Search

Abstract In women who are getting older, the quantity and quality of their follicles or oocytes and decline. This is characterized by decreased ovarian reserve function (DOR), fewer remaining oocytes, and lower quality oocytes. As more women choose to delay childbirth, the decline in fertility associated with age has become a significant concern for modern women. The decline in oocyte quality is a key indicator of ovarian aging. Many studies suggest that age-related changes in oocyte energy metabolism may impact oocyte quality. Changes in oocyte energy metabolism affect adenosine 5'-triphosphate (ATP) production, but how related products and proteins influence oocyte quality remains largely unknown. This review focuses on oocyte metabolism in age-related ovarian aging and its potential impact on oocyte quality, as well as therapeutic strategies that may partially influence oocyte metabolism. This research aims to enhance our understanding of age-related changes in oocyte energy metabolism, and the identification of biomarkers and treatment methods.

Epithelial-derived IL-33 (Interleukin-33), as a member of alarm signals, is a chemical substance produced under harmful stimuli that can promote innate immunity and activate adaptive immune responses. Type 2 inflammation refers to inflammation primarily mediated by Type 2 helper T cells (Th2), Type 2 innate lymphoid cells (ILC2), and related cytokines. Type 2 inflammation manifests in various forms in the lungs, with diseases such as asthma and chronic obstructive pulmonary disease chronic obstructive pulmonary disease (COPD) closely associated with Type 2 inflammation. Recent research suggests that IL-33 has a promoting effect on Type 2 inflammation in the lungs and can be regarded as an alarm signal for Type 2 inflammation. This article provides an overview of the mechanisms and related targets of IL-33 in the development of lung diseases caused by Type 2 inflammation, and summarizes the associated treatment methods. Analyzing lung diseases from a new perspective through the alarm of Type 2 inflammation helps to gain a deeper understanding of the pathogenesis of these related lung diseases. This, in turn, facilitates a better understanding of the latest treatment methods and potential therapeutic targets for diseases, with the expectation that targeting lL-33 can propose new strategies for disease prevention.

Amid the backdrop of globalization, international trade has emerged as a crucial driver of economic development. The People’s Republic of China (PRC), as the instigator and key participant in the “Belt and Road” initiative, has garnered substantial attention for its trade collaborations with other participating countries. While numerous studies have examined the impact of the initiative on the PRC’s export trade, there has been relatively limited research on its influence on imports by Chinese enterprises. Hence, this paper aims to address this gap by utilizing the PRC’s customs import data from 2010 to 2015 and focusing on enterprises located in the PRC’s core cities along the Belt and Road route. The study seeks to analyze the initiative’s impact and the underlying mechanisms it employs to shape their import patterns. The findings of this research demonstrate that the Belt and Road initiative plays a significant role in fostering “quality growth” through two primary channels: product diversity and urban innovation capability. Notably, these effects are particularly pronounced for foreign-funded enterprises, capital goods, and enterprises situated in coastal cities. By using the Belt and Road initiative as a case study, this paper provides valuable insights that can inform efforts to further enhance the impact of international cooperation, actively expand imports, and achieve the high-quality development of foreign trade.

Acetaminophen (APAP)-induced acute kidney injury (APAP-AKI) has turned into one of reasons for clinic obtained renal insufficiency. Magnesium hydride (MgH2), as a solid-state hydrogen source, might be potentially applied in clinical practice. The current study aimed to investigate the protective effect of MgH2 against APAP-AKI. The results showed that MgH2 improved renal function and histological injury in mice of APAP-AKI. MgH2 also had protective effects on APAP-induced cytotoxicity in HK-2 cells. In addition, the increased level of reactive oxygen species (ROS) and expressions of inflammatory cytokines (TNF-α and IL-1β) and pro-apoptotic factors (Bad, Bax, Caspase3, and CytC) induced by APAP were downregulated with MgH2 treatment. Furthermore, the expressions of molecules related to TXNIP/NLRP3/NF-κB pathway (TXNIP, NLRP3, NF-κB p65 and p-NF-κB p65) in renal tissues and HK-2 cells were enhanced by APAP overdose, which were reduced by MgH2 administration. Collectively, this study indicated that MgH2 protects against APAP-AKI by alleviating oxidative stress, inflammation and apoptosis via inhibition of TXNIP/NLRP3/NF-κB signaling pathway.

AbstractObjective We aim to explore the contributing factors of clinical pregnancy outcomes in PCOS patients undergoing their first FET treatment.Methods A retrospective analysis was conducted on 574 PCOS patients undergoing their first FET treatment at a private fertility center from January 2018 to December 2021.Results During the first FET cycle of PCOS patients, progesterone levels (aOR 0.109, 95% CI 0.018-0.670) and endometrial thickness (EMT) (aOR 1.126, 95% CI 1.043-1.419) on the hCG trigger day were associated with the clinical pregnancy rate. Similarly, progesterone levels (aOR 0.055, 95% CI 0.007-0.420) and EMT (aOR 1.179, 95% CI 1.011-1.376) on the hCG trigger day were associated with the live birth rate. In addition, AFC (aOR 1.179, 95% CI 1.011-1.376) was found to be a risk factor for preterm delivery.Conclusions In women with PCOS undergoing their first FET, lower progesterone levels and higher EMT on hCG trigger day were associated with clinical pregnancy and live birth, and AFC was a risk factor for preterm delivery. During FET treatment, paying attention to the patient’s endocrine indicators and follicle status may have a positive effect on predicting and improving the pregnancy outcome of PCOS patients.

Aortic valve calcification (AVC) is a common cardiovascular disease and a risk factor for sudden death. However, the potential mechanisms and effective therapeutic drugs need to be explored. Atorvastatin is a statin that can effectively prevent cardiovascular events by lowering cholesterol levels. However, whether atorvastatin can inhibit AVC by reducing low-density lipoprotein (LDL) and its possible mechanism of action require further exploration. In the current study, we constructed an in vitro AVC model by inducing calcification of the valve interstitial cells. We found that atorvastatin significantly inhibited osteogenic differentiation, reduced the deposition of calcium nodules in valve interstitial cells, and enhanced autophagy in calcified valve interstitial cells, manifested by increased expression levels of the autophagy proteins Atg5 and LC3B-II/I and the formation of smooth autophagic flow. Atorvastatin inhibited the NF-κB signalling pathway and the expression of inflammatory factors mediated by NF-κB in calcified valve interstitial cells. The activation of the NF-κB signalling pathway led to the reversal of atorvastatin's effect on enhancing autophagy and alleviating valve interstitial cell calcification. In conclusion, atorvastatin inhibited the NF-κB signalling pathway by upregulating autophagy, thereby alleviating valve interstitial cell calcification, which was conducive to improving AVC.

Abstract Background Sarcopenia and frailty are both age‐related declines in functional reserve that are linked to adverse health outcomes. It is critical to know about the outcomes of a combination of these conditions. The study aimed to investigate the effects of sarcopenia and frailty on postoperative recovery in elderly patients and to explore risk factors. Methods This prospective cohort study was conducted among 608 patients aged ≥60 years, American Society of Anesthesiologists I‐III, who were scheduled to undergo thoracic (non‐cardiac) and abdominal surgery from 1 March 2022 to 31 October 2022 at the Affiliated Hospital of Xuzhou Medical University. Frailty was measured by the 28‐item frailty index, and sarcopenia was assessed sarcopenia was assessed by skeletal muscle index in computed tomographic scan, handgrip strength and 6‐m walk. Participants were classified as follows: Group A: both sarcopenia and frailty; Group B: sarcopenia only; Group C: frailty only; and Group D: neither frailty nor sarcopenia. The primary outcome was 90‐day morbidity. Multivariable logistic regression model was used to estimate the association between sarcopenia, frailty and 90‐day morbidity. Results The median (interquartile range) age of participants was 68 (64–72) years, and 62.7% were men. The prevalence rates of sarcopenia and frailty were 32.8% and 47.6%, respectively. The 90‐day morbidity in Group A was 58.5%, in Group B was 46.2%, in Group C was 42.0% and in Group D was 28.8%, and the difference was significant (P

C-reactive protein (CRP) is a potential biomarker for evaluating inflammatory responses in patients receiving coronary artery bypass graft surgery. Here, the authors depict a sensitive and reliable colorimetric approach for CRP analysis. In this method, an aptamer specifically binds with CRP and an initiator sequence is released from an arch probe to activate signal amplification. The released initiator sequence hybridizes with the toehold section in the ‘jellyfish’ probe to form a blunt terminus to induce exonuclease III-assisted signal amplification. The method exhibited a low limit of detection of 1.32 ng/ml and high intraday and interday precision for CRP detection. In summary, this colorimetric approach may provide a potential alternative tool for the evaluation of inflammation in patients receiving coronary artery bypass graft and clinical diagnostics of disease.

With growing concerns about global warming, it is crucial to adopt agronomic practices that enhance rice yields from paddy fields while reducing greenhouse gas (GHG) emissions for sustainable agriculture. An optimal nitrogen (N) fertilization rate and planting density are vital to ensure high rice yields, minimize GHG emissions, and understand emission behavior for better field management. We hypothesized that optimizing N application rates and planting density to improve nitrogen use efficiency (NUE) in rice cultivation would reduce resource losses and GHG emissions. To test this hypothesis, we implemented five treatments with a rice straw return cultural system: two planting densities (16 hills m−2 (traditional density, D1) and 20 hills m−2 (25% higher density, D2)) and three N application rates (no N fertilizer (N0), 180 kg N ha−1 (N1), and 144 kg N ha−1 (N2)). The control treatment (CK) was traditional planting density with no N fertilizer. The four new cropping modes were N1D1, N1D2, N2D1, and N2D2. We investigated the effects of N application rates and planting density on rice grain yield, NUE, and GHG emissions in multiple rice-growing seasons. The N1D2 treatment exhibited the highest grain yield over the three years, with a value of 10,452 kg ha−1, representing an increase of 12.2% compared to CK. Moreover, N uptake in N1D2 was the highest, averaging 39.2% (p < 0.05) higher than CK, and 8.5%, 3.5%, and 2.8% (p < 0.05) higher than N1D1, N2D1 and N2D2, respectively. N2D2 exhibited the highest NUE, with a value of 58.99 kg kg−1, surpassing all other treatments over the three years. GHG emissions, global warming potential (GWP), and greenhouse gas intensity (GHGI) in N2D2 were lower than in N1D1, N1D2, and N2D1. Additionally, reducing N application (comparing N1D1 to N2D1) and increasing plant density (comparing N1D1 to N1D2) improved N agronomic efficiency (NAE) and N partial productivity (PFPN). The negative correlation between the NAE and PFPN with GWP and GHG emissions further supports the potential for optimized N management and denser planting density to reduce environmental impact. These findings have important implications for sustainable rice cultivation practices in Southwest China and similar agroecosystems, emphasizing the need for integrated nutrient management strategies to achieve food security and climate change mitigation goals.

It is challenging to precisely measure the slow interseismic crustal-deformation rate from Synthetic Aperture Radar (SAR) data. The long-wavelength orbital errors, owing to the uncertainties in satellite orbit vectors, commonly exist in SAR interferograms, which degrade the precision of the Interferometric SAR (InSAR) products and become the main barrier to extracting interseismic tectonic deformation. In this study, we propose a novel temporal-network orbital correction method that is able to isolate the far-fault tectonic deformation from the mixed long-wavelength signals based on its spatio–temporal characteristic. The proposed approach is straightforward in methodology but could effectively separate the subtle tectonic deformation from glaring orbital errors without ancillary data. Both synthetic data and real Sentinel-1 SAR images are used to validate the reliability and effectiveness of this method. The derived InSAR velocity fields clearly present the predominant left-lateral strike-slip motions of the Tuosuo Lake segment of the Kunlun fault in western China. The fault-parallel velocity differences of 5–6 mm/yr across the fault between areas ~50 km away from the fault trace are addressed. The proposed method presents a significantly different performance from the traditional quadratic approximate method in the far field. Through the implementation of the proposed method, the root mean square error (RMSE) between the LOSGPS and our derived descending InSAR LOS (line of sight) measurements is reduced to less than one-third of the previous study, suggesting its potential to enhance the availability of InSAR technology for interseismic crustal-deformation measurement.

Deficiency in regulatory T cells (Tregs) is an important mechanism underlying the pathogenesis of pediatric aplastic anemia, but its specific mechanism is unclear. In our study, we aimed to investigate whether IL-2/STAT5 can regulate the proliferation of Tregs in aplastic anemia (AA) by regulating their expression of B lymphocyte-induced mature protein-1 (BLIMP-1) or interferon regulatory factor 4 (IRF4). Through clinical research and animal experiments, we found that poor activation of the IL-2/STAT5 signaling pathway may leads to low expression of BLIMP-1 in Tregs of children with AA, which leads to defects in the differentiation and proliferation of Tregs in AA. In AA model mice, treatment with IL-2c reversed the decrease in Treg proportions and reduction in Blimp-1 expression in Tregs by increasing the phosphorylation of Stat5 in Tregs. In AA, deficiency of IRF4 expression in Tregs is closely related to the deficiency of Tregs, but is not regulated by the IL-2/STAT5 pathway.

Friedreich’s ataxia (FRDA) is an autosomal-recessive disorder primarily attributed to biallelic GAA repeat expansions that reduce expression of the mitochondrial protein frataxin (FXN). FRDA is characterized by progressive neurodegeneration, with many patients developing cardiomyopathy that progresses to heart failure and death. The potential to reverse or prevent progression of the cardiac phenotype of FRDA was investigated in a mouse model of FRDA, using an adeno-associated viral vector (AAV8) containing the coding sequence of the FXN gene. The Fxnflox/null::MCK-Cre conditional knockout mouse (FXN-MCK) has an FXN gene ablation that prevents FXN expression in cardiac and skeletal muscle, leading to cardiac insufficiency, weight loss, and morbidity. FXN-MCK mice received a single intravenous injection of an AAV8 vector containing human (hFXN) or mouse (mFXN) FXN genes under the control of a phosphoglycerate kinase promoter. Compared to vehicle-treated FXN-MCK control mice, AAV-treated FXN-MCK mice displayed increases in body weight, reversal of cardiac deficits, and increases in survival without apparent toxicity in the heart or liver for up to 12 weeks postdose. FXN protein expression in heart tissue was detected in a dose-dependent manner, exhibiting wide distribution throughout the heart similar to wild type, but more speckled. These results support an AAV8-based approach to treat FRDA-associated cardiomyopathy.

The different rail transit systems, such as regional railway and urban rail transit, cooperate to form the syncretic railway network (SRN). With the rapid development of SRN, the limited transportation capacity is inadequate to meet the booming passenger flow during peak hours, where cascading failures caused by large passenger flow become a threat to SRN. This paper adopts a state equation to depict the failure-restoration process and investigates detailed restoration strategies considering the characteristics of recoverable and repeatable failures of stations. Specifically, three different restoration strategies—spontaneous restoration strategy (SRS), active restoration strategy (ARS), and hybrid restoration strategy (HRS)—are proposed, and the varying effects of restoration time, restoration probability, restoration objective, and restoration priority for SRN with ARS are compared. These restoration strategies are applied to the actual SRN in Chengdu, where it is found that HRS has a better effect than other strategies. Furthermore, stations in the metro network with higher passenger flow allocate more restoration resources to improve the robustness of SRN, while the restoration effect of SRN increases noticeably with the restoration coefficient and the reserve coefficient. The restoration strategies presented in this paper can improve the safety management of SRN.

Spinal cord injury (SCI) is a severe complication of spinal trauma with high disability and mortality rates. Effective therapeutic methods to alleviate neurobehavioural deficits in patients with SCI are still lacking. In this study, we established a spinal cord contusion (SCC) model in adult Sprague Dawley rats. Induced pluripotent stem cell-derived A2B5+ oligodendrocyte precursor cells (iP-A2B5+OPCs) were obtained from mouse embryonic fibroblasts and injected into the lesion sites of SCC rats. Serological testing and magnetic resonance imaging were employed to determine the effect of iP-A2B5+OPCs cell therapy. The Basso-Beattie-Bresnahan score and inclined plane test were performed on days 1, 3, 7, and 14 after cell transplantation, respectively. Differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) were detected by microarray analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to analyse the biological functions of these lncRNAs and mRNAs. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify variations in the expression of crucial target genes. The results demonstrated that induced pluripotent stem cells exhibited embryonic stem cell-like morphology and could differentiate into diverse neural cells dominated by oligodendrocytes. The neurobehavioural performance of rats treated with iP-A2B5+OPCs transplantation was better than that of rats with SCC without cell transplantation. Notably, we found that 22 lncRNAs and 42 mRNAs were concurrently altered after cell transplantation, and the key lncRNA (NR_037671) and target gene (Cntnap5a) were identified in the iP-A2B5+OPCs group. Moreover, RT-qPCR revealed that iP-A2B5+OPCs transplantation reversed the downregulation of NR_037671 induced by SCC. Our findings indicated that iP-A2B5+OPCs transplantation effectively improves neurological function recovery after SCC, and the mechanism might be related to alterations in the expression of lncRNAs and mRNAs, such as NR_037671 and Cntnap5a.

Abstract Myosin heavy chain 9 (MYH9) plays an important role in a number of diseases. Nevertheless, the function of MYH9 in glioma is unclear. The present research aimed to investigate the role of MYH9 in glioma and determine whether MYH9 is involved in the temozolomide chemoresistance of glioma cells. Our results showed that MYH9 increased the proliferation and temozolomide resistance of glioma cells. The mechanistic experiments showed that the binding of MYH9 to NAP1L1, a potential promoter of tumor proliferation, inhibited the ubiquitination and degradation of NAP1L1 by recruiting USP14. Upregulation of NAP1L1 increased its binding with c-Myc and activated c-Myc, which induced the expression of CCND1/CDK4, promoting glioma cell temozolomide resistance and proliferation. Additionally, we found that MYH9 upregulation was strongly related to patient survival and is therefore a negative factor for patients with glioma. Altogether, our results show that MYH9 plays a role in glioma progression by regulating NAP1L1 deubiquitination. Thus, targeting MYH9 is a potential therapeutic strategy for the clinical treatment of glioma in the future.

Abstract Introduction The effects of deep neuromuscular block (DNMB) on chronic postsurgical pain (CPSP) have not been conclusively determined. Moreover, a limited number of studies have examined the impact of DNMB on long-term recovery quality after spinal surgery. We investigated the impact of DNMB on CPSP and the quality of long-term recovery in patients who had been subjected to spinal surgery. Methods This was a randomized, controlled, double-blind, single-center study performed from May 2022 to November 2022. A total of 220 patients who underwent spinal surgery under general anesthesia were randomly assigned to receive either DNMB (post-tetanic count at 1–2) (the D group) or moderate NMB (MNMB) (train-of-four at 1–3) (the M group). The primary endpoint was the incidence of CPSP. The secondary endpoints included the visual analogue scale (VAS) score in the post-anesthesia recovery unit (PACU), at 12, 24, 48 h and 3 months after surgery; postoperative opioid consumption; quality of recovery-15 (QoR-15) scores on the second postoperative day, before discharge, and 3 months after surgery. Results The incidence of CPSP was significantly lower in the D group (30/104, 28.85%) than in the M group (45/105, 42.86%) (p = 0.035). Besides, VAS scores were significantly reduced at the third month in the D group (p = 0.016). In the PACU and 12 h after surgery, VAS scores were also significantly lower in the D group than in the M group (p

Abstract Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1–34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1–34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1β-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.

TiO2 has demonstrated outstanding performance in electrochemical advanced oxidation processes (EAOPs) due to its structural stability and high oxygen overpotential. However, there is still much room for improving its electrochemical activity. Herein, narrow bandgap manganese oxide (MnOx) was composited with TiO2 nanotube arrays (TiO2 NTAs) that in-situ oxidized on porous Ti sponge, forming the MnOx-TiO2 NTAs anode. XANES and XPS analysis further proved that the composition of MnOx is Mn2O3. Electrochemical characterizations revealed that increasing the composited concentration of MnOx can improve the conductivity and reduce oxygen evolution potential so as to improve the electrochemical activity of the composited MnOx-TiO2 NTAs anode. Meanwhile, the optimal degradation rate of benzoic acid (BA) was achieved using MnOx-TiO2 NTAs with a MnOx concentration of 0.1 mmol L−1, and the role of MnOx was proposed based on DFT calculation. Additionally, the required electrical energy (EE/O) to destroy BA was optimized by varying the composited concentration of MnOx and the degradation voltage. These quantitative results are of great significance for the design and application of high-performance materials for EAOPs.

Perfluorobutane sulfonates (PFBS) have garnered extensive utilization because of their distinctive physicochemical properties. The liver acts as a key target organ for toxicity within the body and is vital for regulating metabolic processes, particularly lipid metabolism. However, there is currently a significant research gap regarding the influences of PFBS on hepatic lipid metabolism, especially in individuals with different dietary statuses. Here, the objective of this research was to examine the effects of PFBS on hepatic function under different dietary conditions. The results suggested that the levels of liver injury biomarkers were significantly upregulated, e.g., transaminase (GPT, GOT), while liver lipid levels were downregulated after exposure to PFBS at concentration of 50 μg/L for 42 days. Moreover, restricted diet further intensified the adverse effects of PFBS on the liver. Metabolomics analysis identified significant alterations in lipid-related metabolites in PFBS-induced hepatotoxicity, PFBS exposure induced a decrease in lysophosphatidylethanolamine and lysophosphatidylcholine. PFBS exposure caused an increase in aldosterone and prostaglandin f2alpha under restricted diet. In PFBS treatment group, histidine metabolism, beta-alanine metabolism, and arginine biosynthesis were the main pathway for PFBS toxicity. Aldosterone-regulated sodium reabsorption as a vital factor in inducing PFBS toxicity in the RD-PFBS treatment group. The analysis of 16S rRNA sequencing revealed that exposure to PFBS resulted in imbalance of gut microbial communities. PFBS exposure induced a decrease in Akkermansia and Lactobacillus, but an increase in Enterococcus. PFBS exposure caused the abundance of Lachnospiraceae_NK4A136_group was significantly elevated under restricted diet. Additionally, disruptions in the expression of genes involved in lipid production and consumption may significantly contribute to lipid imbalance in the liver. This study underscores the importance of recognizing the harmful impact of PFBS on liver function, along with the biotoxicity of contaminant influenced by dietary habits.

Objective Enhanced recovery after surgery (ERAS) has been successfully adopted for the improvement of medical quality and efficacy in many diseases, but the effect thereof for ankle fracture patients can vary. The aim of the present study was to explore the short‐term postoperative outcomes of ERAS among ankle fracture patients. Methods The present study was a retrospective cohort study conducted between January 2019 and May 2019. One hundred and sixty ankle fracture participations (58 males and 102 females, aged 41.71 ± 14.51 years) were included. The participants treated with open reduction and internal fixation were divided into two groups (non‐ERAS vs. ERAS) depending on whether ERAS was applied. Postoperative outcomes included American Orthopedic Foot and Ankle Society (AOFAS) score, length of stay (LOS), hospital cost, complications, and consumption of opioids. To assess the association between the groups and outcomes, generalized estimating equation (GEE) modeling and multivariable linear regression analysis were performed. Results The average follow‐up periods of the participations were 24 months postoperatively. No significant differences were detected between the non‐ERAS group and ERAS group with respect to the demographic of patients in terms of gender, age, Danis‐Weber classification of fracture, dislocation of ankle joint, and comorbidity (P > 0.05). Significant differences in terms of a higher AOFAS score were found in the ERAS group compared with the non‐ERAS group (6.73, 95% CI, 5.10–8.37, p 0.05) and at 24 months postoperatively (PO24M) (0.56, 95% CI, −0.07 to 1.19, P > 0.05). Additionally, the GEE analysis and group‐by‐time interaction of AOFAS score revealed that the ERAS protocol could facilitate faster recovery for ankle fracture patients, with higher PO3M and PO6M (both P

Abstract Background Circular RNAs (circRNAs) are highly enriched in the central nervous system and have been implicated in neurodegenerative diseases. However, whether and how circRNAs contribute to the pathological processes induced by traumatic brain injury (TBI) has not been fully elucidated. Methods We conducted a high-throughput RNA sequencing screen for well-conserved, differentially expressed circRNAs in the cortex of rats subjected to experimental TBI. Circular RNA METTL9 (circMETTL9) was ultimately identified as upregulated post-TBI and further characterized by RT-PCR and agarose gel electrophoresis, Sanger sequencing, and RNase R treatment. To examine potential involvement of circMETTL9 in neurodegeneration and loss of function following TBI, circMETTL9 expression in cortex was knocked-down by microinjection of a shcircMETTL9 adeno-associated virus. Neurological functions were evaluated in control, TBI, and TBI-KD rats using a modified neurological severity score, cognitive function using the Morris water maze test, and nerve cell apoptosis rate by TUNEL staining. Pull-down assays and mass spectrometry were conducted to identify circMETTL9-binding proteins. Co-localization of circMETTL9 and SND1 in astrocytes was examined by fluorescence in situ hybridization and immunofluorescence double staining. Changes in the expression levels of chemokines and SND1 were estimated by quantitative PCR and western blotting. Results CircMETTL9 was significantly upregulated and peaked at 7 d in the cerebral cortex of TBI model rats, and it was abundantly expressed in astrocytes. We found that circMETTL9 knockdown significantly attenuated neurological dysfunction, cognitive impairment, and nerve cell apoptosis induced by TBI. CircMETTL9 directly bound to and increased the expression of SND1 in astrocytes, leading to the upregulation of CCL2, CXCL1, CCL3, CXCL3, and CXCL10, and ultimately to enhanced neuroinflammation. Conclusion Altogether, we are the first to propose that circMETTL9 is a master regulator of neuroinflammation following TBI, and thus a major contributor to neurodegeneration and neurological dysfunction. Graphical Abstract

Extracting entity, relation, and attribute information from unstructured text is crucial for constructing large-scale knowledge graphs (KG). Existing research approaches either focus on entity recognition before relation extraction or employ unified annotation. However, these methods overlook the intrinsic relation between entity recognition and relation extraction, resulting in ineffective handling of triple overlap issues where multiple relations share the same entity in a sentence. To address these challenges, this paper proposes an entity-relation joint extraction model comprising two independent sub-modules: one for extracting the head entity and the other for extracting the tail entity and its corresponding relation. The model generates candidate entities and relations by enumerating token sequences in sentences, and then uses the two sub-modules to predict entities and relations. The predicted entities and relations are jointly decoded to obtain relational triples, avoiding error propagation and solving redundancy, entity overlap, and poor generalization. Extensive experiments demonstrate that our model achieves state-of-the-art performance on WebNLG, NYT, WebNLG*, and NYT* public benchmarks. It outperforms all baselines on the WebNLG* dataset, showing significant improvements in different types of triples: normal, SEO, and EPO by 3.8%, 2.9%, and 5.5%, respectively, compared to ETL-Span. For the NYT* dataset, our method improves by 5.7% in triples of Normal type, thereby confirming its effectiveness.

Abstract Background Total hip arthroplasty (THA) is a successful treatment for many hip diseases. Length of stay (LOS) and hospital cost are crucial parameters to quantify the medical efficacy and quality of unilateral primary THA patients. Clinical variables associated with LOS and hospital costs haven’t been investigated thoroughly. Methods The present study retrospectively explored the contributors of LOS and hospital costs among a total of 452 unilateral primary THA patients from January 2019 to January 2020. All patients received conventional in-house rehabilitation services within our institute prior to discharge. Outcome parameters included LOS and hospital cost while clinical variables included patient characteristics and procedural variables. Multivariable linear regression analysis was performed to assess the association between outcome parameters and clinical variables by controlling confounding factors. Moreover, we analyzed patients in two groups according to their diagnosis with femur neck fracture (FNF) (confine THA) or non-FNF (elective THA) separately. Results Among all 452 eligible participants (266 females and 186 males; age 57.05 ± 15.99 year-old), 145 (32.08%) patients diagnosed with FNF and 307 (67.92%) diagnosed with non-FNF were analyzed separately. Multivariable linear regression analysis revealed that clinical variables including surgery duration, transfusion, and comorbidity (stroke) among the elective THA patients while the approach and comorbidities (stoke, diabetes mellitus, coronary heart disease) among the confine THA patients were associated with a prolonged LOS (P

Abstract Osteoarthritis (OA) is a common and prevalent degenerative joint disease characterized by degradation of the articular cartilage. However, none of disease-modifying OA drugs is approved currently. Teriparatide (PTH (1–34)) might stimulate chondrocyte proliferation and cartilage regeneration via some uncertain mechanisms. Relevant therapies of PTH (1–34) on OA with such effects have recently gained increasing interest, but have not become widespread practice. Thus, we launch this systematic review (SR) to update the latest evidence accordingly. A comprehensive literature search was conducted in PubMed, Web of Science, MEDLINE, the Cochrane Library, and Embase from their inception to February 2022. Studies investigating the effects of the PTH (1–34) on OA were obtained. The quality assessment and descriptive summary were made of all included studies. Overall, 307 records were identified, and 33 studies were included. In vivo studies (n = 22) concluded that PTH (1–34) slowed progression of OA by alleviating cartilage degeneration and aberrant remodeling of subchondral bone (SCB). Moreover, PTH (1–34) exhibited repair of cartilage and SCB, analgesic, and anti-inflammatory effects. In vitro studies (n = 11) concluded that PTH (1–34) was important for chondrocytes via increasing the proliferation and matrix synthesis but preventing apoptosis or hypertrophy. All included studies were assessed with low or unclear risk of bias in methodological quality. The SR demonstrated that PTH (1–34) could alleviate the progression of OA. Moreover, PTH (1–34) had beneficial effects on osteoporotic OA (OPOA) models, which might be a therapeutic option for OA and OPOA treatment.

Objective: Knee osteoarthritis (KOA) is a highly prevalent musculoskeletal disorder characterized by degeneration of cartilage and abnormal remodeling of subchondral bone (SCB). Teriparatide (PTH (1–34)) is an effective anabolic drug for osteoporosis (OP) and regulates osteoprotegerin (OPG)/receptor activator of nuclear factor ligand (RANKL)/RANK signaling, which also has a therapeutic effect on KOA by ameliorating cartilage degradation and inhibiting aberrant remodeling of SCB. However, the mechanisms of PTH (1–34) in treating KOA are still uncertain and remain to be explored. Therefore, we compared the effect of PTH (1–34) on the post-traumatic KOA mouse model to explore the potential therapeutic effect and mechanisms. Methods: In vivo study, eight-week-old male mice including wild-type (WT) (n ​= ​54) and OPG−/− (n ​= ​54) were investigated and compared. Post-traumatic KOA model was created by destabilization of medial meniscus (DMM). WT mice were randomly assigned into three groups: the sham group (WT-sham; n ​= ​18), the DMM group (WT-DMM; n ​= ​18), and the PTH (1–34)-treated group (WT-DMM ​+ ​PTH (1–34); n ​= ​18). Similarly, the OPG−/− mice were randomly allocated into three groups as well. The designed mice were executed at the 4th, 8th, and 12th weeks to evaluate KOA progression. To further explore the chondro-protective of PTH (1–34), the ATDC5 chondrocytes were stimulated with different concentrations of PTH (1–34) in vitro. Results: Compared with the WT-sham mice, significant wear of cartilage in terms of reduced cartilage thickness and glycosaminoglycan (GAG) loss was detected in the WT-DMM mice. PTH (1–34) exhibited cartilage-protective by alleviating wear, retaining the thickness and GAG contents. Moreover, the deterioration of the SCB was alleviated and the expression of PTH1R/OPG/RANKL/RANK were found to increase after PTH (1–34) treatment. Among the OPG−/− mice, the cartilage of the DMM mice displayed typical KOA change with higher OARSI score and thinner cartilage. The damage of the cartilage was alleviated but the abnormal remodeling of SCB didn't show any response to the PTH (1–34) treatment. Compared with the WT-DMM mice, the OPG−/−-DMM mice caught more aggressive KOA with thinner cartilage, sever cartilage damage, and more abnormal remodeling of SCB. Moreover, both the damaged cartilage from the WT-DMM mice and the OPG−/−-DMM mice were alleviated but only the deterioration of SCB in WT-DMM mice was alleviated after the administration of PTH (1–34). In vitro study, PTH (1–34) could promote the viability of chondrocytes, enhance the synthesis of extracellular matrix (ECM) (AGC, COLII, and SOX9) at the mRNA and protein level, but inhibit the secretion of inflammatory cytokines (TNF-α and IL-6). Conclusion: Both wear of the cartilage was alleviated and aberrant remodeling of the SCB was inhibited in the WT mice, but only the cartilage-protective effect was observed in the OPG−/− mice. PTH (1–34) exhibited chondro-protective effect by decelerating cartilage degeneration in vivo as well as by promoting the proliferation and enhancing ECM synthesis of chondrocytes in vitro. The current investigation implied that the rescue of the disturbed SCB is dependent on the regulation of OPG while the chondro-protective effect is independent of modulation of OPG, which provides proof for the treatment of KOA. The translational potential of this article: Systemic administration of PTH (1-34) could exert a therapeutic effect on both cartilage and SCB in different mechanisms to alleviate KOA progression, which might be a novel therapy for KOA.

Abstract Background Preeclampsia (PE) is a pregnancy related disease that affects about 5% of pregnancies. Death receptor 3 (DR3) expression is significantly elevated in both placental tissue and plasma of PE patients. However, whether DR3 was involved in trophoblasts in pathogenesis of PE are not well elucidated. Objective Our research was designed to illustrate the biological roles of DR3 in placental trophoblasts, as well as explain its relevant mechanisms. Methods HTR‐8/SVneo cells viability, migration, invasion, and apoptosis were assessed using MTT, Transwell assay, and flow cytometry analysis, respectively. Levels of DR3, PI3K, and AKT in HTR‐8/SVneo cells were analyzed via reverse transcription‐quantitative polymerase chain reaction assay. Western blot analysis was utilized to assess DR3, p‐PI3K, p‐AKT, PI3K, and AKT protein expression. Results Upregulation of DR3 obviously inhibited HTR‐8/SVneo cells viability, migration, and invasion, as well as promoted HTR‐8/SVneo cells apoptosis, as opposed to the control‐plasmid group. We also found that DR3‐plasmid enhanced cleaved‐caspase3 expression, reduced p‐PI3K and p‐AKT protein expression, and p‐PI3K/PI3K or p‐AKT/AKT ratio in HTR‐8/SVneo cells. Importantly, IGF‐1, a PI3K/AKT signaling pathway agonist, partially reversed the effects of DR3‐plasmid on the cell viability, migration, invasion, apoptosis, and PI3K/AKT signal pathway in HTR‐8/SVneo cells. Conclusion DR3 was involved in PE through regulating placental trophoblast cell physiology via PI3K/AKT pathway, which might be a promising therapeutic target for PE therapy.

Dissolved oxygen (DO) is crucial for fish farming, and when fish experience hypoxic stress, negative effects such as the disruption of normal physiological activities, a decline in aerobic swimming ability, and feeding restriction will occur. In this study, healthy Epinephelus coioides individuals were subjected to hypoxic (DO = 0.6 ± 0.1 mg/L) and reoxygenation treatments (DO = 6.0 ± 0.1 mg/L), with a normoxic group (DO = 6.0 ± 0.1 mg/L) set as the control. Transcriptome sequencing (RNA-seq) was performed on the brains of E. coioides in hypoxia-sensitive (EBW), hypoxia-tolerant (EBS), and normoxic control (CB) groups. In total, 1174 differentially expressed genes (DEGs) were screened from the three groups. KEGG analysis revealed several pathways, including the HIF-1 signaling pathway, and immune-related pathways such as MAPK signaling, microRNAs (miRNAs), and oxidative phosphorylation pathways enriched in the EBS group, and cAMP signaling pathway enriched in the EBW group. Moreover, a variety of significant hypoxia-responsive DEGs involved in energy metabolism and immune reactions were identified in the EBS and EBW groups. qRTPCR analysis showed that the key DEGs HIF-1α, LDH-A, PPARα, PNP, RAB13, DDIT4, TNF-1, and ALDOA were significantly upregulated in the brain tissues of E. coioides under acute hypoxic stress and that their expression returned to normoxic levels after reoxygenation, indicating that they provided energy to the organism and regulated severe damage and lesions appearing in the brains of E. coioides during hypoxic stress to prolong the survival time of the organism. Altogether, these results suggest that hypoxia disrupts the expression patterns of multiple genes in E. coioides and that these genes may participate in resistance and adaptation to hypoxia in the organisms by regulating apoptosis, proliferation, differentiation, and energy metabolism.

PurposeRecent scientific reports have revealed a close association between ferroptosis and the occurrence and development of osteoarthritis (OA). Nevertheless, the precise mechanisms by which ferroptosis influences OA and how to hobble OA progression by inhibiting chondrocyte ferroptosis have not yet been fully elucidated. This study aims to conduct a comprehensive systematic review (SR) to address these gaps.MethodsFollowing the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020, we conducted a comprehensive search of the Embase, Ovid, ProQuest, PubMed, Scopus, the Cochrane Library, and Web of Science databases to identify relevant studies that investigate the association between ferroptosis and chondrocytes in OA. Our search included studies published from the inception of these databases until January 31st, 2023. Only studies that met the predetermined quality criteria were included in this SR.ResultsIn this comprehensive SR, a total of 21 studies that met the specified criteria were considered suitable and included in the current updated synthesis. The mechanisms underlying chondrocyte ferroptosis and its association with OA progression involve various biological phenomena, including mitochondrial dysfunction, dysregulated iron metabolism, oxidative stress, and crucial signaling pathways.ConclusionFerroptosis in chondrocytes has opened an entirely new chapter for the investigation of OA, and targeted regulation of it is springing up as an attractive and promising therapeutic tactic for OA.Systematic review registrationhttps://inplasy.com/inplasy-2023-3-0044/, identifier INPLASY202330044.

BackgroundThe diversity of clinical trajectories in diabetic kidney disease (DKD) has made blood and biochemical urine markers less precise, while renal puncture, the gold standard, is almost impossible in the assessment of diabetic kidney disease, and the value of functional magnetic resonance imaging in the evaluation of diabetic pathological alterations is increasingly recognized.MethodsThe literature on functional magnetic resonance imaging (fMRI) for the assessment of renal alterations in diabetic kidney disease was searched in PubMed, Web of Science, Cochrane Library, and Embase databases. The search time limit is from database creation to March 10, 2023. RevMan was used to perform a meta-analysis of the main parameters of fMRIs extracted from DKD patients and healthy volunteers (HV).Results24 publications (1550 subjects) were included in this study, using five functional MRIs with seven different parameters. The renal blood flow (RBF) values on Arterial spin labeling magnetic resonance imaging (ASL-MRI) was significantly lower in the DKD group than in the HV group. The [WMD=-99.03, 95% CI (-135.8,-62.27), P

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly reduce postprandial blood glucose, inhibit appetite, and delay gastrointestinal emptying. However, it is controversial that some patients are intolerant to GLP-1RAs.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials (RCTs) using GLP-1RAs with documented withdrawal due to gastrointestinal adverse reactions (GI AEs) from their inception to September 28, 2022. After extracting the information incorporated into the studies, a random-effects network meta-analysis was performed within a frequentist framework.Results64 RCTs were finally enrolled, which included six major categories of the GLP-1RA. The sample size of the GLP-1RAs treatment group was 16,783 cases. The risk of intolerable gastrointestinal adverse reactions of Liraglutide and Semaglutide was higher than that of Dulaglutide. Meanwhile, the higher the dose of the same GLP-1RA preparation, the more likely to cause these adverse reactions. These intolerable GI AEs were not significantly related to drug homology or formulations and may be related to the degree of suppression of the appetite center.ConclusionDulaglutide caused the lowest intolerable GI AEs, while Liraglutide and Semaglutide were the highest. For Semaglutide, the higher the dose, the more likely it is to drive GI AEs. Meanwhile, the risk of these GI AEs is independent of the different formulations of the drug. All these findings can effectively guide individualized treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359346, identifier CRD42022359346.

Abstract Neonatal hypoxic‐ischemic encephalopathy (NHIE) is one of the major diseases in newborns during the perinatal stage, which globally is the main reason for children's morbidity and mortality. However, the mechanism of NHIE still remains poorly clear. In this study, the 7‐day‐old rats were subjected to hypoxic‐ischemia (HI), then brain damage was detected. Afterward, the expression of eva‐1 homolog C (EVA1C) was measured in vitro by establishing the oxygen‐glucose deprivation (OGD) model in SHSY5Y cells and human fetal neurons. Subsequently, the potential function and mechanism of EVA1C were explored by silencing EVA1C and alternative splicing prediction. As a result, obvious neurobehavioral impairment and brain infarction were detected through Zea‐Longa score and TTC staining; meanwhile, neuron injury was tested by HE and Nissl staining post HI. Moreover, it was found that the expression of EVA1C was notably upregulated in SHSY5Y cells and human fetal neurons after OGD. In addition, cell survival and growth were increased after silencing EVA1C, which might be associated with alternative splicing. In conclusion, EVA1C interference exhibited potential in promoting neuron survival and growth, associated with exon skipping with the alternative splicing site in 34613318:34687258, which may provide the basis for the therapeutic target and mechanism research of NHIE.

Abstract Background Umbilical cord blood transplantation (UCBT) from unrelated donors is one of the successful treatments for acute leukemia in childhood. The most frequent side effect of UCBT is peri-engraftment syndrome (PES), which is directly associated with the greater prevalence of acute and chronic graft-versus-host-disease (aGvHD and cGvHD). In haploidentical stem cell transplantation, posttransplant cyclophosphamide (PTCY) has been demonstrated to be an effective method against GvHD. However, the effects of PTCY as a GvHD prophylactic in UCBT had not been investigated. This study aimed to evaluate the effects of PTCY on the outcomes of UCBT for pediatric acute leukemia. Methods This retrospective study included 52 children with acute leukemia who underwent unrelated single-unit UCBT after myeloablative conditioning regimens. The results from the PTCY and non-PTCY groups were compared. Results The incidence of transplantation-related mortality in non-PTCY and PTCY were 5% and 10% (p = 0.525), respectively. The incidence of relapse in non-PTCY and PTCY were 5% and 23% (p = 0.095), respectively. Second complete remission status (CR2) was an independent risk factor for relapse-free survival (hazard ratio = 9.782, p = 0.001). The odds ratio for sepsis or bacteremia incidence was significantly greater in the PTCY group (9.524, p = 0.017). PTCY group had increased rates of cytomegalovirus activity and fungal infection. The incidence of PES, aGvHD, cGvHD, and hemorrhagic cystitis in the PTCY group was lower than that in the non-PTCY group, although it was not significantly different. Additionally, higher doses of PTCY (29 mg/kg and 40 mg/kg) were associated with lower incidences of aGvHD and severe GvHD (65% and 29%, respectively) than lower doses (93% and 57%, respectively). Engraftment time and graft failure incidence were similar across groups. Conclusion The results support the safety and efficiency of PTCY as part of PES controlling and GvHD prophylaxis in single-unit UCBT for children with acute leukemia. A PTCY dosage of 29 mg/kg to 40 mg/kg appears to be more effective in GvHD prophylaxis for UCBT patients.

Recombinant adeno-associated virus (AAV) is an effective platform for therapeutic gene transfer; however, tissue-tropism differences between species are a challenge for successful translation of preclinical results to humans. We evaluated the use of in vitro primary hepatocyte cultures to predict in vivo liver-directed AAV expression in different species. We assessed whether in vitro AAV transduction assays in cultured primary hepatocytes from mice, nonhuman primates (NHPs), and humans could model in vivo liver-directed AAV expression of valoctocogene roxaparvovec (AAV5-hFVIII-SQ), an experimental gene therapy for hemophilia A with a hepatocyte-selective promoter. Relative levels of DNA and RNA in hepatocytes grown in vitro correlated with in vivo liver transduction across species. Expression in NHP hepatocytes more closely reflected expression in human hepatocytes than in mouse hepatocytes. We used this hepatocyte culture model to assess transduction efficacy of a novel liver-directed AAV capsid across species and identified which of 3 different canine factor VIII vectors produced the most transgene expression. Results were confirmed in vivo. Further, we determined mechanisms mediating inhibition of AAV5-hFVIII-SQ expression by concomitant isotretinoin using primary human hepatocytes. These studies support using in vitro primary hepatocyte models to predict species translatability of liver-directed AAV gene therapy and improve mechanistic understanding of drug-drug interactions.

Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) gene transfer provided reduced bleeding for adult clinical trial participants with severe hemophilia A. However, pediatric outcomes are unknown. Using a mouse model of hemophilia A, we investigated the effect of vector dose and age at treatment on transgene production and persistence. We dosed AAV5-hFVIII-SQ to neonatal and adult mice based on body weight or at a fixed dose and assessed human factor VIII-SQ variant (hFVIII-SQ) expression through 16 weeks. AAV5-hFVIII-SQ dosed per body weight in neonatal mice did not result in meaningful plasma hFVIII-SQ protein levels in adulthood. When treated with the same total vector genomes per mouse as adult mice, neonates maintained hFVIII-SQ expression into adulthood, although plasma levels were 3- to 4-fold lower versus mice dosed as adults. Mice

Large numbers of power plants are taking biomass energy to replace fossil fuels. However, biomass combustion process deposits a substantial amount of potassium chloride in the boiler pipe, which causes high-temperature corrosion. This paper investigated the corrosion mechanism of aluminide coatings deposited on TP347H stainless steel under experimental conditions with different water vapor content in a simulated biomass combustion environment. H2O promoted the production of more dense multilayer metal oxides in the aluminide coating on the TP347H stainless steel in the presence of water vapor. The coatings suffered the most severe intergranular attack without water vapor. The intergranular corrosion of coatings subjected to 30% water vapor was less severe than that of coatings exposed to 15% water vapor due to the corrosion inhibiting impact of water vapor. It is indicated that water vapor can essentially influence the corrosion process in a biomass combustion environment.

Light and flexible thermoelectric generators operating at room temperature are highly desirable for wearable microelectronics. Here, flexible thermoelectric composites comprising semiconducting Bi2Te3 particles and conductive polymers exhibit a high output power within a small temperature window around room temperature.

Background Rehabilitation is crucial to recovering patients’ dysfunction, improving their life quality, and promoting an early return to their family and society. In China, most patients in rehabilitation units are patients transferred from neurology, neurosurgery, and orthopedics, and most of these patients face problems such as continuously bedridden or varying degrees of limb dysfunction, all of which are risk factors for deep venous thrombosis. The formation of deep venous thrombosis can delay the recovery process and result in significant morbidity, mortality, and higher healthcare costs, so early detection and individualized treatment are needed. Machine learning algorithms can help develop more precise prognostic models, which can be of great significance in the development of rehabilitation training programs. In this study, we aimed to develop a model of deep venous thrombosis for inpatients in the Department of Rehabilitation Medicine at the Affiliated Hospital of Nantong University using machine learning methods. Methods We analyzed and compared 801 patients in the Department of Rehabilitation Medicine using machine learning. Support vector machine, logistic regression, decision tree, random forest classifier, and artificial neural network were used to build models. Results Artificial neural network was the better predictor than other traditional machine learnings. D-dimer levels, bedridden time, Barthel Index, and fibrinogen degradation products were common predictors of adverse outcomes in these models. Conclusions Risk stratification can help healthcare practitioners to achieve improvements in clinical efficiency and specify appropriate rehabilitation training programs.

Osteogenesis imperfecta (OI) is a hereditary skeletal dysplasia with an incidence of approximately 1:15,000 to 20,000. OI is usually caused by the mutation of COL1A1 and COL1A2, which would encode the α-chain of type I collagen. OI is clinically characterized by decreased bone mass, increased risk of bone fragility, blue sclerae, and dentinogenesis.Case presentationA 29-year-old male patient was diagnosed with right tibial plateau fracture caused by slight violence. Physical examination revealed the following: height, 140 cm; weight, 70 kg; body mass index (BMI), 35.71 kg/m2; blue sclera and barrel chest were observed. X-ray examination showed left convex deformity of the thoracic vertebrae with reduced thoracic volume. Laboratory examinations revealed a decrease in both vitamin D and blood calcium levels. Bone mineral density (BMD) was lower than the normal range. After the preoperative preparation was completed, the open reduction and internal fixation of the right tibial plateau fracture were performed. Meanwhile, whole blood samples of this OI patient and the normal control were collected for RNA transcriptome sequencing. The RNA sequence analysis revealed that there were 513 differentially expressed genes (DEGs) between this OI patient and the normal control. KEGG-enriched signaling pathways were significantly enriched in extracellular matrix (ECM)–receptor interactions.ConclusionIn this case, DEGs between this OI patient and the normal control were identified by RNA transcriptome sequencing. Moreover, the possible pathogenesis of OI was also explored, which may provide new evidence for the treatment of OI.

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder affecting women, which can lead to infertility. Infertility, obesity, hirsutism, acne, and irregular menstruation are just a few of the issues that PCOS can be linked to. PCOS has a complicated pathophysiology and a range of clinical symptoms. Chronic low-grade inflammation is one of the features of PCOS. The inflammatory environment involves immune and metabolic disturbances. Numerous organ systems across the body, in addition to the female reproductive system, have been affected by the pathogenic role of immunological dysregulation in PCOS in recent years. Insulin resistance and hyperandrogenism are associated with immune cell dysfunction and cytokine imbalance. More importantly, obesity is also involved in immune dysfunction in PCOS, leading to an inflammatory environment in women with PCOS. Hormone, obesity, and metabolic interactions contribute to the pathogenesis of PCOS. Hormone imbalance may also contribute to the development of autoimmune diseases. The aim of this review is to summarize the pathophysiological role of immune dysregulation in various organ systems of PCOS patients and provide new ideas for systemic treatment of PCOS in the future.

Introduction: Chemotherapy is a common strategy for the treatment of osteosarcoma. However, its therapeutic efficacy is not ideal due to the low targeting, lowbioavailability, and high toxicity of chemotherapy drugs. Nanoparticles can improve the residence time of drugs at tumor sites through targeted delivery. This new technology can reduce the risk to patients and improve survival rates. To achieve this goal, we developed a pHsensitive charge-conversion polymeric micelle [mPEG-b-P(C7-co-CA) micelles] for osteosarcoma-targeted delivery of cinnamaldehyde (CA).Methods: First, an amphiphilic cinnamaldehyde polymeric prodrug [mPEG-b-P(C7-co-CA)] was synthesized through Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT) polymerization and post-modification, and self-assembled into mPEG-b-P(C7-co-CA) micelles in an aqueous solution. The physical properties of mPEG-b-P(C7-co-CA) micelles, such as critical micelle concentration (CMC), size, appearance, and Zeta potential were characterized. The CA release curve of mPEG-b-P(C7-co-CA) micelles at pH 7.4, 6.5 and 4.0 was studied by dialysis method, then the targeting ability of mPEG-b-P(C7-co-CA) micelles to osteosarcoma 143B cells in acidic environment (pH 6.5) was explored by cellular uptakeassay. The antitumor effect of mPEG-b-P(C7-co-CA) micelles on 143B cells in vitro was studied by MTT method, and the level of reactive oxygen species (ROS) in 143B cells after mPEG-b-P(C7-co-CA) micelles treatment was detected. Finally, the effects of mPEG-b-P(C7-co-CA) micelles on the apoptosis of 143B cells were detected by flow cytometry and TUNEL assay.Results: An amphiphilic cinnamaldehyde polymeric prodrug [mPEG-b-P(C7-co-CA)] was successfully synthesized and self-assembled into spheric micelles with a diameter of 227 nm. The CMC value of mPEG-b-P(C7-co-CA) micelles was 25.2 mg/L, and it showed a pH dependent release behavior of CA. mPEG-b-P(C7-co-CA) micelles can achieve chargeconversion from a neutral to a positive charge with decreasing pHs. This charge-conversion property allows mPEG-b-P(C7-co-CA) micelles to achieve 143B cell targeting at pH 6.5. In addition, mPEG-b-P(C7-co-CA) micelles present high antitumor efficacy and intracellular ROS generation at pH 6.5 which can induce 143B cell apoptosis.Discussion: mPEG-b-P(C7-co-CA) micelles can achieve osteosarcoma targeting effectively and enhance the anti-osteosarcoma effect of cinnamaldehyde in vitro. This research provides a promising drug delivery system for clinical application and tumor treatment.

ObjectivesThe aim of this systematic review was to summarize the available literature on gut microbiome (GMB) and osteoarthritis (OA), analyze the correlation between GMB and OA, and explore potential underlying mechanisms.MethodsA systematic search of the PubMed, Embase, Cochrane, and Web of Science with the keywords “Gut Microbiome” and “Osteoarthritis” was conducted to identify the human and animal studies exploring the association between GMB and OA. The retrieval time range was from the database inception to July 31, 2022. Studies reported the other arthritic diseases without OA, reviews, and studies focused on the microbiome in other parts of the body with OA, such as oral or skin, were excluded. The included studies were mainly reviewed for GMB composition, OA severity, inflammatory factors, and intestinal permeability.ResultsThere were 31 studies published met the inclusion criteria and were analyzed, including 10 human studies and 21 animal studies. Human and animal studies have reached a consistent conclusion that GMB dysbiosis could aggravate OA. In addition, several studies have found that alterations of GMB composition can increase intestinal permeability and serum levels of inflammatory factors, while regulating GMB can alleviate the changes. Owing to the susceptibility of GMB to internal and external environments, genetics, and geography, the included studies were not consistent in GMB composition analysis.ConclusionThere is a lack of high-quality studies evaluating the effects of GMB on OA. Available evidence indicated that GMB dysbiosis aggravated OA through activating the immune response and subsequent induction of inflammation. Future studies should focus on more prospective, cohort studies combined with multi-omics to further clarify the correlation.

A liquid-seed assisted synthesis method was developed to prepare nano-sized lamellar SAPO-n zeolite. The aging of liquid-seed results in the dissolution of solid-seed particles and thus adjusts the ability to direct zeolite crystallization. Lamellar SAPO-34 zeolite with thickness of about 50 nm and well-controlled acidity was synthesized and the zeolite yield reaches 80% (SiO2/Al2O3 = 0.4, TEA/Al2O3 = 1.6, liquid-seed contents 3.35%). The bifunctional catalyst consisting of the above prepared SAPO-n and ZnCrOx oxide shows a high space-time yield (STY) of light olefins reaching 212 g•kg−1•h−1 in the reaction of direct conversion of syngas to light olefins.

Background: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with a complicated prognosis. Even though various prognostic evaluations have been applied currently, they usually only use the clinical factors that overlook the molecular underlying DLBCL progression. Therefore, more accurate prognostic assessment needs further exploration. In the present study, we constructed a novel prognostic model based on microtubule associated genes (MAGs).Methods: A total of 33 normal controls and 1360 DLBCL samples containing gene-expression from the Gene Expression Omnibus (GEO) database were included. Subsequently, the univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to select the best prognosis related genes into the MAGs model. To validate the model, Kaplan-Meier curve, and nomogram were analyzed.Results: A risk score model based on fourteen candidate MAGs (CCDC78, CD300LG, CTAG2, DYNLL2, MAPKAPK2, MREG, NME8, PGK2, RALBP1, SIGLEC1, SLC1A1, SLC39A12, TMEM63A, and WRAP73) was established. The K-M curve presented that the high-risk patients had a significantly inferior overall survival (OS) time compared to low-risk patients in training and validation datasets. Furthermore, knocking-out TMEM63A, a key gene belonging to the MAGs model, inhibited cell proliferation noticeably.Conclusion: The novel MAGs prognostic model has a well predictive capability, which may as a supplement for the current assessments. Furthermore, candidate TMEM63A gene has therapeutic target potentially in DLBCL.

BackgroundWe aimed to compare the efficacy of chimeric antigen receptor T (CAR-T) cell therapy with that of autologous stem cell transplantation (auto-HSCT) in relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL).Research design and methodsWe searched eligible publications up to January 31st, 2022, in PubMed, Cochrane Library, Springer, and Scopus. A total of 16 publications with 3484 patients were independently evaluated and analyzed using STATA SE software.ResultsPatients who underwent CAR-T cell therapy showed a better overall response rate (ORR) and partial response (PR) than those treated with auto-HSCT (CAR-T vs. auto-HSCT, ORR: 80% vs. 73%, HR:0.90,95%CI:0.76-1.07,P = 0.001; PR: 20% vs. 14%, HR:0.65,95%CI:0.62-0.68,P = 0.034). No significant difference was observed in 6-month overall survival (OS) (CAR-T vs. auto-HSCT, six-month OS: 81% vs. 84%, HR:1.23,95%CI:0.63-2.38, P = 0.299), while auto-HSCT showed a favorable 1 and 2-year OS (CAR-T vs. auto-HSCT, one-year OS: 64% vs. 73%, HR:2.42,95%CI:2.27-2.79, P < 0.001; two-year OS: 54% vs. 68%, HR:1.81,95%CI:1.78-1.97, P < 0.001). Auto-HSCT also had advantages in progression-free survival (PFS) (CAR-T vs. auto-HSCT, six-month PFS: 53% vs. 76%, HR:2.81,95%CI:2.53-3.11,P < 0.001; one-year PFS: 46% vs. 61%, HR:1.84,95%CI:1.72-1.97,P < 0.001; two-year PFS: 42% vs. 54%, HR:1.62,95%CI:1.53-1.71, P < 0.001). Subgroup analysis by age, prior lines of therapy, and ECOG scores was performed to compare the efficacy of both treatment modalities.ConclusionAlthough CAR-T cell therapy showed a beneficial ORR, auto-HSCT exhibited a better long-term treatment superiority in R/R DLBCL patients. Survival outcomes were consistent across different subgroups.

We provide insights and innovative ideas for China to achieve green development and promote high-quality economic development by studying the impact of air quality on enterprise productivity. This paper uses data from 2008 to 2016 for A-share companies listed on the Shanghai and Shenzhen stock markets, as well as the levels of particulate matter under 2.5 μm in diameter for 214 major Chinese cities. At the same time, this paper innovatively applies regression discontinuity and the Spatial Durbin Model for empirical testing. Considering the endogeneity, we choose the air flow index as an instrumental variable and the generalized space two-stage least squares method for the endogenous test. Additionally, we use dynamic regression and different spatial weight matrix to conduct robustness tests and reselect data from 2008 to 2012 and 2013 to 2016 as samples. Moreover, we test corporate heterogeneity from three perspectives: pollutant type, firm equity, and an industry’s technological level. The results show that the deterioration of local air quality significantly inhibits firm productivity, while the spatial spillover effects of pollution from surrounding cities also have a significant dampening effect on firm productivity. This negative effect is transmitted through research and development innovation capacity, human capital, and government subsidies. This empirical evidence from listed companies can be used for evaluating air quality management to enhance enterprise productivity, as well as to provide policy recommendations for boosting firm productivity through improved air quality.