Exploring the impact of metabolites function on heart failure and coronary heart disease: insights from a Mendelian randomization (MR) study.

BACKGROUND: Heart failure (HF) and coronary heart disease (CHD) are major causes of morbidity and mortality worldwide. While traditional risk factors such as hypertension, diabetes, and smoking have been extensively studied, the role of metabolite functions in the development of these cardiovascular conditions has been less explored. This study employed a Mendelian randomization (MR) approach to investigate the impact of metabolite functions on HF and CHD. METHODS: To assess the causal impacts of specific metabolite risk factors on HF and CHD, this study utilized genetic variants associated with these factors as instrumental variables. Comprehensive genetic and phenotypic data from diverse cohorts, including genome-wide association studies (GWAS) and cardiovascular disease registries, were incorporated into the research. RESULTS: Our results encompass 61 metabolic cell phenotypes, with ten providing strong evidence of the influence of metabolite functions on the occurrence of HF and CHD. We found that elevated levels of erucate (22:1n9), lower levels of α-tocopherol, an imbalanced citrulline-to-ornithine ratio, elevated γ-glutamyl glycine levels, and elevated 7-methylguanine levels independently increased the risk of these cardiovascular conditions. These findings were consistent across different populations and robust to sensitivity analyses. CONCLUSION: This MR study provides valuable insights into the influence of metabolite functions on HF and CHD. However, further investigation is needed to fully understand the precise mechanisms by which these metabolite factors contribute to the onset of these conditions. Such research could pave the way for the development of targeted therapeutic strategies.

Macroscopic Twisting of Chiral Metal Halide Single Crystals Driven by Thermo-Induced Topochemical Dehydration.

Dynamic twisting crystals, combining the features of dynamic crystals and twisting crystals, promise advanced applications in targeted drug delivery, biosensors, microrobots, and spiral optoelectronics. However, the determination of dynamic twisting crystals with specific directions remains a formidable challenge in practical applications. Herein, based on organic-inorganic hybrid metal halide (OIHMH) single crystals, we have realized the chirality-induced macroscopic twisting of single crystals driven by a thermo-induced topochemical dehydration reaction. These crystals exhibit molecular-chirality-induced twisting upon heating, along with reversals in their linear chiroptical circular dichroism and nonlinear chiroptical second harmonic generation circular dichroism. Such an induced twisting has been attributed to the alteration of the helical arrangement of chiral cation post-topochemical dehydration. The feasibility of tuning the macroscopic twisting of OIHMH single crystals and the switching in their linear and nonlinear chiroptical properties might open up new avenues for developing dynamic crystals for microactuating and optoelectronic applications.

Genetic Analysis of Potential Biomarkers and Therapeutic Targets in Ferroptosis from Steroid-Induced Osteonecrosis of the Femoral Head Based on Machine Learning.

OBJECTIVE: To locate the candidate therapeutic target genes involved in ferroptosis in steroid-induced osteonecrosis of the femoral head (SONFH). STUDY DESIGN: Bioinformatics analysis study. Place and Duration of the Study: Department of Orthopaedic Surgery, Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Guangdong, China, from March to July 2023. METHODOLOGY: After processing the gene expression omnibus (GEO) data with the R programming language, differentially expressed ferroptosis-related genes in SONFH were identified. To pinpoint the genes most strongly linked to SONFH in association with ferroptosis, least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE) were employed. Subsequently, the screened essential genes were analysed to investigate immune cell infiltration, and competing endogenous RNA (ceRNA) networks involving these marker genes were constructed. RESULTS: The machine learning algorithms identified three genes i.e., SOCS1 (suppressor of cytokine signalling1), MYCN (N-myc proto-oncogene protein), and KLF2 (Kruppel-like factor 2) as diagnostic feature biomarkers associated with ferroptosis. Additionally, CIBERSORT analysis revealed that alterations in the immune microenvironment, such as Macrophages M1, Monocytes, and T cells CD4 naive, could be linked to SOCS1, MYCN, and KLF2. Moreover, the competing endogenous RNA (ceRNA) network exposed a complex regulatory relationship based on marker genes. CONCLUSION: SOCS1, MYCN, and KLF2 are potential biomarkers associated with ferroptosis in SONFH, pending confirmation in future studies. KEY WORDS: Steroid-induced osteonecrosis of the femoral head, Ferroptosis, Machine learning, Genetic analysis.

Down-regulation of PGAM5 attenuates spinal cord injury-induced neuronal injury by inhibiting ASK-1/p38/NF-kB signaling.

INTRODUCTION: The morbidity and mortality of spinal cord injury (SCI) are increasing year by year. It is of vital importance to ascertain the mechanism of SCI. Phosphoglycerate mutase family member 5 (PGAM5) is viewed as a molecular marker of SCI, but its specific role in SCI is elusive. MATERIAL AND METHODS: Following establishment of the SCI mouse model, the pathological examination of the spinal cord was initially assessed using H&E staining. PGAM5 expression in spinal cord tissues was appraised utilizing immunohistochemistry and RT-qPCR. Subsequently, after the expression of PGAM5 in SCI mice was inhibited by adenovirus transfection, the degree of SCI was determined, and the motor ability of hind limbs was estimated with the BBB score. In addition, the apoptosis of neurons, microglia activation and the generation of inflammatory cytokines in the spinal cord of mice were detected. Next, at the cellular level, PGAM5 expression was inhibited in the BV2 microglial cells induced by lipopolysaccharide (LPS), so as to explore the effects of down-regulation of PGAM5 on the activation, inflammation and apoptosis of neurons. Finally, western blot was applied for the appraisement of apoptosis signal-regulating kinase-1 (ASK-1)/p38/nuclear factor-kappa B (NF-kB) signaling-associated proteins. RESULTS: PGAM5 expression in SCI mice was found to be raised. Inhibition of PGAM5 expression in SCI mice can significantly reduce spinal cord pathological injury, SCI-induced neuronal apoptosis, microglial cell activation and inflammation. The above regulatory process might be realized through the ASK-1/p38/NF-kB signaling pathway mediated by PGAM5. CONCLUSIONS: Down-regulation of PGAM5 attenuated SCI-induced neuronal injury by inhibiting ASK-1/p38/NF-kB signaling.

Causal roles of immune cells in cardiovascular diseases: A Mendelian randomization (MR) study.

Background: Despite being a major global cause of mortality, the exact underlying mechanisms of cardiovascular diseases (CVDs) remain uncertain. This study aimed to elucidate the possible pathological connection between circulating activated immune cell types and the advancement of CVD. Methods: A two-sample Mendelian randomization analysis was performed on publicly available genetic databases to examine the potential causal relationships among 731 immune phenotypes and CVD risks. The study focused on four distinct immune signatures: relative cell counts (RC), absolute cell counts (AC), morphological parameters (MP), and median fluorescence intensities (MFI). A sensitivity analysis was performed to assess the findings' consistency, robustness, and potential pleiotropic effects. Results: Significant associations between CVD and various immunophenotypes were observed in this study. Specifically, two phenotypes exhibited protective effects against CVD. The odds ratio (OR) for activated and secretory CD4+ regulatory T-cells (Tregs) was 0.757 [95% confidence interval (CI): 0.628-0.913; p = 0.004], whereas that for B-cell activating factor receptor on IgD-CD38+ memory B-cells was 0.654 (95% CI: 0.468-0.915; p = 0.013). Conversely, three major immunophenotypes were linked to heightened risks of CVD: CD80 on myeloid dendritic cells (OR: 1.181; 95% CI: 1.015-1.376; p = 0.032), the proportion of CD28+ CD45RA+ CD8+ T-cells in total T-cell population (OR: 1.064; 95% CI: 1.002-1.128; p = 0.041), and the proportion of CD28-CD45RA+ CD8+ T-cells in total T-cell population (OR: 1.005; 95% CI: 1.000-1.011; p = 0.045). Conclusion: This study underscores significant correlations between specific immune phenotypes and the risks associated with CVD onset, thus providing valuable perspectives for forthcoming clinical inquiries.

Impacts of LNAPL types on mechanisms and rate of natural source zone depletion.

Understanding the mechanisms of natural source zone depletion (NSZD) will support an improved understanding of the long-term sustainability of NSZD as a site remedy and how NSZD rates may change over time. This is the first study that has quantified and compared the rate of three NSZD mechanisms (methanogenesis, vaporization, and aqueous biodegradation) between two chemically distinct light non-aqueous phase liquid (LNAPL) source zones (aliphatic-rich naphtha for Zone #1 vs aromatic-rich pyrolysis gasoline for Zone #2) within the same geologic and climate conditions. The rates of NSZD attributable to vaporization (400 mg C/m2/d vs. 300 mg C/m2/d) and aqueous biodegradation (92 mg C/m2/d vs. 67 mg C/m2/d) were similar for Zone #1 and #2; however, the rate of methanogenesis NSZD was 6x higher in Zone #1 (1000 mg C/m2/d vs. 170 mg C/m2/d). These results suggest that the aliphatic hydrocarbons content in an LNAPL source may be a factor in the rate of methanogenesis NSZD. For both Zone #1 and #2, total NSZD rate determined using this "three mechanism" measurement method was in reasonable agreement with two other methods used to measure total NSZD rates (CO2 Gradient Method and Dynamic Closed Chamber Method), validating the "three mechanism" method as a tool to measure the total NSZD rate at a site and to provide an improved understanding of the predominant NSZD mechanism. Overall, this study highlights the importance of LNAPL type and chemical characteristics in determining source zone natural attenuation mechanism and its total rates.

Boosted Second Harmonic Generation of a Chiral Hybrid Lead Halide Resonant to Charge Transfer Exciton from Metal Halide Octahedra to Ligand.

Chiral hybrid organic-inorganic metal halides (HOMHs) offer an ideal platform for the advancement of second-order nonlinear optical (NLO) materials owing to their inherent noncentrosymmetric structures. The enhancement of optical nonlinearity of chiral HOMHs could be achieved by matching the free exciton and/or self-trapped exciton energy levels with desired NLO frequencies. However, the current scarcity of resonance modes and low resonance ratio hamper the further improvements of NLO performance. Herein, we propose a new resonant channel of charge transfer (CT) excited states from metal halide polyhedra to organic ligand to boost the second-order optical nonlinearity of chiral HOMHs. The model lead halide (C7H10N)PbBr3 (C7H10N=1-ethylpyridinium) exhibits a drastically enhanced second harmonic generation in resonance to the deep CT exciton energy, with intensity of up to 111.0 times that of KDP and 10.9 times that of urea. The effective NLO coefficient has been determined to be as high as ~40.2 pm V-1, balanced with a large polarization ratio and high laser damage threshold. This work highlights the contribution of organic ligands in the construction of a resonant channel for enhancing second-order NLO coefficients of metal halides, and thus provides guidelines for designing new chiral HOMHs materials for advanced nonlinear photonic applications.

Multi-stimuli-responsive luminescence enabled by crown ether anchored chiral antimony halide phosphors.

Stimuli-responsive optical materials have provided a powerful impetus for the development of intelligent optoelectronic devices. The family of organic-inorganic hybrid metal halides, distinguished by their structural diversity, presents a prospective platform for the advancement of stimuli-responsive optical materials. Here, we have employed a crown ether to anchor the A-site cation of a chiral antimony halide, enabling convenient control and modulation of its photophysical properties. The chirality-dependent asymmetric lattice distortion of inorganic skeletons assisted by a crown ether promotes the formation of self-trapped excitons (STEs), leading to a high photoluminescence quantum yield of over 85%, concomitant with the effective circularly polarized luminescence. The antimony halide enantiomers showcase highly sensitive stimuli-responsive luminescent behaviours towards excitation wavelength and temperature simultaneously, exhibiting a versatile reversible colour switching capability from blue to white and further to orange. In situ temperature-dependent luminescence spectra, time-resolved luminescence spectra and theoretical calculations reveal that the multi-stimuli-responsive luminescent behaviours stem from distinct STEs within zero-dimensional lattices. By virtue of the inherent flexibility and adaptability, these chiral antimony chlorides have promising prospects for future applications in cutting-edge fields such as multifunctional illumination technologies and intelligent sensing devices.

A retrospective study investigating the clinical significance of body mass index in acute pancreatitis.

Background: Acute pancreatitis is an unpredictable and potentially fatal condition for which no definitive cure is currently available. Our research focused on exploring the connection between body mass index, a frequently overlooked risk factor, and both the onset and progression of acute pancreatitis. Material/Methods: A total of 247 patients with acute pancreatitis admitted to Jiangsu Provincial Hospital of Chinese Medicine from January 2021 to February 2023 were retrospectively reviewed. After screening, 117 patients with complete height and body weight data were selected for detailed assessment. Additionally, 85 individuals who underwent physical examinations at our hospital during this period were compiled to create a control group. The study received ethical approval from the ethics committee of Jiangsu Province Hospital of Chinese Medicine (Ref: No.2022NL-114-02) and was conducted in accordance with the China Good Clinical Practice in Research guidelines. Results: A significant difference in body mass index (BMI) was observed between the healthy group and acute pancreatitis (AP) patients (p < 0.05), with a more pronounced disparity noted in cases of hyperlipidemic acute pancreatitis (p < 0.01). A potential risk for AP was identified at a BMI greater than 23.56 kg/m2 (AUC = 0.6086, p < 0.05). Being in the obese stage I (95%CI, [1.11-1.84]) or having a BMI below 25.4 kg/m2 (95%CI, [1.82-6.48]) are identified as risk factors for adverse AP progression. Moreover, BMI effectively predicts the onset of acute edematous pancreatitis and acute necrotizing pancreatitis (AUC = 0.7893, p < 0.001, cut-off value = 25.88 kg/m2). A higher BMI correlates with increased recurrence rates within a short timeframe (r = 0.7532, p < 0.01). Conclusions: Elevated BMI is a risk factor for both the occurrence and progression of AP, and underweight status may similarly contribute to poor disease outcomes. BMI is crucial for risk prediction and stratification in AP and warrants ongoing monitoring and consideration.

The multilevel extensive diversity across the cynomolgus macaque captured by ultra-deep adaptive immune receptor repertoire sequencing.

The extent to which AIRRs differ among and within individuals remains elusive. Via ultra-deep repertoire sequencing of 22 and 25 tissues in three cynomolgus macaques, respectively, we identified 84 and 114 novel IGHV and TRBV alleles, confirming 72 (85.71%) and 100 (87.72%) of them. The heterogeneous V gene usage patterns were influenced, in turn, by genetics, isotype (for BCRs only), tissue group, and tissue. A higher proportion of intragroup shared clones in the intestinal tissues than those in other tissues suggests a close intra-intestinal adaptive immunity network. Significantly higher mutation burdens in the public clones and the inter-tissue shared IgM and IgD clones indicate that they might target the shared antigens. This study reveals the extensive heterogeneity of the AIRRs at various levels and has broad fundamental and clinical implications. The data generated here will serve as an invaluable resource for future studies on adaptive immunity in health and diseases.

Understanding petroleum vapor fate and transport through high resolution analysis of two distinct vapor plumes.

No field study has provided a detailed characterization of the molecular composition and spatial distribution of a vadose zone plume of petroleum volatile organic compounds (VOCs), which is critical to improve the current understanding of petroleum VOC transport and fate. This is study reports a high-resolution analysis of two distinct vapor plumes emanating from two different light non-aqueous phase liquid (LNAPL) sources (an aliphatic-rich LNAPL for Zone #1vs an aromatic-rich LNAPL for Zone #2) at a large petrochemical site. Although deep soil vapor signatures were similar to the source zone LNAPL signatures, the composition of the shallow soil vapors reflected preferential attenuation of certain hydrocarbons over others during upward transport in the vadose zone. Between deeper and shallower soil gas samples, attenuation of aromatics was observed under all conditions, but important differences were observed in attenuation to aliphatic compound classes. Attenuation of all aliphatic compounds was observed under aerobic conditions but little attenuation of any aliphatics was observed under anoxic conditions without methane. In contrast, under methanogenic conditions, paraffins attenuated more than isoparaffins and naphthenes. These results suggest that isoparafins and naphthenes may present more of a vapor intrusion risk than benzene or other aromatic hydrocarbons commonly considered to be petroleum vapor intrusion risk drivers. While the overall vapor composition changed significantly within the vadose zone, diagnostic ratios of relatively recalcitrant alkylcyclopentanes were preserved in shallow soil vapor samples. These alkylcyclopentanes may be useful for distinguishing between petroleum vapor intrusion and other sources of petroleum VOCs detected in indoor air.

Free Halogen Substitution of Chiral Hybrid Metal Halides for Activating the Linear and Nonlinear Chiroptical Properties.

Halogen substitution has been proven as an effective approach to the band gap engineering and optoelectronic modulation of organic-inorganic hybrid metal halide (OIHMH) materials. Various high-performance mixed halide OIHMH film materials have been primarily obtained through the substitution of coordinated halogens in their inorganic octahedra. Herein, we propose a new strategy of substitution of free halogen outside the inorganic octahedra for constructing mixed halide OIHMH single crystals with chiral structures, resulting in a boost of their linear and nonlinear chiroptical properties. The substitution from DMA4[InCl6]Cl (DMA = dimethylammonium) to DMA4[InCl6]Br crystals through a facile antisolvent vaporization method produces centimeter-scale single crystals with high thermal stability along with high quantum yield photoluminescence, conspicuous circularly polarized luminescence, and greatly enhanced second harmonic generation (SHG). In particular, the obtained DMA4[InCl6]Br single crystal features an intrinsic chiral structure, exhibiting a significant SHG circular dichroism (SHG-CD) response with a highest reported anisotropy factor (gSHG-CD) of 1.56 among chiral OIHMH materials. The enhancements in both linear and nonlinear chiroptical properties are directly attributed to the modulation of octahedral distortion. The mixed halide OIHMH single crystals obtained by free halogen substitution confine the introduced halogens within free halogen sites of the lattice, thereby ensuring the stability of compositions and properties. The successful employment of such a free halogen substitution approach may broaden the horizon of the regulation of structures and the optoelectronic properties of the OIHMH materials.

Fiber-reinforced gelatin/ß-cyclodextrin hydrogels loaded with platelet-rich plasma-derived exosomes for diabetic wound healing.

Diabetic complications with high-glucose status (HGS) cause the dysregulated autophagy and excessive apoptosis of multiple-type cells, leading to the difficulty in wound self-healing. Herein, we firstly developed fiber-reinforced gelatin (GEL)/ß-cyclodextrin (ß-CD) therapeutic hydrogels by the modification of platelet-rich plasma exosomes (PRP-EXOs). The GEL fibers that were uniformly dispersed within the GEL/ß-CD hydrogels remarkably enhanced the compression strengths and viscoelasticity. The PRP-EXOs were encapsulated in the hydrogels via the covalent crosslinking between the PRP-EXOs and genipin. The diabetic rat models demonstrated that the GEL/ß-CD hydrogels and PRP-EXOs cooperatively promoted diabetic wound healing. On the one hand, the GEL/ß-CD hydrogels provided the biocompatible microenvironments and active components for cell adhesion, proliferation and skin tissue regeneration. On the other hand, the PRP-EXOs in the therapeutic hydrogels significantly activated the autophagy and inhibited the apoptosis of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs). The activation of autophagy and inhibition of apoptosis in HUVECs and HSFs induced the blood vessel creation, collagen formation and re-epithelialization. Taken together, this work proved that the incorporation of PRP-EXOs in a wound dressing was an effective strategy to regulate autophagy and apoptosis, and provide a novel therapeutic platform for diabetic wound healing.

Angiotensin IV ameliorates doxorubicin-induced cardiotoxicity by increasing glutathione peroxidase 4 and alleviating ferroptosis.

BACKGROUND: Doxorubicin (DOX)-induced cardiotoxicity is an important cause of poor prognosis in cancer patients treated with DOX. Angiotensin IV (Ang IV) has multiple protective effects against cardiovascular diseases, including diabetic cardiomyopathy and myocardial infarction, but its role in DOX-induced cardiotoxicity is currently unclear. In this study, we investigated the effects of Ang IV on DOX-induced cardiotoxicity. METHODS: The viability of primary cardiomyocytes was measured by Cell Counting Kit-8 assays and Hoechst 33342/propidium iodide staining in vitro. ELISAs (serum cTnT and CK-MB) and echocardiography were performed to assess myocardial injury and cardiac function in vivo. Phalloidin staining, haematoxylin and eosin staining and wheat germ agglutinin staining were conducted to detect cardiomyocyte atrophy. We also performed C11 BODIPY staining, measured the levels of Ptgs2 and malondialdehyde and detected the concentrations of ferrous ions, glutathione and oxidized glutathione to indicate ferroptosis. RESULTS: Ang IV not only attenuated DOX-induced atrophy and cardiomyocyte injury in vitro but also alleviated myocardial injury and improved cardiac function in DOX-treated mice in vivo. Moreover, Ang IV reversed DOX-induced downregulation of glutathione peroxidase 4 (GPX4) and inhibited ferroptosis both in vitro and in vivo. Knockdown of GPX4 by siRNA abolished the cardioprotective effects of Ang IV. Furthermore, Ang IV increased GPX4 levels and ameliorated ferroptosis in RAS-selective lethal 3-treated primary cardiomyocytes. CONCLUSIONS: Ang IV ameliorates DOX-induced cardiotoxicity by upregulating GPX4 and inhibiting ferroptosis. Ang IV may be a promising candidate to protect against DOX-induced cardiotoxicity in the future.

Circularly polarized luminescence and nonlinear optical harmonic generation based on chiral zinc halides.

Chiral hybrid metal halides have grabbed extensive attention in linear and nonlinear chiroptics. Herein, 0D chiral zinc halides, (R-/S-2-MP)ZnCl4, have been fabricated, which demonstrate high efficiency second-order nonlinear optical responses. Incorporating Sb3+ into the chiral zinc halide matrix triggers the circularly polarized luminescence effectively with a balance between quantum yield and luminescence dissymmetry factor.

Promotion of the genipin crosslinked chitosan-fiber hydrogel loaded with sustained release of clemastine fumarate in diabetic wound repair.

Diabetic skin disorders are lingering and refractory clinical diseases. In this study, a genipin-crosslinked porous chitosan fiber (CSF) hydrogel was fabricated to achieve rapid wound healing. By embedding clemastine fumarate (CF) in the CSF hydrogel pores, we synthesised a CSF/CF hydrogel for the treatment of diabetic wounds. The microstructure, chemical elements, spectral variation, mechanical properties, swelling ratios, degradability, and toxicity of the CSF/CF hydrogels were studied. Compared with the typical CS power hydrogel, the porous CSF hydrogel crosslinked with genipin possesses a stable structure and improved physicochemical properties. Moreover, CF was slowly released from the CSF hydrogel. Molecular simulation also showed that CF was evenly embedded inside the cavity formed by the novel CSF hydrogel. The results suggested that CF can resist damage from high glucose levels and promote proliferation, tube formation, and migration of endothelial cells (ECs) and fibroblasts. The CSF/CF hydrogel promoted wound healing in a rat model. Mechanistically, the beneficial effect of CF on wound healing may be related to activation of the MEK/ERK and PI3K/Akt signalling pathways. In conclusion, genipin-crosslinked CSF/CF hydrogel can accelerate wound healing and may be an effective therapeutic method for treating diabetic skin lesions.

Muscle loss 6 months after surgery predicts poor survival of patients with non-metastatic colorectal cancer.

Background: Muscle loss is a common characteristic of cancer-related malnutrition and a predictor of poorer prognosis in oncological patients. This study evaluated the association between altered body composition 6 months after surgery and the prognosis in patients with non-metastatic colorectal cancer. Materials and methods: A total of 314 patients who underwent elective curative surgery were enrolled in the study. The third lumbar CT images on preoperative and 6-months postoperative were collected to calculate the skeletal muscle index (SMI), visceral adiposity index (VATI), and subcutaneous adiposity index (SATI). Sarcopenia was defined by the cut-off values reported in the literature, and risk factors affecting overall survival (OS) and disease-free survival (DFS) in CRC were analyzed using Cox regression models. Results: Eighty-two of 314 patients (26.1%) with CRC were diagnosed with sarcopenia before surgery, the preoperative sarcopenia was not significantly associated with the prognosis of CRC patients. There were significant differences in frequency of complications between patient groups according to sarcopenia (41.5 vs. 21.4%, p = 0.004). The Postoperative LOS (11.21 ± 3.04 vs. 8.92 ± 2.84, p < 0.001) was longer in the sarcopenia group than in the non-sarcopenia group, and 30-d readmission (24.4 vs. 6.0%, p < 0.001) was higher in the sarcopenia group compared to the non-sarcopenia group. In multivariate analysis, 6-months SMI loss > 10% after surgery was independently associated with poorer OS [hazard ratio (HR) = 3.74; 95% confidence interval (CI) 1.96 to 7.12; P < 0.001] and DFS (HR = 3.33; 95% CI, 1.71 to 6.47; P < 0.001). SMI changes were moderately correlated with changes in body mass index (BMI) (R = 0.47, P < 0.001). Conclusion: 6-months muscle loss after surgery may affect overall and disease-free survival and was an independent predictor of prognosis in patients with CRC.

Mechanistic insight into adsorptive removal of ionic NOR and nonionic DEP organic contaminates by clay-biochar composites.

The synthesis of clay-biochar composite has been recognized as an effective way to enhance the removal of pollutants. The interaction between clay mineral and biomass during thermal pyrolysis and the sorption capacity for ionic/nonionic organic containments have not been elaborated. In this study, two types of biochar were obtained from pyrolytic carbonization of the cellulosic-rich corn straw (C) and lignin-rich pine wood (P) at 500 or 700 °C. Typical clay minerals kaolinite and montmorillonite were selected to prepare clay-biochar composite. The results showed that the addition of clay mineral could strengthen dehydration reaction of corn straw biomass and reinforce its carbon structure. Montmorillonite-biochar composite owned more CC functional groups and porous structure than kaolinite-biochar composite. The addition of clay minerals could promote electrostatic attraction of ionic formed norfloxacin (NOR) on clay-pine wood biochar. However, the sorption capacity of nonionic diethyl phthalate (DEP) adsorption on clay-corn straw biochar decreased, owing to that clay increased the compactness of the biochar carbon structure, thus inhabited hydrophobic partition of nonionic organic compounds on disordered carbon fraction. The results from this study provide insights into the suitable contaminated site remediation by clay-biochar composite.

A Deep Learning Model for Accurate Diagnosis of Infection Using Antibody Repertoires.

The adaptive immune receptor repertoire consists of the entire set of an individual's BCRs and TCRs and is believed to contain a record of prior immune responses and the potential for future immunity. Analyses of TCR repertoires via deep learning (DL) methods have successfully diagnosed cancers and infectious diseases, including coronavirus disease 2019. However, few studies have used DL to analyze BCR repertoires. In this study, we collected IgG H chain Ab repertoires from 276 healthy control subjects and 326 patients with various infections. We then extracted a comprehensive feature set consisting of 10 subsets of repertoire-level features and 160 sequence-level features and tested whether these features can distinguish between infected individuals and healthy control subjects. Finally, we developed an ensemble DL model, namely, DL method for infection diagnosis (https://github.com/chenyuan0510/DeepID), and used this model to differentiate between the infected and healthy individuals. Four subsets of repertoire-level features and four sequence-level features were selected because of their excellent predictive performance. The DL method for infection diagnosis outperformed traditional machine learning methods in distinguishing between healthy and infected samples (area under the curve = 0.9883) and achieved a multiclassification accuracy of 0.9104. We also observed differences between the healthy and infected groups in V genes usage, clonal expansion, the complexity of reads within clone, the physical properties in the α region, and the local flexibility of the CDR3 amino acid sequence. Our results suggest that the Ab repertoire is a promising biomarker for the diagnosis of various infections.

Tips and Tricks in surgical reduction of the posterior column of AO/OTA C3 pilon fractures.

BACKGROUND: Accurate posterior column reduction remains a challenging and controversial topic in the management of complex pilon fractures (AO/OTA C3). We aim to report the outcomes of surgical treatment for 22 AO/OTA C3 pilon fracture cases between January 2015 and May 2017 and highlight some traps and tips. METHODS: Three patients underwent two-stage early plating on the posterior column through a posterolateral approach. The remaining 19 patients were treated with two-stage delayed plating on the posterior column: 11 patients were treated with a posterolateral approach, five patients with a modified posteromedial approach, and three patients with a single anterior approach. The reduction of the posterior column was evaluated according to the Burwell-Charnley's radiographic criteria, and functional outcomes were assessed using the American Orthopedic Foot and Ankle Society (AOFAS) scores. RESULTS: Posterior column malreduction occurred in five cases, including in one case that was re-adjusted immediately and in another case that was re-adjusted during a two-staged delayed operation. According to Burwell-Charnley's criteria, the satisfactory rate of fracture reduction was 81.8%. After 1 year, the mean AOFAS score was 81.9 (81.9 ± 9.9); the outcome was excellent in three (20.0%), good in nine (60.0%), and fair in three (20.0%). Excellent or good outcomes were noted in 12 patients (80.0%). CONCLUSIONS: The combined anterior and posterior approach is suggested in the second stage of plating so that the posterior column fragments can be re-adjusted intraoperatively, if necessary. Following these procedures, satisfactory reduction and recovery of good ankle function can be anticipated.