Search

Abstract The LONP1 gene encodes Lon protease, which is responsible for degrading damaged or misfolded proteins and binding mitochondrial DNA. Previously, LONP1 variants have been identified in patients with cerebral, ocular, dental, auricular, and skeletal anomalies (CODAS syndrome) and mitochondrial diseases. Seizures were occasionally observed. However, the association between LONP1 and epilepsy remains elusive. In this study, we performed trio-based whole-exome sequencing in a cohort of 450 patients with unexplained epilepsy and identified four pairs of compound heterozygous LONP1 variants in four unrelated cases. All patients exhibited good responses to anti-seizure medications and demonstrated no developmental delay or intellectual disabilities. The variant allele frequencies observed in this study were absent or low in the general population and were significantly lower than those of benign variants. At least one variant in each biallelic pair affected hydrogen bonding and/or altered protein stability. The CODAS syndrome-associated variants were concentrated in the AAA+ module, especially the α domain. Four of the five mitochondrial disease-associated variants were located in the AAA + domain and the NTD5H and NTD3H subdomains. In contrast, each of the biallelic variants from the patients with pure epilepsy had one variant located in the linker domain, and the other variant located in the mitochondrial targeting sequence or P domain. This study suggested that LONP1 gene is potentially a novel candidate gene for pure epilepsy. The phenotypic variation is associated with the sub-regional effects of variants.

The development of edible vegetable oil is related to food security and people’s quality of life. Literature research method was adopted in this research to analyze the policy and economic environments of edible vegetable oil industry, and on this basis, production scale, sales quantity and brand competition of edible vegetable oil were sorted out. According to the production data of edible vegetable oil from 2013 to 2022, the GM (1,1) model was used to forecast the yields of edible vegetable oil in the next five years. The results revealed that the output of edible vegetable oil will decline in the future. There was a super-large market advantage in the domestic market, and the overall development of edible vegetable oil industry will be stable in the future. It is concluded that the edible vegetable oil industry may face market challenges such as consumer demand reduction, demand structure diversification and complex competition of market players in the future. The study suggested that, first, enterprises need to pay attention to the nutrition and health of edible oil products, which could ensure food quality and safety, and meet the needs of consumers for a healthy life. Second, enterprises should carry out product innovation to develop new oil products with high quality as well as lightweight, and create a new consumption scene. Third, by targeting the niche consumer market, actively expanding the market space of edible oil and stabilizing the market scale of small and medium-sized enterprises, could promote the high-quality development of the edible vegetable oil industry.

Abstract Patients with tissue inflammation or injury often experience aberrant mechanical pain hypersensitivity, one of leading symptoms in clinic. Despite this, the molecular mechanisms underlying mechanical distortion are poorly understood. Canonical transient receptor potential (TRPC) channels confer sensitivity to mechanical stimulation. TRPC3 and TRPC6 proteins, coassembling as heterotetrameric channels, are highly expressed in sensory neurons. However, how these channels mediate mechanical pain hypersensitivity has remained elusive. It is shown that in mice and human, TRPC3 and TRPC6 are upregulated in DRG and spinal dorsal horn under pathological states. Double knockout of TRPC3/6 blunts mechanical pain hypersensitivity, largely by decreasing nociceptor hyperexcitability and spinal synaptic potentiation via presynaptic mechanism. In corroboration with this, nociceptor‐specific ablation of TRPC3/6 produces comparable pain relief. Mechanistic analysis reveals that upon peripheral inflammation, TRPC3/6 in primary sensory neurons get recruited via released bradykinin acting on B1/B2 receptors, facilitating BDNF secretion from spinal nociceptor terminals, which in turn potentiates synaptic transmission through TRPC3/6 and eventually results in mechanical pain hypersensitivity. Antagonizing TRPC3/6 in DRG relieves mechanical pain hypersensitivity in mice and nociceptor hyperexcitability in human. Thus, TRPC3/6 in nociceptors is crucially involved in pain plasticity and constitutes a promising therapeutic target against mechanical pain hypersensitivity with minor side effects.

Proximal gracilis tear is a rare sports-related injury that can easily lead to misdiagnosis and underdiagnosis. Clinical manifestations are dominated by localized pain, tenderness, and dysfunction. Here, we report a therapy of proximal segmental tear of the gracilis and demonstrate its treatment process and clinical outcome. This Technical Note describes in detail the minimally invasive distal gracilis resection technique for the treatment of chronic proximal gracilis ruptures, focusing on the most important technical aspects and thus attempting to introduce this procedure and make it more widely used in the treatment of similar muscle injuries.

The P4HTM gene encodes a transmembrane prolyl 4-hydroxylase, which is responsible for the degradation of hypoxia-inducible transcription factors (HIF) under normoxia. Clinically, biallelic P4HTM variants have been identified in patients with hypotonia, hypoventilation, intellectual disabilities, dysautonomia, epilepsy, and eye abnormalities (HIDEA syndrome). Seizure was one of the most prominent symptoms. However, the clinical features of patients with epilepsy associated with P4HTM variants remain unclear. In this report, we describe a one-month-old infant with HIDEA syndrome caused by compound heterozygous P4HTM variants (c.300dupG/p.Gly103Argfs*22 and c.488C > T/p.Ala163Val). The infant presented with clonic seizures of focal onset that responded well to valproate, but with profound intellectual disability and global developmental delay at the last follow-up at 3 years old. A review of the existing literature indicates that seizures in this population typically begin early in infancy, manifest in multiple types, and are relatively well controlled. Epilepsy seemed unrelated to developmental outcomes or disease progression. Valproate, which has HIF-1α inhibiting properties, may be a promising treatment avenue for this population.

Femoral head fractures are relatively uncommon high-energy injuries and usually associated with traumatic hip dislocation. Pipkin classified these fractures into 4 types according to the location of the head fragment related to the fovea and associated lesions on the femoral neck or acetabulum. Traditional open reduction and internal fixation for femoral head fracture has been proven to be effective, but it could be associated with significant complications. Arthroscopic fixation with screws is a less-invasive alternative to open reduction and internal fixation that offers several advantages. However, technical challenges could be encountered during the procedure and catastrophic consequences could occur in cases of fixation failure. Therefore, we propose an effective arthroscopic technique for Pipkin type I (small fracture caudal to the fovea capitis) femoral head fractures that uses an absorbable suture anchors. The anchors provide initial stability to the fracture fragments, and then the sutures are tied in a double-pulley fashion to further secure the fracture. Finally, a triangular suture bridge (“letter V”) is created, which supplies a convenient and stable fixation for proper femoral head fracture.

Edible vegetable oils could provide energy, essential fatty acids and various micronutrients required in the body. However, vegetable oils, being rich in unsaturated fatty acids, are susceptible to oxidation to produce a series of oxidation products that are harmful to health after consumption, due to environmental factors during processing and storage. Therefore, this paper introduced the causes of oxidation in edible vegetable oils, the mechanism of lipid autoxidation, the main oxidation pathways and the hazards of oil oxidation, and the research progress of antioxidation on edible vegetable oils were also reviewed, including low-temperature storage, gas-conditioned storage and adding single or combined antioxidants. Meanwhile, the current problems on the lipid oxidation and the antioxidant measures in edible vegetable oils were discussed. This work could be expected to provide some references for the researches focusing on the oxidative stability of edible vegetable oils.

Detect the expression of Farnesoid X Receptor(FXR), Multiple Drug Resistance Associated Protein-1(MRP-1) and Solute Carrier Family 7, Member 5 (SLC7A5) in hepatocellular carcinoma(HCC) of rat model, so as to provide new therapeutic targets for gene therapy of HCC. Sixty male Wistar rats were randomly divided into three groups. The rats in experimental group were given 0.2% diethylnitrosamine (DEN) by gavage with a dose of 10 mg/kg, 3 times a week, and it stopped at 12 weeks. The control group rats were given physiological saline by gavage, while the sham operation group did not receive anything by gavage. At 10 weeks, one rat in the experimental group was euthanized, and the changes of livers were recorded. The procedure was repeated at 12 weeks. After 12 weeks, HCC only occurred in the experimental group. After confirming the formation of the tumor through pathological examination, liver tissues and tumor tissues were taken from the three groups. FXR, MRP-1 and SLC7A5 expression in liver tissues and tumor tissues was detected. After 7 weeks the rats in experimental group ate less, and their weight was significantly reduced. Three months later, HCC was detected in 15 rats in the experimental group. The ratio of FXR/GAPDH mRNA, MRP-1/GAPDH mRNA, SLC7A5/GAPDH mRNA were significantly different among the three groups. Under the light microscope the FXR protein, MRP-1 protein, and SLC7A5 protein react with their respective antibodies, and they showed granular expression. Every pathological section included different numbers of positive cells in each group. FXR expression in HCC of rats was significantly lower than that in normal liver tissues, but MRP-1 and SLC7A5 expression in HCC were significantly higher than that in normal liver tissues, suggesting that drugs targeting FXR, MRP-1 and SLC7A5 may be new strategies for the treatment of HCC.

Information technology (IT) innovation development within non-IT firms has been a key interest, but it is fraught with challenges because these firms lack sufficient IT knowledge. This study takes a resource dependence perspective to examine how engaging interlocking directorates with IT firms, or IT interlocks, affects non-IT firms' innovation outcomes. Despite the acknowledged role of board interlocks in knowledge transfer, the role of IT interlocks in transferring IT knowledge has not been studied. Using a large-scale panel dataset of Chinese public firms between 2000 and 2020, our findings reveal that IT interlocks of non-IT firms positively impact their IT innovation by transferring IT knowledge, particularly when the interlocked IT firms are knowledge-intensive. Our research contributes to the information systems literature by affirming IT interlocks' positive impact on innovation outcomes and highlighting the value of specific board relational capital in transferring external knowledge in need. It also offers practical implications for non-IT firms overcoming innovation challenges by establishing directorate connections with IT firms. [ABSTRACT FROM AUTHOR]

Abstract Background Three‐dimensional visualization preoperative evaluation (3D‐VPE) and enhanced recovery after surgery (ERAS) have been suggested to improve outcomes of cancer surgery in patients, yet little is known regarding their clinical benefit in patients with gallbladder cancer (GBC). We hypothesized that the combination of 3D‐VPE and ERAS would improve the outcome of patients undergoing surgery for GBC. Objective This study aimed to determine if 3D‐VPE and ERAS can improve the outcomes and overall survival in patients with GBC, establishing a novel patient management strategy for GBC. Methods A total of 227 patients with GBC were recruited and divided into two groups: those who received traditional treatment between January 2000 and December 2010 (n = 86; the control group) and those who underwent 3D‐VPE and ERAS between January 2011 and December 2017 (n = 141). Univariate and multivariate analyses were employed to assess the relationship among disease stages, lymph node invasion, and cell differentiation between the two groups. Cox regression analysis was used to investigate patient survival in these groups. Results Patients who underwent 3D‐VPE and ERAS showed a significantly higher R0 resection rate (67.4% vs. 20.9%, p

Not only is scrap steel an indispensable ferritic raw material for the modern steel industry, but it is also the only green raw material that can replace iron ore in large quantities. The quality of the scrap steel directly affects the quality of molten steel, which makes it necessary to sort and grade scrap steel before it enters the furnace. Most iron and steel enterprises determine the grade of scrap steel mainly by visual inspection and caliper-based measurements by quality management personnel. As a result, this process is prone to human errors and low efficiency. Therefore, given that the major challenges of scrap inspection include the many categories of scrap, complex actual detection scenarios, and challenges in manual system connection, a deep learning network model CSSNet was proposed for scrap classification and rating based on the Squeeze-Excitation (SE) attention mechanism, and images of the scrap unloading process were collected for model training and validation. First, a 1∶3 physical model of scrap steel quality inspection was built to simulate this process. High-resolution visual sensors were used to collect images of diverse types of scrap steel in the scene of trucks unloading scrap steel. Then, a cross-stage local network was used to extract the features of the collected scrap images, the spatial pyramid structure was used to solve the problem of feature loss, and the attention mechanism was used to focus on the correlation between channels and retain the channel with the most feature information. Finally, model training and validation were done using two datasets containing seven labels for classification. In the model prediction stage, the constructed scrap steel quality inspection model CSSNet was used to judge the scrap steel category and quality to verify the accuracy and detection efficiency of the model. Based on the self-made scrap steel validation dataset, its performance was compared with mainstream single-stage object detection packages such as YOLOv4, YOLOv5s, and the two-stage object detection model Faster R-CNN. The model was found to be able to effectively rate different grades of scrap steel, with the classification accuracy rate of all categories has reached 83.7% and an mAP value of 88.8%. The performance of the CSSNet model is better than the other three target detection models. CSSNet can not only fully meet the needs of the actual production applications in terms of accuracy, real-time performance, and identification and rating efficiency but also surpass the traditional manual scrap quality inspection method, address multiple issues in the evaluation of scrap steel quality, and realize automated scrap steel quality testing.

Antimicrobial resistance has become a global problem that poses great threats to human health. Antimicrobials are widely used in broiler chicken production and consequently affect their gut microbiota and resistome. To better understand how continuous antimicrobial use in farm animals alters their microbial ecology, we used a metagenomic approach to investigate the effects of pulsed antimicrobial administration on the bacterial community, antibiotic resistance genes (ARGs) and ARG bacterial hosts in the feces of broiler chickens. Chickens received three 5-day courses of individual or combined antimicrobials, including amoxicillin, chlortetracycline and florfenicol. The florfenicol administration significantly increased the abundance of mcr-1 gene accompanied by floR gene, while amoxicillin significantly increased the abundance of genes encoding the AcrAB-tolC multidrug efflux pump (marA, soxS, sdiA, rob, evgS and phoP). These three antimicrobials all led to an increase in Proteobacteria. The increase in ARG host, Escherichia, was mainly attributed to the β-lactam, chloramphenicol and tetracycline resistance genes harbored by Escherichia under the pulsed antimicrobial treatments. These results indicated that pulsed antimicrobial administration with amoxicillin, chlortetracycline, florfenicol or their combinations significantly increased the abundance of Proteobacteria and enhanced the abundance of particular ARGs. The ARG types were occupied by the multidrug resistance genes and had significant correlations with the total ARGs in the antimicrobial-treated groups. The results of this study provide comprehensive insight into pulsed antimicrobial-mediated alteration of chicken fecal microbiota and resistome.

Engineered cementitious composites (ECC) is famous for its excellent tensile deformability and crack width control ability. Steel reinforced ECC beams under shear loading exhibit brittle behaviors, which leads to a lack of structural safety. The reliability-based shear capacity model of steel reinforced ECC beams needs to be established for ensuring the structural shear safety. In this research, a test database of steel reinforced ECC beams under shear loading was constructed based on the given selecting principles. Through considering the shear resistance provided by fibers, the shear capacity model of steel reinforced ECC beams was preliminary established. The statistical characteristics of random variables were described and determined, and reliability index was calculated through Monte Carlo simulation. It is found that reliability index increases with increasing ECC strength, while decreases with increasing stirrup strength or stirrup ratio, especially at the high partial factor of ECC. For different target reliability indexes, the recommended partial factors of ECC are obtained through calibration. This research supplies a useful reference for the shear design of steel reinforced ECC beams in the actual engineering.

ABSTRACTAsparaginase-associated pancreatitis (AAP) is a common and fatal complication after ASNase treatment in acute lymphoblastic leukemia(ALL). Here, a total of 1063 pediatric ALL patients treated with SCCLG-ALL-2016 regimen were collected since October 2016 to June 2020, including 35 patients with AAP. The clinical characteristics of AAP and non-AAP patients were compared. In AAP patients, the possible factors that affected the recurrence of AAP were analyzed, and the possible risk factors related to ALL-relapse were discussed. The results showed that age was a risk factor (P = .017) that affect the occurrence of AAP. In AAP patients, AAP tended to develop after the second use of PEG-ASNase (25.71%). In the follow-up chemotherapy, 17 patients re-exposed to ASNase and 7 cases developed AAP again with a percentage was 41.2%. There were no special factors that related with the recurrence of AAP. This study also found no association between the occurrence of AAP and prognosis of ALL, with the 4-year incidence of ALL relapse in AAP and non-AAP patients were 15.9% v.s.11.7% (HR: 1.009, 95% CI:0.370–2.752, P = .986), and there were no special factors that related with the ALL relapse among AAP patients. Based on the above results, the occurrence of AAP is related to age and should be vigilant after the second use of PEG-ASNase after use in pediatric ALL patients. Moreover, AAP is not associated with ALL relapse, but there is a high AAP recurrence rate when re-exposure to ASNase.