Effects of plant-derived protein and rapeseed oil on growth performance and gut microbiomes in rainbow trout.

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 ß-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.

Lysosomal Ion Channels and Lysosome-Organelle Interactions.

Intracellular organelles exchange their luminal contents with each other via both vesicular and non-vesicular mechanisms. By forming membrane contact sites (MCSs) with ER and mitochondria, lysosomes mediate bidirectional transport of metabolites and ions between lysosomes and organelles that regulate lysosomal physiology, movement, membrane remodeling, and membrane repair. In this chapter, we will first summarize the current knowledge of lysosomal ion channels and then discuss the molecular and physiological mechanisms that regulate lysosome-organelle MCS formation and dynamics. We will also discuss the roles of lysosome-ER and lysosome-mitochondria MCSs in signal transduction, lipid transport, Ca 2+ transfer, membrane trafficking, and membrane repair, as well as their roles in lysosome-related pathologies.

Circ_0020123 regulates autophagy, glycolysis, and malignancy by upregulating IRF4 through eliminating miR-193a-3p-mediated suppression of IRF4 in non-small cell lung cancer.

Circular RNA is related to the tumorigenesis of various cancers. Circular RNA hsa_circ_0020123 (circ_0020123) has been uncovered to promote non-small cell lung cancer (NSCLC) progression. However, the regulatory mechanism of circ_0020123 in NSCLC is unclear. The quantitative real-time polymerase chain reaction was employed to detect the levels of circ_0020123, microRNA (miR)-193a-3p, and IRF4 interferon regulatory factor 4 (IRF4) in NSCLC tissues and cells. Loss-of-function experiments were performed to analyze the impacts of circ_0020123 silencing on NSCLC cell malignancy, autophagy, and glycolysis. Protein levels were detected using western blotting. The regulatory mechanism of circ_0020123 was analyzed by bioinformatics analysis and validated by the dual-luciferase reporter, RNA immunoprecipitation assay, and RNA pull-down assay. Xenograft assay was performed to verify the biological function of circ_0020123. We observed an overt elevation in circ_0020123 expression in NSCLC samples and cells, and NSCLC patients with high circ_0020123 expression had a poor prognosis. Circ_0020123 knockdown constrained xenograft tumor growth in vivo and curbed cell proliferation, migration, and glycolysis, and accelerated cell apoptosis and autophagy in NSCLC cells in vitro. Circ_0020123 could absorb miR-193a-3p to regulate IRF4 expression. miR-193a-3p silencing overturned circ_0020123 knockdown-mediated impacts on NSCLC cell malignancy, autophagy, and glycolysis. And IRF4 overexpression reversed miR-193a-3p mimic-mediated effects on NSCLC cell malignancy, autophagy, and glycolysis. Circ_0020123 promoted glycolysis and tumor growth by upregulating IRF4 through sequestering miR-193a-3p in NSCLC, offering a novel mechanism by which circ_0020123 is responsible for the malignancy, autophagy, and glycolysis of NSCLC cells.

Resveratrol promotes lysosomal function via ER calcium-dependent TFEB activation to ameliorate lipid accumulation.

Abnormal lipid accumulation is associated to the development of metabolic diseases such as hepatic steatosis and lipid storage diseases. Pharmacological agents that can attenuate lipid accumulation therefore have therapeutic potentials for these diseases. Resveratrol (RSV), a natural active substance found in fruits and nuts, has been reported to effectively reduce the intracellular lipid accumulation, but the underlying mechanisms of RSV remain elusive. Here, we show that RSV triggers an endoplasmic reticulum (ER)- Ca2+ signaling that activates transcriptional factor EB (TFEB), a master transcriptional regulator of autophagic and lysosomal biogenesis. Moreover, RSV activates protein phosphatase 2A (PP2A), which binds and dephosphorylates TFEB, promoting its nuclear translocation and the expression of TFEB target genes required for autophagosome and lysosomal biogenesis. Notably, genetic inhibition of TFEB significantly ameliorates RSV-mediated lipid clearance. Taken together, these data link RSV-induced ER calcium signaling, PP2A and TFEB activation to promote autophagy and lysosomal function, by which RSV may trigger a cellular self-defense mechanism that effectively mitigate lipid accumulation commonly associated with many metabolic diseases.

Genetic engineering of the precursor supply pathway for the overproduction of the nC14-surfactin isoform with promising MEOR applications.

BACKGROUND: Surfactin, a representative biosurfactant of lipopeptide mainly produced by Bacillus subtilis, consists of a cyclic heptapeptide linked to a ß-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.

Injectable stress relaxation gelatin-based hydrogels with positive surface charge for adsorption of aggrecan and facile cartilage tissue regeneration.

BACKGROUND: Cartilage injury and pathological degeneration are reported in millions of patients globally. Cartilages such as articular hyaline cartilage are characterized by poor self-regeneration ability due to lack of vascular tissue. Current treatment methods adopt foreign cartilage analogue implants or microfracture surgery to accelerate tissue repair and regeneration. These methods are invasive and are associated with the formation of fibrocartilage, which warrants further exploration of new cartilage repair materials. The present study aims to develop an injectable modified gelatin hydrogel. METHOD: The hydrogel effectively adsorbed proteoglycans secreted by chondrocytes adjacent to the cartilage tissue in situ, and rapidly formed suitable chondrocyte survival microenvironment modified by ε-poly-L-lysine (EPL). Besides, dynamic covalent bonds were introduced between glucose and phenylboronic acids (PBA). These bonds formed reversible covalent interactions between the cis-diol groups on polyols and the ionic boronate state of PBA. PBA-modified hydrogel induced significant stress relaxation, which improved chondrocyte viability and cartilage differentiation of stem cells. Further, we explored the ability of these hydrogels to promote chondrocyte viability and cartilage differentiation of stem cells through chemical and mechanical modifications. RESULTS: In vivo and in vitro results demonstrated that the hydrogels exhibited efficient biocompatibility. EPL and PBA modified GelMA hydrogel (Gel-EPL/B) showed stronger activity on chondrocytes compared to the GelMA control group. The Gel-EPL/B group induced the secretion of more extracellular matrix and improved the chondrogenic differentiation potential of stem cells. Finally, thus hydrogel promoted the tissue repair of cartilage defects. CONCLUSION: Modified hydrogel is effective in cartilage tissue repair.

Postconditioning With Red-Blue Light Therapy Improves Survival of Random Skin Flaps in a Rat Model.

BACKGROUND: Random skin flap ischemic necrosis is a serious challenge in reconstructive surgery. Photobiomodulation is a noninvasive effective technique to improve microcirculation and neovascularization. Photobiomodulation with red or blue light has been separately proven to partially prevent skin flap necrosis, but the synergistic effect of red and blue light not been elucidated. Our experiment evaluated the impact of postconditioning with red-blue light therapy on the viability of random flaps. METHODS: Thirty Sprague-Dawley male rats (male, 12 weeks) with a cranially based random pattern skin flap (3 × 8 cm) were divided into 3 groups: control group, red light group, and red-blue light group. On postoperative day 7, flap survival was observed and recorded using transparent graph paper, flaps were obtained and stained with hematoxylin and eosin, and microvessel density was measured. Micro-computed tomography was used to measure vascular volume and vascular length. On days 0, 3, and 7 after surgery, blood flow was measured by laser Doppler. To investigate the underlying mechanisms, the amount of nitric oxide (NO) metabolites in the flap tissue was assessed on days 3, 5, and 7 after surgery. RESULTS: The mean percentage of skin flap survival was 59 ± 10% for the control group, 69 ± 7% for the red light group, and 79 ± 9% for the red-blue light group (P < 0.01). The microvessel density was 12.3 ± 1.2/mm2 for the control group, 31.3 ± 1.3/mm2 for the red light group, and 36.5 ± 1.4/mm2 for the red-blue light group (P < 0.01). Both vascular volume and total length in the red-blue light group showed significantly increased compared with the red light and control group (P < 0.01). Blood flow in the red-blue light treated flap showed significantly increased at postsurgery days 3 and 7 compared with the red light and control group (P < 0.01). The level of the NO metabolites was significantly increased in flap tissues belonging to the red-blue light group compared with the other 2 groups (P < 0.01). CONCLUSIONS: This study showed that postconditioning with red-blue light therapy can enhance the survival of random skin flap by improving angiogenesis and NO releasing.

Curcumin suppresses the stemness of non-small cell lung cancer cells via promoting the nuclear-cytoplasm translocation of TAZ.

Curcumin has been shown to suppress the progression of lung cancer, however, the underlying mechanisms are largely unknown. Here, we aimed to investigate the effects of curcumin on the stemness of non-small cell lung cancer (NSCLC) cells. We found that curcumin reduced the sphere formation ability at the concentrations without affecting the cell viability of NSCLC cells and normal pulmonary epithelial cells, which is evident by the decrease of sphere size and number. In addition, curcumin decreased ALDH activity and the expression of stemness markers (CD133, EpCAM, Oct4). RNA sequencing analysis revealed that the Hippo pathway was mostly enriched in cells with curcumin treatment. Indeed, the expression of cancer stem cell markers was significantly decreased by curcumin treatment by analyzing the RNA sequencing data. Gene set enrichment analysis (GSEA) showed that curcumin negatively regulated the cancer stem cell function and positively modulated cancer stem cell differentiation ability. Furthermore, curcumin enhanced the cisplatin sensitivity of NSCLC cells. Mechanistically, it was found that curcumin promoted the nuclear-cytoplasm translocation of TAZ, but not YAP, the critical effectors of Hippo pathway. In addition, curcumin destabilzed TAZ protein stability and promoted TAZ protein degradation in lung cancer cells, which is dependent on the proteasome degradation system, not by autophagy lysosome degradation system. Overexpression of TAZ rescued the inhibition of curcumin on the stemness of lung cancer cells. Thus, our results suggest that curcumin can attenuate the stemness of lung cancer cells through promoting TAZ protein degradation and thus activating Hippo pathway.

[The new target of Rapamycin: lysosomal calcium channel TRPML1].

Rapamycin (Rap) is an immunosuppressant, which is mainly used in the anti-rejection of organ transplantation. Meanwhile, it also shows great potential in the fields of anticancer, neuroprotection and anti-aging. Rap can inhibit the activity of mammalian target of Rap (mTOR). It activates the transcription factor EB (TFEB) to up-regulate lysosomal function and eliminates the inhibitory effect of mTOR on ULK1 (unc-51 like autophagy activating kinase 1) to promote autophagy. Recent research showed that Rap can directly activate the lysosomal cation channel TRPML1 in an mTOR-independent manner. TRPML1 activation releases lysosomal calcium. Calcineurin functions as the sensor of the lysosomal calcium signal and activates TFEB, thus promoting lysosome function and autophagy. This finding has greatly broadened and deepened our understanding of the pharmacological roles of Rap. In this review, we briefly introduce the canonical Rap-mTOR-ULK1/TFEB signaling pathway, and then discuss the discovery of TRPML1 as a new target of Rap and the pharmacological potential of this novel Rap-TRPML1-Calcineurin-TFEB pathway.

Activities of daily living, life orientation, and health-related quality of life among older people in nursing homes: a national cross-sectional study in China.

PURPOSE: This study aimed to explore the current status of activities of daily living (ADLs), life orientation, and health-related quality of life (HRQoL) among older people in nursing homes and to further examine the mediating role of life orientation in the impact of ADLs on HRQoL. METHODS: A national cross-sectional study was conducted among older people aged 60 and above in nursing homes by the randomly stratified cluster sampling method. The status of ADLs, life orientation and HRQoL were measured using an ADL scale, a life orientation scale and the SF-12v2 scale, respectively. Multiple linear regression models were used to identify explanatory factors associated with ADLs, life orientation, and HRQoL. The potential mediating role of life orientation in the relationship between ADL and HRQoL was explored by mediation analysis. RESULTS: The overall prevalence of ADL disability was 52.67%, and 84.37% of older people in nursing homes had a negative life orientation. The mean scores of physical health and mental health among older people in nursing homes were 45.44 ± 6.46 and 42.67 ± 8.48, respectively. Some sociodemographic characteristics were associated with poor physical health and mental health. After adjustments were made for covariates, the life orientation score mediated 13.81% of the total effect of the ADL score on physical component score of HRQoL and mediated 45.33% of the mental component score of HRQoL. CONCLUSION: A sizeable proportion of older people had ADL disability and negative life orientation, and HRQoL was poor among older Chinese people in nursing homes. Life orientation partially mediates the relationship between ADLs and HRQoL.

ZBP-89 and Sp1 contribute to Bak expression in hepatocellular carcinoma cells.

BACKGROUND: Kruppel family member zinc binding protein 89 (ZBP-89), also known as ZNF148, regulates Bak expression via binding to GC-rich promoter domain. It is not clear if other GC-rich binding factors, such as Sp family members, can interact with ZBPp-89 on Bak expression. This study aims to elucidate the mechanism of Bak expression regulation by ZBP-89 and Sp proteins, based on in vitro experiment and The Cancer Genome Atlas (TCGA) hepatocellular carcinoma (HCC) data cohort. METHODS: We downloaded TCGA hepatocellular carcinoma (HCC) cohort data to analysis the association of Bak transcription level with ZBP-89 and Sp proteins transcription level. HCC cell lines and liver immortal non-tumour cell lines were used for mechanism study, including western blotting analysis, expression vector mediated gene expression and siRNA interference. RESULTS: Results showed that cancer tissues have higher Bak transcription level compared with adjacent non-cancer tissues. Bak transcription level was correlated with Sp1 and Sp3 expression level, while no correlation was found in ZBP-89 and Bak, neither Sp2 nor Sp4. Mithramycin A (MMA) induced Bak expression in a dose-dependent manner. Western blotting results showed Sp1 overexpression increased Bak expression both in liver immortal non-tumour cells and HCC cells. Interference Sp1 expression could inhibit Bak expression alone. ZBP-89 siRNA suppressed Bak expression even in the presence of MMA treatment and S1 overexpression. Additionally, Bak and Sp1 level were associated with HCC patient survival. CONCLUSIONS: Bak expression required ZBP-89 and Sp1 cooperative regulation simultaneously.

Resection arthrodesis using distraction osteogenesis then plating as a hybrid surgical technique for the management of bone sarcomas of the distal tibia.

PURPOSE: We report the oncological and functional results of limb salvage for bone sarcomas involving the distal tibia using hybrid surgical technique of resection arthrodesis by bone transport then plating. METHODS: Five patients (mean age 18.6 years) with primary distal tibial sarcomas (two Ewing's sarcomas and three osteosarcomas) were treated by this method. The average duration of follow-up is 53 months. All patients accepted distraction osteogenesis with a standard technique using external fixator after wide (four cases) or marginal (one case) resection in the first operation. They were re-admitted for the second surgical treatment (plate insertion and removal of the external fixator) one to two months after they achieved the necessary limb length and desired alignment. RESULTS: Solid union of the lengthening site and sound fusion of the ankle were achieved in all five patients with full and unassisted weight bearing. The mean lengthening was 11.8 cm (range 8-14 cm) and the external fixation index (EFI) was 29.3 days/cm (range 22.8-36.3 days/cm). The mean functional score according to the rating system of the Musculoskeletal Tumour Society was 88% (83-90%). One patient showed poor response to chemotherapy, had local recurrence of sarcoma one year after plating, and was treated with above-knee amputation. CONCLUSIONS: In carefully selected patients with primary distal tibial sarcomas, this hybrid method can effectively eliminate tumor lesion, reconstruct function, and shorten the length of wearing an external fixator by a meticulous conversion to internal fixator.

Processing imbalanced medical data at the data level with assisted-reproduction data as an example.

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.

Multifunctional Bagasse Foam with Improved Thermal Insulation and Flame Retardancy by a Borax-Induced Self-Assembly and Ambient Pressure Drying Technique.

Cellulose foams are considered an effective alternative to plastic foam, because of their advantages of low density, high porosity, low thermal conductivity, and renewable nature. However, they still suffer from complex processing, poor mechanical properties, and flammability. As an agricultural waste, bagasse is rich in cellulose, which has attracted much attention. Inspired by the fact that borate ions can effectively enhance the strength of plant tissue by their cross-linking with polysaccharides, the present work designs and fabricates a series of multifunctional bagasse foams with robust strength and improved thermal insulation and flame retardancy via a unique borax-induced self-assembly and atmospheric pressure drying route using bagasse as a raw material, borate as a cross-linking agent, and chitosan as an additive. As a result, the optimized foam exhibits a high porosity (93.5%), a high hydrophobic water contact angle (150.4°), a low thermal conductivity (63.4 mW/(m·K) at 25 °C), and an outstanding flame retardancy. The present study provides a novel and inspiring idea for large-scale production of cellulose foams through an environmentally friendly and cost-effective approach.

Structural basis for sugar perception by Drosophila gustatory receptors.

Insects rely on a family of seven transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities, such as sweet and bitter. We report structures of Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBDs, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBDs. Sugar binding to LBDs induces local conformational changes, which are subsequently transferred to the PD to cause channel opening. Our studies reveal a structural basis for sugar recognition and activation of GRs.

A prion-like domain of TFEB mediates the co-aggregation of TFEB and mHTT.

The aggregation of mutant HTT (huntingtin; mHTT) is a hallmark of Huntington disease (HD). mHTT aggregates interact and sequester dozens of proteins and affect diverse key cellular functions. Here we report that TFEB (transcription factor EB), a master regulator of lysosome biogenesis and autophagy, is yet another protein that co-aggregates with mHTT. We also found the mHTT-TFEB co-aggregation is mediated by a prion-like domain (PrLD) near the N terminus of TFEB. Our findings point out a possible limitation for therapeutic strategies targeting TFEB to clear mHTT, and also provided a possible explanation for controversies that TFEB overexpression lowered soluble mHTT in some HD models but failed to reduce mHTT aggregates or HD pathology in others. Moreover, we found that TFE3, another MiT family transcription factor that shares overlapping functions with TFEB, lacks PrLD and does not co-aggregate with mHTT, and thus might serve as an alternative drug target for HD.

Characterization of TIM-3 Expression and Its Correlation with TNF-α and IFN-γ in Patients with Surgically Resected Lung Adenocarcinoma.

Objective: T cell immunoglobulin and mucin-containing protein-3 (TIM-3) is an important immune checkpoint, but its role in lung cancer is still not clear. In this study, we investigated TIM-3 protein expression and its correlation with TNF-α and IFN-γ by examining the tissues of patients with lung adenocarcinoma. Methods: We detected the mRNA quantity of TIM-3, TNF-α, and IFN-γ in 40 surgically resected specimens from patients with lung adenocarcinoma by real-time quantitative polymerase chain reaction (qRT-PCR). The protein expression of TIM-3, TNF-α, and IFN-γ was assessed in normal tissues, paracarcinoma tissues, and tumor tissues by western blotting, respectively. The relevance between the expression and clinicopathological information of the patients was analyzed. Results: The results showed that the expression level of TIM-3 was higher in tumor tissues than normal tissues and paracancerous tissues (P < 0.05). On the contrary, the expression of TNF-α and IFN-γ in tumor tissues was lower than normal tissues and paracarcinoma tissues (P < 0.05). However, the expression levels of IFN-γ mRNA were not observed to be significantly different between cancerous tissues and adjacent tissues. While TIM-3 protein expression in cancer tissues of patients with lymph node metastasis was higher than in patients without metastasis, the expression of TNF-α and IFN-γ was lower (P < 0.05). Importantly, the expression of TIM-3 was negatively correlated with the expression of TNF-α and IFN-γ, and the expression of TNF-α was found to be positively correlated with IFN-γ in the patient. Conclusion: The high expression of TIM-3, the low expression of TNF-α and IFN-γ, and the synergistic effect of TNF-α and IFN-γ in patients with lung adenocarcinoma were closely related to poor clinicopathological characteristics. Overexpression of TIM-3 may play an important role in the relationship between TNF-α and IFN-γ secretion and poor clinicopathological characteristics.

Correction: Zheng et al. Glycolysis-Related SLC2A1 Is a Potential Pan-Cancer Biomarker for Prognosis and Immunotherapy. Cancers 2022, 14, 5344.

The authors wish to make the following corrections to this paper [...].

Debridement-Reconstruction-Docking Management System Versus Ilizarov Technique for Lower-Extremity Osteomyelitis.

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 debridement-reconstruction-docking (DRD) system for 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-probability-weighted 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-probability-weighted 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 (-6.9 days/cm, 95% CI; -8.3 to -5.5; 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.

Addition of bevacizumab to EGFR tyrosine kinase inhibitors in advanced NSCLC: an updated systematic review and meta-analysis.

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 <75 years and the Asian population had significantly prolonged PFS (HR = 0.69, 95% CI: 0.52-0.91; HR = 0.71, 95% CI: 0.58-0.87; respectively). The superiority of EGFR-TKI and bevacizumab combination therapy against EGFR-TKI monotherapy in improving PFS was more significant in the erlotinib regimen subgroup. The risk of grade≥3 TRAEs was remarkably higher in the combination therapy group (HR = 1.73, 95% CI: 1.39-2.16). Conclusion: Addition of bevacizumab to EGFR-TKI therapy provided significantly better PFS and ORR for EGFR-mutant advanced NSCLC patients, though with higher risk of grade≥3 TRAEs. Patients who ever smoked, aged <75 years, and Asian population might benefit more from the combination regimen. Systematic Review Registration: This systematic review and meta-analysis was registered in the PROSPERO database (CRD42023401926).