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Photodynamic therapy (PDT) has attracted widespread attention from researchers as an emerging cancer treatment method. There have been many reports on various types of NIR-II photosensitizers for imaging and treatment of tumor sites. However, there are few reports on the development of NIR-II organic small molecule photosensitizers that have intelligent response to the tumor microenvironment, precise imaging, real-time treatment, and high biocompatibility. In this work, we developed a series of NIR-II photosensitizers (RBTs) with near-infrared excitation, good photostability, and large Stokes shift. Among them, RBT-Br exhibited higher reactive oxygen species (ROS) generation efficiency due to the introduction of halogen heavy atoms to enhance intersystem crossing (ISC). It is noteworthy that RBT-Br can generate singlet oxygen (1O2) and superoxide anion radicals (•O2-) simultaneously under 730 nm laser. Subsequently, we used molecular engineering technology to construct three pH-responsive NIR-II photosensitizers (RBT-pHs) by utilizing the closure of the lactam ring, among which RBT-pH-1 (pKa = 6.78) is able to be directionally activated under the stimulation of tumor micro-acid environment, with its fluorescence emission window reaching 933 nm. Subsequently, RBT-pH-1 NPs encapsulated in DSPE-mPEG5k were applied for PDT treatment of mouse tumors. The results showed that RBT-pH-1 NPs were activated by the acidic tumor microenvironment and generated ROS under laser excitation, exhibiting precise tumor imaging and significant tumor growth inhibition. We look forward to these multifunctional NIR-II organic small molecule photosensitizers providing a more efficient approach for clinical treatment of tumors. STATEMENT OF SIGNIFICANCE: : A reversible pH-switchable NIR-II nano-photosensitizer RBT-pH-1 NPs (pKa = 6.76) is developed for precise imaging and PDT therapy of mouse tumors, which can be effectively used for targeted enrichment and activation of tumor micro-acid environments. The results show that this NIR-II photosensitizer generates ROS through tumor micro-acid environment stimulation and laser triggering, showing precise tumor imaging guidance and significant tumor growth inhibition.

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2C is a highly conserved picornaviral non-structural protein with ATPase activity and plays a multifunctional role in the viral life cycle as a promising target for anti-picornavirus drug development. While the structure-function of enteroviral 2Cs have been well studied, cardioviral 2Cs remain largely uncharacterized. Here, an endogenous ATP molecule was identified in the crystal structure of 2C from encephalomyocarditis virus (EMCV, Cardiovirus A). The ATP is bound into the ATPase active site with a unique compact conformation. Notably, the γ-phosphate of ATP directly interacts with Arg311 (conserved in cardioviral 2Cs), and its mutation significantly inhibits the ATPase activity. Unexpectedly, this mutation remarkably promotes 2C self-oligomerization and viral replication efficiency. Molecular dynamic simulations showed that the Arg311 side chain is highly dynamic, indicating it may function as a switch between the activation state and the inhibition state of ATPase activity. A hexameric ring model of EMCV 2C full length indicated that the C-terminal helix may get close to the N-terminal amphipathic helices to form a continuous positive region for RNA binding. The RNA-binding studies of EMCV 2C revealed that the RNA length is closely associated with the RNA-binding affinities and indicated that the substrate may wrap around the outer surface of the hexamer. Our studies provide a biochemical framework to guide the characterization of EMCV 2C and the essential role of arginine in cardioviral 2C functions. IMPORTANCE: Encephalomyocarditis virus (Cardiovirus A) is the causative agent of the homonymous disease, which may induce myocarditis, encephalitis, and reproductive disorders in various mammals. 2C protein is functionally indispensable and a promising target for drug development involving broad-spectrum picornaviral inhibitors. Here, an endogenous ATP molecule with a unique conformation was discovered by a combination of protein crystallography and high-performance liquid chromatography in the encephalomyocarditis virus (EMCV) 2C structure. Biochemical and structural characterization analysis of EMCV 2C revealed the critical role of conserved Arg311 in ATPase activity and self-oligomerization of EMCV 2C. The viral replication kinetics and infectivity study suggested that the residue negatively regulated the infectivity titer and virus encapsulation efficiency of EMCV and is, therefore, crucial for 2C protein to promote viral replication. Our systemic structure-function analysis provides unique insights into the function and regulation mechanism of cardioviral 2C protein.

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[Purpose] This study aims to investigate the effects of robotic exoskeleton-assisted gait training on a pediatric patient with peripheral polyneuropathy. [Participant and Methods] A 10-year-old boy with lower extremity weakness attributed to peripheral polyneuropathy underwent a two-week program comprising 10 rehabilitation sessions of powered robotic exoskeleton-assisted gait training (REGT). He was evaluated before and after treatment using the 10-meter walk test, 6-minute walk test, Berg Balance Scale, the Timed Up and Go Test, the Functional Reach Test, the Modified Functional Reach Test, hip and knee flexion/extension angles, and cardiopulmonary exercise testing. [Results] The patient demonstrated improved gait speed, balance, joint mobility, cadence, the maximum oxygen consumption and metabolic equivalents after the REGT. [Conclusion] Robotic exoskeleton devices could provide additional benefits to pediatric patients with peripheral polyneuropathy, pending larger studies to confirm the significance of treatment.

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Traumatic main bronchus rupture is a relatively rare injury in thoracic trauma, which is extremely critical, with a mortality rate as high as 70% - 80%. The complete rupture and displacement of the traumatic cervical trachea can lead to asphyxia, hypoxia, and cardiac arrest, even death of the patient in a short time. We performed emergency surgery with the support of extracorporeal membrane oxygenation for a case of traumatic cervical tracheal trunk complete rupture and displacement combined with cardiac arrest and achieved a successful rescue. We summarized our experience and found that timely surgical reconstruction of the airway is the key to increasing the traumatic main bronchus rupture survival of patients.

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Houttuynia cordata Thunb., also known as Yuxingcao in Chinese, is a perennial herb in the Saururaceae family. It is highly regarded for its medicinal properties, particularly in treating respiratory infections and inflammatory conditions, as well as boosting the human immune system. However, the lack of genomic information has hindered research on the functional genomics and potential improvements of H. cordata. In this study, we present the assembly of a near-complete genome of H. cordata and investigate the biosynthesis pathway of flavonoids, specifically quercetin, using genomics, transcriptomics, and metabolomics analysis. The genome of H. cordata diverged from Saururus chinensis around 33.4 million years ago and consists of 2.24 Gb with 76 chromosomes (4n = 76), which underwent three whole-genome duplication (WGD) events. These WGDs played a crucial role in shaping H. cordata's genome and influencing gene families associated with its medicinal properties. Through metabolomics and transcriptomics analysis, we identified key genes involved in the ß-oxidation process for houttuynin biosynthesis, one of the volatile oils responsible for its fishy-smell. Additionally, utilizing the reference genome, we effectively identified genes involved in flavonoid biosynthesis, particularly quercetin metabolism in H. cordata. This discovery has paramount implications for understanding the regulatory mechanisms of active pharmaceutical ingredient production in traditional Chinese medicine. Overall, the high-quality genome of H. cordata serves as a crucial resource for future functional genomics research and provides a solid foundation for genetic improvement of H. cordata for the benefit of human health.

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Flight behaviours of birds have been extensively studied from different angles such as their kinematics, aerodynamics and more general, their migration patterns. Nevertheless, much is still unknown about the daily foraging flight activity and behaviour of breeding birds, and potential differences among males and females. The recent development of miniaturized accelerometers allows us a glimpse into the daily life of a songbird. Here, we tagged 13 male and 13 female pied flycatchers (Ficedula hypoleuca) with accelerometers and used machine learning approaches to analyse their flight activity and effort during the chick rearing period. We found that during two hours of foraging, chick-rearing pied flycatchers were flying on average 13.7% of the time. Almost all flights (>99%) were short flights lasting less than 10s. Flight activity changed throughout the day and was highest in the morning and lowest in the early afternoon. Male pied flycatcher had lower wing loading than females, and in-flight accelerations were inversely correlated with wing loading. Despite this, we found no significant differences in flight duration and intensity between sexes. This suggests that males possess a higher potential flight performance, which they did not fully utilize during foraging flights.

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Objectives: To summarize the clinical characteristics, outcomes and identify risk factors of Acinetobacter baumannii (AB) meningitis in children. Methods: This was a single-center, retrospective study. Children hospitalized between January 2016 and December 2021 who were diagnosed with AB meningitis were included. The clinical characteristics and outcomes were reviewed. Risk factors were determined using univariate analyses (chi-square and Mann-Whitney U tests). Results: Seventeen patients were included; 15 cases were secondary to neurosurgery, and two were neonates with primary bacterial meningitis. Common symptoms included fever, convulsions and nervous system abnormalities. Cerebrospinal fluid (CSF) tests typically showed increased white blood cell counts dominated by neutrophils, reduced glucose levels and elevated protein levels. Ten patients were successfully treated (successful treatment [ST] group); seven had failed treatment (failed treatment [FT] group). Univariate analyses revealed that mechanical ventilation, routine white cell counts in the peripheral blood, procalcitonin, protein in the CSF, septic shock and carbapenem-resistant AB (CRAB) differed significantly between the groups. Conclusion: AB meningitis in children has a high mortality rate. FT was associated with mechanical ventilation, septic shock, CRAB, lower peripheral leukocyte counts, higher protein levels in the CSF and procalcitonin. Larger studies are needed to identify independent risk factors for adverse outcomes.

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Human-virtual object interaction is common in both entertainment and work settings. This study investigated the movement time (MT) and subjective rating of difficulty (SRD) for moving a virtual cuboid in a 3D space. The participants wore an augmented reality (AR) headset, picked up a virtual cuboid, and placed it on an assigned target. They rated the SRD of the task on a five-point scale. The effects of the 3D coordinate of the target, sex, and handedness on the MT were analysed. The error placement rate was also recorded. Significant effects of spatial coordinates were found on both MT and SRD. Both single- and two-stage MT modelling were conducted using segmented and unsegmented MT data, respectively. The insignificant prediction error between the models indicates that the two-stage MT model is not superior to the single-stage one. The findings of this study are beneficial to software designers in designing user-friendly AR applications.

This study explores the movement time, subjective rating of difficulty, and error placement rate in positioning a virtual object in a 3D space. Regression movement time models were developed using both unsegmented and segmented movement time data. The findings provide insightful perspectives for software designers in designing user-friendly augmented reality applications.

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BACKGROUND: Differences of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. In more than 50% of human DSD cases, a molecular diagnosis is not available. In intensively farmed pig populations, the incidence of XX DSD pigs is relatively high, leading to economic losses for pig breeders. Interestingly, in the majority of 38, XX DSD pigs, gonads still develop into testis-like structures or ovotestes despite the absence of the testis-determining gene (SRY). However, the current understanding of the molecular background of XX DSD pigs remains limited. METHODS: Anatomical and histological characteristics of XX DSD pigs were analysed using necropsy and HE staining. We employed whole-genome sequencing (WGS) with 10× Genomics technology and used de novo assembly methodology to study normal female and XX DSD pigs. Finally, the identified variants were validated in 32 XX DSD pigs, and the expression levels of the candidate variants in the gonads of XX DSD pigs were further examined. RESULTS: XX DSD pigs are characterised by the intersex reproductive organs and the absence of germ cells in the seminiferous tubules of the gonads. We identified 4,950 single-nucleotide polymorphisms (SNPs) from non-synonymous mutations in XX DSD pigs. Cohort validation results highlighted two specific SNPs, "c.218T > C" in the "Interferon-induced transmembrane protein 1 gene (IFITM1)" and "c.1043C > G" in the "Newborn ovary homeobox gene (NOBOX)", which were found exclusively in XX DSD pigs. Moreover, we verified 14 candidate structural variants (SVs) from 1,474 SVs, identifying a 70 bp deletion fragment in intron 5 of the WW domain-containing oxidoreductase gene (WWOX) in 62.5% of XX DSD pigs. The expression levels of these three candidate genes in the gonads of XX DSD pigs were significantly different from those of normal female pigs. CONCLUSION: The nucleotide changes of IFITM1 (c.218T > C), NOBOX (c.1043 C > G), and a 70 bp deletion fragment of the WWOX were the most dominant variants among XX DSD pigs. This study provides a theoretical basis for better understanding the molecular background of XX DSD pigs. DSD are conditions affecting development of the gonads or genitalia. These disorders can happen in many different types of animals, including pigs, goats, dogs, and people. In people, DSD happens in about 0.02-0.13% of births, and in pigs, the rate is between 0.08% and 0.75%. Pigs have a common type of DSD where the animal has female chromosomes (38, XX) but no SRY gene, which is usually found on the Y chromosome in males. XX DSD pigs may look like both males and females on the outside and have testis-like or ovotestis (a mix of ovary and testis) gonads inside. XX DSD pigs often lead to not being able to have piglets, slower growth, lower chance of survival, and poorer meat quality. Here, we used a method called whole-genome de novo sequencing to look for variants in the DNA of XX DSD pigs. We then checked these differences in a larger group of pigs. Our results reveal the nucleotide changes in IFITM1 (c.218T > C), NOBOX (c.1043 C > G), and a 70 bp deletion fragment in intron 5 of the WWOX, all linked to XX DSD pigs. The expression levels of these three genes were also different in the gonads of XX DSD pigs compared to normal female pigs. These variants are expected to serve as valuable molecular markers for XX DSD pigs. Because pigs are a lot like humans in their genes, physiology, and body structure, this research could help us learn more about what causes DSD in people.

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Glioma segmentation is a crucial task in computer-aided diagnosis, requiring precise discrimination between lesions and normal tissue at the pixel level. Popular methods neglect crucial edge information, leading to inaccurate contour delineation. Moreover, global information has been proven beneficial for segmentation. The feature representations extracted by convolution neural networks often struggle with local-related information owing to the limited receptive fields. To address these issues, we propose a novel edge-aware segmentation network that incorporates a dual-path gradient-guided training strategy with Fourier edge-enhancement for precise glioma segmentation, a.k.a. GFNet. First, we introduce a Dual-path Gradient-guided Training strategy with Fourier edge-enhancement for precise glioma segmentation, a.k.a. GFNet. First, we introduce a Dual-path Gradient-guided Training strategy (DGT) based on a Siamese network guiding the optimizing direction of one path by the gradient from the other path. DGT pays attention to the indistinguishable pixels with large weight-updating gradient, such as the pixels near the boundary, to guide the network training, addressing hard samples. Second, to further perceive the edge information, we derive a Fourier Edge-enhancement Module (FEM) to augment feature edges with high-frequency representations from the spectral domain, providing global information and edge details. Extensive experiments on public glioma segmentation datasets, BraTS2020 and Medical Segmentation Decathlon (MSD), demonstrate that GFNet achieves competitive performance compared to other state-of-the-art methods, both qualitatively and quantitatively.

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PURPOSE: Following acute myocardial infarction (AMI), patients with diabetes mellitus (DM) have a poorer prognosis than those without DM. This study aimed to investigate the benefit of cardiac rehabilitation on cardiorespiratory fitness in patients with AMI, examining whether this effect varied depending on DM and glycated hemoglobin (HbA1c) levels. METHODS: Data were collected from the medical records of 324 patients diagnosed with AMI who were subsequently referred to participate in a supervised exercise-based cardiac rehabilitation program. Cardiorespiratory fitness was assessed using cardiopulmonary exercise testing before and at 3 and 6 mo after the start of cardiac rehabilitation. Linear mixed models were used to evaluate changes in cardiorespiratory fitness between patients with and without DM during the follow-up period. RESULTS: In total, 106 patients (33%) had DM. Both patients with and without DM showed a significant improvement in cardiorespiratory fitness from baseline to the 6-mo follow-up. However, the improvement was significantly lower in patients with DM than in those without DM (1.9 ± 1.5 vs. 3.7 ± 3.2 mL/kg/min, P < .001). Among patients with DM, those with HbA1c levels < 7% showed a greater improvement in cardiorespiratory fitness than those with HbA1c ≥ 7% (2.7 ± 1.5 vs. 1.1 ± 1.8 mL/kg/min, P < .001) during the follow-up period. CONCLUSIONS: Improvements in cardiorespiratory fitness following cardiac rehabilitation were significantly lower in patients with AMI and DM. The response to cardiac rehabilitation in patients is influenced by HbA1c levels. These findings suggest potential implications for individualizing cardiac rehabilitation programming and ensuring optimal glycemic control in patients with AMI and DM.

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Premature ovarian insufficiency (POI) is the main cause of infertility in women. Some cases of POI are thought to be caused by genetic defects and the clinical outcomes of these patients are unknown. Here, we performed whole-exome sequencing of the peripheral blood of a cohort of 55 subjects with POI and identified one heterozygous missense variant in FOXL2 (c.1045G>C; p.Arg349Gly) and two heterozygous missense variants in ERCC6 (c.379G>A; p.Val127Ile and c.4223A>C; p.Glu1408 Ala) in four POI patients. All of these heterozygous mutations were predicted to be deleterious and were parentally inherited from their heterozygous fathers. The mRNA and protein expression of FOXL2 and ERCC6 were absent or decreased in the patients. The patients carrying the variants of FOXL2 (c.1045G>C; p.Arg349Gly) and ERCC6 (c.379G>A; p.Val127Ile) failed to conceive in two and four assisted reproductive cycles, respectively. Another patient and her sister carrying the ERCC6 (c.4223A>C; p.Glu1408 Ala) variant achieved good clinical outcomes after assisted reproductive therapy. Our findings support the possible roles of FOXL2 and ERCC6 in POI and might contribute to the genetic counseling of POI patients.

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A thermosensitive and injectable hydrogel composed of chitosan (CS), chitosan biguanide hydrochloride (CSG) and collagen (CO) could embed umbilical cord mesenchymal stem cells (UC-MSCs), then was applied for the type 2 diabetes mellitus (T2DM) treatment in vivo. UC-MSCs could adhere well on CS/CSG/CO hydrogel surface and cell division could be clearly observed. Especially, UC-MSCs maintained alive till they grew in CS/CSG/CO hydrogel for 8 days, while the amount of UC-MSCs was limited due to the steric hindrance in hydrogel. To T2DM mice contrastive treatment by intraperitoneal injection for thirteen weeks, UC-MSCs + Hydrogel group could improve the impaired glucose tolerance, maintain glucose homeostasis in vivo, and restore islet morphology for T2DM mice. The immunofluorescence staining and western blot experiments further displayed that both the nuclear antigen Ki67 for cell proliferation and pancreatic duodenal homeobox-1 (Pdx1) expression in UC-MSCs + Hydrogel group were significantly higher than the expressions in untreated T2DM group and treated UC-MSCs + PBS group, which indicated that UC-MSCs + Hydrogel elevated ß cell transcriptional activity. Moreover, the positivity rates of iNOS and CD163 in UC-MSCs + Hydrogel group were generally decreased and increased, respectively, compared to those in untreated T2DM group and treated UC-MSCs + PBS group. It displayed that UC-MSCs + Hydrogel could reduce M1 macrophage expression and increase M2 macrophage polarization in T2DM mice.

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This study aimed to establish the preparation process of peptide-calcium chelates (TMP-Ca) using skipjack tuna meat and investigate the function and mechanism of TMP-Ca in an osteoporosis model of rats. The results indicated that trypsin is more suitable for preparing the Ca-chelating hydrolysates of tuna meat, and the optimal hydrolysis conditions were derived as follows: digestion time 4 h, material-liquid ratio 1:10, and enzyme dose 3%. The conditions for chelating Ca with tuna meat hydrolysate were optimized to be chelation time 50 min, temperature 50 °C, pH 8.0, and a peptide-Ca ratio 1:10. The prepared hydrolysate was subjected to ultrafiltration, and the fraction (TMP) (MW <1 kDa) showed the highest Ca chelation rate (51.27 ± 1.42%) and was made into the peptide-Ca chelates (TMP-Ca). In osteoporotic rats, TMP-Ca significantly improved the decrease in ovarian indexes caused by retinoic acid. It also elevated serum Ca, phosphorus, and bone turnover indexes, increased the number of bone trabeculae, and improved bone microstructure. In addition, we confirmed that TMP-Ca could regulate the OPG/TRAF6 pathway to reduce osteoclast differentiation, inhibit bone resorption, and promote bone formation. Therefore, TMP-Ca could significantly ameliorate osteoporosis, and this study provides a functional component for the preparation of healthcare products using skipjack tuna meat to treat osteoporosis.

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BACKGROUND: Uncertainty remains about the long-term effects of air pollutants (AP) on multiple diseases, especially subtypes of cardiovascular disease (CVD). We aimed to assess the individual and joint associations of fine particulate matter (PM2.5), along with its chemical components, nitrogen dioxide (NO2) and ozone (O3), with risks of 32 health conditions. METHODS: A total of 17,566 participants in Sichuan Province, China, were included in 2018 and followed until 2022, with an average follow-up period of 4.2 years. The concentrations of AP were measured using a machine-learning approach. The Cox proportional hazards model and quantile g-computation were applied to assess the associations between AP and CVD. RESULTS: Per interquartile range (IQR) increase in PM2.5 mass, NO2, O3, nitrate, ammonium, organic matter (OM), black carbon (BC), chloride, and sulfate were significantly associated with increased risks of various conditions, with hazard ratios (HRs) ranging from 1.06 to 2.48. Exposure to multiple air pollutants was associated with total cardiovascular disease (HR 1.75, 95% confidence intervals (CIs) 1.62-1.89), hypertensive diseases (1.49, 1.38-1.62), cardiac arrests (1.52, 1.30-1.77), arrhythmia (1.76, 1.44-2.15), cerebrovascular diseases (1.86, 1.65-2.10), stroke (1.77, 1.54-2.03), ischemic stroke (1.85, 1.61-2.12), atherosclerosis (1.77, 1.57-1.99), diseases of veins, lymphatic vessels, and lymph nodes (1.32, 1.15-1.51), pneumonia (1.37, 1.16-1.61), inflammatory bowel diseases (1.34, 1.16-1.55), liver diseases (1.59, 1.43-1.77), type 2 diabetes (1.48, 1.26-1.73), lipoprotein metabolism disorders (2.20, 1.96-2.47), purine metabolism disorders (1.61, 1.38-1.88), anemia (1.29, 1.15-1.45), sleep disorders (1.54, 1.33-1.78), renal failure (1.44, 1.21-1.72), kidney stone (1.27, 1.13-1.43), osteoarthritis (2.18, 2.00-2.39), osteoporosis (1.36, 1.14-1.61). OM had max weights for joint effects of AP on many conditions. CONCLUSIONS: Long-term exposure to increased levels of multiple air pollutants was associated with risks of multiple health conditions. OM accounted for substantial weight for these increased risks, suggesting it may play an important role in these associations.

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BACKGROUND: Bi-allelic variants in DNAH11 have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown. METHODS: A collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men. Whole-exome sequencing was employed for variant screening, and Sanger sequencing confirmed the identified variants. Morphological and ultrastructural analyses of sperm were conducted using Scanning Electron Microscopy and Transmission Electron Microscopy. Western Blot Analysis and Immunofluorescence Analysis were utilized to assess protein levels and localization. ICSI was performed to evaluate its efficacy in achieving favorable pregnancy outcomes for individuals with DNAH11 variants. RESULTS: In this study, we identified seven novel variants in the DNAH11 gene in four asthenoteratozoospermia subjects. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated, instead of inner dynein arms (IDA) proteins DNAH1 and DNAH6. Two out of four individuals with DNAH11 variants achieved clinical pregnancies through ICSI. The findings confirm the association between male infertility and bi-allelic deleterious variants in DNAH11, resulting in the aberrant assembly of sperm flagella and contributing to asthenoteratozoospermia. Importantly, ICSI emerges as an effective intervention for overcoming reproductive challenges caused by DNAH11 gene variants.

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BACKGROUND: Although tumor cells undergoing epithelial-mesenchymal transition (EMT) typically exhibit spindle morphology in experimental models, such histomorphological evidence of EMT has predominantly been observed in rare primary spindle carcinomas. The characteristics and transcriptional regulators of spontaneous EMT in genetically unperturbed non-spindled carcinomas remain underexplored. METHODS: We used primary culture combined with RNA sequencing (RNA-seq), single-cell RNA-seq (scRNA-seq), and in situ RNA-seq to explore the characteristics and transcription factors (TFs) associated with potential spontaneous EMT in non-spindled breast carcinoma. RESULTS: Our primary culture revealed carcinoma cells expressing diverse epithelial-mesenchymal traits, consistent with epithelial-mesenchymal plasticity. Importantly, carcinoma cells undergoing spontaneous EMT did not necessarily exhibit spindle morphology, even when undergoing complete EMT. EMT was a favored process, whereas mesenchymal-epithelial transition appeared to be crucial for secondary tumor growth. Through scRNA-seq, we identified TFs that were sequentially and significantly upregulated as carcinoma cells progressed through the EMT process, which correlated with increasing VIM expression. Once upregulated, the TFs remained active throughout the EMT process. ZEB1 was a key initiator and sustainer of EMT, as indicated by its earliest significant upregulation in the EMT process, its exact correlation with VIM expression, and the reversal of EMT and downregulation of EMT-upregulated TFs upon ZEB1 knockdown. The correlation between ZEB1 and vimentin expression in triple-negative breast cancer and metaplastic breast carcinoma tumor cohorts further highlighted its role. The immediate upregulation of ZEB2 following that of ZEB1, along with the observation that the knockdown of ZEB1 or ZEB2 downregulates both ZEB1 and ZEB2 concomitant with the reversal of EMT, suggests their functional cooperation in EMT. This finding, together with that of a lack of correlation of SNAI1, SNAI2, and TWIST1 expression with the mesenchymal phenotype, indicated EMT-TFs have a context-dependent role in EMT. Upregulation of EMT-related gene signatures during EMT correlated with poor patient outcomes, highlighting the biological importance of the model. Elevated EMT gene signatures and increased ZEB1 and ZEB2 expression in vimentin-positive compared to vimentin-negative carcinoma cells within the corresponding primary tumor tissue confirmed ZEB1 and ZEB2 as intrinsic, instead of microenvironmentally-induced, EMT regulators, and vimentin as an in vivo indicator of EMT. CONCLUSIONS: Our findings provide insights into the characteristics and transcriptional regulators of spontaneous EMT in primary non-spindled carcinoma.

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Flavonol-metal complexes can enhance the biological activity of flavonols. Inspired by the potential of ruthenium-based drugs in pharmaceutical applications, seven flavonol-Ru (II) complexes were synthesized to evaluate their biological activities. Among these compounds, compounds 8, 11, and 12 showed potent antioxidant activities. Compound 12 exhibited superior anti-inflammatory activity to natural quercetin, which served as a positive control. This study is the first to report the free radical scavenging abilities and antioxidant activity of flavonol-Ru (II) complexes. Furthermore, compound 12 demonstrated comparable efficacy to 5-FU against human non-small-cell lung cancer cells (A549). These results strongly support the potential of flavonol-Ru (II) agents.

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Advances in materials science are increasingly dependent on the development of multifunctional materials capable of improving system efficiency and reducing the environmental impact. In this study, two zero-dimensional (0D) cadmium-based organic-inorganic hybrid materials (BEMPD)2CdBr4 (BEMPD-Br, 1) and (BEMPD)2CdBr2Cl2 (BEMPD-ClBr, 2) (BEMPD = 1-(2-bromoethyl)-1-methylpiperidine) were prepared by halogen doping. Compound 2 is a mixed halide in which there are two halogen sites, Cl and Br, and in a disordered state, which has a regulatory effect on the structural distortion and properties of the compound. The Curie temperatures of compounds 1 and 2 are 348 and 390 K, respectively, and the UV-vis absorption spectra showed that the direct band gaps of compounds 1 and 2 were 4.68 and 4.8 eV, respectively. In addition, room-temperature photoluminescence experiments show broadband emission peaks at 717 and 683 nm for compounds 1 and 2, respectively, with fluorescence lifetimes of 2.414 and 3.915 µs. These 0D hybrids provide an avenue for the development of smart materials and optoelectronic devices, and also provide positive clues for manipulating the properties of organic-inorganic hybrid compounds.

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Background: The 2015 American Thyroid Association (ATA) guidelines added thyroid lobectomy (TL) as the appropriate treatment for low-risk differentiated thyroid cancer (DTC). We aimed to investigate the population-level factors that influence the utilization of TL. Methods: The Surveillance, Epidemiology and End Results (SEER) database was queried for all DTC patients fitting low-risk criteria as defined by the ATA. Trends in total thyroidectomy (TT) and TL were identified using a Cochrane-Armitage test. Multivariable logistic regression identified patient and socioeconomic characteristics associated with TL, and difference-in-difference analysis was used to control for secular trends over time. Results: A total of 43,526 patients with low-risk DTC were identified in the SEER database; 39,411 pre-2015 and 4115 post-2015. After 2015, TT continued to outnumber TL (76.2% vs 23.8%), although the rate of TL increased significantly (11.6% to 23.8%, P < 0.001). However, difference-in-difference analysis found that age > 55 (OR 1.11, 95% CI 1.01-1.19, P < 0.001) and rurality (OR 1.16, 95% CI 1.05-1.28, P < 0.001) were independently associated with TT. TL was associated with T1 disease (OR 1.11, 95% CI 1.04-1.19, P = 0.001). Conclusion: Although the 2015 ATA guideline update led to an increase in TL for low-risk DTC, most patients still underwent TT. Age and neighborhood significantly impact the odds of receiving guideline-appropriate TL for low-risk DTC, especially for T2 disease.