CCDC181 is required for sperm flagellum biogenesis and male fertility in mice.

The structural integrity of the sperm flagellum is essential for proper sperm function. Flagellar defects can result in male infertility, yet the precise mechanisms underlying this relationship are not fully understood. CCDC181, a coiled-coil domain-containing protein, is known to localize on sperm flagella and at the basal regions of motile cilia. Despite this knowledge, the specific functions of CCDC181 in flagellum biogenesis remain unclear. In this study, Ccdc181 knockout mice were generated. The absence of CCDC181 led to defective sperm head shaping and flagellum formation. Furthermore, the Ccdc181 knockout mice exhibited extremely low sperm counts, grossly aberrant sperm morphologies, markedly diminished sperm motility, and typical multiple morphological abnormalities of the flagella (MMAF). Additionally, an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified, with CCDC181 regulating the localization of LRRC46 within sperm flagella. These findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.

Homozygous CCDC146 mutation causes oligoasthenoteratozoospermia in humans and mice.

Infertility represents a significant health concern, with sperm quantity and quality being crucial determinants of male fertility. Oligoasthenoteratozoospermia (OAT) is characterized by reduced sperm motility, lower sperm concentration, and morphological abnormalities in sperm heads and flagella. Although variants in several genes have been implicated in OAT, its genetic etiologies and pathogenetic mechanisms remain inadequately understood. In this study, we identified a homozygous nonsense mutation (c.916C>T, p.Arg306*) in the coiled-coil domain containing 146 ( CCDC146) gene in an infertile male patient with OAT. This mutation resulted in the production of a truncated CCDC146 protein (amino acids 1-305), retaining only two out of five coiled-coil domains. To validate the pathogenicity of the CCDC146 mutation, we generated a mouse model ( Ccdc146 mut/mut ) with a similar mutation to that of the patient. Consistently, the Ccdc146 mut/mut mice exhibited infertility, characterized by significantly reduced sperm counts, diminished motility, and multiple defects in sperm heads and flagella. Furthermore, the levels of axonemal proteins, including DNAH17, DNAH1, and SPAG6, were significantly reduced in the sperm of Ccdc146 mut/mut mice. Additionally, both human and mouse CCDC146 interacted with intraflagellar transport protein 20 (IFT20), but this interaction was lost in the mutated versions, leading to the degradation of IFT20. This study identified a novel deleterious homozygous nonsense mutation in CCDC146 that causes male infertility, potentially by disrupting axonemal protein transportation. These findings offer valuable insights for genetic counseling and understanding the mechanisms underlying CCDC146 mutant-associated infertility in human males.

Therapeutic targets for muscle weakness in older adults: proteome-wide Mendelian randomization and colocalization analyses.

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 < 6.82 × 10-5), Mendelian randomization analysis revealed that three proteins were causally associated with low grip strength. Increased MGP (OR = 0.85) and HP (OR = 0.96) decreased the risk of low grip strength, whereas elevated ART4 (OR = 1.06) increased the risk of low grip strength. None of the three proteins had reverse causality with low grip strength. Bayesian co-localization suggested that MGP shared the same variant with low grip strength (coloc.abf-PPH4 = 0.826). Further downstream analyses showed that MGP, which is highly expressed in musculoskeletal system, is a potential novel target for muscle weakness. CONCLUSIONS: The proteome-wide Mendelian randomization investigation identified three proteins associated with the risk of muscle weakness. MGP, HP, and ART4 deserve further investigation as potential therapeutic targets for muscle weakness.

Association between delayed ambulation and increased risk of adverse events after lumbar fusion surgery in elderly patients.

PURPOSE: The relationship between delayed ambulation (DA) and postoperative adverse events (AEs) following transforaminal lumbar interbody fusion (TLIF) in elderly patients remains elusive. The aim of our study was to evaluate the effects of DA on the postoperative AEs including complications, readmission and prolonged length of hospital stay (LOS). METHODS: This was a retrospective analysis of a prospectively established database of elderly patients (aged 65 years and older) who underwent TLIF surgery. The early ambulation (EA) group was defined as patients ambulated within 48 h after surgery, whereas the delayed ambulation (DA) group was patients ambulated at a minimum of 48 h postoperatively. The DA patients were 1:1 propensity-score matched to the EA patients based on age, gender and the number of fused segments. Univariate analysis was used to compare postoperative outcomes between the two groups, and multivariate logistic regression analysis was used to identify risk factors for adverse events and DA. RESULTS: After excluding 125 patients for various reasons, 1025 patients (≤ 48 h: N = 659 and > 48 h: N = 366) were included in the final analysis. After propensity score matching, there were 326 matched patients in each group. There were no significant differences in the baseline data and the surgery-related variables between the two groups (p > 0.05). The patients in the DA group had a significant higher incidence of postoperative AEs (46.0% vs. 34.0%, p = 0.002) and longer LOS (p = 0.001). Multivariate logistic regression identified that age, operative time, diabetes, and DA were independently associated with postoperative AEs, whereas greater age, higher international normalized ratio, and intraoperative estimated blood loss were identified as independent risk factors for DA. CONCLUSIONS: Delayed ambulation was an independent risk factor for postoperative AEs after TLIF in elderly patients. Older age, increased intraoperative blood loss and worse coagulation function were associated with delayed ambulation.

Characterizing mid-infrared micro-ring resonator with frequency conversion.

Due to the high cost, low-performance lasers and detectors in the mid-infrared (MIR) band, the development of MIR-integrated devices is very slow. Here, we demonstrate an effective method to characterize the parameters of MIR devices by using frequency conversion technology. We designed and fabricated rib waveguides and the micro-ring resonators (MRRs) on a silicon-on-sapphire platform. The MIR laser for the test is generated by difference frequency generation, and the transmission spectrum of the MIR-MRRs is detected by sum frequency generation. The experimental results show that the waveguide transmission loss is 4.5 dB/cm and the quality factor of the micro-ring reaches 38000, which is in good agreement with the numerical simulations. This work provides a useful method to characterize MIR integrated devices based on the frequency conversion technique, which can boost the development of MIR integrated optics in the future.

Glucoconjugated monoterpene indole alkaloids with xanthine oxidase inhibitory activity from Ophiorrhiza japonica.

Continued interest in the bioactive alkaloids led to the isolation of five undescribed alkaloids (1-5), ophiorglucidines A-E, and seven known analogues (6-12) from the water-soluble fraction of Ophiorrhiza japonica. The structures were elucidated based on spectroscopic data and quantum calculations as well as X-ray crystallographic analysis. The structure of 1 was characterized as a hexacyclic skeleton including a double bridge linking the indole and the monoterpene moieties, which is the first report of a single crystal with this type of structure. Moreover, the inhibitory effect of zwitterionic indole alkaloid glycosides on xanthine oxidase was found for the first time. The alkaloids 2 and 3, both of which have a pentacyclic zwitterionic system, were more active than the reference inhibitor, allopurinol (IC50 = 11.1 µM) with IC50 values of 1.0 µM, and 2.5 µM, respectively. Structure-activity relationships analyses confirmed that the carbonyl group at C-14 was a key functional group responsible for the inhibitory effects of these alkaloids.

Coagulation and fibrinolytic markers offer utility when distinguishing between benign and malignant gallbladder tumors: A cross-sectional study.

BACKGROUND: The metabolic or proliferative abnormalities that are characteristic of tumor cells can lead to abnormal fibrinolysis or coagulation system activity, with certain tumors exhibiting hypercoagulability or existing in a fibrinolytic state. However, the utility of biomarkers of coagulation and fibrinolysis when seeking to differentiate between benign gallbladder disease and malignant gallbladder tumors remains uncertain. METHODS: This study included a total of 81 patients with benign gallbladder polyps and 94 patients with malignant gallbladder tumors. Pre-biopsy or pretreatment levels of PT, APTT, FIB, D-dimer, FDP, PLT, PIC, TAT, TM, and t-PAIC from these patients were compared using Mann-Whitney tests. The baseline data of the patients were analyzed using chi-square tests, and the diagnostic utility of these biomarkers in distinguishing between benign and malignant gallbladder lesions was evaluated using ROC curves, and Spearman correlation analysis was employed to assess the correlation between these indicators and tumor parameters. RESULTS: The average age of malignant gallbladder tumor group was higher than benign gallbladder polyp group. And the base line analysis showed that there was a statistic difference in age, history of smoking, drinking, biliary tract disease, BMI of over weight between these two groups. In patients with malignant gallbladder tumors, FIB, D-dimer, FDP, PIC, TAT, TM, and t-PAIC levels were significantly elevated relative to those in patients affected by benign gallbladder polyp. The AUC for FIB, D-dimer, and FDP was 0.8469, 0.6514, 0.5950, while for PIC, TAT, TM, t-PAIC and four biomarker combined diagnosed was 0.8455, 0.6554, 0.7130, 0.6806, and 0.8859. Among these, TM was associated with the vascular invasion of tumor patients; TAT and t-PAIC were associated with neural invasion; D-dimer and FDP were related to the maximum tumor diameter; and FDP had a certain correlation with the tumor stage. CONCLUSIONS: In gallbladder tumor patients, conventional coagulation metrics like FIB, D-dimer, and FDP, as well as newer thrombotic indicators such as PIC, TAT, TM, and t-PAIC, were obviously increased. Correlations with tumor parameters suggested their potential as biomarkers to distinguish benign from malignant gallbladder growths.

The impact of frailty on clinical outcomes of older patients undergoing enhanced recovery after lumbar fusion surgery: a prospective cohort study.

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.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Preparation and properties of two-dimensional Ti2CTxMXene based on electroetching method.

The continuous advancements in wearable electronics have drawn significant attention toward 2D MXenes materials for energy storage owing to their abundant availability, adaptability, and distinctive physicochemical properties. Two unresolved concerns currently revolve around environmental pollution by F-containing etching and finite kinetics caused because of re-stacking of nanosheets. In this study, Al was electrochemically etched from porous Ti2AlC electrodes without the use of fluorine, through a selective electrochemical etching process in dilute hydrochloric acid. Subsequently, Ti2CTxMXene was vertically grown on carbon fiber (CF) substrates. The resulting Ti2CTx@CF electrodes are lightweight, thin, and flexible, exhibiting a surface capacitance of 330 mF cm-2at a constant current density of 1 mA cm-2after 2000 cycles. They display a surface capacitance retention of 96.16% and a high energy density of 45.3µWh cm-2at a power density of 0.497 mW cm-2. These metrics underscore the Ti2CTx@CF electrode's commendable multifunctionality, electrochemical performance, ion transport efficiency, and charge storage capacity. Moreover, a flexible energy storage electrode material with a high area capacity was developed by combining Ti2CTxMXene nanosheets, possessing a large specific surface area, with a flexible carbon fabric substrate.

Quantum entanglement and interference at 3 µm.

Given the important advantages of the mid-infrared optical range (2.5 to 25 µm) for biomedical sensing, optical communications, and molecular spectroscopy, extending quantum information technology to this region is highly attractive. However, the development of mid-infrared quantum information technology is still in its infancy. Here, we report on the generation of a time-energy entangled photon pair in the mid-infrared wavelength band. By using frequency upconversion detection technology, we observe the two-photon Hong-Ou-Mandel interference and demonstrate the time-energy entanglement between twin photons at 3082 nm via the Franson-type interferometer, verifying the indistinguishability and nonlocality of the photons. This work is very promising for future applications of optical quantum technology in the mid-infrared band, which will bring more opportunities in the fields of quantum communication, precision sensing, and imaging.

A comprehensive sampling of mitogenomes shows the utility to infer phylogeny of termites (Blattodea: Termitoidae).

The mitogenome sequence data have been widely used in inferring the phylogeny of insects. In this study, we determined the complete mitogenome for Macrotermes sp. (Termitidae, Macrotermitinae) using next-generation sequencing. Macrotermes sp. possesses a typical insect mitogenome, displaying an identical gene order and gene content to other existing termite mitogenomes. We present the first prediction of the secondary structure of ribosomal RNA genes in termites. The rRNA secondary structures of Macrotermes sp. exhibit similarities to closely related insects and also feature distinctive characteristics in their helical structures. Together with 321 published mitogenomes of termites as ingroups and 8 cockroach mitogenomes as outgroups, we compiled the most comprehensive mitogenome sequence matrix for Termitoidae to date. Phylogenetic analyses were conducted using datasets employing different data coding strategies and various inference methods. Robust relationships were recovered at the family or subfamily level, demonstrating the utility of comprehensive mitogenome sampling in resolving termite phylogenies. The results supported the monophyly of Termitoidae, and consistent relationships within this group were observed across different analyses. Mastotermitidae was consistently recovered as the sister group to all other termite families. The families Hodotermitidae, Stolotermitidae, and Archotermopsidae formed the second diverging clade, followed by the Kalotermitidae. The Neoisoptera was consistently supported with strong node support, with Stylotermitidae being sister to the remaining families. Rhinotermitidae was found to be non-monophyletic, and Serritermitidae nested within the basal clades of Rhinotermitidae and was sister to Psammotermitinae. Overall, our phylogenetic results are largely consistent with earlier mitogenome studies.

Chromones from the endophytic fungus Bipolaris eleusines.

Eight previously undescribed chromones eleusineketones A-H (1-8), as well as eight known compounds (9-16), were isolated from the endophytic fungus Bipolaris eleusines. These planar structures were created using an in-depth analysis of their spectral data, which included 1D, 2D, and HRESIMS data. Furthermore, the absolute configurations of compounds 1, 2, and 6 were determined by spectroscopic analysis and quantum chemical computational approaches, and compound 5 was determined by single-crystal X-ray diffraction analysis. The cytotoxic activity assay revealed that compounds 1 and 5 both inhibited MDA-MB-231 cells with IC50 values of 14.48 µM and 17.99 µM, respectively.

Comparison of Four Nutritional Screening Tools for Predicting Postoperative Adverse Events Following Degenerative Spinal Deformity Surgery.

STUDY DESIGN: A retrospective study. OBJECTIVE: To compare the mini nutritional assessment-short form (MNA-SF), geriatric nutritional risk index, prognostic nutritional index (PNI), and preoperative serum albumin level as predictors of postoperative adverse events (AEs) in degenerative spine deformity (DSD) patients. SUMMARY OF BACKGROUND DATA: Although various nutritional screening tools have been well evaluated in patients undergoing spinal fusion surgery, the most suitable tool for the DSD population remains uncertain at present. PATIENTS AND METHODS: The authors reviewed consecutive patients who underwent thoracolumbar fusion surgery for DSD between August 2016 and May 2023. Four screening tools were used to assess preoperative nutritional status. Patients were divided into two categories according to each screening tool, and the four screening tools were compared regarding their predictive power for postoperative AEs, including the rates of extended length of hospital stays (LOS), complications, and readmission within three months. Physical functional indicators such as time to first ambulation, nonhome discharge, and postoperative LOS were assessed as secondary outcome measures. A multivariable logistic regression analysis was used to identify factors associated with postoperative AEs. RESULTS: A total of 228 patients were included. The demographic characteristics, underlying disease, and magnitude of correction were not significantly different between well-nourished and malnourished groups. The nutritional risks shown by MNA-SF and albumin level were significantly associated with infectious complications ( P <0.05). The nutritional risk shown by MNA-SF was significantly associated with nonhome discharge, prolonged postoperative LOS (12.5±8.2 vs. 10.3±6.1, P =0.039), and delayed ambulation (3.7±2.1 vs. 2.2±1.8, P =0.001). Multivariable logistic regression revealed that PNI <50 was significantly associated with total AEs and minor AEs after DSD surgery. CONCLUSIONS: PNI was significantly associated with the incidence of total AEs and minor AEs, while preoperative albumin level and MNA-SF were more effective in predicting postoperative infectious complications and delayed recovery of physical function, respectively. LEVEL OF EVIDENCE: Level III.

Development and external validation of a predictive model for prolonged length of hospital stay in elderly patients undergoing lumbar fusion surgery: comparison of three predictive models.

PURPOSE: This study aimed to develop a predictive model for prolonged length of hospital stay (pLOS) in elderly patients undergoing lumbar fusion surgery, 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. The primary outcome measure was pLOS, which was defined as the LOS greater than the 75th percentile. All patients were grouped as pLOS group and non-pLOS. Three models (including logistic regression, single-classification tree and random forest algorithms) for predicting pLOS were developed using training dataset and internal validation using testing dataset. Finally, online tool based on our model 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). Multivariate logistic analyses revealed that older age (odds ratio [OR] 1.06, p < 0.001), higher BMI (OR 1.08, p = 0.002), number of fused segments (OR 1.41, p < 0.001), longer operative time (OR 1.02, p < 0.001), and diabetes (OR 1.05, p = 0.046) were independent risk factors for pLOS in elderly patients undergoing lumbar fusion surgery. The single-classification tree revealed that operative time ≥ 232 min, delayed ambulation, and BMI ≥ 30 kg/m2 as particularly influential predictors for pLOS. A random forest model was developed using the remaining 14 variables. Intraoperative EBL, operative time, delayed ambulation, age, number of fused segments, BMI, and RBC count were the most significant variables in the final model. The predictive ability of our three models was comparable, with no significant differences in AUC (0.73 vs. 0.71 vs. 0.70, respectively). The logistic regression model had a higher net benefit for clinical intervention than the other models. The nomogram was developed, and the C-index of external validation for PLOS was 0.69 (95% CI, 0.65-0.76). CONCLUSION: This investigation produced three predictive models for pLOS in elderly patients undergoing lumbar fusion surgery. 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 predictive model could inform physicians about elderly patients with a high risk of pLOS after surgery.

Development and external validation of a nomogram for predicting postoperative adverse events in elderly patients undergoing lumbar fusion surgery: comparison of three predictive models.

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.

Deep learning-driven diagnosis of multi-type vertebra diseases based on computed tomography images.

Background: Osteoporotic vertebral compression fractures (OVCFs) are the most common type of fragility fracture. Distinguishing between OVCFs and other types of vertebra diseases, such as old fractures (OFs), Schmorl's node (SN), Kummell's disease (KD), and previous surgery (PS), is critical for subsequent surgery and treatment. Combining with advanced deep learning (DL) technologies, this study plans to develop a DL-driven diagnostic system for diagnosing multi-type vertebra diseases. Methods: We established a large-scale dataset based on the computed tomography (CT) images of 1,051 patients with OVCFs from Luhe Hospital and used data of 46 patients from Xuanwu Hospital as alternative hospital validation dataset. Each patient underwent one examination. The dataset contained 11,417 CT slices and 19,718 manually annotated vertebrae with diseases. A two-stage DL-based system was developed to diagnose five vertebra diseases. The proposed system consisted of a vertebra detection module (VDModule) and a vertebra classification module (VCModule). Results: The training and testing dataset for the VDModule consisted of 9,135 and 3,212 vertebrae, respectively. The VDModule using the ResNet18-based Faster region-based convolutional neural network (R-CNN) model achieved an area under the curve (AUC), false-positive (FP) rate, and false-negative (FN) rate of 0.982, 1.52%, and 1.33%, respectively, in the testing dataset. The training dataset for VCModule consisted of 14,584 and 47,604 diseased and normal vertebrae, respectively. The testing dataset consisted of 4,489 and 15,122 diseased and normal vertebrae, respectively. The ResNet50-based VCModule achieved an average sensitivity and specificity of 0.919 and 0.995, respectively, in diagnosing four kinds of vertebra diseases except for SN in the testing dataset. In the alternative hospital validation dataset, the ResNet50-based VCModule achieved an average sensitivity and specificity of 0.891 and 0.989, respectively, in diagnosing four kinds of vertebra diseases except for SN. Conclusions: Our proposed DL system can accurately diagnose four vertebra diseases and has strong potential to facilitate the accurate and rapid diagnosis of vertebral diseases.

Mesophyll conductance limits photosynthesis in fluctuating light under combined drought and heat stresses.

Drought and heat stresses usually occur concomitantly in nature, with increasing frequency and intensity of both stresses expected due to climate change. The synergistic agricultural impacts of these compound climate extremes are much greater than those of the individual stresses. However, the mechanisms by which drought and heat stresses separately and concomitantly affect dynamic photosynthesis have not been thoroughly assessed. To elucidate this, we used tomato (Solanum lycopersicum) seedlings to measure dynamic photosynthesis under individual and compound stresses of drought and heat. Individual drought and heat stresses limited dynamic photosynthesis at the stages of diffusional conductance to CO2 and biochemistry, respectively. However, the primary limiting factor for photosynthesis shifted to mesophyll conductance under the compound stresses. Compared with the control, photosynthetic carbon gain in fluctuating light decreased by 38%, 73%, and 114% under the individual drought, heat, and compound stresses, respectively. Therefore, compound stresses caused a greater reduction in photosynthetic carbon gain in fluctuating light conditions than individual stress. These findings highlight the importance of mitigating the effects of compound climate extremes on crop productivity by targeting mesophyll conductance and improving dynamic photosynthesis.

Cloning, phylogenetic and expression analysis of two MyoDs in yellowtail kingfish (Seriola lalandi).

Yellowtail kingfish (Seriola lalandi) is a pelagic piscivore distributed circumglobally. Owing to its great market value, the growth mechanism of S. lalandi, including muscle development and growth, is a hot research topic. The myoblast determination protein (MyoD) gene has been shown to play an important role in formation of myoblasts and the function of somites in fish. The open reading frame (ORF) sequences of MyoD1 and MyoD2 in S. lalandi encoded 298 and 263 amino acids possessing three common characteristic domains, respectively, containing a myogenic basic domain, a bHLH domain, and a ser-rich region (helix III). S. lalandi MyoDs shared the highest identity with the MyoDs of S. dumerili. MyoDs are highly expressed in white muscle (P < 0.05) in S. lalandi. The expression level of MyoD1 mRNA was higher than that of MyoD2 mRNA during embryonic and early developmental stages, indicating that the two MyoD isoforms may have different roles in muscle formation. Moreover, the mRNA expression of MyoDs in the brain, pituitary, liver and muscle of endocrine growth axis were analyzed in the various sizes and ages stages. The expression levels of MyoDs in the different sizes and ages of S. lalandi showed that expression of both these genes was particularly high in 400-g fish and 2-year-old fish (P < 0.05). Moreover, the increases in the mRNA expression and plasma levels of growth hormone (GH) and insulin-like growth factor (IGF-I) were accompanied by an increase in mRNA expression of MyoDs, indicating the roles of GH and IGF-I in muscle development and growth of S. lalandi. Overall, the expression profiles of genes associated with muscle development are the first step taken towards deciphering fast growth mechanism in this important Seriola fish.

Observation of a Photonic Orbital Gauge Field.

Gauge field is widely studied in natural and artificial materials. With an effective magnetic field for uncharged particles, many intriguing phenomena are observed in several systems like photonic Floquet topological insulator. However, previous researches about the gauge field mostly focus on limited dimensions such as the Dirac spinor in graphene materials. Here, an orbital gauge field based on photonic triangular lattices is first proposed and experimentally observed. Disclination defects with Frank angle Ω created on such lattices breaks the original lattice symmetry and generates purely geometric gauge field operating on orbital basis functions. Interestingly, it is found that bound states near zero energy with the orbital angular momentum (OAM) l = 2 are intensively confined at the disclination as gradually expanding Ω. Moreover, the introduction of a vector potential field breaks the time-reversal symmetry of the orbital gauge field, experimentally manifested by the chiral transmission of light on helical waveguides. The orbital gauge field further suggests fantastic applications of manipulating the vortex light in photonic integrated devices.