[Corrigendum] Effects of miR­340 overexpression and knockdown on the proliferation and metastasis of NSCLC cell lines.

Following the publication of the above article, an interested reader drew to the authors' attention that, with the 'Adjacent' row (top row) of immunohistochemical images shown in Fig. 2 on p. 646, the fourth and fifth panels along (the 'RAB11A' and 'RAB9A' data panels) contained an overlapping section of data, such that data which were intended to show the results from differently performed experiments had apparently been derived from the same original source. After consulting their original data, the authors were able to determine that the duplication of these panels had inadvertently occurred during the process of compiling Fig. 2. The revised version of Fig. 2, featuring the correct data for the 'Adjacent/RAB9A' experiment, is shown below. The authors confirm that the error associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum. Furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 44: 643­651, 2019; DOI: 10.3892/ijmm.2019.4213].

High frequency of GATA2 variants in patients with pulmonary fungal disease without immunocompromised risk factors: a retrospective study.

Background: The global incidence of pulmonary fungal diseases is on the rise. Individuals harboring underlying immunocompromised conditions such as human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), malignant tumors, or those who have undergone organ transplantation, among others, are particularly susceptible to fungal infections. However, in clinical practice, certain patients diagnosed with pulmonary fungal infections exhibit no discernible risk factors for immunosuppression. GATA2, a pivotal transcription factor governing hematopoiesis, is implicated in GATA2 deficiency, predisposing individuals to fungal infections. This study aims to scrutinize GATA2 variants in adult patients afflicted with pulmonary fungal infections devoid of recognized risk factors for immunosuppression. Methods: A cohort of adult patients (aged 18-65 years old, n=22) diagnosed with pulmonary fungal diseases lacking underlying immunosuppression risk factors, treated at Sun Yat-sen Memorial Hospital from January 2016 to December 2021, underwent Sanger sequencing of the GATA2 gene. Results: Among the 22 patients devoid of immunocompromised risk factors and diagnosed with pulmonary fungal diseases, 17 patients (77.3%) exhibited single nucleotide variants (SNVs) within the exons of the GATA2 gene. Notably, exon 3 variants were present in 7 cases (41.2%), exon 4 variants in 10 cases (58.8%), and exon 5 variants in 11 cases (64.7%), emerging as the most prevalent exonic variants within GATA2. Among the 17 patients harboring GATA2 SNVs, a total of 28 SNVs were identified. Of these, eight variants (NM_001145661.2:c.33G>A, NM_001145661.2:c.523C>T, NM_001145661.2:c.77A>G, NM_001145661.2:c.545C>T, NM_001145661.2:c.7G>A, NM_001145661.2:c.1406A>G, NM_001145661.2:c.977A>G, NM_001145661.2:c.742A>C) were identified as missense mutations with the potential to alter the structure and function of the GATA2 protein on the basis of multiple in silico predictive programs interpretation. One nonsense mutation (NM_001145661.2:c.664A>T) was classified as "likely pathogenic" according to 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Conclusions: GATA2 variants are prevalent among patients afflicted with pulmonary fungal infections in the absence of traditional immunosuppressive risk factors. Further investigations are warranted to elucidate the impact of GATA2 variants on the expression and functionality of the GATA2 protein.

Cecal necroptosis triggers lethal cardiac dysfunction in TNF-induced severe SIRS.

Tumor necrosis factor (TNF) induces systemic inflammatory response syndrome (SIRS), and severe SIRS can serve as a model for studying animal death caused by organ failure. Through strategic cecectomy, we demonstrate that necroptosis in the cecum initiates the death process in TNF-treated mice, but it is not the direct cause of death. Instead, we show that it is the cardiac dysfunction downstream of cecum damage that ultimately leads to the death of TNF-treated mice. By in vivo and ex vivo physiological analyses, we reveal that TNF and the damage-associated molecular patterns (DAMPs) released from necroptotic cecal cells jointly target cardiac endothelial cells, triggering caspase-8 activation and subsequent cardiac endothelial damage. Cardiac endothelial damage is a primary cause of the deterioration of diastolic function in the heart of TNF-treated mice. Our research provides insights into the pathophysiological process of TNF-induced lethality.

Systemic immune-inflammation index predicts short-term mortality in acute ischemic stroke with severe stenosis of internal carotid artery associated pneumonia.

BACKGROUND: We aimed to investigate the relationship between systemic immune-inflammation index (SII) and short-term mortality in acute ischemic stroke (AIS) with internal carotid artery (ICA) severe stenosis and stroke associated pneumonia (SAP) patients. METHODS: Information on general demographic, laboratory data, CT angiography, magnetic resonance angiography, or digital subtraction angiography were obtained. The predictive power was evaluated by assessing the area under the receiver operating characteristic (ROC) curve. The logistic regression was performed to assess the association of SII and short-term mortality in severe stenosis ICA-AIS and SAP patients. RESULT: Among 342 patients with severe stenosis ICA-AIS and SAP, death occurred in 66 patients during 120 days follow-up. Multivariate regression analyses indicated that increased SII predicts higher mortality in 120 days follow-up, and the risk of short-term mortality in SII > 666.31 × 109/L group is increased 4.671-fold. Patients with SII > 666.31 × 109/L had higher proportion of male, hypertension, smoking, higher admission NIHSS score, higher systolic blood pressure, and higher proportion of 120 days mortality. Higher SII predicted a worse 120 days mortality was worked out by Kaplan-Meier methods. CONCLUSION: An elevated SII was remarkably associated with 120 days mortality in severe stenosis ICA-AIS and SAP patients.

A reference for selecting an appropriate method for generating glioblastoma organoids from the application perspective.

Glioblastoma organoids (GBOs) serve as a powerful and reliable tool to study glioblastoma stem cells (GSCs) and glioblastoma (GBM). GBOs can be derived from different materials using different methods. To identify the predominant generation methods and the most applications of GBOs, we searched four databases (PubMed, Embase, Web of Science, and Wiley Online Laboratory) from August 2021 to August 2023. After screening, 42 out of 295 articles were included and analyzed. GBOs in these articles were generated using only one material, such as tumor tissues, tumor cells, and gene-edited multifunctional stem cells, or simultaneously using two materials, such as tumor cells and normal organoids. Methodologically, direct cultivation of GBM cells or tissues was the most commonly used method to generate GBOs. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) were the frequently used multifunctional stem cells to generate GBOs by simultaneously silencing P53, NF1, and PTEN using CRISPR/Cas9. In terms of applications, GBOs generated by direct cultivation of GBM tissue had the most applications, including molecular mechanisms, therapy, and culture technique. This review provides a theoretical reference for selecting an appropriate method to generate GBOs when studying GSCs and GBM.

Charge balanced aggregation: A universal approach to aqueous organic nanocrystals.

Organic nanocrystals, particularly those composed of conjugated molecules, hold immense potential for various applications. However, their practical utility is often hindered by the challenge of achieving stable aqueous dispersions, which are essential for biological compatibility and effective delivery. This study introduces a novel and versatile strategy for preparing stable aqueous organic nanocrystals using a modified reprecipitation method. We demonstrate the broad applicability of this approach by successfully preparing a diverse library of nanocrystals from 27 conjugated molecules. Our findings reveal a charge-balanced aggregation mechanism for nanocrystal formation, highlighting the crucial role of surface charge in controlling particle size and stability. Based on this mechanism, we establish a comprehensive molecular combination strategy that directly links molecular properties to colloidal behaviour, enabling the straightforward prediction and preparation of stable aqueous dispersions without the need for excipients. This strategy provides a practical workflow for tailoring the functionality of these nanocrystals for a wide range of applications. To illustrate their therapeutic potential, we demonstrate the enhanced efficacy of these nanocrystals in treating acute ulcerative colitis, myocardial ischemia/reperfusion injury, and cancer in mouse models. This work paves the way for developing next-generation nanomaterials with tailored functionalities for diverse biomedical applications.

Impact of Surgical Parathyroidectomy on Craniofacial Morphology in Patients With Renal Failure.

PURPOSE: Parathyroidectomy is beneficial in tertiary hyperparathyroidism (THPT) consequent to chronic renal failure. The craniofacial morphology of patients who undergo total parathyroidectomy and autologous transplantation (tPTX + AT) has not been widely studied. This study assessed the efficacy of tPTX + AT in THPT and evaluated possible improvements in craniofacial features. METHODS: This retrospective analysis included patients who were diagnosed with medically refractory THPT and had undergone tPTX + AT between September 2013 and May 2021. The VAS was used to evaluate improvements in various symptoms including bone pain and pruritus. Changes in serum calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone (iPTH) levels were also assessed. The impact of the procedure was assessed by comparing two-photon X-ray bone mineral density measurements obtained 1 year before and after surgery. RESULTS: The VAS of pain and pruritus decreased significantly on the first postoperative day (P < 0.05). Calcium levels changed significantly (from 2.50 ± 0.22 mmol/L to 2.10 ± 0.26 mmol/L) on postoperative day 1 (P = 0.0000); iPTH levels also declined substantially on this day, reducing from 211.00 (122.10, 252.80) to 5.04 (2.96, 9.40) pmol/L. Bone mineral density increased significantly across various regions including the greater trochanter of the femur, intertrochanteric area, total hip, and third lumbar vertebra (P < 0.05). The angles between the upper incisor and mandibular plane and the lower lip and Ricketts E line (drawn from the tip of the nose to the soft tissue area) also improved (P = 0.043, P = 0.001). CONCLUSION: Total parathyroidectomy and autologous transplantation can rapidly alleviate bone pain and skin itching in THPT. It may also improve bone density and facial soft tissue.

Versatile Underwater Pressure Sensitive Adhesive: UV Curing Synthesis and Substrate-Independent Adhesion.

The demand for underwater pressure sensitive adhesives (PSAs) is rapidly increasing in fields such as underwater engineering and biomedicine. However, the achievement of underwater adhesion of PSAs remains a challenge because of the hydration layer that hinders the interaction between the adhesive and the substrate. Herein, a new type of underwater PSA was synthesized by the copolymerization of hydrophobic unsaturated poly(1,2-butylene oxide) (UPBO) and hydrophilic itaconic acid monomers using solvent-free ultraviolet curing. The PSA has demonstrated substrate-independent underwater adhesion strengths ranging from 108 to 141 kPa on both hydrophilic (glass, wood, steel) and hydrophobic (PET, PMMA, PTFE) substrates. The underwater adhesion performance of PSA remains stable during 30 adhesion-detachment cycles and incubation in water for 20 days. Notably, PSA shows cytocompatibility, antimicrobial, and degradable properties and can be used for rapid hemostasis of skin wounds. Experimental characterizations confirm that the process of underwater adhesion is achieved by hydrophobic alkyl side chains of the PBO chain segments, which repel water at the adhesive-substrate interface. This study should provide both practical and facile design strategies for multifunctional underwater PSAs that can be used in a variety of applications.

Vebreltinib for Advanced Non-Small Cell Lung Cancer Harboring c-Met Exon 14 Skipping Mutation: A Multicenter, Single-Arm, Phase II KUNPENG Study.

PURPOSE: The KUNPENG study aimed to evaluate the efficacy and safety of vebreltinib (also known as bozitinib, APL-101, PLB-1001, and CBT-101), a potent and highly selective inhibitor of c-mesenchymal-epithelial transition (MET), in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring c-Met alterations. METHODS: This multicenter, multicohort, open-label, single-arm, phase II trial enrolled patients with c-Met dysregulated, locally advanced or metastatic NSCLC from January 2020 to August 2022 across 17 centers. Cohort 1 included patients with MET exon 14 skipping (METex14)-mutant NSCLC who had not previously received MET inhibitors. Participants were administered vebreltinib at a dosage of 200 mg twice a day in 28-day cycles. The primary end point was the objective response rate (ORR), and the key secondary end point was the duration of response (DoR), both evaluated by a blinded independent review committee according to the RECIST version 1.1. RESULTS: As of August 9, 2022, 52 patients had been enrolled in cohort 1, of whom 35 (67.3%) were treatment-naïve. The ORR reached 75% (95% CI, 61.1 to 86). Among treatment-naïve patients, the ORR was 77.1% (95% CI, 59.9 to 89.6), and in previously treated patients, it was 70.6% (95% CI, 44.0 to 89.7). The disease control rate was 96.2%, with a median DoR of 15.9 months, a median progression-free survival of 14.1 months, and a median overall survival of 20.7 months. The most common treatment-related adverse events were peripheral edema (82.7%), QT prolongation (30.8%), and elevated serum creatinine (28.8%). CONCLUSION: Vebreltinib has shown promising efficacy and a favorable safety profile in patients with METex14-mutant NSCLC.

Spectrum and characteristics of germline PALB2 pathogenic variants in 1556 early-onset breast cancer patients in China.

PURPOSE: Limited data are available regarding the partner and localizer of BRCA2 (PALB2) in Chinese patients with early breast cancer. This study aimed to assess the spectrum and characteristics of germline PALB2 pathogenic variants in this population. METHODS: Peripheral blood samples were collected from 1556 patients diagnosed with BRCA1/2-negative early-onset breast cancer. All coding regions and exon‒intron boundaries of the PALB2 genes were screened through next-generation sequencing. RESULTS: The prevalence of PALB2 pathogenic variants was approximately 0.77% in the cohort. Eleven PALB2 pathogenic variants were identified in twelve participants, including five frameshift mutations and six nonsense mutations. All other variants were detected once, except for PALB2 c.1056_1057del (detected twice). Two PALB2 carriers (2/12, 16.7%) have documented family history of breast cancer and/or ovarian cancer. Patients with a positive family history exhibited a threefold higher possibility of being identified as PALB2 carriers than those without a family history (2% vs. 0.69%), although the difference was not statistically significant (p = 0.178). Compared to non-carriers, PALB2 carriers has a tendency to appear in younger age (≤ 30 years) (25% vs 14.4%), human epidermal growth factor receptor-2 (HER2)-negative status (83.3% vs. 70.2%), and diagnosed with invasive micropapillary carcinoma (16.7% vs 3.1%). CONCLUSION: The prevalence of the germline PALB2 pathogenic variants was approximately 0.77% in Chinese patients with BRCA1/2-negative early-onset breast cancer. Our findings is crucial for understanding population-specific genetic risks and offering insights that can enhance genetic counseling and genetic testing strategies in this population.

Sodium chloride promotes macrophage pyroptosis and aggravates rheumatoid arthritis by activating SGK1 through GABA receptors Slc6a12.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and the production of autoantibodies. Previous studies have indicated an association between high-salt diets (HSD) and an increased risk of RA, yet the underlying mechanisms remain unclear. Macrophage pyroptosis, a pro-inflammatory form of cell death, plays a pivotal role in RA. In this study, we demonstrate that HSD exacerbates the severity of arthritis in collagen-induced arthritis (CIA) mice, correlating with macrophage infiltration and inflammatory lesions. Given the significant alterations observed in macrophages from CIA mice subjected to HSD, we specifically investigate the impact of HSD on macrophage responses in the inflammatory milieu of RA. In our in vitro experiments, pretreatment with NaCl enhances LPS-induced pyroptosis in RAW.264.7 and THP-1 cells through the p38 MAPK/NF-κB signaling pathway. Subsequent experiments reveal that Slc6a12 inhibitors and SGK1 silencing inhibit sodium-induced activation of macrophage pyroptosis and the p38 MAPK/NF-κB signaling pathway, whereas overexpression of the SGK1 gene counteracts the effect of sodium on macrophages. In conclusion, our findings verified that high salt intake promotes the progression of RA and provided a detailed elucidation of the activation of macrophage pyroptosis induced by sodium transportation through the Slc6a12 channel.

Multi-dimensional cell-free DNA-based liquid biopsy for sensitive early detection of gastric cancer.

BACKGROUND: Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality. METHODS: We collected a prospective study cohort of 110 stage I-II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation. RESULTS: Our cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942-0.982) in the study cohort, 0.972 (95% CI: 0.953-0.992) in the first validation cohort and 0.937 (95% CI: 0.890-0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified. CONCLUSIONS: We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.

Injectable Self-Healing Antibacterial Hydrogels with Tailored Functions by Loading Peptide Nanofiber-Biomimetic Silver Nanoparticles.

Polymer hydrogels find extensive application in biomedicine, serving specific purposes such as drug delivery, biosensing, bioimaging, cancer therapy, tissue engineering, and others. In response to the growing threat of bacterial infections and the escalating resistance to conventional antibiotics, this research introduces a novel injectable, self-healing antimicrobial hydrogel comprising bioactive aldolized hyaluronic acid (AHA) and quaternized chitosan (QCS). This designed QCS/AHA hydrogel incorporates self-assembling peptide nanofibers (PNFs) and small-sized silver nanoparticles (AgNPs) for tailored functionality. The resulting hybrid QCS/AHA/PNF/AgNPs hydrogel demonstrates impressive rheological characteristics, broad-spectrum antimicrobial efficacy, and high biocompatibility. Notably, its antimicrobial effectiveness against Escherichia coli and S. aureus surpasses 99.9%, underscoring its potential for treating infectious wounds. Moreover, the rheological analysis confirms its excellent shear-thinning and self-healing properties, enabling it to conform closely to irregular wound surfaces. Furthermore, the cytotoxicity assessment reveals its compatibility with human umbilical vein endothelial cells, exhibiting no significant adverse effects. The combined attributes of this bioactive QCS/AHA/PNF/AgNPs hydrogel position it as a promising candidate for antimicrobial applications and wound healing.

SMARCA5 reprograms AKR1B1-mediated fructose metabolism to control leukemogenesis.

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.

Immune checkpoint activity exacerbate renal interstitial fibrosis progression by enhancing PD-L1 expression in renal tubular epithelial cells.

Renal interstitial fibrosis (RIF) is often associated with inflammatory cell infiltration and no effective therapy. Programmed death cell-1 (PD-1) and its ligand PD-L1 were playing critical roles in T cell coinhibition and exhaustion, but the role in RIF is unclear. Here the data analyses of serum from 122 IgA nephrology (IgAN) patients showed that high level of soluble PD-1(sPD-1) was an independent risk factor for RIF and renal function progression. PD-L1 was also overexpressed in renal interstitial tissues from both IgAN patients with high level of sPD-1 and the unilateral ureteral obstruction (UUO) mouse. PD-L1 was significantly overexpressed in HK-2 cells with upregulated collagen and α-SMA when stimulated by inflammation or hypoxia in vitro. Additionally, matrix metalloproteinases (MMP-2) could increase the level of sPD-1 in culture supernatant when added in co-culture system of HK-2 and jurkat cells, which implied serum sPD-1 of IgAN might be cleaved by MMP-2 from T cells infiltrated into the tubulointerstitial inflammatory microenvironment. Crucially, injection of PD-L1 fusion protein, the blocker of sPD-1, could ameliorate kidney fibrosis in UUO mice by increasing T cell coinhibition and exhaustion, suggesting the therapeutic potential of PD-L1 fusion targeting for renal fibrosis. Take together, it reveals a novel causal role of sPD-1 in serum and PD-L1 of renal interstitial tissues in the development of renal fibrosis of IgAN, and targeting sPD-1 in serum by PD-L1 fusion protein is a potential therapeutic approach to prevent renal fibrosis of IgAN.

Phosphorylation of caspase-8 by RSKs via organ-constrained effects controls the sensitivity to TNF-induced death.

Caspase-8 (Casp8) serves as an initiator of apoptosis or a suppressor of necroptosis in context-dependent manner. Members of the p90 RSK family can phosphorylate caspase-8 at threonine-265 (T265), which can inactivate caspase-8 for bypassing caspase-8-mediated blockade of necroptosis and can also decrease caspase-8 level by promoting its degradation. Mutating T265 in caspase-8 to alanine (A) in mice blocked TNF-induced necroptotic cecum damage but resulted in unexpectedly massive injury in the small intestine. Here, we show RSK1, RSK2, and RSK3 redundantly function in caspase-8 phosphorylation, and the duodenum is the most severely affected part of the small intestine when T265 phosphorylation of caspase-8 was prevented. Eliminating caspase-8 phosphorylation resulted in a duodenum-specific increase in basal caspase-8 protein level, which shall be responsible for the increased sensitivity to TNF-induced damage. Apoptosis of intestinal epithelial cells (IECs) was predominant in the duodenum of TNF-treated Rsk1-/-Rsk2-/-Rsk3-/- and Casp8T265A/T265A mice, though necroptosis was also observed. The heightened duodenal injury amplified systemic inflammatory responses, as evidenced by the contribution of hematopoietic cells to the sensitization of TNF-induced animal death. Further analysis revealed that hematopoietic and non-hematopoietic cells contributed differentially to cytokine production in response to the increased cell death. Collectively, RSKs emerges as a previously overlooked regulator that, via tissue/organ-constrained inactivating caspase-8 and/or downregulating caspase-8 protein level, controls the sensitivity to TNF-induced organ injury and animal death.

Comparative Biomechanical Stability of the Fixation of Different Miniplates in Restorative Laminoplasty after Laminectomy: A Finite Element Study.

A novel H-shaped miniplate (HSM) was specifically designed for restorative laminoplasties to restore patients' posterior elements after laminectomies. A validated finite element (FE) model of L2/4 was utilized to create a laminectomy model, as well as three restorative laminoplasty models based on the fixation of different miniplates after a laminectomy (the RL-HSM model, the RL-LSM model, and the RL-THM model). The biomechanical effects of motion and displacement on a laminectomy and restorative laminoplasty with three different shapes for the fixation of miniplates were compared under the same mechanical conditions. This study aimed to validate the biomechanical stability, efficacy, and feasibility of a restorative laminoplasty with the fixation of miniplates post laminectomy. The laminectomy model demonstrated the greatest increase in motion and displacement, especially in axial rotation, followed by extension, flexion, and lateral bending. The restorative laminoplasty was exceptional in preserving the motion and displacement of surgical segments when compared to the intact state. This preservation was particularly evident in lateral bending and flexion/extension, with a slight maintenance efficacy observed in axial rotation. Compared to the laminectomy model, the restorative laminoplasties with the investigated miniplates demonstrated a motion-limiting effect for all directions and resulted in excellent stability levels under axial rotation and flexion/extension. The greatest reduction in motion and displacement was observed in the RL-HSM model, followed by the RL-LSM model and then the RL-THM model. When comparing the fixation of different miniplates in restorative laminoplasties, the HSMs were found to be superior to the LSMs and THMs in maintaining postoperative stability, particularly in axial rotation. The evidence suggests that a restorative laminoplasty with the fixation of miniplates is more effective than a conventional laminectomy due to the biomechanical effects of restoring posterior elements, which helps patients regain motion and limit load displacement responses in the spine after surgery, especially in axial rotation and flexion/extension. Additionally, our evaluation in this research study could benefit from further research and provide a methodological and modeling basis for the design and optimization of restorative laminoplasties.

HOXB5 promotes the progression and metastasis of osteosarcoma cells by activating the JAK2/STAT3 signalling pathway.

Objective: To investigate the involvement of the homeobox gene B5 (HOXB5) in the progression and metastasis of osteosarcoma. Methods: The expression of HOXB5 in human osteosarcoma tissues and its correlation with clinical indicators were investigated using bioinformatics analysis and immunohistochemical labelling. Human osteosarcoma cells (HOS, MG63, U2OS, and Saos-2) and normal human osteoblasts (hFOB1.19) were cultivated. The expression of HOXB5 in these cells was detected using western blotting (WB) and RT‒PCR. Two cell lines exhibiting elevated HOXB5 expression were chosen and divided into three groups: the blank group (mock), control group (control) and transfection group (shHOXB5). The transfection group was infected with lentivirus expressing shRNAs targeting HOXB5. The transfection efficiency was detected by WB. Cell proliferation suppression was measured by CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays; the percentage of apoptotic cells was determined by flow cytometry; and cell migration and invasion were detected via the Transwell chamber test. WB was utilized to determine the protein expression of genes linked to metastasis (MMP2, MMP9), apoptosis (Bax, Bcl-2), and the JAK2/STAT3 pathway (JAK2, p-JAK2, STAT3, p-STAT3). Results: In osteosarcoma tissues, HOXB5 expression was elevated and strongly correlated with distant metastasis. Silencing HOXB5 reduced the proliferation, migration and invasion of osteosarcoma cells; prevented the progression and metastasis of tumours in tumour-bearing nude mice; and reduced the activation of key proteins in the JAK2/STAT3 signalling pathway. Conclusion: Through the JAK2/STAT3 signalling pathway, HOXB5 plays a crucial role in the malignant progression of osteosarcoma and is a promising target for osteosarcoma treatment.

METTL3 facilitates prostate cancer progression via inducing HOXC6 m6A modification and stabilizing its expression through IGF2BP2-dependent mechanisms.

HOXC6 (Homeobox C6) and methyltransferase-like 3 (METTL3) have been shown to be involved in the progression of prostate cancer (PCa). However, whether HOXC6 performs oncogenic effects in PCa via METTL3-mediated N6-methyladenosine (m6A) modification is not yet reported. The Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, scratch, sphere formation assays were applied for cell growth, invasion, migration and stemness analyses. Glycolysis was evaluated by measuring glucose consumption, lactate generation and ATP/ADP ratio. The N6-methyladenine (m6A) modification profile was determined by RNA immunoprecipitation (Me-RIP) assay. The proteins that interact with PGK1 (phosphoglycerate kinase 1) were confirmed by Co-immunoprecipitation assay. Tumor formation experiments in mice were conducted for in vivo assay. PCa tissues and cells showed highly expressed HOXC6 and METTL3. Functionally, the silencing of HOXC6 or METTL3 suppresses PCa cell proliferation, invasion, migration, stemness, and glycolysis. Moreover, METTL3-induced HOXC6 m6A modification to stabilize its expression. In addition, the m6A reader IGF2BP2 directly recognized and bound to HOXC6 mRNA, and maintained its stability, and was involved in the regulation of HOXC6 expression by METTL3. Furthermore, IGF2BP2 knockdown impaired PCa cell proliferation, invasion, migration, stemness, and glycolysis by regulating HOXC6. Besides that HOXC6 interacted with the glycoytic enzyme PGK1 in PCa cells. In vivo assays further showed that METTL3 silencing reduced the expression of HOXC6 and PGK1, and impeded PCa growth. METTL3 promoted PCa progression by maintaining HOXC6 expression in an m6A-IGF2BP2-dependent mechanism.