The prediction of pCR and chemosensitivity for breast cancer patients using DLG3, RADL and Pathomics signatures based on machine learning and deep learning.

BACKGROUND: Limited studies have investigated the predictive value of multiomics signatures (radiomics, deep learning features, pathological features and DLG3) in breast cancer patients who underwent neoadjuvant chemotherapy (NAC). However, no study has explored the relationships among radiomic, pathomic signatures and chemosensitivity. This study aimed to predict pathological complete response (pCR) using multiomics signatures, and to evaluate the predictive utility of radiomic and pathomic signatures for guiding chemotherapy selection. METHODS: The oncogenic function of DLG3 was explored in breast cancer cells via DLG3 knockdown. Immunohistochemistry (IHC) was used to evaluate the relationship between DLG3 expression and docetaxel/epirubin sensitivity. Machine learning (ML) and deep learning (DL) algorithms were used to develop multiomics signatures. Survival analysis was conducted by K-M curves and log-rank. Multivariate logistic regression analysis was used to develop nomograms. RESULTS: A total of 311 patients with malignant breast tumours who underwent NAC were retrospectively included in this multicentre study. Multiomics (DLG3, RADL and PATHO) signatures could accurately predict pCR (AUC: training: 0.900; testing: 0.814; external validation: 0.792). Its performance is also superior to that of clinical TNM staging and the single RADL signature in different cohorts. Patients in the low DLG3 group more easily achieved pCR, and those in the high RADL Signature_pCR and PATHO_Signature_pCR (OR = 7.93, 95 % CI: 3.49-18, P < 0.001) groups more easily achieved pCR. In the TEC regimen NAC group, patients who achieved pCR had a lower DLG3 score (4.00 ± 2.33 vs. 6.43 ± 3.01, P < 0.05). Patients in the low RADL_Signature_DLG3 and PATHO_Signature_DLG3 groups had lower DLG3 IHC scores (P < 0.05). Patients in the high RADL signature, PATHO signature and DLG3 signature groups had worse DFS and OS. CONCLUSIONS: Multiomics signatures (RADL, PATHO and DLG3) demonstrated great potential in predicting the pCR of breast cancer patients who underwent NAC. The RADL and PATHO signatures are associated with DLG3 status and could help doctors or patients choose proper neoadjuvant chemotherapy regimens (TEC regimens). This simple, structured, convenient and inexpensive multiomics model could help clinicians and patients make treatment decisions.

Anti-Melanogenic Effects of Takifugu flavidus Muscle Hydrolysate in B16F10 Melanoma Cells and Zebrafish.

Abnormal melanogenesis can lead to hyperpigmentation. Tyrosinase (TYR), a key rate-limiting enzyme in melanin production, is an important therapeutic target for these disorders. We investigated the TYR inhibitory activity of hydrolysates extracted from the muscle tissue of Takifugu flavidus (TFMH). We used computer-aided virtual screening to identify a novel peptide that potently inhibited melanin synthesis, simulated its binding mode to TYR, and evaluated functional efficacy in vitro and in vivo. TFMH inhibited the diphenolase activities of mTYR, reducing TYR substrate binding activity and effectively inhibiting melanin synthesis. TFMH indirectly reduced cAMP response element-binding protein phosphorylation in vitro by downregulating melanocortin 1 receptor expression, thereby inhibiting expression of the microphthalmia-associated transcription factor, further decreasing TYR, tyrosinase related protein 1, and dopachrome tautomerase expression and ultimately impeding melanin synthesis. In zebrafish, TFMH significantly reduced black spot formation. TFMH (200 µg/mL) decreased zebrafish TYR activity by 43% and melanin content by 52%. Molecular dynamics simulations over 100 ns revealed that the FGFRSP (T-6) peptide stably binds mushroom TYR via hydrogen bonds and ionic interactions. T-6 (400 µmol/L) reduced melanin content in B16F10 melanoma cells by 71% and TYR activity by 79%. In zebrafish, T-6 (200 µmol/L) inhibited melanin production by 64%. TFMH and T-6 exhibit good potential for the development of natural skin-whitening cosmetic products.

Generalizable transcriptome-based tumor malignant level evaluation and molecular subtyping towards precision oncology.

In cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients. Here, through in-depth integration of tumor transcriptome and patients' prognoses across cancers, we investigated dysregulated and prognosis-associated genes and catalogued such important genes in a cancer type-dependent manner. Utilizing the expression matrices of these genes, we built models to quantitatively evaluate the malignant levels of tumors across cancers, which could add value to the clinical staging system for improved prediction of patients' survival. Furthermore, we performed a transcriptome-based molecular subtyping on hepatocellular carcinoma, which revealed three subtypes with significantly diversified clinical outcomes, mutation landscapes, immune microenvironment, and dysregulated pathways. As tumor transcriptome was commonly profiled in clinical practice with low experimental complexity and cost, this work proposed easy-to-perform approaches for practical clinical promotion towards better healthcare and precision oncology of cancer patients.

A dual dynamically cross-linked hydrogel promotes rheumatoid arthritis repair through ROS initiative regulation and microenvironment modulation-independent triptolide release.

High oxidative stress and inflammatory cell infiltration are major causes of the persistent bone erosion and difficult tissue regeneration in rheumatoid arthritis (RA). Triptolide (TPL) has become a highly anticipated anti-rheumatic drug due to its excellent immunomodulatory and anti-inflammatory effects. However, the sudden drug accumulation caused by the binding of "stimulus-response" and "drug release" in a general smart delivery system is difficult to meet the shortcoming of extreme toxicity and the demand for long-term administration of TPL. Herein, we developed a dual dynamically cross-linked hydrogel (SPT@TPL), which demonstrated sensitive RA microenvironment regulation and microenvironment modulation-independent TPL release for 30 days. The abundant borate ester/tea polyphenol units in SPT@TPL possessed the capability to respond and regulate high reactive oxygen species (ROS) levels on-demand. Meanwhile, based on its dense dual crosslinked structure as well as the spontaneous healing behavior of numerous intermolecular hydrogen bonds formed after the breakage of borate ester, TPL could remain stable and slowly release under high ROS environments of RA, which dramatically reduced the risk of TPL exerting toxicity while maximized its long-term efficacy. Through the dual effects of ROS regulation and TPL sustained-release, SPT@TPL alleviated oxidative stress and reprogrammed macrophages into M2 phenotype, showing marked inhibition of inflammation and optimal regeneration of articular cartilage in RA rat model. In conclusion, this hydrogel platform with both microenvironment initiative regulation and TPL long-term sustained release provides a potential scheme for rheumatoid arthritis.

Identification of a novel inflammatory-related gene signature to evaluate the prognosis of gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is a highly aggressive malignancy with a heterogeneous nature, which makes prognosis prediction and treatment determination difficult. Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours. Inflammation also affects the prognosis of GC patients. Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis. However, the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear. AIM: To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients. METHODS: In this study, the mRNA expression profiles and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) database (GSE66229). An inflammatory-related gene prognostic signature model was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database. GC patients from the GSE26253 cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent prognostic factors, and a prognostic nomogram was established. The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram. The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram. Gene set enrichment analysis was performed to explore the potential regulatory pathways involved. The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT. Finally, we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents. RESULTS: A prognostic model consisting of three inflammatory-related genes (MRPS17, GUF1, and PDK4) was constructed. Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients. According to the risk score, GC patients were stratified into high- and low-risk groups, and patients in the high-risk group had significantly worse prognoses according to age, sex, TNM stage and Lauren type. Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging. Finally, the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group, indicating a link between inflammation-related genes and drug sensitivity. CONCLUSION: In conclusion, we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.

Pulsatile Flow Increases METTL14-induced m6A modification and attenuates septic cardiomyopathy: an experimental study.

INTRODUCTION: Septic cardiomyopathy is a sepsis-mediated cardiovascular complication with severe microcirculatory malperfusion. Emerging evidence has highlighted the protective effects of pulsatile flow in case of microcirculatory disturbance, yet the underlying mechanisms are still elusive. The objective of this study was to investigate the mechanisms of N6-methyladenosine (m6A) modification in the alleviation of septic cardiomyopathy associated with extracorporeal membrane oxygenation (ECMO)-generated pulsatile flow. METHODS: Rat model with septic cardiomyopathy was established and was supported under ECMO either with pulsatile or non-pulsatile flow. Peripheral perfusion index (PPI) and cardiac function parameters were measured using ultrasonography. Dot blot assay was applied to examine the m6A level, while qRT-PCR, Western blot, immunofluorescence, and immunohistochemistry were used to measure the expressions of related genes. RNA immunoprecipitation assay was performed to validate the interaction between molecules. RESULTS: The ECMO-generated pulsatile flow significantly elevates microcirculatory PPI, improves myocardial function, protects the endothelium, and prolongs survival in rat models with septic cardiomyopathy. The pulsatile flow mediates the METTL14-mediated m6A modification to zonula occludens- (ZO-) 1 mRNA which stabilizes the ZO-1 mRNA depending on the presence of YTHDF2. The pulsatile flow suppresses the PI3K-Akt signaling pathway, of which the downstream molecule Foxo1, a negative transcription factor of METTL14, binds to the METTL14 promoter and inhibits the METTL14-induced m6A modification. CONCLUSION: The ECMO-generated pulsatile flow increases METTL14-induced m6A modification in ZO-1 and attenuates the progression of septic cardiomyopathy, suggesting that pulsatility might be a new therapeutic strategy in septic cardiomyopathy by alleviating microcirculatory disturbance.

Hispidulin targets PTGS2 to improve cyclophosphamide-induced cystitis by suppressing NLRP3 inflammasome.

Interstitial cystitis (IC) is a chronic bladder inflammation. Inhibition of prostaglandin G/H synthase 2 (PTGS2) is the most common method for controlling inflammation-related diseases. This study aimed to analyze the effects of hispidulin on the PTGS2 and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammation in experimental IC models. A binding activity between hispidulin and PTGS2 was measured using molecular docking. Human urothelial cells (SV-HUC-1) were stimulated by 2 ng/mL of interleukin (IL)-1ß for 24 h and cultured in a medium with different concentrations of hispidulin (2.5, 5, 10, 20 µM) for 24 h to observe the expressions of PTGS2 and NLRP3 protein. Cells overexpressing PTGS2 were established by PTGS2 cDNA transfection. In the IL-1ß-treated cells, the NLRP3 inflammasome was measured after 20 µM hispidulin treatment. In rats, animals were performed with three injections of 40 mg/kg cyclophosphamide (CYP) and orally treated with 50 mg/kg/day hispidulin or ibuprofen for 3 days. The bladder pain was measured using Von Frey filaments, and the bladder pathology was observed using hematoxylin and eosin (H&E) staining. The expressions of PTGS2 and NLRP3 inflammasome were also observed in the bladder tissues. A good binding activity was found between hispidulin and PTGS2 (score = - 8.9 kcal/mol). The levels of PTGS2 and NLRP3 inflammasome were decreased with the hispidulin dose increase in the IL-1ß-treated cells (p < 0.05). Cells overexpressing PTGS2 weakened the protective effects of hispidulin in the IL-1ß-treated cells (p < 0.01). In the CYP-treated rats, hispidulin treatment improved the bladder pain through decreasing the nociceptive score (p < 0.01) and suppressed the bladder inflammation through suppressing the expressions of PTGS2 and NLRP3 inflammasome in bladder tissues (p < 0.01). Additionally, the results of ibuprofen treatment were similar to the effects of hispidulin in the CYP-treated rats. This study demonstrates that hispidulin may be a new alternative drug for the IC treatment that binds PTGS2 to perform its functions.

Scapular dislocation following radical surgical excision of lung sarcomatoid carcinoma: A rare case report.

RATIONALE: Scapular prolapse is a rare complication of thoracotomy. Only a few cases of scapular prolapse after thoracotomy have been reported. Here, we report the case of a 52-year-old male patient who underwent standard posterior thoracotomy for lung sarcomatoid carcinoma invading the left upper chest wall. PATIENT CONCERNS: The surgery was performed to remove some ribs and chest wall muscles; however, no reconstruction or repair of the chest wall defect was performed. The patient experienced a sharp pain and severe limitation of movement of the left shoulder within 1 month of receiving adjuvant therapy. DIAGNOSES: The patient was diagnosed with left intrathoracic scapular prolapse after careful consideration of medical history, physical examination, and chest radiography. INTERVENTIONS: We performed closed manual reduction because the patient refused to undergo surgery. OUTCOMES: The patient's shoulder pain and movement limitation were significantly relieved, but the symptoms relapsed. After repeated closed manual reduction, the patient was instructed not to abduct the shoulder joint above 90°. The patient did not relapse during a 1-year observation period. CONCLUSION: If scapular prolapse occurs, manual or surgical reduction can be selected based on the needs. If a patient refuses to undergo surgery, manual reduction can be an effective treatment method.

Clinicopathological Characteristics of Breast Cancer Patients with HER-2 Low Expression Receiving Neoadjuvant Therapy.

INTRODUCTION: Human epidermal growth factor receptor-2 (HER-2) low expression breast malignant tumors have become a research hotspot in recent years, but it is still unclear whether HER-2 low expression represents a special subtype of breast cancer. However, this molecular type requires more effective treatment regimens in the neoadjuvant therapy stage. METHODS: This study enrolled breast cancer patients who were treated at Harbin Medical University Cancer Hospital with neoadjuvant treatment between October 2011 and May 2019 and was a single-center retrospective study. RESULTS: A total of 1,053 breast cancer patients who received preoperative therapy, including 279 (26%) HER-2 low expression patients, were included in this retrospective study. The HER-2 low expression group had a higher proportion of patients under 50 years old than the other two molecular subtype groups (p = 0.047, 62.0% vs. 57.2% and 52.5%), and the percentage of patients with Ki67 index above 15% was lower than that in HER-2-negative and HER-2-positive patients (p < 0.001, 50.2% vs. 63.6% and 71.5%). Most of the patients with HER-2 low expression were hormone receptor (HR) positive (p < 0.001, 85.7% vs. 60.4% and 36.0%), and their pathologic complete response (pCR) rate after neoadjuvant therapy was significantly lower than that of HER-2-negative and HER-2-positive patients (p < 0.001, 5.7% vs. 11.8% and 20.5%). The results of the subgroup analysis showed HR-positive patients with HER-2 low expression had a lower pCR rate (p < 0.001, 4.6% vs. 14.6%) and objective response rate (p = 0.001, 77.8% vs. 91.0%) than HER-2-positive patients and had no significant difference in these rates compared to HER-2-negative patients. There were no significant differences in overall survival (OS) and disease-free survival (DFS) up to 67 months (the median follow-up time) among HER-2 low, HER-2-negative, and HER-2-positive patients. The results of Cox hazard proportional showed that the Ki67 index and T stage (T3) were independent influencing factors for DFS. In terms of OS, Ki67 index, P53, T stage, and objective response were independent influencing factors for OS in HER-2 low expression patients. CONCLUSIONS: In general, further studies are needed to confirm that HER-2 low expression is a special breast cancer molecular subtype. The efficacy of neoadjuvant therapy in patients with HER-2 low expression is relatively poor, and the efficacy of neoadjuvant therapy can predict the prognosis of patients with HER-2 low expression.

Chlorella pyrenoidosa as a potential bioremediator: Its tolerance and molecular responses to cadmium and lead.

Heavy metal contamination negatively affects plants and animals in water as well as soils. Some microalgae can remove heavy metal contaminants from wastewater. The aim of this study was to screen green microalgae (GM) to identify those that tolerate high concentrations of toxic heavy metals in water as possible candidates for phytoremediation. Analyses of the tolerance, physiological parameters, ultrastructure, and transcriptomes of GM under Cd/Pb treatments were conducted. Compared with the other GM, Chlorella pyrenoidosa showed stronger tolerance to high concentrations of Cd/Pb. The reduced glutathione content and peroxidase activity were higher in C. pyrenoidosa than those in the other GM. Ultrastructural observations showed that, compared with other GM, C. pyrenoidosa had less damage to the cell surface and interior under Cd/Pb toxicity. Transcriptome analyses indicated that the "peroxisome" and "sulfur metabolism" pathways were enriched with differentially expressed genes under Cd/Pb treatments, and that CpSAT, CpSBP, CpKAT2, Cp2HPCL, CpACOX, CpACOX2, and CpACOX4, all of which encode antioxidant enzymes, were up-regulated under Cd/Pb treatments. These results show that C. pyrenoidosa has potential applications in the remediation of polluted water, and indicate that antioxidant enzymes contribute to Cd/Pb detoxification. These findings will be useful for producing algal strains for the purpose of bioremediation in water contamination.

Camera-based Respiratory Imaging for Thoracic Asymmetry in Thoracic Surgery Patients.

The current tool for assessing thoracic asymmetry of thoracic surgery patients is inappropriate for timely or frequent clinical routines due to its dependency on empirical physical examinations or specialized machines. This study investigates the camera-based respiratory imaging for screening thoracic asymmetry, in an intelligent and convenient way. The respiratory heatmaps are generated based on the respiratory magnitudes, phases and angles extracted from the chest video, and bilateral chest region of interest are compared statistically. Due to the variability of chest respiratory direction, spatial enhancement (SDR and SPCA) algorithms are proposed to magnify the respiratory energy. The proposed framework was validated in a clinical trial involving 31 patients, recorded by a smartphone camera. A high correlation was found between the camera measurements and patients' thoracic status in both the visual imaging and quantified indices. The respiratory imaging of camera shows a clear potential for assessing chest abnormalities of thoracic surgery patients.

Advances in Research on Marine-Derived Lipid-Lowering Active Substances and Their Molecular Mechanisms.

Hyperlipidemia (HLP) is a metabolic disorder caused by abnormal lipid metabolism. Recently, the prevalence of HLP caused by poor dietary habits in the population has been increasing year by year. In addition, lipid-lowering drugs currently in clinical use have shown significant improvement in blood lipid levels, but are accompanied by certain side effects. However, bioactive marine substances have been shown to possess a variety of physiological activities such as hypoglycemic, antioxidant, antithrombotic and effects on blood pressure. Therefore, the hypolipidemic efficacy of marine bioactive substances with complex and diverse structures has also attracted attention. This paper focuses on the therapeutic role of marine-derived polysaccharides, unsaturated fatty acids, and bioactive peptides in HLP, and briefly discusses the main mechanisms by which these substances exert their hypolipidemic activity in vivo.

Environment and social support for smoking cessation among community smokers in Beijing, China.

INTRODUCTION: This study investigated the relationship between environment support, social support and smoking cessation, to provide suggestions for the construction of environment and social support for tobacco control. METHODS: This was a secondary analysis based on two cross-sectional surveys of adult smokers who participated in the six-month community smoking cessation intervention projects in Beijing. The study subjects were divided into a successful group (n=159) and an unsuccessful group (n=253). The status of the environment support, community tobacco exposure, and social support were compared between groups. A structural equation model (SEM) was established for Confirmatory Factor Analysis. RESULTS: The univariate analysis showed that there were differences in smoking cessation outcomes among smokers with different home tobacco regulations, workplace tobacco regulations and number of smokers in the family. Differences in 6-month smoking reduction were also found with different promotion levels of anti-tobacco messaging and the frequency of smoking events at home. The logistic regression analysis indicated that home tobacco regulations (OR=1.30; 95% CI: 1.00-1.69), workplace tobacco regulations (OR=1.27; 95% CI: 1.05- 1.54), and frequency of smoking events at home (OR=1.15; 95% CI: 1.02-1.29), were associated with smoking cessation. The results of the SEM showed that environment support (ß=0.39; 95% CI: 0.05-0.73, p=0.026) and social support (ß=0.37; 95% CI: 0.05-0.68, p=0.022) had influence on smoking cessation. CONCLUSIONS: Environment support and social support are related to smoking cessation. Attention should be paid to the smoking regulations at home and workplace, anti-tobacco messaging, and social support by the family. TRIAL REGISTRATION: The study was registered on the official website of the China Clinical Trial Registration Center. Identifier: ChiCTR1900024991.

Affinity Purification and Molecular Characterization of Angiotensin-Converting Enzyme (ACE)-Inhibitory Peptides from Takifugu flavidus.

An affinity chromatography filler of CNBr-activated Sepharose 4B-immobilized ACE was used to purify ACE-inhibitory peptides from Takifugu flavidus protein hydrolysate (<1 kDa). Twenty-four peptides with an average local confidence score (ALC) ≥ 80% from bounded components (eluted by 1 M NaCl) were identified by LC-MS/MS. Among them, a novel peptide, TLRFALHGME, with ACE-inhibitory activity (IC50 = 93.5 µmol·L-1) was selected. Molecular docking revealed that TLRFALHGME may interact with the active site of ACE through H-bond, hydrophobic, and electrostatic interactions. The total binding energy (ΔGbinding) of TLRFALHGME was estimated to be -82.7382 kJ·mol-1 by MD simulations, indicating the favorable binding of peptides with ACE. Furthermore, the binding affinity of TLRFALHGME to ACE was determined by surface plasmon resonance (SPR) with a Kd of 80.9 µmol, indicating that there was a direct molecular interaction between them. TLRFALHGME has great potential for the treatment of hypertension.

Waterborne Tebuconazole Exposure Induces Male-Biased Sex Differentiation in Zebrafish (Danio rerio) Larvae via Aromatase Inhibition.

Tebuconazole is a widely used fungicide for various crops that targets sterol 14-α-demethylase (CYP51) in fungi. However, attention has shifted to aromatase (CYP19) due to limited research indicating its reproductive impact on aquatic organisms. Herein, zebrafish were exposed to 0.5 mg/L tebuconazole at different developmental stages. The proportion of males increased significantly after long-term exposure during the sex differentiation phase (0-60, 5-60, and 19-60 days postfertilization (dpf)). Testosterone levels increased and 17ß-estradiol and cyp19a1a expression levels decreased during the 5-60 dpf exposure, while the sex ratio was equally distributed on coexposure with 50 ng/L 17ß-estradiol. Chemically activated luciferase gene expression bioassays determined that the male-biased sex differentiation was not caused by tebuconazole directly binding to sex hormone receptors. Protein expression and phosphorylation levels were specifically altered in the vascular endothelial growth factor signaling pathway despite excluding the possibility of tebuconazole directly interacting with kinases. Aromatase was selected for potential target analysis. Molecular docking and aromatase activity assays demonstrated the interactions between tebuconazole and aromatase, highlighting that tebuconazole poses a threat to fish populations by inducing a gender imbalance.

Naples score: a novel prognostic biomarker for breast cancer patients undergoing neoadjuvant chemotherapy.

BACKGROUND AND PURPOSE: The Naples Score (NPS) is a novel prognostic indicator that has been used in various cancers, but its potential in breast malignant tumor patients receiving neoadjuvant chemotherapy (NAC) has not been discovered. This study aimed to investigate the relationship between NPS and overall survival (OS) and disease-free survival (DFS) in breast cancer patients. METHODS: A total of 217 breast cancer patients undergoing NAC were incorporated into this retrospectively research. K-M survival curves and log-rank tests are used to determine OS and DFS. Cox regression model was used to evaluate the relationship between NPS and OS and DFS. Nomogram was developed based on the results of multivariate Cox regression analysis. Prognostic models were internally validated using bootstrapping and the consistency index (C-index). RESULTS: Age group was correlated with NPS (p < 0.05). Low and moderate Naples risk patients had higher 5-year OS and DFS rates than high risk Naples patients (93.8% vs. 75.4% vs. 60.0%; X2 = 9.2, P = 0.01; 82.4% vs 64.5% vs 43.7%; X2 = 7.4, P = 0.024; respectively). The nomogram based on demonstrated good performance in predicting OS and DFS (AUC = 0.728, 0.630; respectively). CONCLUSIONS: In breast cancer patients who have undergone NAC, NPS is a novel prognostic indicator. NPS combined with clinicopathological features showed good predictive ability, and its performance was better than that of traditional pathological TNM staging.

Plant cadmium resistance 10 enhances tolerance to toxic heavy metals in poplar.

Toxic heavy metals originating from human activities have caused irreversible harm to the environment. Toxic heavy metal ions absorbed by crop plants can seriously threaten human health. Therefore, decreasing heavy metal contents in crop plants is an urgent need. The plant cadmium resistance protein (PCR) is a heavy metal ion transporter. In this study, PePCR10 was cloned from Populus euphratica. Bioinformatics analyses revealed its transmembrane structure and gene sequence motifs. The transcript profile of PePCR10 was analyzed by RT-qPCR, and its transcript levels increased under toxic heavy metal (cadmium, lead, aluminum) treatments. Subcellular localization analyses in tobacco cells revealed that PePCR10 localizes at the plasma membrane. Compared with wild type (WT), PePCR10-overexpressing lines showed significantly higher values for plant height, root length, fresh weight, and dry weight under heavy metal stress. Electrolyte leakage, nitroblue tetrazolium staining, and chlorophyll fluorescence analyses indicated that Cd/Al tolerance in PePCR10-overexpressing lines was stronger than that in WT. The Cd/Al contents were lower in the PePCR10-overexpressing lines than in WT under Cd/Al stress. Our results show that PePCR10 can reduce the heavy metal content in poplar and enhance its Cd/Al tolerance. Hence, PePCR10 is a candidate genetic resource for effectively reducing heavy metal accumulation in crops.

Populus euphratica plant cadmium resistance 2 mediates Cd tolerance by root efflux of Cd ions in poplar.

KEY MESSAGE: Populus euphratica PePCR2 increases Cd resistance by functioning as a Cd extrusion pump and by mediating the expression of genes encoding other transporters. Cadmium (Cd) is a non-essential, toxic metal that negatively affects plant growth. Plant cadmium resistance (PCR) proteins play key roles in the response to heavy metal stress. In this study, we isolated the gene PePCR2 encoding a plant PCR from Populus euphratica. PePCR2 gene transcription was induced by Cd, and its transcript level peaked at 24 h after exposure, at a level approximately 18-fold higher than that at 0 h. The PePCR2 protein was localized to the plasma membrane. Compared with yeast cells harboring the empty vector, yeast cells expressing PePCR2 showed enhanced Cd tolerance and a lower Cd content. Compared with wild-type (WT) plants, poplar overexpressing PePCR2 showed higher Cd resistance. Net Cd2+ efflux measurements showed that Cd2+ efflux from the roots was 1.5 times higher in the PePCR2-overexpressing plants than in WT plants. Furthermore, compared with WT plants, the PePCR2-overexpressing plants showed increased transcript levels of ABCG29, HMA5, PDR2, YSL7, and ZIP1 and decreased transcript levels of NRAMP6, YSL3, and ZIP11 upon exposure to Cd. These data show that PePCR2 increased Cd resistance by acting as a Cd extrusion pump and/or by regulating other Cd2+ transporters to decrease Cd toxicity in the cytosol. The results of this study identify a novel plant gene with potential applications in Cd removal, and provide a theoretical basis for reducing Cd toxicity and protecting food safety.

Populus euphratica plant cadmium tolerance PePCR3 improves cadmium tolerance.

Contamination of soils with toxic heavy metals is a major environmental problem. Growing crop plants that can promote the efflux of heavy metals is an effective strategy in contaminated soils. The plant cadmium resistance (PCR) protein is involved in the translocation of heavy metals, specifically zinc and cadmium (Cd). In this study, yeast expressing Populus euphratica PCR3 (PePCR3) showed enhanced Cd tolerance and decreased Cd accumulation under Cd treatment. Real-time quantitative PCR analyses revealed up-regulation of PePCR3 in poplar seedlings under Cd stress. Localization analysis revealed that PePCR3 localizes at the plasma membrane. The plant growth and biomass were greater in PePCR3-overexpressing (OE) transgenic hybrid poplar lines than in wild type (WT). Physiological parameters analyses indicated that, compared with WT, PePCR3-OE transgenic lines were more tolerant to Cd. In addition, more Cd was excreted in the roots of the PePCR3-OE transgenic lines than in those of WT, but the remaining Cd in transgenic lines was more translocated into the stems and leaves. Eight genes encoding transporters showed increased transcript levels in PePCR3-OE transgenic lines under Cd treatment, implying that PePCR3 interacts with other transporters to translocate Cd. Thus, PePCR3 may be an important genetic resource for generating new lines that can enhance Cd translocation to phytoremediation in contaminated soils.

Prediction of nonsentinel lymph node metastasis in breast cancer patients based on machine learning.

BACKGROUND: Develop the best machine learning (ML) model to predict nonsentinel lymph node metastases (NSLNM) in breast cancer patients. METHODS: From June 2016 to August 2022, 1005 breast cancer patients were included in this retrospective study. Univariate and multivariate analyses were performed using logistic regression. Six ML models were introduced, and their performance was compared. RESULTS: NSLNM occurred in 338 (33.6%) of 1005 patients. The best ML model was XGBoost, whose average area under the curve (AUC) based on 10-fold cross-verification was 0.722. It performed better than the nomogram, which was based on logistic regression (AUC: 0.764 vs. 0.706). CONCLUSIONS: The ML model XGBoost can well predict NSLNM in breast cancer patients.