Longitudinal ultrasound-based AI model predicts axillary lymph node response to neoadjuvant chemotherapy in breast cancer: a multicenter study.

OBJECTIVES: Developing a deep learning radiomics model from longitudinal breast ultrasound and sonographer's axillary ultrasound diagnosis for predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: Breast cancer patients undergoing NAC followed by surgery were recruited from three centers between November 2016 and December 2022. We collected ultrasound images for extracting tumor-derived radiomics and deep learning features, selecting quantitative features through various methods. Two machine learning models based on random forest were developed using pre-NAC and post-NAC features. A support vector machine integrated these data into a fusion model, evaluated via the area under the curve (AUC), decision curve analysis, and calibration curves. We compared the fusion model's performance against sonographer's diagnosis from pre-NAC and post-NAC axillary ultrasonography, referencing histological outcomes from sentinel lymph node biopsy or axillary lymph node dissection. RESULTS: In the validation cohort, the fusion model outperformed both pre-NAC (AUC: 0.899 vs. 0.786, p < 0.001) and post-NAC models (AUC: 0.899 vs. 0.853, p = 0.014), as well as the sonographer's diagnosis of ALN status on pre-NAC and post-NAC axillary ultrasonography (AUC: 0.899 vs. 0.719, p < 0.001). Decision curve analysis revealed patient benefits from the fusion model across threshold probabilities from 0.02 to 0.98. The model also enhanced sonographer's diagnostic ability, increasing accuracy from 71.9% to 79.2%. CONCLUSION: The deep learning radiomics model accurately predicted the ALN response to NAC in breast cancer. Furthermore, the model will assist sonographers to improve their diagnostic ability on ALN status before surgery. CLINICAL RELEVANCE STATEMENT: Our AI model based on pre- and post-neoadjuvant chemotherapy ultrasound can accurately predict axillary lymph node metastasis and assist sonographer's axillary diagnosis. KEY POINTS: Axillary lymph node metastasis status affects the choice of surgical treatment, and currently relies on subjective ultrasound. Our AI model outperformed sonographer's visual diagnosis on axillary ultrasound. Our deep learning radiomics model can improve sonographers' diagnosis and might assist in surgical decision-making.

TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes.

AIM: To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children. METHODS: This study consists of two surveys. A total of 40 T1DM children was included in the first survey. Because no participant has DR, retina thinning was used as a surrogate indicator for DR. The lowest 25% participants with the thinnest macular retinal thickness were included into the case group, and the others were controls. The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay, and compared between the case and control groups. Four DMS with a potential role in diabetes were identified. The second survey included 27 T1DM children, among which four had DR. The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing. RESULTS: In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δß|>0.1 and Adj.P<0.05), and 328 of these were identified with a significance of Adj.P<0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls. Pyrosequencing revealed that the transcription elongation regulator 1 like (TCERG1L, cg07684215) gene was hypermethylated in the four T1DM children with DR (P=0.018), which was consistent with the result from the first survey. The methylation status of the other three DMS (cg26389052, cg25192647, and cg05413694) showed no difference (all P>0.05) between participants with and without DR. CONCLUSION: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

Modulating extracellular matrix stiffness: a strategic approach to boost cancer immunotherapy.

The interplay between extracellular matrix (ECM) stiffness and the tumor microenvironment is increasingly recognized as a critical factor in cancer progression and the efficacy of immunotherapy. This review comprehensively discusses the key factors regulating ECM remodeling, including the activation of cancer-associated fibroblasts and the accumulation and crosslinking of ECM proteins. Furthermore, it provides a detailed exploration of how ECM stiffness influences the behaviors of both tumor and immune cells. Significantly, the impact of ECM stiffness on the response to various immunotherapy strategies, such as immune checkpoint blockade, adoptive cell therapy, oncolytic virus therapy, and therapeutic cancer vaccines, is thoroughly examined. The review also addresses the challenges in translating research findings into clinical practice, highlighting the need for more precise biomaterials that accurately mimic the ECM and the development of novel therapeutic strategies. The insights offered aim to guide future research, with the potential to enhance the effectiveness of cancer immunotherapy modalities.

BeM(CO)3- (M = Co, Rh, Ir) and BeM(CO)3 (M = Ni, Pd, Pt): Triply bonded terminal beryllium in zero oxidation state.

We perform detailed potential energy surface explorations of BeM(CO)3- (M = Co, Rh, Ir) and BeM(CO)3 (M = Ni, Pd, Pt) using both single-reference and multireference-based methods. The present results at the CASPT2(12,12)/def2-QZVPD//M06-D3/def2-TZVPPD level reveal that the global minimum of BeM(CO)3- (M = Co, Rh, Ir) and BePt(CO)3 is a C3v symmetric structure with an 1A1 electronic state, where Be is located in a terminal position bonded to M along the center axis. For other cases, the C3v symmetric structure is a low-lying local minimum. Although the present complexes are isoelectronic with the recently reported BFe(CO)3- complex having a B-Fe quadruple bond, radial orbital-energy slope (ROS) analysis reveals that the highest occupied molecular orbital (HOMO) in the title complexes is slightly antibonding in nature, which bars a quadruple bonding assignment. Similar weak antibonding nature of HOMO in the previously reported BeM(CO)4 (M = Ru, Os) complexes is also noted in ROS analysis. The bonding analysis through energy decomposition analysis in combination with the natural orbital for chemical valence shows that the bonding between Be and M(CO)3q (q = -1 for M = Co, Rh, Ir and q = 0 for M = Ni, Pd, Pt) can be best described as Be in the ground state (1S) interacting with M(CO)30/- via dative bonds. The Be(spσ) → M(CO)3q σ-donation and the complementary Be(spσ) ← M(CO)3q σ-back donation make the overall σ bond, which is accompanied by two weak Be(pπ) ← M(CO)3q π-bonds. These complexes represent triply bonded terminal beryllium in an unusual zero oxidation state.

A facile cellulose finishing strategy through in-situ growth of sliver-doped manganese dioxide assisted by amine-quinone for improving indoor living quality.

Nowadays, various harmful indoor pollutants especially including bacteria and residual formaldehyde (HCHO) seriously threaten human health and reduce the quality of public life. Herein, a universal substrate-independence finishing approach for efficiently solving these hybrid indoor threats is demonstrated, in which amine-quinone network (AQN) was employed as reduction agent to guide in-situ growth of Ag@MnO2 particles, and also acted as an adhesion interlayer to firmly anchor nanoparticles onto diverse textiles, especially for cotton fabrics. In contrast with traditional hydrothermal or calcine methods, the highly reactive AQN ensures the efficient generation of functional nanoparticles under mild conditions without any additional catalysts. During the AQN-guided reduction, the doping of Ag atoms onto cellulose fiber surface optimized the crystallinity and oxygen vacancy of MnO2, providing cotton efficient antibacterial efficiency over 90 % after 30 min of contact, companying with encouraging UV-shielding and indoor HCHO purification properties. Besides, even after 30 cycles of standard washing, the Ag@MnO2-decorated textiles can effectively degrade HCHO while well-maintaining their inherent properties. In summary, the presented AQN-mediated strategy of efficiently guiding the deposition of functional particles on fibers has broad application prospects in the green and sustainable functionalization of textiles.

NLRP3 inflammasome activation triggers severe inflammatory liver injury in N, N-dimethylformamide-exposed mice.

N,N-dimethylformamide (DMF) is a widely utilized chemical solvent with various industrial applications. Previous studies have indicated that the liver is the most susceptible target to DMF exposure, whereas the underlying mechanisms remain to be elucidated. This study aimed to investigate the role of NLRP3 inflammasome in DMF-induced liver injury in mice by using two NLRP3 inflammasome inhibitors, Nlrp3-/- mice, Nfe2l2-/- mice, and a macrophage-depleting agent. RNA sequencing revealed that endoplasmic reticulum (ER) stress and NLRP3 inflammasome-associated pathways were activated in the mouse liver after acute DMF exposure, which was validated by Western blotting. Interestingly, DMF-induced liver injury was effectively suppressed by two inflammasome inhibitors, MCC950 and Dapansutrile. In addition, knockout of Nlrp3 markedly attenuated DMF-induced liver injury without affecting the metabolism of DMF. Furthermore, silencing Nfe2l2 aggravated the liver injury and the NLRP3 inflammasome activation in mouse liver. Finally, the depletion of hepatic macrophages by clodronate liposomes significantly reduced the liver damage caused by DMF. These results suggest that NLRP3 inflammasome activation is the upstream molecular event in the development of acute liver injury induced by DMF.

Ginsenoside Rg1 Induces Autophagy in Colorectal Cancer through Inhibition of the Akt/mTOR/p70S6K Pathway.

This study aimed to elucidate the anti-colon cancer mechanism of ginsenoside Rg1 in vitro and in vivo. Cell viability rate was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tetrazolium assay. The inhibitory effect of ginsenoside Rg1 against CT26 cell proliferation gradually increased with increasing concentration. The in vivo experiments also demonstrated an antitumor effect. The monodansylcadaverine (MDC), transmission electron microscopy (TEM), and expression of autophagy marker proteins confirmed that ginsenoside Rg1 induced autophagy in vitro. Ginsenoside Rg1 induced autophagy death of CT26 cells, but this effect could be diminished by autophagy inhibitor (3-methyladenine, 3-MA). Additionally, in a xenograft model, immunohistochemical analysis of tumor tissues showed that the LC3 and Beclin-1 proteins were highly expressed in the tumors from the ginsenoside Rg1-treated nude mice, confirming that ginsenoside Rg1 also induced autophagy in vivo. Furthermoer, both in vivo and in vitro, the protein expressions of p-Akt, p-mTOR, and p-p70S6K were inhibited by ginsenoside Rg1, which was verified by Akt inhibitors. These results indicated that the mechanism of ginsenoside Rg1 against colon cancer was associated with autophagy through inhibition of the Akt/mTOR/p70S6K signaling pathway.

New frontiers in salivary extracellular vesicles: transforming diagnostics, monitoring, and therapeutics in oral and systemic diseases.

Salivary extracellular vesicles (EVs) have emerged as key tools for non-invasive diagnostics, playing a crucial role in the early detection and monitoring of diseases. These EVs surpass whole saliva in biomarker detection due to their enhanced stability, which minimizes contamination and enzymatic degradation. The review comprehensively discusses methods for isolating, enriching, quantifying, and characterizing salivary EVs. It highlights their importance as biomarkers in oral diseases like periodontitis and oral cancer, and underscores their potential in monitoring systemic conditions. Furthermore, the review explores the therapeutic possibilities of salivary EVs, particularly in personalized medicine through engineered EVs for targeted drug delivery. The discussion also covers the current challenges and future prospects in the field, emphasizing the potential of salivary EVs in advancing clinical practice and disease management.

Alternative pre-mRNA splicing in stem cell function and therapeutic potential: A critical review of current evidence.

Alternative splicing is a crucial regulator in stem cell biology, intricately influencing the functions of various biological macromolecules, particularly pre-mRNAs and the resultant protein isoforms. This regulatory mechanism is vital in determining stem cell pluripotency, differentiation, and proliferation. Alternative splicing's role in allowing single genes to produce multiple protein isoforms facilitates the proteomic diversity that is essential for stem cells' functional complexity. This review delves into the critical impact of alternative splicing on cellular functions, focusing on its interaction with key macromolecules and how this affects cellular behavior. We critically examine how alternative splicing modulates the function and stability of pre-mRNAs, leading to diverse protein expressions that govern stem cell characteristics, including pluripotency, self-renewal, survival, proliferation, differentiation, aging, migration, somatic reprogramming, and genomic stability. Furthermore, the review discusses the therapeutic potential of targeting alternative splicing-related pathways in disease treatment, particularly focusing on the modulation of RNA and protein interactions. We address the challenges and future prospects in this field, underscoring the need for further exploration to unravel the complex interplay between alternative splicing, RNA, proteins, and stem cell behaviors, which is crucial for advancing our understanding and therapeutic approaches in regenerative medicine and disease treatment.

Clinical spectrum, over 12-year follow-up and experience of SGLT2 inhibitors treatment on patients with glycogen storage disease type Ib: a single-center retrospective study.

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment. RESULTS: In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients. CONCLUSION: Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.

[Analysis of 141 cases with benign upper airway occupying in infant].

Objective:To analyze and summarize the clinical characteristics, diagnosis, treatment and prognosis of benign upper airway space occupancy in infants. Methods:The clinical data of 141 cases with begin upper airway space from January 2012 to January 2022 were analyzed. Among them, 101 were male and 68 were female, the age is 0-3 years old. In which there were 24 newborns. The clinical characteristics, auxiliary examination and treatment results were summarized and analyzed. Results:The main clinical manifestations of 141 infants were dyspnea and/or laryngeal wheezing, including 116 cases of congenital cyst of tongue, 15 cases of hair polyps, 4 cases of nasopharyngeal second pharyngeal fissure cysts, 2 cases of congenital laryngeal cysts, 2 cases of pharyngeal bronchial cyst, 1 case of nasopharyngeal teratoma and 1 case of myofibroma. All the infants had completed the corresponding examination and treatment. The diagnosis was clear, and there was no missed diagnosis or misdiagnosis. Among them, 19 infants with congenital cyst of tongue were given cyst puncture to relieve dyspnea. 2 cases of congenital cyst of tongue recurred half a year after operaion, and then they underwent reoperation. The prognosis of the remaining infants were good. Conclusion:The most common occupying of benign upper airway space occupancy is cyst, and low-temperature plasma resection under endoscope is the main treatment method. Timely puncture therapy is also a safe and effective treatment for infants who are dyspnea and life threatening.

Multiple Bonding in AeN- (Ae = Ca, Sr, Ba).

Quantum chemical calculations using ab initio methods at the MRCI+Q(8,9)/def2-QZVPPD and CCSD(T)/def2-QZVPPD levels as well as density functional theory are reported for the diatomic molecules AeN- (Ae = Ca, Sr, Ba). The nature of the bonds is analyzed with a variety of methods. The anions CaN- and SrN- have electronic triplet (3Π) ground states with nearly identical bond dissociation energies De ~57 kcal/mol calculated at the MRCI+Q(8,9)/def2-QZVPPD level of theory. In contrast, the heavier homologue BaN- has a singlet (1Σ+) ground state, which is only 1.1 kcal/mol below the triplet (3Σ-) state. The computed bond dissociation energy of (1Σ+) BaN- is 68.4 kcal/mol. The calculations at the CCSD(T)-full/def2-QZVPPD and BP86-D3(BJ)/def2-QZVPPD levels of theory are in reasonable agreement with the MRCI+Q(8,9)/def2-QZVPPD data except for the singlet (1Σ+) state, which has a large multireference character. The calculated atomic partial charges given by the CM5, Voronoi and Hirshfeld methods suggest small to medium-sized charge donation toward Ae atom Ae←N- for most electronic states. In contrast, the NBO method predicts for all species medium to large electronic charge donation toward nitrogen Ae→N-, which is due to the neglect of the (n)p AOs of Ae atoms as genuine valence orbitals.

Manufacturing, quality control, and GLP-grade preclinical study of nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles.

BACKGROUND: Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. METHODS: haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. RESULTS: The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at - 80°C, 3 months at - 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 108 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. CONCLUSION: haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.

Aerobic Anoxygenic Phototrophic Bacteria in the Marine Environments Revealed by Raman/Fluorescence-Guided Single-Cell Sorting and Targeted Metagenomics.

Aerobic anoxygenic phototrophic bacteria (AAPB) contribute profoundly to the global carbon cycle. However, most AAPB in marine environments are uncultured and at low abundance, hampering the recognition of their functions and molecular mechanisms. In this study, we developed a new culture-independent method to identify and sort AAPB using single-cell Raman/fluorescence spectroscopy. Characteristic Raman and fluorescent bands specific to bacteriochlorophyll a (Bchl a) in AAPB were determined by comparing multiple known AAPB with non-AAPB isolates. Using these spectroscopic biomarkers, AAPB in coastal seawater, pelagic seawater, and hydrothermal sediment samples were screened, sorted, and sequenced. 16S rRNA gene analysis and functional gene annotations of sorted cells revealed novel AAPB members and functional genes, including one species belonging to the genus Sphingomonas, two genera affiliated to classes Betaproteobacteria and Gammaproteobacteria, and function genes bchCDIX, pucC2, and pufL related to Bchl a biosynthesis and photosynthetic reaction center assembly. Metagenome-assembled genomes (MAGs) of sorted cells from pelagic seawater and deep-sea hydrothermal sediment belonged to Erythrobacter sanguineus that was considered as an AAPB and genus Sphingomonas, respectively. Moreover, multiple photosynthesis-related genes were annotated in both MAGs, and comparative genomic analysis revealed several exclusive genes involved in amino acid and inorganic ion metabolism and transport. This study employed a new single-cell spectroscopy method to detect AAPB, not only broadening the taxonomic and genetic contents of AAPB in marine environments but also revealing their genetic mechanisms at the single-genomic level.

Transplantation of gut microbiota derived from patients with schizophrenia induces schizophrenia-like behaviors and dysregulated brain transcript response in mice.

Schizophrenia (SCZ), as a neurodevelopmental disorder and devastating disease, affects approximately 1% of the world population. Although numerous studies have attempted to elucidate the causes of SCZ occurrence, it is not clearly understood. Recently, the emerging roles of the gut microbiota in a range of brain disorders, including SCZ, have attracted much attention. While the molecular mechanism of gut microbiota in regulating the pathogenesis of SCZ is still lacking. Here, we first confirmed the difference of gut microbiome between SCZ patients and healthy controls, and then, we performed fecal microbiota transplantation (FMT) to clarify the roles of SCZ patients-derived microbiota in a specific pathogen free (SPF) mice model. 16 S rDNA sequencing confirmed that a significant difference of gut microbiome was present between two groups of FMT mice, which has a similar trend with the above human gut microbiome. Furthermore, we found that transplantation of fecal microbiota from SCZ patients into SPF mice was sufficient to induce schizophrenia-like (SCZ-like) symptoms, such as deficits in sociability and hyperactivity. Furthermore, the brains of mice colonized with SCZ microbiota displayed dysregulated transcript response and alternative splicing of SCZ-relevant genes. Moreover, 10 key genes were identified to be correlated with SCZ by an integrative transcriptome data analysis. Finally, 4 key genes were identified to be correlated with the 12 differential genera between two groups of FMT mice. Our results thus demonstrated that the gut microbiome might modify the transcriptomic profile in the brain, thereby modulating social behavior, and our present study can help better understand the link between gut microbiota and SCZ pathogenesis through the gut-brain axis.

Exogenous 24-Epibrassinolide Enhanced Drought Tolerance and Promoted BRASSINOSTEROID-INSENSITIVE2 Expression of Quinoa.

Brassinosteroids (BRs) are involved in the regulation of biotic and abiotic stresses in plants. The molecular mechanisms of BRs that alleviate the drought stress in quinoa have rarely been reported. Here, quinoa seedlings were treated with 24-epibrassinolide (EBR) and we transiently transferred CqBIN2 to the quinoa seedlings' leaves using VIGS technology to analyze the molecular mechanism of the BR mitigation drought stress. The results showed that EBR treatment significantly increased the root growth parameters, the antioxidant enzyme activities, and the osmolyte content, resulting in a decrease in the H2O2, O2∙-, and malondialdehyde content in quinoa. A transcriptome analysis identified 8124, 2761, and 5448 differentially expressed genes (DEGs) among CK and Drought, CK and EBR + Drought, and Drought and EBR + Drought groups. WGCNA divided these DEGs into 19 modules in which these characterized genes collectively contributed significantly to drought stress. In addition, the EBR application also up-regulated the transcript levels of CqBIN2 and proline biosynthesis genes. Silenced CqBIN2 by VIGS could reduce the drought tolerance, survival rate, and proline content in quinoa seedlings. These findings not only revealed that exogenous BRs enhance drought tolerance, but also provided insight into the novel functions of CqBIN2 involved in regulating drought tolerance in plants.

Resveratrol mediates mitochondrial function through the sirtuin 3 pathway to improve abnormal metabolic remodeling in atrial fibrillation.

This study investigated the impact of resveratrol on abnormal metabolic remodeling in atrial fibrillation (AF) and explored potential molecular mechanisms. An AF cell model was established by high-frequency electrical stimulation of HL-1 atrial muscle cells. Resveratrol concentrations were optimized using CCK-8 and flow cytometry. AF-induced increases in ROS and mitochondrial calcium, along with decreased adenosine triphosphate (ATP) and mitochondrial membrane potential, were observed. Resveratrol mitigated these changes and maintained normal mitochondrial morphology. Moreover, resveratrol acted through the SIRT3-dependent pathway, as evidenced by its ability to suppress AF-induced acetylation of key metabolic enzymes. SIRT3 overexpression controls acetylation modifications, suggesting its regulatory role. In conclusion, resveratrol's SIRT3-dependent pathway intervenes in AF-induced mitochondrial dysfunction, presenting a potential therapeutic avenue for AF-related metabolic disorders. This study sheds light on the role of resveratrol in mitigating AF-induced mitochondrial remodeling and highlights its potential as a novel treatment for AF.

MB16 - (M=Sc, Y, La): Perfect Bowl-Like Boron Clusters.

The introduction of transition-metal doping has engendered a remarkable array of unprecedented boron motifs characterized by distinctive geometries and bonding, particularly those heretofore unobserved in pure boron clusters. In this study, we present a perfect (no defects) boron framework manifesting an inherently high-symmetry, bowl-like architecture, denoted as MB16 - (M=Sc, Y, La). In MB16 -, the B16 is coordinated to M atoms along the C5v-symmetry axis. The bowl-shaped MB16 - structure is predicted to be the lowest-energy structure with superior stability, owing to its concentric (2 π+10 π) dual π aromaticity. Notably, the C5v-symmetry bowl-like B16 - is profoundly stabilized through the doping of an M atom, facilitated by strong d-pπ interactions between M and boron motifs, in conjunction with additional electrostatic stabilization by an electron transfer from M to the boron motifs. This concerted interplay of covalent and electrostatic interactions between M and bowl-like B16 renders MB16 - a species of exceptional thermodynamic stability, thus making it a viable candidate for gas-phase experimental detection.

Diagnostic and prognostic nomograms for laryngeal carcinoma patients with lung metastasis: a SEER-based study.

PURPOSE: To establish two nomograms to quantify the risk of lung metastasis (LM) in laryngeal carcinoma (LC) and predict the overall survival of LC patients with LM. METHODS: Totally 9515 LC patients diagnosed histologically from 2000 to 2019 were collected from the Surveillance, Epidemiology, and End Results database. The independent diagnostic factors for LM in LC patients and prognostic factors for LC patients with LM were identified by logistic and Cox regression analysis, respectively. Nomograms were established based on regression coefficients and evaluated by receiver operating characteristic curve, calibration curves, and decision curve analysis. RESULTS: Patients with supraglottis, higher pathological grade, higher N stage, and distant metastasis (bone, brain, or liver) were more likely to have LM (P < 0.05). Chemotherapy, surgery and radiotherapy were independent factors of the overall survival of LC patients with LM (P < 0.05). The area under curve of diagnostic nomogram were 0.834 and 0.816 in the training and validation cohort respectively. For the prognostic nomogram, the area under curves of 1-, 2-, and 3-years were 0.735, 0.734, and 0.709 in the training cohort and 0.705, 0.803, and 0.809 in the validation cohort. The calibration curves and decision curve analysis indicated good performance of the nomograms. CONCLUSION: Distant metastasis (bone, brain, or liver) and N stage should be considered for prediction of LM in LC patients. Chemotherapy is the most significant influencing prognostic factor improving the survival of LC patients with LM. Two nomograms may benefit for providing better precautionary measures and treatment decision.