Plasma Metabolic Profiles-Based Prediction of Induction Chemotherapy Efficacy in Nasopharyngeal Carcinoma: Results of a Bidirectional Clinical Trial.

PURPOSE: The efficacy of induction chemotherapy (IC) as a primary treatment for advanced nasopharyngeal carcinoma (NPC) remains a topic of debate, with a lack of dependable biomarkers for predicting its efficacy. This study seeks to establish a predictive classifier utilizing plasma metabolomics profiling. EXPERIMENTAL DESIGN: A total of 166 NPC patients enrolled in the clinical trial NCT05682703 and undergoing IC were included in the study. Plasma lipoprotein profiles were obtained using 1H-NMR before and after IC treatment. An AI-assisted radiomics method was developed to effectively evaluate the efficacy. Metabolic biomarkers were identified through a machine learning approach based on a discovery cohort and subsequently validated in a validation cohort that mimicked the most unfavorable scenario in real-world. RESULTS: Our research findings indicate that the effectiveness of IC varies among individual patients, with a correlation observed between efficacy and changes in metabolite profiles. Utilizing machine learning techniques, it was determined that the XGB model exhibited notable efficacy, attaining an Area Under the Curve (AUC) value of 0.792 (95% CI, 0.668-0.913). In the validation cohort, the model exhibited strong stability and generalizability with an AUC of 0.786 (95%CI, 0.533-0.922). CONCLUSION: In this study, we found that dysregulation of plasma lipoprotein may result in resistance to IC in NPC patients. The prediction model constructed based on the plasma metabolites' profile as good predictive capabilities and potential for real-world generalization. This discovery has implications for the development of treatment strategies and may offer insight into potential targets for enhancing the effectiveness of IC.

The influence of manual segmentation strategies and different phases selection on machine learning-based computed tomography in renal tumors: a systematic review and meta-analysis.

BACKGROUND: Delineating the region/volume of interest (ROI/VOI) and selecting the phases are of importance in developing machine learning (ML). The results will change when choosing different methods of drawing the ROI/VOI and selecting different phases. However, there is no related standard for delineating the ROI/VOI and selecting the phases in renal tumors to develop ML based on computed tomography (CT). METHODS: The PubMed and Web of Science were searched for related studies published until March 1, 2023. Inclusion criteria were studies that developed ML models in renal tumors from CT images. And the binary diagnostic accuracy data were extracted to obtain the outcomes, such as sensitivity (SE), specificity (SP), accuracy (ACC), and area under the curve (AUC). RESULTS: Twenty-three papers were included in the meta-analysis with a pooled SE of 87% (95% CI 85-88%), SP of 82% (95% CI 79-85%), and AUC of 91% (95% CI 89-93%) in phases; a pooled SE of 82% (95% CI 80-84%), SP of 85% (95% CI 83-86%), and AUC of 90% (95% CI 88-93%) in phases combined with delineating strategies, respectively. In all different combinations, the contour-focused and single phase produce the highest AUC of 93% (95% CI 90-95%). In subgroup analyses (sample size, year of publication, and geographical distribution), the performance was acceptable on phases and phases combined strategies. CONCLUSIONS: To explore the effect of manual segmentation strategies and different phases selection on ML-based CT, we find that the method of single phase (CMP or NP) combined with contour-focused was considered a better strategy compared to the other strategies.

Effect of longitudinal changes of cachexia on the efficacy and toxicity of immune checkpoint inhibitors in esophageal squamous cell cancer (ESCC) patients.

PURPOSE: Immune checkpoint inhibitors (ICIs) have enhanced survival in advanced esophageal squamous cell cancer (ESCC) patients, but their efficacy varies. Cachexia, characterized by muscle loss and significant weight loss, might influence ICI response. This study examines the relationship between cachexia's longitudinal changes and ICI outcomes in ESCC patients. METHODS: ESCC patients undergoing at least two ICI cycles from 2017 to 2021 were studied. Cachexia's baseline and evolving patterns during ICI treatment were observed. Kaplan-Meier and Cox regression analyses were used to assess cachexia's effect on ICI efficacy. Chi-square tests were used to determine cachexia's link to immune-related adverse effects (irAEs). RESULTS: Two hundred seventy-eight ICI-treated patients had a median progression-free survival (PFS) of 5.78 months and overall survival (OS) of 8.3 months. Pretreatment cachexia led to worse outcomes: PFS 7.87 versus 5.3 months, time to progression (TTP) 10.9 versus 6.1 months, and OS 14.3 versus 9.2 months. Irreversible cachexia showed the poorest results. Cachexia's changes weren't associated with irAEs. CONCLUSION: Baseline and evolving cachexia significantly impact ICI efficacy in ESCC patients. Continuous cachexia monitoring during ICI therapy is crucial for optimal ESCC management.

BCLAF1 drives esophageal squamous cell carcinoma progression through regulation of YTHDF2-dependent SIX1 mRNA degradation.

Esophageal cancer ranks among the most prevalent malignant tumors, and esophageal squamous cell carcinoma (ESCC) constitutes its predominant histological form. Despite its impact, a thorough insight into the molecular intricacies of ESCC's development is still incomplete, which hampers the advancement of targeted molecular diagnostics and treatments. Recently, B-cell lymphoma-2-associated transcription factor 1 (BCLAF1) has come under investigation for its potential involvement in tumor biology, yet its specific role and mechanism in ESCC remain unclear. In this study, we observed a marked increase in BCLAF1 expression in ESCC tissues, correlating with advanced tumor stages and inferior patient outcomes. Our comprehensive in vitro and in vivo studies show that BCLAF1 augments glycolytic activity and the proliferation, invasion, and spread of ESCC cells. By employing mass spectrometry, we identified YTHDF2 as a key protein interacting with BCLAF1 in ESCC, with further validation provided by colocalization, co-immunoprecipitation, and GST pull-down assay. Further investigations involving MeRIP-seq and RIP-seq, alongside transcriptomic analysis, highlighted SIX1 mRNA as a molecule significantly upregulated and modified by N6-methyladenosine (m6A) in BCLAF1 overexpressing cells. BCLAF1 was found to reduce the tumor-suppressive activities of YTHDF2, and its effects on promoting glycolysis and cancer progression were shown to hinge on SIX1 expression. This research establishes that BCLAF1 fosters glycolysis and tumor progression in ESCC through the YTHDF2-SIX1 pathway in an m6A-specific manner, suggesting a potential target for future therapeutic intervention.

The development of a novel zeolite-based assay for efficient and deep plasma proteomic profiling.

Plasma proteins are considered the most informative source of biomarkers for disease diagnosis and monitoring. Mass spectrometry (MS)-based proteomics has been applied to identify biomarkers in plasma, but the complexity of the plasma proteome and the extremely large dynamic range of protein abundances in plasma make the clinical application of plasma proteomics highly challenging. We designed and synthesized zeolite-based nanoparticles to deplete high-abundance plasma proteins. The resulting novel plasma proteomic assay can measure approximately 3000 plasma proteins in a 45 min chromatographic gradient. Compared to those in neat and depleted plasma, the plasma proteins identified by our assay exhibited distinct biological profiles, as validated in several public datasets. A pilot investigation of the proteomic profile of a hepatocellular carcinoma (HCC) cohort identified 15 promising protein features, highlighting the diagnostic value of the plasma proteome in distinguishing individuals with and without HCC. Furthermore, this assay can be easily integrated with all current downstream protein profiling methods and potentially extended to other biofluids. In conclusion, we established a robust and efficient plasma proteomic assay with unprecedented identification depth, paving the way for the translation of plasma proteomics into clinical applications.

Effects of different treatment modalities on cardiovascular disease in ARR-positive hypertensive patients.

Data on the prognosis of clinically undiagnosed hypertensive patients who are aldosterone-to-renin ratio (ARR) positive are still scarce. Therefore, we investigated the clinical characteristics of clinically undiagnosed hypertensive patients who were ARR-positive and the influence of their different treatments on the occurrence and development of complications. A total of 285 hypertensive patients data with ARR ≥ 3.8 in the Second People's Hospital of Huai'an from January 2019 to December 2021 were collected, and 135 undiagnosed hypertensive patients were ultimately included in the analysis. According to their treatment strategy in various clinical departments, 135 patients were divided into the operation, spironolactone and control groups. Then, the clinical characteristics and the occurrence and development of complications in the three groups were compared. The results suggested that: (1) Only 34 (11.9%) of 285 hypertensive patients with ARR ≥ 3.8 were clearly diagnosed with Primary aldosteronism (PA) through functional tests, and the blood pressure (BP) compliance rate was only 50.30% during follow-up. (2) Based on exclusion criteria, 135 undiagnosed hypertensive patients were eventually included in the analysis. Patients in the surgery group had lower blood potassium levels and higher aldosterone levels than those in the other two groups, and their risk of new cerebrovascular complications was lower than that of the patients in the spironolactone group. (3) The risk of new cerebrovascular complications in the spironolactone group was 9.520 times higher than that of the control group, and this risk mainly occurred in patients with ARR values of 3.8-5.7. On the whole, surgery remains a good option for hypertensive patients with severe hyperaldosteronism and hypokalemia and those unable to undergo confirmatory tests; however, spironolactone therapy in patients with clinically undiagnosed hypertension, especially those with 3.8 ≤ ARR < 5.7, confered a higher risk of new cerebrovascular complications.

The mechanism of extracellular CypB promotes glioblastoma adaptation to glutamine deprivation microenvironment.

Glioblastoma, previously known as glioblastoma multiform (GBM), is a type of glioma with a high degree of malignancy and rapid growth rate. It is highly dependent on glutamine (Gln) metabolism during proliferation and lags in neoangiogenesis, leading to extensive Gln depletion in the core region of GBM. Gln-derived glutamate is used to synthesize the antioxidant Glutathione (GSH). We demonstrated that GSH levels are also reduced in Gln deficiency, leading to increased reactive oxygen species (ROS) levels. The ROS production induces endoplasmic reticulum (ER) stress, and the proteins in the ER are secreted into the extracellular medium. We collected GBM cell supernatants cultured with or without Gln medium; the core and peripheral regions of human GBM tumor tissues. Proteomic analysis was used to screen out the target-secreted protein CypB. We demonstrated that the extracellular CypB expression is associated with Gln deprivation. Then, we verified that GBM can promote the glycolytic pathway by activating HIF-1α to upregulate the expression of GLUT1 and LDHA expressions. Meanwhile, the DRP1 was activated, increasing mitochondrial fission, thus inhibiting mitochondrial function. To explore the specific mechanism of its regulation, we constructed a si-CD147 knockout model and added human recombinant CypB protein to verify that extracellular CypB influenced the expression of downstream p-AKT through its cell membrane receptor CD147 binding. Moreover, we confirmed that p-AKT could upregulate HIF-1α and DRP1. Finally, we observed that extracellular CypB can bind to the CD147 receptor, activate p-AKT, and upregulate HIF-1α and DRP1 in order to promote glycolysis while inhibiting mitochondrial function to adapt to the Gln-deprived microenvironment.

The application of machine learning based on computed tomography images in the identification of renal tumors in children.

Background: The clinical manifestations of Wilms tumor and non-Wilms tumor in children are similar, and the only way to confirm the diagnosis is by postoperative pathology. Computed tomography (CT) is one of the main methods for preoperative diagnosis of the two, but it is also difficult to distinguish because it is easily affected by the subjective influence and the experience of the radiologists. Methods: The CT images of 82 children with renal tumors admitted to the Department of Pediatric Urology, Shandong Provincial Hospital from January 2011 to March 2022 were retrospectively analyzed. First, we drew the two-dimensional (2D) region of interest (ROI) of the largest cross-section on the corticomedullary phase (CMP) and nephrogenic phase (NP) images, and extracted seven types of 107 features in the ROI. Then, the texture features with similarity greater than 95% and repetition less than 90% were screened out, and the remaining texture features were further screened by analysis of variance (ANOVA) and recursive feature elimination (RFE). Finally, 15 texture feature were used to build the machine learning (ML) models. We used the synthetic minority oversampling technique (SMOTE) and 10-fold cross-validation to build ML models and verified them in the training, testing, and internal validation sets. The area under the receiver-operating characteristic curve (AUC) and calibration curve were used to evaluate the diagnostic performance. Results: We collected 77 CMP and 81 NP images, which were randomly divided into the training set and the testing set according to the ratio of 7:3. In the internal validation of CMP, the Mean-PCC-ANOVA-5-AE pipeline model achieved the highest AUC 0.792 [95% confidence interval (CI): 0.653-0.930], and its accuracy (ACC), sensitivity (SEN), and specificity (SPE) were 0.833, 0.539 and 0.927, respectively. Correspondingly, in NP, the Mean-PCC-ANOVA-2-LR pipeline model achieved the highest AUC 0.655 (95% CI: 0.485-0.82) in the internal validation. The ACC, SEN, and SPE were 0.696, 0.539, and 0.744, respectively. Conclusions: The ML models based on CT images have good diagnostic efficiency in differentiating Wilms tumors from non-Wilms tumors in children.

Copper and Copper Complexes in Tumor Therapy.

Copper (Cu), a crucial trace element in physiological processes, has garnered significant interest for its involvement in cancer progression and potential therapeutic applications. The regulation of cellular copper levels is essential for maintaining copper homeostasis, as imbalances can lead to toxicity and cell death. The development of drugs that target copper homeostasis has emerged as a promising strategy for anticancer treatment, with a particular focus on copper chelators, copper ionophores, and novel copper complexes. Recent research has also investigated the potential of copper complexes in cancer therapy.

VLDL and LDL Subfractions Enhance the Risk Stratification of Individuals Who Underwent Epstein-Barr Virus-Based Screening for Nasopharyngeal Carcinoma: A Multicenter Cohort Study.

Serological tests for Epstein-Barr virus (EBV) antibodies have been widely conducted for the screening of nasopharyngeal carcinoma (NPC) in endemic areas. Further risk stratification of NPC can be achieved through plasma lipoprotein and metabolic profiles. A total of 297 NPC patients and 149 EBV-positive participants are enrolled from the NCT03919552 and NCT05682703 cohorts for plasma nuclear magnetic resonance (NMR) metabolomic analysis. Small, dense very low density lipoprotein particles (VLDL-5) and large, buoyant low density lipoprotein particles (LDL-1) are found to be closely associated with nasopharyngeal carcinogenesis. Herein, an NMR-based risk score (NRS), which combines lipoprotein subfractions and metabolic biomarkers relevant to NPC, is developed and well validated within a multicenter cohort. Combining the median cutoff value of the NRS (N50) with that of the serological test for EBV antibodies, the risk stratification model achieves a satisfactory performance in which the area under the curve (AUC) is 0.841 (95% confidence interval: 0.811-0.871), and the positive predictive value (PPV) reaches 70.08% in the combined cohort. These findings not only suggest that VLDL-5 and LDL-1 particles can serve as novel risk factors for NPC but also indicate that the NRS has significant potential in personalized risk prediction for NPC.

A NIR-II Photoacoustic Probe for High Spatial Quantitative Imaging of Tumor Nitric Oxide in Vivo.

Nitric oxide (NO) exhibits both pro- and anti-tumor effects. Therefore, real-time in vivo imaging and quantification of tumor NO dynamics are essential for understanding the conflicting roles of NO played in pathophysiology. The current molecular probes, however, cannot provide high-resolution imaging in deep tissues, making them unsuitable for these purposes. Herein, we designed a photoacoustic probe with an absorption maximum beyond 1000 nm for high spatial quantitative imaging of in vivo tumor NO dynamics. The probe exhibits remarkable sensitivity, selective ratiometric response behavior, and good tumor-targeting abilities, facilitating ratiometric imaging of tumor NO throughout tumor progression in a micron-resolution level. Using the probe as the imaging agent, we successfully quantified NO dynamics in tumor, liver and kidney. We have pinpointed an essential concentration threshold of around 80 nmol/cm3 for NO, which plays a crucial role in the "double-edged-sword" function of NO in tumors. Furthermore, we revealed a reciprocal relationship between the NO concentration in tumors and that in the liver, providing initial insights into the possible NO-mediated communication between tumor and the liver. We believe that the probe will help resolve conflicting aspects of NO biology and guide the design of imaging agents for tumor diagnosis and anti-cancer drug screening.

Exposure to high dose of polystyrene nanoplastics causes trophoblast cell apoptosis and induces miscarriage.

BACKGROUND: With rapid increase in the global use of various plastics, microplastics (MPs) and nanoplastics (NPs) pollution and their adverse health effects have attracted global attention. MPs have been detected out in human body and both MPs and NPs showed female reproductive toxicological effects in animal models. Miscarriage (abnormal early embryo loss), accounting for 15-25% pregnant women worldwide, greatly harms human reproduction. However, the adverse effects of NPs on miscarriage have never been explored. RESULTS: In this study, we identified that polystyrene (PS) plastics particles were present in women villous tissues. Their levels were higher in villous tissues of unexplained recurrent miscarriage (RM) patients vs. healthy control (HC) group. Furthermore, mouse assays further confirmed that exposure to polystyrene nanoplastics (PS-NPs, 50 nm in diameter, 50 or 100 mg/kg) indeed induced miscarriage. In mechanism, PS-NPs exposure (50, 100, 150, or 200 µg/mL) increased oxidative stress, decreased mitochondrial membrane potential, and increased apoptosis in human trophoblast cells by activating Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3 signaling through mitochondrial pathway. The alteration in this signaling was consistent in placental tissues of PS-NPs-exposed mouse model and in villous tissues of unexplained RM patients. Supplement with Bcl-2 could efficiently suppress apoptosis in PS-NPs-exposed trophoblast cells and reduce apoptosis and alleviate miscarriage in PS-NPs-exposed pregnant mouse model. CONCLUSIONS: Exposure to PS-NPs activated Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3, leading to excessive apoptosis in human trophoblast cells and in mice placental tissues, further inducing miscarriage.

C1q/Tumor Necrosis Factor-Related Protein-9 Is a Novel Vasculoprotective Cytokine That Restores High Glucose-Suppressed Endothelial Progenitor Cell Functions by Activating the Endothelial Nitric Oxide Synthase.

BACKGROUND: This study investigated whether gCTRP9 (globular C1q/tumor necrosis factor-related protein-9) could restore high-glucose (HG)-suppressed endothelial progenitor cell (EPC) functions by activating the endothelial nitric oxide synthase (eNOS). METHODS AND RESULTS: EPCs were treated with HG (25 mmol/L) and gCTRP9. Migration, adhesion, and tube formation assays were performed. Adiponectin receptor 1, adiponectin receptor 2, and N-cadherin expression and AMP-activated protein kinase, protein kinase B, and eNOS phosphorylation were measured by Western blotting. eNOS activity was determined using nitrite production measurement. In vivo reendothelialization and EPC homing assays were performed using Evans blue and immunofluorescence in mice. Treatment with gCTRP9 at physiological levels enhanced migration, adhesion, and tube formation of EPCs. gCTRP9 upregulated the phosphorylation of AMP-activated protein kinase, protein kinase B, and eNOS and increased nitrite production in a concentration-dependent manner. Exposure of EPCs to HG-attenuated EPC functions induced cellular senescence and decreased eNOS activity and nitric oxide synthesis; the effects of HG were reversed by gCTRP9. Protein kinase B knockdown inhibited eNOS phosphorylation but did not affect gCTRP9-induced AMP-activated protein kinase phosphorylation. HG impaired N-cadherin expression, but treatment with gCTRP9 restored N-cadherin expression after HG stimulation. gCTRP9 restored HG-impaired EPC functions through both adiponectin receptor 1 and N-cadherin-mediated AMP-activated protein kinase /protein kinase B/eNOS signaling. Nude mice that received EPCs treated with gCTRP9 under HG medium showed a significant enhancement of the reendothelialization capacity compared with those with EPCs incubated under HG conditions. CONCLUSIONS: CTRP9 promotes EPC migration, adhesion, and tube formation and restores these functions under HG conditions through eNOS-mediated signaling mechanisms. Therefore, CTRP9 modulation could eventually be used for vascular healing after injury.

Identification and Validation of Lipid Metabolism Gene FASN-Associated miRNA in Wilms Tumor.

miRNA has been a research hotspot in recent years and its scope of action is very wide, involving the regulation of cell proliferation, differentiation, apoptosis, and other biological behaviors. This study intends to explore the role of miRNA in the lipid metabolism and development of Wilms tumor (WT) by detecting and analyzing the differences in the expression profiles of miRNAs between the tumor and adjacent normal tissue. Gene detection was performed in tumor tissues and adjacent normal tissues of three cases of WT to screen differentially expressed miRNAs (DEMs). According to our previous research, FASN, which participates in the lipid metabolism pathway, may be a target of WT. The starBase database was used to predict FASN-targeted miRNAs. The above two groups of miRNAs were intersected to obtain FASN-targeted DEMs and then GO Ontology (GO) functional enrichment analysis of FASN-targeted DEMs was performed. Finally, the FASN-targeted DEMs were compared and further verified by qRT‒PCR. Through gene sequencing and differential analysis, 287 DEMs were obtained, including 132 upregulated and 155 downregulated miRNAs. The top ten DEMs were all downregulated. Fourteen miRNAs targeted by the lipid metabolism-related gene FASN were predicted by starBase. After intersection with the DEMs, three miRNAs were finally obtained, namely, miR-107, miR-27a-3p, and miR-335-5p. GO enrichment analysis was mainly concentrated in the Parkin-FBXW7-Cul1 ubiquitin ligase complex and response to prostaglandin E. Further experimental verification showed that miR-27a-3p was significantly correlated with WT (P = 0.0018). Imbalanced expression of miRNAs may be involved in the occurrence and development of WT through lipid metabolism. The expression of miR-27a-3p is related to the malignant degree of WT, and it may become the target of diagnosis, prognosis, and treatment of WT in the later stage.

Oleic and linoleic acids promote chondrocyte apoptosis by inhibiting autophagy via downregulation of SIRT1/FOXO1 signaling.

Osteoarthritis (OA) is a complex joint disease that currently has no cure. OA involves metabolic disorders in chondrocytes and an imbalance between autophagy and apoptosis. As a common risk factor for OA, obesity induces changes in the fatty acid composition of synovial fluid, thereby disturbing chondrocyte homeostasis. However, whether unsaturated fatty acids affect the development of OA by regulating chondrocyte autophagy remains unclear. This study aimed to determine the effects of oleic and linoleic acids on chondrocyte autophagy and related mechanisms. Based on the mass spectrometry results, the levels of multiple unsaturated fatty acids, including oleic and linoleic acids, in the synovial fluid of patients with OA and obesity were significantly higher than those in patients with OA only. Moreover, we found that FOXO1 and SIRT1 were downregulated after oleic and linoleic acids treatment of chondrocytes, which inhibited chondrocyte autophagy. Importantly, the upregulation of SIRT1 and FOXO1 expression not only increased the level of autophagy but also improved the expression of chondrocyte extracellular matrix proteins. Furthermore, upregulated SIRT1 and FOXO1 expression alleviated the destruction of the articular cartilage in an OA rat model. Our results suggest that SIRT1/FOXO1 signaling can alleviate oleic acid- and linoleic acid-induced cartilage degradation both in vitro and in vivo and that the SIRT1/FOXO1 pathway may serve as an effective treatment target for inhibiting OA progression.

Chemotherapy-related symptom networks in distinct subgroups of Chinese patients with gastric cancer.

Objective: This study aims to identify distinct subgroups among gastric cancer patients undergoing chemotherapy (CTX), delineate associated symptom networks, and ascertain the clinical and sociodemographic variables contributing to diverse symptom patterns. Methods: Conducted in eastern China, our investigation involved gastric cancer patients receiving CTX. We gathered data using the M.D. Anderson Symptom Inventory Gastrointestinal Cancer Module along with clinical and sociodemographic variables. Subgroups were discerned based on symptom severity through latent profile analysis, and subsequent comparisons were made regarding the symptom networks in different subgroups. Results: The analysis encompassed 677 eligible gastric cancer patients, revealing three profiles: "Profile 1: low class" (n = 354, 52.3%), "Profile 2: moderate class" (n = 222, 32.8%), and "Profile 3: all high class" (n = 101, 14.9%). Nausea-vomiting exhibited robust associations in the symptom networks of all subgroups, whereas sadness-distress, and taste change-lack of appetite were notably linked with Profile 1 and Profile 2. Distress emerged as a core symptom in Profile 1, lack of appetite dominated the symptom network in Profile 2, and fatigue attained the highest strength in Profile 3. Distinct symptom profiles were influenced by variables such as education level, CTX combined with surgical or herbal treatment, psychological resilience, and social support. Conclusions: Patients within different subgroups manifest individualized patterns of symptom profiles. Analyzing demographics, disease characteristics, and psychosocial information among diverse subgroups facilitates healthcare providers in devising more personalized and targeted symptom management strategies, thereby alleviating the symptom burden on patients.

Defective Homologous Recombination Repair By Up-Regulating Lnc-HZ10/Ahr Loop in Human Trophoblast Cells Induced Miscarriage.

Human trophoblast cells are crucial for healthy pregnancy. However, whether the defective homologous recombination (HR) repair of dsDNA break (DSB) in trophoblast cells may induce miscarriage is completely unknown. Moreover, the abundance of BRCA1 (a crucial protein for HR repair), its recruitment to DSB foci, and its epigenetic regulatory mechanisms, are also fully unexplored. In this work, it is identified that a novel lnc-HZ10, which is highly experssed in villous tissues of recurrent miscarriage (RM) vs their healthy control group, suppresses HR repair of DSB in trophoblast cell. Lnc-HZ10 and AhR (aryl hydrocarbon receptor) form a positive feedback loop. AhR acts as a transcription factor to promote lnc-HZ10 transcription. Meanwhile, lnc-HZ10 also increases AhR levels by suppressing its CUL4B-mediated ubiquitination degradation. Subsequently, AhR suppresses BRCA1 transcription; and lnc-HZ10 (mainly 1-447 nt) interacts with γ-H2AX; and thus, impairs its interactions with BRCA1. BPDE exposure may trigger this loop to suppress HR repair in trophoblast cells, possibly inducing miscarriage. Knockdown of murine Ahr efficiently recovers HR repair in placental tissues and alleviates miscarriage in a mouse miscarriage model. Therefore, it is suggested that AhR/lnc-HZ10/BRCA1 axis may be a promising target for alleviation of unexplained miscarriage.

Factors influencing cadmium accumulation in plants after inoculation with rhizobacteria: A meta-analysis.

Rhizobacteria have the potential to enhance phytoremediation by generating substances that stimulate plant development and influence the effectiveness of cadmium (Cd) remediation by adjusting Cd availability via metal solubilization. Furthermore, rhizobacterial inoculation affects plants' metal tolerance and uptake by controlling the expression of several metal transporters, channels, and metal chelator genes. A meta-analysis was conducted to quantitatively assess the effects of rhizobacteria on Cd accumulation in plants using 207 individual observations from 47 articles. This meta-analysis showed an average Cd concentration increase of 8.09 % in plant cells under rhizobacteria treatment. The effects of different plant-microbial interactions on the bioaccumulation of Cd in plants varied. Selecting the proper rhizobacteria-plant association is essential to affect Cd buildup in plant roots and shoots. A more extended planting period (>30 days) and a suitable soil pH (<6, 7-8) would aid in the phytoextraction of Cd from the soil. This study comprehensively and quantitatively investigated the effects of plants, rhizobacteria, soil pH, planting period, experimental sites, and plant organs on plant Cd accumulation. According to the analysis of explanatory factors, plant species, planting period, soil pH, and rhizobacteria species have a more decisive influence on Cd accumulation than other factors. The results provide information for future research on the successful remediation of soils contaminated with Cd. More investigations are required to elucidate the intricate interactions between plant roots and microorganisms.

Construction and application of nasopharyngeal carcinoma-specific big data platform based on electronic health records.

OBJECTIVE: To establish a nasopharyngeal carcinoma-specific big data platform based on electronic health records (EHRs) to provide data support for real-world study of nasopharyngeal carcinoma. METHODS: A multidisciplinary expert team was established for this project. Based on industry standards and practical feasibility, the team designed the nasopharyngeal carcinoma data element standards including 14 modules and 640 fields. Data from patients diagnosed with nasopharyngeal carcinoma who visited Southern Hospital after 1999 were extracted from 15 EHRs systems and were cleaned, structured, and standardized using information technologies such as machine learning and natural language processing. In addition, a series of measures such as quality control and data encryption were taken to ensure data quality and patient privacy. At the platform application level, 10 functional modules were designed according to the needs of nasopharyngeal carcinoma research. RESULTS: As of 1 October 2022, the Big Data platform has included 11,617patients, of whom 8228 (70.83 %) were male and 3389 (29.17 %) were female, with a median age of 48 years (interquartile range, 40 years). The data in the platform were validated to have a high level of completeness and accuracy, especially for key variables such as social demographics, laboratory tests and vital signs. Currently, six projects involving risk factors, early diagnosis, treatment efficacy and prevention of treatment-related toxic reactions have been conducted on the platform. CONCLUSIONS: We have established a high-quality NPC-specific big data platform by integrating heterogeneous data from multiple sources in the EHR. The platform provides an effective tool and strong data support for real-world studies of nasopharyngeal carcinoma, which helps to improve research efficiency, reduce costs, and improve the quality of research results. We expect to promote multicenter nasopharyngeal carcinoma data sharing in the future to facilitate the generation of high-quality real-world evidence in nasopharyngeal carcinoma. This article may provide some reference value for other comprehensive hospitals to establish a big data platform for nasopharyngeal carcinoma.