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Despite much research in the field of island biogeography, mechanisms regulating insular diversity remain elusive. Here, we aim to explore mechanisms underlying plant species-area relationships in two tropical archipelagoes in the South China Sea. We found positive plant species-area relationships for both coral and continental archipelagoes. However, our results showed that different mechanisms contributed to similar plant species-area relationships between the two archipelagoes. For coral islands, soil nutrients and spatial distance among communities played major roles in shaping plant community structure and species diversity. By contrast, the direct effect of island area, and to a lesser extent, soil nutrients determined plant species richness on continental islands. Intriguingly, increasing soil nutrients availability (N, P, K) had opposite effects on plant diversity between the two archipelagoes. In summary, the habitat quality effect and dispersal limitation are important for regulating plant diversity on coral islands, whereas the passive sampling effect, and to a lesser extent, the habitat quality effect are important for regulating plant diversity on continental islands. More generally, our findings indicate that island plant species-area relationships are outcomes of the interplay of both niche and neutral processes, but the driving mechanisms behind these relationships depends on the type of islands.

Cadmium (Cd) is a naturally occurring toxic heavy metal that adversely affects plant germination, growth, and development. While the effects of Cd have been described on many crop species including rice, maize, wheat and barley, few studies are available on cadmium’s effect on Tartary buckwheat which is a traditional grain in China. We examined nine genotypes and found that 30 µM of Cd reduced the root length in seedlings by between 4 and 44% and decreased the total biomass by 7 to 31%, compared with Cd-free controls. We identified a significant genotypic variation in sensitivity to Cd stress. Cd treatment decreased the total root length and the emergence and growth of lateral roots, and these changes were significantly greater in the Cd-sensitive genotypes than in tolerant genotypes. Cd resulted in greater wilting and discoloration in sensitive genotypes than in tolerant genotypes and caused more damage to the structure of root and leaf cells. Cd accumulated in the roots and shoots, but the concentrations in the sensitive genotypes were significantly greater than in the more tolerant genotypes. Cd treatment affected nutrient uptake, and the changes in the sensitive genotypes were greater than those in the tolerant genotypes, which could maintain their concentrations closer to the control levels. The induction of SOD, POD, and CAT activities in the roots and shoots was significantly greater in the tolerant genotypes than in the sensitive genotypes. We demonstrated that Cd stress reduced root and shoot growth, decreased plant biomass, disrupted nutrient uptake, altered cell structure, and managed Cd-induced oxidative stress differently in the sensitive and tolerant genotypes of Tartary buckwheat.

There has been much debate on what, including evolutionary history, ecological processes or environmental change, might contribute to species extinctions. In this study, we explored how evolutionary attributes and life forms were correlated with extinction risk of Chinese flowering plants. We defined genus-level extinction risk as the ratio of threatened species over all species in each plant genus. We compiled data on extinction risk for 2731 genera representing 27332 angiosperm species from the IUCN Red List threatened species assessments. We quantified the strength of phylogenetic signal in extinction risk and used phylogenetic generalized linear mixed models to test the effects of evolutionary age, genus size, and evolutionary distinctiveness on extinction risk. We found woody plants suffered greater extinction risk than herbs. There were significant phylogenetic signals in extinction risk, but the signal was stronger in herbaceous plants than in woody plants. Genus size and genus stem age were both negatively associated with extinction risk. In constrast, we found positive correlations between evolutionary distinctiveness and extinction risk. We further indentified many genera (e.g., Cynomorium, Mytilaria, Kingdonia, Scheuchzeria, Brasenia, and Manglietia) had both high evolutionary distinctiveness and high extinction risk. Our study shows that the extinction risk of Chinese flowering plant is not randomly distributed across genera but has strong evolutionary predisposition. We suggest information on life forms, genus size, genus stem age, and evolutionary distinctiveness be considered when making priority for the protection of Chinese flowering plants.

As plants are sessile organisms, they are inevitably exposed to a variety of environmental stimuli that trigger rapid changes in the generation and disposal of reactive oxygen species such as hydrogen peroxide (H2O2). A major H2O2 scavenging system in plant cells is the ascorbate-glutathione cycle, in which ascorbate peroxidase (APX) catalyzes the conversion of H2O2 into water employing ascorbate as specific electron donor. In higher plants, distinct APX isoforms can occur in multiple subcellular compartments, including chloroplasts, mitochondria, and peroxisomes and the cytosol, to modulate organellar and cellular levels of H2O2. It is well established that APX plays crucial roles in protecting plant cells against diverse environmental stresses, as well as in plant growth and development. Apart from ascorbate, recently, APXs have been found to have a broader substrate specificity and possess chaperone activity, hence participating various biological processes. In this review, we describe the antioxidant properties of APXs and highlight their novel roles beyond ‘ascorbate peroxidases’.

Substantial advancements have been made in recent years in comprehending immune memory, which enhances the secondary response through prior infections. The ability of vertebrate T and B lymphocytes to exhibit classic recall responses has long been regarded as a distinguishing characteristic. However, natural killer (NK) cells have been found to acquire immunological memory in a manner akin to T and B cells. The fundamental principles derived from the investigation of NK cell memory offer novel insights into innate immunity and have the potential to pave the way for innovative strategies to enhance therapeutic interventions against multiple diseases including cancer. Here, we reviewed the fundamental characteristics, memory development and regulatory mechanism of NK cell memory. Moreover, we will conduct a comprehensive evaluation of the accomplishments, obstacles, and future direction pertaining to the utilization of NK cell memory in the field of cancer immunotherapy.

In this study, a composite process consisting of laser surface texture imitating fish scale shapes and plasma electrolytic oxidation (PEO) was used on the surface of aluminum alloy metals to prepare wear- and corrosion-resistant coatings. Before the conventional plasma electrolytic oxidation, the laser was used to prepare the imitation fish scale shape texture on the aluminum alloy surface. It was found that the PEO coating could cover the splash ablation particles left by the laser, while the imitation fish scale shape structure was enough to improve the tribological properties of the PEO coating, and the coating prepared by the combination of the two processes had a more stable friction coefficient, excellent corrosion resistance, and good resistance to abrasion corrosion. In this paper, the microstructure and composition of the coatings were characterized by metallurgical microscopy, XRD, and energy dispersive spectroscopy (EDS), and the protection mechanism and the physical model of the coatings prepared by the composite process were presented and discussed. In summary, the use of the composite process provides a feasible idea for improving the performance of aluminum alloys.

Abstract Background HDAC4 is a key regulator of chondrocyte hypertrophy and skeletal development, but it is not clear whether the increase in vascular invasion at growth plates is related to HDAC4 expression. To determine it, we investigated the relationship between HDAC4 and angiogenesis in both in vivo and in vitro models. Methods HDAC4 was deleted in Col2α1-Cre; HDAC4fl/fl mice. Growth of the Col2α1-Cre; HDAC4d/d mice was compared with HDAC4fl/fl mice at postnatal days 2, 4, 6, and 8. X-rays were taken to examine skeletal development. At postnatal days 14 and 21, mice were euthanized for specimen collection. Murine chondrocytes were isolated from the ventral parts of rib cages of 6-day-old mice (C57Bl/6) and transfected with a vector expressing HDAC4 as a fusion protein with green fluorescent protein (GFP). Relative expression levels of HDAC4, VEGF, and Hif1α were measured in these cells by Western blot, RT-qPCR, enzyme-linked immunosorbent, histology, and immunohistochemistry assays. Results The Col2α1-Cre; HDAC4d/d mice were markedly smaller compared with the control mice. At postnatal days 14 and 21, the Col2α1-Cre; HDAC4d/d mice exhibited a shortened growth plate, a larger secondary ossification center, and stronger staining of CD31 and CD34 compared to control mice. The isolated chondrocyte cells exhibited a high transfection efficiency of HDAC4 which resulted in the detection of a significant decrease in VEGF and Hif1α levels compared with the control chondrocytes. Conclusions HDAC4 expression in chondrocytes contributes to angiogenesis in the growth plate, and its absence in vivo negatively affects growth plates.

Alternate tillage (AT) has the potential to reduce inputs and improve soil quality and crop yield, but there has been no research on the effect of AT on soil and wheat in a rice–wheat rotation system. In this study, field experiments were conducted to examine the effects of four tillage management methods (conventional tilling (CT) in each crop (RCT–WCT), no tilling (NT) in rice and conventional tilling in wheat (RNT–WCT, AT1), conventional tilling in rice and no tilling in wheat (RCT–WNT, AT2), and no tilling in each crop (RNT–WNT)) on the physical properties of soil, wheat growth, and yield. At the 0–5 cm soil layer, CT in the wheat season increased bulk density (BD) and decreased total properties, but it decreased BD at the 5–40 cm soil layer, and the effect of RCT–WCT was significantly greater than that of RNT–WCT. CT in the wheat season increased the root activity, root dry weight, net photosynthetic rate, leaf area index, antioxidant enzyme activities, and yield, and there was no significant effect between RCT–WCT and RNT–WCT. RNT-WCT has the potential to reduce inputs and maintain wheat yields.

Owing to their sessile life habit, plants are continuously subjected to a broad range of environmental stresses. During periods of (a)biotic stresses, reactive oxygen species (ROS) levels can rise excessively, leading to oxidative stress. Glutathione reductase (GR) plays an important role in scavenging the ROS and maintenance of redox potential of the cell during oxidative stress. To enhance ROS scavenging capacity, and hence stress tolerance, the Arabidopsis thalianaGR2 (AtGR2) gene was expressed from the tobacco plastid (chloroplast) genome, the main source of ROS production in plant photosynthetic tissues, in this study. Leaves of transplastomic tobacco plants had about seven times GR activity and 1.5 times total glutathione levels compared to wild type. These transplastomic tobacco plants showed no discernible phenotype and exhibited more tolerance to methyl viologen-induced oxidative stress than wild-type control plants. The results indicate that introducing AtGR2 in chloroplasts is an efficient approach to increase stress tolerance. This study also provides evidence that increasing antioxidant enzyme via plastid genome engineering is an alternative to enhance plant’s tolerance to stressful conditions.

Nicotinamide adenine dinucleotide (NAD) is a pivotal coenzyme that has emerged as a central hub linking redox equilibrium and signal transduction in living cells. The homeostasis of NAD is required for plant growth, development, and adaption to environmental stresses. Quinolinate phosphoribosyltransferase (QPRT) is a key enzyme in NAD de novo synthesis pathway. T-DNA-based disruption of QPRT gene is embryo lethal in Arabidopsis thaliana. Therefore, to investigate the function of QPRT in Arabidopsis, we generated transgenic plants with decreased QPRT using the RNA interference approach. While interference of QPRT gene led to an impairment of NAD biosynthesis, the QPRT RNAi plants did not display distinguishable phenotypes under the optimal condition in comparison with wild-type plants. Intriguingly, they exhibited enhanced sensitivity to an avirulent strain of Pseudomonas syringae pv. tomato (Pst-avrRpt2), which was accompanied by a reduction in salicylic acid (SA) accumulation and down-regulation of pathogenesis-related genes expression as compared with the wild type. Moreover, oxidative stress marker genes including GSTU24, OXI1, AOX1 and FER1 were markedly repressed in the QPRT RNAi plants. Taken together, these data emphasized the importance of QPRT in NAD biosynthesis and immunity defense, suggesting that decreased antibacterial immunity through the alteration of NAD status could be attributed to SA- and reactive oxygen species-dependent pathways.

RNA interference (RNAi) has emerged as a novel and feasible strategy for pest management. Methods for cost-effective production and stable delivery of double-stranded RNA (dsRNA) to the target insects are crucial for the wide application of RNAi for pest control. In this study, we tested the expression of dsRNA in RNaseIII-deficient Escherichia coli HT115 which was then fed to Plagiodera versicolora larvae, an insect pest of Salicaceae plants worldwide. By targeting six potential genes, including actin (ACT), signal recognition particle protein 54k (SRP54), heat shock protein 70 (HSC70), shibire (SHI), cactus (CACT), and soluble N-ethylmaleimide-sensitive fusion attachment proteins (SNAP), we found that feeding bacteria-expressed dsRNA successfully triggered the silencing of the five target genes tested and the suppression of ACT and SRP54 genes caused significant mortality. Our results suggest that the oral delivery of bacteria-expressed dsRNA is a potential alternative for the control of P. versicolora, and that ACT and SRP54 genes are the potent targets.

Plastid transformation for the expression of recombinant proteins and entire metabolic pathways has become a promising tool for plant biotechnology. However, large-scale application of this technology has been hindered by some technical bottlenecks, including lack of routine transformation protocols for agronomically important crop plants like rice or maize. Currently, there are no standard or commercial plastid transformation vectors available for the scientific community. Construction of a plastid transformation vector usually requires tedious and time-consuming cloning steps. In this study, we describe the adoption of an in vivo Escherichia coli cloning (iVEC) technology to quickly assemble a plastid transformation vector. The method enables simple and seamless build-up of a complete plastid transformation vector from five DNA fragments in a single step. The vector assembled for demonstration purposes contains an enhanced green fluorescent protein (GFP) expression cassette, in which the gfp transgene is driven by the tobacco plastid ribosomal RNA operon promoter fused to the 5′ untranslated region (UTR) from gene10 of bacteriophage T7 and the transcript-stabilizing 3′UTR from the E. coli ribosomal RNA operon rrnB. Successful transformation of the tobacco plastid genome was verified by Southern blot analysis and seed assays. High-level expression of the GFP reporter in the transplastomic plants was visualized by confocal microscopy and Coomassie staining, and GFP accumulation was ~9% of the total soluble protein. The iVEC method represents a simple and efficient approach for construction of plastid transformation vector, and offers great potential for the assembly of increasingly complex vectors for synthetic biology applications in plastids.

Abstract Endocrine resistance poses a significant clinical challenge for patients with hormone receptor-positive and human epithelial growth factor receptor 2-negative (HR + HER2−) breast cancer. Dysregulation of estrogen receptor (ER) and ERBB signaling pathways is implicated in resistance development; however, the integration of these pathways remains unclear. While SMAD4 is known to play diverse roles in tumorigenesis, its involvement in endocrine resistance is poorly understood. Here, we investigate the role of SMAD4 in acquired endocrine resistance in HR + HER2− breast cancer. Genome-wide CRISPR screening identifies SMAD4 as a regulator of 4-hydroxytamoxifen (OHT) sensitivity in T47D cells. Clinical data analysis reveals downregulated SMAD4 expression in breast cancer tissues, correlating with poor prognosis. Following endocrine therapy, SMAD4 expression is further suppressed. Functional studies demonstrate that SMAD4 depletion induces endocrine resistance in vitro and in vivo by enhancing ER and ERBB signaling. Concomitant inhibition of ER and ERBB signaling leads to aberrant autophagy activation. Simultaneous inhibition of ER, ERBB, and autophagy pathways synergistically impacts SMAD4-depleted cells. Our findings unveil a mechanism whereby endocrine therapy-induced SMAD4 downregulation drives acquired resistance by integrating ER and ERBB signaling and suggest a rational treatment strategy for endocrine-resistant HR + HER2− breast cancer patients.

Abstract Background Depression and sleep disturbances are associated with increased risks of various diseases and mortality, but their impacts on mortality in cancer survivors remain unclear. The objective of this study was to characterize the independent and joint associations of depressive symptoms and sleep disturbances with mortality outcomes in cancer survivors. Methods This population-based prospective cohort study included cancer survivors aged ≥ 20 years (n = 2947; weighted population, 21,003,811) from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 cycles. Depressive symptoms and sleep disturbances were self-reported. Depressive symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9). Death outcomes were determined by correlation with National Death Index records through December 31, 2019. Primary outcomes included all-cause, cancer-specific, and noncancer mortality. Results During the median follow-up of 69 months (interquartile range, 37–109 months), 686 deaths occurred: 240 participants died from cancer, 146 from heart disease, and 300 from other causes. Separate analyses revealed that compared with a PHQ-9 score (0–4), a PHQ-9 score (5–9) was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.28; 95% CI, 1.03–1.59), and a PHQ-9 score (≥ 10) was associated with greater risk of all-cause mortality (HR, 1.37; 95% CI, 1.04–1.80) and noncancer mortality (HR, 1.45; 95% CI, 1.01–2.10). Single sleep disturbances were not associated with mortality risk. In joint analyses, the combination of a PHQ-9 score ≥ 5 and no sleep disturbances, but not sleep disturbances, was associated with increased risks of all-cause mortality, cancer-specific mortality, and noncancer mortality. Specifically, compared with individuals with a PHQ-9 score of 0–4 and no sleep disturbances, HRs for all-cause mortality and noncancer mortality in individuals with a PHQ-9 score of 5–9 and no sleep disturbances were 1.72 (1.21–2.44) and 1.69 (1.10–2.61), respectively, and 2.61 (1.43–4.78) and 2.77 (1.27–6.07), respectively, in individuals with a PHQ-9 score ≥ 10 and no sleep disturbances; HRs for cancer-specific mortality in individuals with a PHQ-9 score ≥ 5 and no sleep disturbances were 1.95 (1.16–3.27). Conclusions Depressive symptoms were linked to a high risk of mortality in cancer survivors. The combination of a PHQ-9 score (≥ 5) and an absence of self-perceived sleep disturbances was associated with greater all-cause mortality, cancer-specific mortality, and noncancer mortality risks, particularly in individuals with a PHQ-9 score (≥ 10).

Abstract Previously, we found that patients with estrogen receptor (ER)-positive, HER2-low breast cancer are resistant to neoadjuvant chemotherapy (NACT) and have worse outcomes than those who achieve pathological complete response (pCR) after NACT. This study aimed to investigate the prognosis and influencing factors in these patients. A total of 618 patients with ER-positive breast cancer who received standard thrice-weekly NACT were enrolled, including 411 patients with ER-positive, HER2-low breast cancer. Data on the clinicopathological features of these patients before and after NACT were collected. Univariate and multivariate Cox regression analyses were used to identify the independent factors affecting 5-year disease-free survival (DFS). Among the ER-positive, HER2-low patients, 49 (11.9%) achieved a pCR after NACT. A significant difference in survival was observed between patients with and without residual disease after NACT. Additionally, changes in immunohistochemical markers and tumor stages before and after NACT were found to be significant. According to univariate and multivariate analyses, cN_stage (P = 0.002), ER (P = 0.002) and Ki67 (P = 0.023) expression before NACT were significantly associated with 5-year DFS, while pT_stage (P = 0.015), pN_stage (P = 0.029), ER (P = 0.020) and Ki67 (P

Abstract Utrophin (UTRN), known as a tumor suppressor, potentially regulates tumor development and the immune microenvironment. However, its impact on breast cancer’s development and treatment remains unstudied. We conducted a thorough examination of UTRN using both bioinformatic and in vitro experiments in this study. We discovered UTRN expression decreased in breast cancer compared to standard samples. High UTRN expression correlated with better prognosis. Drug sensitivity tests and RT-qPCR assays revealed UTRN’s pivotal role in tamoxifen resistance. Furthermore, the Kruskal–Wallis rank test indicated UTRN’s potential as a valuable diagnostic biomarker for breast cancer and its utility in detecting T stage of breast cancer. Additionally, our results demonstrated UTRN’s close association with immune cells, inhibitors, stimulators, receptors, and chemokines in breast cancer (BRCA). This research provides a novel perspective on UTRN’s role in breast cancer’s prognostic and therapeutic value. Low UTRN expression may contribute to tamoxifen resistance and a poor prognosis. Specifically, UTRN can improve clinical decision-making and raise the diagnosis accuracy of breast cancer.

Double-stranded RNA (dsRNA)-degrading enzyme (dsRNase) is one of the negative factors influencing the RNA interference (RNAi) effect in Colorado potato beetle (CPB). We have previously shown that plastid-mediated RNAi (PM-RNAi) can be utilized to control CPB. In this study, we aimed to test whether silencing dsRNase could increase the RNAi effect in CPB via PM-RNAi. We generated transplastomic potato (Solanum tuberosum) plants expressing dsRNA targeting shibire (dsSHI) of CPB. St-dsSHI plants (transplastomic plants expressing dsSHI) showed much less potent RNAi response than transplastomic potato plants expressing dsRNAs targeting CPB Shrub (St-dsSHR) or β-Actin (St-dsACT), two CPB-resistant transplastomic lines generated previously. The three types of transplastomic lines have weak (St-dsSHI), moderate (St-dsSHR) and strong (St-dsACT) resistant levels to CPB. Treatment with in vitro-synthesized dsdsRNase1/2 (a fusion dsRNA targeting dsRNase1 and dsRNase2 of CPB) led to enhanced suppression of dsRNase1 and dsRNase2 in CPB larvae fed with St-dsSHI plants and dsRNase2 in CPB larvae fed with St-dsSHR plants. St-dsSHR or St-dsSHI plants showed significantly reduced CPB larva weight or damaged area by CPB feeding. These results demonstrate that dsRNase-silencing approach could improve the effect of PM-RNAi when the silencing of target genes has weak or moderate strength of the insecticidal effects. The findings provide a new proof-of-concept to enhance crop resistance to insect herbivores to via an “RNAi-of-RNAi” approach. [ABSTRACT FROM AUTHOR]

Abstract Background Breast cancer (BC) is the most common malignant tumor around the world. Timely detection of the tumor progression after treatment could improve the survival outcome of patients. This study aimed to develop machine learning models to predict events (defined as either (1) the first tumor relapse locally, regionally, or distantly; (2) a diagnosis of secondary malignant tumor; or (3) death because of any reason.) in BC patients post-treatment. Methods The patients with the response of stable disease (SD) and progressive disease (PD) after neoadjuvant chemotherapy (NAC) were selected. The clinicopathological features and the survival data were recorded in 1 year and 5 years, respectively. Patients were randomly divided into the training set and test set in the ratio of 8:2. A random forest (RF) and a logistic regression were established in both of 1-year cohort and the 5-year cohort. The performance was compared between the two models. The models were validated using data from the Surveillance, Epidemiology, and End Results (SEER) database. Results A total of 315 patients were included. In the 1-year cohort, 197 patients were divided into a training set while 87 were into a test set. The specificity, sensitivity, and AUC were 0.800, 0.833, and 0.810 in the RF model. And 0.520, 0.833, and 0.653 of the logistic regression. In the 5-year cohort, 132 patients were divided into the training set while 33 were into the test set. The specificity, sensitivity, and AUC were 0.882, 0.750, and 0.829 in the RF model. And 0.882, 0.688, and 0.752 of the logistic regression. In the external validation set, of the RF model, the specificity, sensitivity, and AUC were 0.765, 0.812, and 0.779. Of the logistics regression model, the specificity, sensitivity, and AUC were 0.833, 0.376, and 0.619. Conclusion The RF model has a good performance in predicting events among BC patients with SD and PD post-NAC. It may be beneficial to BC patients, assisting in detecting tumor recurrence.

Abstract Effective disinfection of contaminated surfaces is essential for preventing the transmission of pathogens. In this study, we investigated the UV irradiance and wavelength distribution of a 222-nm ultraviolet C (UVC) excimer lamp and its disinfection efficacy against microorganisms in laboratory conditions. By using a carrier quantitative germicidal test with stainless steel sheets as carriers, we examined the disinfection effect of the 222-nm UVC lamp on three standard strains-Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. We tested the disinfection efficacy under different conditions by adjusting irradiation time, as well as the state and temperature of the stainless steel carriers. Our results indicated that a bacterial suspension in PBS and not-dried stainless steel carriers yielded better disinfection than in TSB and dried carriers. Additionally, carrier temperature had no significant impact on disinfection efficacy. When utilizing a bacterial suspension in PBS and non-dried carriers at a temperature of 20 °C, the three bacteria were eliminated by 222-nm UVC excimer lamp irradiation in just 15 s. In contrast, when using a bacterial suspension in TSB and dried carriers at temperatures of 20 °C, 4 °C, or − 20 °C, the three bacteria were eradicated by 222-nm UVC excimer lamp irradiation in 60 s. Comparatively, the LPM lamp required more than 10 min to achieve the same disinfection effect. Our data demonstrate that the 222-nm UVC excimer lamp has higher irradiance and a more potent microbial disinfection effect than the LPM lamp, requiring significantly less irradiation time to achieve the same disinfection effect under identical conditions. Furthermore, the 222-nm UVC excimer lamp exhibited a substantial disinfection effect on bacterial propagules at low temperatures. Our findings support the optimization of “tunnel-type” cold-chain goods disinfection devices, providing an alternative, highly efficient, and practical tool to combat the spread of SARS-CoV-2 through cold-chain systems. Graphical Abstract

Plastid-mediated RNA interference (PM-RNAi) has emerged as a promising strategy for pest control. Expression from the plastid genome of stable double-stranded RNAs (dsRNAs) targeted against essential insect genes can effectively control some herbivorous beetles, but little is known about the efficacy of the transplastomic approach in other groups of pest insects, especially nonchewing insects that do not consume large amounts of leaf material. Here we have investigated the susceptibility of the western flower thrip (WFT, Frankliniella occidentalis), a notorious pest in greenhouses and open fields, to PM-RNAi. We show that WFTs ingest chloroplasts and take up plastidexpressed dsRNAs. We generated a series of transplastomic tobacco plants expressing dsRNAs and hairpin RNAs (hpRNAs) targeted against four essential WFT genes. Unexpectedly, we discovered plastid genome instability in transplastomic plants expressing hpRNAs, suggesting that dsRNA cassettes are preferable over hpRNA cassettes when designing PM-RNAi strategies. Feeding studies revealed that, unlike nuclear transgenic plants, transplastomic plants induced a potent RNAi response in WFTs, causing efficient suppression of the targeted genes and high insect mortality. Our study extends the application range of PM-RNAi technology to an important group of nonchewing insects, reveals design principles for the construction of dsRNAexpressing transplastomic plants, and provides an efficient approach to control one of the toughest insect pests in agriculture and horticulture. [ABSTRACT FROM AUTHOR]

The escalating global energy concerns have underscored the urgent need for energy conservation, particularly within the refrigerated industry. The imperative of optimizing the performance of open refrigerated display cabinets (ORDC) has become increasingly pronounced. This study sought to investigate the impact of condensate water recycling on ORDC operations through experiment, focusing on the influence of condensate water flowrate, temperature, and heat exchanger length on key performance indicators such as thermal entrainment factor (TEF), coefficient of performance (COP), and heat transfer efficiency enhancement (η). The findings revealed that the flowrate of condensate water wielded the most substantial impact on system performance, leading to noteworthy increases of 10.42% in COP and 7.05% in η, while TEF experienced a reduction of 4.33% within a flow rate range from 0 ml/min to 54 ml/min. Notably, an optimal flowrate of 54 ml/min was identified. Conversely, the temperature of condensate water exhibited minimal influence on system performance. Increasing the length of the heat exchanger demonstrated a linear correlation with improved system performance. In practical applications, the enhancements in COP, η, and TEF, compared to scenarios without a condensate water recycling system, ranged from 2.23% to 5.80%, 1.21% to 3.68%, and 0.37% to 2.09%, respectively.

BackgroundPathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is associated with favorable outcomes in breast cancer patients. Identifying reliable predictors for pCR can assist in selecting patients who will derive the most benefit from NAC. The prognostic nutritional index (PNI) serves as an indicator of nutritional status and systemic immune competence. It has emerged as a prognostic biomarker in several malignancies; however, its predictive value for pCR in breast cancer remains uncertain. The objective of this study is to assess the predictive value of pretreatment PNI for pCR in breast cancer patients.MethodsA total of 1170 patients who received NAC in two centers were retrospectively analyzed. The patients were divided into three cohorts: a training cohort (n=545), an internal validation cohort (n=233), and an external validation cohort (n=392). Univariate and multivariate analyses were performed to assess the predictive value of PNI and other clinicopathological factors. A stepwise logistic regression model for pCR based on the smallest Akaike information criterion was utilized to develop a nomogram. The C-index, calibration plots and decision curve analysis (DCA) were used to evaluate the discrimination, calibration and clinical value of the model.ResultsPatients with a high PNI (≥53) had a significantly increased pCR rate (OR 2.217, 95% CI 1.215-4.043, p=0.009). Tumor size, clinical nodal status, histological grade, ER, Ki67 and PNI were identified as independent predictors and included in the final model. A nomogram was developed as a graphical representation of the model, which incorporated the PNI and five other factors (AIC=356.13). The nomogram demonstrated satisfactory calibration and discrimination in the training cohort (C-index: 0.816, 95% CI 0.765-0.866), the internal validation cohort (C-index: 0.780, 95% CI 0.697-0.864) and external validation cohort (C-index: 0.714, 95% CI 0.660-0.769). Furthermore, DCA indicated a clinical net benefit from the nomogram.ConclusionThe pretreatment PNI is a reliable predictor for pCR in breast cancer patients. The PNI-based nomogram is a low-cost, noninvasive tool with favorable predictive accuracy for pCR, which can assist in determining individualized treatment strategies for breast cancer patients.

Abstract Mitochondrial function, as the core of the cell's energy metabolism, is firmly connected to cancer metabolism and growth. However, the involvement of long noncoding RNAs (lncRNAs) related to mitochondrial function in breast cancer (BRCA) has not been thoroughly investigated. As a result, the objective of this research was to dissect the prognostic implication of mitochondrial function-related lncRNAs and their link to the immunological microenvironment in BRCA. The Cancer Genome Atlas (TCGA) database was used to acquire clinicopathological and transcriptome information for BRCA samples. Mitochondrial function-related lncRNAs were recognized by coexpression analysis of 944 mitochondrial function-related mRNAs obtained from the MitoMiner 4.0 database. A novel prognostic signature was built in the training cohort using integrated analysis of mitochondrial function-related lncRNA and the corresponding clinical information through univariate analysis, lasso regression, and stepwise multivariate Cox regression analysis. The prognostic worth was judged in the training cohort and validated in the test cohort. In addition, functional enrichment and immune microenvironment analyses were performed to explore the risk score on the basis of the prognostic signature. An 8-mitochondrial function-related lncRNA signature was generated by integrated analysis. Individuals within the higher-risk category had a worse overall survival rate (OS) (training cohort: P

As the electric capacity of wind turbine increases, heat dissipation in pitch cabinets becomes challenging owing to the limited space and rotating conditions. To cool down the pitch cabinet more effectively and allow heat dissipation, we designed and implemented a pulsating heat pipe (PHP) in this study. We designed PHP parameters and conducted performance tests to compare the cooling performance of the fabricated PHP with that of an air-based cooling system in a 1.5 MW wind turbine. The results demonstrated steady PHP operation under rotating conditions (17.3 rpm). At a heat load of 1000 W, the evaporator outlet temperature was only 76.1 °C. However, increasing the ambient temperature adversely affected PHP operation, resulting in higher temperature and thermal resistance. The heat-pipe-based cooling system lowered the insulated gate bipolar transistor (IGBT) temperature by about 20.4 °C in relation to the air-based cooling system, while being suitable under varied conditions. Additionally, the system could successfully operate when the heat load of IGBT was 2350 W, corresponding to a 7 MW electric capacity of the wind turbine. Reducing the manufacturing cost of the heat pipe would further enhance the applicability of this system for pitch cabinet IGBT cooling, such as decreasing payback period.

In this study, we analyzed the relationship between the refrigerant distribution of a multiparallel evaporator and the structural design of a distributor to address uneven distribution of gas–liquid refrigerants in multiparallel evaporators under variable operating conditions. Herein, we proposed the shunting concept of “flow pattern setting and critical distribution” and designed a theoretical model for a rectifying nozzle-type critical distributor (RNCD). We built the experimental bench of a multiparallel evaporator using an RNCD and compared the cooling time of each cold storage, the superheat of each branch pipe, the cooling capacity of each cold storage, and the pressure drop of the distributor. Further, we investigated the shunting performance of the RNCD. The experimental results showed that the evaporation temperatures were −32 °C to −24 °C when cold storage temperatures of −22 °C to −14 °C, respectively. The unevenness of superheat at the outlet of each evaporator branch pipe of the RNCD was 0.0884–0.1275, while the unevenness associated with the refrigeration capacity of each cold storage was 0.1424–0.1714. This study provides basic research information to solve the problem of uneven refrigerant distribution when considering gas–liquid two-phase flow in multiparallel evaporators under variable operating conditions.

Abstract Background The role of postmastectomy radiation therapy (PMRT) in clinical T1-2N1 breast cancer patients who achieve axillary pathological complete response (ypN0) after neoadjuvant chemotherapy (NAC) is controversial. Methods Data from cT1-2N1 breast cancer patients who converted to ypN0 after NAC and subsequent surgery were retrospectively analyzed. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan‒Meier method. Univariate and multivariate Cox regression models were applied to investigate the correlations between clinical or pathological parameters and survival. Results From 2012–2019, we identified 116 cases for analysis, including 31 (26.7%) who received PMRT and 85 (73.3%) who did not. At a median follow-up time of 56.4 months, the 5-year DFS and OS rates were 90.2% and 96.7% with PMRT and 93.7% and 97.3% without PMRT, respectively. PMRT did not affect either DFS (p = 0.234) or OS (p = 0.878). On multivariate analyses, no differences in DFS or OS between the two groups were detected, taking into consideration the following factors: age, molecular subtype, Ki67 index, cT stage, and in-breast pathologic complete response (DFS: HR 2.260; 95% CI 0.465–10.982; p = 0.312. OS: HR 1.400; 95% CI 0.138–14.202; p = 0.776). This nonsignificant difference was also consistent in subgroup analyses (all p > 0.05). Conclusions PMRT has limited ability to confer DFS or OS benefits for cT1-2N1 breast cancer patients who achieved axillary pathological complete response after NAC and total mastectomy. It is imperative to conduct prospective studies to investigate the safety and feasibility of omitting PMRT. Trial registration: This research was approved by the Ethics Committee of The First Affiliated Hospital of Chongqing Medical University (ID: No. 2021–442).

In recent years, with the development of data centers toward high heat flux density, traditional air-cooled has gradually failed to meet the cooling requirements. So the liquid cooling for data centers is an important area for future development, and current research focuses on developing efficient heat sink structures or constructing energy-saving cold source schemes. However, to-date, there has been no integration of these two facets and consequently current results are limited by a lack of comprehensive analysis of the entire cooling system. Consequently, liquid cooling for data centers was developed in this study, and a comprehensive thermal management performance analysis was conducted, including a heat sink and cold source. A minimum energy consumption analysis was performed to determine an optimal thermal management strategy by constructing a 4.8 kW data center cooling system, containing 400 W for each chip, with the aid of TRNSYS software. Taking 70 °C as the safe temperature for the chips, the power consumption of pumps and an air-cooled chiller were explored by analyzing the internal relationships between server inlet temperature, chiller supply water temperature, ambient temperature, and rates of water flow; and optimal thermal management was achieved. In addition, the corresponding fitted correlations for the optimal rates of water flow for different chiller supply water temperatures, are provided to guide the optimal design of cooling systems.

Propose Neoadjuvant chemotherapy has been widely used in locally advanced and inflammatory breast cancer. Generally, complete pathological response after neoadjuvant chemotherapy treatment predicts survival. Studies have shown that patient-derived organoids can be used in cancer research and drug development. Therefore, we aimed to generate a living organoid biobank from biopsy samples to predict the response of patients to neoadjuvant chemotherapy.Method We generated a living organoid biobank from locally advanced breast cancer patients receiving neoadjuvant chemotherapy. When the patient received neoadjuvant chemotherapy, the organoids were treated with similar drugs, thereby simulating the situation of the patient receiving treatment.Result We successfully constructed organoids from breast cancer biopsies, demonstrating that organoids can be generated from a small sample of tissue. The phenotype of breast cancer organoid often agreed with the original breast cancer according to the blinded histopathological analysis of H&E stain tissue and organoid sections. In addition, our data confirm that the patient’s response to chemotherapy closely matches the organoids’ response to drugs.Conclusion Our data indicate that patient-derived organoids can be used to predict the clinical response of breast cancer patients to neoadjuvant chemotherapy in vitro and to screen drugs that have different effects on different patients. Key messageComplete pathological response (pCR) after adjuvant chemotherapy can predict, survival, therefore, predicting patient response to neoadjuvant chemotherapy is critical.Patient-derived organoids (PDOs) matched the original tumour in terms of histopathology, hormone receptor levels and HER2 receptor status.Patient-derived organoids can predict the responsiveness of patient to neoadjuvant chemotherapy.

A novel label-free optical fiber biosensor, based on a microcavity fiber Mach–Zehnder interferometer, was developed and practically demonstrated for DNA detection. The biosensor was fabricated using offset splicing standard communication single-mode fibers (SMFs). The light path of the sensor was influenced by the liquid sample in the offset open cavity. In the experiment, a high sensitivity of −17,905 nm/RIU was achieved in the refractive index (RI) measurement. On this basis, the probe DNA (pDNA) was immobilized onto the sensor’s surface using APTES, enabling real-time monitoring of captured complementary DNA (cDNA) samples. The experimental results demonstrate that the biosensor exhibited a high sensitivity of 0.32 nm/fM and a limit of detection of 48.9 aM. Meanwhile, the sensor has highly repeatable and specific performance. This work reports an easy-to-manufacture, ultrasensitive, and label-free DNA biosensor, which has significant potential applications in medical diagnostics, bioengineering, gene identification, environmental science, and other biological fields.

Timely detection of highly infectious pathogens is essential for preventing and controlling public health risks. However, most traditional testing instruments require multiple tedious steps and ultimately testing in hospitals and third-party laboratories. The sample transfer process significantly prolongs the time to obtain test results. To tackle this aspect, a portable fiber optic surface plasmon resonance (FO-SPR) device was developed for the real-time detection of infectious pathogens. The portable device innovatively integrated a compact FO-SPR sensing component, a signal acquisition and processing system, and an embedded power supply unit. A gold-plated fiber is used as the FO-SPR sensing probe. Compared with traditional SPR sensing systems, the device is smaller size, lighter weight, and higher convenience. To enhance the detection capacity of pathogens, a monolayer graphene was coated on the sensing region of the FO-SPR sensing probe. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was used to evaluate the performance of the portable device. The device can accurately detect the SARS-CoV-2 spike S1 protein in phosphate-buffered saline (PBS) and artificial saliva within just 20 min, and the device successfully detected cultured SARS-CoV-2 virus. Furthermore, the FO-SPR probe has long-term stability, remaining stable for up to 8 days. It could distinguish between the SARS-CoV-2 spike protein and the MERS-CoV spike protein. Hence, this FO-SPR device provides reliable, rapid, and portable access to test results. It provides a promising point-of-care testing (POCT) tool for on-site screening of infectious pathogens.

Objective Shenkang injection (SKI) has been widely used in China for many years for the treatment of kidney disease. The objective of this systematic review was to assess the efficacy of Shenkang injection for the treatment of acute kidney injury (AKI).Methods A search was conducted across seven databases, encompassing data from the inception of each database through October 8th, 2023. Randomized controlled trials comparing SKI-treated AKI patients with control subjects were extracted. The main outcome measure was serum creatinine (SCr) levels. Secondary outcomes included blood urea nitrogen (BUN), serum cystatin C (CysC), 24-h urine protein (24 h-Upro) levels, APACHE II score and adverse reactions.Results This meta-analysis included eleven studies, and the analysis indicated that, compared with the control group, SKI significantly decreased SCr [WMD = −23.31, 95% CI (-28.06, −18.57); p

Highlights 1. Avidin-stabilized gold nanoclusters (Av–Au NCs) were synthesized for the first time by a water-bath method. 2. The synthesized Av–Au NCs not only exhibited intense blue and red emissions under 374 nm excitation, but also retained the native functionality of avidin to bind to biotin. 3. The fluorescent signal amplification system constructed by the interaction of Av–Au NCs with biotin was successfully applied to detect target DNA in vitro.

Accurate spinal tuberculosis (TB) diagnosis is of utmost importance for adequately treating and managing the disease. Given the need for additional diagnostic tools, this study aimed to investigate the utility of host serum miRNA biomarkers for diagnosing and distinguishing spinal tuberculosis (STB) from pulmonary tuberculosis (PTB) and other spinal diseases of different origins (SDD). For a case-controlled investigation, a total of 423 subjects were voluntarily recruited, with 157 cases of STB, 83 cases of SDD, 30 cases of active PTB, and 153 cases of healthy controls (CONT) in 4 clinical centers. To discover the STB-specific miRNA biosignature, a high-throughput miRNA profiling study was performed in the pilot study with 12 cases of STB and 8 cases of CONT using the Exiqon miRNA PCR array platform. A bioinformatics study identified that the 3-plasma miRNA combination (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) might serve as a candidate biomarker for STB. The subsequent training study developed the diagnostic model using multivariate logistic regression in training data sets, including CONT(n=100) and STB (n=100). Youden’s J index determined the optimal classification threshold. Receiver Operating Characteristic (ROC) curve analysis showed that 3-plasma miRNA biomarker signatures have an area under the curve (AUC) = 0.87, sensitivity = 80.5%, and specificity = 80.0%. To explore the possible potential to distinguish spinal TB from PDB and other SDD, the diagnostic model with the same classification threshold was applied to the analysis of the independent validation data set, including CONT(n=45), STB(n=45), brucellosis spondylitis (BS, n=30), PTB (n=30), spinal tumor (ST, n=30) and pyogenic spondylitis (PS, n=23). The results showed diagnostic model based on three miRNA signatures could discriminate the STB from other SDD groups with sensitivity=80%, specificity=96%, Positive Predictive Value (PPV)=84%, Negative Predictive Value (NPV)=94%, the total accuracy rate of 92%. These results indicate that this 3-plasma miRNA biomarker signature could effectively discriminate the STB from other spinal destructive diseases and pulmonary tuberculosis. The present study shows that the diagnostic model based on 3-plasma miRNA biomarker signature (hsa-miR-506-3p, hsa-miR-543, hsa-miR-195-5p) may be used for medical guidance to discriminate the STB from other spinal destructive disease and pulmonary tuberculosis.

Aiming at improving the handling efficiency and acquiring the satisfactory antivibration effect and damping performance, a quad-bundle spacer damper of 500 kV extra high voltage transmission lines was designed and developed based on a new rubber structure. Firstly, a mathematical vibration model of the spacer damper was constructed, and the structures of the defect-prone parts of the spacer damper were analyzed. Then, the structure was optimized based on the defect analysis, the clamp with fast installation as well as removal and the damper joint with superior performance were designed. On this basis, a new quad-bundle spacer damper was developed. Last but not least, the handling efficiency of the new quad-bundle spacer damper was evaluated, and performance tests were conducted according to the IEC standards. The evaluation and test results show that the handling efficiency, antivibration effect, and damping performance of the new quad-bundle spacer damper are significantly improved compared with those of the regular quad-bundle spacer damper, which provides a guarantee for the safe operation of 500 kV extra high voltage transmission lines.

BackgroundTo characterize the clinicopathological features and evaluate the neoadjuvant chemotherapy (NACT) efficacy of patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer.MethodsA total of 905 breast cancer patients who received 4 cycles of thrice-weekly standard NACT in the First Affiliated Hospital of Chongqing Medical University were retrospectively enrolled, including 685 cases with HER2-low expression and 220 cases with HER2-negative expression. Clinicopathological features were compared between patients with HER2-negative and HER2-low expression. Univariate and multivariate logistic regression analyses were used to find the independent factors of achieving a pathological complete response (pCR) after NACT.ResultsThere were significant differences in stage_N (P = 0.014), histological grade (P = 0.001), estrogen receptor (ER) status (P < 0.001), progesterone receptor (PgR) status (P < 0.001), NACT regimens (P = 0.032) and NACT efficacy (P = 0.037) between patients with HER2-negative and HER2-low expression breast cancer. In subgroup analysis, histological grade (P = 0.032), ER (P = 0.002), Ki-67 (P < 0.001) and HER2 status (P = 0.025) were independent predictors of achieving a pCR in ER-positive breast cancer. And the nomogram for pCR in ER-positive breast cancer showed great discriminatory ability with an AUC of 0.795. The calibration curve also showed that the predictive ability of the nomogram was a good fit to actual observations. Then, in the analysis of ER-negative breast cancer, only stage_N (P = 0.001) and Ki-67 (P = 0.018) were independent influencing factors of achieving a pCR in ER-negative breast cancer.ConclusionHER2-low breast cancer was a different disease from HER2-negative breast cancer in clinicopathological features. Moreover, the NACT efficacy of HER2-low breast cancer patients was poorer.

Abstract Background Chemotherapy is widely used to treat hepatocellular carcinoma (HCC). Although sorafenib (SO) is the only chemotherapy drug approved by FDA for treatment of HCC, it is associated with several disadvantages including low water solubility, low bioavailability, lack of targeting and easily causes systemic toxicity. In recent years, nanocarriers have shown promise in drug delivery to effectively solve these problems. Herein, we used SO-loaded nanocarriers to overcome the defects of chemotherapy during treatment of HCC. Specifically, we encapsulated pH-sensitive hollow mesoporous Prussian blue nanoparticles (HMPB) with SO (an inhibitor of multi-kinase and accelerant of ferroptosis) to act as carriers and facilitate drug release. We also coated its surface with a layer of pH-responsive chitosan (CS) to block the drug and increase biocompatibility. Finally, we successfully constructed HP/SO/CS nanocomposites for targeted delivery of chemotherapeutic drugs, with the aim of initiating chemotherapy and ferroptosis for dual treatment of tumors. In vitro and in vivo experiments were performed for evaluation of the nanocomposites’ anti-tumor efficacy by using liver cancer cells and mice, respectively. Results The nanocomposites specifically targeted tumor cells through enhancing permeability and retention (EPR) effect. Results from in vitro experiments showed that the nanocarriers not only promoted cell apoptosis and reduced the number of cells for chemotherapy, but also promoted accumulation of reactive oxygen species (ROSs). In vivo experiments showed that mice in the nanocomposite-treated group exhibited the smallest tumor sizes and body weights, with no obvious damage to normal tissues and organs. Conclusion Taken together, these findings indicated that nanocarriers had an effective inhibitory effect on HCC cells. This safe and multifunctional treatment model was a valuable option for the treatment of HCC, as well as other cancers. Graphical Abstract

Abstract Ferroptosis is a new form of regulated cell death (RCD), and its emergence has provided a new approach to the progression and drug resistance of breast cancer (BRCA). However, there is still a great gap in the study of ferroptosis-related genes in BRCA, especially luminal-type BRCA patients. We downloaded the mRNA expression profiles and corresponding clinical data of BRCA patients from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) databases. Then, we built a prognostic multigene signature with ferroptosis-related differentially expressed genes (DEGs) in the METABRIC cohort and validated it in the TCGA cohort. The predictive value of this signature was investigated in terms of the immune microenvironment and the probability of a response to immunotherapy and chemotherapy. The patients were divided into a high-risk group and a low-risk group according to the ferroptosis-associated gene signature, and the high-risk group had a worse overall survival (OS). The risk score based on the 10 ferroptosis-related gene-based signature was determined to be an independent prognostic predictor in both the METABRIC and TCGA cohorts (HR, 1.41, 95% CI, 1.14–1.76, P = 0.002; HR, 2.19, 95% CI, 1.13–4.26, P = 0.02). Gene set enrichment analysis indicated that the term “cytokine-cytokine receptor interaction” was enriched in the high-risk score subgroup. Moreover, the immune infiltration scores of most immune cells were significantly different between the two groups, the low-risk group was much more sensitive to immunotherapy, and six drugs might have potential therapeutic implications in the high-risk group. Finally, a nomogram incorporating a classifier based on the 10 ferroptosis-related genes, tumor stage, age and histologic grade was established. This nomogram showed favorable discriminative ability and could help guide clinical decision-making for luminal-type breast carcinoma.

PurposeThis study aimed to determine the effect of neoadjuvant chemotherapy (NAC) on circulating levels of reproductive hormones and evaluate the correlation of hormone changes after NAC with hormone receptors expression alterations and relapse-free survival (RFS) outcomes in breast cancer.MethodsInformation from 181 breast cancer patients who received NAC was retrospectively analyzed. For hormones parameters, the median and interquartile range (IQR) were provided at baseline and the end of NAC then was compared by Wilcoxon signed-rank test. Categorical variables were represented as numbers and percentages and were compared via two-sided chi-square and Fisher's tests. The RFS outcomes were compared between patients according to hormone changes using the log-rank test. Univariate and multivariate survival analyses with hazard ratios (HR) and 95% confidence intervals (95% CI) were carried out using Cox regression.ResultsSex steroids including estradiol, progesterone, testosterone, and dehydroepiandrosterone sulfate (DHEAS) levels decreased significantly after NAC among both premenopausal and postmenopausal patients (all P

Angiogenesis is crucial in the development and progression of tumors. This study examined the relationship between angiogenesis-related lncRNAs (AR-lncRNAs) and breast cancer (BC) immunity and prognosis. We used univariate Cox regression analysis to obtain AR-lncRNAs closely related to BC prognosis. Cluster analysis of BC patients was performed using non-negative matrix factorization (NMF) analysis according to the expression of AR-lncRNAs that were prognostically relevant. An AR-lncRNA risk model (AR-lncM) was created using LASSO regression analysis to predict the prognosis and survival of BC patients. Subsequently, the effect of LINC01614 on cell migration and invasion was verified by Transwell and Western blot assays, and the CCK-8 assay detected its impact on cell sensitivity to tamoxifen. Finally, we obtained 17 AR-lncRNAs from the TCGA database that were closely associated with the prognosis of BC patients. Based on the expression of these AR-lncRNAs, BC patients were divided into five clusters using NMF analysis. Cluster 1 was found to have a better prognosis, higher expression of immune checkpoints, and higher levels of immune cell infiltration. Furthermore, an AR-LncM model was created using ten prognostic-related AR-lncRNAs. The model’s risk predictive performance was validated using survival analysis, timeROC curves, and univariate and multivariate Cox analysis. The most interesting gene in the model, LINC01614, was found to regulate epithelial-mesenchymal transition (EMT) and tamoxifen sensitivity in BC cells, implying that LINC01614 could be a potential therapeutic target for BC patients.

Abstract Background The aim of this study was to evaluate the relationship between pre-treatment plasma fibrinogen (Fib) level and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients and to assess the role of plasma Fib as a predictive factor. Methods Data from 1004 consecutive patients with invasive breast cancer who received NAC and subsequent surgery were retrospectively analysed. Both univariate and multivariate analyses based on logistic regression model were performed to identify clinicopathological factors associated with pCR to NAC. Cox regression model was used to determine the correlation between clinical or pathological parameters and recurrence-free survival (RFS). The Kaplan-Meier method and the log-rank test were applied in the survival analysis. Results The median value of Fib, rather than other plasma coagulation parameters, was significantly increased in non-pCR patients compared with pCR patients (P = 0.002). Based on the cut-off value estimated by the receiver operating characteristic (ROC) curve analysis, patients were divided into low or high Fib groups (Fib 5 cm group (77.5% vs 58.4%, log-rank, P = 0.0168). Conclusions This study demonstrates that low pre-treatment plasma Fib (Fib

Ferroptosis, a novel form of regulated cell death (RCD), has garnered increasing attention in studies on numerous human diseases in the last decade. Emerging evidence has indicated that the pathological process of ferroptosis involves the overloaded production of reactive oxygen species (ROS), followed by aberrant accumulation of lipid peroxidation in an iron-dependent manner, accompanied with an increased uptake of polyunsaturated fatty acids into the cellular membrane, further unfolding an ancient vulnerability in multiple context. The unique nature of ferroptosis differentiates it from other forms of RCD, as it is intricately associated with several biological processes, including the metabolism of iron, amino acids, synthesis of ROS and lipid peroxidation. Accordingly, inducers and inhibitors designed to target the key processes of ferroptosis have been extensively studied. Characterized by its distinct properties as mentioned above and its inducible nature, ferroptosis has been widely implicated in several diseases, and numerous studies have focused on identifying effective therapeutic targets for multiple human diseases, including in cancer, by targeting this process. In the present review, recent studies on the involvement of ferroptosis in several types of cancer are summarized and the findings discussed, highlighting the need for increased contemplation of its involvement in the study of cancer, particularly in the clinical setting. A comprehensive summary of the biological mechanisms underlying ferroptosis, the implications of the multiple inducers of ferroptosis, as well as immunotherapy targeting ferroptosis in different types of cancer is provided in this review to highlight the pathophysiological role of ferroptosis in carcinogenesis, to serve as an aid in future studies on the role of ferroptosis in cancer.

BackgroundMetastatic rectal cancer (mRC) of the breast is an extremely rare clinical situation. There are few reported cases in domestic or foreign literature. The clinicopathologic characteristics along with the diagnostic and therapeutic strategies of such cases remain relatively unclear. Here, we would like to provide our comprehensive insights into this rare entity.MethodsWe present a case that till now is the first reported breast metastasis from rectal cancer pathologically diagnosed as a signet-ring cell carcinoma, and we review the current literature on this rare event. The detailed clinical data, histopathology, management, and follow-up aspects were gathered for analysis.ResultsA total of 15 cases were collected including the current case. Breast metastases from rectal cancer present at an average age of 47.7 years (range, 28 to 69 years) and appear with an average interval of 28.4 months (range, 5 months to 18 years) following primary tumor diagnoses. Of the 15 cases, 8 and 5 are pathologically diagnosed as adenocarcinomas and mucinous adenocarcinomas, respectively. Most cases (11/15) are accompanied by extramammary metastases. About half of the breast metastases (7/15) were to the left. In all cases, the main complaints were palpable mass. The average maximum diameter of the metastatic mass is 2.7 cm (range, 1–11 cm). The majority (8/12) of cases with accessible therapy information exclude the option of local surgery.ConclusionPrevious cancer history and accurate immunohistochemistry data play critical roles to distinguish mammary metastasis from a primary neoplasm of the breast. Mastectomy and molecular-targeted drugs should be considered with priority if systemic condition supports them.

Breast cancer (BC) is the second leading cause of death among women and is highly heterogeneous. Three pyroptosis (PR) subtypes were identified in patients with BC from the Cancer Genome Atlas Database (TCGA) cohorts using 20 PR-related regulators, which illustrate a strong association between BC prognosis and PR. Lung metastasis commonly occurs in the advanced stages of BC, resulting in a poor quality of life. Eight differentially expressed (DE) lncRNAs were identified using LASSO–Cox analysis between PR-related and BC lung metastasis. Moreover, a BRCA risk-score (RS) model was established using multivariate Cox regression, which correlated with prognosis in TCGA-BRCA. Clinical characteristics, tumor mutation burden, and tumor immune cell infiltration were extensively investigated between high- and low-RS groups. Similarly, a lower RS implied longer overall survival, greater inflammatory cell infiltration, and better immunotherapeutic response to PD-1 blockers. Our findings provide a foundation for future studies targeting PR and confirme that RS could predict the prognosis of patients with BC.

Purpose: While a pathologic complete response (pCR) is regarded as a surrogate endpoint for pos-itive outcomes in breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC), fore-casting the prognosis of non-pCR patients is still an open issue. This study aimed to create and evaluate nomogram models for estimating the likelihood of disease-free survival (DFS) for non-pCR patients. Methods: A retrospective analysis of 607 non-pCR BC patients was conducted (2012–2018). After converting continuous variables to categorical variables, variables entering the model were progressively identified by univariate and multivariate Cox regression analyses, and then pre-NAC and post-NAC nomogram models were developed. Regarding their discrimination, ac-curacy, and clinical value, the performance of the models was evaluated by internal and external validation. Two risk assessments were performed for each patient based on two models; patients were separated into different risk groups based on the calculated cut-off values for each model, including low-risk (assessed by the pre-NAC model) to low-risk (assessed by the post-NAC model), high-risk to low-risk, low-risk to high-risk, and high-risk to high-risk groups. The DFS of different groups was assessed using the Kaplan–Meier method. Results: Both pre-NAC and post-NAC nomogram models were built with clinical nodal (cN) status and estrogen receptor (ER), Ki67, and p53 status (all p < 0.05), showing good discrimination and calibration in both internal and external validation. We also assessed the performance of the two models in four subtypes, with the tri-ple-negative subtype showing the best prediction. Patients in the high-risk to high-risk subgroup have significantly poorer survival rates (p < 0.0001). Conclusion: Two robust and effective nomo-grams were developed to personalize the prediction of DFS in non-pCR BC patients treated with NAC.

Breast cancer (BC) is a lethal malignancy with a poor prognosis. Necroptosis is critical in the progression of cancer. However, the expression of genes involved in necroptosis in BC and their association with prognosis remain unclear. We investigated the predictive potential of necroptosis-related genes in BC samples from the TCGA dataset. We used LASSO regression to build a risk model consisting of twelve necroptosis-related genes in BC. Using the necroptosis-related risk model, we were able to successfully classify BC patients into high- and low-risk groups with significant prognostic differences (p = 4.872 × 10 −7). Additionally, we developed a matched nomogram predicting 5, 7, and 10-year overall survival in BC patients based on this necroptosis-related risk model. Our next step was to perform multiple GSEA analyses to explore the biological pathways through which these necroptosis-related risk genes influence cancer progression. For these twelve risk model genes, we analyzed CNV, SNV, OS, methylation, immune cell infiltration, and drug sensitivity in pan-cancer. In addition, immunohistochemical data from the THPA database were used to validate the protein expression of these risk model genes in BC. Taken together, we believe that necroptosis-related genes are considered potential therapeutic targets in BC and should be further investigated.