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Background: Recent research highlights the importance of muscular strength as a key factor in physical fitness, a strong indicator of overall mortality risk, and a vital target for preventing chronic diseases. This study used a proteome-wide Mendelian randomization analysis plus colocalization analysis for low hand grip strength to explore potential therapeutic targets for muscle weakness. Methods: We conducted two two-sample Mendelian randomization analyses from four cohorts to identify and validate the causal relationship between plasma proteins and low grip strength. We also employed bidirectional Mendelian randomization analysis with Steiger filtering, Bayesian co-localization, and phenotype scanning to detect reverse causality, thereby consolidating our Mendelian randomization findings. Downstream analyses were also undertaken of identified proteins, including knockout models, enrichment analyses, and protein-protein interaction networks. Finally, we assessed the druggability of the identified proteins. Results: At Bonferroni significance (P

Abstract Reinforcement learning (RL) stands as one of the three fundamental paradigms within machine learning and has made a substantial leap to build general-purpose learning systems. However, using traditional electrical computers to simulate agent-environment interactions in RL models consumes tremendous computing resources, posing a significant challenge to the efficiency of RL. Here, we propose a universal framework that utilizes a photonic integrated circuit (PIC) to simulate the interactions in RL for improving the algorithm efficiency. High parallelism and precision on-chip optical interaction calculations are implemented with the assistance of link calibration in the hybrid architecture PIC. By introducing similarity information into the reward function of the RL model, PIC-RL successfully accomplishes perovskite materials synthesis task within a 3472-dimensional state space, resulting in a notable 56% improvement in efficiency. Our results validate the effectiveness of simulating RL algorithm interactions on the PIC platform, highlighting its potential to boost computing power in large-scale and sophisticated RL tasks.

Abstract Background The burden of lumbar degenerative diseases (LDD) has increased substantially with the unprecedented aging population. Identifying elderly patients with high risk of postoperative adverse events (AEs) and establishing individualized perioperative management is critical to mitigate added costs and optimize cost-effectiveness to the healthcare system. We aimed to develop a predictive tool for AEs in elderly patients with transforaminal lumbar interbody fusion (TLIF), utilizing multivariate logistic regression, single classification and regression tree (hereafter, “classification tree”), and random forest machine learning algorithms. Methods This study was a retrospective review of a prospective Geriatric Lumbar Disease Database (age ≥ 65). Our outcome measure was postoperative AEs, including prolonged hospital stays, postoperative complications, readmission, and reoperation within 90 days. Patients were grouped as either having at least one adverse event (AEs group) or not (No-AEs group). Three models for predicting postoperative AEs were developed using training dataset and internal validation using testing dataset. Finally, online tool was developed to assess its validity in the clinical setting (external validation). Results The development set included 1025 patients (mean [SD] age, 72.8 [5.6] years; 632 [61.7%] female), and the external validation set included 175 patients (73.2 [5.9] years; 97 [55.4%] female). The predictive ability of our three models was comparable, with no significant differences in AUC (0.73 vs. 0.72 vs. 0.70, respectively). The logistic regression model had a higher net benefit for clinical intervention than the other models. A nomogram based on logistic regression was developed, and the C-index of external validation for AEs was 0.69 (95% CI 0.65–0.76). Conclusion The predictive ability of our three models was comparable. Logistic regression model had a higher net benefit for clinical intervention than the other models. Our nomogram and online tool ( https://xuanwumodel.shinyapps.io/Model_for_AEs/ ) could inform physicians about elderly patients with a high risk of AEs within the 90 days after TLIF surgery.

Objective Compensation characteristics of spinal sagittal malalignment according to pelvic incidence (PI) have yet to be elucidated. This study aimed to investigate the difference in compensatory segments according to PI in elderly patients with degenerative lumbar spinal stenosis (DLSS). Methods This retrospective study included 196 patients (143 females, 53 males) suffering from DLSS with an average age of 66.73 years in our department. Sagittal parameters were obtained on the whole spinal lateral radiograph, including T1‐T12 slope (T1S‐T12S), Cobb angle (CA) of the functional units of the thoracic spine, thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), PI, the ratio of PT to PI (PT/PI), PI minus LL mismatch (PI‐LL), sagittal vertical axis (SVA). Patients were divided into the low and high PI groups according to the median value of PI. With reference to the value of SVA and PI‐LL, each PI group was further grouped into the balance subgroup (SVA 10°), and imbalance subgroup (SVA ≥50 mm). Independent samples t‐test/Mann–Whitney U test, one‐way ANOVA/Kruskal‐Wallis test, and Person correlation analysis were utilized for statistical test. Results The median value of PI was 47.65°. 96 and 100 patients were assigned to low and high PI groups, respectively. Correlation analysis indicated that the T8‐T12 slope and T10‐T12 slope were associated with PI‐LL in the high and low PI groups, respectively (all, p

Kidney disease can be caused by various internal and external factors that have led to a continual increase in global deaths. Current treatment methods can alleviate but do not markedly prevent disease development. Further research on kidney disease has revealed the crucial function of epigenetics, especially acetylation, in the pathology and physiology of the kidney. Histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyllysine readers jointly regulate acetylation, thus affecting kidney physiological homoeostasis. Recent studies have shown that acetylation improves mechanisms and pathways involved in various types of nephropathy. The discovery and application of novel inhibitors and activators have further confirmed the important role of acetylation. In this review, we provide insights into the physiological process of acetylation and summarise its specific mechanisms and potential therapeutic effects on renal pathology.

Abstract Objective To generate a compensatory classification to evaluate sagittal spinal malalignment with lumbar degeneration. Methods We included 162 patients with low back pain who underwent full-length spinal radiography in our hospital from August 2019 to October 2021. Using full-length spine X-rays, we measured pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), C7 slope (C7S), thoracolumbar kyphosis (TLK), and C7 sagittal vertical axis (SVA). We also recorded the Oswestry Disability Index (ODI) and visual analog scale (VAS). Patients were divided into four groups based on the SRS-Schwab classification and four other groups based on the compensatory classification. Results ODI correlated with age, SS, LL, TK, C7-SVA, SRS-Schwab classification, and compensatory classification. Lumbar VAS score correlated with LL, TK, C7-SVA, SRS-Schwab classification, and compensatory classification. Leg VAS score only correlated with LL. Hidden imbalance and imbalance with compensation had more significant PT and larger TK than balance patients. The symptoms of the four compensatory classification groups gradually worsened. Conclusion The spinal-pelvic sagittal balance in patients with lumbar degeneration based on pelvic and thoracic compensation can reflect spinal balance and symptoms. This parameter might help evaluate spine sagittal alignment in elderly patients with lumbar degeneration.

Abstract Objective Cervical sagittal alignment changes (CSACs) influence outcomes and health-related quality-of-life. Anterior cervical discectomy and fusion (ACDF), laminectomy with fusion (LCF), and laminoplasty (LP) are common treatments for multisegmental cervical spondylotic myelopathy; however, these approaches need to be compared. Methods Our study included 167 patients who underwent ACDF, LCF, or LP. Patients were divided into four groups according to C2-C7 Cobb angle (CL): kyphosis (CL

Abstract Purpose This retrospective cross-sectional study investigated variations in the ratio of cervical lordosis to C7 slope (CL/C7S) at different stages of global sagittal balance to better understand how global sagittal alignment affects cervical alignment. Methods A total of 255 patients with the degenerative lumbar disease were retrospectively studied within a single medical center. Whole spine radiographs were used to evaluate sagittal parameters, mainly including occiput-C2 lordosis (OC2), cervical lordosis (CL), C7 slope (C7S), the ratio of cervical lordosis to C7 slope (CL/C7S), cervical sagittal vertical axis (CSVA), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), PI minus LL mismatch (PI–LL), and sagittal vertical axis (SVA). Patients were divided into the balance group (SVA 10°), and imbalance group (SVA > 50 mm). Results Significant correlations were found between CL/C7S and OC2 (r = − 0.334), CSVA (r = − 0.504), PI–LL (r = 0.189), and SVA (r = 0.309). Multivariable linear regression analysis indicated that patients in the hidden imbalance group had lower CL/C7S than those in the balance group (B = − 0.234, P

Background: Disc height (DH) change is considered one of the most critical factors in assessing intervertebral disc degeneration (IVD). Pfirrmann et al. developed a scoring system for disc degeneration evaluation based on changes in DH in magnetic resonance imaging (MRI). While the relationship between DH measurements and Pfirrmann scores for disc degeneration has been explored, the validity of different DH measuring techniques or their connection with disc degeneration is yet uncertain. The present study investigates intra-rater and inter-rater agreement and reliability of different DH measurement methods on MRI and evaluates the relationship between different DH measurement methods and Pfirrmann scores of IVD degeneration, as well as between different Pfirrmann scores and clinical outcomes. Methods: Adult patients with MRI scans of the lumbar spine were recruited. Eight DH measuring techniques were tested for intra-rater and inter-rater agreement and reliability. Bland and Altman's Limits of Agreement (LOA) was used to evaluate intra-rater and inter-rater agreements. Intra-rater and inter-rater reliability were evaluated using intra-class correlations (ICC) with 95 % confidence intervals (95 % CI). The association between DH and Pfirrmann scores was examined using one-way ANOVA. Results: Excellent intra-rater reliability was reported for 332 participants on DH (ranging from 0.912 (0.901, 0.923) to 0.973 (0.964, 0.981) and from 0.902 (0.892, 0.915) to 0.975 (0.962, 0.985) by two independent raters). All measuring methods had high intra-rater agreement, except for methods 4 and 5. All methods had good-to-excellent of inter-rater reliability on DH (ICCs ranging from 0.812 (0.795, 0.828) to 0.995 (0.994, 0.995)) except for the posterior disc material length of method 5 (ICC 0.740 (0.718, 0.761)). Methods 1 to 6 for evaluating DH in patients with spondylolisthesis had poor inter-rater reliability. The IVD levels with grades IV and V in Pfirrmann scores had significantly lower DH than the IVD levels with grades I to III in Pfirrmann scores. IVD levels with grades IV and V in Pfirrmann scores had significantly higher VAS and ODI than IVD levels with grades I in Pfirrmann scores. Conclusion: A good-to-excellent intra-rater and inter-rater reliability was achieved on most DH measuring methods on MRI following a standardized and structured protocol. However, small anatomical structures and different tissue borders could influence measurements. Additionally, DH can differentiate between grade IV and V Pfirrmann scores, and severe IVD degeneration (IV and V Pfirrmann) is linked to clinical outcomes.

Signal transducer and activator of transcription 3 (STAT3) is a cell-signal transcription factor that has attracted considerable attention in recent years. The stimulation of cytokines and growth factors can result in the transcription of a wide range of genes that are crucial for several cellular biological processes involved in pro- and anti-inflammatory responses. STAT3 has attracted considerable interest as a result of a recent upsurge in study because of their role in directing the innate immune response and sustaining inflammatory pathways, which is a key feature in the pathogenesis of many diseases, including renal disorders. Several pathological conditions which may involve STAT3 include diabetic nephropathy, acute kidney injury, lupus nephritis, polycystic kidney disease, and renal cell carcinoma. STAT3 is expressed in various renal tissues under these pathological conditions. To better understand the role of STAT3 in the kidney and provide a theoretical foundation for STAT3-targeted therapy for renal disorders, this review covers the current work on the activities of STAT3 and its mechanisms in the pathophysiological processes of various types of renal diseases.

Abstract Purpose The prevalence of degenerative spinal deformity (DSD) and the increased cost of correction surgery impose substantial burdens on the health care and insurance system. The aim of our study was to investigate the effects of the implementation of Enhanced Recovery After Surgery (ERAS) protocol on postoperative outcomes after complex spinal surgery. Methods A retrospective analysis of prospectively established database of DSD was performed. The consecutive patients who underwent open correction surgery for degenerative spinal deformity between August 2016 and February 2022 were reviewed. We extracted demographic data, preoperative radiographic parameters, and surgery-related variables. The ERAS patients were 1:1 propensity-score matched to a historical cohort by the same surgical team based on age, gender, BMI, and number of levels fused. We then compared the length of hospital stay (LOS), physiological functional recovery, and the rates of complications and readmissions within 90 days after surgery between the groups. Results There were 108 patients included, 54 patients in the ERAS cohort, and 54 patients matched control patients in the historical cohort. The historical and ERAS cohorts were not significantly different regarding demographic characteristics, comorbidities, preoperative parameters, operative time, and reoperation rate (P > 0.05). Patients in the ERAS group had significantly shorter postoperative LOS (12.0 days vs. 15.1 days, P = 0.001), average days of drain and urinary catheters placement (3.5 days vs. 4.4 days and 1.9 days vs 4.8 days, respectively), and lower 90-day readmission rate (1.8% vs. 12.9%, P = 0.027). The first day of assisted-walking and bowel movement occurred on average 1.9 days (2.5 days vs. 4.4 days, P = 0.001) and 1.7 days (1.9 days vs. 3.6 days, P = 0.001) earlier respectively in the ERAS group. Moreover, the rate of postoperative urinary retention (3.7% vs. 16.7%, P = 0.026) and surgical site infection (0% vs. 7.4%, P = 0.046) were significantly lower with ERAS protocol applied. Conclusions Our study confirmed that the ERAS protocol was safe and essential for patients undergoing thoracolumbar deformity surgery for DSD. The ERAS protocol was associated with a shorter postoperative LOS, a lower rate of 90-day readmission, less rehabilitation discharge, and less postoperative complications.

Abstract Objective To analyze the correlation between the changes in cervical curvature and the sagittal parameters of spino-pelvic and clinical efficacy after posterior laminoplasty (LP). Methods The patients with cervical spondylosis treated with LP from June 2018 to December 2020 were reviewed. The preoperative and follow-up spine full-length films were measured. The measured data included C2–C7 Cobb angle, C2–7 sagittal vertical axis (SVA), T1 slope (T1S), pelvic incidence, sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis (TK), and C7-SVA. Japanese Orthopaedic Association (JOA) score and neck disability index (NDI) score were recorded before surgery and follow-up. Results There were 56 patients in this study. There were no significant differences in spino-pelvic sagittal parameters before and after surgery; however, the JOA score significantly improved. The changes in postoperative cervical lordosis correlated with SS, PT, LL, T1S, and C7-SVA (P

Abstract Study design Retrospective cohort study. Purpose The aim of our study was to determine the rates and indications of reoperations following primary lumbar fusion, as well as the independent risk factors for early and late reoperation. Methods We retrospectively reviewed patients who underwent lumbar fusion surgery between January 2017 and March 2020. All patients were followed up for more than 2 years. Characteristics, laboratory tests, primary diagnosis and surgery-related variables were compared among the early reoperation ( 3 months) and the non-reoperation groups. Multivariable logistic regression analysis was used to identify independent risk factors for early and late reoperations. Results Of 821 patients included in our studies, 34 patients underwent early reoperation, and 36 patients underwent late reoperation. The cumulative reoperation rate was about 4.1% (95% CI 3.8–4.5%) at 3 months, 6.2% (95% CI 5.9–6.5%) at 1 year and 8.2% (95% CI 8.0–8.5%) at 3 years. Multivariable analysis indicated that osteoporosis (odds ratio [OR] 3.6, 95% CI 1.2–10.5, p = 0.02) and diabetes (OR 2.1, 95% CI 1.1–4.5, p = 0.04) were independently associated with early reoperation and multilevel fusion (OR 2.4, 95% CI 1.1–5.4, p = 0.03) was independently associated with late reoperation. Conclusions The most common reasons for early reoperation and late operation were surgical site infection and adjacent segment diseases, respectively. Osteoporosis and diabetes were independent risk factors for early reoperation, and multilevel fusion was independent risk factor for late reoperation. Surgeons should pay more attention to these patients, and future studies should consider the effects of follow-up periods on results.

Abstract Background The compensatory mechanisms for cervical lordosis change after laminectomy with fusion was not clear. The objective of this study was to evaluate the compensatory behaviors for cervical lordosis change after laminectomy with fusion. Methods This was a retrospective radiological analysis of 43 patients with cervical spondylotic myelopathy who underwent laminectomy with fusion (LCF). The following cervical parameters were measured: C2-7 Cobb angle (C2-7), occiput-C2 angle (O-C2), the cervical sagittal vertical axis (cSVA), and T1 slope (T1S). The difference was calculated for all angle parameters between the two time points using the following formula: the amount of change (Δ) = (value at the follow-up)—(preoperative value). Non-parametric tests and the t-test were used to compare the difference. The Pearson correlation test was performed, and stepwise multiple regression analysis was performed to determine the best correlation between ∆cSVA and ∆T1S. Results The mean age of 43 patients was 65.51 ± 9.80 years. All patients were classified into two subgroups based on ΔcSVA: Group M (maintained) and, Group I (increased). The preoperative O-C2, C2-7, T1S, and cSVA were similar between Group M and group I (p = 0.950, p = 0.731, p = 0.372, and p = 0.152, respectively). Postoperative O-C2 and postoperative cSVA were significantly different (p = 0.036 and p = 0.004, respectively). ∆O-C2, ∆T1S and ∆cSVA were significantly different between the two groups (p = 0.006, p = 0.000, and p = 0.000, respectively). ΔcSVA had significant correlations with ΔO-C2 neutral angle (r = 0.377) and ΔT1S (r = 0.582). A linear regression equation was established: ΔcSVA = 0.602 + 0.103 * ΔT1S (R = 0.582, R2 = 0.339). Conclusions The decrease of TIS should be the first and foremost compensation for the loss of lordosis in C2-7 segments after LCF. When the change of T1S alone can not prevent the deterioration of cervical sagittal balance, further increases in the O-C2 segment occur.

Abstract Background Measurement of T1 slope (T1S) can be difficult due to the anatomical positioning of the shoulders. And thoracic inlet angle (TIA) was a morphological parameter and not changed by the position. We proposed a new parameter, TIA minus C0-7 angle (TIA-C07), to evaluate C2-7 SVA in order to overcome the T1S imperfection. Methods This was a retrospective radiological analysis of symptomatic subjects. The following cervical parameters were measured: Cervical lordosis angle (CL), C0-7 angle (C0-7), occiput-C2 lordosis angle (O-C2), C2-7 sagittal vertical axis (C2–7 SVA), TIA and TIA-C07. The Pearson correlation test was calculated, and the stepwise multiple regression analysis was conducted to determine the best predictor for C2-7 SVA. A paired sample t test was used to compare the predicted and measured C2-7 SVA. Results The mean age of 113 patients was 60.02 ± 9.67. The average O-C2, CL, C0-7, TIA, TIA-C07 and C2-C7 SVA was 29.24 ± 8.48°, 13.67 ± 11.22°, 42.91 ± 11.44°, 76.07 ± 9.54°, 33.16 ± 13.18° and 21.34 ± 11.42 mm. The predictive formula was founded: C2-7 SVA = 2.80 + 0.56 * (TIA—C07) (R = 0.645, R2 = 0.416). There was no statistical difference between the predicted and the measured C2-7 SVA (t = 0.085, P = 0.933). Conclusions TIA and C0-7 mismatch may significantly impact cervical alignment, and a greater T1A-C07 was related to a greater degree of C2-7 SVA. TIA-C07 may be a more important predictor for C2-7 SVA.

Blast disease caused by the fungus Magnaporthe grisea results in significant yield losses of cereal crops across the world. To date, very few regulatory genes contributing to blast resistance in grass species have been identified and the genetic basis of blast resistance in cereals remains elusive. Here, a core collection of foxtail millet (Setaria italica) containing 888 accessions was evaluated through inoculation with the blast strain HN-1 and a genome-wide association study (GWAS) was performed to detect regulators responsible for blast disease resistance in foxtail millet. The phenotypic variation of foxtail millet accessions inoculated with the blast strain HN-1 indicated that less than 1.60% of the samples were highly resistant, 35.25% were moderately resistant, 57.09% were moderately susceptible, and 6.08% were highly susceptible. The geographical pattern of blast-resistant samples revealed that a high proportion of resistant accessions were located in lower latitude regions where the foxtail millet growing season has higher rain precipitation. Using 720000 SNP markers covering the Setaria genome, GWAS showed that two genomic loci from chromosomes 2 and 9 were significantly associated with blast disease resistance in foxtail millet. Finally, eight putative genes were identified using rice blast-related transcriptomic data. The results of this work lay a foundation for the foxtail millet blast resistance biology and provide guidance for breeding practices in this promising crop species and other cereals.

PurposeTo investigate the influence of changes in T1 slope (T1S) and cervical sagittal vertical axis (CSVA) on cervical laminoplasty outcomes.MethodsEighty-one patients with cervical spondylotic myelopathy (CSM) treated with cervical laminoplasty were enrolled in this study. Demographic parameters included age and follow-up time. Imaging data included occiput-C2 lordosis (OC2), C2–C7 Cobb angle (CL), T1S, CSVA. Outcome assessment indicators included the Japanese Orthopedic Association (JOA) score, JOA recovery rate, and neck disability index (NDI). All patients were grouped based on preoperative T1S and variation in CL after surgery, respectively. Patients with decreased CL postoperatively were further grouped according to whether they were combined with T1S reduction.ResultsThere were no significant differences in the final JOA score, JOA recovery rate, or NDI between patients with different T1S. Patients with loss of CL postoperatively had lower JOA score and JOA recovery rate, but higher NDI than patients with sustained CL. Furthermore, patients with CL loss but compensate for it with reduction in T1S had lower CSVA, higher JOA score and JOA recovery rate than those with CL loss alone.ConclusionsDecreased T1S postoperatively prevents the tendency of the cervical spine to tilt forward by regulating CSVA and facilitates recovery of neurological function after cervical laminoplasty.

BackgroundThe rate and volume of lumbar spinal fusion (LSF) surgery performed for patients aged 75 years and older increased in recent years. The purposes of our study were to identify factors associated with postoperative dissatisfaction and evaluate the predictive value of comprehensive geriatric assessment (CGA) for dissatisfaction at 2 years after elective short-segment (one- or two- level) LSF in patients aged 75 and older.MethodsThis was a retrospective study using a prospectively collected database of consecutive patients (aged 75 and older) who underwent elective short-segment transforaminal lumbar interbody fusion surgery for degenerative diseases from June 2018 to May 2020. Preoperative CGA consisting six domains was performed for each patient 1 day before the operative day. Univariate and multivariate analyses were performed to identify factors that predict for dissatisfaction with surgical treatment. The primary outcome was patient satisfaction with LSF surgery, as measured by the North American Spine Society (NASS) satisfaction scale. Secondary outcomes included postoperative complications, the length of stay, visual analog scale (VAS), and Oswestry Disability Index.ResultsA total of 211 patients were available for a follow-up at 2 years and included in our final study cohort with a mean age of 80.0 years. A total of 175 patients (82.9%) were included in the satisfied group, and 36 patients (17.1%) were included in the not dissatisfied group. In the dissatisfied group, there was a higher incidence of postoperative complications (30.6% vs. 14.3%, p = 0.024) and greater VAS scores for lower back (4.3 ± 1.9 vs. 1.3 ± 1.4, p = 0.001) and leg (3.9 ± 2.1 vs. 0.9 ± 1.3, p = 0.001). Multivariate regression analysis revealed that patients with greater CCI score [odd ratio (OR) 2.56, 95% CI, 1.12–5.76; p = 0.030 for CCI 1 or 2 and OR 6.20, 95% CI, 1.20–28.69; p = 0.024], and depression (OR 3.34, 95% CI, 1.26–9.20; p = 0.016) were more likely to be dissatisfied compared with patients with the CCI score of 0 and without depression.ConclusionsSatisfaction after LSF in older patients (aged 75 and older) was similar to that of previously reported younger patients. Preoperative depression and higher CCI scores were independent risk factors for postoperative dissatisfaction two years after LSF surgery. These results help inform decision-making when considering LSF surgery for patients aged 75 and older.

Hydrogen energy is an important technical route to achieve carbon peak and carbon neutrality. Direct injection hydrogen engine is one of the ways of hydrogen energy application. It has the advantages of high thermal efficiency and limit/reduce abnormal combustion phenomena. In order to explore the cycle characteristics of direct injection hydrogen engine, based on a 2.0L direct injection hydrogen engine, an experimental study on the cycle characteristics of direct injection hydrogen engine was carried out. The experimental results show that cycle variation increases from 0.67% to 1.02% with the increasing of engine speed. The cycle variation decreases from 1.52% to 0.64% with the increasing of engine load. As the equivalence ratio increases, the cycle variation first decreases significantly from 2.52% to 0.35% and then stabilizes. The ignition advance angle has a better angle to minimize the cycle variation. An experimental study on the influence of the start of injection on the cycle variation was carried out. As the engine speed/engine load is 2000 rpm/4bar, the cycle variation increases from 0.72% to 2.42% with the start of injection changing from −280°CA to −180°CA; then rapidly decreases to 0.99%, and then increases to 2.26% with the start of injection changing from −180°CA to −100°CA. The experimental results show that SOI could cause significant influence on cycle variation because of intake valve closing and shortening mixing time, and both the process of intake valve closing and lagging the SOI could cause the cycle variation to increase. The SOI remarkably affects the cycle variation at low engine load/equivalence ratio and high engine speed. This study lays the foundation for the follow-up research of hydrogen engine performance matching of the cycle variation.

ObjectiveCervical sagittal parameters have been widely used to predict clinical outcomes in patients with cervical spondylotic myelopathy (CSM). This study aims to coin a novel cervical sagittal parameter defined as the ratio of cervical sagittal vertical axis to T1 slope (CSVA/T1S) and to investigate the correlation between CSVA/T1S and postoperative HRQOL after laminoplasty.MethodsA total of 102 CSM patients treated with cervical laminoplasty from our database were retrospectively reviewed. All patients were followed up for >12 months. Radiological parameters were measured using lateral cervical radiographs, including occiput-C2 lordosis (OC2), cervical lordosis (CL), CSVA, and T1S. Clinical parameters included the Japanese Orthopedic Association (JOA) score, neck disability index (NDI), and JOA recovery rate. Patients were grouped by preoperative T1S, T1S-CL, and CSVA/T1S value, respectively. Clinical and radiological outcomes were compared between the groups.ResultsPatients with high CSVA/T1S had greater OC2 and CSVA but lower CL than those in the low CSVA/T1S group pre-and postoperatively. With respect to HRQOL results, the final NDI was 12.46 ± 9.11% in the low CSVA/T1S group, which was significantly lower than that in the high CSVA/T1S group (17.68 ± 8.81%, P = 0.040). Moreover, only CSVA/T1S was detected to be significantly correlated with final NDI (r = 0.310, P = 0.027). No significant correlation was found between clinical results and other cervical sagittal parameters, including T1S, CSVA, and T1S-CL.ConclusionsPreoperative CSVA/T1S was correlated with postoperative NDI in patients with CSM after cervical laminoplasty. Patients with low preoperative CSVA/T1S achieved better neurological function improvement after cervical laminoplasty. Cervical laminoplasty could be an appropriate choice for patients with lower preoperative CSVA/T1S.

Ginsenosides are major bioactive compounds found in Panax ginseng that exhibit various pharmaceutical properties. Dammarenediol-II, the nucleus of dammarane-type ginsenosides, is a promising candidate for pharmacologically active triterpenes. Dammarenediol-II synthase (DDS) cyclizes 2,3-oxidosqualene to produce dammarenediol-II. Based on the native terpenoids synthetic pathway, a dammarane-type ginsenosides synthetic pathway was established in Chlamydomonas reinhardtii by introducing P. ginseng PgDDS, CYP450 enzyme (PgCYP716A47), or/and Arabidopsis thaliana NADPH-cytochrome P450 reductase gene (AtCPR), which is responsible for producing dammarane-type ginsenosides. To enhance productivity, strategies such as “gene loading” and “culture optimizing” were employed. Multiple copies of transgene expression cassettes were introduced into the genome to increase the expression of the key rate-limiting enzyme gene, PgDDS, significantly improving the titer of dammarenediol-II to approximately 0.2 mg/L. Following the culture optimization in an opt2 medium supplemented with 1.5 mM methyl jasmonate under a light:dark regimen, the titer of dammarenediol-II increased more than 13-fold to approximately 2.6 mg/L. The C. reinhardtii strains engineered in this study constitute a good platform for the further production of ginsenosides in microalgae.

The elderly population in developed countries has increased rapidly in recent years; the elderly may be at greater risk of protein deficiency due to dietary, socio-economic, dental, and physical restrictions. Therefore, to address the issue of protein deficiency in elderly people, the present study aimed to enhance the protein content of high-gluten flour noodles, an Asian staple food, by supplementing them with soybean protein isolate (SPI) powder. The effect of SPI addition (5–20%, w/w) on composition, quality, texture, physical and sensory properties, and glycemic index (GI) of high-gluten flour noodles was investigated. The noodles made only from high-gluten flour served as control. In comparison to control noodles, 20% SPI noodles showed a rise in protein and moisture content from 16.17% to 30.64% and 36.06 to 44.84%, respectively. The cooking yield and cooking loss increased with an increase in SPI concentration compared to control noodles. Color characteristics analysis revealed the decreasing trend in brightness and yellowness of SPI noodles with minimal L* and b* values at a 20% SPI concentration. The addition of SPI also resulted in a decrease in the hardness and tensile strength of the noodles. The sensory analysis showed that 5% SPI noodles were more similar to control noodles in terms of flavor, taste, and overall acceptability. Moreover, the addition of SPI to the noodles significantly decreased the GI of the noodles reaching the standard of low-GI food. The findings of the current study indicate that soy protein noodles, besides supplementing the desired nutrients, may also prevent the risk of diabetes in elderly people.

Background: Recent research showed that cross-notation magnitude knowledge of fractions and decimals was related to better performance in fraction arithmetic, but it remains unclear whether it made an independent contribution to fraction arithmetic longitudinally when other cognitive variables are considered. Aims: To examine the extent to which children's earlier knowledge of cross-notation magnitude predicted subsequent performance in fraction addition and subtraction as well as fraction multiplication and division longitudinally. Sample: Three hundred and fifty-four Chinese children (Mage = 112.1 months). Methods: During the first wave of assessment, a range of cognitive abilities of children were measured, including within-notation fraction and decimal magnitude comparisons, whole-number arithmetic fluency, non-verbal intelligence, attentive behaviours, counting recall, word-level reading, and phonological awareness. Twelve months later, the same children were assessed again with two tasks of fraction arithmetic: fraction addition and subtraction as well as fraction multiplication and division. Results and Conclusions: Multiple linear regressions showed that within-notation fraction and decimal magnitude knowledge predicted fraction addition and subtraction longitudinally, after the effects of working memory, nonverbal intelligence, language skills, attentive behaviour, and whole-number arithmetic were controlled. Cross-notation magnitude knowledge made independent contributions to fraction addition and subtraction longitudinally beyond the influence of within-notation fraction and decimal magnitude knowledge and other covariates. However, within-notation fraction and decimal magnitude knowledge were not associated with fraction multiplication and division, whereas cross-notation magnitude knowledge remained a unique predictor. These findings suggest that it may be useful to incorporate cross-notation knowledge in the assessments of children's mathematics abilities and teaching.

Objective: The purpose of this study was to compare the levels of 8-oxoG and 8-oxodG in urine of patients with cervical carcinoma and healthy women to evaluate their influences on cervical carcinoma. Methods: In this study, urine samples were collected from 70 patients with cervical carcinoma, 24 patients with one-year follow-up, and 100 healthy women. The contents of 8-oxodG and 8-oxoG in urine were assayed by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Results: The levels of 8-oxoG and 8-oxodG were higher in patients with cervical carcinoma (P < 0.000), while AUC of 8-oxoG and 8-oxodG was higher than 0.7. Specifically, the high-risk HPV (HR-HPV) positive group had higher 8-oxoG levels (P < 0.000), but there was no difference in 8-oxodG levels. Yet, 8-oxoG level was associated with lymphatic metastasis, lymph-vascular space infiltration (LVSI) and stromal infiltration, while 8-oxodG level was affected by the differentiation degree and stromal infiltration. According to statistics, the distinct cut-off index of lymphatic metastasis was 7.282 nmol/mmol creatinine. After operation, the concentrations of 8-oxoG and 8-oxodG dropped significantly (8-oxoG P < 0.000, 8-oxodG P = 0.004). Except for chemotherapy group, the urinary 8-oxoG dose of all treatment groups and 8-oxodG dose of chemo-radiotherapy group declined obviously. Conclusions: 8-oxoG may be a potential biomarker for cervical carcinoma.

Microglia are intrinsic immune cells of the central nervous system and play a dual role (pro-inflammatory and anti-inflammatory) in the homeostasis of the nervous system. Neuroinflammation mediated by microglia serves as an important stage of ischemic hypoxic brain injury, cerebral hemorrhage disease, neurodegeneration and neurotumor of the nervous system and is present through the whole course of these diseases. Microglial membrane protein or receptor is the basis of mediating microglia to play the inflammatory role and they have been found to be upregulated by recognizing associated ligands or sensing changes in the nervous system microenvironment. They can then allosterically activate the downstream signal transduction and produce a series of complex cascade reactions that can activate microglia, promote microglia chemotactic migration and stimulate the release of proinflammatory factor such as TNF-α, IL-β to effectively damage the nervous system and cause apoptosis of neurons. In this paper, several representative membrane proteins or receptors present on the surface of microglia are systematically reviewed and information about their structures, functions and specific roles in one or more neurological diseases. And on this basis, some prospects for the treatment of novel coronavirus neurological complications are presented.

Abstract Background Cerebral cryptococcomas is a rare form of central nervous system cryptococcosis. Most previous cases were mistaken for neoplasm before surgery. We present a case of cerebral cryptococcomas whose radiological profiles resembled demyelinating disease, especially tumefactive demyelinating lesion. Case presentation A 40-year-old male was admitted for 1-week-long unconsciousness. Brain MRI revealed a rim-enhanced mass within the corpus callosum body. Central nervous system demyelinating disease was suspected. Empirical corticosteroid treatment led to some improvement, but his condition deteriorated 2 months later. Brain MRI revealed punctate new foci. Cryptococcus neoformans was detected in cerebrospinal fluid. Cryptococcus antigen test was positive in his current and previous cerebrospinal fluid samples. The patient died despite standard antifungal treatment. Conclusion Diagnosis of cerebral cryptococcomas is challenging. It may mimic demyelinating diseases.

Abstract As a common chronic respiratory disease, the incidence of asthma is increasing in recent years worldwide. Airway remodeling is the primary pathological basis of refractory asthma, but the studies about the underlying mechanism of airway remodeling was a lack. In the study, we aimed to investigate the effects and mechanisms of miR‐326 on airway remodeling in airway smooth muscle cells (ASMCs). The results showed that transforming growth factor‐β1 (TGF‐β1) accelerated matrix protein deposition by increasing the expression levels of collagen I and fibronectin, and promoted proliferative ability of ASMCs. However, miR‐326 was significantly downregulated in TGF‐β1‐treated ASMCs. MiR‐326 mimics robustly decreased the collagen I and fibronectin levels and inhibited cell proliferation of TGF‐β1‐treated ASMCs. Luciferase assay investigated that tumor necrosis factor superfamily member 14 (TNFSF14) was a direct target of miR‐326. The expression of TNFSF14 was negatively regulated by miR‐326. Moreover, exogenous TNFSF14 effectively reversed the inhibitory effects of miR‐326 overexpression on the expression levels of collagen I and fibronectin, and promoted cell proliferation of TGF‐β1‐treated ASMCs. In conclusion, miR‐326 suppressed matrix protein deposition and cell proliferation of TGF‐β1‐treated ASMCs via inhibiting TNFSF14. MiR‐326 might be a promising novel therapeutic target for asthma.

Abstract Background Species of the Anopheles hyrcanus group are widely distributed in Palearctic and Oriental regions and some of them are important malaria vectors. The cryptic species of An. hyrcanus group was almost impossible to identify based only on their morphology. The phylogenetic relationship of An. hyrcanus group was also not clear. Methods Five members of An. hyrcanus group were identified by rDNA ITS2 sequencing as An. yatsushiroensis, An. belenrae, An. kleini, An. lesteri and An. sineroides. The mitochondrial genome fragments were sequenced and annotated using the mitochondrial genome of An. sinensis as reference. Based on the four segments and Joint Data sequences of these species, and other four anopheline species downloaded from GenBank, intraspecific as well as interspecific genetic distances were calculated and the phylogenetic trees were reconstructed by the methods of neighbor joining, maximum parsimony, minimum evolution and maximum likelihood. Findings Four parts of mitochondrial genomes, which were partial fragments COI + tRNA + COII (F5), ATP6 + COIII(F7 + F8), ND1(F19) and lrRNA (F21), were obtained. All fragments were connected as one sequence (referred as Joint Data), which had a total length of 3393 bp. All fragment sequences were highly conservative within species, with the maximum p distance (0.026) calculated by F19 of An. belenrae. The pairwise interspecific p distance calculated by each fragment showed minor or even no difference among An. sinensis, An. kleini and An. belenrae. However, interspecific p distances calculated by the Joint Data sequence ranged from 0.004 (An. belenrae vs An. kleini) to 0.089 (An. sineroides vs An. minimus), and the p distances of the six members of An. hyrcanus group were all less than 0.029. The phylogenetic tree showed two major clades: all subgenus Anopheles species (including six members of An. hyrcanus group, An. atroparvus and An. quadrimaculatus A) and subgenus Cellia (including An. dirus and An. minimus). The An. hyrcanus group was divided into two clusters as ((An. lesteri, An. sineroides) An. yatsushiroensis) and ((An. belenrae, An. sinensis) An. kleini)). Conclusions The An. hyrcanus group in this study could be divided into two clusters, in one of which An. belenrae, An. sinensis and An. kleini were most closely related. More molecular markers would make greater contribution to phylogenetic analysis.

Lycopene cyclase needs to be inhibited by the blockers like pyridine or imidazole in the lycopene accumulation of Blakeslea trispora. This work investigated how pyridine and imidazole impacted the basal metabolism of B. trispora, the results helped us understand how they could affect the lycopene production and application, and see the metabolic risks from different inhibitors. In this study, the highest yield of lycopene with pyridine was obtained at 176 mg/L without amino acids supplement, and got more lycopene at 237 mg/L adding tyrosine, lysine, proline all together as 0.01 mol/L each in fermented broth. GC-MS and Principal Component Analysis (PCA) were used to find that amino acids, fatty acids, organic acids including phosphoric acid, carbon source and imidazole derivatives played the most important roles in lycopene fermentation with imidazole, differently, fatty acids, carbon source, and pyridine derivatives were more significant in the pyridine process and it was remarkable that the residual of both blockers' derivatives would bring the potential risks on applications of lycopene products. Predominantly, durene met 0.35 mg/g DCW with imidazole and piperidine formaldehyde attained 0.24 mg/g DCW with pyridine after the end of lycopene fermentations.

Abstract Lesinurad is an oral inhibitor of urate-anion exchanger transporter 1 and has been approved by the US Food and Drug Administration for combination therapy with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with refractory gout. In the present study, a sensitive and specific ultra high-performance liquid chromatography with tandem mass spectrometry assay was established and verified for the determination of lesinurad in rat plasma and was described in details for the first time. Chromatographic separation of lesinurad and diazepam (internal standard, IS) was performed on a Rapid Resolution HT C18 column (3.0 × 100 mm, 1.8 µm) using methanol–water (70:30, v/v) as the mobile phase at a flow rate of 0.3 mL/min. Lesinurad and IS were extracted from plasma by liquid–liquid extraction using ethyl acetate. The mass spectrometric detection was carried out using an electrospray ionization source in positive mode. Multiple reaction monitoring was used for quantification of the precursor to product ion at m/z 405.6 → 220.9 for lesinurad and m/z 285.1 → 192.8 for IS. The assay was well validated for selectivity, accuracy, precision, recovery, linearity, matrix effects, and stability. The verified method was applied to obtain the pharmacokinetic parameters and concentration–time profiles for lesinurad after oral/intravenous administration in rats. The study might provide an important reference and a necessary complement for the qualitative and quantitative evaluation of lesinurad.

Abstract Background Anopheles sinensis (Diptera: Culicidae) is a primary vector of Plasmodium vivax and Brugia malayi in most regions of China. In addition, its phylogenetic relationship with the cryptic species of the Hyrcanus Group is complex and remains unresolved. Mitochondrial genome sequences are widely used as molecular markers for phylogenetic studies of mosquito species complexes, of which mitochondrial genome data of An. sinensis is not available. Methods An. sinensis samples was collected from Shandong, China, and identified by molecular marker. Genomic DNA was extracted, followed by the Illumina sequencing. Two complete mitochondrial genomes were assembled and annotated using the mitochondrial genome of An. gambiae as reference. The mitochondrial genomes sequences of the 28 known Anopheles species were aligned and reconstructed phylogenetic tree by Maximum Likelihood (ML) method. Findings The length of complete mitochondrial genomes of An. sinensis was 15,076 bp and 15,138 bp, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and an AT-rich control region. As in other insects, most mitochondrial genes are encoded on the J strand, except for ND5, ND4, ND4L, ND1, two rRNA and eight tRNA genes, which are encoded on the N strand. The bootstrap value was set as 1000 in ML analyses. The topologies restored phylogenetic affinity within subfamily Anophelinae. The ML tree showed four major clades, corresponding to the subgenera Cellia, Anopheles, Nyssorhynchus and Kerteszia of the genus Anopheles. Conclusions The complete mitochondrial genomes of An. sinensis were obtained. The number, order and transcription direction of An. sinensis mitochondrial genes were the same as in other species of family Culicidae.

Abstract: The aim of the current study was to investigate the effects of a lactic acid bacteria inoculant (Lactobacillus plantarum, LP), fibrolytic enzyme (EN), combination of LP and EN (LP+EN) on fermentation quality, nutritive characteristics and in vitro digestibility of total mixed ration (TMR) silages containing 0, 7.5 and 15.0% (on dry matter basis) of rape (Brassica campestris L.) straw (RS) (denoted as CTMR, LTMR and MTMR, respectively). After ensiling for 60 days, TMR silages without additives were well preserved, but MTMR had higher pH than CTMR and LTMR. There were no differences in other parameters of fermentation quality, microbial composition, nutrition and in vitro digestibility between CTMR and LTMR except for yeast and mold number and crude protein (CP) content. CTMR and LTMR silage had higher CP content, in vitro neutral detergent fiber digestibility (IVNDFD) and in vitro acid detergent fiber digestibility (IVADFD), lower acid detergent fiber (ADF) content than MTMR silage. LP and EN decreased pH and increased dry matter (DM) recovery of TMR silages. LP+EN improved the fermentation quality, nutritive characteristics and in vitro digestibility of TMR silages, showed by lower pH, ADF content, higher lactic acid content, in vitro dry matter digestibility (IVDMD) and IVNDFD. Therefore, It was suggested that TMR silage contained 7.5% RS on a DM basis and treated with LP+EN can be as a useful feed for ruminant.

The transforming growth factor-β (TGF-β), in which overexpression has been associated with various diseases, has become an attractive molecular target for the treatment of cancers. Thirty-two quinoxaline-derivatives of 3-substituted-4-(quinoxalin-6-yl) pyrazoles 14a⁻d, 15a⁻d, 16a⁻d, 17a⁻d, 18a⁻d, 19a⁻d, 25a, 25b, 25d, 26a, 26b, 26d, 27b, and 27d were synthesized and evaluated for their activin TGF-β type I receptor kinase and p38α mitogen activated protein (MAP) kinase inhibitory activity in enzymatic assays. Among these compounds, the most active compound 19b inhibited TGF-β type I receptor kinase phosphorylation with an IC50 value of 0.28 µM, with 98% inhibition at 10 µM. Compound 19b also had good selectivity index of >35 against p38α MAP kinase, with 9.0-fold more selective than clinical candidate, compound 3 (LY-2157299). A molecular docking study was performed to identify the mechanism of action of the synthesized compounds and their good binding interactions were observed. ADMET prediction of good active compounds showed that these ones possess good pharmacokinetics and drug-likeness behavior.

Nine new pregnane alkaloids (1–9), together with eight known alkaloids (10–17), were isolated from the whole herb of Pachysandra terminalis. Their structures were elucidated on the basis of spectroscopic analyses. In addition, the isolates were examined for their ability to inhibit the migration of MDA-MB-231 cells induced by the chemokine epidermal growth factor (EGF). Alkaloids 1, 5, 7, 9, 12, and 17 presented significant anti-metastasis activities compared with the positive reagent, LY294002.

In the title compound, (NH4)2[Fe(C10H12N2O8)(H2O)]·3H2O, the FeII center is in a distorted pentagonal-bipyramidal geometry. Two carboxylate O and two N atoms from the ethylenediaminetetraacetate (EDTA) ion and one O atom from coordinated water comprise the equatorial plane. Two other carboxylate O atoms from the EDTA ion occupy the apical sites. Both ammonium cations and all water molecules function as hydrogen-bond donors, and ten N—H...O and nine O—H...O hydrogen bonds form a three-dimensional network between the complex anions, cations and the water molecules.

Background: Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. Enhanced recovery after surgery (ERAS) can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains. Materials and methods: An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged =75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP = 3). The preoperative variables, operative data, postoperative outcomes, and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay after surgery. Results: A total of 245 patients (age of 79.8 ± 3.4 year) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between nonfrail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery. Conclusion: Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults. [ABSTRACT FROM AUTHOR]