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Background: Fetal midgut volvulus is a rare disease, with a high risk of potentially life-threatening fetal complications., Purpose: The aim of this study was to retrospectively analyze the imaging findings of fetal midgut volvulus diagnosed by magnetic resonance imaging (MRI) and explore its value in non-invasive prenatal diagnosis., Methods: A retrospective collection of data from 156 fetuses suspected of intestinal obstruction by ultrasound examination in our hospital was conducted. All ultrasound examinations showed fetal intestinal dilation and fetal MRI diagnosis suspected midgut volvulus in 32 cases (32/156), of which 18 cases (18/32) that underwent surgical treatment in the neonatal period were confirmed to have midgut volvulus. MRI signs in the 18 fetuses with midgut volvulus were analyzed., Results: During MRI examination, all 18 fetuses showed gastric and/or intestinal dilatation, most of which showed different degrees of obstruction in T1-weighted images (WIs) and T2WIs, showing the "black and white sign" (14/18), "whirlpool sign" (10/18), and "coffee bean sign" (6/18). High signal intensity changes in diffusion-weighted imaging sequences were observed in intestinal tubes with ischemia and infarction. Direct signs of vascular torsion were observed in some cases (8/18). MRI signs indicated fetal midgut volvulus with hydramnios (16/18), meconium pseudocyst (7/18), meconium peritonitis (4/18), testicular hydrocele (3/18), and secondary pulmonary dysplasia (6/18). Operations confirmed the diagnosis of segmental midgut volvulus in 15 cases, complete midgut volvulus in 3 cases, and combined with intestinal atresia in 8 cases., Conclusion: Prenatal MRI plays an important role in the diagnosis of fetal midgut volvulus and the discovery of its complications, which can guide the treatment after birth and provide a reference for the prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kou, Song, Gao and Zhou.)

Schizophrenia is recognized as one of the most severe psychiatric disorders, with its pathogenesis likely involving genetic, epigenetic, developmental, and environmental factors. Members of the Methyl-CpG Binding Domain (MBD) Family play a crucial role in the regulation of genomic DNA methylation, and studies have implicated the association between MBD family and neurodevelopmental disorders. Copy number variations (CNVs) are a significant genetic basis for human genomic variation, also playing a critical role in the genetic processes of schizophrenia. Therefore, we aimed to evaluate the susceptibility of MBD family CNVs to schizophrenia by exploring and validating them in two separate populations using CNVplex™ and qPCR methods, and to explore the relationship between MBD family CNVs and clinical phenotypes in the overall population using chi-square tests and Fisher's exact tests. Results suggest that an increase in MBD1 gene copy number and a deficiency in MBD2 gene copy number may be associated with the risk of schizophrenia. The deficiency in MBD2 gene copy number may increase the risk of delusion of reference and delusion of persecutory in the overall sample, as well as in males. This research provides preliminary evidence supporting the association between MBD family CNVs and schizophrenia, highlighting the potential role of the MBD family in the pathogenesis of schizophrenia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives: This study aims to report the clinical, biological, and imaging features of cross-sectional study of neurosyphilis patients with leptomeningeal enhancement of spinal cord. Here, 51 neurosyphilis patients with leptomeningeal enhancement of spinal cord positivity are described, offering a promise in terms of early diagnosis, thereby enabling timely detection and treatment., Methods: We retrospectively included all neurosyphilis patients enrolled in this study from December 2019 to January 2024. We identified 51 included patients with leptomeningeal enhancement of spinal cord positivity. Their neuroimaging, socio-demographical, clinical status, presentations, and laboratory manifestations were reported retrospectively., Results: Magnetic resonance imaging showed lumbar or conus medullaris and cauda equina radial enhancement in 72.7%, leptomeningeal enhancement of cervical spine in 65.9%, and thoracic involvement in 55.3%. Twenty of 51 neurosyphilis patients completed the follow-up. Among the 20 patients, the lesioned region in half of patients was decreased or disappeared after therapy. The predominant phenotype was tabes dorsalis. Median age at onset was 51 years, and 72.5% were male. Urinary incontinence was found in 33.3% of patients, and memory deterioration in 39.2%. The most frequent physical sign was Argyll Robertson pupil (45.1%). The levels of white blood cells (25/28, 89.3%) and protein concentration (23/28, 82.9%) of cerebrospinal fluid were reduced in more patients after therapy., Conclusion: In this study, we first concurrently investigated the clinical course and the biological and imaging features of leptomeningeal enhancement of spinal cord. Leptomeningeal enhancement of spinal cord is common with neurosyphilis. Our findings can be useful for raising clinical awareness to select patients with symptoms of myelopathy in whom MRI images should be investigated., Competing Interests: The authors declare no competing interests., (© 2024 Zhang et al.)

Ultraviolet radiations (UVR) produce harmful entities and reactive oxygen species (ROS) in skin cells, leading to skin photoaging. Caviar extract (CE) showed outstanding effects in delaying skin aging, but the underlying mechanism remains largely unknown. In this study, we prepared CE with acid protease and examined the anti-skin photoaging effects. The results showed that CE performed no cytotoxicity to HaCaT cells. For antioxidant properties, the EC50 values of DPPH and ABTS radical scavenging activity for CE were 1.27 and 5.20 mg/mL, respectively. It significantly reduced NF-κB, MMP-3 and MMP-9 protein expression levels, and increased IκB and TIMP-1 expression level in UVA-irradiated HaCaT cells. In the skin aging mice model, CE reduced the degree of UV-induced skin photoaging. Histological study confirmed that CE can ameliorate the adverse effects of UV exposure on the skin. Moreover, we found that CE could enhance the activities of Superoxide dismutase (SOD), and increased the contents of hydroxyproline (HYP) in photoaged mice skin. And CE elevated the protein expression level of COL17A1, KRT10, and KRT14 in mice skin. Taken together, our results bright systemic and new insights of CE into preventing UV-induced skin photoaging., (© 2024 American Society for Photobiology.)

Background: While Parkinsonism plus syndrome (PPS) is one of several atypical manifestations in neurosyphilis patients, its clinical features and brain-related manifestations are inadequately documented. In this cross-sectional study, we endeavored to indicate some key clinical and imaging features of neurosyphilis patients, particularly those specific to PPS., Methods: We retrospectively included all syphilis patients enrolled in the study from January 2021 to February 2024. All in all, 54 neurosyphilis patients with PPS were recruited. Their socio-demographical features, clinical status, presentations, laboratory manifestations and neuroimaging were analyzed retrospectively., Results: The predominant phenotype was general paresis (GP). Median age at onset was 50 years, and 87.0 % of the patients were male. Bradykinesia (53.7 %) was the most common manifestation of PPS in neurosyphilis patients. The most frequent physical sign was orofacial dyskinesia (the Candy sign), which accounted for 51.9 % of cases. In nearly three quarters (71.1 %), magnetic resonance imagery revealed temporal, hippocampal lobe, or whole brain atrophy, while 13.3 % exhibited basal ganglia lacunar infarction, and 22.2 % cases had focal demyelination in the cerebral peduncle, cerebellum, frontal lobe, parietal lobe, hippocampus and/or lateral vertical., Conclusions: Neurosyphilis patients exhibited PPS in involving bradykinesia, tremor rigidity and, in most cases, GP. Brain atrophy and basal ganglia lesion were the most common imaging findings in neurosyphilis patients with PPS. Our results should help to elucidate PPS characteristics PPS and neuroimaging mechanisms in neurosyphilis patients with PPS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: Thyroid-stimulating hormone (TSH) has been identified as an independent risk factor for non-alcoholic fatty liver disease (NAFLD), TSH binds to the TSH receptor (TSHR) to exert its function. However, the underlying mechanisms by which TSHR influences NAFLD development remain unclear. This study investigates the role of miR374b in NAFLD progression., Methods: Firstly, a rat model of non-alcoholic fatty liver was constructed and divided into a normal group and a model group. The liver tissue pathology and fat accumulation were detected by Oil Red O staining and hematoxylin-eosin staining. Western blot and Real time PCR were used to detect for the impact of TSHR/miR-374b/C/EBP β/ FoxO1 pathway in the NAFLD model, and the expression of relevant inflammatory factors in each group was detected by ELISA assay. A NAFLD cell model was constructed using HepG2 cells, TSHR overexpression and interference, combined with miR-374b inhibitor and mimics, were transfected simultaneously to demonstrate TSHR/miR-374b/C/EBP β/ The mechanism of FoxO1 adipogenesis in vitro., Results: TSHR stimulates miR374b secretion in human liver cancer cells (HepG2) and promotes lipid accumulation in the liver. Deficiency of miR374b in HepG2 cells attenuated NAFLD progression. Mechanistically, TSH increases miR374b expression, which then suppresses the transcription of its target genes, CCAAT/enhancer binding protein-b ( C/EBP β ) and Forkhead Box Protein O1 ( FOXO1 ). This suppression influences the expression of downstream lipid metabolism proteins, including PPARγ, SREBP2, and SREBP1c. Additionally, miR374b directly targets the 3'UTR of C/EBP β and FOXO1 , establishing a negative feedback loop in lipid metabolism., Conclusion: These findings suggest that TSHR-induced upregulation of miR374b accelerates NAFLD progression by modulating lipid metabolism pathways through C/EBP β and FOXO1., Competing Interests: Juyi Li was contributed as first author. The authors report no conflicts of interest in this work., (© 2024 Li et al.)

Air pollutants have been investigated to be associated with many health issues. Recently, increasing epidemiological studies have suggested the association between air pollution exposure and risk of frailty with inconsistent findings. This systematic review and meta-analysis was to summarize and evaluate effects of exposure to various air pollutants on risk of frailty. PubMed, Embase, Scopus and Web of Science were systematically searched for relevant studies published before May 11, 2024. Studies that explored the potential relationship between exposure to air pollutants (PM 2.5 , PM 10 , O 3 , NO x , solid fuel, secondhand tobacco, and air quality) and risk of frailty were included. The quality of cross-sectional and cohort studies was evaluated using an eight-item assessment instrument for epidemiological studies and Newcastle-Ottawa Scale, respectively. A total of 9,929 papers were retrieved, of which 20 met the inclusion criteria. Meta-analysis indicated that PM 2.5 exposure was significantly associated with frailty assessed by the frailty index [OR (95% CI): 1.24 (1,11-1.38) per 10 μg/m 3 increment]. Moreover, solid fuel exposures were significantly associated with an increased risk of frailty assessed by the frailty phenotype [OR (95% CI): 1.91 (1.09-3.34)] or the frailty index [OR (95% CI): 1.25 (1.11-1.41)]. Exposure to PM 2.5 and solid fuel increases the risk of frailty. Environmental protection policies and public health measures should be developed to reduce PM 2.5 concentrations. Effective measures, such as improving stoves and using clean fuels, should be taken to reduce indoor air pollution levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Peripherally inserted central catheters (PICC) are increasingly used in clinical practice, which also leads to an increased incidence of PICC-related thrombosis. Local thrombus formation could be prevented by limb ischemic preconditioning (IPC). This study aimed to determine whether IPC can prevent deep vein thrombosis in patients with PICC., Methods: A total of 600 breast cancer patients receiving PICC were randomized into two groups between July 2016 and July 2018 at the Department of Radiation Oncology. In the preconditioning group, 5 min of ischemic preconditioning was performed three times before PICC, whereas no preconditioning was performed in the sham group. The coagulation function levels, the PICC-related complications, the length of hospital stay, the cost of hospitalization, and the satisfaction of patients were compared., Results: The coagulation function levels of patients in the preconditioning group were more normal than in patients from the sham group. In total, 56/300 patients in the sham group had presence of PICC-related thrombosis, with only 23/300 in the IPC group, with no significant difference in other complications between the two groups. However, a longer hospital stay was observed in the sham group compared to the IPC group. Moreover, the cost of hospitalization was also reduced in the IPC group, which also improved the satisfaction of patients., Conclusion: Limb ischemic preconditioning may attenuate the severity of vein thrombosis in patients with PICC, which contributes to reducing the incidence of PICC-related thrombosis in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Kou, Zhao, Liu, He, Wang, Zhu, Ma and Wang.)

Recent trials have highlighted the cardiotoxicity of ribociclib, a CDK4/6 inhibitor, particularly its association with QT prolongation. However, studies on the link between CDK4/6 inhibitors and cardiotoxic events show inconsistent results, and the factors influencing these events and related drug interactions remain underexplored. To address these uncertainties, our study utilizes the FDA adverse event reporting system database (Q1 2015 to Q1 2024) to examine the cardiotoxic events of CDK4/6 inhibitors in breast cancer patients. We employed a comprehensive analytical framework, applying disproportionality methods including Bayesian confidence propagation neural network, proportional reporting ratio, and reporting odds ratio. Our findings highlight significant variability in cardiotoxic events among different CDK4/6 inhibitors, with ribociclib (IC: 0.26, 95%CI: 0.18-0.34) exhibiting pronounced cardiotoxicity. Notably, ribociclib was associated with serious cardiotoxic events such as torsade de pointes/QT prolongation (IC: 2.11, 95% CI: 1.90-2.29) and conduction defects (IC: 2.07, 95% CI: 1.87-2.23). For the first time, palbociclib has been identified with positive signals for cardiotoxic events at the preferred terms level, including pulmonary oedema, increased blood pressure, myocardial infarction, and cardiac flutter. Moreover, multivariable logistic regression and Bayesian network analyses reveal that age, geographic location, and the number of concomitant medications significantly influence cardiotoxic events. Our study also highlights significant drug interactions that increase the probability of specific cardiotoxic outcomes, notably with drugs like sertraline, lansoprazole, capecitabine, and torasemide. These findings highlight the need for personalized treatment plans to mitigate cardiotoxic events and improve patient safety., (© 2024 UICC.)

Cyclopamine, a compound found in wild Veratrum has shown promising potential as a lead anti-cancer drug by effectively blocking cancer signaling pathways. However, its complex chemical structure poses challenges for artificial synthesis, thus limiting its supply and downstream drug production. This study comprehensively utilizes induction, system optimization, and transgenic technologies to establish an efficient suspension culture system for the high-yield production of cyclopamine and its precursor, veratramine. Experimental results demonstrate that methyl jasmonate (MeJA) effectively promotes the content of veratramine and cyclopamine in Veratrum californicum var. callus tissue, while yeast extract (YE) addition significantly increases cell biomass. The total content of veratramine and cyclopamine reached 0.0638 mg after synergistic treatment of suspension system with these two elicitors. And the content of the two substances was further increased to 0.0827 mg after the optimization by response surface methodology. Subsequently, a genetic transformation system for V. californicum callus was established and a crucial enzyme gene VnOSC1, involved in the steroidal alkaloid biosynthesis pathway, was screened and identified for genetic transformation. Combined suspension culture and synergistic induction system, the total content of the two substances in transgenic suspension system was further increased to 0.1228 mg, representing a 276.69% improvement compared to the initial culture system. This study proposes a complete and effective genetic transformation and cultivation scheme for V. californicum tissue cells, achieving milligram-level production of the anticancer agent cyclopamine and its direct precursor veratramine for the first time. It provides a theoretical basis for the industrial-scale production of these substances., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The neuroimaging basis of intelligence remains elusive; however, there is a growing body of research employing connectome-based predictive modeling to estimate individual intelligence scores, aiming to identify the optimal set of neuroimaging features for accurately predicting an individual's cognitive abilities. Compared to adults, the disparities in cognitive performance among children and adolescents are more likely to captivate individuals' interest and attention. Limited research has been dedicated to exploring neuroimaging markers of intelligence specifically in the pediatric population. In this study, we utilized resting-state functional magnetic resonance imaging (fMRI) and intelligence quotient (IQ) scores of 170 healthy children and adolescents obtained from a public database to identify brain functional connectivity markers associated with individual intellectual behavior. Initially, we extracted and summarized relevant resting-state features from whole-brain or functional network connectivity that were most pertinent to IQ scores. Subsequently, these features were employed to establish prediction models for both performance and verbal IQ scores. Within a 10-fold cross-validation framework, our findings revealed that prediction models based on whole-brain functional connectivity effectively predicted performance IQ scores( R = 0.35 , P = 2.2 × 10 - 4 ) but not verbal IQ scores( R = 0.12 , P = 0.20 ). Results of prediction models based on brain functional network connectivity further demonstrated the exceptional predictive ability of the default mode network (DMN) and fronto-parietal task control network (FTPN) for performance IQ scores ( R = 0.71 , P = 2.2 × 10 - 18 ). The above findings have also been validated using an independent dataset. Our findings suggest that the performance IQ of children and adolescents primarily relies on the connectivity of brain regions associated with DMN and FTPN. Moreover, variations in intellectual performance during childhood and adolescences are closely linked to alterations in brain functional network connectivity., (© 2024 International Society for Developmental Neuroscience.)

Ag + , as a good bactericidal reagent, has been extensively used to prevent the growth and spread of bacteria and viruses. However, overcommit of Ag + would leave residues in environments, which is toxic to the human body even under minimal exposure. In this case, a fast and high selective sensing method based on field effect transistors (FET) has been proposed for monitoring Ag + in aqueous solutions. Through coordination interaction, Ag  +  could be spontaneously adsorbed on the surface of the sensing material MoS 2 and affect its electronic carrier transport behavior. The MoS 2 -based FET sensor show outstanding sensing performance to Ag + including short response time (60 s), good linear relationship (R 2 = 0.97), low detection limit (10 -10  mol/L) and high selectivity, which could meet the permissible criterion of Ag + in drinking water by the World Health Organization (0.93 × 10 -6  mol/L). This study will promote the application of FET sensors in environmental analysis, and provide important guidance to realize rapid, on-site or in-situ monitoring of heavy metals in aqueous solutions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Zhinan Guo, Cuiyun Kou, Li Niu, Haiguo Hu, Yiyu Luo has patent #CN202310973437.2 pending to Guangzhou University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To compare the accuracy and safety of robot-assisted and navigation-assisted screw placement in atlantoaxial dislocation surgery. Methods: A retrospective analysis was conducted on the clinical data of 49 patients with atlantoaxial dislocation treated consecutively at the Honghui Hospital of Xi'an Jiaotong University from April 2022 to December 2023. Among them, 27 were male and 22 were female, aged (44.2±11.7) years. Based on the date of surgery, 29 patients (from April 2022 to April 2023) received the S8 navigation-assisted screw placement (navigation group), 20 patients (from May to December 2023) received Mazor robot-assisted screw placement (robot group). The accuracy of screw placement, screw placement time, operation time, intraoperative blood loss, and intraoperative complications were recorded and compared between the two groups. The Japanese Orthopedic Association (JOA) score and visual analog scale (VAS) score of pain were adopted to evaluate the recovery of cervical spinal cord function and cervical and shoulder pain at preoperative period and 3-month follow-up, and the occurrence of complications was observed. Results: A total of 196 screws were inserted in 49 patients. In the navigation-assisted group, a total of 116 screws were inserted with an accuracy rate of 93.1% (108/116); in contrast, in the robot-assisted group, a total of 80 screws were inserted with an accuracy rate of 97.5% (78/80) ( P =0.040). The mean screw placement time, operation time, and blood loss in the navigation-assisted group were all significantly lower than those in the robot-assisted group [(37.8±3.4)min vs (48.4±4.6)min, (127.7±15.3)min vs (165.7±12.1)min and (205.8±13.6)ml vs (290.6±11.2) ml, respectively all P <0.01]. One case experienced intraoperative venous plexus injury in the robot-assisted group. Postoperatively, all patients experienced significant relief in neck pain symptoms, and neurological symptoms recovered to varying degrees. The VAS and JOA scores at 3 months post-surgery for both groups showed statistically significant improvements compared to pre-surgery (all P <0.01), but there was no statistically significant difference between the two groups (all P >0.05). Conclusions: Both robot-assisted and navigation-assisted screw placement show high accuracy and safety in atlantoaxial dislocation surgery. Compared to navigation, robot assistance increases the surgical time and blood loss, but significantly improves the accuracy of screw placement.

Efforts have been conducted on cyanobacterial genome editing, yet achieving genome editing in cyanophages remains challenging. Editing cyanophage genomes is crucial for understanding and manipulating their interactions with cyanobacterial hosts, offering potential solutions for controlling cyanobacterial blooms. In this study, we developed a streamlined CRISPR-Cas12a-based method for efficient cyanophage genome editing and then applied this method to the cyanophages A-1(L) and A-4(L) of Anabeana sp. PCC.7120. Multiple hypothetical genes were edited and knocked out from these two cyanophage genomes, generating viable mutants with varying capabilities to inhibit cyanobacterial growth. All these mutants displayed significant inhibitory effects on the host, indicating that these genes were non-essential for phage life cycle and the deletion led to little impairment of the cyanophages in infectious efficiency to their host. By iterative and simultaneous gene knockouts in cyanophage A-4(L), we achieved the minimal genome mutant with a 2400 bp reduction in genome size, representing a 5.75 % decrease compared to the wild type (WT). In conclusion, these cyanophage mutants can facilitate the identification of nonessential genes for cyanophages biology and the insertion of foreign genes for synthetic biology research. This advancement holds promise in addressing the widespread issue of water blooms and the associated environmental hazards., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

There are high rates of human immunodeficiency virus (HIV) and Treponema pallidum coinfection, HIV can increase the incidence and disability rate of neurosyphilis. However, there is a lack of data about the risk factors associated with the development of symptomatic neurosyphilis (SNS). We retrospectively reviewed the medical records of inpatients with concurrent syphilis and HIV infection who underwent a lumbar puncture and completed cerebrospinal fluid (CSF) examination. Sixty inpatients were consecutively enrolled from Beijing Ditan Hospital between January 2015 and March 2023. The clinical and laboratory features were evaluated between the SNS and asymptomatic neurosyphilis (ANS) groups. All patients were male, 25% (15/60) patients were diagnosed with ANS, and 75% (45/60) patients were diagnosed with SNS. Meningovascular neurosyphilis was the most prevalent clinical form in this study. Age, CD4 cell count, highly active antiretroviral therapy use, and serum HIV viral load showed no statistically significant differences between the 2 groups. The SNS group lacked early detection of syphilis (P < .001) and did not get previous adequate therapy for syphilis (P < .001) than the ANS group, as well as a higher initial serum toluidine red unheated serum test (TRUST) titer, current serum TRUST titer, CSF white blood cell count (WBC), protein concentration, and CSF TRUST titer (P = .014, P = .042, P = .01, P = .007, and P = .007, respectively). In multivariable logistic regression, high CSF WBC count (odds ratio = 1.08; P = .032) and previous treatment of syphilis (odds ratio = 0.01; P = .049) related to the SNS. Lack of antisyphilis treatment in the early stage of syphilis and a higher CSF WBC count are related risk factors for SNS in HIV-infected patients. Meningovascular neurosyphilis should get more attention in young patients with cryptogenic stroke., Competing Interests: The author have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To compare the effectiveness of robot-assisted and traditional freehand screw placement in the treatment of atlantoaxial dislocation., Methods: The clinical data of 55 patients with atlantoaxial dislocation who met the selection criteria between January 2021 and January 2024 were retrospectively analyzed. According to different screw placement methods, they were divided into the traditional group (using the traditional freedhand screw placement, 31 cases) and the robot group (using the Mazor X robot-assisted screw placement, 24 cases). There was no significant difference in gender, age, body mass index, etiology, and preoperative visual analogue scale (VAS) score, cervical spine Japanese Orthopaedic Association (JOA) score between the two groups ( P >0.05). The operation time, intraoperative blood loss, operation cost, and intraoperative complications were recorded and compared between the two groups. The VAS score and cervical spine JOA score were used to evaluate the improvement of pain and cervical spinal cord function before operation and at 1 month after operation. CT examination was performed at 3 days after operation, and the accuracy of screw placement was evaluated according to Neo grading criteria., Results: All the 55 patients successfully completed the operation. The operation time, intraoperative blood loss, and operation cost in the robot group were significantly higher than those in the traditional group ( P <0.05). A total of 220 C 1 and C 2 pedicle screws were inserted in the two groups, and 94 were inserted in the robot group, with an accuracy rate of 95.7%, among them, 2 were inserted by traditional freehand screw placement due to bleeding caused by intraoperative slip. And 126 pedicle screws were inserted in the traditional group, with an accuracy rate of 87.3%, which was significantly lower than that in the robot group ( P <0.05). There were 1 case of venous plexus injury in the robot group and 3 cases in the traditional group, which improved after pressure hemostasis treatment. No other intraoperative complication such as vertebral artery injury or spinal cord injury occurred in both groups. All patients were followed up 4-16 months with an average of 6.6 months, and there was no significant difference in the follow-up time between the two groups ( P >0.05). Postoperative neck pain significantly relieved in both groups, and neurological symptoms relieved to varying degrees. The VAS score and cervicle spine JOA score of both groups significantly improved at 1 month after operation when compared with preoperative scores ( P <0.05), and there was no significant difference in the score change between the two groups ( P >0.05)., Conclusion: In the treatment of atlantoaxial dislocation, the accuracy of robot-assisted screw placement is superior to the traditional freedhand screw placement.

The genus Silurus , an important group of catfish, exhibits heterogeneous distribution in Eurasian freshwater systems. This group includes economically important and endangered species, thereby attracting considerable scientific interest. Despite this interest, the lack of a comprehensive phylogenetic framework impedes our understanding of the mechanisms underlying the extensive diversity found within this genus. Herein, we analyzed 89 newly sequenced and 20 previously published mitochondrial genomes (mitogenomes) from 13 morphological species to reconstruct the phylogenetic relationships, biogeographic history, and species diversity of Silurus . Our phylogenetic reconstructions identified eight clades, supported by both maximum-likelihood and Bayesian inference. Sequence-based species delimitation analyses yielded multiple molecular operational taxonomic units (MOTUs) in several taxa, including the Silurus asotus complex (four MOTUs) and Silurus microdorsalis (two MOTUs), suggesting that species diversity is underestimated in the genus. A reconstructed time-calibrated tree of Silurus species provided an age estimate of the most recent common ancestor of approximately 37.61 million years ago (Ma), with divergences among clades within the genus occurring between 11.56 Ma and 29.44 Ma, and divergences among MOTUs within species occurring between 3.71 Ma and 11.56 Ma. Biogeographic reconstructions suggested that the ancestral area for the genus likely encompassed China and the Korean Peninsula, with multiple inferred dispersal events to Europe and Central and Western Asia between 21.78 Ma and 26.67 Ma and to Japan between 2.51 Ma and 18.42 Ma. Key factors such as the Eocene-Oligocene extinction event, onset and intensification of the monsoon system, and glacial cycles associated with sea-level fluctuations have likely played significant roles in shaping the evolutionary history of the genus Silurus .

The fish gut microbiome is well known for its role in degrading nutrients to improve the host's digestion and absorption efficiency. In this study, we focused on the core physiological adaptability during the various reproductive stages of the black Amur bream ( Megalobrama terminalis ) to explore the interaction mechanisms among the fish host gut mucosal structure, gut enzyme activity, and gut microbial metabolism in the course of the host's reproductive cycle. Our findings showed that M. terminalis exhibited locomotion metabolic type (aids in sporting) in the reproductive stage, and a change to visceral metabolic type (aids in digestion) during non-reproductive and post-reproductive stage phases. The impact of metabolic type selection and energy demand during various reproductive stages on fish nutrition strategy and digestive function was substantial. Our resulted showed that mitochondria in intestinal epithelial cells of reproductive M. terminalis appeared autophagy phenomenon, and the digestive enzyme activities in the intestines of reproductive M. terminalis were lower than those in the non-reproductive and post-reproductive individuals. Moreover, these differences in nutrition strategy have a prominent impact on the gut microbiome of reproductive M. terminalis , compared to non-reproductive and post-reproductive samples. Our findings showed that reproductive females had lower levels of alpha diversity compared to non-reproductive and post-reproductive females. Our results also showed a greater functional variety and an increase in functional genes related to carbohydrate, lipid, amino acid, cofactors, and vitamin metabolic pathways in the NRS and PRS group. It is noteworthy that an enrichment of genes encoding putative enzymes implicated in the metabolism of taurine and hypotaurine was observed in the RS samples. Our findings illustrated that the stability and resilience of the gut bacterial community could be shaped in the wild fish host-microbiome interactions during reproductive life history.

Objective: It is well known that macro-thyroid-stimulating hormone (macro-TSH) could interfere with the detection of TSH. The anti-TSH autoantibody is an essential component of macro-TSH. However, the epidemiological characteristics and the clinical interference of the anti-TSH autoantibody are unclear., Methods: In this study, the radioimmunoprecipitation technique was used to detect the anti-TSH autoantibody. Platforms with different detection mechanisms were applied to measure the TSH in patients with the anti-TSH autoantibody. Polyethylene glycol (PEG) precipitation was used to determine the immunoassay interference., Results: The prevalence of the anti-TSH autoantibody in patients with mild subclinical hypothyroidism (SCH) and autoimmune thyroiditis, but normal thyroid function, was 4.78%. All 10 patients with anti-TSH antibodies had autoimmune diseases, with five of them having significant clinical test interference., Conclusion: The appearance of the anti-TSH antibody is not associated with thyroid autoantibodies. The presence of the anti-TSH autoantibody can interfere with the detection of TSH and can affect clinical diagnosis and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Meng, Ni, Liu, Wang, Li, Chai, Kou, Zhang and Zhang.)

Polygonati rhizoma, known for its distinct yellow rhizomes, is a common therapeutic and culinary plant in Far East Asia. The hue of medicinal plants is closely tied to the flavonoid biosynthesis and content levels. In this research, the fibrous root and taproot of Polygonatum kingianum Coll.et Hemsl. were studied to explore the secondary metabolite expression and flavonoid biosynthesis mechanisms using transcriptomics and metabolomics. Metabolic analysis identified that the differentially accumulated metabolites (DAMs) in the fibrous root and taproot were predominantly flavonoids, steroids, alkaloids, and phenolic acids. Overall, 200 flavonoids were identified in P. kingianum Coll.et Hemsl., with 170 exhibiting variances between the fibrous root and taproot. The transcriptome analysis revealed that a total of 289 unigenes encoding 32 enzymes were annotated into four flavonoid biosynthesis pathways, which include phenylpropanoid biosynthesis pathway, flavonoid biosynthesis pathway, isoflavonoid biosynthesis pathway, and flavone and flavonol biosynthesis pathway. The integration of transcriptomic and metabolomic data elucidated that the 76 differentially expressed genes (DEGs) encoding 13 enzyme genes ( HCT , CCOMT , C4H , C3'H , CHI , PGT1 , FLS , F3'H , CHS , ANR , DFR , F3'5'H , and LAR ) and 15 DAMs preferred to be regulated in the flavonoid biosynthesis pathway. The expression of 10 DEGs was validated by qRT-PCR, agreeing with the same results by RNA-Seq. These findings shed light into the biosynthesis of secondary metabolites in P. kingianum Coll.et Hemsl., offering valuable information for the sustainable utilization and enhancement of this plant species.

Objective: SET domain-containing protein 1A (SETD1A) histone lysine N-methyltransferase may serve as a biomarker for the auxiliary diagnosis and treatment assessment of schizophrenia (SCZ). The aim of this study was to compare serum levels of SETD1A protein between patients with SCZ and health controls., Methods: Patients with SCZ and health controls were recruited from the Sixth Hospital of Changchun and the 'Survey on Chronic Diseases and Risk Factors among Adults in Jilin Province', respectively. The quantifications of lysine N-methyltransferase in peripheral serum were conducted by the ELISA method, and data was analyzed using the R software., Results: Forty patients with SCZ (mean age: 33.97 ± 5.99 years) and forty healthy controls (mean age: 39.07 ± 4.62 years) were included. There was significantly lower concentration of SETD1A protein in the SCZ group compared with the control group (P < 0.001). This significant difference still exists after stratification by sex (P < 0.05)., Conclusion: Our study demonstrates that decreased levels of serum SETD1A protein may be utilized as a possible peripheral biomarker for schizophrenia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Phospholipase A2(PLA2) superfamily is recognized as being involved in the pathogenesis of schizophrenia by affecting lipid homeostasis in cell membranes. We hypothesized that PLA2 gene copy number variation (CNV) may affect PLA2 enzyme expression and be associated with schizophrenia risk. This study indicated that in the discovery stage, an increased copy number of PLA2G6 and the deletion of PLA2G3, PLA2G4A, PLA2G4F and PLA2G12F was associated with increased risk of schizophrenia. CNV segments involving six PLA2 genes were detected in publicly available datasets, including two deletion segments specific to the PLA2G4A gene. The relationship between the deletion of PLA2G4A and susceptibility to schizophrenia was then reaffirmed in the validation group of 806 individuals. There was a significant correlation between PLA2G4A deletion and the symptoms of poverty of thought in male patients and erotomanic delusion in females. Furthermore, ELISA results demonstrate a significant decrease in peripheral blood cytosolic PLA2(cPLA2) levels in patients with the PLA2G4A deletion genotype compared to those with normal and copy number duplicate genotypes. These data suggest that the functional copy number deletion in the PLA2G4A gene is associated with the risk of schizophrenia and clinical phenotypes by reducing the expression of cPLA2, which may be an indicator of susceptibility to schizophrenia., (© 2024. The Author(s).)

Economic resilience provides a new perspective for megacities to achieve sustainable development when facing multiple shocks, and its accurate evaluation is an essential prerequisite for optimizing urban governance. There are currently no generally accepted methods for empirical evaluation or measuring economic resilience, and the present study aims to contribute to in both the research field and methodology. The present study sets dimensions and indicators based on economic resilience's theoretical and empirical research and used Decision Making Trial and Evaluation Laboratory (DEMATEL) and Interactive Structural Modeling (ISM) methods to exclude the effect indicators and divide the indicator hierarchy, respectively. Subsequently, the present study conducts model validation using Chinese megacities as a case study. The game theory weighting method, which combines the Analytic Hierarchy Process (AHP) and Entropy methods, is used to calculate indicator weights, and the VIKOR (VIseKriterijumska Optimizacija i KOmpromisno Resenje) method is used to evaluate and compare economic resilience of megacities. The research findings indicate that the evaluation model constructed in the present study included 15 indicators (after excluding three effect indicators) divided into four levels. After merging the levels, they correspond to three dimensions: resistance, recoverability, and adaptability. In addition, using Chinese megacities as a case study, the evaluation results found that Beijing, Shanghai, and Shenzhen have high economic resilience, Tianjin and Guangzhou have moderate economic resilience, Chengdu has low economic resilience, and Chongqing has the lowest economic resilience. This result is consistent with previous studies and verifies the model's effectiveness. The present study also found that megacities with lower levels of economic resilience exhibit a more significant upward trend, as well as the highest and higher proportion of economic resilience in Chinese megacities depending on time passes, indicating that megacities' economic resilience is weakening. The evaluation result obtained in the present study is more specific, precise, and focused on depicting the distribution differences and development trends of economic resilience at the urban level., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To identify risk factors for the development of non-thyroidal illness syndrome (NTIS) in patients with systemic lupus erythematosus (SLE)., Methods: A retrospective analysis of 517 SLE patients and 1034 age-and sex-matched healthy population was conducted to compare the prevalence of NTIS in these two groups, and to analyze the laboratory and clinical characteristics of SLE patients with NTIS. Finally Logistic regression analysis was used to determine the risk factors for NTIS in SLE patients., Results: The prevalence of NTIS in the SLE patients was significantly higher than that in controls (39.7% vs. 1.0%, P < 0.001). In SLE patients, compared with euthyroidism patients, NTIS patients exhibited higher levels of neutrophils, hepatic enzymes, kidney damage markers, inflammatory markers and SLE disease activity index (SLEDAI). They also had a higher incidence of organ insufficiency and positive antibodies such as anti-ds-DNA antibodies and anti-SSA antibodies. However, NTIS patients had lower levels of hemoglobin, lymphocytes, platelets, serum albumin, and complement. Additionally, NTIS patients had a shorter duration of lupus and lower utilization of disease-modifying antirheumatic drugs (DMARDs) (P < 0.05). Logistic regression analysis showed that elevated SLEDAI (OR = 1.060, 95%CI 1.022-1.099, P = 0.002), elevated systemic immune-inflammation index (SII) (OR = 1.003, 95%CI 1.001-1.007, P = 0.026), elevated erythrocyte sedimentation rate (ESR) (OR = 1.019, 95%CI 1.010-1.028, P < 0.001), and hepatic insufficiency (OR = 1.916, 95% CI 1.173-3.131, P = 0.009) were independent risk factors for the development of NTIS in SLE. DMARDs treatment (OR = 0.495, 95% CI 0.306-0.799, P < 0.001) was an independent protective factor for NTIS., Conclusions: Inflammatory activity in SLE patients is associated with the development of NTIS. Key Points • Inflammatory activity indexes such as SLEDAI, SII, and ESR are independent risk factors for NTIS in SLE patients., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Despite the importance of understanding how intelligence is ingrained in the function and structure of the brain in some neurological disorders, the alterations of intelligence-associated neurological factors in atypical neurodevelopmental disorders, such as attention deficit/hyperactivity disorder (ADHD), are limited. Therefore, we aimed to explore the relationship between the brain functional and morphological characteristics and the intellectual performance of 139 patients with ADHD. Resting-state functional and T1-weighted structural magnetic resonance imaging (MRI) data and intellectual-performance data of the patients were collected. The MRI data were preprocessed to extract four indicators characterizing the participants' brain features: fractional amplitude of low-frequency fluctuation, regional homogeneity, and gray and white matter volumes. Then, we used a two-layer feature-selection method with support vector regression models based on three kernel functions to predict the verbal and performance intelligent quotients of the patients, along with ten fold cross-validation to evaluate the models' predictive performance. All models showed good performance; the correlation coefficients between the predicted and observed values for each predictive phenotypic variable were >0.41, with statistical significance. The brain features that could best predict the intellectual performance of the patients were concentrated in the superior and inferior frontal gyrus of the prefrontal areas, the angular gyrus and precuneus of the parietal lobe, the inferior and middle temporal gyrus of the temporal lobe, and part of the cerebellar regions. Thus, the voxel-based brain-feature indicators could adequately predict the intellectual performance of patients with ADHD, providing a foundation for future neuroimaging studies of this disorder., (© 2024 International Society for Developmental Neuroscience.)

Background: There is little evidence on the association between patterns of unhealthy lifestyle and mental health among young adults., Method: This study included a total of 28,978 young adults aged 18 to 44 years old in Guangdong province in south China, which was conducted from September to December in 2022. We used latent class analysis to classify the patterns of unhealthy lifestyle among young adults and used multiple logistic regression to explore their associations with depressive and anxiety symptoms., Result: The weighted prevalence of depressive and anxiety symptoms were 28.0 % and 19.5 %, respectively. The cumulative effect of unhealthy lifestyles on depressive and anxiety symptoms was significant. Five patterns of unhealthy lifestyle were classified. Compared to the relatively healthy lifestyle class, the class with more unhealthy lifestyles (OR = 6.54, 95 % CI: 5.70-7.51) and insufficient sleep (OR = 6.16, 95 % CI: 4.92-7.70) had higher risk for depressive and anxiety symptoms. Meaningfully, having adequate mental health literacy could reduce the risk of depressive and anxiety symptoms from unhealthy lifestyle by half., Limitations: The cross-section design study limited causal inferences, and the self-report information may lead to recall bias., Conclusions: Unhealthy lifestyles have a negative impact on depressive and anxiety symptoms through independent, cumulative and combined effects, and they could be interrelated. Unhealthy lifestyle patterns differed in younger population by socio-demographic characteristics and mental health literacy. Health-care professionals and policymakers may provide programs to intervene multiple unhealthy lifestyles and improve mental health literacy by integrating healthy lifestyle education to promote youngers' mental health., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest on this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cyanobacteria, which have a photoautotrophic lifestyle, are threatened by ultraviolet solar rays and the reactive oxygen species generated during photosynthesis. They can adapt to environmental conditions primarily because of their DNA damage response and repair mechanisms, notably an efficient homologous recombination repair system. However, research on double-strand break (DSB) repair pathways, including the Holliday junction (HJ) resolution process, in Synechocystis sp. PCC6803 is limited. Here, we report that SynRuvC from cyanobacteria Synechocystis sp. PCC6803 has classical HJ resolution activity. We investigated the structural specificity, sequence preference, and biochemical properties of SynRuvC. SynRuvC strongly preferred Mn 2+ as a cofactor, and its cleavage site predominantly resides within the 5'-TG↓(G/A)-3' sequence. Interestingly, novel flap endonuclease and replication fork intermediate cleavage activities of SynRuvC were also determined, which distinguish it from other reported RuvCs. To explore the effect of SynRuvC on cell viability, we constructed a knockdown mutant and an overexpression strain of Synechocystis sp. PCC6803 ( synruvC KD and synruvC OE ) and assessed their survival under a variety of conditions. Knockdown of synruvC increased the sensitivity of cells to MMS, HU, and H 2 O 2 . The findings suggest that a novel RuvC family HJ resolvase SynRuvC is important in a variety of DNA repair processes and stress resistance in Synechocystis sp. PCC6803., Competing Interests: JZ was employed by the company Suzhou XinBio Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Gu, Yang, Kou, Peng, Yang, Zhang, Jin, Han, Wang and Shen.)

Triterpene esters comprise a class of secondary metabolites that are synthesized by decorating triterpene skeletons with a series of oxidation, glycosylation, and acylation modifications. Many triterpene esters with important bioactivities have been isolated and identified, including those with applications in the pesticide, pharmaceutical, and cosmetic industries. They also play essential roles in plant defense against pests, diseases, physical damage (as part of the cuticle), and regulation of root microorganisms. However, there has been no recent summary of the biosynthetic pathways and biological functions of plant triterpene esters. Here, we classify triterpene esters into five categories based on their skeletons and find that C-3 oxidation may have a significant effect on triterpenoid acylation. Fatty acid and aromatic moieties are common ligands present in triterpene esters. We further analyze triterpene ester synthesis-related acyltransferases (TEsACTs) in the triterpene biosynthetic pathway. Using an evolutionary classification of BAHD acyltransferases (BAHD-ATs) and serine carboxypeptidase-like acyltransferases (SCPL-ATs) in Arabidopsis thaliana and Oryza sativa, we classify 18 TEsACTs with identified functions from 11 species. All the triterpene-skeleton-related TEsACTs belong to BAHD-AT clades IIIa and I, and the only identified TEsACT from the SCPL-AT family belongs to the CP-I subfamily. This comprehensive review of the biosynthetic pathways and bioactivities of triterpene esters provides a foundation for further study of their bioactivities and applications in industry, agricultural production, and human health., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: With the rapid growth of global aging, frailty has become a serious public health burden, affecting the life quality of older adults. Depressive symptoms (depression hereafter) and sleep quality are associated with frailty, but the pathways in which sleep quality and depression affect frailty remain unclear., Method: This cross-sectional study included 1866 community-dwelling older adults. Demographic characteristics and health-related data of them was collected, and we also assessed frailty, depression, and sleep quality. Descriptive statistics were carried out and ordinal logistic regression analysis was used to identify the factors correlated with frailty. Spearman correlation analysis and mediation analysis were employed to assess associations between sleep quality, depression and frailty. Two-sided p  < 0.05 was considered as significant., Results: The results showed that 4.1% older adults were frail and 31.0% were pre-frail. Ordinal logistic regression showed that age, consumptions of vegetables, exercise, sleep quality, depression, number of chronic diseases, chronic pain, and self-rated health were correlated with frailty. Spearman correlation analysis revealed that frailty was associated with depression and sleep quality. There was a mediation effect that sleep quality was a significant and positive predictor of frailty (total effect = 0.0545, 95% boot CI = 0.0449-0.0641), and depression was a mediator between sleep quality and frailty (mediation effect = 60.4%)., Conclusion: Depression and poor sleep quality may be early indicators of frailty in older adults. Improving the sleep quality and psychological state of older adults can improve frailty, which is beneficial for healthy aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Yu, Bai, Wu, Geng, Zhang, Liu, Meng, Gao, Li and Kou.)

This study aimed to evaluate whether there is a causal relationship between autoimmune thyroid disorders (AITDs) and telomere length (TL) in the European population and whether there is reverse causality. In this study, Mendelian randomization (MR) and colocalization analysis were conducted to assess the potential causal relationship between AITDs and TL using summary statistics from large-scale genome-wide association studies, followed by analysis of the relationship between TL and thyroid stimulating hormone and free thyroxine (FT4) to help interpret the findings. The inverse variance weighted (IVW) method was used to estimate the causal estimates. The weighted median, MR-Egger and leave-one-out methods were used as sensitivity analyses. The IVW method results showed a significant causal relationship between autoimmune hyperthyroidism and TL (β = -1.93 × 10 -2 ; p = 4.54 × 10 -5 ). There was no causal relationship between autoimmune hypothyroidism and TL (β = -3.99 × 10 -3 ; p = 0.324). The results of the reverse MR analysis showed that genetically TL had a significant causal relationship on autoimmune hyperthyroidism (IVW: odds ratio (OR) = 0.49; p = 2.83 × 10 -4 ) and autoimmune hypothyroidism (IVW: OR = 0.86; p = 7.46 × 10 -3 ). Both horizontal pleiotropy and heterogeneity tests indicated the validity of our bidirectional MR study. Finally, colocalization analysis suggested that there were shared causal variants between autoimmune hyperthyroidism and TL, further highlighting the robustness of the results. In conclusion, autoimmune hyperthyroidism may accelerate telomere attrition, and telomere attrition is a causal factor for AITDs., (© 2024 John Wiley & Sons Ltd.)

Introduction: This meta-analysis aims to provide evidence-based medical evidence for formulating rational treatment strategies and evaluating the prognosis of brain metastasis (BM) patients by assessing the effectiveness of the graded prognostic assessment (GPA) model in predicting the survival prognosis of patients with BM after whole-brain radiotherapy (WBRT)., Methods: A comprehensive search was conducted in multiple databases, including the China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), PubMed, Wanfang database, Cochrane Library, Web of Science, and Embase. Cohort studies that met the inclusion and exclusion criteria were selected. The quality of the included literature was evaluated using the Newcastle-Ottawa Scale, and all statistical analyses were performed with R version 4.2.2. The effect size (ES) was measured by the hazard ratio (HR) of overall survival (OS). The OS rates at 3, 6, 12, and 24 months of patients with BM were compared between those with GPAs of 1.5-2.5, 3.0, and 3.5-4.0 and those with GPAs of 0-1 after WBRT., Results: A total of 1,797 participants who underwent WBRT were included in this study. The meta-analysis revealed a significant association between GPA and OS rates after WBRT: compared with BM patients with GPA of 0-1, 3-month OS rates after WBRT were significantly higher in BM patients with GPA of 1.5-2.5 (HR = 0.48; 95% CI: 0.40-0.59), GPA of 3 (HR = 0.38; 95% CI: 0.25-0.57), and GPA of 3.5-4 (HR = 0.28; 95% CI: 0.15-0.52); 6-month OS rates after WBRT were significantly higher in BM patients with GPA of 1.5-2.5 (HR = 0.48; 95% CI: 0.41-0.56), GPA of 3 (HR = 0.33; 95% CI: 0.24-0.45), and GPA of 3.5-4 (HR = 0.24; 95% CI: 0.16-0.35); 12-month OS rates after WBRT were significantly higher in BM patients with GPA of 1.5-2.5 (HR = 0.49; 95% CI: 0.41-0.58), GPA of 3 (HR = 0.48; 95% CI: 0.32-0.73), and GPA of 3.5-4 (HR = 0.31; 95% CI: 0.12-0.79); and 24-month OS rates after WBRT were significantly higher in BM patients with GPA of 1.5-2.5 (HR = 0.49; 95% CI: 0.42-0.58), GPA of 3 (HR = 0.49; 95% CI: 0.32-0.74), and GPA of 3.5-4 (HR = 0.38; 95% CI: 0.15-0.94)., Conclusion: BM patients with higher GPAs generally exhibited better prognoses and survival outcomes after WBRT compared to those with lower GPAs., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023422914., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Geng, Kou and Wang.)

Background: Accumulating evidence suggests that the gut microbiota and its metabolites may be involved in autoimmune hypothyroidism. However, the causal association between gut microbiota, metabolites and autoimmune hypothyroidism remains to be determined., Methods: Instrumental variables were screened from the GWAS datasets of 211 gut microbiota taxonomic groups, gut microbiota-derived metabolites, and autoimmune hypothyroidism. Univariable Mendelian randomization (MR) and multivariable Mendelian randomization (MVMR) were used to analyse the potential causal relationship between autoimmune hypothyroidism, these metabolites, or these microbiota. During the MR analysis, we alternated multiple MR methods with different model assumptions to assess the consistency and robustness of the findings: inverse variance weighted (IVW), weighted median, MR pleiotropy residual sum and outlier (MRPRESSO) and MR-Egger methods. Reverse MR analysis was performed to assess the possibility of reverse causality. Finally, enrichment analyses were used to investigate potential biofunctions., Results: The IVW results of univariable MR showed that the phyla Actinobacteria, genus DefluviitaleaceaeUCG011, genus Eggerthella, family Defluviitaleaceae, genus Subdoligranulum, genus RuminococcaceaeUCG011, and genus Intestinimonas were associated with autoimmune hypothyroidism. After FDR adjustment, the absence of a causal relationship between gut microbiota and autoimmune hypothyroidism ( P FDR > 0.05) suggested a possible marginal association. The results on gut metabolites showed that N-(3-furoyl)glycine, pipecolate, phenylalanine, allantoin, indololactate and alanine were associated with autoimmune hypothyroidism. After FDR correction, only indololactate was associated with hypothyroidism (OR=1.592; 95% CI, 1.228-2.065; P FDR = 0.036). Family Defluviitaleaceae and genus DefluviitaleaceaeUCG011 were suggestively significant in the MVMR. The results of reverse MR analysis showed no reverse causality between autoimmune hypothyroidism and the identified gut microbiota. Enrichment analysis revealed that several key regulatory pathways were significantly enriched., Conclusion: This study supported that there were beneficial or detrimental causal effects of gut microbiota and its metabolites on autoimmune hypothyroidism risk, which provides more theoretical support for mechanistic research on the "thyroid-gut" axis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Yuan, Liu, Tang, Meng, Wang, Li, Chai, Kou, Yang, Li, Zhang, Guan and Zhang.)

Sodium-ion batteries (SIBs) as a replaceable energy storage technology have attracted extensive attention in recent years. The design and preparation of advanced anode materials with high capacity and excellent cycling performance for SIBs still face enormous challenges. Herein, a solution method is developed for in situ synthesis of anti-aggregation tellurium nanorods/reduced graphene oxide (Te NR/rGO) composite. The material working as the sodium-ion battery (SIB) anode achieves a high reversible capacity of 338 mAh g -1 at 5 A g -1 and exhibits up to 93.4% capacity retention after 500 cycles. This work demonstrates an effective preparation method of nano-Te-based composites for SIBs.

Since the introduction of the concept of narcolepsy, there has been a proliferation of discussions about its association with psychiatry. To elucidate the causal role of narcolepsy in the three psychiatric disorders [i.e., schizophrenia (SCZ), major depressive disorder (MDD), and attention-deficit hyperactivity disorder (ADHD)], we applied a bidirectional Mendelian randomization study using two stages (discovery stage and validation stage) and data from three different genome-wide association studies of narcolepsy. The estimates from different stages were combined using fixed-effects meta-analysis. Our findings suggest that narcolepsy is associated with an increased risk of SCZ. Conversely, MDD may be causally related to narcolepsy. A causal relationship between narcolepsy and ADHD was excluded., Competing Interests: Declaration of competing interest The authors declare they have no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background and Purpose: Vitamin D can both stimulate and inhibit adipogenesis, indicating that associations of the vitamin D level with some metabolic disorders may be nonlinear. This cross-sectional study aims to explore potential nonlinear associations of the 25-hydroxy vitamin D [25(OH)D] level with metabolic syndrome (MetS) and its components. Methods: Adults without previously diagnosed specific noncommunicable disease were selected from the National Health and Nutrition Examination Survey 2017-2018 ( n  = 870). Their demographic, physical, and laboratory data were obtained. The associations of serum 25(OH)D with MetS and its components were analyzed using logistic regression. Restricted cubic spline was applied to flexibly model the nonlinear association if the nonlinearity test was statistically significant. Results: The 25(OH)D level was inversely associated with risk of MetS [adjusted odds ratio (OR) = 0.986; 95% confidence interval (CI) = 0.978-0.993] and most MetS components, but not with the risk of raised triglycerides (adjusted OR = 0.996; 95% CI = 0.988-1.005). The association of serum 25(OH)D with central obesity risk was significantly nonlinear ( P for the nonlinearity test: 0.037). The OR for risk of central obesity decreased rapidly with increase in serum 25(OH)D concentration until the concentration reached 50 nmol/L, and then, the intensity of decrease in OR slowed down. Conclusions: Vitamin D is inversely associated with MetS, but not all MetS components. A nonlinear association between the vitamin D level and risk of central obesity has been found for the first time among the adult population, which reflects the complex roles of vitamin D in lipid metabolism. Although vitamin D deficiency (<50 nmol/L) was defined to avoid abnormal calcium and phosphorus metabolism, preventing its deficiency may also be beneficial for reduction of central obesity risk.

Context: Many observational studies have reported on the association between educational attainment (EA) and thyroid function, but the causal relationship remains unclear., Objective: We aimed to obtain causal effects of EA on thyroid function and to quantify the mediating effects of modifiable risk factors., Methods: Two-sample mendelian randomization (MR) was performed by using summary statistics from large genome-wide association studies (GWAS) to assess the effect of EA on thyroid function, including hypothyroidism, hyperthyroidism, thyrotropin (TSH), and free thyroxine (FT4). A multivariable analysis was conducted to assess the mediating role of smoking and help to explain the association between EA and thyroid function. Similar analysis was further performed using data from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2002., Results: In MR analysis, EA was causally associated with TSH (β = .046; 95% CI, 0.015-0.077; P = 4.00 × 10-3), rather than hypothyroidism, hyperthyroidism, and FT4. Importantly, smoking could serve as a mediator in the association between EA and TSH, in which the mediating proportion was estimated to be 10.38%. After adjusting for smoking in the multivariable MR analysis, the β value of EA on TSH was attenuated to 0.030 (95% CI, 0.016-0.045; P = 9.32 × 10-3). Multivariable logistic regression model in NHANES suggested a dose-response relationship between TSH (quartile [Q]4 vs Q1: odds ratio = 1.33; 95% CI, 1.05-1.68; P for trend = .023) and EA. Smoking, systolic blood pressure, and body mass index partially mediated the association between EA and TSH, with the proportion of the mediation effects being 43.82%, 12.28%, and 6.81%, respectively., Conclusion: There is a potentially causal association between EA and TSH, which could be mediated by several risk factors, such as smoking., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Social resilience is a key factor in disaster management, but compared to resilience in other fields, research on social resilience is still limited to assessment or evaluation, and there is still a lack of dynamic and procedural research, which is also a challenge. This article constructs a causal feedback model and a system dynamics model of social resilience during the COVID-19 epidemic, so as to analyze the dynamic characteristics and improvement path of social resilience. After verifying the effectiveness of the model, model simulation is conducted and the following important conclusions are drawn: social resilience dynamically changes during the research cycle and is influenced by social entity behavior and social mechanisms; The sensitivity factors for the two variables that measure social resilience, namely panic degree and damage degree, are the real-time information acquisition of public and the epidemic awareness of local government, respectively. Therefore, the path to enhancing social resilience should be pursued from both the public and government perspectives, including improving the public's ability to access real-time information, increasing the timeline of government information disclosure, and enhancing local governments' understanding and awareness of the epidemic., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kou, Yang. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Peritoneal dialysis (PD) use has increased in the United States since 2009, but how this has affected disparities in PD use is unclear. We used data from the United States Renal Data System to identify a cohort of incident dialysis patients from 2009 to 2019. We used logistic regression models to examine how odds of PD use changed by demographic characteristics. The incident PD population increased by 203% from 2009 to 2019, and the odds of PD use increased in every subgroup. PD use increased more among older people because the odds for those aged 75 years or older increased 15% more per 5-year period compared with individuals aged 18-44 years (odds ratio [OR] 1.68, 95% confidence interval [CI], 1.64 to 1.73 versus OR 1.46, 95% CI, 1.42 to 1.50). The odds of PD use increased 5% more per 5-year period among Hispanic people compared with White people (OR 1.58, 95% CI, 1.53 to 1.63 versus OR 1.51, 95% CI, 1.48 to 1.53). There was no difference in odds of PD initiation among people who were Black, Asian, or of another race. The odds of PD use increased 5% more for people living in urban areas compared with people living in nonurban areas (5-year OR 1.54, 95% CI, 1.52 to 1.56 versus 5-year OR 1.46, 95% CI, 1.42 to 1.50). The odds of PD use increased 7% more for people living in socioeconomically advantaged areas compared with people living in more deprived areas (5-year OR 1.60, 95% CI, 1.56 to 1.63 for neighborhoods with lowest Social Deprivation Index versus 5-year OR 1.50, 95% CI, 1.48 to 1.53 in the most deprived areas). Expansion of PD use led to a reduction in disparities for older people and for Hispanic people. Although PD use increased across all strata of socioeconomic deprivation, the gap in PD use between people living in the least deprived areas and those living in the most deprived areas widened., (Copyright © 2023 by the American Society of Nephrology.)

The aim of this study was to determine whether the age-Male-ALBI-Platelet (aMAP) score is applicable in community settings and how to maximise its role in risk stratification. A total of thousand five hundred and three participants had an aMAP score calculated at baseline and were followed up for about 10 years to obtain information on liver cancer incidence and death. After assessing the ability of aMAP to predict liver cancer incidence and death in terms of differentiation and calibration, the optimal risk stratification threshold of the aMAP score was explored, based on absolute and relative risks. The aMAP score achieved higher area under curves (AUCs) (almost all above 0.8) within 10 years and exhibited a better calibration within 5 years. Regarding absolute risk, the risk of incidence of and death from liver cancer showed a rapid increase after an aMAP score of 55. The cumulative incidence (5-year: 8.3% vs. 1.3% and 10-year: 20.9% vs. 3.6%) and mortality (5-year: 6.7% vs. 1.1% and 10-year: 17.5% vs. 3.1%) of liver cancer in individuals with an aMAP score of ≥55 were significantly higher than in those with a score of <55 (Grey's test p  < .001). In terms of relative risk, the risk of death from liver cancer surpassed that from other causes after an aMAP score of ≥55 [HR = 1.38(1.02-1.87)]. Notably, the two types of death risk had opposite trends between the subpopulation with an aMAP score of ≥55 and < 55. To conclude, this study showed the value of the aMAP score in community settings and recommends using 55 as a new risk stratification threshold to guide subsequent liver cancer screening., (© 2023 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Background: China has a high mortality from nasopharyngeal carcinoma (NPC). The NPC mortality trends in China from 2006 to 2020 were described and analyzed to understand its epidemiological characteristics by region and sex and to explore age, period, and cohort effects., Methods: This study utilized NPC mortality data from the China Health Statistical Yearbook. A joinpoint regression model was used to fit the standardized NPC mortality and age-specific mortality. The age-period-cohort model was applied to investigate age, period, and cohort effects on NPC mortality risk., Results: The results showed that the NPC mortality rate in China has been declining steadily. From 2006 to 2020, the standardized NPC mortality rate in most age groups showed a significant downward trend. The annual percentage change was smaller in rural areas than in urban areas. The mortality risks of rural males and rural females from 2016 to 2020 were 1.139 times and 1.080 times those from 2011 to 2015, respectively. Both urban males born in 1984-1988 and rural males born in 1979-1983 exhibited an increasing trend in NPC mortality risk., Conclusions: Our study confirmed the effectiveness of NPC prevention and treatment strategies in China from 2006 to 2020. However, it underscored the urgent need for targeted interventions in rural areas to further reduce NPC mortality rates., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The copolymer ethylene-octene (POE) has good aging resistance and is an inexpensive asphalt additive compared to the styrene-butadiene-styrene copolymer (SBS). However, POE is easy to segregate in asphalt during storage at high temperatures. Grafting glycidyl methacrylate (GMA) onto the molecular backbone of POE (i.e., POE- g -GMA) may solve this problem, for the epoxy groups in GMA can react with the active groups in asphalt. Asphalt modified with linear and crosslinked POE- g -GMA were prepared, and the hot storage stability, physical properties and thermal oxidation aging properties were discussed in detail. The results show that linear and low-degree crosslinked POE- g -GMA-modified asphalts are storage-stable at high temperatures via measurements of the difference in softening points and small-angle X-ray scattering (SAXS) characterizations from macro and micro perspectives. The difference in softening points (ΔSP) between the upper and lower ends is no more than 3.5 °C for modified asphalts after 48 h of being in an oven at 163 °C. More importantly, the crosslinking modification of POE- g -GMA can further increase the softening point and reduce the penetration as well as rheological properties via conventional physical property, dynamic shear rheometer (DSR) and multiple-stress creep recovery (MSCR) tests. Furthermore, asphalt modified with crosslinked POE- g -GMA reveals better aging resistance via measurements of the performance retention rate and electron paramagnetic resonance (EPR) characterizations after a rolling thin film oven test (RTFOT). This work may provide further guidelines for the application of polymers in asphalt.

The gut microbiome is thought to play vital roles in host fitness and local adaptation to new environments, thereby facilitating the invasion of the host species. The Nile tilapia ( Oreochromis niloticus ) (NT) is an aggressive and omnivorous species that competes with native fishes for food resources, and it has successfully invaded much of the Pearl River basin in China. Here, we investigated the gut microbiomes of invasive Nile tilapia and indigenous black Amur bream (BA) in the same river section using high-throughput 16S rRNA gene sequencing. The results indicated that the gut microbiome of NT had several special characteristics, e.g., higher alpha diversity and greater niche breadth, compared with the bream. The gut microbiota of the small size of Nile tilapia (NTS) and small size of black Amur bream (BAS) groups were dominated by Proteobacteria, while those of the NTS and large size of Nile tilapia (NTL) and BAS and large size of black Amur bream (BAL). BAL and NTL were characterized by Firmicutes and Fusobacteriota, respectively. We found that Pseudomonas , Cetobacterium , Ralstonia , and Romboutsia were biomarkers of the NTS, NTL, BAS, and BAL groups, respectively. Moreover, the results collectively suggested that the clustering coefficients of BAL and NTL networks were greater than those of BAS and NTS networks, and BAS had the smallest network among the four groups. Positive interactions between two ASVs dominated the BAS, NTS, and NTL networks, while the proportion of negative interactions between two ASVs in the BAL network was remarkably increased. Low levels of interspecies competition in the NT gut microbiome would contribute to high diversity in the dietary niches and would also benefit the survival and local adaptation of the host. Our results identified specific biomarkers of gut microbial species in invasive Nile tilapia and provided useful information concerning how to monitor and manage invasive Nile tilapia populations.

Deep learning is currently being used to automate surface defect detection in aluminum. The common target detection models based on neural networks often have a large number of parameters and a slow detection speed, which is not conducive to real-time detection. Therefore, this paper proposes a lightweight aluminum surface defect detection model, M2-BL-YOLOv4, based on the YOLOv4 algorithm. First, in the YOLOv4 model, the complex CSPDarkNet53 backbone network was modified into an inverted residual structure, which greatly reduced the number of parameters in the model and increased the detection speed. Second, a new feature fusion network, BiFPN-Lite, is designed to improve the fusion ability of the network and further improve its detection accuracy. The final results show that the mean average precision of the improved lightweight YOLOv4 algorithm in the aluminum surface defect test set reaches 93.5%, the number of model parameters is reduced to 60% of the original, and the number of frames per second (FPS) detected is 52.99, which increases the detection speed by 30%. The efficient detection of aluminum surface defects is realized., (© 2023. The Author(s).)

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common progressive liver disease worldwide. It can cause liver cancer and possibly death. Abnormal immune infiltration is involved in the progression of NAFLD. The aim of this study was to identify and validate the hub immune-related genes in NAFLD., Methods: Microarray data were downloaded from Gene Expression Omnibus, and immune-related differentially expressed genes (IRDEGs) were obtained. A protein-protein interaction network was used to further screen. The diagnostic value of the IRDEGs was evaluated by receiver operating characteristic curves. Differences in immune infiltration levels were analyzed using single-sample gene set enrichment analysis. Hub IRDEGs were identified by correlation analysis with immune infiltration levels. Finally, molecular experiments were used to confirm the expression of the hub IRDEGs and explore their roles in NAFLD., Results: We obtained 18 IRDEGs. Five hub genes were further identified by protein-protein interaction network, receiver operating characteristic curves and correlation analysis: AQP9, BACH2, CD4, IL17RE and S100A9. Based on functional enrichment analysis, the hub genes were enriched primarily in many immune-related pathways. In NAFLD, AQP9, CD4, and IL17RE expression was significantly reduced, whereas BACH2 and S100A9 expression was elevated. PCR, oil red O staining and triglyceride detection revealed that the knock-down of BACH2 and S100A9 reduced lipid accumulation in NAFLD cells., Conclusion: This study provided insight into the profile of immune infiltration underlying NAFLD and identified AQP9, BACH2, CD4, IL17RE and S100A9 as ancillary diagnostic indicators of NAFLD. And BACH2 and S100A9 might be therapeutic targets for NAFLD., Competing Interests: The authors state that they have no conflicts of interest in this work., (© 2023 Li et al.)

This study aimed to assess the relationship between dietary sodium/potassium intake and cognition in elderly individuals with hypertension. We designed a cross-sectional study based on the 2011-2014 National Health and Nutrition Examination Survey (NHANES) 2011-2014. A multivariable-logistic regression analysis was performed to analyze the relationship between sodium/potassium intake and cognitive impairment. Restricted cubic spline (RCS) based on regression analysis to assess the nonlinear dose-response relationship between dietary sodium intake and cognitive performance. Out of the 2276 participants included in this study, 1670 patients had hypertension. Compared with the lowest quartile of dietary sodium intake, the lowest weighted odds ratio of cognitive impairment in DSST was observed in Q4 (OR = 0.45, 0.29-0.70), and a similar trend was observed in AFT (OR = 0.34, 0.18-0.65). After adjusting the covariates, the lowest weighted multivariable-adjusted OR of cognitive impairment in DSST were also observed in Q4 (OR = 0.47, 0.26-0.84) compared with the lowest quartile of dietary sodium intake. The RCS results showed that dietary sodium intake was U-shaped and associated with the risk of cognitive impairment in the DSST (P non-linearity  = 0.0067). In addition, no significant association was observed between dietary potassium intake and different dimensions of cognitive performance. In conclusion, excessively high and low low dietary sodium were associated with impairment of specific processing speed, sustained attention, and working memory for elderly patients with hypertension in the United States. However, no association was observed between dietary potassium intake and cognition., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Positive associations between the risk of schizophrenia and the level of white blood cells (WBC) count have been suggested by observational studies. However, the causality of this association is still unclear., Methods: We used a group of bidirectional two-sample Mendelian randomization (MR) analyses to estimate the causal relationship between schizophrenia and WBC count traits (i.e., WBC count, lymphocyte count, neutrophil count, basophil count, eosinophil count, and monocyte count). The threshold of FDR-adjusted P < 0.05 was considered as showing potential evidence of a causal effect. Instrument variables were included based on the genome-wide significance threshold (P < 5 × 10 - 8 ) and linkage disequilibrium (LD) clumping (r 2  < 0.01). In total, 81, 95, 85, 87, 76, and 83 schizophrenia-related single nucleotide polymorphisms (SNPs) were used as genetic instruments from Psychiatric Genomics Consortium for six WBC count traits, respectively. And in reverse MR analysis, 458, 206, 408, 468, 473, and 390 variants extracted from six WBC count traits were utilized as genetic instruments, which were obtained from a recent large-scale Genome-Wide Association Study (GWAS)., Results: Genetically predicted schizophrenia was positively associated with the level of WBC count [odds ratio (OR) 1.017, 95% confidence interval (CI) 1.008-1.026; P = 7.53 × 10 - 4 ], basophil count (OR 1.014, 95%CI 1.005-1.022; P = 0.002), eosinophil count (OR 1.021, 95%CI 1.011-1.031; P = 2.77 × 10 - 4 ), monocyte count (OR 1.018, 95%CI 1.009-1.027; P = 4.60 × 10 - 4 ), lymphocyte count (OR 1.021, 95%CI 1.012-1.030; P = 4.51 × 10 - 5 ), and neutrophil count (OR 1.013, 95%CI 1.005-1.022; P = 0.004). WBC count traits are not associated with the risk of schizophrenia in our reverse MR results., Conclusion: Schizophrenia is associated with elevated levels of WBC count (i.e., higher WBC count, lymphocyte count, neutrophil count, basophil count, eosinophil count, and monocyte count)., (© 2023. The Author(s).)

Introduction: Systemic lupus erythematosus (SLE) and hypothyroidism often coexist in observational studies; however, the causal relationship between them remains controversial., Methods: Complementary genetic approaches, including genetic correlation, Mendelian randomization (MR), and colocalization analysis, were conducted to assess the potential causal association between SLE and primary hypothyroidism using summary statistics from large-scale genome-wide association studies. The association between SLE and thyroid-stimulating hormone (TSH) was further analyzed to help interpret the findings. In addition, findings were verified using a validation data set, as well as through different MR methods with different model assumptions., Results: The linkage disequilibrium score regression revealed a shared genetic structure between SLE and primary hypothyroidism, with the significant genetic correlation estimated to be 0.2488 (P = 6.00 × 10-4). MR analysis with the inverse variance weighted method demonstrated a bidirectional causal relationship between SLE and primary hypothyroidism. The odds ratio (OR) of SLE on primary hypothyroidism was 1.037 (95% CI, 1.013-1.061; P = 2.00 × 10-3) and that of primary hypothyroidism on SLE was 1.359 (95% CI, 1.217-1.520; P < 0.001). The OR of SLE on TSH was 1.007 (95% CI, 1.001-1.013; P = 0.032). However, TSH was not causally associated with SLE (P = 0.152). Similar results were found using different MR methods. In addition, colocalization analysis suggested that shared causal variants existed between SLE and primary hypothyroidism. The results of the validation analysis indicated a bidirectional causal relationship between SLE and primary hypothyroidism, as well as shared loci., Conclusion: In summary, a bidirectional causal relationship between SLE and primary hypothyroidism was observed with complementary genetic approaches., Competing Interests: Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cholesterol serves as a key precursor for many high-value chemicals such as plant-derived steroidal saponins and steroidal alkaloids, but a plant chassis for effective biosynthesis of high levels of cholesterol has not been established. Plant chassis have significant advantages over microbial chassis in terms of membrane protein expression, precursor supply, product tolerance, and regionalization synthesis. Here, using Agrobacterium tumefaciens-mediated transient expression technology, Nicotiana benthamiana, and a step-by-step screening approach, we identified nine enzymes (SSR1-3, SMO1-3, CPI-5, CYP51G, SMO2-2, C14-R-2, 8,7SI-4, C5-SD1, and 7-DR1-1) from the medicinal plant Paris polyphylla and established detailed biosynthetic routes from cycloartenol to cholesterol. Specfically, we optimized HMGR, a key gene of the mevalonate pathway, and co-expressed it with the PpOSC1 gene to achieve a high level of cycloartenol (28.79 mg/g dry weight, which is a sufficient amount of precursor for cholesterol biosynthesis) synthesis in the leaves of N. benthamiana. Subsequently, using a one-by-one elimination method we found that six of these enzymes (SSR1-3, SMO1-3, CPI-5, CYP51G, SMO2-2, and C5-SD1) were crucial for cholesterol production in N. benthamiana, and we establihed a high-efficiency cholesterol synthesis system with a yield of 5.63 mg/g dry weight. Using this strategy, we also discovered the biosynthetic metabolic network responsible for the synthesis of a common aglycon of steroidal saponin, diosgenin, using cholesterol as a substrate, obtaining a yield of 2.12 mg/g dry weight in N. benthamiana. Our study provides an effective strategy to characterize the metabolic pathways of medicinal plants that lack a system for in vivo functional verification, and also lays a foundation for the synthesis of active steroid saponins in plant chassis., (Copyright © 2023 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)