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Amidst the rapid advancements in materials science, the exploration of aerogel-based biomaterials has garnered extensive attention across diverse sectors, including biomedicine, energy, architecture, and sensing. Comprehensive studies have unveiled the utilization of organic, inorganic, and hybridized materials for aerogel preparation, catapulting aerogel-based biomaterials to global prominence. Endowed with distinctive properties, including low density, a hierarchical porous network, high porosity, and nanoscale micropores, aerogels have exhibited a broad spectrum of applications, particularly in the realm of tissue engineering. The deployment of aerogel-based biomaterials in tissue engineering is in a dynamic phase of development, with available reports indicating varying degrees of exploration in fields such as blood vessels, soft tissues, nerves, skin, muscles, heart, bronchial tubes, bone, and cartilage—an evolutionary process. This paper offers a comprehensive review of the evolution of aerogel properties and preparation processes, encapsulating strategic insights for the application of aerogel-based biomaterials in tissue engineering. It succinctly summarizes recent developments in tissue engineering research, emphasizing their significance. Additionally, the review outlines future prospects for the application of aerogels in tissue engineering and envisions challenges arising from current studies. Through this thorough exploration of aerogel-based biomaterials in tissue engineering, the paper aspires to make a profound impact on regenerative medicine, offering innovative and effective application strategies for biomedicine.

Abstract Analyzing the influence of tourism on carbon emission has significant implications for promoting the sustainable development of tourism. Based on the panel data of 31 tourist cities in China from 2005 to 2022, this study utilizes a structural equation model to explore the carbon reduction effect of tourism development and its influencing mechanism. The results show that: (1) The overall carbon emission efficiency of tourism cities first decreased and then increased, rised to a peak of 0.923 in 2022. (2) Tourism development has a significant positive impact on carbon emission efficiency, and there are three influence paths: tourism → environmental regulation → carbon emission efficiency, tourism → environmental regulation → industrial structure → carbon emission efficiency, and tourism → industrial structure → carbon emission efficiency. (3) The influence of tourism development on carbon emission efficiency mainly depends on the direct effect, and the development of tourism also indirectly affect the industrial structure. Environmental regulation also mainly depends on the direct effect on carbon emission efficiency. (4) Foreign direct investment lead to the reduction of carbon emission efficiency in both direct and indirect aspects.

Abstract Background Characterizing cancer molecular subtypes is crucial for improving prognosis and individualized treatment. Integrative analysis of multi-omics data has become an important approach for disease subtyping, yielding better understanding of the complex biology. Current multi-omics integration tools and methods for cancer subtyping often suffer challenges of high computational efficiency as well as the problem of weight assignment on data types. Results Here, we present an efficient multi-omics integration via weighted affinity and self-diffusion (MOSD) to dissect cancer heterogeneity. MOSD first construct local scaling affinity on each data type and then integrate all affinities by weighted linear combination, followed by the self-diffusion to further improve the patients’ similarities for the downstream clustering analysis. To demonstrate the effectiveness and usefulness for cancer subtyping, we apply MOSD across ten cancer types with three measurements (Gene expression, DNA methylation, miRNA). Conclusions Our approach exhibits more significant differences in patient survival and computationally efficient benchmarking against several state-of-art integration methods and the identified molecular subtypes reveal strongly biological interpretability. The code as well as its implementation are available in GitHub: https://github.com/DXCODEE/MOSD .

BackgroundIn elderly individuals suffering from hip fractures, a prolonged hospital length of stay (PLOS) not only heightens the probability of patient complications but also amplifies mortality risks. Yet, most elderly hip fracture patients present compromised baseline health conditions. Additionally, PLOS leads to increased expenses for patient treatment and care, while also diminishing hospital turnover rates. This, in turn, jeopardizes the prompt allocation of beds for urgent cases.MethodsA retrospective study was carried out from October 2021 to November 2023 on 360 elderly hip fracture patients who underwent surgical treatment at West China Hospital. The 75th percentile of the total patient cohort’s hospital stay duration, which was 12 days, was used to define prolonged hospital length of stay (PLOS). The cohort was divided into training and testing datasets with a 70:30 split. A predictive model was developed using the random forest algorithm, and its performance was validated and compared with the Lasso regression model.ResultsOut of 360 patients, 103 (28.61%) experienced PLOS. A Random Forest classification model was developed using the training dataset, identifying 10 essential variables. The Random Forest model achieved perfect performance in the training set, with an area under the curve (AUC), balanced accuracy, Kappa value, and F1 score of 1.000. In the testing set, the model’s performance was assessed with an AUC of 0.846, balanced accuracy of 0.7294, Kappa value of 0.4325, and F1 score of 0.6061.ConclusionThis study aims to develop a prognostic model for predicting delayed discharge in elderly patients with hip fractures, thereby improving the accuracy of predicting PLOS in this population. By utilizing machine learning models, clinicians can optimize the allocation of medical resources and devise effective rehabilitation strategies for geriatric hip fracture patients. Additionally, this method can potentially improve hospital bed turnover rates, providing latent benefits for the healthcare system.

NAD(P)HX dehydratase (NAXD) gene is one of the key enzymes encoding the nicotinamide nucleotide repair system, reportedly associated with Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 (PEBEL2). Here, we generated an induced pluripotent stem cell (iPSC) line from the dermal fibroblasts (HDFs) of a PEBEL2 patient who carried biallelic mutations, c.101_102delTA(p.Thr35Phefs*63) and c.318C > G (p.Ile160Met) in NAXD. These iPSCs showed stable amplification in vitro, expressed pluripotent markers, and differentiated spontaneously into three germ layers, as well as NAXD mutations with normal karyotype.

Drosophila spermatogenesis involves the renewal of germline stem cells, meiosis of spermatocytes, and morphological transformation of spermatids into mature sperm. We previously demonstrated that Ocnus (ocn) plays an essential role in spermatogenesis. The ValRS-m (Valyl-tRNA synthetase, mitochondrial) gene was down-regulated in ocn RNAi testes. Here, we found that ValRS-m-knockdown induced complete sterility in male flies. The depletion of ValRS-m blocked mitochondrial behavior and ATP synthesis, thus inhibiting the transition from spermatogonia to spermatocytes, and eventually, inducing the accumulation of spermatogonia during spermatogenesis. To understand the intrinsic reason for this, we further conducted transcriptome-sequencing analysis for control and ValRS-m-knockdown testes. The differentially expressed genes (DEGs) between these two groups were selected with a fold change of ≥2 or ≤1/2. Compared with the control group, 4725 genes were down-regulated (dDEGs) and 2985 genes were up-regulated (uDEGs) in the ValRS-m RNAi group. The dDEGs were mainly concentrated in the glycolytic pathway and pyruvate metabolic pathway, and the uDEGs were primarily related to ribosomal biogenesis. A total of 28 DEGs associated with mitochondria and 6 meiosis-related genes were verified to be suppressed when ValRS-m was deficient. Overall, these results suggest that ValRS-m plays a wide and vital role in mitochondrial behavior and spermatogonia differentiation in Drosophila.

Abstract Background Treating lateral compression type 1 (LC1) pelvic ring injuries in older patients is controversial. This study evaluated surgical treatments combined with ERAS for treating LC1 pelvic fractures in the elderly. Methods In this retrospective study, patients who underwent surgery with INFIX (supra-acetabular spinal pedicle screws, and a subcutaneous connecting rod; the experimental group) or superior pubic ramus cannulated screw (the control group) fixation of LC1 pelvic fracture from January 2019 to January 2022 were reviewed. Injury radiography and computed tomography were performed to determine the Young–Burgess classification. All patients performed standardized early rehabilitation exercises after surgery and were followed up for > 12 months. After surgery, the Matta score and the visual analog scale (VAS) were evaluated, and the postoperative weight-bearing time and the length of stay (LOS) were recorded. The Barthel index and the Majeed score were evaluated at 4 months after surgery and at the last follow-up. Results Fifty-three patients were included. Thirty-two patients included in the experimental group had a mean age of 75.0 ± 6.2 (range, 66–86) years, and the other 21 patients in the control group had a mean age of 74.6 ± 4.6 (range, 68–83) years. The mean follow-up time was 13.1 ± 1.6 (range, 12–18) months in the experimental group and 13.4 ± 1.3 (range, 12–16) months in the control group. There were no significant differences in follow-up time between the groups (P > 0.05). The mean VAS score, time to weight-bearing, and LOS were 2.0 ± 0.7 (range, 1–3), 1.1 ± 0.3 (range, 1–2) d, and 5.8 ± 0.9 (range, 4–7) d in the experimental group and 2.3 ± 1.2 (range, 1–5), 2.5 ± 1.6 (range, 1–7) d, and 6.1 ± 1.6 (range, 5–11) d in the control group, respectively. Between the two groups, there was a significant difference in the postoperative time to weight-bearing (P 0.05). No bedrest-related complications occurred in either group. The Matta score was 90.6% in the experimental group and 90.4% in the control group (P > 0.05). At the 4-months follow-up, the experimental group had a better Barthel index and Majeed score compared with the control group, which were 86.1 ± 6.2 (range, 70–95) vs. 81.2 ± 4.1 (range, 75–90) and 86.3 ± 3.3 (range, 78–91) vs. 80.3 ± 3.9 (range, 76–86), respectively. The experimental group had better early rehabilitation effect than the control group. There was no significant difference in Barthel index and Majeed score between the two groups at the last follow-up (P > 0.05). Conclusion Both INFIX and intramedullary superior pubic ramus cannulated screws can successfully treat LC1 pelvic fractures and reduce bed rest complications among older patients.

Abstract Background Testis is the only organ supporting sperm production and with the largest number of proteins and tissue-specific proteins in animals. In our previous studies, we have found that knockdown of ocnus (ocn), a testis-specific gene, resulted in much smaller testis with no germ cells in Drosophila melanogaster. However, the molecular consequences of ocn knockdown in fly testes are unknown. Results In this study, through iTRAQ quantitative proteomics sequencing, 606 proteins were identified from fly abdomens as having a significant and at least a 1.5-fold change in expression after ocn knockdown in fly testes, of which 85 were up-regulated and 521 were down-regulated. Among the differential expressed proteins (DEPs), apart from those proteins involved in spermatogenesis, the others extensively affected biological processes of generation of precursor metabolites and energy, metabolic process, and mitochondrial transport. Protein-protein interaction (PPI) analyses of DEPs showed that several kinases and/or phosphatases interacted with Ocn. Re-analyses of the transcriptome revealed 150 differential expressed genes (DEGs) appeared in the DEPs, and their changing trends in expressions after ocn knockdown were consistent. Many common down-regulated DEGs and DEPs were testis-specific or highly expressed in the testis of D. melanogaster. Quantitative RT-PCR (qRT-PCR) confirmed 12 genes appeared in both DEGs and DEPs were significantly down-regulated after ocn knockdown in fly testes. Furthermore, 153 differentially expressed phosphoproteins (DEPPs), including 72 up-regulated and 94 down-regulated phosphorylated proteins were also identified (13 phosphoproteins appeared in both up- and down-regulated groups due to having multiple phosphorylation sites). In addition to those DEPPs associated with spermatogenesis, the other DEPPs were enriched in actin filament-based process, protein folding, and mesoderm development. Some DEPs and DEPPs were involved in Notch, JAK/STAT, and cell death pathways. Conclusions Given the drastic effect of the ocn knockdown on tissue development and testis cells composition, the differences in protein abundance in the ocn knockdown flies might not necessarily be the direct result of differential gene regulation due to the inactivation of ocn. Nevertheless, our results suggest that the expression of ocn is essential for Drosophila testis development and that its down-regulation disturbs key signaling pathways related to cell survival and differentiation. These DEPs and DEPPs identified may provide significant candidate set for future studies on the mechanism of male reproduction of animals, including humans.

Abstract Background Debates exist on the treatment decision of the stage II/III colorectal cancer (CRC) due to the insufficiency of the current TNM stage‐based risk stratification system. Epithelial–mesenchymal transition (EMT) and tumor microenvironment (TME) have both been linked to CRC progression in recent studies. We propose to improve the prognosis prediction of CRC by integrating TME and EMT. Methods In total, 2382 CRC patients from seven datasets and one in‐house cohort were collected, and 1640 stage II/III CRC patients with complete survival information and gene expression profiles were retained and divided into a training cohort and three independent validation cohorts. Integrated analysis of 398 immune, stroma, and epithelial‐mesenchymal transition (ISE)‐related genes identified an ISE signature independently associated with the recurrence of CRC. The underlying biological mechanism of the ISE signature and its influence on adjuvant chemotherapy was further explored. Results We constructed a 26‐gene signature which was significantly associated with poor outcome in Training cohort (p

Background: The integrity of the radial head is critical to maintaining elbow joint stability. For radial head fractures requiring surgical treatment, headless compression cannulated screw fixation is a less invasive scheme that has fewer complications. The aim of this study was to compare the mechanical stability of different fixation devices, including headless compression cannulated screws and mini-T-plates, for the fixation of transversely unstable radial head fractures.Methods: Forty identical synthetic radius bones were used to construct transverse unstable radial head fracture models. Parallel, cross, and tripod headless compression cannulated screw fixation and mini-T plate fixation were applied. The structural stiffness of each group was compared by static shear loading. Afterward, cyclic loading was performed in each of the three directions of the radial head, and the shear stability of each group was compared by calculating the maximum radial head displacement at the end of the cycle.Findings: The mini-T plate group had the lowest structural stiffness (51.8 ± 7.7 N/mm) and the highest relative displacement of the radial head after cyclic loading (p < 0.05). The tripod headless compression cannulated screw group had the highest structural stiffness among all screw groups (p < 0.05). However, there was no significant difference in the relative displacement of the radial head between the screw groups after cyclic loading in different directions (p > 0.05).Interpretation: In conclusion, the biomechanical stability of the mini-T plate for fixation of transverse unstable radial head fractures is lower than that of headless compression cannulated screws. Tripod fixation provides more stable fixation than parallel and cross fixation with headless compression cannulated screws for the treatment of transversely unstable radial head fractures.

Bone regeneration following trauma, tumor resection, infection, or congenital disease is challenging. Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia. It can result in complications affecting multiple systems including the musculoskeletal system. The increased number of diabetes-related fractures poses a great challenge to clinical specialties, particularly orthopedics and dentistry. Various pathological factors underlying DM may directly impair the process of bone regeneration, leading to delayed or even non-union of fractures. This review summarizes the mechanisms by which DM hampers bone regeneration, including immune abnormalities, inflammation, reactive oxygen species (ROS) accumulation, vascular system damage, insulin/insulin-like growth factor (IGF) deficiency, hyperglycemia, and the production of advanced glycation end products (AGEs). Based on published data, it also summarizes bone repair strategies in diabetic conditions, which include immune regulation, inhibition of inflammation, reduction of oxidative stress, promotion of angiogenesis, restoration of stem cell mobilization, and promotion of osteogenic differentiation, in addition to the challenges and future prospects of such approaches.

Objectives: This study sought to derive and validate a simple model combining traditional clinical risk factors with biomarkers and imaging indicators easily obtained from routine preoperative examinations to predict functionally significant coronary artery disease (CAD) in Chinese populations. Methods: We developed five models from a derivation cohort of 320 patients retrospective collected. In the derivation cohort, we assessed each model discrimination using the area under the receiver operating characteristic curve (AUC), reclassification using the integrated discrimination improvement (IDI) and net reclassification improvement (NRI), calibration using the Hosmer-Lemeshow test, and clinical benefit using decision curve analysis (DCA) to derive the optimal model. The optimal model was internally validated by bootstrapping, and external validation was performed in another cohort including 96 patients. Results: The optimal model including 5 predictors (age, sex, hyperlipidemia, hs-cTnI and LVEF) achieved an AUC of 0.807 with positive NRI and IDI in the derivation cohort. Moreover, the Hosmer-Lemeshow test showed a good fit, and the DCA demonstrated good clinical net benefit. The C-statistic calculated by bootstrapping internal validation was 0.798, and the calibration curve showed adequate calibration (Brier score = 0.179). In the external validation cohort, the optimal model performance was acceptable (AUC = 0.704; Brier score = 0.20). Finally, a nomogram based on this model was constructed to facilitate its use in clinical practice. Conclusions: A simple model combined clinical risk factors with hs-cTnI and LVEF improving the prediction of functionally significant CAD in Chinese populations. This attractive model may be a choice for clinicians to risk stratification for CAD.

To address the problems of slow convergence speed, easy to fall into local minima and low convergence accuracy presented by previous algorithms in DC distribution network fault location, this paper adopts the improved artificial bee colony slime mould algorithm (SMA) to improve and solve. On the basis of SMA, an adaptive adjustable feedback factor and an improved crossover operator are introduced to improve the convergence speed; artificial bee colony (ABC) algorithm is introduced to improve the search ability to jump out of local minima, and the artificial bee colony slime mould algorithm (ISMA) is formed. Firstly, based on the six-terminal DC distribution network topology, a mathematical model of bipolar short-circuit fault as well as single-pole grounded short-circuit fault is established based on a fault occurring between G-VSC and W-VSC as an example. Then the principle of the improved ISMA is introduced in detail, and a suitable fitness function is established as the measure of fault location in DC distribution network. Finally, experimental simulations are conducted to obtain fault points from the optimization search and compare them with the actual values to verify the accuracy of the algorithm. In addition, the efficiency and robustness of ISMA are further verified by comparing with other algorithms.

Calcium silicate-based cement is a promising material for filling root canals. However, it has several drawbacks to its clinical application, including difficult operation and low curing strength. In this study, we successfully prepared an ultrafine tricalcium silicate powder and investigated the effects of this ultrafine powder on the performance of the premixed tricalcium silicate cement, including the curing process, setting time, hydration products, microstructure, injectivity, fluidity, and compressive strength. The results demonstrate that the addition of ultrafine tricalcium silicate powder alters the hydration product content and product morphology of the premixed cement. By increasing the content of the ultrafine powder, the injectable property of the cement can be increased to more than 95%, the fluidity can be increased from 18 mm to 35 mm, and the curing time can be shortened from 13 h to 11 h. Notably, the addition of the ultrafine powder greatly enhances the compressive strength of the hardened cement, which increases from 20.6 MPa to 51.0 MPa. These results indicate that altering the particle size distribution of the powder is an effective method for enhancing the physicochemical and mechanical properties of tricalcium silicate cement as a root canal filling material.

IntroductionCalf muscular vein thrombosis (CMVT) is a common complication in geriatric hip fracture patients. Despite its high incidence, prior research on the topic is limited. The occurrence of CMVT in patients will prolong the preoperative waiting time and even lead to serious thromboembolic events, which can be detrimental to the patient’s prognosis. Therefore, this study aimed to identify the risk factors for preoperative CMVT in geriatric hip fracture patients and construct a nomogram model to predict the risk of preoperative CMVT in patients.Materials and methodsGeriatric hip fracture patients who underwent surgery between January 2019 and January 2022 were included. The patients were categorized into two groups depending on whether they had preoperative CMVT, confirmed through Color Doppler ultrasound or venography examination. Univariate and multivariate logistic regression analyses were used to analyze demographic characteristics, medical history, comorbidities, and laboratory tests. A nomogram was constructed to predict preoperative CMVT in geriatric hip fracture patients based on the results of the multivariate logistic regression.ResultsThree hundred and eighty-eight geriatric hip fracture patients, including one hundred and thirty-four patients with CMVT and two hundred and fifty-four patients without CMVT, were ultimately included in our study. After multivariable logistic regression analysis, the time from injury to admission, smoking history, serum albumin levels, and D-dimer levels was identified as independent risk factors and was entered into a nomogram model. The nomogram showed robust discrimination, with an area under the receiver operating characteristic curve of 0.805. The calibration curve showed strong agreement between the CMVT probabilities predicted by the nomogram and the actual probabilities. The decision curve analysis illustrates the excellent clinical utility of the model.ConclusionWe have constructed a new nomogram prediction model that can effectively predict the risk of preoperative CMVT in geriatric hip fracture patients based on their medical history and blood test results. This model can help clinicians make individualized predictions of CMVT that are tailored to each patient’s unique circumstances.

Summary: Chronic neurodegeneration and acute injuries lead to neuron losses via diverse processes. We compared retinal ganglion cell (RGC) responses between chronic glaucomatous conditions and the acute injury model. Among major RGC subclasses, αRGCs and intrinsically photosensitive RGCs (ipRGCs) preferentially survive glaucomatous conditions, similar to findings in the retina subject to axotomy. Focusing on an αRGC intrinsic factor, Osteopontin (secreted phosphoprotein 1 [Spp1]), we found an ectopic neuronal expression of Osteopontin (Spp1) in other RGCs subject to glaucomatous conditions. This contrasted with the Spp1 downregulation subject to axotomy. αRGC-specific Spp1 elimination led to significant αRGC loss, diminishing their resiliency. Spp1 overexpression led to robust neuroprotection of susceptible RGC subclasses under glaucomatous conditions. In contrast, Spp1 overexpression did not significantly protect RGCs subject to axotomy. Additionally, SPP1 marked adult human RGC subsets with large somata and SPP1 expression in the aqueous humor correlated with glaucoma severity. Our study reveals Spp1’s role in mediating neuronal resiliency in glaucoma.

Various wounds caused by burns, trauma, surgery, and genetic irregularities, including acute and chronic wounds, pose a huge burden on global healthcare. Many therapeutic strategies, such as nanomedicine and regenerative medicine, have been applied to wound repair and skin regeneration. As a promising and exciting nanomaterial, metal–organic frameworks (MOFs) encompass many desirable properties, including crystalline porous structure, tunable size, good mechanical stability, large specific surface area, and exceptional chemical stability. Most importantly, the performance of MOFs can be modulated by changing synthesis steps and conditions. MOFs can release metal ions to modulate cellular behaviors and kill various microorganisms, which meets this dual agent release therapeutic strategy for wound healing and skin regeneration. Additionally, MOFs can act as carriers for delivering bioactive agents in a desired manner. Recently, an increasing number of researchers have conducted many studies on applying various MOFs in wound healing and skin regeneration. Based on this, we perform this study to report the current status and further perspective of MOFs-based therapeutic strategy. Furthermore, the molecular process of wound healing and the fabrication of MOFs were also discussed.

Thiamine pyrophosphokinase (TPK) deficiency, is a rare autosomal recessive disorder of congenital metabolic dysfunction caused by variants in the TPK1 gene. TPK1 variants can lead to thiamine metabolic pathway obstacles, and its clinical manifestations are highly variable. We describe two cases of TPK deficiency with completely different phenotypes and different therapeutic effects, and 26 cases of previously reported were retrospectively reviewed to improve our understanding of the clinical and genetic features of the disease. Patients with TPK deficiency present with ataxia, dysarthria, dystonia, disturbance of consciousness, seizures, and other nervous system dysfunction. Different gene variant sites may lead to different clinical features and therapeutic effects. Gene analysis is important for the diagnosis of TPK deficiency caused by TPK1 variants, and thiamine supplementation has been the mainstay of treatment for TPK deficiency to date.

Abstract Background This study aimed to develop a radiogenomic prognostic prediction model for colorectal cancer (CRC) by investigating the biological and clinical relevance of intratumoural heterogeneity. Methods This retrospective multi-cohort study was conducted in three steps. First, we identified genomic subclones using unsupervised deconvolution analysis. Second, we established radiogenomic signatures to link radiomic features with prognostic subclone compositions in an independent radiogenomic dataset containing matched imaging and gene expression data. Finally, the prognostic value of the identified radiogenomic signatures was validated using two testing datasets containing imaging and survival information collected from separate medical centres. Results This multi-institutional retrospective study included 1601 patients (714 females and 887 males; mean age, 65 years ± 14 [standard deviation]) with CRC from 5 datasets. Molecular heterogeneity was identified using unsupervised deconvolution analysis of gene expression data. The relative prevalence of the two subclones associated with cell cycle and extracellular matrix pathways identified patients with significantly different survival outcomes. A radiogenomic signature-based predictive model significantly stratified patients into high- and low-risk groups with disparate disease-free survival (HR = 1.74, P = 0.003). Radiogenomic signatures were revealed as an independent predictive factor for CRC by multivariable analysis (HR = 1.59, 95% CI:1.03–2.45, P = 0.034). Functional analysis demonstrated that the 11 radiogenomic signatures were predominantly associated with extracellular matrix and immune-related pathways. Conclusions The identified radiogenomic signatures might be a surrogate for genomic signatures and could complement the current prognostic strategies.

Abstract Bone defects still pose various challenges in osteology. As one treatment method for bone defects, tissue engineering requires biomaterials with good biocompatibility and stem cells with good differentiation. This study aimed to fabricate a 3D-printed polylactic acid and hydroxyapatite (PLA/HA) composite scaffold with urine-derived stem cells (USCs) to study its therapeutic effect in a rat model of skull defects. USCs were isolated and extracted from the urine of healthy adult males and inoculated onto PLA/HA and PLA scaffolds fabricated by 3D printing technology. A total of 36 skull defect models in eighteen Sprague–Dawley rats were randomly divided into a control group (no treatment of the defects), PLA group (treated with PLA scaffolds with USCs), and PLA/HA group (treated with PLA/HA scaffolds with USCs). The therapeutic efficacy was evaluated by real-time PCR, microcomputed tomography (micro-CT), and immunohistochemistry at 4, 8, and 12 weeks. We found that the PLA/HA scaffold loaded with USCs effectively promoted new bone regeneration in the defect area. CT images showed that in the PLA/HA group, the defect area was almost entirely covered by newly formed bone (coverage of 96.7 ± 1.6%), and the coverage was greater than that in the PLA group (coverage of 74.6 ± 1.9%) at 12 weeks. Histology and immunohistochemical staining showed the highest new bone formation on the PLA/HA scaffolds containing USCs in the defect site at 12 weeks. These findings demonstrate the broad application prospects of PLA/HA scaffolds with USCs in bone tissue engineering. Graphical abstract

Abstract In Drosophila ovary, niche is composed of somatic cells, including terminal filament cells (TFCs), cap cells (CCs) and escort cells (ECs), which provide extrinsic signals to maintain stem cell renewal or initiate cell differentiation. Niche establishment begins in larval stages when terminal filaments (TFs) are formed, but the underlying mechanism for the development of TFs remains largely unknown. Here we report that transcription factor longitudinals lacking (Lola) is essential for ovary morphogenesis. We showed that Lola protein was expressed abundantly in TFCs and CCs, although also in other cells, and lola was required for the establishment of niche during larval stage. Importantly, we found that knockdown expression of lola induced apoptosis in adult ovary, and that lola affected adult ovary morphogenesis by suppressing expression of Regulator of cullins 1b (Roc1b), an apoptosis-related gene that regulates caspase activation during spermatogenesis. These findings significantly expand our understanding of the mechanisms controlling niche establishment and adult oogenesis in Drosophila.

Summary: The wiring of visual circuits requires that retinal neurons functionally connect to specific brain targets, a process that involves activity-dependent signaling between retinal axons and their postsynaptic targets. Vision loss in various ophthalmological and neurological diseases is caused by damage to the connections from the eye to the brain. How postsynaptic brain targets influence retinal ganglion cell (RGC) axon regeneration and functional reconnection with the brain targets remains poorly understood. Here, we established a paradigm in which the enhancement of neural activity in the distal optic pathway, where the postsynaptic visual target neurons reside, promotes RGC axon regeneration and target reinnervation and leads to the rescue of optomotor function. Furthermore, selective activation of retinorecipient neuron subsets is sufficient to promote RGC axon regeneration. Our findings reveal a key role for postsynaptic neuronal activity in the repair of neural circuits and highlight the potential to restore damaged sensory inputs via proper brain stimulation.

Vascularization plays a crucial role in transporting and exchanging nutrients and oxygen between implanted grafts with the host tissue. In the biofabrication of the implanted grafts, remodeling the vascular networks can accelerate vascularized tissue repair and regeneration. Given the heterogeneity of vascular networks in vascularized tissues, traditional scaffold manufacturing techniques cannot effectively achieve vascular with various scales in vitro and in vivo biomimetic. In recent years, 3D bioprinting technologies have been widely used in fabricating various 3D grafts for tissue repair and regeneration due to their shape customizability, simple manufacturing procedure, reproducibility, and precise multi-dimensional control. With the rapid development of 3D bioprinting technologies, bioprinting-based biofabrication strategies have been gradually applied in the construction of various vascularized tissues. Based on this background, our study aimed to review recent advances, challenges, and future perspectives in biofabrication strategies based on bioprinting for vascularized tissue repair and regeneration. The bioprinting techniques, bioinks, seed cells, and growth factors used for vascularized tissue construction were also enrolled in this review. In addition, the bioprinting history, vessel formation mechanism, and histology of vascular networks in vascularized tissue were also discussed.

BackgroundBilateral posterior hip dislocation and femoral head fracture are rare injuries, which may be the earliest case report that focuses on treatment with open reduction via the direct anterior approach (DAA) for bilateral symmetrical Pipkin type II fracture within 5 years of the follow-up period.Case reportWe present a case of bilateral posterior dislocation with a femoral head fracture (Pipkin II) of the hip in 47-year-old woman caused by a high-velocity accident. The dislocation was successfully reduced under general anesthesia at a local hospital and transferred to a tertiary center for surgical management. She was surgically treated with internal fixation using three Herbert screws on the bilateral hips. The DAA was used during surgery. Follow-up for 5 years was performed, and functional outcomes were evaluated using the D'Aubigné range of motion and modified Harris hip score. The range of motion in the bilateral hip was satisfactory, with no signs of post-traumatic arthritis, heterotopic ossification, or avascular necrosis of the femoral head.ConclusionSurgical management of bilateral Pipkin type II fractures was performed successfully with open reduction and internal fixation using a safe and reliable direct anterior approach, with good functional outcomes at 5-year follow-up.

Axarus fungorum (Albu, 1980) exhibits certain adaptations to different aquatic environments, appearing as an important evaluation element for freshwater quality monitoring. In this study, complete mitogenome of A. fungorum was provided for the first time to define the systematic and phylogenetic history of this taxon. The whole mitogenome is 15,696 bp long with high A + T content that consists of 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and a noncoding control region. ML analysis showed support for monophyly of Chironominae and close relationship between A. fungorum and Chironomus generic genera.

PurposeThe objective of this study was to evaluate the association between thyroid hormone and bone mineral density (BMD) among euthyroid adults.MethodsThis cross-sectional study researched the information from the National Health and Nutrition Examination Survey 2007–2010. We included 3,759 euthyroid participants finally. We used multivariate linear regression models to evaluate the linear relationship between the thyroid hormone profile and BMD. Subgroup analyses stratified by gender and age were further performed. Moreover, the nonlinear relationship was characterized by fitted smoothing curves and generalized additive models, and logistic regression models were used to determine the association of thyroid-stimulating hormone (TSH) and thyroxine (T4) with previous fractures.ResultsThe weighted multivariable linear regression models showed no association between TSH and BMD. Free thyroxine (FT4), T4, free triiodothyronine (FT3), and total triiodothyronine (T3) were negatively associated with the total femur BMD and the total spine BMD after adjusting for all covariates. Subgroup analyses demonstrated that all groups had a negative association between T4 and BMD, even in patients with osteopenia/osteoporosis. The nonlinear relationship characterized by smooth curve fittings and generalized additive models suggested that an obvious U-shaped, an inverted U -shaped, and an L - shaped curve was exhibited between thyroid hormone and BMD in the different subgroups. In addition, normal high-level T4 was associated with an increased prevalence of previous fractures than normal low-level T4.ConclusionsIn this sample of euthyroid adults, T4 exhibits a negative correlation with BMD, regardless of age and gender, in subjects with either normal or lowered BMD. Moreover, high-normal FT4 was associated with an increased prevalence of previous fractures. TSH was not associated with variations of BMD and the fracture risk.

The number of skeletal muscle injuries derived from myopathies, exercise, and trauma, is growing due to increasing sports activities in normal life of people. Skeletal muscle has a robust capacity for regeneration following injury. However, few if any effective therapeutic options for volumetric muscle loss are available. Poor repair of muscle injury will lead to skeletal muscle dysfunction, resulting in physical pain and even seriously compromising daily life. As a new technology of biomedicine, 3D bioprinting is widely used in the field of tissue engineering and regenerative medicine due to its enormous advantages. 3D bioprinting creates biological structures similar to that of protists by precisely constructing a specified geometric shape at micro/nano levels, thus addressing the unmet needs in tissue replacement and organ transplantation. With the further application of bioprinting in various tissue repairs, more and more researchers utilized 3D bioprinting in skeletal muscle regeneration. Various bioinks, such as alginate, gelatin, fibrin hydrogels, and extracellular matrix (ECM), loaded with functional seed cells or growth factors have been applied to fabricating 3D bioprinted constructs with complicated inner structures for skeletal muscle regeneration. Therefore, we conducted this review to report the skeletal muscle regeneration process, the development status of bioprinting technology, and the mechanism of promoting skeletal muscle repair. In addition, the current challenges and further perspectives of skeletal muscle regeneration by bioprinting are also discussed in this study.

Background: There is still no gold standard treatment for Neer type V distal clavicle fractures. This study was designed to evaluate the therapeutic effects of accelerated rehabilitation in treating Neer type V fractures using anatomical locking plate (ALP) fixation with additional coracoclavicular (CC) ligament augmentation. Methods: In this retrospective study, patients who underwent ALP fixation with additional suture anchor fixation of acute Neer type V distal clavicle fracture from January 2016 to January 2021 were reviewed. Injury radiography and computed tomography (CT) were performed to determine the Neer classification. All patients performed standardized early rehabilitation exercises after surgery and were followed up for more than 12 months. The Constant–Murley score (CMS); the disabilities of the arm, shoulder, and hand (DASH) questionnaire; visual analog scale (VAS); and the percentage of modified CC distance (MCCD%) were evaluated at the last follow-up. Results: Thirty-two patients were included in this study. The mean follow-up time was 31.1 ± 10.4 months. All patients achieved bone union 6–8 weeks (7.2 ± 0.7 weeks) after surgery and were allowed to return to normal daily life. No surgery-related complications occurred in any case. The MCCD% value at the last follow-up (104.7% ± 8.5%) significantly decreased compared with preoperative MCCD% value (162.8% ± 7.2%) (p

Abstract Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology or site of disease pathology. To address these mechanisms and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus Foundation, and the Melza M. and Frank Theodore Barr Foundation collaborated to bring together key opinion leaders and experts in the field of neurodegenerative disease for a virtual meeting titled “Solving Neurodegeneration”. This “think-tank” style meeting focused on uncovering common mechanistic roots of neurodegenerative disease and promising targets for new treatments, catalyzed by the goal of finding new treatments for glaucoma, the world’s leading cause of irreversible blindness and the common interest of the three hosting foundations. Glaucoma, which causes vision loss through degeneration of the optic nerve, likely shares early cellular and molecular events with other neurodegenerative diseases of the central nervous system. Here we discuss major areas of mechanistic overlap between neurodegenerative diseases of the central nervous system: neuroinflammation, bioenergetics and metabolism, genetic contributions, and neurovascular interactions. We summarize important discussion points with emphasis on the research areas that are most innovative and promising in the treatment of neurodegeneration yet require further development. The research that is highlighted provides unique opportunities for collaboration that will lead to efforts in preventing neurodegeneration and ultimately vision loss.

Abstract Background The invasive and complicated procedures involving the use of traditional stem cells limit their application in bone tissue engineering. Cell-free, tissue-engineered bones often have complex scaffold structures and are usually engineered using several growth factors (GFs), thus leading to costly and difficult preparations. Urine-derived stem cells (USCs), a type of autologous stem cell isolated noninvasively and with minimum cost, are expected to solve the typical problems of using traditional stem cells to engineer bones. In this study, a graphene oxide (GO)-modified silk fibroin (SF)/nanohydroxyapatite (nHA) scaffold loaded with USCs was developed for immunomodulation and bone regeneration. Methods The SF/nHA scaffolds were prepared via lyophilization and cross-linked with GO using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxy succinimide (NHS). Scaffolds containing various concentrations of GO were characterized using scanning electron microscopy (SEM), the elastic modulus test, Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectrometer (XPS). Examinations of cell adhesion, proliferation, viability, morphology, alkaline phosphatase activity, and osteogenesis-related gene expression were performed to compare the osteogenesis-related biological behaviors of USCs cultured on the scaffolds. The effect of USC-laden scaffolds on the differentiation of macrophages was tested using ELISA, qRT-PCR, and immunofluorescence staining. Subcutaneous implantations in rats were performed to evaluate the inflammatory response of the USC-laden scaffolds after implantation. The scaffolds loaded with USCs were implanted into a cranial defect model in rats to repair bone defects. Micro-computed tomography (μCT) analyses and histological evaluation were performed to evaluate the bone repair effects. Results GO modification enhanced the mechanical properties of the scaffolds. Scaffolds containing less than 0.5% GO had good biocompatibility and promoted USC proliferation and osteogenesis. The scaffolds loaded with USCs induced the M2-type differentiation and inhibited the M1-type differentiation of macrophages. The USC-laden scaffolds containing 0.1% GO exhibited the best capacity for promoting the M2-type differentiation of macrophages and accelerating bone regeneration and almost bridged the site of the rat cranial defects at 12 weeks after surgery. Conclusions This composite system has the capacity for immunomodulation and the promotion of bone regeneration and shows promising potential for clinical applications of USC-based, tissue-engineered bones.

Breathing, and the motor circuits that control it, is essential for life. At the core of respiratory circuits are Dbx1-derived interneurons, which generate the rhythm and pattern of breathing, and phrenic motor neurons (MNs), which provide the final motor output that drives diaphragm muscle contractions during inspiration. Despite their critical function, the principles that dictate how respiratory circuits assemble are unknown. Here, we show that coordinated activity of a type I cadherin (N-cadherin) and type II cadherins (Cadherin-6, -9, and -10) is required in both MNs and Dbx1-derived neurons to generate robust respiratory motor output. Both MN- and Dbx1-specific cadherin inactivation in mice during a critical developmental window results in perinatal lethality due to respiratory failure and a striking reduction in phrenic MN bursting activity. This combinatorial cadherin code is required to establish phrenic MN cell body and dendritic topography; surprisingly, however, cell body position appears to be dispensable for the targeting of phrenic MNs by descending respiratory inputs. Our findings demonstrate that type I and II cadherins function cooperatively throughout the respiratory circuit to generate a robust breathing output and reveal novel strategies that drive the assembly of motor circuits.

BackgroundThe association of high-sensitivity C-reactive protein (hsCRP) and anemia with postoperative acute kidney injury (AKI) in neonates with congenital heart disease (CHD) is still unclear. The purpose of this study was to examine whether anemia-associated AKI is modulated by hsCRP in neonates.MethodsThis study included 253 consecutive neonatal patients who underwent CHD surgery in a national tertiary hospital. We investigated the association between postoperative AKI with baseline hsCRP, anemia, and their interaction by multivariable logistic regression analyses.ResultsThe incidence of AKI was 24.1% in the entire cohort. After being adjusted for covariates, hsCRP level was negatively correlated with AKI (P

Objectives: To explore the association between left atrial (LA) strain and the GRACE score in patients with acute coronary syndrome (ACS) and to investigate the utility of LA function in predicting short-term adverse cardiovascular events post ACS. Methods: This retrospective study included ACS patients who underwent coronary angiography (CAG) in two independent cohorts from October 2020 to July 2022. The patients were classified into low-intermediate risk group and high-risk group based on the GRACE score. All participants underwent a transthoracic echocardiogram, with LA strain analysis before CAG. Correlation analysis was used to determine the relationship between LA strain and the GRACE score. The predictive value of LA strain was examined utilizing the area under the curve (AUC). Participants were followed for 10.5 ± 2.9 months for the primary endpoint of major adverse cardiovascular events (MACE). Results: A total of 229 patients were included in this study, including 196 in the primary group and 33 in the validation group. Spearman’s correlation analysis showed there was a moderate negative correlation between the GRACE and left atrial reservoir strain (LASr) in both the primary (r = −0.63, P < 0.001) and validation (r = −0.73, P < 0.001) cohorts. Receiver operator characteristic (ROC) curve analysis showed that the AUC of LASr for prediction of the high-risk group was 0.86. Taking LASr 19.6% as the cut-off value, the sensitivity and specificity were 0.71 and 0.92, respectively. The cut-off value of 19.6% remains good at identifying high-risk group in the validation group (AUC = 0.87, sensitivity: 77.8%, specificity: 95.8%). Furthermore, 49 patients reached the endpoint in the primary cohort during the follow-up. On multivariable regression analysis, LASr (P = 0.03) was the independent echocardiographic predictor for the primary endpoint, rather than left atrial volume index (LAVI). Conclusions: LASr can identify high-risk patients with ACS as defined by the GRACE score and may be superior to Max LAVI in predicting incidents of MACE in the short-term following ACS.

Background: Tranexamic acid (TXA) has been widely applied to reduce perioperative bleeding. Recently, several studies focused on the administration of TXA in the treatment for with intertrochanteric fracture patients treated with intramedullary fixation. However, the efficacy and safety of TXA in these studies remain controversial. Therefore, we performed this systematic review and meta-analysis to investigate the efficacy and safety of TXA in intertrochanteric fracture patients treated with intramedullary fixation.Methods: We systematically searched electronic databases, including Cochrane, PubMed, and EMBASE, up to 16 May 2022. The efficacy and safety of TXA was evaluated in four aspects, which were bleeding-related outcomes, non-bleeding-related outcomes, thromboembolic events, and other complications. The outcomes of these studies were extracted and analyzed by RevMan Manager 5.4.Results: Finally, nine randomized controlled trials, involving nine hundred and seventy-two intertrochanteric fracture patients treated with TXA, were enrolled in this study. In the bleeding-related outcomes, TXA group was significantly lower than the control group in terms of total blood loss (MD = −219.42; 95% CI, −299.80 to −139.03; p < 0.001), intraoperative blood loss (MD = −36.81; 95% CI, −54.21 to −19.41; p < 0.001), hidden blood loss (MD = −189.23; 95% CI, −274.92 to −103.54; p < 0.001), and transfusion rate (RR = 0.64; 95% CI, 0.49 to 0.85; p = 0.002). Moreover, the postoperative hemoglobin on day 3 of the TXA group was significantly higher than that of the control group (MD = 5.75; 95% CI, 1.26 to 10.23; p = 0.01). In the non-bleeding-related outcomes, the length of hospital stays was significantly shorter in the TXA group (MD = −0.67; 95% CI, −1.12 to −0.23; p = 0.003). In terms of thromboembolic events, there was no significant differences between the TXA group and control group in deep vein thrombosis, pulmonary embolism, myocardial infarction, and ischemic stroke. As for complications and mortality, there was no significant differences between the TXA group and control group in respiratory infection, renal failure, and postoperative mortality within 1 year.Conclusion: TXA is an effective and safe drug for perioperative bleeding control in intertrochanteric fracture patients treated with intramedullary fixation. However, the long-term efficacy of TXA still needs to be investigated by large-scale multicenter randomized controlled trials.Level of evidence: II, Systematic review and Meta-analysis.Systematic Review Registration:https://inplasy.com/, identifier [INPLASY202280027]

Bridge displacement is an important part of safety evaluations. Currently, bridge displacement monitoring uses only a few measurement points, making it difficult to evaluate safety. To address this problem, we propose a multi-point displacement synchronous monitoring method. The structural surface has abundant natural texture features, so we use the feature points of the structural surface as the displacement measurement points and propose a feature point displacement calculation method. Furthermore, we conduct experiments on a beam in the laboratory and obtain the beam’s multi-point displacement monitoring results. The monitoring results show that the displacement of some feature points is mismatched. We propose the use of the structural deflection curve to eliminate the feature point displacement mismatches. This method uses the maximum rotation angle of the deflection curve to eliminate displacement mismatches. The results indicate that it is effective to eliminate displacement mismatches in simple structures, such as simply supported beams. Finally, we obtain the test beam’s multi-point displacement synchronous monitoring results. Compared with the 3D laser scanning measurement method, the maximum error of the monitoring results is 8.70%. Research shows that the main reason for the monitoring error is image noise, and the noise interference problem due to its application in practical bridges requires further investigation. Compared with traditional displacement monitoring, this method has significant economic, efficiency, and data integrity advantages. The method has application prospects for multi-point displacement monitoring of simple structures, such as simply supported beams.

Abstract Gene targeting of Cdc42 GTPase has been shown to inhibit platelet activation. In this study, we investigated a hypothesis that inhibition of Cdc42 activity by CASIN, a small molecule Cdc42 Activity-Specific INhibitor, may down regulate platelet activation and thrombus formation. We investigated the effects of CASIN on platelet activation in vitro and thrombosis in vivo. In human platelets, CASIN, but not its inactive analog Pirl7, blocked collagen induced activation of Cdc42 and inhibited phosphorylation of its downstream effector, PAK1/2. Moreover, addition of CASIN to washed human platelets inhibited platelet spreading on immobilized fibrinogen. Treatment of human platelets with CASIN inhibited collagen or thrombin induced: (a) ATP secretion and platelet aggregation; and (b) phosphorylation of Akt, ERK and p38-MAPK. Pre-incubation of platelets with Pirl7, an inactive analog of CASIN, failed to inhibit collagen induced aggregation. Washing of human platelets after incubation with CASIN eliminated its inhibitory effect on collagen induced aggregation. Intraperitoneal administration of CASIN to wild type mice inhibited ex vivo aggregation induced by collagen but did not affect the murine tail bleeding times. CASIN administration, prior to laser-induced injury in murine cremaster muscle arterioles, resulted in formation of smaller and unstable thrombi compared to control mice without CASIN treatment. These data suggest that pharmacologic targeting of Cdc42 by specific and reversible inhibitors may lead to the discovery of novel antithrombotic agents.

Abstract Background Elevated levels of periostin (Postn) in the cartilage and bone are associated with osteoarthritis (OA). However, it remains unknown whether Postn loss-of-function can delay or prevent the development of OA. In this study, we sought to better understand the role of Postn in OA development and assessed the functional impact of Postn deficiency on post-traumatic and age-related OA in mice. Methods The effects of Postn deficiency were studied in two murine experimental OA models using Postn −/− (n = 32) and littermate wild-type (wt) mice (n = 36). Post-traumatic OA was induced by destabilization of the medial meniscus (DMM) in 10-week-old mice (n = 20); age-related OA was analyzed in 24-month-old mice (n = 13). Cartilage degeneration was assessed histologically using the OARSI scoring system, and synovitis was evaluated by measuring the synovial lining cell layer and the cells density in the synovial stroma. Bone changes were measured by μCT analysis. Serum levels of Postn were determined by ELISA. Expression of Postn and collagenase-3 (MMP-13) was measured by immunostaining. RNA-seq was performed on chondrocytes isolated from 21-day old Postn −/− (n = 3) and wt mice (n = 3) to discover genes and pathways altered by Postn knockout. Results Postn −/− mice exhibited significantly reduced cartilage degeneration and OARSI score relative to wt mice in post-traumatic OA after 8 weeks (maximum: 2.37 ± 0.74 vs. 4.00 ± 1.20, P = 0.011; summed: 9.31 ± 2.52 vs. 21.44 ± 6.01, P = 0.0002) and spontaneous OA (maximum: 1.93 ± 0.45 vs. 3.58 ± 1.16, P = 0.014; summed: 6.14 ± 1.57 vs. 11.50 ± 3.02, P = 0.003). Synovitis was significantly lower in Postn −/− mice than wt only in the DMM model (1.88 ± 1.01 vs. 3.17 ± 0.63; P = 0.039). Postn −/− mice also showed lower trabecular bone parameters such as BV/TV, vBMD, Tb.Th, and Tb.N and high Tb. Sp in both models. Postn −/− mice had negligible levels of serum Postn compared with wt. Immunofluorescent studies of cartilage indicated that Postn −/− mice expressed lower MMP-13 levels than wt mice. RNA-seq revealed that cell-cell-adhesion and cell-differentiation processes were enriched in Postn −/− mice, while those related to cell-cycle and DNA-repair were enriched in wt mice. Conclusions Postn deficiency protects against DMM-induced post-traumatic and age-related spontaneous OA. RNA-seq findings warrant further investigations to better understand the mechanistic role of Postn and its potential as a therapeutic target in OA.

Abstract An increasing amount of evidence has proven the vital role of circular RNAs (circRNAs) in cancer progression. However, there remains a dearth of knowledge on the function of circRNAs in triple-negative breast cancer (TNBC). Utilizing a circRNA microarray dataset, four circRNAs were identified to be abnormally expressed in TNBC. Among them, circBACH2 was most significantly elevated in TNBC cancerous tissues and its high expression was positively correlated to the malignant progression of TNBC patients. In normal human mammary gland cell line, the overexpression of circBACH2 facilitated epithelial to mesenchymal transition and cell proliferation. In TNBC cell lines, circBACH2 knockdown suppressed the malignant progression of TNBC cells. Mechanistically, circBACH2 sponged miR-186-5p and miR-548c-3p, thus releasing the C-X-C chemokine receptor type 4 (CXCR4) expression. The interference of miR-186-5p/miR-548c-3p efficiently promoted the cell proliferation, migration, and invasion suppressed by circBACH2 knockdown in the TNBC cell lines. Finally, circBACH2 knockdown repressed the growth and lung metastasis of TNBC xenografts in nude mice. In summary, circBACH2 functions as an oncogenic circRNA in TNBC through a novel miR-186-5p/miR-548c-3p/CXCR4 axis.

Abstract Mitogenomes have been widely used for phylogenetic reconstruction of various Dipteran groups, but specifically for chironomid, they have not been carried out to resolve the relationships. Diamesinae (Diptera: Chironomidae) are important bioindicators for freshwater ecosystem monitoring, but its evolutionary history remains uncertain for lack of information. Here, coupled with one previously published and 30 new mitogenomes of Diamesinae, we carried out comparative mitogenomic analysis and phylogenetic analysis. Mitogenomes of Diamesinae were conserved in structure, and all genes arranged in the same order as the ancestral insect mitogenome. All protein‐coding genes in Diamesinae were under stronger purifying selection than those of other nonbiting midge species, which may exhibit signs of adaptation to life at cold living conditions. Phylogenetic analyses strongly supported the monophyly of Diamesinae, with Boreheptagyiini deeply nested within Diamesini. In addition, phylogenetic relationship of selected six genera was resolved, except Sympotthastia remained unstable. Our study revealed that the mitogenomes of Diamesinae are highly conserved, and they are practically useful for phylogenetic inference.

BackgroundPost-operative mortality risk assessment for geriatric patients with hip fractures (HF) is a challenge for clinicians. Early identification of geriatric HF patients with a high risk of post-operative death is helpful for early intervention and improving clinical prognosis. However, a single significant risk factor of post-operative death cannot accurately predict the prognosis of geriatric HF patients. Therefore, our study aims to utilize a machine learning approach, random forest algorithm, to fabricate a prediction model for post-operative death of geriatric HF patients.MethodsThis retrospective study enrolled consecutive geriatric HF patients who underwent treatment for surgery. The study cohort was divided into training and testing datasets at a 70:30 ratio. The random forest algorithm selected or excluded variables according to the feature importance. Least absolute shrinkage and selection operator (Lasso) was utilized to compare feature selection results of random forest. The confirmed variables were used to create a simplified model instead of a full model with all variables. The prediction model was then verified in the training dataset and testing dataset. Additionally, a prediction model constructed by logistic regression was used as a control to evaluate the efficiency of the new prediction model.ResultsFeature selection by random forest algorithm and Lasso regression demonstrated that seven variables, including age, time from injury to surgery, chronic obstructive pulmonary disease (COPD), albumin, hemoglobin, history of malignancy, and perioperative blood transfusion, could be used to predict the 1-year post-operative mortality. The area under the curve (AUC) of the random forest algorithm-based prediction model in training and testing datasets were 1.000, and 0.813, respectively. While the prediction tool constructed by logistic regression in training and testing datasets were 0.895, and 0.797, respectively.ConclusionsCompared with logistic regression, the random forest algorithm-based prediction model exhibits better predictive ability for geriatric HF patients with a high risk of death within post-operative 1 year.

Background: Increasing evidence have depicted that DNA repair–related genes (DRGs) are associated with the prognosis of colorectal cancer (CRC) patients. Thus, the aim of this study was to evaluate the impact of DNA repair–related gene signature (DRGS) in predicting the prognosis of CRC patients.Method: In this study, we retrospectively analyzed the gene expression profiles from six CRC cohorts. A total of 1,768 CRC patients with complete prognostic information were divided into the training cohort (n = 566) and two validation cohorts (n = 624 and 578, respectively). The LASSO Cox model was applied to construct a prediction model. To further validate the clinical significance of the model, we also validated the model with Genomics of Drug Sensitivity in Cancer (GDSC) and an advanced clear cell renal cell carcinoma (ccRCC) immunotherapy data set.Results: We constructed a prognostic DRGS consisting of 11 different genes to stratify patients into high- and low-risk groups. Patients in the high-risk groups had significantly worse disease-free survival (DFS) than those in the low-risk groups in all cohorts [training cohort: hazard ratio (HR) = 2.40, p < 0.001, 95% confidence interval (CI) = 1.67–3.44; validation-1: HR = 2.20, p < 0.001, 95% CI = 1.38–3.49 and validation-2 cohort: HR = 2.12, p < 0.001, 95% CI = 1.40–3.21). By validating the model with GDSC, we could see that among the chemotherapeutic drugs such as oxaliplatin, 5-fluorouracil, and irinotecan, the IC50 of the cell line in the low-risk group was lower. By validating the model with the ccRCC immunotherapy data set, we can clearly see that the overall survival (OS) of the objective response rate (ORR) with complete response (CR) and partial response (PR) in the low-risk group was the best.Conclusions: DRGS is a favorable prediction model for patients with CRC, and our model can predict the response of cell lines to chemotherapeutic agents and potentially predict the response of patients to immunotherapy.

Radiographic imaging is routinely used to evaluate treatment response in solid tumors. Here, the authors present a multi-task deep learning approach that allows simultaneous tumor segmentation and response prediction from longitudinal images in a multi-center study on rectal cancer.

Background: Data regarding the association between sleep apnea (SA) and atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) are still limited. We aim to investigate the association of both types of SA, obstructive sleep apnea (OSA) and central sleep apnea (CSA), and nocturnal hypoxemia with AF in HCM. Methods: A total of 606 patients with HCM who underwent sleep evaluations were included. Logistic regression was used to assess the association between sleep disorder and AF. Results: SA was presented in 363 (59.9%) patients, of whom 337 (55.6%) had OSA and 26 (4.3%) had CSA. Patients with SA were older, more often male, had a higher body mass index, and more clinical comorbidities. Prevalence of AF was higher in patients with CSA than patients with OSA and without SA (50.0% versus 24.9% and 12.8%, p < 0.001). After adjustment for age, sex, body mass index, hypertension, diabetes mellitus, cigarette use, New York Heart Association class and severity of mitral regurgitation, SA (OR, 1.79; 95% CI, 1.09–2.94) and nocturnal hypoxemia (higher tertile of percentage of total sleep time with oxygen saturation < 90% [OR, 1.81; 95% CI, 1.05–3.12] compared with lower tertile) were significantly associated with AF. The association was much stronger in the CSA group (OR, 3.98; 95% CI, 1.56–10.13) than in OSA group (OR, 1.66; 95% CI, 1.01–2.76). Similar associations were observed when analyses were restricted to persistent/permanent AF. Conclusion: Both types of SA and nocturnal hypoxemia were independently associated with AF. Attention should be paid to the screening of both types of SA in the management of AF in HCM.

Currently, measurement points in bridge structural health monitoring are limited. Consequently, structural damage identification is challenging due to sparse monitoring data. Hence, a structural full-field displacement monitoring and damage identification method under natural texture conditions is proposed in this work. Firstly, the feature points of a structure were extracted via image scale-invariant feature transform. Then, the mathematical model was analyzed respecting the relative position change of the feature points before and after deformation, and a calculation theory was proposed for the structure’s full-field displacement vector (FFDV). Next, a test beam was constructed to obtain the FFDV calculation results for the beam under different damage conditions. Validation results showed that the maximum length error of the FFDV was 0.48 mm, while the maximum angle error was 0.82°. The FFDV monitoring results for the test beam showed that the rotation angle of the displacement vector at the damage location presented abnormal characteristics. Additionally, a damage identification index was proposed for the rotation-angle change rate. Based on the validation test, the index was proven to be sensitive to the damage location. Finally, a structural damage identification program was proposed based on the FFDV monitoring results. The obtained results will help to expand structural health monitoring data and fundamentally solve damage identification issues arising from sparse monitoring data. This study is the first to implement structural full-field displacement monitoring under natural texture conditions. The proposed method exhibits outstanding economic benefits, efficiency, and visualization advantages compared with the conventional single-point monitoring method.

Abstract. Background. Coronary atherosclerotic plaque could go through rapid progression and induce adverse cardiac events. This study aimed to evaluate the impacts of smoking status on clinical outcomes of coronary non-target lesions. Methods. Consecutive patients with coronary heart disease who underwent two serial coronary angiographies were included. All coronary non-target lesions were recorded at first coronary angiography and analyzed using quantitative coronary angiography at both procedures. Patients were grouped into non-smokers, quitters, and smokers according to their smoking status. Clinical outcomes including rapid lesion progression, lesion re-vascularization, and myocardial infarction were recorded at second coronary angiography. Multivariable Cox regression analysis was used to investigate the association between smoking status and clinical outcomes. Results. A total of 1255 patients and 1670 lesions were included. Smokers were younger and more likely to be male compared with non-smokers. Increase in percent diameter stenosis was significantly lower (2.7 [0.6, 7.1] % vs. 3.5 [0.9, 8.9]%) and 3.4 [1.1, 7.7]%, P = 0.020) in quitters than those in smokers and non-smokers. Quitters tended to have a decreased incidence of rapid lesions progression (15.8% [76/482] vs. 21.6% [74/342] and 20.6% [89/431], P = 0.062), lesion re-vascularization (13.1% [63/482] vs. 15.5% [53/432] and 15.5% [67/431], P = 0.448), lesion-related myocardial infarction (0.8% [4/482] vs. 2.6% [9/342] and 1.4% [6/431], P = 0.110) and all-cause myocardial infarction (1.9% [9/482] vs. 4.1% [14/342] and 2.3% [10/431], P = 0.128) compared with smokers and non-smokers. In multivariable analysis, smoking status was not an independent predictor for rapid lesion progression, lesion re-vascularization, and lesion-related myocardial infarction except that a higher risk of all-cause myocardial infarction was observed in smokers than non-smokers (hazards ratio: 3.00, 95% confidence interval: 1.04–8.62, P = 0.042). Conclusion. Smoking cessation mitigates the increase in percent diameter stenosis of coronary non-target lesions, meanwhile, smokers are associated with increased risk for all-cause myocardial infarction compared with non-smokers.

Mutations in CARS2 gene, encoding for the mitochondrial cysteinyl-tRNA synthetase, has been reported to be associated with early-onset epileptic encephalopathy (EOEE). Here, we generated an induced pluripotent stem cell (iPSC) line from the human dermal fibroblasts (HDFs) of an one-year-old boy with EOEE carrying homozygous c.1426G > A mutation in CARS2 gene. These iPSCs exhibited stable amplification, expressed pluripotent markers, and differentiated spontaneously into three germ layers in vitro.

Abstract Large‐scale screening of molecules heavily relies on phenotyping of small living organisms during preclinical development. However, deep profiling candidate therapeutics on whole animals typically requires laborious manipulations and anesthetic treatment using traditional techniques or automated tools. Here, a novel fish capsule system that combines automated zebrafish encapsulating technology and droplet microarray strategy for in vivo functional screening of mono/polytherapies is described. This platform enables automated, rapid zebrafish orientation and immobilization in agarose to generate large‐scale fish capsules by using a microfluidic device. Based on the effect of discontinuous dewetting, the prompt trapping of fish capsules in the aqueous arrays is successfully demonstrate. This system provides the capability to integrate pharmaceutical treatments with real‐time multispectral microscopic imaging in a simple, pipetting‐free and highly parallel manner. Coupling with machine learning algorithms, a small library of compounds is screened and analyzed, and clues about how to exploit compound combinations as therapeutic candidates are obtained. It is believed that this proposed strategy can be readily applied to multiple fields and is especially useful in the exploration of combinatorial drugs with limited amounts of samples and resources to accelerate the identification of novel therapeutics for precision medicines.

The continuous expansion of the scale of power grid construction has led to the emergence and development of the uninterrupted operation of the unmanned aerial vehicle (UAV) distribution network. However, in the actual power production process, due to the limitations of operating conditions and environment, power safety accidents are inevitable. With the support of intelligent technology, the monitoring effect and application level of the safety monitoring system for the uninterrupted operation of the UAV distribution network have been improved. Unified planning and scheduling were carried out throughout the job implementation process. The efficiency of equipment safety management has been strengthened, which is of great practical significance to the safe production of electric power. Based on the analysis of the environmental characteristics and implementation difficulties of the unmanned aerial vehicle distribution network, this paper studied the safety monitoring system and method by combining the high intelligence and high-efficiency characteristics of the learning control robot technology. The designed unmanned aerial vehicle distribution network safety monitoring system and method were tested. In order to understand the effect of the system intuitively, this paper analyzed from three aspects: system sensitivity, anti-interference, and data acquisition and management. It also contrasted with traditional monitoring systems. The test data showed that the sensitivity test value of the traditional monitoring system in the R1 circuit with the lowest voltage intensity was 71.3%. In the R4 circuit with the strongest voltage intensity, the test value only reached 84.4%. The test values of the system in this paper in the two types of circuits were 85.6% and 93.3%, respectively. In the data acquisition and management test, the acquisition and management rates under the highest numerical information could reach more than 97%. It can be seen that it has strong feasibility in actual operation.

Identifying the phenotypes and interactions of various cells is the primary objective in cellular heterogeneity dissection. A key step of this methodology is to perform unsupervised clustering, which, however, often suffers challenges of the high level of noise, as well as redundant information. To overcome the limitations, we proposed self-diffusion on local scaling affinity (LSSD) to enhance cell similarities’ metric learning for dissecting cellular heterogeneity. Local scaling infers the self-tuning of cell-to-cell distances that are used to construct cell affinity. Our approach implements the self-diffusion process by propagating the affinity matrices to further improve the cell similarities for the downstream clustering analysis. To demonstrate the effectiveness and usefulness, we applied LSSD on two simulated and four real scRNA-seq datasets. Comparing with other single-cell clustering methods, our approach demonstrates much better clustering performance, and cell types identified on colorectal tumors reveal strongly biological interpretability.

Green economy is environmentally friendly economy, which is important for the sustainable economic development and environmental protection. Based on the panel data of 30 provinces and cities in China, a three-stage super-efficient SBM-DEA (slack-based model-data envelopment analysis) model is constructed to evaluate the efficiency of green economy and analyze its regional differences. The results show that, first, the random error factor and external environmental conditions significantly affect the efficiency of green economy. Second, the green economic efficiency in China from 2010 to 2019 is stable and needs to be further improved. Third, through regional comparison, it is found that the green economy efficiency in eastern China is higher than those in central and western China and the green economy efficiency in northeast China is the lowest. Finally, green economy efficiency does not simply depend on the economic development, the regional differences of green economy efficiency results from the combined effects of different geographical resources endowment, different economic development characteristics, and different environmental protection policies in different regions of China. Based on the research findings, corresponding policy suggestions are put forward to improve the efficiency of green economy.