Comparison of the safety and efficacy of three superficial skin closure methods for multi-layer wound closure in total knee arthroplasty: a multicenter, prospective, randomized controlled trial.

BACKGROUND: Good wound healing is critical to infection prophylaxis and satisfactory rehabilitation in Total Knee Arthroplasty (TKA). Currently, two techniques, i.e., barbed continuous subcuticular suture without skin adhesive or combined use skin adhesive (n-butyl-2) are being used for superficial wound closure of TKA. While a new skin adhesive (2-octyl) with self-adhesive mesh has been employed as an alternative to conventional surgical skin closure in TKA, its superiority, especially in reducing wound complications and improving wound cosmetic outcomes has not been investigated. This study aimed to compare 2-octyl, n-butyl-2, and no skin adhesive in terms of safety and efficacy in TKA superficial wound closure. METHODS: We conducted a multicenter, prospective, randomized controlled study in 105 patients undergoing primary TKA between May 2022 and October 2023. Each patient's knee was randomized to receive 2-octyl, n-butyl-2, or no skin adhesive skin closure with all using barbed continuous sutures in deep tissue. Wounds were followed 1, 3, 5 days, 2, 6 weeks, and 3 months after surgery. Wound discharge, complications, cosmetic outcomes, patient satisfaction, and wound-related costs were compared among these three methods. RESULTS: Wound discharge was less in 2-octyl group and n-butyl-2 group than in non-adhesive group at 1 day, with the discharge only being less in 2-octyl group than in the non-adhesive group at day 3 and day 5 days (P < 0.05). There was no statistical difference in the incidence of other wound complications among the groups (P > 0.05). The 2-octyl group achieved better cosmetic effects than the other two groups in 6 weeks and 3 months (P < 0.05). Compared to the non-adhesive group, 2-octyl group scored higher in overall patient satisfaction score in 2 weeks and incurred lower costs (P < 0.05). CONCLUSIONS: Skin closure in TKA using 2-octyl adhesive material showed superiority when compared to no skin adhesive or n-butyl-2, in reducing wound discharge, improving the cosmetic outcomes, without increasing wound complications. In addition, the use of 2-octyl yielded better patient satisfaction and also was less costly compared to no skin adhesive. Our study exhibited that 2-octyl was a safe and effective wound closure technique for patients undergoing TKA. TRIAL REGISTRATION: This study has been registered at Clinical Trials. Gov (No. ChiCTR210046442).

ReadCurrent: a VDCNN-based tool for fast and accurate nanopore selective sequencing.

Nanopore selective sequencing allows the targeted sequencing of DNA of interest using computational approaches rather than experimental methods such as targeted multiplex polymerase chain reaction or hybridization capture. Compared to sequence-alignment strategies, deep learning (DL) models for classifying target and nontarget DNA provide large speed advantages. However, the relatively low accuracy of these DL-based tools hinders their application in nanopore selective sequencing. Here, we present a DL-based tool named ReadCurrent for nanopore selective sequencing, which takes electric currents as inputs. ReadCurrent employs a modified very deep convolutional neural network (VDCNN) architecture, enabling significantly lower computational costs for training and quicker inference compared to conventional VDCNN. We evaluated the performance of ReadCurrent across 10 nanopore sequencing datasets spanning human, yeasts, bacteria, and viruses. We observed that ReadCurrent achieved a mean accuracy of 98.57% for classification, outperforming four other DL-based selective sequencing methods. In experimental validation that selectively sequenced microbial DNA from human DNA, ReadCurrent achieved an enrichment ratio of 2.85, which was higher than the 2.7 ratio achieved by MinKNOW using the sequence-alignment strategy. In summary, ReadCurrent can rapidly classify target and nontarget DNA with high accuracy, providing an alternative in the toolbox for nanopore selective sequencing. ReadCurrent is available at https://github.com/Ming-Ni-Group/ReadCurrent.

A comprehensive adsorption and desorption study on the interaction of DNA oligonucleotides with TiO2 nanolayers.

The utilization of TiO2 nanolayers that possess excellent biocompatibility and physical properties in DNA sensing and sequencing remains largely to be explored. To examine their applicability in gene sequencing, a comprehensive study on the interaction of DNA oligonucleotides with TiO2 nanolayers was performed through adsorption and desorption experiments. TiO2 nanolayers with 10 nm thickness were fabricated via magnetron sputtering onto a 6-inch silicon wafer. A simple chip block method, validated via quartz crystal microbalance experiments with dissipation monitoring (QCM-D), was proposed to study the adsorption behaviors and interaction mechanisms under a variety of critical influencing factors, including DNA concentration, length, and type, adsorption time, pH, and metal ions. It is determined that the adsorption takes 2 h to reach saturation in the MES solution and the adsorption capacity is significantly enhanced by lowering the pH due to the isoelectric point being pH = 6 for TiO2. The adsorption percentages of nucleobases are largely similar in the MES solution while following 5T = 5G > 5C > 5A in HEPES buffer for an adsorption duration of 2.5 h. Through pre-adsorption experiments, it is deduced that DNA oligonucleotides are horizontally adsorbed on the nanolayer. This further demonstrates that mono-, di-, and tri-valent metal ions promote the adsorption, whereas Zn2+ has strong adsorption by inducing DNA condensation. Based on the desorption experiments, it is revealed that electrostatic force dominates the adsorption over van der Waals force and hydrogen bonds. The phosphate group is the main functional group for adsorption, and the adsorption strength increases with the length of the oligonucleotide. This study provides comprehensive data on the adsorption of DNA oligonucleotides onto TiO2 nanolayers and clarifies the interaction mechanisms therein, which will be valuable for applications of TiO2 in DNA-related applications.

Increase 68Ga-FAPI Uptake in Urogenital Tuberculosis.

ABSTRACT: Urogenital tuberculosis is one of common sites of extrapulmonary tuberculosis. A 60-year-old man with an elevated prostate-specific antigen level underwent multiparametric MRI, which revealed abnormal signals in the prostate. However, the 68Ga-PSMA PET/CT results were unrevealing. Subsequent 68Ga-FAPI PET/CT imaging revealed intense radioactivity uptake in the prostate and mild radioactivity uptake in the left kidney, which was eventually proven due to tuberculosis.

Novel ß-amyloid PET Imaging Study of [18F]92 in Patients with Cognitive Decline.

[18F]-4-((E)-(((E)-4-(2-(2-(2-Fluoroethoxy)ethoxy)ethoxy)benzylidene)-hydrazono)methyl)-N-methylaniline ([18F]92) is a novel positron emission tomography (PET) tracer previously reported to exhibit high binding affinity to aggregated ß-amyloid (Aß). This study aims to report a fully automated radiosynthesis procedure for [18F]92, explore its radioactive distribution in the brains of healthy subjects, and investigate its potential application value in the early diagnosis of Alzheimer's disease (AD). The fully automated radiosynthesis of [18F]92 was performed on the AllinOne module. Thirty one participants were recruited for this study. Dynamic [18F]92 PET imaging was conducted over 0-90 min period to assess time-activity curves (TAC) and standardized uptake value ratio (SUVR) curves in cognitively normal (CN) subjects. All participants were visually classified as either positive (+) or negative (-). Semiquantitative analyses of [18F]92 were performed by calculating SUVRs in different regions of interest. Furthermore, the study analyzed the relationships between global SUVR and plasma AD biomarkers, including Aß42, Aß40, P-tau181, and T-tau. The automated radiosynthesis of [18F]92 was completed within 50 min, yielding a radiochemical purity of greater than 95% and a radiochemical yield of 36 ± 3% (nondecay-corrected). Among the participants, 15 were estimated as Aß (-) and 16 as Aß (+). TACs indicated that [18F]92 rapidly crossed the blood-brain barrier within 10 min, followed by a rapid decrease, which then slowed down in the last 50-90 min. SUVR curves revealed that SUVR values stabilized around 60-70 min after injection and reached an equilibrium between 70 and 90 min, primarily in the cerebral cortex. SUVRs of Aß (+) participants were significantly higher than those of Aß (-) individuals within the cerebral cortex. In addition, Aß42 and the Aß42/Aß40 ratio exhibited negative correlations with global SUVR, while plasma P-tau181 and the P-tau181/T-tau ratio displayed positive correlations with global SUVR. [18F]92 exhibits excellent pharmacokinetic properties in the human brain and can be synthesized automatically on a large scale. [18F]92 is a promising and reliable radiotracer for estimating Aß pathology accumulation, providing valuable assistance in AD diagnosis and guiding clinical trials of therapeutic drugs.

Dual roles of CD11b+CD33+HLA-DR-/lowCD14- myeloid-derived suppressor cells with a granulocytic morphology following allogeneic hematopoietic stem cell transplantation: from inflammation promoters to immune suppressors within 90 days.

Introduction: Granulocytic myeloid-derived suppressor cells (G-MDSCs) show fast recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) constituting the major part of peripheral blood in the early phase. Although G-MDSCs mediate immune suppression through multiple mechanisms, they may also promote inflammation under specific conditions. Methods: G-MDSCs were isolated from 82 patients following allo-HSCT within 90 days after allo-HSCT, and their interactions with autologous CD3+ T-cells were examined. T-cell proliferation was assessed by flow cytometry following CFSE staining, while differentiation and interferon-γ secretion were characterized using chemokine receptor profiling and ELISpot assays, respectively. NK cell cytotoxicity was evaluated through co-culture with K562 cells. An aGVHD xenogeneic model in humanized mice was employed to study the in vivo effects of human leukocytes. Furthermore, transcriptional alterations in G-MDSCs were analyzed via RNA sequencing to investigate functional transitions. Results: G-MDSCs promoted inflammation in the early-stage, by facilitating cytokine secretion and proliferation of T cells, as well as their differentiation into pro-inflammatory T helper subsets. At day 28, patients with a higher number of G-MDSCs exhibited an increased risk of developing grades II-IV aGvHD. Besides, adoptive transfer of G-MDSCs from patients at day 28 into humanized mice exacerbated aGvHD. However, at day 90, G-MDSCs led to immunosuppression, characterized by upregulated expression of indoleamine 2,3-dioxygenase gene and interleukin-10 secretion, coupled with the inhibition of T cell proliferation. Furthermore, transcriptional analysis of G-MDSCs at day 28 and day 90 revealed that 1445 genes were differentially expressed. These genes were associated with various pathways, revealing the molecular signatures of early post-transplant differentiation in G-MDSCs. In addition, genes linked to the endoplasmic reticulum stress were upregulated in patients without aGvHD. The acquisition of immunosuppressive function by G-MDSCs may depend on the activation of CXCL2 and DERL1 genes. Conclusion: Our findings revealed the alteration in the immune characteristics of G-MDSCs within the first 90 days post-allo-HSCT. Moreover, the quantity of G-MDSCs at day 28 may serve as a predictive indicator for the development of aGvHD.

Formation of a planar biomimetic membrane with a novel zwitterionic polymer for nanopore sequencing.

Biological membranes containing transmembrane channels play a crucial role in numerous cellular processes, and mimicking of cell membranes has garnered significant interest in various biomedical applications, particularly nanopore sequencing technology, where remarkable progress has been made with nanopore membranes. Considering the fragility of biomimetic membranes formed by artificial lipids and the limited mimicry of those formed by common block copolymers, this study developed a novel amphiphilic polymer by covalently linking hydrophilic heads of phospholipids to the ends of hydrophobic poly(dimethyl siloxane) (PDMS) chains. The absence of hydrophilic blocks allowed for good control over the polydispersity of this polymer within a narrow range. The high flexibility of PDMS chains, combined with relatively uniform molecular weights, would confer enhanced stability and robustness to polymeric membranes. Dynamic light scattering measurements and microdroplet formation tests demonstrated good amphipathic properties of these novel polymers when maintaining an appropriate hydrophilic-hydrophobic ratio. Moreover, the high similarity between the hydrophilic heads and natural phospholipids makes this polymer more compatible with biomolecules. A successful protein insertion experiment confirmed both the stability of this polymeric membrane and its compatibility with membrane proteins. As a result, this novel amphiphilic polymer exhibits great potential for biomembrane mimicking and paves a new path for material design in biomedical applications.

Associations of CSF BACE1 with amyloid pathology, neurodegeneration, and cognition in Alzheimer's disease.

Β-site amyloid precursor protein (APP) cleaving enzyme (BACE1) is a crucial protease in the production of amyloid-ß (Aß) in Alzheimer's disease (AD) patients. However, the side effects observed in clinical trials of BACE1 inhibitors, including reduction in brain volume and cognitive worsening, suggest that the exact role of BACE1 in AD pathology is not fully understood. To further investigate this, we examined cerebrospinal fluid (CSF) levels of BACE1 and its cleaved product sAPPß that reflects BACE1 activity in the China Aging and Neurodegenerative Disorder Initiative cohort. We found significant correlations between CSF BACE1 or sAPPß levels and CSF Aß40, Aß42, and Aß42/Aß40 ratio, but not with amyloid deposition detected by 18F-Florbetapir PET. Additionally, CSF BACE1 and sAPPß levels were positively associated with cortical thickness in multiple brain regions, and higher levels of sAPPß were linked to increased cortical glucose metabolism in frontal and supramarginal areas. Interestingly, individuals with higher baseline levels of CSF BACE1 exhibited slower rates of brain volume reduction and cognitive worsening over time. This suggests that increased levels and activity of BACE1 may not be the determining factor for amyloid deposition, but instead, may be associated with increased neuronal activity and potentially providing protection against neurodegeneration in AD.

Cerebrospinal Fluid Proteomics Identifies Potential Biomarkers for Early-Onset Alzheimer's Disease.

Background: Early-onset Alzheimer's disease (EOAD) exhibits a notable degree of heterogeneity as compared to late-onset Alzheimer's disease (LOAD). The proteins and pathways contributing to the pathophysiology of EOAD still need to be completed and elucidated. Objective: Using correlation network analysis and machine learning to analyze cerebrospinal fluid (CSF) proteomics data to identify potential biomarkers and pathways associated with EOAD. Methods: We employed mass spectrometry to conduct CSF proteomic analysis using the data-independent acquisition method in a Chinese cohort of 139 CSF samples, including 40 individuals with normal cognition (CN), 61 patients with EOAD, and 38 patients with LOAD. Correlation network analysis of differentially expressed proteins was performed to identify EOAD-associated pathways. Machine learning assisted in identifying crucial proteins differentiating EOAD. We validated the results in an Western cohort and examined the proteins expression by enzyme-linked immunosorbent assay (ELISA) in additional 9 EOAD, 9 LOAD, and 9 CN samples from our cohort. Results: We quantified 2,168 CSF proteins. Following adjustment for age and sex, EOAD exhibited a significantly greater number of differentially expressed proteins than LOAD compared to CN. Additionally, our data indicates that EOAD may exhibit more pronounced synaptic dysfunction than LOAD. Three potential biomarkers for EOAD were identified: SH3BGRL3, LRP8, and LY6 H, of which SH3BGRL3 also accurately classified EOAD in the Western cohort. LY6 H reduction was confirmed via ELISA, which was consistent with our proteomic results. Conclusions: This study provides a comprehensive profile of the CSF proteome in EOAD and identifies three potential EOAD biomarker proteins.

Nanopore sequencing of forensic short tandem repeats using QNome of Qitan Technology.

Devices of nanopore sequencing can be highly portable and of low cost. Thus, nanopore sequencing is promising in in-field forensic applications. Previous investigations have demonstrated that nanopore sequencing is feasible for genotyping forensic short tandem repeats (STRs) by using sequencers of Oxford Nanopore Technologies. Recently, Qitan Technology launched a new portable nanopore sequencer and became the second supplier in the world. Here, for the first time, we assess the QNome (QNome-3841) for its accuracy in nanopore sequencing of STRs and compare with MinION (MinION Mk1B). We profile 54 STRs of 21 unrelated individuals and 2800M standard DNA. The overall accuracy for diploid STRs and haploid STRs were 53.5% (378 of 706) and 82.7% (134 of 162), respectively, by using QNome. The accuracies were remarkably lower than those of MinION (diploid STRs, 84.5%; haploid, 90.7%), with a similar amount of sequencing data and identical bioinformatics analysis. Although it was not reliable for diploid STRs typing by using QNome, the haploid STRs were consistently correctly typed. The majority of errors (58.8%) in QNome-based STR typing were one-repeat deviations of repeat units in the error from true allele, related with homopolymers in repeats of STRs.

CodonBERT: a BERT-based architecture tailored for codon optimization using the cross-attention mechanism.

MOTIVATION: Due to the varying delivery methods of mRNA vaccines, codon optimization plays a critical role in vaccine design to improve the stability and expression of proteins in specific tissues. Considering the many-to-one relationship between synonymous codons and amino acids, the number of mRNA sequences encoding the same amino acid sequence could be enormous. Finding stable and highly expressed mRNA sequences from the vast sequence space using in silico methods can generally be viewed as a path-search problem or a machine translation problem. However, current deep learning-based methods inspired by machine translation may have some limitations, such as recurrent neural networks, which have a weak ability to capture the long-term dependencies of codon preferences. RESULTS: We develop a BERT-based architecture that uses the cross-attention mechanism for codon optimization. In CodonBERT, the codon sequence is randomly masked with each codon serving as a key and a value. In the meantime, the amino acid sequence is used as the query. CodonBERT was trained on high-expression transcripts from Human Protein Atlas mixed with different proportions of high codon adaptation index codon sequences. The result showed that CodonBERT can effectively capture the long-term dependencies between codons and amino acids, suggesting that it can be used as a customized training framework for specific optimization targets. AVAILABILITY AND IMPLEMENTATION: CodonBERT is freely available on https://github.com/FPPGroup/CodonBERT.

DeepSS2GO: protein function prediction from secondary structure.

Predicting protein function is crucial for understanding biological life processes, preventing diseases and developing new drug targets. In recent years, methods based on sequence, structure and biological networks for protein function annotation have been extensively researched. Although obtaining a protein in three-dimensional structure through experimental or computational methods enhances the accuracy of function prediction, the sheer volume of proteins sequenced by high-throughput technologies presents a significant challenge. To address this issue, we introduce a deep neural network model DeepSS2GO (Secondary Structure to Gene Ontology). It is a predictor incorporating secondary structure features along with primary sequence and homology information. The algorithm expertly combines the speed of sequence-based information with the accuracy of structure-based features while streamlining the redundant data in primary sequences and bypassing the time-consuming challenges of tertiary structure analysis. The results show that the prediction performance surpasses state-of-the-art algorithms. It has the ability to predict key functions by effectively utilizing secondary structure information, rather than broadly predicting general Gene Ontology terms. Additionally, DeepSS2GO predicts five times faster than advanced algorithms, making it highly applicable to massive sequencing data. The source code and trained models are available at https://github.com/orca233/DeepSS2GO.

Terf2ip deficiency accelerates non-alcoholic steatohepatitis through regulating lipophagy and fatty acid oxidation via Sirt1/AMPK pathway.

BACKGROUND & AIMS: Our previous study has demonstrated that Telomeric repeat-binding factor 2-interacting protein 1(Terf2ip), played an important role in hepatic ischemia reperfusion injury. This study is aimed to explore the function and mechanism of Terf2ip in non-alcoholic steatohepatitis (NASH). METHODS: The expression of Terf2ip was detected in liver tissue samples obtained from patients diagnosed with NASH. Mice NASH models were constructed by fed with high-fat diet (HFD) or methionine/choline deficient diet (MCD) in Terf2ip knockout and wild type (WT) mice. To further investigate the role of Terf2ip in NASH, adeno-associated viruses (AAV)-Terf2ip was administrated to mice. RESULTS: We observed a significant down-regulation of Terf2ip levels in the livers of NASH patients and mice NASH models. Terf2ip deficiency was associated with an exacerbation of hepatic steatosis in mice under HFD or MCD. Additionally, Terf2ip deficiency impaired lipophagy and fatty acid oxidation (FAO) in NASH models. Mechanically, we discovered that Terf2ip bound to the promoter region of Sirt1 to regulate Sirt1/AMPK pathway activation. As a result, Terf2ip deficiency was shown to inhibit lipophagy through the AMPK pathway, while the activation of Sirt1 alleviated steatohepatitis in the livers of mice. Finally, re-expression of Terf2ip in hepatocyes alleviated liver steatosis, inflammation, and restored lipophagy. CONCLUSIONS: These results revealed that Terf2ip played a protective role in the progression of NASH through regulating lipophagy and FAO by binding to Sirt1 promoter. Our findings provided a potential therapeutic target for the treatment of NASH.

Biomechanical role of bone grafting for calcaneal fracture fixation in the presence of bone defect: A finite element analysis.

BACKGROUND: The purpose of this study was to compare the biomechanical stress and stability of calcaneal fixations with and without bone defect, before and after bone grafting, through a computational approach. METHODS: A finite element model of foot-ankle complex was reconstructed, impoverished with a Sanders III calcaneal fracture without bone defect and with moderate and severe bone defects. Plate fixations with and without bone grafting were introduced with walking stance simulated. The stress and fragment displacement of the calcaneus were evaluated. FINDINGS: Moderate and severe defect increased the calcaneus stress by 16.11% and 32.51%, respectively and subsequently decreased by 10.76% and 20.78% after bone grafting. The total displacement was increased by 3.99% and 24.26%, respectively by moderate and severe defect, while that of posterior joint facet displacement was 86.66% and 104.44%. The former was decreased by 25.73% and 35.96% after grafting, while that of the latter was reduced by 88.09% and 84.78% for moderate and severe defect, respectively. INTERPRETATION: Our finite element prediction supported that bone grafting for fixation could enhance the stability and reduce the risk of secondary stress fracture in cases of bone defect in calcaneal fracture.

A benchmark for evaluation of structure-based online tools for antibody-antigen binding affinity.

The prediction of binding affinity changes caused by missense mutations can elucidate antigen-antibody interactions. A few accessible structure-based online computational tools have been proposed. However, selecting suitable software for particular research is challenging, especially research on the SARS-CoV-2 spike protein with antibodies. Therefore, benchmarking of the mutation-diverse SARS-CoV-2 datasets is critical. Here, we collected the datasets including 1216 variants about the changes in binding affinity of antigens from 22 complexes for SARS-CoV-2 S proteins and 22 monoclonal antibodies as well as applied them to evaluate the performance of seven binding affinity prediction tools. The tested tools' Pearson correlations between predicted and measured changes in binding affinity were between -0.158 and 0.657, while accuracy in classification tasks on predicting increasing or decreasing affinity ranged from 0.444 to 0.834. These tools performed relatively better on predicting single mutations, especially at epitope sites, whereas poor performance on extremely decreasing affinity. The tested tools were relatively insensitive to the experimental techniques used to obtain structures of complexes. In summary, we constructed a list of datasets and evaluated a range of structure-based online prediction tools that will explicate relevant processes of antigen-antibody interactions and enhance the computational design of therapeutic monoclonal antibodies.

Non-traumatic osteonecrosis of the femoral head induced by steroid and alcohol exposure is associated with intestinal flora alterations and metabolomic profiles.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a severe disease that primarily affects the middle-aged population, imposing a significant economic and social burden. Recent research has linked the progression of non-traumatic osteonecrosis of the femoral head (NONFH) to the composition of the gut microbiota. Steroids and alcohol are considered major contributing factors. However, the relationship between NONFH caused by two etiologies and the microbiota remains unclear. In this study, we examined the gut microbiota and fecal metabolic phenotypes of two groups of patients, and analyzed potential differences in the pathogenic mechanisms from both the microbial and metabolic perspectives. METHODS: Utilizing fecal samples from 68 NONFH patients (32 steroid-induced, 36 alcohol-induced), high-throughput 16 S rDNA sequencing and liquid chromatography with tandem mass spectrometry (LC-MS/MS) metabolomics analyses were conducted. Univariate and multivariate analyses were applied to the omics data, employing linear discriminant analysis effect size to identify potential biomarkers. Additionally, functional annotation of differential metabolites and associated pathways was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Subsequently, Spearman correlation analysis was employed to assess the potential correlations between differential gut microbiota and metabolites. RESULTS: High-throughput 16 S rDNA sequencing revealed significant gut microbial differences. At the genus level, the alcohol group had higher Lactobacillus and Roseburia, while the steroid group had more Megasphaera and Akkermansia. LC-MS/MS metabolomic analysis indicates significant differences in fecal metabolites between steroid- and alcohol-induced ONFH patients. Alcohol-induced ONFH (AONFH) showed elevated levels of L-Lysine and Oxoglutaric acid, while steroid-induced ONFH(SONFH) had increased Gluconic acid and Phosphoric acid. KEGG annotation revealed 10 pathways with metabolite differences between AONFH and SONFH patients. Correlation analysis revealed the association between differential gut flora and differential metabolites. CONCLUSIONS: Our results suggest that hormones and alcohol can induce changes in the gut microbiota, leading to alterations in fecal metabolites. These changes, driven by different pathways, contribute to the progression of the disease. The study opens new research directions for understanding the pathogenic mechanisms of hormone- or alcohol-induced NONFH, suggesting that differentiated preventive and therapeutic approaches may be needed for NONFH caused by different triggers.

VENOARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION REDUCES MYOCARDIAL AND MITOCHONDRIAL DAMAGE IN ACUTE MYOCARDIAL INFARCTION.

ABSTRACT: Background: Myocardial infarction (MI) is a common cardiovascular disease with a high fatality rate once accompanied by cardiogenic shock. The efficacy of extracorporeal membrane oxygenation (ECMO) in treating MI is controversial. Methods: MI was induced by ligating the left anterior descending artery (LAD) in adult male rats. Groups were defined as follows: MI group, reperfusion for 90 min after 30 min of LAD occlusion; MI + ECMO group, reperfusion and ECMO were performed for 90 min immediately after 30 min of LAD occlusion; prolonged MI + ECMO group, ECMO was used immediately after 30 min of occlusion with persistent occlusion of the LAD for an additional 30 min, followed by 90 min of reperfusion. The myocardial infarct size and mitochondrial morphology and function data were collected and compared of each group. Results: The ECMO groups had a smaller myocardial infarct size and larger percentage ejection fraction. Compared with the prolonged MI + ECMO group, the immediate reperfusion group had a lower percentage of infarct size (63.28% vs. 17.97% vs. 31.22%, MI vs. MI + ECMO vs. prolonged MI + ECMO). Mitochondria isolated from the ischemic zone showed an intact mitochondrial structure, including fewer voids and broken cristae, and preserved activity of mitochondrial complex II and complex IV in ECMO groups. Conclusions: ECMO support in MI can reduce myocardial injury despite delayed coronary reperfusion.

Soil properties constrain forest understory plant distributions along an elevation gradient.

Projections of spatial biodiversity dynamics under climate warming are often based on models including only climate variables, and when non-climatic factors (e.g. soil) are included, data are often at much coarser spatial resolutions than those experienced by plants. Field studies along elevation gradients permit the gathering of detailed soil data, while still covering a wide climatic gradient. Here, an intensive field survey of four spring forest herbs along an elevation gradient showed that soil properties had substantial impacts on the occurrence/abundance of all species, and that soil effects were more pronounced at higher elevations. For Trillium erectum and Claytonia caroliniana, very infrequent occurrences at high elevation were strongly associated with rare microsites with high pH or nutrients. In a seven-year transplant experiment with T. erectum, we found that individuals grew to much smaller sizes at high than low elevation, suggesting that environmental factors rather than dispersal limitation constrain the species' upper range limit, despite substantial warming in recent decades. Our study demonstrates that soil factors interact strongly with climate to determine plant range limits along climatic gradients. Unsuitable soils for plants at high elevations or latitudes may represent an important constraint on future plant migration and biodiversity change. This article is part of the theme issue 'Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere'.

Effective dose of intranasal remimazolam for preoperative sedation in preschool children: a dose-finding study using Dixon's up-and-down method.

Background: Most preschool children are distressed during anesthesia induction. While current pharmacological methods are useful, there is a need for further optimization to an "ideal" standard. Remimazolam is an ultra-short-acting benzodiazepine, and intranasal remimazolam for pre-induction sedation may be promising. Methods: This study included 32 preschool children who underwent short and minor surgery between October 2022 and January 2023. After pretreatment with lidocaine, remimazolam was administered to both nostrils using a mucosal atomizer device. The University of Michigan Sedation Score (UMSS) was assessed for sedation 6, 9, 12, 15, and 20 min after intranasal atomization. We used Dixon's up-and-down method, and probit and isotonic regressions to determine the 50% effective dose (ED50) and 95% effective dose (ED95) of intranasal remimazolam for pre-induction sedation. Results: Twenty-nine pediatric patients were included in the final analysis. The ED50 and ED95 of intranasal remimazolam for successful pre-induction sedation, when processed via probit analysis, were 0.65 (95% confidence interval [CI], 0.59-0.71) and 0.78 mg/kg (95% CI, 0.72-1.07), respectively. In contrast, when processed by isotonic regression, they were 0.65 (95% CI: 0.58-0.72 mg/kg) and 0.78 mg/kg (95% CI: 0.69-1.08 mg/kg), respectively. At 6 min after intranasal remimazolam treatment, 81.2% (13/16) of "positive" participants were successfully sedated with a UMSS ≧ 1. All the "positive" participants were successfully sedated within 9 min. Conclusion: Intranasal remimazolam is feasible for preschool children with a short onset time. For successful pre-induction sedation, the ED50 and ED95 of intranasal remimazolam were 0.65 and 0.78 mg/kg, respectively.

Deep Learning Imaging Reconstruction Algorithm for Carotid Dual Energy CT Angiography: Opportunistic Evaluation of Cervical Intervertebral Discs-A Preliminary Study.

Thus, the aim of this study is to evaluate the performance of deep learning imaging reconstruction (DLIR) algorithm in different image sets derived from carotid dual-energy computed tomography angiography (DECTA) for evaluating cervical intervertebral discs (IVDs) and compare them with those reconstructed using adaptive statistical iterative reconstruction-Veo (ASiR-V). Forty-two patients who underwent carotid DECTA were included in this retrospective analysis. Three types of image sets (70 keV, water-iodine, and water-calcium) were reconstructed using 50% ASiR-V and DLIR at medium and high levels (DLIR-M and DLIR-H). The diagnostic acceptability and conspicuity of IVDs were assessed using a 5-point scale. Hounsfield Units (HU) and water concentration (WC) values of the IVDs; standard deviation (SD); and coefficient of variation (CV) were calculated. Measurement parameters of the 50% ASIR-V, DLIR-M, and DLIR-H groups were compared. The DLIR-H group showed higher scores for diagnostic acceptability and conspicuity, as well as lower SD values for HU and WC than the ASiR-V and DLIR-M groups for the 70 keV and water-iodine image sets (all p < .001). However, there was no significant difference in scores and SD among the three groups for the water-calcium image set (all p > .005). The water-calcium image set showed better diagnostic accuracy for evaluating IVDs compared to the other image sets. The inter-rater agreement using ASiR-V, DLIR-M, and DLIR-H was good for the 70 keV image set, excellent for the water-iodine and water-calcium image sets. DLIR improved the visualization of IVDs in the 70 keV and water-iodine image sets. However, its improvement on color-coded water-calcium image set was limited.