Research hotspots and frontiers of neoadjuvant therapy in triple-negative breast cancer: a bibliometric analysis of publications between 2002 and 2023.

Triple-negative breast cancer (TNBC) is a highly aggressive type of breast cancer with poor prognosis, and neoadjuvant therapy (NAT) has emerged as an important component in managing advanced-stage patients by providing surgical opportunities and improving survival outcomes. A search of publications on NAT for TNBC from 2002 to 2023 was conducted through the Web of Science core collection. A comprehensive bibliometric analysis was conducted on the data using CiteSpace, VOSviewer, and Bibliometrix. The analysis revealed a continuous and steady growth in the number of articles published in this field over the past 20 years. The United States has made significant contributions to this field, with The University of Texas MD Anderson Cancer Center publishing the most articles. Loibl, S. from Germany was found to be the most published author with 54 articles. Analysis of the journals showed that the Journal of Clinical Oncology is the most cited journal. Combined with the keyword co-occurrence analysis and clustering analysis, current research topic focuses on treatment regimens and disease prognosis. Dual-map overlay of the journals indicates that the research trend is gradually shifting from molecular biology and genetics to immunology and clinical research. Combination therapy, including immunotherapy, may be the future direction for NAT treatment of TNBC. Overall, this study provides valuable insights into the current research status, latest advancements, and emerging development trend of NAT for TNBC.

Identification of TFRC as a biomarker for pulmonary arterial hypertension based on bioinformatics and experimental verification.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disease. However, there is a paucity of studies that reflect the available biomarkers from separate gene expression profiles in PAH. METHODS: The GSE131793 and GSE113439 datasets were combined for subsequent analyses, and batch effects were removed. Bioinformatic analysis was then performed to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) and a protein-protein interaction (PPI) network analysis were then used to further filter the hub genes. Functional enrichment analysis of the intersection genes was performed using Gene Ontology (GO), Disease Ontology (DO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA). The expression level and diagnostic value of hub gene expression in pulmonary arterial hypertension (PAH) patients were also analyzed in the validation datasets GSE53408 and GSE22356. In addition, target gene expression was validated in the lungs of a monocrotaline (MCT)-induced pulmonary hypertension (PH) rat model and in the serum of PAH patients. RESULTS: A total of 914 differentially expressed genes (DEGs) were identified, with 722 upregulated and 192 downregulated genes. The key module relevant to PAH was selected using WGCNA. By combining the DEGs and the key module of WGCNA, 807 genes were selected. Furthermore, protein-protein interaction (PPI) network analysis identified HSP90AA1, CD8A, HIF1A, CXCL8, EPRS1, POLR2B, TFRC, and PTGS2 as hub genes. The GSE53408 and GSE22356 datasets were used to evaluate the expression of TFRC, which also showed robust diagnostic value. According to GSEA enrichment analysis, PAH-relevant biological functions and pathways were enriched in patients with high TFRC levels. Furthermore, TFRC expression was found to be upregulated in the lung tissues of our experimental PH rat model compared to those of the controls, and the same conclusion was reached in the serum of the PAH patients. CONCLUSIONS: According to our bioinformatics analysis, the observed increase of TFRC in the lung tissue of human PAH patients, as indicated by transcriptomic data, is consistent with the alterations observed in PAH patients and rodent models. These data suggest that TFRC may serve as a potential biomarker for PAH.

Association between four insulin resistance surrogates and the risk of esophageal cancer: a prospective cohort study using the UK Biobank.

PURPOSE: This study explored the association between triglyceride-glucose (TyG), TyG index with body mass index (TyG-BMI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), metabolic score for insulin resistance (IR) (METS-IR) and the risk of esophageal cancer. METHODS: A total of 388,900 participants from the United Kingdom Biobank from 2006 to 2010 were included. Fine-Gray models, restricted cubic spline (RCS), and receiver operating characteristic (ROC) curves were used to assess the association between the four IR surrogates and the risk of esophageal cancer, specifically, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). RESULTS: Ten years after recruitment, 0.16% (95%CI 0.11-0.26%) had esophageal cancer and 4.17% (95%CI 3.86-4.46%) are deceased. For each standard deviation increase in the TyG index, TyG-BMI, TG/HDL-C, and METS-IR, the risk of EAC increased by Hazard ratios (HR)1.16, 1.37, 1.08, and 1.36, respectively (all P < 0.05), while the risk of ESCC decreased by HRs 0.80, 0.67, 0.77, and 0.65, respectively. RCS analysis indicated that most relationships were nonlinear (P < 0.05). ROC curves showed that METS-IR had a more robust diagnostic efficacy than TyG, TyG-BMI, and TG/HDL-C. CONCLUSION: TyG index, TyG-BMI, TG/HDL-C, and METS-IR were closely associated with the risk of EAC and ESCC. Additionally, METS-IR surpassed the other three IR indices in predicting and diagnosing the risks of EAC and ESCC. The METS-IR is expected to become a more effective metric for identifying populations at early risk of esophageal cancer and for improving risk stratification.

Multiple Structural and Phase Transformations of MOF and Selective Hydrocarbon Gas Separation in its Amorphous, Glass Phase States.

The first wide-view image of multiple structural and phase transformations for MOFs from crystal state transformations further to the extreme limit approaching liquid/glass phase, was presented based on a square-layer framework of [Co2(pybz)2(CH3COO)2]·DMF (Co2). The process involves i) an initial crystalline transformation brings to a 3-fold interpenetrated and ordered vacancies contained framework [Co(pybz)2(CH3OH)2]·2CH3OH (CoM) due to in-situ disassemble-reassemble, ii) thermal induced departure of a pair of cis-form coordinated methanol in CoM leads to amorphous framework (a-dCoM), iii) glass transition (Tg = 566 K) to super-cooled liquid (scl-dCoM, spanning 38 K), iv) obtaining MOF glass g-dCoM upon quenching the super-cooled liquid, and v) re-crystallization of super-cooled liquid to six-fold interpenetrated dia-net framework [Co(pybz)2]6n (rec-dCoM) under heating above 604 K. The access to glass from CoM, provides a new self-perturbation strategy to create more MOF glasses without melting. The wider pore size distribution in amorphous/glassy MOFs than crystalline precursor realized the first time selective hydrocarbon gas separation by breakthrough experiments, which bring efficient separation of 1:99 C2H2/C2H4 by either a-dCoM or g-dCoM and produce polymer grade C2H4 with purity ≥ 99.5% after a single adsorption process. Furthermore, the mixture of 50:50 C3H6/C3H8 can be separated by a-dCoM.

Electricity generated by upstream proton diffusion in two-dimensional nanochannels.

The movement of ions along the pressure-driven water flow in narrow channels, known as downstream ionic transport, has been observed since 1859 to induce a streaming potential and has enabled the creation of various hydrovoltaic devices. In contrast, here we demonstrate that proton movement opposing the water flow in two-dimensional nanochannels of MXene/poly(vinyl alcohol) films, termed upstream proton diffusion, can also generate electricity. The infiltrated water into the channel causes the dissociation of protons from functional groups on the channel surface, resulting in a high proton concentration inside the channel that drives the upstream proton diffusion. Combined with the particularly sluggish water diffusion in the channels, a small water droplet of 5 µl can generate a voltage of ~400 mV for over 330 min. Benefiting from the ultrathin and flexible nature of the film, a wearable device is built for collecting energy from human skin sweat.

Review of the Predictive Value of Biomarkers in Sepsis Mortality.

Sepsis is a leading cause of mortality among severely ill individuals, primarily due to its potential to induce fatal organ dysfunction. For clinicians, it is vital to have appropriate indicators, including the physiological status and personal experiences of patients with sepsis, to monitor the condition and assess prognosis. This approach aids in preventing the worsening of the illness and reduces mortality. Recent guidelines for sepsis focus on improving patient outcomes through early detection and timely treatment. Nonetheless, identifying severe cases and predicting their prognoses remain challenging. In recent years, there has been considerable interest in utilising the C-reactive protein (CRP)/albumin ratio (CAR) to evaluate the condition and forecast the prognosis of patients with sepsis. This research concentrates on the significance of CAR in the pathological process of sepsis, its association with prognosis, and the latest developments in employing procalcitonin, lactic acid, CRP, and other potential biomarkers. The CAR, with its predictive value for sepsis prognosis and mortality, is increasingly used as a clinical biochemical marker in diagnosing and monitoring patients with sepsis.

Deciphering the molecular landscape: evolutionary progression from gynecomastia to aggressive male breast cancer.

BACKGROUND: Gynecomastia denotes the benign proliferation of glandular breast tissue and stands as a recognized risk factor for male breast cancer. Nonetheless, the underlying carcinogenic mechanisms orchestrating the progression from gynecomastia to cancer remain poorly understood. METHODS: This study employed single-cell RNA sequencing (scRNA-seq) to meticulously dissect the cellular landscape of gynecomastia and unravel potential associations with male breast cancer at a single-cell resolution. Pseudotime and evolutionary analyses were executed to delineate the distinct features characterizing gynecomastia and male breast cancer. The TCGA database, along with cell-cell communication analysis and immunohistochemistry staining, was harnessed to validate differential gene expression, specifically focusing on CD13. RESULT: From the copy number variation profiles and evolutionary tree, we inferred shared mutation characteristics (18p+ and 18q+) underpinning both conditions. The developmental trajectory unveiled an intriguing overlap between gynecomastia and malignant epithelial cells. Moreover, the differential gene CD13 emerged as a common denominator in both gynecomastia and male breast cancer when compared with normal mammary tissue. Cell-cell interaction analysis and communication dynamics within the tumor microenvironment spotlighted distinctions between CD13+ and CD13- subsets, with the former exhibiting elevated expression of FGFR1-FGF7. CONCLUSIONS: Our investigation provides novel insights into the evolutionary progression from gynecomastia to male breast cancer, shedding light on the pivotal role of CD13 in driving this transition. The identification of CD13 as a potential therapeutic target suggests the feasibility of CD13-targeted interventions, specifically tailored for male breast cancer treatment.

Accurate measurement of the frequency offset of the laser based on electromagnetically induced transparency.

We propose a method using electromagnetically induced transparency (EIT) to measure the frequency offset of the laser relative to a cavity's resonance frequency, thereby reducing the laser detuning when preparing Rydberg atoms. Laser reflection by the vapor cell enables observation of two EIT peaks corresponding to the co-propagating and counter-propagating beams, and the peaks' position is related to laser detuning, allowing us to estimate the frequency offset of the probe and coupling lasers. The method reduces the measurement uncertainty compared to directly observing saturated absorption spectroscopy (SAS) and EIT, making it suitable for applications that require strict control over laser detuning.

IMU/Magnetometer-Based Azimuth Estimation with Norm Constraint Filtering.

A typical magnetometer-based measurement-while-drilling (MWD) system determines the azimuth of the bottom hole assembly during the drilling process by employing triaxial accelerometers and magnetometers. The geomagnetic azimuth solution is susceptible to magnetic interference, especially strong magnetic interference and so a rotary norm constraint filtering (RNCF) method for azimuth estimation, designed to support a gyroscope-aided magnetometer-based MWD system, is proposed. First, a new magnetic dynamical system, one whose output is observed by the magnetometers triad, is designed based on the Coriolis equation of the desired geomagnetic vector. Second, given that the norm of the non-interfered geomagnetic vector can be approximated as a constant during a short-term drilling process, a norm constraint procedure is introduced to the Kalman filter. This is achieved by the normalization of the geomagnetic part of the state vector of the dynamical system and is undertaken in order to obtain a precise geomagnetic component. Simulation and actual drilling experiments show that the proposed RNCF method can effectively improve the azimuth measurement precision with 98.5% over the typical geomagnetic solution and 37.1% over the KF in a RMSE sense when being strong magnetic interference environment.

Comparison of smokers' mortality with non-smokers following out-of-hospital cardiac arrests: a systematic review and meta-analysis.

OBJECTIVE: Although some studies have linked smoking to mortality after out-of-hospital cardiac arrests (OHCAs), data regarding smoking and mortality after OHCAs have not yet been discussed in a meta-analysis. Thus, this study conducted this systematic review to clarify the association. METHODS: The study searched Medline-PubMed, Web of Science, Embase and Cochrane libraries between January 1972 and July 2022 for studies that evaluated the association between smoking and mortality after OHCAs. Studies that reportedly showed relative risk estimates with 95% confidence intervals (CIs) were included. RESULTS: Incorporating a collective of five studies comprising 2477 participants, the analysis revealed a lower mortality risk among smokers in the aftermath of OHCAs compared with non-smokers (odds ratio: 0.77; 95% CI 0.61-0.96; P < 0.05). Egger's test showed no publication bias in the relationship between smoking and mortality after OHCAs. CONCLUSIONS: After experiencing OHCAs, smokers had lower mortality than non-smokers. However, due to the lack of data, this 'smoker's paradox' still needs other covariate effects and further studies to be considered valid.

Efficacy and safety of novel immune checkpoint inhibitor-based combinations versus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer: A network meta-analysis.

BACKGROUND: Patients with extensive-stage small cell lung cancer (ES-SCLC) have an exceptionally poor prognosis and immune checkpoint inhibitors (ICIs) combined with etoposide-platinum is recommended as standard first-line therapy. However, which combination pattern is the best still remains unknown. This network meta-analysis was performed to compare the efficacy and safety of currently available patterns including an antiangiogenic agent containing regimen and probed into the most appropriate therapy for patients. METHODS: Hazard ratios (HRs) and odds ratios (ORs) were generated using R software. The outcomes of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events of grade 3 or higher (grade ≥ 3 adverse events [AEs]) were analyzed. RESULTS: A total of 10 randomized controlled trials (RCTs) involving 5544 patients were included for analysis. Drug combination patterns included adebrelimab, atezolizumab, durvalumab, durvalumab plus tremelimumab, ipilimumab, pembrolizumab, serplulimab, benmelstobart plus anlotinib, tislelizumab, tiragolumab plus atezolizumab and toripalimab in combination with chemotherapy. The novel antiangiogenic agent containing regimen benmelstobart + anlotinib + chemotherapy showed the highest possibility to present the best PFS and OS versus chemotherapy. Compared with ICI plus chemotherapy, it also achieved significantly better PFS and presented a tendency of OS benefit. As for safety and toxicity, patients treated with benmelstobart + anlotinib + chemotherapy and durvalumab + tremelimumab + chemotherapy suffered a higher likelihood of more grade ≥ 3 AEs without unexpected AEs. CONCLUSION: PD-1/PD-L1 inhibitors-based combinations are associated with significant improvement in both PFS and OS for treatment-naïve ES-SCLC patients. Benmelstobart plus anlotinib with chemotherapy (CT) yielded better survival benefit versus CT alone or other ICIs + CT with caution for more adverse effects along with the addition of an antiangiogenic agent.

Supramolecular Interactions Induce Dynamics in Metal-Organic Layers to Selectively Separate Acetylene from Carbon Dioxide.

We report the synthesis and structural characterization of a 2D metal-organic framework with AB-packing layers, [Co2(pybz)2(CH3COO)2]·DMF (Co2, pybz= 4-(4-pyridyl)benzoate), containing a stable (4,4)-grid network fabricated by paddle-wheel nodes, ditopic pybz, and acetate ligands. After removal of the guest, the layer structure is retained but reorganized into an ABCD packing mode in the activated phase (Co2a). Consequently, the intralayer square windows (7.2 × 5.0 Å2) close, while the interlayer separation is decreased slightly from 3.69 to 3.45 Å, leaving a narrow gap. Importantly, the dangling methyl group of the acetate with H-bonds to the adjacent layers and also the well-distributed π-π interactions between the aromatic rings of neighboring layers facilitate the structural stability. These weak supramolecular interactions further allow for favorable dynamic exfoliation of the layers, which promotes efficient adsorption of C2H2 (41.6 cm3 g-1) over CO2 with an adsorption ratio of 6.3 (0.5 bar, 298 K). The effective separation performance of equimolar C2H2/CO2 was verified by cycling breakthrough experiments and was even tolerable to moisture (R.H = 52%). DFT calculations, in situ PXRD, and PDF characterization reveal that the favorable retention of C2H2 rather than that of CO2 is due to its H-bond formation with the paddle-wheel oxygen atoms that triggers the increase in interlayer separation during C2H2 adsorption.

Daidzein protects endothelial cells against high glucose-induced injury through the dual-activation of PPARα and PPARγ.

Endothelial damage caused by persistent glucose and lipid metabolism disorders is the main reason of diabetic vascular diseases. Daidzein exerts positive effects on vascular dysfunction. Peroxisome proliferator-activated receptors (PPARs) regulate critically glucose and lipid metabolism. However, the interaction of daidzein to PPARs is still insufficiently explored. In this study, the cell proliferation was detected by EdU. The intrinsic activity and binding affinity of daidzein for human PPARs (hPPARs) were estimated by transactivation reporter gene test and HPLC-UV method, respectively. Daidzein significantly reversed high glucose (HG, at 30 mmol/l)-induced injury in HUVECs, which was inhibited by both PPARα and PPARγ antagonist, but no PPARß antagonist. Daidzein selectively activated hPPARα and hPPARγ1, but weakly hPPARß. Additionally, daidzein also bound to both hPPARα and hPPARγ1. The findings suggested that daidzein may be a PPARα and PPARγ dual-agonist. The amelioration of daidzein on HUVECs from hyperglycemia may be mediated by the activation of PPARα and PPARγ receptors.

PEGylated-liposomal astaxanthin ameliorates Aß neurotoxicity and Alzheimer-related phenotypes by scavenging formaldehyde.

Alzheimer's disease (AD), which is a prevailing type of dementia, presents a significant global health concern. The current therapies do not meet clinical expectations. Amyloid-beta (Aß) has been found to induce endogenous formaldehyde (FA) accumulation by inactivating FA dehydrogenase (FDH); in turn, excessive FA triggers Aß aggregation that eventually leads to AD onset. Hence, scavenging FA by astaxanthin (ATX, a strong exogenous antioxidant) may be pursued as a promising disease-modifying approach. Here, we report that liposomal nanoparticles coupled with PEG (PEG-ATX@NPs) could enhance water-solubility of ATX and alleviate cognitive impairments by scavenging FA and reducing Aß deposition. To enable drug delivery to the brain, liposomes were used to encapsulate ATX and then coupled with PEG, which produced liposomal nanoparticles (PEGATX@NPs) with a diameter of <100 nm. The PEG-ATX@NPs reduced Aß neurotoxicity by both degrading FA and reducing FA-induced Aß assembly in vitro. Intraperitoneal administration of PEG-ATX@NPs in APPswe/PS1dE9 mice (APP/PS1, a familial model of AD), not only decreased the levels of brain FA and malondialdehyde (MDA, a typical product of oxidative stress), but also attenuated both intracellular Aß oligomerization and extracellular Aß-related senile plaque (SP) formation. These pathological changes were accompanied by rescued ability of spatial learning and memory. Collectively, PEG-ATX@NPs improved the water-solubility, bioavailability, and effectiveness of ATX. Thus, it has the potential to be developed as a safe and effective strategy for treating AD.

Altered functional connectivity in patients with post-stroke fatigue: A resting-state fMRI study.

BACKGROUND: Post-stroke fatigue (PSF) was a common complication after stroke. This study aimed to explore the neuroimaging mechanism of PSF, which was rarely studied. METHODS: Patients with the first episode of ischemic stroke were recruited from the First Affiliated Hospital of Wenzhou Medical University between March 2021 and December 2022. The fatigue severity scale (FSS) was used to assess fatigue symptoms. PSF was diagnosed by a neurologist based on the FSS score and PSF diagnostic criteria. All the patients were scanned by resting-state functional MRI (rs-fMRI). Precuneus, the posterior node of default-mode network (pDMN), was related to fatigue. Therefore, imaging data were further analyzed by the seed-based resting-state functional connectivity (FC) approach, with the left (PCUN.L) and right precuneus (PCUN.R) being the seeds. RESULTS: A total of 70 patients with acute ischemic stroke were finally recruited, comprising 40 patients with PSF and 30 patients without PSF. Both the PCUN.L and PCUN.R seeds (pDMN) exhibited decreased FC with the prefrontal lobes located at the anterior part of DMN (aDMN), and the FC values were negatively correlated with FSS scores (both p < 0.001). These two seeds also exhibited increased FC with the right insula, and the FC values were positively correlated with FSS scores (both p < 0.05). CONCLUSION: The abnormal FC between the aDMN and pDMN was associated with PSF. Besides, the insula, related to interoception, might also play an important role in PSF.

Diurnal regulation of alternative splicing associated with thermotolerance in rice by two glycine-rich RNA-binding proteins.

Rice (Oryza sativa L.) production is threatened by global warming associated with extreme high temperatures, and rice heat sensitivity is differed when stress occurs between daytime and nighttime. However, the underlying molecular mechanism are largely unknown. We show here that two glycine-rich RNA binding proteins, OsGRP3 and OsGRP162, are required for thermotolerance in rice, especially at nighttime. The rhythmic expression of OsGRP3/OsGRP162 peaks at midnight, and at these coincident times, is increased by heat stress. This is largely dependent on the evening complex component OsELF3-2. We next found that the double mutant of OsGRP3/OsGRP162 is strikingly more sensitive to heat stress in terms of survival rate and seed setting rate when comparing to the wild-type plants. Interestingly, the defect in thermotolerance is more evident when heat stress occurred in nighttime than that in daytime. Upon heat stress, the double mutant of OsGRP3/OsGRP162 displays globally reduced expression of heat-stress responsive genes, and increases of mRNA alternative splicing dominated by exon-skipping. This study thus reveals the important role of OsGRP3/OsGRP162 in thermotolerance in rice, and unravels the mechanism on how OsGRP3/OsGRP162 regulate thermotolerance in a diurnal manner.

The self-compatibility is acquired after polyploidization: a case study of Brassica napus self-incompatible trilinear hybrid breeding system.

Self-incompatibility plays a vital role in angiosperms, by preventing inbreeding depression and maintaining genetic diversity within populations. Following polyploidization, many angiosperm species transition from self-incompatibility to self-compatibility. Here, we investigated the S-locus in Brassicaceae and identified distinct origins for the sRNA loci, SMI and SMI2 (SCR Methylation Inducer 1 and 2), within the S-locus. The SMI loci were found to be widespread in Cruciferae, whereas the SMI2 loci were exclusive to Brassica species. Additionally, we discovered four major S-haplotypes (BnS-1, BnS-6, BnS-7, and BnS-1300) in rapeseed. Overexpression of BnSMI-1 in self-incompatible Brassica napus ('S-70S1300S6 ') resulted in a significant increase in DNA methylation in the promoter regions of BnSCR-6 and BnSCR-1300, leading to self-compatibility. Conversely, by overexpressing a point mutation of BnSmi-1 in the 'S-70S1300S6 ' line, we observed lower levels of DNA methylation in BnSCR-6 and BnSCR-1300 promoters. Furthermore, the overexpression of BnSMI2-1300 in the 'SI-326S7S6 ' line inhibited the expression of BnSCR-7 through transcriptional repression of the Smi2 sRNA from the BnS-1300 haplotype. Our study demonstrates that the self-compatibility of rapeseed is determined by S-locus sRNA-mediated silencing of SCR after polyploidization, which helps to further breed self-incompatible or self-compatible rapeseed lines, thereby facilitating the utilization of heterosis.

Printable Counter Electrode with Metal Nitride as the Conductive Medium for Perovskite Solar Cells.

Perovskite solar cells (PSCs) with a booming high power conversion efficiency (PCE) are on their road toward industrialization. A proper design of the counter electrode (CE) with low cost, high conductivity, chemical stability, and good interface contact with the other functional layer atop the perovskite layer is vital for the overall performance of PSCs. Herein, the application of titanium nitride (TiN) is reported as a conductive medium for the printable CE in hole-conductor-free mesoscopic PSCs. TiN improves the conductivity of the CE and reduces the resistivity from 20 to 10 mΩ∙cm. TiN also improves the wettability of the CE with perovskite and enhances the back interface contact, which promotes charge collection. On the other hand, TiN is chemically stable during processing and undergoes no distinguishable chemical reaction with halide perovskite. Devices with TiN as the conductive media in the CE deliver a champion PCE of 19.01%. This work supplies a considerable choice for the CE design of PSCs toward industrial applications.