The complete chloroplast genome of Mussaenda pubescens and phylogenetic analysis.

The chloroplast (cp) genome sequence of Mussaenda pubescens, a promising resource that is used as a traditional medicine and drink, is important for understanding the phylogenetic relationships among the Mussaenda family and genetic improvement and reservation. This research represented the first comprehensive description of the morphological characteristics of M. pubescens, as well as an analysis of the complete cp genome and phylogenetic relationship. The results indicated a close relationship between M. pubescens and M. hirsutula based on the morphological characteristics of the flower and leaves. The cp was sequenced using the Illumina NovaSeq 6000 platform. The results indicated the cp genome of M. pubescens spanned a total length of 155,122 bp, including a pair of inverted repeats (IRA and IRB) with a length of 25,871 bp for each region, as well as a large single-copy (LSC) region and a small single-copy (SSC) region with lengths of 85,370 bp and 18,010 bp, respectively. The results of phylogenetic analyses demonstrated that species within the same genus displayed a tendency to group closely together. It was suggested that Antirhea, Cinchona, Mitragyna, Neolamarckia, and Uncaria might have experienced an early divergence. Furthermore, M. hirsutula showed a close genetic connection to M. pubescens, with the two species having partially overlapping distributions in China. This study presents crucial findings regarding the identification, evolution, and phylogenetic research on Mussaenda plants, specifically targeting M. pubescens.

Autosis: a new form of cell death in myocardial ischemia-reperfusion injury.

Cardiomyocytes undergo a variety of cell death events during myocardial ischemia‒reperfusion injury (MIRI). Understanding the causes of cardiomyocyte mortality is critical for the prevention and treatment of MIRI. Among the various types of cell death, autosis is a recently identified type of autophagic cell death with distinct morphological and chemical characteristics. Autosis can be attenuated by autophagy inhibitors but not reversed by apoptosis or necrosis inhibitors. In recent years, it has been shown that during the late phase of reperfusion, autosis is activated, which exacerbates myocardial injury. This article describes the characteristics of autosis, autophagic cell death, and the relationship between autophagic cell death and autosis; reviews the mechanism of autosis in MIRI; and discusses its clinical significance.

Trace the origin of yak meat in Xizang based on stable isotope combined with multivariate statistics.

In this study, the feasibility of tracing the origin of yak meat in Xizang Autonomous Region based on stable isotope combined with multivariable statistics was researched. The δ13C, δ15N, δ2H and δ18O in yak meat were determined by stable isotope ratio mass spectrometry, and the data were analyzed by analysis of variance, fisher discriminant analysis (FDA), back propagation (BP) neural network and orthogonal partial least squares discrimination analysis (OPLS-DA). The results showed that the δ13C, δ15N, δ2H and δ18O had significant differences among different origins (P < 0.05). The overall original correct discrimination rate of fisher discriminant analysis was 89.7 %, and the correct discrimination rate of cross validation was 88.2 %. The correct classification rate of BP neural network based on training set was 93.38 %, and the correct classification rate of BP neural network based on test set was 89.83 %. The OPLS-DA model interpretation rate parameter R2Y was 0.67, the model prediction rate parameter Q2 was 0.409, which could distinguish yak meat from seven different producing areas in Xizang Autonomous Region. The results showed that the origin of yak meat in Xizang Autonomous Region can be traced based on stable isotope combined with multivariate statistics.

MnO2/Ce6 microbubble-mediated hypoxia modulation for enhancing sono-photodynamic therapy against triple negative breast cancer.

Sono-photodynamic therapy (SPDT) has emerged as a promising treatment modality for triple negative breast cancer (TNBC). However, the hypoxic tumor microenvironment hinders the application of SPDT. Herein, in this study, a multifunctional platform (MnO2/Ce6@MBs) was designed to address this issue. A sono-photosensitizer (Ce6) and a hypoxia modulator (MnO2) were loaded into microbubbles and precisely released within tumor tissues under ultrasound irradiation. MnO2in situ reacted with the excess H2O2 and H+ and produced O2 within the TNBC tumor, which alleviated hypoxia and augmented SPDT by increasing ROS generation. Meanwhile, the reaction product Mn2+ was able to achieve T1-weighted MRI for enhanced tumor imaging. Additionally, Ce6 and microbubbles served as a fluorescence imaging contrast agent and a contrast-enhanced ultrasound imaging agent, respectively. In in vivo anti-tumor studies, under the FL/US/MR imaging guidance, MnO2/Ce6@MBs combined with SPDT significantly reversed tumor hypoxia and inhibited tumor growth in 4T1-tumor bearing mice. This work presents a theragnostic system for reversing tumor hypoxia and enhancing TNBC treatment.

Correction: MnO2/Ce6 microbubble-mediated hypoxia modulation for enhancing sono-photodynamic therapy against triple negative breast cancer.

Correction for 'MnO2/Ce6 microbubble-mediated hypoxia modulation for enhancing sono-photodynamic therapy against triple negative breast cancer' by Ping Li et al., Biomater. Sci., 2024, https://doi.org/10.1039/d3bm00931a.

Effects of sampling time and location on the geographical origin traceability of protected geographical indication (PGI) Hongyuan yak milk: Based on stable isotope ratios.

Hongyuan yak milk is a protected geographical indication (PGI) product of rich nutritional value, which is popular among consumers. Stable isotope ratio analysis (SIRA) is an effective way to protect the authenticity of the geographical origin of PGI products, and it is crucial to study the factors affecting stable isotopes. Firstly, we proved that the SIRA could be used to identify the geographical origin of Hongyuan yak milk, and that the identification accuracy in combination with δ13C and δ18O was 100 %. Secondly, we analyzed the effect of sampling selection on the stable isotopes of Hongyuan yak milk in practical applications, which showed that sampling time influenced the δ13C, δ2H, and δ18O, while the sampling locations did not. There were interactions between the effect of sampling time and location on δ2H and δ18O. These results provide a reliable method for identifying PGI products and also provide new guidance on sampling models.

Rapid authenticity assessment of PGI Hongyuan yak milk based on SICRIT-QTOF MS.

Hongyuan (HY) yaks live in a pollution-free environment, making HY yak milk a green food, but their short milk production period and low milk yield make yak milk precious and expensive. The phenomenon of counterfeiting HY yak milk with ordinary milk from other origins has already occurred, so the authenticity assessment of HY yak milk is necessary. This study developed a rapid soft ionisation by chemical reaction in transfer quadrupole time-of-flight mass spectrometry (SICRIT-QTOF MS) for HY yak milk differences assessment. Principal component analysis and orthogonal least squares discriminant analysis showed differences between HY milk and the other three origins. Twenty-eight differential compounds were screened out by variable importance in projection, fold change, P-value, and database matching. Furthermore, six characteristic compounds (proline, 2-hydroxy-3-methylbutyric acid, and l-isoleucine, etc.) of HY samples were putatively identified. The study demonstrated that SICRIT-QTOF MS has great potential for rapidly distinguishing the milk origin.

Alleviated NCOA4-mediated ferritinophagy protected RA FLSs from ferroptosis in lipopolysaccharide-induced inflammation under hypoxia.

OBJECTIVE: Ferroptosis is a reactive oxygen species (ROS)- and iron-dependent form of non-apoptotic cell death process. Previous studies have demonstrated that ferroptosis participates in the development of inflammatory arthritis. However, the role of ferroptosis in rheumatoid arthritis (RA) inflammatory hypoxic joints remains unclear. This study sought to explore the underlying mechanism of ferroptosis on lipopolysaccharide (LPS)-induced RA fibroblast-like synoviocytes (FLSs). METHODS: FLSs, isolated from patients with RA, were treated with LPS and ferroptosis inducer (erastin and RSL-3), and ferroptosis inhibitor (Fer-1 and DFO), respectively. The cell viability was measured by CCK-8. The cell death was detected by flow cytometer. The proteins level were tested by Western blot. The cytosolic ROS and lipid peroxidation were determined using DCFH-DA and C11-BODIPY581/591 fluorescence probes, respectively. The small interfering RNA (siRNA) was used to knock down related proteins. The levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), iron, inflammatory cytokines (IL6 and IL8), and LDH were analyzed by commercial kits. RESULTS: Ferroptosis was activated by LPS in RA FLS with increased cellular damage, ROS and lipid peroxidation, intracellular Fe and IL8, which can be further amplified by ferroptosis inducer (erastin and RSL-3) and inhibited by ferroptosis inhibitor (Fer-1 and DFO). Mechanistically, LPS triggered ferroptosis via NCOA4-mediated ferritinophagy in RA FLSs, and knockdown of NCOA4 strikingly prevent the process of ferroptosis. Intriguingly, LPS-induced RA FLSs became insensitive to ferroptosis and NCOA4-mediated ferritinophagy under hypoxia compared with normoxia. Knockdown of HIF-1α reverted ferroptosis and ferritinophagy evoking by LPS-induced RA FLSs inflammation under hypoxia. In addition, low dose of auranofin (AUR) induced re-sensitization of ferroptosis and ferritinophagy through inhibiting the expression of HIF-1α under hypoxia. CONCLUSIONS: NCOA4-mediated ferritinophagy was a key driver of ferroptosis in inflammatory RA FLSs. The suppression of NCOA4-mediated ferritinophagy protected RA FLSs from ferroptosis in LPS-induced inflammation under hypoxia. Targeting HIF-1α/NCOA4 and ferroptosis could be an effective and valuable therapeutic strategy for synovium hyperplasia in the patients with RA.

Long non-coding RNA NBR2 suppresses the progression of colorectal cancer by downregulating miR-19a to regulate M2 macrophage polarization.

Colorectal cancer (CRC) is a malignant tumor of the gastrointestinal tract that significantly impacts the health of patients and lacks promising methods of diagnosis. Tumor-associated macrophages (TAMs) are involved in CRC progression, and their function is regulated by long non-coding RNAs (lncRNAs). The lncRNA NBR2 was recently reported as an oncogene, whose function in CRC remains uncertain. The present study aimed to investigate the biological function of lncRNA NBR2 in the progression of CRC and its underlying molecular mechanisms. Ten pairs of clinical CRC and para-carcinoma tissues were collected to determine the expression levels of lncRNA NBR2 and miR-19a, and the polarization state of TAMs. Quantitative reverse transcriptase-polymerase chain reaction was used to evaluate the expression of miR-19a, and western blotting was used to determine the expression levels of tumor necrosis factor-α, human leukocyte antigen-DR, arginase-1, CD163, CD206, interleukin-4, AMP-activated protein kinase (AMPK), p-AMPK, hypoxia-inducible factor-1α (HIF-1α), protein kinase B (AKT), p-AKT, mechanistic target of rapamycin (mTOR), and p-mTOR in TAMs. The proliferative ability of HCT-116 cells was detected using the CCK8 assay, and the migratory ability of HCT-116 cells was evaluated using the Transwell assay. The interaction between lncRNA NBR2 and miR-19a was determined using the luciferase assay. The lncRNA NBR2 was downregulated and miR-19a was highly expressed in CRC cells, accompanied by a high M2 polarization. Downregulated miR-19a promoted M1 polarization, activated AMPK, suppressed HIF-1α and AKT/mTOR signaling pathways, and promoted antitumor properties in NBR2-overexpressed TAMs, which were all reversed by the introduction of the miR-19a mimic. LncRNA NBR2 was verified to target miR-19a in macrophages according to the results of the luciferase assay. Collectively, lncRNA NBR2 may suppress the progression of CRC by downregulating miR-19a to regulate M2 macrophage polarization.

Molecular markers of type II alveolar epithelial cells in acute lung injury by bioinformatics analysis.

In this study, we aimed to identify molecular markers associated with type II alveolar epithelial cell injury in acute lung injury (ALI) models using bioinformatics methods. The objective was to provide new insights for the diagnosis and treatment of ALI/ARDS. We downloaded RNA SEQ datasets (GSE109913, GSE179418, and GSE119123) from the Gene Expression Omnibus (GEO) and used R language package to screen differentially expressed genes (DEGs). DEGs were annotated using Gene Ontology (GO), and their pathways were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG). DEGs were imported into the STRING database and analyzed using Cytoscape software to determine the protein network of DEGs and calculate the top 10 nodes for the hub genes. Finally, potential therapeutic drugs for the hub genes were predicted using the DGIdb database. We identified 78 DEGs, including 70 up-regulated genes and 8 down-regulated genes. GO analysis revealed that the DEGs were mainly involved in biological processes such as granulocyte migration, response to bacterial-derived molecules, and cytokine-mediated signaling pathways. Additionally, they had cytokine activity, chemokine activity, and receptor ligand activity, and functioned in related receptor binding, CXCR chemokine receptor binding, G protein-coupled receptor binding, and other molecular functions. KEGG analysis indicated that the DEGs were mainly involved in TNF signaling pathway, IL-17 signaling pathway, NF-κB signal pathway, chemokine signal pathway, cytokine-cytokine receptor interaction signal pathway, and others. We identified eight hub genes, including IRF7, IFIT1, IFIT3, PSMB8, PSMB9, BST2, OASL2, and ZBP1, which were all up-regulated genes. We identified several hub genes of type II alveolar epithelial cells in ALI mouse models using bioinformatics analysis. These results provide new targets for understanding and treating of ALI.

Sirtuins and autophagy in lipid metabolism.

Sirtuins are a family of NAD+ -dependent deacetylases that regulate some important biological processes, including lipid metabolism and autophagy, through their deacetylase function. Autophagy is a new discovery in the field of lipid metabolism, which may provide a new idea for the regulation of lipid metabolism. There are many tandem parts in the regulation process of lipid metabolism and autophagy of sirtuins protein family. This paper summarized these tandem parts and proposed the possibility of sirtuins regulating lipid autophagy, as well as the interaction and synergy between sirtuins protein family. Currently, some natural drugs have been reported to affect metabolism by regulating sirtuins, some of which regulate autophagy by targeting sirtuins.

SMG-BERT: integrating stereoscopic information and chemical representation for molecular property prediction.

Molecular property prediction is a crucial task in various fields and has recently garnered significant attention. To achieve accurate and fast prediction of molecular properties, machine learning (ML) models have been widely employed due to their superior performance compared to traditional methods by trial and error. However, most of the existing ML models that do not incorporate 3D molecular information are still in need of improvement, as they are mostly poor at differentiating stereoisomers of certain types, particularly chiral ones. Also,routine featurization methods using only incomplete features are hard to obtain explicable molecular representations. In this paper, we propose the Stereo Molecular Graph BERT (SMG-BERT) by integrating the 3D space geometric parameters, 2D topological information, and 1D SMILES string into the self-attention-based BERT model. In addition, nuclear magnetic resonance (NMR) spectroscopy results and bond dissociation energy (BDE) are integrated as extra atomic and bond features to improve the model's performance and interpretability analysis. The comprehensive integration of 1D, 2D, and 3D information could establish a unified and unambiguous molecular characterization system to distinguish conformations, such as chiral molecules. Intuitively integrated chemical information enables the model to possess interpretability that is consistent with chemical logic. Experimental results on 12 benchmark molecular datasets show that SMG-BERT consistently outperforms existing methods. At the same time, the experimental results demonstrate that SMG-BERT is generalizable and reliable.

New Insights into the Mutual Promotion of Rosacea, Anxiety, and Depression from Neuroendocrine Immune Aspects.

Rosacea is a common chronic inflammatory skin disease with a complex etiology and undefined pathogenesis, and there is still a lack of targeted clinical treatment. Patients with rosacea are at a higher risk of anxiety and depression compared to the healthy population. Compared to skin conditions such as acne and psoriasis, rosacea has been much less studied in relation to multiple-etiology psychiatric disorders such as anxiety and depression. In contrast to the mainstream belief that the causal association between rosacea and psychiatric disorders is that rosacea increases the psychological burden of patients and thus triggers psychiatric disorders simply by altering their facial appearance, this review outlines the possible common mechanisms between rosacea and anxiety and depression disorders, starting from the pathophysiological mechanisms of transient receptor potential family cation channels, HPA axis, and Th1/Th17 cell polarization. It envisages the possibility of the neuroendocrine-immune interplay between rosacea and anxiety and depression, and new ideas on the complex causal relationship between rosacea and psychiatric disorders, offering more orientations to open up new therapeutic approaches for rosacea.

Nesfatin-1 alleviates hyperoxia-induced lung injury in newborn mice by inhibiting oxidative stress through regulating SIRT1/PGC-1α pathway.

Bronchopulmonary dysplasia (BPD) is a pulmonary disease commonly observed in premature infants and it is reported that oxidative stress is a critical induction factor in BPD and is considered as a promising target for treating BPD. Nesfatin-1 is a brain-gut peptide with inhibitory effects on food intake, which is recently evidenced to show suppressive effect on oxidative stress. The present study aims to explore the therapeutic effect and mechanism of Nesfatin-1 in BPD mice. AECIIs were extracted from newborn rats and exposed to hyperoxia for 24 h, followed by treatment with 5 and 10 nM Nesfatin-1. Declined cell viability, increased apoptotic rate, upregulated Bax, downregulated Bcl-2, increased release of ROS and MDA, and suppressed SOD activity were observed in hyperoxia-treated AECIIs, which were extremely reversed by Nesfatin-1. Newborn rats were exposed to hyperoxia, followed by treated with 10 µg/kg Nesfatin-1 and 20 µg/kg Nesfatin-1. Severe pathological changes, elevated MDA level, and declined SOD activity were observed in lung tissues of BPD mice, which were rescued by Nesfatin-1. Furthermore, the protective effect of Nesfatin-1 on hyperoxia-challenged AECIIs was abolished by silencing SIRT1. Collectively, Nesfatin-1 alleviated hyperoxia-induced lung injury in newborn mice by inhibiting oxidative stress through regulating SIRT1/PGC-1α pathway.

Combinations of Vitamin A and Vitamin E Metabolites Confer Resilience against Amyloid-ß Aggregation.

Alzheimer's disease is characterized by the presence in the brain of amyloid plaques formed by the aberrant deposition of the amyloid-ß peptide (Aß). Since many vitamins are dysregulated in this disease, we explored whether these molecules contribute to the protein homeostasis system by modulating Aß aggregation. By screening 18 fat-soluble and water-soluble vitamin metabolites, we found that retinoic acid and α-tocopherol, two metabolites of vitamin A and vitamin E, respectively, affect Aß aggregation both in vitro and in a Caenorhabditis elegans model of Aß toxicity. We then show that the effects of these two vitamin metabolites in specific combinations cancel each other out, consistent with the "resilience in complexity" hypothesis, according to which the complex composition of the cellular environment could have an overall protective role against protein aggregation through the simultaneous presence of aggregation promoters and inhibitors. Taken together, these results indicate that vitamins can be added to the list of components of the protein homeostasis system that regulate protein aggregation.

A New and Effective Method to Trace Tibetan Chicken by Amino Acid Profiling.

As a "rare bird on the plateau", the Tibetan chicken is rich in nutrition and has high medicinal value. In order to quickly and effectively identify the source of food safety problems and to label fraud regarding this animal, it is necessary to identify the geographical traceability of the Tibetan chicken. In this study, Tibetan chicken samples from four different cities in Tibet, China were analyzed. The amino acid profiles of Tibetan chicken samples were characterized and further subjected to chemometric analyses, including orthogonal least squares discriminant analysis, hierarchical cluster analysis, and linear discriminant analysis. The original discrimination rate was 94.4%, and the cross-validation rate was 93.3%. Moreover, the correlation between amino acid concentrations and altitudes in Tibetan chicken was studied. With the increase in altitude, all amino acid contents showed a normal distribution. For the first time, amino acid profiling has been comprehensively applied to trace the origin of plateau animal food with satisfactory accuracy.

Cr3+-ZnGa2O4@Pt for Light-Triggered Dark Catalytic Regeneration of Nicotinamide Coenzymes without Other Electron Mediators.

Photocatalysts for regeneration of reduced nicotinamide adenine dinucleotide (NADH) usually work with continuous lighting and electron mediators, which causes impracticability under dark conditions, risk of NADH reoxidation, and complex separation. To solve these problems, we present a new catalyst of tiny Pt nanoparticles photodeposited on chromium-doped zinc gallate (CZGO@Pt). Upon being light-triggered, the photogenerated electrons are stored in the traps of CZGO and then gradually released and transferred by Pt to directly reduce NAD+ after stoppage of illumination. Three lighting modes are compared to demonstrate the feasibility and advantage of this light-triggered dark catalysis. Within 4 h of reaction, the in-the-dark NADH yield reaches 75.0% under prelighting CZGO@5%Pt and it reaches 80.0% under prelighting CZGO@5%Pt and triethanolamine (TEOA). However, the NADH yield is only 53.5% under continuous lighting of CZGO@5%Pt, TEOA, and NAD+. Consequently, the light-triggered dark catalytic regeneration of NADH not only saves energy and operates easily but also significantly elevates the NADH yield. It thus would secure wide interests and applications in places where no light or only intermittent light is available.

Mapping a Country Image from Global News Reports about COVID-19 Pandemic.

The outbreak of the coronavirus disease of 2019 (COVID-19) pandemic has infected hundreds of millions of people worldwide and caused millions of deaths. This study used media analysis and correlation analysis to elucidate the significant differences in the ways in which news reports from 228 countries discussed a specific country when covering the COVID-19 pandemic. Media reports analysed in this study were collected from the Global Database of Events, Language, and Tone project (GDELT). These differences were found to be deeply embedded in the economic, socio-political, and cultural contexts of different countries. The findings reinforced the hypothetical assumption in framing theory and promoted a measurable and upscaled use of framing theory into macro geography studies. This study highlights the urgent need of a geo-political examination of COVID-19 in the global context-an area with insufficient interest from interdisciplinary perspective beyond epidemiology. Further research can be of great value for the promotion of an effective international cooperation mechanism to curb the spread of COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s12061-022-09498-4.

Complete Remission of Vulvar Squamous Cell Carcinoma After Volumetric Modulated Arc Therapy in Copper Smelting and Purification Workers: A Case Report.

Vulvar squamous cell carcinoma (VSCC) is the most frequent vulvar neoplasia, with invasiveness and metastasis. Typically, surgery is the preferred treatment. Radiotherapy is commonly used for unresectable locally advanced tumors and for early-stage patients who are at risk of serious complications from surgery or have a severe concomitant disease that prevents them from undergoing surgery. Compared to external irradiation, three-dimensional conformal radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT), various studies using volumetric modulated arc therapy (VMAT) alone in early-stage VSCC have been reported rarely. In this case, the patient had a large skin lesion and no lymph node metastasis. Surgical excision would seriously affect the urinary function and vulvar shape, so radical radiotherapy was given. To ensure the radiation dose for the radical treatment effect and to avoid high-dose radiation to normal organs, the volumetric intensity-modulated radiotherapy technique was chosen. After treatment, the patient's vulvar appearance returned to normal, and the tumor achieved complete remission without further surgery or chemotherapy, with no local recurrence or associated toxic side effects. This suggests that the efficacy of VMAT alone in early-stage VSCC is accurate and worthy of clinical promotion. The patient had been engaged in copper smelting and purification for many years, and it is unusual for her to have skin lesions with such a large surface area. In conjunction with her previous history of nasal basal cell carcinoma, the mechanism of oxidative stress during metal exposure should be further clinically examined, as it may be crucial in the formation and progression of malignancies.

Fusing 2D and 3D molecular graphs as unambiguous molecular descriptors for conformational and chiral stereoisomers.

The rapid progress of machine learning (ML) in predicting molecular properties enables high-precision predictions being routinely achieved. However, many ML models, such as conventional molecular graph, cannot differentiate stereoisomers of certain types, particularly conformational and chiral ones that share the same bonding connectivity but differ in spatial arrangement. Here, we designed a hybrid molecular graph network, Chemical Feature Fusion Network (CFFN), to address the issue by integrating planar and stereo information of molecules in an interweaved fashion. The three-dimensional (3D, i.e., stereo) modality guarantees precision and completeness by providing unabridged information, while the two-dimensional (2D, i.e., planar) modality brings in chemical intuitions as prior knowledge for guidance. The zipper-like arrangement of 2D and 3D information processing promotes cooperativity between them, and their synergy is the key to our model's success. Experiments on various molecules or conformational datasets including a special newly created chiral molecule dataset comprised of various configurations and conformations demonstrate the superior performance of CFFN. The advantage of CFFN is even more significant in datasets made of small samples. Ablation experiments confirm that fusing 2D and 3D molecular graphs as unambiguous molecular descriptors can not only effectively distinguish molecules and their conformations, but also achieve more accurate and robust prediction of quantum chemical properties.