The analysis suggests people should pay more attention to bone health during early adulthood. Large randomized clinical trials are needed to confirm the long-term benefits of boosting calcium intake during early adulthood. But if the results are validated, taking calcium supplements, or eating more calcium-rich foods between the ages of 20 and 35 may help individuals build healthier bones and prevent fractures and osteoporosis later in life.

A Nomogram to Predict Recurrence-Free Survival Following Surgery for Vestibular Schwannoma.

Background: Vestibular schwannoma (VS) is the most common benign tumor of the posterior fossa. The recurrence of VS has always received widespread attention. This study aimed to develop a nomogram to predict Recurrence-free survival (RFS) following resection of VS. Methods: A total of 425 patients with VS who underwent resection at the Department of Neurosurgery in Chinese PLA General Hospital between January 2014 and December 2020 were enrolled in this retrospective study. The medical records and follow-up data were collected. Cox regression analysis was used to screen prognostic factors and construct the nomogram. The predictive accuracy and clinical benefits of the nomogram were validated using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Results: The Cox regression analysis revealed that age (HR = 0.96; 95% CI 0.94 - 0.99; p < 0.01), EOR (HR = 4.65; 95% CI 2.22 - 9.74; p < 0.001), and Ki-67 (HR = 1.16; 95% CI 1.09 - 1.23; p < 0.001) were all significantly correlated with recurrence, and they were finally included in the nomogram model. The concordance index of the nomogram was 0.86. The areas under the curve (AUCs) of the nomogram model of 3-, 4- and 5-year were 0.912, 0.865, and 0.809, respectively. A well-fitted calibration curve was also generated for the nomogram model. The DCA curves also indicated that the nomogram model had satisfactory clinical utility compared to the single indicators. Conclusions: We developed a nomogram that has high accuracy in predicting RFS in patients after resection of VS. All of the included prognostic factors are easy to obtain. The nomogram can improve the postoperative management of patients and assist clinicians in individualized clinical treatment. Furthermore, we generated a web-based calculator to facilitate clinical application: https://abc123-123.shinyapps.io/VS-RFS/.