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Abstract Objective Data imbalance is a pervasive issue in medical data mining, often leading to biased and unreliable predictive models. This study aims to address the urgent need for effective strategies to mitigate the impact of data imbalance on classification models. We focus on quantifying the effects of different imbalance degrees and sample sizes on model performance, identifying optimal cut-off values, and evaluating the efficacy of various methods to enhance model accuracy in highly imbalanced and small sample size scenarios. Methods We collected medical records of patients receiving assisted reproductive treatment in a reproductive medicine center. Random forest was used to screen the key variables for the prediction target. Various datasets with different imbalance degrees and sample sizes were constructed to compare the classification performance of logistic regression models. Metrics such as AUC, G-mean, F1-Score, Accuracy, Recall, and Precision were used for evaluation. Four imbalance treatment methods (SMOTE, ADASYN, OSS, and CNN) were applied to datasets with low positive rates and small sample sizes to assess their effectiveness. Results The logistic model’s performance was low when the positive rate was below 10% but stabilized beyond this threshold. Similarly, sample sizes below 1200 yielded poor results, with improvement seen above this threshold. For robustness, the optimal cut-offs for positive rate and sample size were identified as 15% and 1500, respectively. SMOTE and ADASYN oversampling significantly improved classification performance in datasets with low positive rates and small sample sizes. Conclusions The study identifies a positive rate of 15% and a sample size of 1500 as optimal cut-offs for stable logistic model performance. For datasets with low positive rates and small sample sizes, SMOTE and ADASYN are recommended to improve balance and model accuracy.

The transmission network is generally considered as three-phase balanced, while the consideration of three-phase unbalance is mainly on distribution networks. However, with the increasingly interconnection of renewable energy, such as wind energy, onto transmission networks, non-adoption of commutation long transmission lines usually results in unbalanced line parameters. Therefore, developing reliable three-phase power flow algorithms for transmission and distribution (T&D) systems becomes more and more important for the reliable and safe operation of emerging power systems. Among the many three-phase power flow algorithms, Newton Raphson method (NRM) and its variants occupy a large share, due to their ability in dealing with multiple sources and looped sub-networks. However, they are sensitive to the initial value, and can hardly ensure convergence to a physically meaningful solution with improper initial values, especially for three-phase unbalanced system. To this end, a general three-phase power flow method for T&D systems is proposed based on the holomorphic embedding method (HEM), and the advantages of the proposed method compared with traditional NRM in solving the power flow problem to a physically meaningful solution are theoretically analyzed. Based on the IEEE 33 system, the modified IEEE 123 system, and a regional power grid in China, it is verified that the proposed method has the advantages of high computational efficiency, reliable converging ability, and independence to the initial value.

Abstract Background Rainbow trout (Oncorhynchus mykiss) is becoming popular with the increased demand for fish protein. However, the limited resources and expense of fish meal and oil have become restrictive factors for the development of the rainbow trout related industry. To solve this problem, plant-derived proteins and vegetable oils have been developed as alternative resources. The present study focuses on evaluating the effects of two experimental diets, FMR (fish meal replaced with plant-derived protein) and FOR (fish oil replaced with rapeseed oil), through the alteration of the gut microbiota in triploid rainbow trout. The commercial diet was used in the control group (FOM). Results Amplicon sequencing of the 16S and 18S rRNA genes was used to assess the changes in gut bacteria and fungi. Our analysis suggested that the α-diversity of both bacteria and fungi decreased significantly in the FMR and FOR groups, and β-diversity was distinct between FOM/FMR and FOM/FOR based on principal coordinate analysis (PCoA). The abundance of the Planctomycetota phylum increased significantly in the FMR group, while that of Firmicutes and Bacteroidetes decreased. We also found that the fungal phylum Ascomycota was significantly increased in the FMR and FOR groups. At the genus level, we found that the abundance of Citrobacter was the lowest and that of pathogenic Schlesneria, Brevundimonas, and Mycoplasma was highest in the FMR and FOR groups. Meanwhile, the pathogenic fungal genera Verticillium and Aspergillus were highest in the FMR and FOR groups. Furthermore, canonical correspondence analysis (CCA) and network analysis suggested that the relatively low-abundance genera, including the beneficial bacteria Methylobacterium, Enterococcus, Clostridium, Exiguobacterium, Sphingomonas and Bacteroides and the fungi Papiliotrema, Preussia, and Stachybotrys, were positively correlated with plant protein or rapeseed oil. There were more modules that had the above beneficial genera as the hub nodes in the FMR and FOR groups. Conclusions Our study suggested that the FMR and FOR diets could affect the gut microbiome in rainbow trout, which might offset the effects of the dominant and pathogenic microbial genera. This could be the underlying mechanism of explaining why no significant difference was observed in body weight between the different groups.

Background: The synergistic effects of antiangiogenic inhibitor bevacizumab and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) therapy were encouraging in patients with EGFR-mutant advanced NSCLC, though some controversy remains. The specific subgroup of patients who might benefit most from the EGFR-TKI and bevacizumab combination therapy is yet to be determined.Methods: Randomized clinical trials (RCTs) that had compared the clinical efficacy of EGFR-TKI and bevacizumab combination therapy with EGFR-TKI monotherapy in treating EGFR-mutant advanced NSCLC patients published before 23 December 2022 were searched in the Cochrane, PubMed and Embase. We performed a meta-analysis for the overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events with a grade equal or more than 3 (grade≥3 TRAEs). Subgroup analyses of PFS and OS stratified by clinical characteristics and treatment were conducted.Results: We included 10 RCTs involving 1520 patients. Compared with EGFR-TKI monotherapy, addition of bevacizumab to EGFR-TKI resulted in a significantly higher PFS (hazard ratio (HR) = 0.74, 95% confidence interval (95% CI): 0.62–0.87)) and ORR (risk ratio (RR) = 1.07, 95% CI: 1.01–1.13). However, no significant difference in OS (HR = 0.96, 95% CI: 0.83–1.12) was noticed. Patients with EGFR-mutant advanced NSCLC receiving combination therapy showed PFS improvement regardless of gender (male or female), Eastern Cooperative Oncology Group performance status (0 or 1), baseline central nervous system (CNS) metastasis (presence or absence) and EGFR mutation type (19del or 21L858R). Subgroup analyses showed that, with the treatment of bevacizumab and EGFR-TKI, patients who ever smoked achieved significantly better OS and PFS benefits (HR = 0.68, 95% CI: 0.48–0.95; HR = 0.59, 95% CI: 0.46–0.74, respectively), and those aged

In this work, we proposed a facile one-pot pyrolysis method to conveniently manufacture lignin-derived carbon materials with graded porous construction for use in supercapacitors. The renewable lignin was selected as precursor, while the potassium citrate was used as a pore-forming agent. The properties of the prepared lignin-derived carbon (LAC) and the performance for supercapacitor application were thoroughly evaluated. The LAC at optimal preparation conditions shows a layered porous structure with a large specific surface area of 3174 cm2 g−1 and pore volume of 2.796 cm3 g−1, where the specific capacitance reach to 241 F g−1 at 1 A g−1 scan rate in 6 M KOH electrolyte solution. At the same time, the specific capacitance remains at 220 F g−1 even at an excessive scan velocity of 20 A g−1, while the capacitance retention is still close to 91.3%. The capacitance retention rate is stable above 95% after 10,000 charge/discharge cycles, which shows the desired long-time stability. All these results demonstrate the outstanding properties of the new prepared LAC material and the considerable application potential in the field of electrical energy storage.

Hydrogen has been used to suppress tumor growth with considerable efficacy. Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration. We have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based biomaterials. However, the underlying mechanism of hydrogen's role in cancer treatment remains ambiguous. Here, we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based biomaterials. We find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins, as demonstrated by the in vitro RNA sequencing and protein expression analysis. Then, the P53 proteins disrupt the membrane potential of mitochondria, activate autophagy, suppress the reactive oxygen species in cancer cells, and finally result in tumor suppression. The anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a mouse. We also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2 μL/mm3 per day, which is much lower than that required for hydrogen inhalation. Taken together, these findings reveal the release of H2 from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway, which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.

Magnesium alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. Magnesium has been proven to promote distraction osteogenesis. However, its mechanism of promoting distraction osteogenesis is not thoroughly studied. In this work, a high-purity magnesium pin developed and applied in rat femur distraction osteogenesis. Mechanical test, radiological and histological analysis suggested that high-purity magnesium pin can promote distraction osteogenesis and shorten the consolidation time. Further RNA sequencing investigation found that alternative Wnt signaling was activated. In further bioinformatics analysis, it was found that the Hedgehog pathway is the upstream signaling pathway of the alternative Wnt pathway. We found that Ptch protein is a potential target of magnesium and verified by molecular dynamics that magnesium ions can bind to Ptch protein. In conclusion, HP Mg implants have the potential to enhance bone consolidation in the DO application, and this process might be via regulating Ptch protein activating Hedgehog-alternative Wnt signaling.

Abstract Background Surfactin, a representative biosurfactant of lipopeptide mainly produced by Bacillus subtilis, consists of a cyclic heptapeptide linked to a β-hydroxy fatty acid chain. The functional activity of surfactin is closely related to the length and isomerism of the fatty acid chain. Results In this study, the fatty acid precursor supply pathway in Bacillus subtilis 168 for surfactin production was strengthened through two steps. Firstly, pathways competing for the precursors were eliminated with inactivation of pps and pks. Secondly, the plant medium-chain acyl-carrier protein (ACP) thioesterase (BTE) from Umbellularia californica was overexpressed. As a result, the surfactin titer after 24 h of cultivation improved by 34%, and the production rate increased from 0.112 to 0.177 g/L/h. The isoforms identified by RP-HPLC and GC–MS showed that the proportion of nC14-surfactin increased 6.4 times compared to the control strain. A comparison of further properties revealed that the product with more nC14-surfactin had higher surface activity and better performance in oil-washing. Finally, the product with more nC14-surfactin isoform had a higher hydrocarbon-emulsification index, and it increased the water-wettability of the oil-saturated silicate surface. Conclusion The obtained results identified that enhancing the supply of fatty acid precursor is very essential for the synthesis of surfactin. At the same time, this study also proved that thioesterase BTE can promote the production of nC14-surfactin and experimentally demonstrated its higher surface activity and better performance in oil-washing. These results are of great significance for the MEOR application of surfactin. Graphic abstract

Cellulose sponge was proposed to an attractive bio-absorbent owing to its highly efficient, low-cost, biodegradable, and renewable sourcing. In this work, the wasted cotton linter as raw materials, the highly porous and lightweight cellulose sponges were synthesized via a facile chemical crosslinking and freeze-drying process. The resultant cellulose sponge (CA) exhibited an interconnected three-dimensional porous structure through crosslinked with N,N′-methylene bisacrylamide (MBA), which was beneficial to remove organic dyestuffs. The effects of various factors including solution pH, contact time, initial dye concentration, and ionic strength on the adsorption behavior were investigated in detail. Herein, Langmuir isotherm models were selected to determine the adsorption capacity, and the maximum theoretical adsorption capacity for Methylene blue (MB) and Crystal violet (CV) was 123.46 and 76.63 mg/g, respectively. Particularly, the results of kinetic and thermodynamic tests showed that the adsorption performance was a spontaneous endothermic reaction and the adsorption process followed the pseudo-second-order kinetic. Furthermore, cellulose sponges could maintain maximum adsorption capacity even after twelve cycles. Therefore, the eco-friendly cellulose sponge would be a promising adsorbent for effective wastewater treatment.

Recently, the chemical conversion of the greenhouse gas CO2 into value-added methanol has been of great interest. To address this issue, ZnO nanorods were synthesized by a facile microwave assisted technique and selected as support in Cu/ZnO catalyst. Herein, structure-activity relationship of the as-prepared catalysts in CO2 hydrogenation to methanol were elucidated in detail using different characterization technique including N2 physisorption, XRD, TPR, TEM, XPS and insitu DRIFTS (CO chemisorption) etc. Interestingly, rodlike ZnO hosted the highly dispersed Cu species, stronger Cu-support interaction at the interface in comparison with another reference CuZn-C sample, which was supported on commercial ZnO. In particular, EPR and XPS analysis evidenced the direct electron transfer from ZnO support to Cu species in CuZn-R, thereby facilitating the formation of O vacancies. These positive factors could provide the extremely active sites for CO2 hydrogenation and be correlated to the better catalytic activity. Indeed, the calculated TOFmethanol for CuZn-R was approximately ten times larger than that of CuZn-C sample. The results implied that the morphology structure of ZnO support, which could induce various crystal planes and amounts of defects and/or imperfections, possessed a critical role on the catalytic performance. This finding might shed light on the design of efficient catalysts for catalytic conversion of the undesirable CO2. Keywords: Morphology, Cu/ZnO, CO2 hydrogenation, Methanol, Synergy

Introduction: Liver fibrosis staging is of great importance for reducing unnecessary injuries and prompting treatment in chronic viral hepatitis B patients. Liver biopsy is not suitable to act a screening method although it is a gold standard because of various shortcomings. This study aimed to establish a predictive nomogram as a convenient tool to effectively identify potential patients with different stages of liver fibrosis for patients with chronic hepatitis B.Methods: A nomogram for multinomial model was developed in a training set to calculate the probability for each stage of fibrosis and tested in a validation set. Fibrosis stages were subgrouped as followed: severe fibrosis/cirrhosis (F3–F4), moderate fibrosis (F2), and nil-mild fibrosis (F0–F1). The indicators were demographic characteristics and biochemical indicators of patients. Continuous indicators were divided into several groups according to the optimal candidate value generated by the decision tree.Results: This study recruited 964 HBV patients undergoing percutaneous liver biopsy. The multinomial model with 10 indicators was transformed into the final nomogram. The calibration plot showed a good agreement between nomogram-predicted and observed probability of different fibrosis stages. Areas under the receiver operating characteristics (AUROCs) for severe fibrosis/cirrhosis were 0.809 for training set and 0.879 for validation set. For moderate fibrosis, the AUROCs were 0.75 and 0.781. For nil-mild fibrosis, the AUROCs were 0.792 and 0.843. All the results above showed great predictive performance in predicting the stage of fibrosis by our nomogram.Conclusion: Our model demonstrated good discrimination and extensibility in internal and external validation. The proposed nomogram in this study resulted in great reliability and it can be widely used as a convenient and efficient way.

Chronic refractory wounds are one of the most serious complications of diabetes, and the effects of common treatments are limited. Chiral hydrogel combined with dimethyloxalyglycine (DMOG) as a dressing is a promising strategy for the treatment of chronic wounds. In this research, we have developed a DMOG-loaded supramolecular chiral amino-acid-derivative hydrogel for wound dressings for full-thickness skin regeneration of chronic wounds. The properties of the materials, the ability of sustained release drugs, and the ability to promote angiogenesis were tested in vitro, and the regeneration rate and repair ability of full-thickness skin were tested in vivo. The chiral hydrogel had the ability to release drugs slowly. It can effectively promote cell migration and angiogenesis in vitro, and promote full-thickness skin regeneration and angiogenesis in vivo. This work offers a new approach for repairing chronic wounds completely through a supramolecular chiral hydrogel loaded with DMOG.

Two pore channels (TPCs) are implicated in vesicle trafficking, virus infection, and autophagy regulation. As Na+- or Ca2+-permeable channels, TPCs have been reported to be activated by NAADP, PI(3,5)P2, and/or high voltage. However, a comparative study on the function and regulation of the three mammalian TPC subtypes is currently lacking. Here, we used the electrophysiological recording of enlarged endolysosome vacuoles, inside-out and outside-out membrane patches to examine the three TPCs of rabbit (Oryctolagus cuniculus, or Oc) heterologously expressed in HEK293 cells. While PI(3,5)P2 evoked Na+ currents with a potency order of OcTPC1 > OcTPC3 > OcTPC2, only OcTPC2 displayed a strict dependence on PI(3,5)P2. Both OcTPC1 and OcTPC3 were activatable by PI3P and OcTPC3 was also activated by additional phosphoinositide species. While OcTPC2 was voltage-independent, OcTPC1 and OcTPC3 showed voltage dependence with OcTPC3 depending on high positive voltages. Finally, while OcTPC2 preferred a luminal pH of 4.6–6.0 in endolysosomes, OcTPC1 was strongly inhibited by extracytosolic pH 5.0 in both voltage-dependent and -independent manners, and OcTPC3 was inhibited by pH 6.0 but potentiated by pH 8.0. Thus, the three OcTPCs form phosphoinositide-activated Na+ channels with different ligand selectivity, voltage dependence, and extracytosolic pH sensitivity, which likely are optimally tuned for function in specific endolysosomal populations.

Background: Non-small cell lung cancer (NSCLC) is the most common malignancy worldwide. MiR-199a-5p has been reported to play important roles in multiple tumors, inclusive of NSCLC. However, little is definitively known pertaining to its explicit mechanism of action in NSCLC.Methods: The expressions of miR-199a-5p and hypoxia-inducible factor-1α (HIF-1α) mRNA were quantified employing qRT-PCR. H1299 and A549 cells were transiently transfected with miR-199a-5p mimics or inhibitors. Then, CCK-8 assays, flow cytometry analysis, and Transwell assay were performed for detecting cell proliferation, cell cycle, apoptosis, migration, and invasion of NSCLC cells, respectively. HIF-1α, signal transducer and activator of transcription 3 (STAT3), and p-STAT3 expressions were detected via Western blotting. Bioinformatic analysis and dual-luciferase assay were performed to investigate the interactions among miR-199a-5p, HIF-1α, and STAT3. Xenograft models were established with nude mice for further analyzing the bevacizumab resistance of NSCLC cells.Results: MiR-199a-5p expression was markedly attenuated in NSCLC tissues and cell lines. Overexpression of miR-199a-5p repressed the proliferation, migration, and invasion but induced the apoptosis of NSCLC cells. HIF-1α was identified as a direct target of miR-199a-5p. There was a positive feedback loop among miR-199a-5p, HIF-1α, and STAT3. Co-transfection of HIF-1α or STAT3 overexpression plasmids counteracted the effects of miR-199a-5p. In vivo experiments indicated that the feedback loop was in association with the bevacizumab resistance of NSCLC cells.Conclusion: MiR-199a-5p blocked the progression of NSCLC and sensitized NSCLC cells to bevacizumab by suppressing HIF-1α and STAT3, while the HIF-1α/STAT3 axis suppressed the expression of miR-199a-5p, which forms a positive feedback loop to promote the sustaining progression of NSCLC.

Carbon dioxide reforming of ethanol over Rh/CeO2 catalyst was deeply investigated at different reaction temperatures of 450–700 °C and reactant ratios (CO2/ethanol from 1 to 3) under atmospheric pressure. The obtained results indicated that Rh/CeO2 catalyst presented a promising activity and stability for syngas production from renewable bio-ethanol instead of conventional methane. Typically, CO2-rich conditions (CO2/ethanol = 3) were favorable for reaction process and dynamic coke cleaning, which led to remarkably stable performance over 65 h on stream. The strong redox capacity of CeO2 support might also accelerate CO2 activation and prevent the carbon accumulation over the catalyst surface. Additionally, tunable H2/CO ratios were available by changing the CO2/ethanol ratios. The results from characterization of samples before and after catalytic tests allowed to establish the relationship between textural properties and catalytic performance.

The effect of various factors on the catalytic performance of iso-butane formation over CuZnZrAl/Pd-β hybrid catalyst via synthesis gas or CO2 hydrogenation has been deeply investigated in this work. It was interesting to note that the iso-butane/n-butane ratio value was much higher than that of thermodynamic equilibrium (about 1/1), whose value was directly related to the reaction condition using this hybrid catalyst. In order to further clearly clarify this finding, various experimental reaction factors were selected to investigate the formation of iso-butane. The results revealed that increasing temperature, H2/COx, CO2/COx, and/or Pd loading possessed an inhibiting effect on the iso-butane yield. High selectivity of iso-butane could be achieved by increasing the reaction pressure, W/F and the weight ratio of CuZnZrAl methanol catalyst to Pd-β catalyst. It is also noted that the addition of water seriously suppressed the reaction activity, resulting in the low ratio of iso-butane/n-butane. A possible reaction route was elucidated based on the latest results. This might shed light on the development of a high efficient catalyst for iso-butane production from synthesis gas or CO2 hydrogenation. Keywords: Iso-butane, Synthesis gas, CO2, CuZnZrAl/Pd-β hybrid catalyst

Oil/water separation is a field of high significance as it might efficiently resolve the contamination of industrial oily wastewater and other oil/water pollution. In this paper, an environmentally-friendly hydrophobic aerogel with high porosity and low density was successfully synthesized with renewable pomelo peels (PPs) as precursors. Typically, a series of sponge aerogels (HPSA-0, HPSA-1 and HPSA-2) were facilely prepared via high-speed dispersion, freeze-drying and silanization with methyltrimethoxysilane. Indeed, the physical properties of aerogel such as density and pore diameter could be tailored by different additives (filter paper fibre and polyvinyl alcohol). Hence, their physico-chemical properties including internal morphology and chemical structure were characterized in detail by Fourier transform infrared, Brunauer–Emmett–Teller, X-ray diffraction, scanning electron microscope, Thermal gravimetric analyzer (TG) etc. Moreover, the adsorption capacity was further determined and the results revealed that the PP-based aerogels presented excellent adsorption performance for a wide range of oil products and/or organic solvents (crude oil 49.8 g g−1, soya bean oil 62.3 g g−1, chloroform 71.3 g g−1 etc.). The corresponding cyclic tests showed the absorption capacity decreased slightly from 94.66% to 93.82% after 10 consecutive cycles, indicating a high recyclability.

It is highly desirable that efficient recoverable heterogeneous catalysts should be developed to replace the costly biocatalysts used in producing structured phospholipids (SPLs) with medium-chain fatty acids (MCFAs). Thus, mesoporous propyl and phenyl sulfonic acid-functionalized SBA-15 materials synthesized via surface modification methods were investigated for the soybean lecithin interesterification with methyl caprate or caprylate. The physicochemical properties of the synthesized solid acids were deeply studied by small-angle X-ray diffraction, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared and pyridine adsorption, etc. to build the possible structure−performance relationships. The results revealed that amounts of organosulfonic acid groups were successfully grafted onto the SBA-15 support, and most of the surface acid sites contained in the as-prepared organic−inorganic hybrid samples were assigned as strong Brӧnsted acid sites. Notably, the functionalized SBA-15 materials exhibited promising catalytic behaviors in producing MCFA-enriched SPLs under mild conditions (40 °C, 6 h) when compared with commercial Amberlyst-15 and typical phospholipases or lipases, mostly due to their high surface area, ordered structure and adequate Brӧnsted acid sites. Besides, the as-prepared materials could be easily recycled five times without obvious deactivation. This work might shed light on alternative catalysts for SPL production instead of the costly enzymes.

Introduction: The difficulty in treating lung adenocarcinoma (LUAD) is caused by a shortage of knowledge about the biological mechanisms and a lack of treatment choices. Objectives: The aim of this study was to identify a valuable molecular target for the treatment of LUAD. Methods: Using multiple databases, we screened for hub genes in LUAD using Cytoscape and explored the expression and prognosis of DLG associated protein 5 (DLGAP5) in LUAD. We investigated the genetic variation, functional enrichment, and epigenetic activity of DLGAP5. Furthermore, we evaluated the relationship between the tumor microenvironment (TME) and DLGAP5. Results: Our study identified 10 hub genes in LUAD: CDC45, KIAA0101, DLGAP5, CDT1, NCAPG, CCNB1, CDCA5, CDC20, KIF11, and AURKA. We discovered that DLGAP5 was overexpressed and associated with poor prognosis in LUAD. DLGAP5 exhibited an overall genetic variation frequency of 2%, and its DNA promoter was hypomethylated in LUAD (p < 0.05). The expression of DLGAP5 in LUAD showed a positive correlation with the majority of N6-methyladenosine (m6A)-methylation genes. Additionally, DLGAP5 was primarily associated with the cell cycle in LUAD. Notably, there was a significant favorable association between DLGAP5 and CD274, CTLA4, HAVCR2, and LAG3 in LUAD. Conclusion: DLGAP5 may be a therapeutic target for LUAD, as it affects cancer cells proliferation and development through the regulation of cell-cycle checkpoints and modulation of immune cell infiltration and immune checkpoints in the TME. [ABSTRACT FROM AUTHOR]

Background: Osteomyelitis causes marked disability and is one of the most challenging diseases for orthopaedists to treat because of the considerable rate of infection recurrence. In this study, we proposed and assessed the debridementreconstruction-docking (DRD) systemfor the treatment of lower-extremity osteomyelitis. This procedure comprises 3 surgical stages and 2 preoperative assessments; namely, pre-debridement assessment, debridement, pre-reconstruction assessment, reconstruction, and docking-site management. We evaluated the use of the DRD system compared with the Ilizarov technique, which is defined as a 1-stage debridement, osteotomy, and bone transport. Methods: This retrospective cohort included 289 patients who underwent either DRD or the Ilizarov technique for the treatment of lower-extremity osteomyelitis at a single institution between January 2013 and February 2021 and who met the eligibility criteria. The primary outcome was the rate of infection recurrence. Secondary outcomes included the external fixator index (EFI), refracture rate, and the Paley classification for osseous and functional results. An inverse-probabilityweighted regression adjustment model was utilized to estimate the effect of the DRD system and Ilizarov technique on the treatment of lower-extremity osteomyelitis. Results: A total of 131 and 158 patients underwent DRD or the Ilizarov technique, respectively. The inverse-probabilityweighted regression adjustment model suggested that DRD was associated with a significant reduction in infection recurrence (risk ratio [RR], 0.26; 95% confidence interval [CI], 0.13 to 0.50; p < 0.001) and EFI (26.9 days/cm, 95% CI; 28.3 to25.5; p < 0.001). Patients in the DRD group had better Paley functional results than those in the Ilizarov group (ridit score, 0.55 versus 0.45; p < 0.001). There was no significant difference between the 2 groups in the rate of refracture (RR, 0.87; 95% CI, 0.42 to 1.79; p = 0.71) and Paley osseous results (ridit score, 0.51 versus 0.49; p = 0.39). Conclusions: In this balanced retrospective cohort of patients with lower-extremity osteomyelitis, the use of the DRD system was associated with a reduced rate of infection recurrence, a lower EFI, and better Paley functional results compared with the use of the Ilizarov technique. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]