Recognition of cyanobacteria promoters via Siamese network-based contrastive learning under novel non-promoter generation.

It is a vital step to recognize cyanobacteria promoters on a genome-wide scale. Computational methods are promising to assist in difficult biological identification. When building recognition models, these methods rely on non-promoter generation to cope with the lack of real non-promoters. Nevertheless, the factitious significant difference between promoters and non-promoters causes over-optimistic prediction. Moreover, designed for E. coli or B. subtilis, existing methods cannot uncover novel, distinct motifs among cyanobacterial promoters. To address these issues, this work first proposes a novel non-promoter generation strategy called phantom sampling, which can eliminate the factitious difference between promoters and generated non-promoters. Furthermore, it elaborates a novel promoter prediction model based on the Siamese network (SiamProm), which can amplify the hidden difference between promoters and non-promoters through a joint characterization of global associations, upstream and downstream contexts, and neighboring associations w.r.t. k-mer tokens. The comparison with state-of-the-art methods demonstrates the superiority of our phantom sampling and SiamProm. Both comprehensive ablation studies and feature space illustrations also validate the effectiveness of the Siamese network and its components. More importantly, SiamProm, upon our phantom sampling, finds a novel cyanobacterial promoter motif ('GCGATCGC'), which is palindrome-patterned, content-conserved, but position-shifted.

The maize PLASTID TERMINAL OXIDASE (PTOX) locus controls the carotenoid content of kernels.

Carotenoids perform a broad range of important functions in humans; therefore, carotenoid biofortification of maize (Zea mays L.), one of the most highly produced cereal crops worldwide, would have a global impact on human health. PLASTID TERMINAL OXIDASE (PTOX) genes play an important role in carotenoid metabolism; however, the possible function of PTOX in carotenoid biosynthesis in maize has not yet been explored. In this study, we characterized the maize PTOX locus by forward- and reverse-genetic analyses. While most higher plant species possess a single copy of the PTOX gene, maize carries two tandemly duplicated copies. Characterization of mutants revealed that disruption of either copy resulted in a carotenoid-deficient phenotype. We identified mutations in the PTOX genes as being causal of the classic maize mutant, albescent1. Remarkably, overexpression of ZmPTOX1 significantly improved the content of carotenoids, especially ß-carotene (provitamin A), which was increased by ~threefold, in maize kernels. Overall, our study shows that maize PTOX locus plays an important role in carotenoid biosynthesis in maize kernels and suggests that fine-tuning the expression of this gene could improve the nutritional value of cereal grains.

DMGL-MDA: A dual-modal graph learning method for microbe-drug association prediction.

The interaction between human microbes and drugs can significantly impact human physiological functions. It is crucial to identify potential microbe-drug associations (MDAs) before drug administration. However, conventional biological experiments to predict MDAs are plagued by drawbacks such as time-consuming, high costs, and potential risks. On the contrary, computational approaches can speed up the screening of MDAs at a low cost. Most computational models usually use a drug similarity matrix as the initial feature representation of drugs and stack the graph neural network layers to extract the features of network nodes. However, different calculation methods result in distinct similarity matrices, and message passing in graph neural networks (GNNs) induces phenomena of over-smoothing and over-squashing, thereby impacting the performance of the model. To address these issues, we proposed a novel graph representation learning model, dual-modal graph learning for microbe-drug association prediction (DMGL-MDA). It comprises a dual-modal embedding module, a bipartite graph network embedding module, and a predictor module. To assess the performance of DMGL-MDA, we compared it against state-of-the-art methods using two benchmark datasets. Through cross-validation, we illustrated the superiority of DMGL-MDA. Furthermore, we conducted ablation experiments and case studies to validate the effective performance of the model.

Low-intensity ultrasound ameliorates brain organoid integration and rescues microcephaly deficits.

Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses reveal that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays reveal that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model. Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage.

Multiple Enol-Keto Isomerization and Excited-State Unidirectional Intramolecular Proton Transfer Generate Intense, Narrowband Red OLEDs.

A novel series of excited-state intramolecular proton transfer (ESIPT) emitters, namely, DPNA, DPNA-F, and DPNA-tBu, endowed with dual intramolecular hydrogen bonds, were designed and synthesized. In the condensed phase, DPNAs exhibit unmatched absorption and emission spectral features, where the minor 0-0 absorption peak becomes a major one in the emission. Detailed spectroscopic and dynamic approaches conclude fast ground-state equilibrium among enol-enol (EE), enol-keto (EK), and keto-keto (KK) isomers. The equilibrium ratio can be fine-tuned by varying the substitutions in DPNAs. Independent of isomers and excitation wavelength, ultrafast ESIPT takes place for all DPNAs, giving solely KK tautomer emission maximized at >650 nm. The spectral temporal evolution of ESIPT was resolved by a state-of-the-art technique, namely, the transient grating photoluminescence (TGPL), where the rate of EK* → KK* is measured to be (157 fs)-1 for DPNA-tBu, while a stepwise process is resolved for EE* → EK* → KK*, with a rate of EE* → EK* of (72 fs)-1. For all DPNAs, the KK tautomer emission shows a narrowband emission with high photoluminescence quantum yields (PLQY, ∼62% for DPNA in toluene) in the red, offering advantages to fabricate deep-red organic light-emitting diodes (OLED). The resulting OLEDs give high external quantum efficiency with a spectral full width at half-maximum (FWHM) as narrow as ∼40 nm centered at 666-670 nm for DPNAs, fully satisfying the BT. 2020 standard. The unique ESIPT properties and highly intense tautomer emission with a small fwhm thus establish a benchmark for reaching red narrowband organic electroluminescence.

Single-cell profiling reveals kidney CD163+ dendritic cell participation in human lupus nephritis.

OBJECTIVES: The current work aimed to provide a comprehensive single-cell landscape of lupus nephritis (LN) kidneys, including immune and non-immune cells, identify disease-associated cell populations and unravel their participation within the kidney microenvironment. METHODS: Single-cell RNA and T cell receptor sequencing were performed on renal biopsy tissues from 40 patients with LN and 6 healthy donors as controls. Matched peripheral blood samples from seven LN patients were also sequenced. Multiplex immunohistochemical analysis was performed on an independent cohort of 60 patients and validated using flow cytometric characterisation of human kidney tissues and in vitro assays. RESULTS: We uncovered a notable enrichment of CD163+ dendritic cells (DC3s) in LN kidneys, which exhibited a positive correlation with the severity of LN. In contrast to their counterparts in blood, DC3s in LN kidney displayed activated and highly proinflammatory phenotype. DC3s showed strong interactions with CD4+ T cells, contributing to intrarenal T cell clonal expansion, activation of CD4+ effector T cell and polarisation towards Th1/Th17. Injured proximal tubular epithelial cells (iPTECs) may orchestrate DC3 activation, adhesion and recruitment within the LN kidneys. In cultures, blood DC3s treated with iPTECs acquired distinct capabilities to polarise Th1/Th17 cells. Remarkably, the enumeration of kidney DC3s might be a potential biomarker for induction treatment response in LN patients. CONCLUSION: The intricate interplay involving DC3s, T cells and tubular epithelial cells within kidneys may substantially contribute to LN pathogenesis. The enumeration of renal DC3 holds potential as a valuable stratification feature for guiding LN patient treatment decisions in clinical practice.

TBC1D5 reverses the capability of HIF-2α in tumor progression and lipid metabolism in clear cell renal cell carcinoma by regulating the autophagy.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is known for abnormal lipid metabolism and widespread activation of HIF-2α. Recently, the importance of autophagy in ccRCC has been focused, and it has potential connections with HIF-2α and lipid metabolism. However, the specific regulatory mechanism between HIF-2α, autophagy, and lipid metabolism in ccRCC is still unclear. METHODS: In this study, Bioinformatics Analysis and Sequencing of the whole transcriptome were used to screen our target. The expression of TBC1D5 in renal clear cell carcinoma was confirmed by database analysis, immunohistochemistry, PCR and Western blot. The effects of TBC1D5 on tumor cell growth, migration, invasion and lipid metabolism were examined by CCK8, Transwell and oil red staining, and the mechanism of TBC1D5 on autophagy was investigated by Western blot, fluorescence microscopy and electron microscopy. Chloroquine and rapamycin were used to verified the key role of autophagy in effects of TBC1D5 on tumor cell. The regulatory mechanism of TBC1D5 in renal clear cell carcinoma (RCC) was investigated by shhif-2α, shTBC1D5, mimic, inhibitor, ChIP and Luciferase experiments. The animal model of ccRCC was used to evaluate the biological function of TBC1D5 in vivo. RESULTS: In this study, TBC1D5 was found to be an important bridge between autophagy and HIF-2α. Specifically, TBC1D5 is significantly underexpressed in ccRCC, serving as a tumor suppressor which inhibits tumor progression and lipid accumulation, and is negatively regulated by HIF-2α. Further research has found that TBC1D5 regulates the autophagy pathway to reverse the biological function of HIF-2α in ccRCC. Mechanism studies have shown that HIF-2α regulates TBC1D5 through hsa-miR-7-5p in ccRCC, thereby affecting tumor progression and lipid metabolism through autophagy. CONCLUSIONS: Our research reveals a completely new pathway, HIF-2α/hsa-miR-7-5p/TBC1D5 pathway affects ccRCC progression and lipid metabolism by regulating autophagy.

Melatonin as an immunomodulator in CD19-targeting CAR-T cell therapy: managing cytokine release syndrome.

BACKGROUND: Chimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment resistance or relapse. However, the emergence of cytokine release syndrome (CRS) as a side effect poses a challenge to the widespread application of CAR-T cell therapies. Melatonin, a natural hormone produced by the pineal gland known for its antioxidant and anti-inflammatory properties, has been explored for its potential immunomodulatory effects. Despite this, its specific role in mitigating CAR-T cell-induced CRS remains poorly understood. METHODS: In this study, our aim was to investigate the potential of melatonin as an immunomodulatory agent in the context of CD19-targeting CAR-T cell therapy and its impact on associated side effects. Using a mouse model, we evaluated the effects of melatonin on CAR-T cell-induced CRS and overall survival. Additionally, we assessed whether melatonin administration had any detrimental effects on the antitumor efficacy and persistence of CD19 CAR-T cells. RESULTS: Our findings demonstrate that melatonin effectively mitigated the severity of CAR-T cell-induced CRS in the mouse model, leading to improved overall survival outcomes. Remarkably, melatonin administration did not compromise the antitumor effectiveness or persistence of CD19 CAR-T cells, indicating its compatibility with therapeutic goals. These results suggest melatonin's potential as an immunomodulatory compound to alleviate CRS without compromising the therapeutic benefits of CAR-T cell therapy. CONCLUSION: The study's outcomes shed light on melatonin's promise as a valuable addition to the existing treatment protocols for CAR-T cell therapies. By attenuating CAR-T cell-induced CRS while preserving the therapeutic impact of CAR-T cells, melatonin offers a potential strategy for optimizing and refining the safety and efficacy profile of CAR-T cell therapy. This research contributes to the evolving understanding of how to harness immunomodulatory agents to enhance the clinical application of innovative cancer treatments.

Modulation of Intermolecular Interactions in Organic Emitters for Highly Efficient Organic Light-Emitting Diodes.

The adverse aggregated-caused quenching (ACQ) problem of most electroluminescent materials existing in highly doped thin films is one of the key factors impeding the commercialization of high-efficiency organic light-emitting diodes (OLEDs) panel. Whereas, by delicately constructing and modulating moderate intermolecular interactions, some aggregates have been demonstrated to present distinct luminescent properties such as tunable emission spectra, improved photoluminescence quantum yields, different emission mechanism and enhanced horizontal transition dipole ratio (Θ) of emitting layer, providing feasible solution for ACQ problem. The luminescence from newly generated emissive state in aggregates is different from the traditional "isolated" molecules in organic electronics and will possess novel properties and applications. Herein, we summarize the different types of intermolecular interactions within emitter aggregates exhibiting distinct luminescent mechanisms, as well as their effects on photoluminescent and electroluminescent properties, offering reliable reference for the advancement of highly efficient OLEDs utilizing aggregated emitters.

Personality and cognition: shoal size discrimination performance is related to boldness and sociability among ten freshwater fish species.

Several studies have reported that animals' personalities are often correlated with individual differences in cognition. Here, we tested whether personality is related to cognition across species, focusing on 10 freshwater fishes and a task relevant for fitness, the ability to discriminate shoal size. Bolder species exhibited more 'shuttle' behavior for information sampling during shoal selection and showed high performance (HP) in the numerical discrimination than shyer species, i.e., low performance (LP) species. Species at both the high and low ends of sociability showed LP, possibly due to loosened selection pressure because of either no need to perform shoal size discrimination tasks frequently in nature for very high sociability species or decreased willingness and motivation to join and stay within shoals for very low sociability species. Notably, the numerical discrimination was sensitive to the numerical contrast ratio in LP species but not in HP species, suggesting that the numerical system used for size discrimination also varied between species. Overall, we demonstrated the interspecies relationship between personality and shoal size discrimination across fish species, suggesting an evolutionary link between numerical abilities and behavior.

N6 methyladenosine eraser FTO suppresses Staphylococcus aureus-induced ferroptosis of bone marrow mesenchymal stem cells to ameliorate osteomyelitis through regulating the MDM2/TLR4/SLC7A11 signaling pathway.

Osteomyelitis is a bone destructive inflammatory disease caused by infection. Ferroptosis is closely related to multiple inflammatory diseases, but the role of ferroptosis in Staphylococcus aureus (SA)-induced osteomyelitis remains unknown. In the present study, we found that SA treatment promoted the accumulation of iron, Fe2+ , lipid peroxide, and malondialdehyde, increased TFRC and reduced FTH1 and GPX4 to trigger ferroptosis in rat bone marrow mesenchymal stem cells (BMSCs). Interestingly, increased level of N6 methyl adenosine (m6A) modification along with decreased expression level of m6A eraser FTO were observed in SA-induced BMSCs, while upregulating FTO alleviated SA-triggered ferroptosis and protected cell viability in BMSCs. Mechanistically, MDM2 was identified as a target of FTO-mediated m6A demethylation, and FTO upregulation promoted MDM2 instability to downregulated TLR4 signal and elevate the expression of SLC7A11 and GPX4 in SA-induced BMSCs. Functional recovery experiments verified that overexpressing MDM2 or TLR4 reversed the inhibiting effect of FTO upregulation on ferroptosis in SA-treated BMSCs. Additionally, FTO upregulation restrained ferroptosis and pathological damage to bone tissue in SA-induced osteomyelitis model rats. Altogether, m6A eraser FTO alleviates SA-induced ferroptosis in osteomyelitis models partly through inhibiting the MDM2-TLR4 axis.

Comprehensive Review of Drug-Drug Interaction Prediction Based on Machine Learning: Current Status, Challenges, and Opportunities.

Detecting drug-drug interactions (DDIs) is an essential step in drug development and drug administration. Given the shortcomings of current experimental methods, the machine learning (ML) approach has become a reliable alternative, attracting extensive attention from the academic and industrial fields. With the rapid development of computational science and the growing popularity of cross-disciplinary research, a large number of DDI prediction studies based on ML methods have been published in recent years. To give an insight into the current situation and future direction of DDI prediction research, we systemically review these studies from three aspects: (1) the classic DDI databases, mainly including databases of drugs, side effects, and DDI information; (2) commonly used drug attributes, which focus on chemical, biological, and phenotypic attributes for representing drugs; (3) popular ML approaches, such as shallow learning-based, deep learning-based, recommender system-based, and knowledge graph-based methods for DDI detection. For each section, related studies are described, summarized, and compared, respectively. In the end, we conclude the research status of DDI prediction based on ML methods and point out the existing issues, future challenges, potential opportunities, and subsequent research direction.

Huaier inhibits cholangiocarcinoma cells through the twist1/FBP1/Wnt/ß-catenin axis.

BACKGROUND: Although Huaier granules can be used as prospective anti-cholangiocarcinoma drugs, the mechanism of action of Huaier granules in cholangiocarcinoma is not clear. The anti-cholangiocarcinoma effect of Huaier granules was validated in cell line research. In vitro experiments were conducted to investigate the signalling pathways affected by Huaier in CCA cells. METHODS AND RESULTS: Real-time quantitative PCR (RT‒qPCR) and Western blot analysis were performed to analyse gene expression in CCA cells. MTT assays, scratch tests, and Transwell assays were used to explore the effects on the proliferation and metastasis of CCA cells. Chromatin immunoprecipitation assays were performed to reveal the potential underlying mechanisms involved. Twist1 was upregulated in human CCA tissues. In addition, its expression levels were negatively related to FBP1 expression levels. Mechanistically, Twist1 can bind to the region of the FBP1 promoter to reduce its expression. Huaier plays an indispensable role in suppressing Twist1 expression to inhibit the Twist1/FBP1/Wnt/ß-catenin axis. Then, we verified the effect of Huaier in vitro. CONCLUSIONS: These findings suggested that Huaier granules were capable of inhibiting CCA development through regulating the Twist1/FBP1/Wnt/ß-catenin signalling axis and provided a novel orientation for the development of novel anti-CCA drugs.

Discovery of novel coumarin-based KRAS-G12C inhibitors from virtual screening and Rational structural optimization.

KRAS-G12C inhibitors has been made significant progress in the treatment of KRAS-G12C mutant cancers, but their clinical application is limited due to the adaptive resistance, motivating development of novel structural inhibitors. Herein, series of coumarin derivatives as KRAS-G12C inhibitors were found through virtual screening and rational structural optimization. Especially, K45 exhibited strong antiproliferative potency on NCI-H23 and NCI-H358 cancer cells harboring KRAS-G12C with the IC50 values of 0.77 µM and 1.50 µM, which was 15 and 11 times as potent as positive drug ARS1620, respectively. Furthermore, K45 reduced the phosphorylation of KRAS downstream effectors ERK and AKT by reducing the active form of KRAS (KRAS GTP) in NCI-H23 cells. In addition, K45 induced cell apoptosis by increasing the expression of anti-apoptotic protein BAD and BAX in NCI-H23 cells. Docking studies displayed that the 3-naphthylmethoxy moiety of K45 extended into the cryptic pocket formed by the residues Gln99 and Val9, which enhanced the interaction with the KRAS-G12C protein. These results indicated that K45 was a potent KRAS-G12C inhibitor worthy of further study.

Regional differences in the effects of various Stokes drifts on the cooling of the marine environment under different wave conditions.

The WAVEWATCHIII model is employed to simulate Stokes drift, utilizing four distinct schemes integrated into the SBPOM circulation model. Deviations between simulated values and observations from the Optimum Interpolation Sea Surface Temperature (OISST) dataset unveil significant variations, particularly in regions characterized by pronounced swell. The northern hemisphere exhibits the highest deviations, reaching up to 0.3 °C during the March-April-May (MAM) and December-January-February (DJF) periods, while the Antarctic Circumpolar Current (ACC) consistently displays smaller deviations of approximately 0.1 °C. Deviations from Argo buoy measurements hover around 0.1 °C, except in the northern hemisphere where they escalate to approximately 1.5 °C. A comparative analysis of simulation results and Argo buoy measurements reveals an increasing deviation trend with a higher proportion of swell in specific sea areas, particularly evident in simulations utilizing approximate parameterization schemes. Notably, the Phillips profile scheme exhibits optimal performance, while the monochromatic profile scheme peaks with a simulated deviation of 0.13 °C. In contrast, the wave spectrum profile scheme consistently demonstrates applicability across diverse wave conditions and accurately captures the mixed layer at various depths. This study highlights the importance of the coupled WAVEWATCHIII-SBPOM model in accurately modeling future ocean conditions, providing valuable insight into the field of environmental science.

Ultra-high order mode-assisted optical differentiator for edge detection with high tunability.

An optical spatial differentiator based on the photonic spin Hall effect (PSHE) with high tunability is presented. By utilizing the characteristics of ultra-high order modes in the symmetrical metal cladding waveguide, the Fresnel reflection coefficient spectrum exhibits a narrow peak width and low trough at the resonant incident angles, resulting in high sensitivity to changes in the incident angle-induced spatial shift caused by the PSHE (the highest ∂(|r s/r p|)/∂ θ value can reach 107). After polarization transformation and extinction, the output field demonstrates differential operation with respect to the input field. When applied to edge detection, our differentiator can achieve tunable resolution edge images by adjusting the incident angle. Our proposed edge detection scheme has potential applications for cellular and molecular imaging through two-dimensional extension via the target rotation.

Prediction of programmed death-1 expression status in non-small cell lung cancer based on intratumoural and peritumoral computed tomography (CT) radiomics nomogram.

AIMS: This study aimed to predict the expression of programmed death-1 (PD-1) in non-small cell lung cancer (NSCLC) using intratumoral and peritumoral computed tomography (CT) radiomics nomogram. MATERIALS AND METHODS: Two hundred patients pathologically diagnosed with NSCLC from two hospitals were retrospectively analyzed. Of these, 159 NSCLC patients from our hospital were randomly divided into a training cohort (n=96) and an internal validation cohort (n=63) at a ratio of 6:4, while 41 NSCLC patients from another medical institution served as the external validation cohort. The radiomic features of the gross tumor volume (GTV) and peritumoral volume (PTV) were extracted from the CT images. Optimal radiomics features were selected using least absolute shrinkage and selection operator regression analysis. Finally, a CT radiomics nomogram of clinically independent predictors combined with the best rad-score was constructed. RESULTS: Compared with the 'GTV' and 'PTV' radiomics models, the combined 'GTV + PTV' radiomics model showed better predictive performance, and its area under the curve (AUC) values in the training, internal validation, and external validation cohorts were 0.90 (95% confidence interval [CI]: 0.83-0.97), 0.85 (95% CI: 0.74-0.96) and 0.78 (95% CI: 0.63-0.92). The nomogram constructed by the rad-score of the 'GTV + PTV' radiomics model combined with clinical independent predictors (prealbumin and monocyte) had the best performance, with AUC values in each cohort being 0.92 (95% CI: 0.85-0.98), 0.88 (95% CI: 0.78-0.97), and 0.80 (95% CI: 0.66-0.94), respectively. CONCLUSION: The intratumoral and peritumoral CT radiomics nomogram may facilitate individualized prediction of PD-1 expression status in patients with NSCLC.

Successful treatment with efgartigimod as an add-on therapy in acute attack of anti-AQP4 antibody-positive NMOSD: a case report.

BACKGROUND: Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune demyelinating disease characterized by recurrent myelitis and optic neuritis. It is associated with high rates of relapse and disability. The main treatment strategies for acute attacks include intravenous methylprednisolone pulse (IVMP) treatment and rescue treatment with plasma exchange (PLEX). Recently, the blockade of neonatal Fc receptor (FcRn)-IgG interaction has gained momentum as a therapeutic strategy. Efgartigimod, the first approved FcRn inhibitor for treating generalized myasthenia gravis, has shown impressive safety, efficacy, and tolerability, and is being regarded as "PLEX in a bottle". CASE DESCRIPTION: We report a 65-year-old female patient who was diagnosed with anti-AQP4 antibody positive NMOSD. Add-on treatment with efgartigimod to IVMP and intravenous immunoglobulin (IVIG) at the second acute relapse showed favorable results. CONCLUSION: This case suggests that efgartigimod is a potentially effective add-on therapy in acute attacks of AQP4-IgG-positive NMOSD.

The presence and clinical significance of autoantibodies in amyotrophic lateral sclerosis: a narrative review.

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS.

Management of infected bone defects of the femoral shaft by Masquelet technique: sequential internal fixation and nail with plate augmentation.

BACKGROUND: To evaluate the effectiveness of a sequential internal fixation strategy and intramedullary nailing with plate augmentation (IMN/PA) for bone reconstruction in the management of infected femoral shaft defects using the Masquelet technique. METHODS: We performed a retrospective descriptive cohort study of 21 patients (mean age, 36.4 years) with infected bone defects of the femoral shaft treated by the Masquelet technique with a minimum follow-up of 18 months after second stage. After aggressive debridement, temporary stabilisation (T1) was achieved by an antibiotic-loaded bone cement spacer and internal fixation with a bone cement-coated locking plate. At second stage (T2), the spacer and the locking plate were removed following re-debridement, and IMN/PA was used as definitive fixation together with bone grafting. We evaluated the following clinical outcomes: infection recurrence, bone union time, complications, and the affected limb's knee joint function. RESULTS: The median and quartiles of bone defect length was 7 (4.75-9.5) cm. Four patients required iterative debridement for infection recurrence after T1. The median of interval between T1 and T2 was 10 (9-19) weeks. At a median follow-up of 22 (20-27.5) months, none of the patients experienced recurrence of infection. Bone union was achieved at 7 (6-8.5) months in all patients, with one patient experiencing delayed union at the distal end of bone defect due to screws loosening. At the last follow-up, the median of flexion ROM of the knee joint was 120 (105-120.0)°. CONCLUSIONS: For infected femoral shaft bone defects treated by the Masquelet technique, sequential internal fixation and IMN/PA for the reconstruction can provide excellent mechanical stability, which is beneficial for early functional exercise and bone union, and does not increase the rate of infection recurrence.