Investigation of prognostic values of immune infiltration and LGMN expression in the microenvironment of osteosarcoma.

BACKGROUND: Osteosarcoma (OS), the most common primary malignant bone tumor, predominantly affects children and young adults and is characterized by high invasiveness and poor prognosis. Despite therapeutic advancements, the survival rate remains suboptimal, indicating an urgent need for novel biomarkers and therapeutic targets. This study aimed to investigate the prognostic significance of LGMN expression and immune cell infiltration in the tumor microenvironment of OS. METHODS: We performed an integrative bioinformatics analysis utilizing the GEO and TARGET-OS databases to identify differentially expressed genes (DEGs) associated with LGMN in OS. We conducted Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to explore the biological pathways and functions. Additionally, we constructed protein-protein interaction (PPI) networks, a competing endogenous RNA (ceRNA) network, and applied the CIBERSORT algorithm to quantify immune cell infiltration. The diagnostic and prognostic values of LGMN were evaluated using the area under the receiver operating characteristic (ROC) curve and Cox regression analysis. Furthermore, we employed Consensus Clustering Analysis to explore the heterogeneity within OS samples based on LGMN expression. RESULTS: The analysis revealed significant upregulation of LGMN in OS tissues. DEGs were enriched in immune response and antigen processing pathways, suggesting LGMN's role in immune modulation within the TME. The PPI and ceRNA network analyses provided insights into the regulatory mechanisms involving LGMN. Immune cell infiltration analysis indicated a correlation between high LGMN expression and increased abundance of M2 macrophages, implicating an immunosuppressive role. The diagnostic AUC for LGMN was 0.799, demonstrating its potential as a diagnostic biomarker. High LGMN expression correlated with reduced overall survival (OS) and progression-free survival (PFS). Importantly, Consensus Clustering Analysis identified two distinct subtypes of OS, highlighting the heterogeneity and potential for personalized medicine approaches. CONCLUSIONS: Our study underscores the prognostic value of LGMN in osteosarcoma and its potential as a therapeutic target. The identification of LGMN-associated immune cell subsets and the discovery of distinct OS subtypes through Consensus Clustering Analysis provide new avenues for understanding the immunosuppressive TME of OS and may aid in the development of personalized treatment strategies. Further validation in larger cohorts is warranted to confirm these findings.

Lycium ruthenicum water extract preserves retinal ganglion cells in chronic ocular hypertension mouse models.

Lycium ruthenicum Murray (LR), known as "black goji berry" or "black wolfberry", is widely utilized in chinese herbal medicine. LR fruit showed its antioxidant and/or anti-inflammation activity in treating cardiac injury, experimental colitis, nonalcoholic fatty liver disease, fatigue, and aging. Glaucoma is the leading cause of irreversible blindness. Besides elevated intraocular pressure (IOP), oxidative stress and neuroinflammation were recognized to contribute to the pathogenesis of glaucoma. This study investigated the treatment effects of LR water extract (LRE) on retinal ganglion cells (RGCs) threatened by sustained IOP elevation in a laser-induced chronic ocular hypertension (COH) mouse model and the DBA/2J mouse strain. The antioxidation and anti-inflammation effects of LRE were further tested in the H2O2-challenged immortalized microglial (IMG) cell line in vitro. LRE oral feeding (2 g/kg) preserved the function of RGCs and promoted their survival in both models mimicking glaucoma. LRE decreased 8-hydroxyguanosine (oxidative stress marker) expression in the retina. LRE reduced the number of Iba-1+ microglia in the retina of COH mice, but not in the DBA/2J mice. At the mRNA level, LRE reversed the COH induced HO-1 and SOD-2 overexpressions in the retina of COH mice. Further in vitro study demonstrated that LRE pretreatment to IMG cells could significantly reduce H2O2 induced oxidative stress through upregulation of GPX-4, Prdx-5, HO-1, and SOD-2. Our work demonstrated that daily oral intake of LRE can be used as a preventative/treatment agent to protect RGCs under high IOP stress probably through reducing oxidative stress and inhibiting microglial activation in the retina.

BMA-based Mendelian randomization identifies blood metabolites as causal candidates in pregnancy-induced hypertension.

Pregnancy-induced hypertension (PIH), a prominent determinant of maternal mortality and morbidity worldwide, is hindered by the absence of efficacious biomarkers for early diagnosis, contributing to suboptimal outcomes. Here, we explored potential causal relationships between blood metabolites and the risk of PIH using Mendelian randomization (MR). We employed a two-sample univariable MR approach to empirically estimate the causal relationships between 249 circulating metabolites and PIH. Inverse variance weighted, MR-egger, weight median, simple mode, and weighted mode methods were used for causal estimates. The exposure-to-outcome directionality was confirmed with the MR Steiger test. The Bayesian model averaging MR (MR-BMA) method was applied to detect the predominant causal metabolic traits with alignment for pleiotropy effects. In the primary analysis, analyzing 249 metabolites, we identified 25 causally linked to PIH, including 11 lipid-related traits and 6 associated with fatty acid (un)saturation. Importantly, MR-BMA analyses corroborated the total concentration of branched-chain amino acids(total-BCAA) to be the highest rank causal metabolite, followed by leucine (Leu), phospholipids to total lipids ratio in medium LDL (M-LDL-PL-pct), and Val (all P < 0.05). The directionality of causality predicted by univariable MR and MR-BMA for these metabolites remained consistent. This study highlights the causal connection between metabolites and PIH risk. It highlighted BCAAs as the strongest causal candidates warranting further investigation. Since PIH typically occurs in the second and third trimesters, extending these findings could inform earlier strategies to reduce its risk. Directed acyclic graph of the MR framework investigating the causal relationship between metabolites and PIH. MR: Mendelian randomization; GIVs: genetic instrument variables; SNPs: single-nucleotide polymorphism; IVW: inverse variance weighted; WM: weighted median; PIH: pregnancy-induced hypertension; SM: significant metabolite; MR-BMA: Bayesian model averaging MR.

NAT1 inhibits liver metastasis of colorectal cancer by regulating EMT and glycolysis.

Metastasis is the primary cause of cancer-related deaths, and colorectal cancer (CRC) liver metastasis is a major poor prognostic factor in CRC. NAT1 (N-acetyltransferase 1) plays a crucial role in the invasive and metastatic processes of colorectal cancer. The role and molecular mechanism of NAT1 on tumor cells were verified by establishing a cell model of overexpression and knockdown of NAT1, and further verified by establishing a liver metastasis model of colorectal cancer for animal experiments. In vivo and in vitro experiments have demonstrated that overexpression of NAT1 reduces the ability of metastasis and invasion of colorectal cancer cells. NAT1 overexpression inhibits the PI3K/AKT/mTOR signaling pathway, thereby suppressing the EMT (epithelial-mesenchymal transition) process and glycolytic ability of tumor cells. Additionally, decreased glycolytic ability results in reduced VEGF (Vascular endothelial growth factor) expression in colorectal cancer cells. The decreased VEGF expression leads to decreased angiogenesis and vascular permeability in liver metastases, ultimately reducing the occurrence of liver metastasis. Our findings highlight that overexpression of NAT1 significantly inhibits the PI3K/AKT/mTOR signaling pathway, thereby suppressing EMT, glycolytic ability, and VEGF expression in colorectal cancer cells, collectively preventing the development of liver metastasis.

Association between driving pressure-guided ventilation and postoperative pulmonary complications in surgical patients: a meta-analysis with trial sequential analysis.

BACKGROUND: Prior studies have reported inconsistent results regarding the association between driving pressure-guided ventilation and postoperative pulmonary complications (PPCs). We aimed to investigate whether driving pressure-guided ventilation is associated with a lower risk of PPCs. METHODS: We systematically searched electronic databases for RCTs comparing driving pressure-guided ventilation with conventional protective ventilation in adult surgical patients. The primary outcome was a composite of PPCs. Secondary outcomes were pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS). Meta-analysis and subgroup analysis were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CI). Trial sequential analysis (TSA) was used to assess the conclusiveness of evidence. RESULTS: Thirteen RCTs with 3401 subjects were included. Driving pressure-guided ventilation was associated with a lower risk of PPCs (RR 0.70, 95% CI 0.56-0.87, P=0.001), as indicated by TSA. Subgroup analysis (P for interaction=0.04) found that the association was observed in non-cardiothoracic surgery (nine RCTs, 1038 subjects, RR 0.61, 95% CI 0.48-0.77, P< 0.0001), with TSA suggesting sufficient evidence and conclusive result; however, it did not reach significance in cardiothoracic surgery (four RCTs, 2363 subjects, RR 0.86, 95% CI 0.67-1.10, P=0.23), with TSA indicating insufficient evidence and inconclusive result. Similarly, a lower risk of pneumonia was found in non-cardiothoracic surgery but not in cardiothoracic surgery (P for interaction=0.046). No significant differences were found in atelectasis and ARDS between the two ventilation strategies. CONCLUSIONS: Driving pressure-guided ventilation was associated with a lower risk of postoperative pulmonary complications in non-cardiothoracic surgery but not in cardiothoracic surgery. SYSTEMATIC REVIEW PROTOCOL: INPLASY 202410068.

Toll-like Receptor Agonist CBLB502 Protects Against Radiation-induced Intestinal Injury in Mice.

BACKGROUND/AIM: The small intestine is one of the organs most vulnerable to ionizing radiation (IR) damage. However, methods to protect against IR-induced intestinal injury are limited. CBLB502, a Toll-like receptor 5 (TLR5) agonist from Salmonella flagellin, exerts radioprotective effects on various tissues and organs. However, the molecular mechanisms by which CBLB502 protects against IR-induced intestinal injury remain unclear. Thus, this study aimed to elucidate the mechanisms underlying IR-induced intestinal injury and the protective effects of CBLB502 against this condition in mice. MATERIALS AND METHODS: Mice were administered 0.2 mg/kg CBLB502 before IR at different doses for different time points, and then the survival rate, body weight, hemogram, and histopathology of the mice were analyzed. RESULTS: CBLB502 reduced IR-induced intestinal injury. RNA-seq analysis revealed that different doses and durations of IR induced different regulatory patterns. CBLB502 protected against intestinal injury mainly after IR by reversing the expression of IR-induced genes and regulating immune processes and metabolic pathways. CONCLUSION: This study preliminarily describes the regulatory mechanism of IR-induced intestinal injury and the potential molecular protective mechanism of CBLB502, providing a basis for identifying the functional genes and molecular mechanisms that mediate protection against IR-induced injury.

Embracing the future: Integrating ChatGPT into China's nursing education system.

This article delves into the role of ChatGPT within the rapidly evolving field of artificial intelligence, especially highlighting its significant potential in nursing education. Initially, the paper presents the notable advancements ChatGPT has achieved in facilitating interactive learning and providing real-time feedback, along with the academic community's growing interest in this technology. Subsequently, summarizing the research outcomes of ChatGPT's applications in nursing education, including various clinical disciplines and scenarios, showcases the enormous potential for multidisciplinary education and addressing clinical issues. Comparing the performance of several Large Language Models (LLMs) on China's National Nursing Licensure Examination, we observed that ChatGPT demonstrated a higher accuracy rate than its counterparts, providing a solid theoretical foundation for its application in Chinese nursing education and clinical settings. Educational institutions should establish a targeted and effective regulatory framework to leverage ChatGPT in localized nursing education while assuming corresponding responsibilities. Through standardized training for users and adjustments to existing educational assessment methods aimed at preventing potential misuse and abuse, the full potential of ChatGPT as an innovative auxiliary tool in China's nursing education system can be realized, aligning with the developmental needs of modern teaching methodologies.

Long non­coding RNA lung cancer­associated transcript 1 regulates ferroptosis via microRNA­34a­5p­mediated GTP cyclohydrolase 1 downregulation in lung cancer cells.

Ferroptosis, a recently discovered type of programmed cell death triggered by excessive accumulation of iron­dependent lipid peroxidation, is linked to several malignancies, including non­small cell lung cancer. Long non­coding RNAs (lncRNAs) are involved in ferroptosis; however, data on their role and mechanism in cancer therapy remains limited. Therefore, the aim of the present study was to identify ferroptosis­associated mRNAs and lncRNAs in A549 lung cancer cells treated with RAS­selective lethal 3 (RSL3) and ferrostatin­1 (Fer­1) using RNA sequencing. The results demonstrated that lncRNA lung cancer­associated transcript 1 (LUCAT1) was significantly upregulated in lung adenocarcinoma and lung squamous cell carcinoma tissues. Co­expression analysis of differentially expressed mRNAs and lncRNAs suggested that LUCAT1 has a crucial role in ferroptosis. LUCAT1 expression was markedly elevated in A549 cells treated with RSL3, which was prevented by co­incubation with Fer­1. Functionally, overexpression of LUCAT1 facilitated cell proliferation and reduced the occurrence of ferroptosis induced by RSL3 and Erastin, while inhibition of LUCAT1 expression reduced cell proliferation and increased ferroptosis. Mechanistically, downregulation of LUCAT1 resulted in the downregulation of both GTP cyclohydrolase 1 (GCH1) and ferroptosis suppressor protein 1 (FSP1). Furthermore, inhibition of LUCAT1 expression upregulated microRNA (miR)­34a­5p and then downregulated GCH1. These results indicated that inhibition of LUCAT1 expression promoted ferroptosis by modulating the downregulation of GCH1, mediated by miR­34a­5p. Therefore, the combination of knocking down LUCAT1 expression with ferroptosis inducers may be a promising strategy for lung cancer treatment.

Inhibition of UBA52 induces autophagy via EMC6 to suppress hepatocellular carcinoma tumorigenesis and progression.

Ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) has a role in the occurrence and development of tumours. However, the mechanism by which UBA52 regulates hepatocellular carcinoma (HCC) tumorigenesis and progression remains poorly understood. By using the Cell Counting Kit (CCK-8), colony formation, wound healing and Transwell assays, we assessed the effects of UBA52 knockdown and overexpression on the proliferation and migration of HCC cells in vitro. By establishing subcutaneous and metastatic tumour models in nude mice, we evaluated the effects of UBA52 on HCC cell proliferation and migration in vivo. Through bioinformatic analysis of data from the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases, we discovered that UBA52 is associated with autophagy. In addition, we discovered that HCC tissues with high UBA52 expression had a poor prognosis in patients. Moreover, knockdown of UBA52 reduced HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, knockdown of UBA52 induced autophagy through EMC6 in HCC cells. These findings suggest that UBA52 promoted the proliferation and migration of HCC cells through autophagy regulation via EMC6 and imply that UBA52 may be a viable novel treatment target for HCC patients.

Unraveling the Role of RNase L Knockout in Alleviating Immune Response Activation in Mice Bone Marrow after Irradiation.

Ionizing radiation (IR) induces severe hematopoietic injury by causing DNA and RNA damage as well as activating the immune responses, necessitating the development of effective therapeutic strategies. Ribonuclease L (RNase L) as an innate immune response pathway is triggered by exogenous and endogenous abnormal dsRNA under viral infection and dyshomeostasis, thereby activating the immune responses. Thus, we investigated the effect of RNase L on irradiation-induced bone marrow damage using RNase L knockout (RNase L-/-) mice. Phenotypic analysis revealed that RNase L knockout mitigates irradiation-induced injury in the bone marrow. Further investigation into the mechanism of RNase L by RNA-seq, qRT-PCR, and CBA analysis demonstrated that RNase L deficiency counteracts the upregulation of genes related to immune responses induced by irradiation, including cytokines and interferon-stimulated genes. Moreover, RNase L deficiency inhibits the increased levels of immunoglobulins in serum induced by irradiation. These findings indicate that RNase L plays a role in the immune response induced by irradiation in the bone marrow. This study further enhances our understanding of the biological functions of RNase L in the immune response induced by irradiation and offers a novel approach for managing irradiation-induced bone marrow injury through the regulation of RNase L activation.

Quality and Dependability of ChatGPT and DingXiangYuan Forums for Remote Orthopedic Consultations: Comparative Analysis.

BACKGROUND: The widespread use of artificial intelligence, such as ChatGPT (OpenAI), is transforming sectors, including health care, while separate advancements of the internet have enabled platforms such as China's DingXiangYuan to offer remote medical services. OBJECTIVE: This study evaluates ChatGPT-4's responses against those of professional health care providers in telemedicine, assessing artificial intelligence's capability to support the surge in remote medical consultations and its impact on health care delivery. METHODS: We sourced remote orthopedic consultations from "Doctor DingXiang," with responses from its certified physicians as the control and ChatGPT's responses as the experimental group. In all, 3 blindfolded, experienced orthopedic surgeons assessed responses against 7 criteria: "logical reasoning," "internal information," "external information," "guiding function," "therapeutic effect," "medical knowledge popularization education," and "overall satisfaction." We used Fleiss κ to measure agreement among multiple raters. RESULTS: Initially, consultation records for a cumulative count of 8 maladies (equivalent to 800 cases) were gathered. We ultimately included 73 consultation records by May 2023, following primary and rescreening, in which no communication records containing private information, images, or voice messages were transmitted. After statistical scoring, we discovered that ChatGPT's "internal information" score (mean 4.61, SD 0.52 points vs mean 4.66, SD 0.49 points; P=.43) and "therapeutic effect" score (mean 4.43, SD 0.75 points vs mean 4.55, SD 0.62 points; P=.32) were lower than those of the control group, but the differences were not statistically significant. ChatGPT showed better performance with a higher "logical reasoning" score (mean 4.81, SD 0.36 points vs mean 4.75, SD 0.39 points; P=.38), "external information" score (mean 4.06, SD 0.72 points vs mean 3.92, SD 0.77 points; P=.25), and "guiding function" score (mean 4.73, SD 0.51 points vs mean 4.72, SD 0.54 points; P=.96), although the differences were not statistically significant. Meanwhile, the "medical knowledge popularization education" score of ChatGPT was better than that of the control group (mean 4.49, SD 0.67 points vs mean 3.87, SD 1.01 points; P<.001), and the difference was statistically significant. In terms of "overall satisfaction," the difference was not statistically significant between the groups (mean 8.35, SD 1.38 points vs mean 8.37, SD 1.24 points; P=.92). According to how Fleiss κ values were interpreted, 6 of the control group's score points were classified as displaying "fair agreement" (P<.001), and 1 was classified as showing "substantial agreement" (P<.001). In the experimental group, 3 points were classified as indicating "fair agreement," while 4 suggested "moderate agreement" (P<.001). CONCLUSIONS: ChatGPT-4 matches the expertise found in DingXiangYuan forums' paid consultations, excelling particularly in scientific education. It presents a promising alternative for remote health advice. For health care professionals, it could act as an aid in patient education, while patients may use it as a convenient tool for health inquiries.

Personalized Porous Gelatin Methacryloyl Sustained-Release Nicotinamide Protects Against Noise-Induced Hearing Loss.

There are no Food and Drug Administration-approved drugs for treating noise-induced hearing loss (NIHL), reflecting the absence of clear specific therapeutic targets and effective delivery strategies. Noise trauma is demonstrated results in nicotinamide adenine dinucleotide (NAD+) downregulation and mitochondrial dysfunction in cochlear hair cells (HCs) and spiral ganglion neurons (SGNs) in mice, and NAD+ boosted by nicotinamide (NAM) supplementation maintains cochlear mitochondrial homeostasis and prevents neuroexcitatory toxic injury in vitro and ex vivo, also significantly ameliorated NIHL in vivo. To tackle the limited drug delivery efficiency due to sophisticated anatomical barriers and unique clearance pathway in ear, personalized NAM-encapsulated porous gelatin methacryloyl (PGMA@NAM) are developed based on anatomy topography of murine temporal bone by micro-computed tomography and reconstruction of round window (RW) niche, realizing hydrogel in situ implantation completely, NAM sustained-release and long-term auditory preservation in mice. This study strongly supports personalized PGMA@NAM as NIHL protection drug with effective inner ear delivery, providing new inspiration for drug-based treatment of NIHL.

Clinical outcomes of arthroscopic all-inside anterior talofibular ligament suture augmentation repair versus modified suture augmentation repair for chronic ankle instability patients.

BACKGROUND: To compare the clinical efficacies of arthroscopic anterior talofibular ligament suture augmentation repair and modified suture augmentation repair in patients with chronic ankle instability (CAI). METHODS: From October 2019 to August 2020, 100 patients with CAI were enrolled after propensity score matching analysis and observed for two years. Among them, 50 underwent modified suture augmentation repair and the other 50 underwent suture augmentation repair. The clinical efficacies of CAI treatments were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) clinical rating scale, visual analog scale (VAS), and anterior drawer test scores. RESULTS: The postoperative AOFAS score of the modified suture augmentation repair group (83.8 ± 11.3) was significantly higher than that of the suture augmentation repair group (76.3 ± 11.3; P = 0.001). The VAS (P = 0.863) and anterior drawer test (P = 0.617) scores were not significantly different between the two treatment groups. CONCLUSION: Both the modified suture augmentation repair and suture augmentation repair demonstrated good clinical efficacies. The AOFAS score of the modified suture augmentation repair group was superior to that of the conventional suture augmentation repair group. Thus, modified suture augmentation repair is a feasible and practical surgical technique for CAI treatment.

Mechanistic insights into the effects of diuron exposure on Alexandrium pacificum.

Diuron (N-(3,4-dichlorophenyl)-N,N­dimethylurea, DCMU), a ureic herbicide, is extensively used in agriculture to boost crop productivity; however, its extensive application culminates in notable environmental pollution, especially in aquatic habitats. Therefore, the present study investigated the effect of diuron on the dinoflagellate Alexandrium pacificum, which is known to induce harmful algal blooms (HAB), and its potential to biodegrade DCMU. Following a four-day DCMU exposure, our results revealed that A. pacificum proficiently assimilated DCMU at concentrations of 0.05 mg/L and 0.1 mg/L in seawater, attaining a complete reduction (100 % efficiency) after 96 h for both concentrations. Moreover, evaluations of paralytic shellfish toxins content indicated that cells subjected to higher DCMU concentrations (0.1 mg/L) exhibited reductions of 73.4 %, 86.7 %, and 75 % in GTX1, GTX4, and NEO, respectively. Exposure to DCMU led to a notable decrease in A. pacificum's photosynthetic efficacy, accompanied by increased levels of reactive oxygen species (ROS) and suppressed cell growth, with a growth inhibition rate of 41.1 % at 72 h. Proteomic investigations pinpointed the diminished expression levels of specific proteins like SxtV and SxtW, linked to paralytic shellfish toxins (PSTs) synthesis, as well as key proteins associated with Photosystem II, namely PsbA, PsbD, PsbO, and PsbU. Conversely, proteins central to the cysteine biosynthesis pathways exhibited enhanced expression. In summary, our results preliminarily resolved the molecular mechanisms underlying the response of A. pacificum to DCMU and revealed that DCMU affected the synthesis of PSTs. Meanwhile, our data suggested that A. pacificum has great potential in scavenging DCMU.

Establishment and application of TSDPSO-SVM model combined with multi-dimensional feature fusion method in the identification of fracture-related infection.

Fracture-related infection (FRI) is one of the most common and intractable complications in orthopedic trauma surgery. This complication can impose severe psychological burdens and socio-economic impacts on patients. Although the definition of FRI has been proposed recently by an expert group, the diagnostic criteria for FRI are not yet standardized. A total of 4761 FRI patients and 4761 fracture patients (Non-FRI) were included in the study. The feature set of patients included imaging characteristics, demographic information, clinical symptoms, microbiological findings, and serum inflammatory markers, which were reduced by the Principal Component Analysis. To optimize the Support Vector Machine (SVM) model, the Traction Switching Delay Particle Swarm Optimization (TSDPSO) algorithm, a recognition method was proposed. Moreover, five machine learning models, including TSDPSO-SVM, were employed to distinguish FRI from Non-FRI. The Area under the Curve of TSDPSO-SVM was 0.91, at least 5% higher than that of other models. Compared with the Random Forest, Backpropagation Neural Network (BP), SVM and eXtreme Gradient Boosting (XGBoost), TSDPSO-SVM demonstrated remarkable accuracy in the test set ([Formula: see text]). The recall of TSDPSO-SVM was 98.32%, indicating a significant improvement ([Formula: see text]). Compared with BP and SVM, TSDPSO-SVM exhibited significantly superior specificity, false positive rate and precision ([Formula: see text]. The five models yielded consistent results in the training and testing of FRI patients across different age groups. TSDPSO-SVM is validated to have the maximum overall prediction ability and can effectively distinguish between FRI and Non-FRI. For the early diagnosis of FRI, TSDPSO-SVM may provide a reference basis for clinicians, especially those with insufficient experience. These results also lay a foundation for the intelligent diagnosis of FRI. Furthermore, these findings exhibit the application potential of this model in the diagnosis and classification of other diseases.

The role of mitochondria-related lncRNAs in characterizing the immune landscape and supervising the prognosis of osteosarcoma.

Mitochondrial damage is related to the functional properties of immune cells as well as to tumorigenesis and progression. Nevertheless, there is an absence concerning the systematic evaluation of mitochondria-associated lncRNAs (MALs) in the immune profile and tumor microenvironment of osteosarcoma patients. Based on transcriptomic and clinicopathological data from the TARGET database, MAL-related patterns were ascertained by consistent clustering, and gene set variation analysis of the different patterns was completed. Next, a MAL-derived scoring system was created using Cox and LASSO regression analyses and validated by Kaplan-Meier and ROC curves. The GSEA, ESTIMATE, and CIBERSORT algorithms were utilized to characterize the immune status and underlying biological functions in the different MAL score groups. MAL-derived risk scores were well stabilized and outperformed traditional clinicopathological features to reliably predict 5-year survival in osteosarcoma cohorts. Moreover, patients with increased MAL scores were observed to suffer from poorer prognosis, higher tumor purity, and an immunosuppressive microenvironment. Based on estimated half-maximal inhibitory concentrations, the low-MAL score group benefited more from gemcitabine and docetaxel, and less from thapsigargin and sunitinib compared to the high-MAL score group. Pan-cancer analysis demonstrated that six hub MALs were strongly correlated with clinical outcomes, immune subtypes, and tumor stemness indices in various common cancers. Finally, we verified the expression patterns of hub MALs in osteosarcoma with qRT-PCR. In summary, we identified the crosstalk between prognostic MALs and tumor-infiltrating immune cells in osteosarcoma, providing a potential strategy to ameliorate clinical stratification management.

A case report of rib osteosarcoma and literature review.

About half of osteosarcomas occur near the knee joint, but other sites such as the humerus, upper femur, fibula, spine, and ilium can also occur. However, rib osteosarcoma is rarely reported. Here, we report the case of a 17-year-old female who was found to have a left dorsal mass on physical examination. Computed tomography (CT) revealed bone destruction in the seventh rib, leading to surgery for mass excision. Pathological results suggested chondroblastic osteosarcoma. After surgery, the patient was treated with chemotherapy and is doing well.

Mendelian randomization study of gastroesophageal reflux disease and major depression.

This study systematically investigated the causal relationship between gastroesophageal reflux disease (GERD) and major depression (MD). Single-nucleotide polymorphisms (SNPs) associated with disorders of interest were screened via the genome-wide association study (GWAS) enrolling individuals of European descent. Summary-level data for GERD and MD were extracted from the UK Biobank. The inverse-variance-weighted (IVW) method was utilized as the primary analysis. Sensitivity analyses were performed using the MR-Egger method, the Maximum likelihood method, the MR-pleiotropy residual sum outlier (MR-PRESSO) method, and MR-robust adjusted profile score (MR-RAPS) method. MR-Egger regression, heterogeneity tests, pleiotropy tests, and leave-one-out tests were also performed to analyze sensitivity. The MR Steiger test was used to verify the directionality of the exposure to the outcome. An available website tool (https://shiny.cnsgenomics.com/mRnd/) was used to calculate the statistical power of MR analysis. Meta-analysis was applied to test MD's average genetically predicted effect on GERD. Our MR study showed a bidirectional causal association between MD and GERD. Regarding MD to GERD, there was a positive association between them; the ORs were 1.500 (95% CI = 1.320-1.704; P = 4.91E-10) and 2.058 (95% CI = 1.868-2.267; P = 2.20E-48) in the IVW method, respectively. In addition, the meta-analysis also showed a strong positive causal association between MD and GERD. When exposure and outcome were reversed, genetic predisposition to GERD was significantly associated with the overall Risk of advanced MD (ieu-a-1187, OR = 1.982, 95% CI = 1.694-2.319, P = 1.41E-17; ieu-b-102, OR = 1.612, 95% CI = 1.530-2.700, P = 1.15E-70). Our study provides 100% power to detect the causal effect of MD on GERD and vice versa. Genetically predicted MD was positively associated with higher GERD risk, and vice versa. Our study reminds clinicians to pay attention to screening for GERD when diagnosing and treating MD and vice versa. Moreover, there may be positive feedback between MD and GERD when treating and preventing one disorder may benefit the treatment and prevention of the other.

Toll-like Receptor Agonist CBLB502 Protects Against Cisplatin-induced Liver and Kidney Damage in Mice.

BACKGROUND/AIM: CBLB502, a Toll-like receptor-5 agonist derived from Salmonella flagellin, exerts protective roles against irradiation and chemical drugs in mammalian tissues and stimulates tissue regeneration. This study aimed to investigate whether CBLB502 can protect against liver and kidney damage induced by the chemotherapeutic drug cisplatin (CDDP) and the underlying mechanism of the protective effect. MATERIALS AND METHODS: Mice were pretreated with CBLB502 [0.2 mg/kg, intraperitoneal (i.p.) injection] 0.5 h prior to administration of CDDP (20 mg/kg, i.p. injection), and analyses of the liver and kidney indices, blood biochemistry, and histopathology were performed. RESULTS: Pretreatment with CBLB502 alleviated CDDP-induced liver and kidney damage. RNA sequencing and bioinformatic analysis indicated that CDDP induced a similar damage-promoting gene regulation pattern in the liver and kidney. CBLB502 protected against liver and kidney damage only after CDDP treatment primarily via different pathways. However, some CBLB502-regulated genes were common between the liver and kidney, including those involved in blood coagulation, fibrinolysis, hemostasis, apoptotic regulation, NF-kappaB signaling, and response to lipopolysaccharide, suggesting a general protective effect by CBLB502. CONCLUSION: Our data provide insights into the protective mechanism of CBLB502 against CDDP-induced tissue damage in the liver and kidney and might provide a basis for future studies on functional genes and regulatory mechanisms that mediate protection against chemoradiotherapy-induced damage.

Utilization of lipidic food waste as low-cost nutrients for enhancing the potentiality of biofuel production from engineered diatom under temperature variations.

The scarcity of natural fossil fuels presents a promising opportunity for the development of renewable microalgae-based biofuels. However, the current microalgae cultivation is unable to effectively address the high costs of the production of biofuels. To tackle this challenge, this study focused on recruiting engineered Phaeodactylum tricornutum (FabG-OE) to enhance biomass accumulation and lipid production by employing food waste hydrolysate under temperature variations. The biomass and lipid accumulations of FabG-OE were improved effectively in mixed culture medium and food waste hydrolysate at a volume ratio (v/v) of 80:20 at 30 °C. It was found that oxidative stress might contribute to the overexpression of lipogenic genes, thereby leading to lipogenesis at 30 °C. Upscaling cultivation of FabG-OE at 30 °C using a semi-continuous strategy and batch strategy was conducted to achieve 0.73 and 0.77 g/L/d of biomass containing 0.35 and 0.38 g/L/d of lipid, respectively. In summary, these findings provide valuable insights for advancing microalgae-based biofuel production.