Novel fluorescence probe for ClO- in living cells: Based on FRET mechanism.

Hypochlorous acid (HClO) as a kind of reactive oxygen species (ROS) plays a vital role in many biological processes. Organic fluorescence probes have attracted great interests for the detection of HClO, due to their relatively high selectivity and sensitivity, satisfactory spatiotemporal resolution and good biocompatibility. Constructing fluorescence probes to detect HClO with advantages of large Stokes shift, wide emission gap, near infrared emission and good water solubility is still challenging. In this work, a new ratiometric fluorescence probe (named HCY) for HClO was developed. FRET-based HCY was constructed by bonding a coumarin and a flavone fluorophore. In absence of HClO, HCY exists FRET process, however, FRET is inhibited in the presence of HClO because the conjugated double bond broke. Due to the good match of the emission spectrum of the donor and the absorption spectrum of the acceptor, the FRET system appears favorable energy transfer efficiency. HCY showed high sensitivity and rapid response time. The linearity between the ratios of fluorescence intensity and concentration of HClO was established with a low limit of detection. What's more, HCY was also applied for fluorescence images of HClO in RAW264.7 cells.

Effectiveness of different intrusion modes of maxillary anterior teeth with mini-implants in clear aligner treatment: a three-dimensional finite element analysis.

BACKGROUND: The intrusion of maxillary anterior teeth is often required and there are various intrusion modes with mini-implants in clear aligner treatment. The objective of this study was to evaluate the effectiveness of maxillary anterior teeth intrusion with different intrusion modes, aiming to provide references for precise and safe intrusion movements in clinical practice. METHODS: Cone-beam computed tomography and intraoral optical scanning data of a patient were collected. Finite element models of the maxilla, maxillary dentition, periodontal ligaments (PDLs), clear aligner (CA), attachments, and mini-implants were established. Different intrusion modes of the maxillary anterior teeth were simulated by changing the mini-implant site (between central incisors, between central and lateral incisor, between lateral incisor and canine), loading site (between central incisors, on central incisor, between central and lateral incisor, between lateral incisor and canine), and loading mode (labial loading and labiolingual loading). Ten conditions were generated and intrusive forces of 100 g were applied totally. Then displacement tendency of the maxillary anterior teeth and CA, and stress of the PDLs were analyzed. RESULTS: For the central incisor under condition L14 and for the canine under conditions L11, L13, L23, and L33, the intrusion amount was negative. Under other conditions, the intrusion amount was positive. The labiolingual angulation of maxillary anterior teeth exhibited positive changes under all conditions, with greater changes under linguoincisal loading. The mesiodistal angulation of canine exhibited positive changes under labial loading, while negative changes under linguoincisal loading except for condition L14. CONCLUSIONS: The intrusion amount, labiolingual and mesiodistal angulations of the maxillary anterior teeth were affected by the mini-implant site, loading site, and loading mode. Labial and linguoincisal loading may have opposite effects on the intrusion amount of maxillary anterior teeth and the mesiodistal angulation of canine. The labiolingual angulation of the maxillary incisors would increase under all intrusion modes, with greater increases under linguoincisal loading.

Site-selective S-gem-difluoroallylation of unprotected peptides with 3,3-difluoroallyl sulfonium salts.

Bench-stable 3,3-difluoroallyl sulfonium salts (DFASs), featuring tunable activity and their editable C-ß and gem-difluoroallyl group, proved to be versatile fluoroalkylating reagents for site-selective S-gem-difluoroallylation of cysteine residues in unprotected peptides. The reaction proceeds with high efficiency under mild conditions (ambient temperature and aqueous and weak basic conditions). Various protected/unprotected peptides, especially bioactive peptides, are site-selectively S-gem-difluoroallylated. The newly added gem-difluoroallyl group and other functional groups derived from C-ß of DFASs are poised for ligation with bio-functional groups through click and radical chemistry. This stepwise "doubly orthogonal" modification of peptides enables the construction of bioconjugates with enhanced complexity and functionality. This proof of principle is successfully applied to construct a peptide-saccharide-biotin chimeric bioconjugate, indicating its great potential application in medicinal chemistry and chemical biology.

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OBJECTIVES: To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage (HIBD) and to explore its mechanisms via the PI3K/AKT signaling pathway, aiming to provide a basis for the clinical application of melatonin. METHODS: Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group, an HIBD group, and a melatonin group (n=9 each). The neonatal rat HIBD model was established using the classic Rice-Vannucci method. Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining. Autophagy-related protein levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunofluorescence staining and Western blot analysis. Phosphorylated phosphoinositide 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) protein expression levels were measured by immunohistochemistry and Western blot. The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis. RESULTS: Twenty-four hours post-modeling, neurons in the sham operation group displayed normal size and orderly arrangement. In contrast, neurons in the HIBD group showed swelling and disorderly arrangement, while those in the melatonin group had relatively normal morphology and more orderly arrangement. Nissl bodies were normal in the sham operation group but distorted in the HIBD group; however, they remained relatively intact in the melatonin group. The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group, but was reduced in the melatonin group compared to the HIBD group (P<0.05). The number of p-PI3K+ and p-AKT+ cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group (P<0.05). LC3 and Beclin-1 protein expression levels were higher, and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group (P<0.05); however, in the melatonin group, LC3 and Beclin-1 levels decreased, and p-PI3K and p-AKT increased compared to the HIBD group (P<0.05). The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K+ and p-AKT+ cells between the two groups (P<0.05). CONCLUSIONS: Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD, thereby alleviating HIBD. This mechanism is associated with the PI3K/AKT pathway.

Collagen/Curdlan composite sponge for rapid hemostasis and skin wound healing.

Collagen's unique properties promise hemostatic potential, but its sponge form's stability and mechanics need improvement. In this study, we developed a series of homeostatic sponges by co-assembling collagen and curdlan at different ratios into hydrogels, followed by freeze-drying treatment. The incorporation of curdlan into collagen sponges has been found to significantly enhance the sponge's properties, including increased porosity, elevated water uptake, improved elasticity, and enhanced resistance to degradation. In vitro cytotoxicity and hemolysis assays have demonstrated the biocompatibility and nontoxicity of composite sponges. In mouse liver perforation and incision models, the composite sponges achieved rapid coagulation within 67 s and 75 s, respectively, outperforming gauze and gelatin sponge in reducing blood loss. Furthermore, composite sponges demonstrated superior wound healing potential in mice full-thickness skin defects model, with accelerated healing rates observed at days 3, 7, and 14 compared to the control group. Overall, collagen/curdlan composite sponge show promise for hemostasis and wound healing applications.

MicroRNA-1205 promotes breast cancer cell metastasis by regulating epithelial-to-mesenchymal transition via targeting of CDK3.

Metastasis poses a huge obstacle to the survival of breast cancer patients. The microRNA miR-1205 acts as a tumor suppressor in various cancers, but its roles in breast cancer and metastasis remain unclear. To elucidate its function in breast cancer progression, we analyzed miR-1205 expression in human tumor samples and carried out a series of functional studies in in vitro and in vivo. miR-1205 was expressed more highly in metastatic breast tumor samples than in non-metastatic samples and was associated with lymph node metastasis, clinical stage, and poor prognosis. Moreover, miR-1205 promoted breast cancer cell invasiveness in vitro and metastasis in mice by directly targeting CDK3 and reducing CDK3 protein levels. We also showed that CDK3 interacts with Snail protein, inducing Snail degradation via the ubiquitin-proteasome system and potentially affecting epithelial-to-mesenchymal transition. Furthermore, analysis of clinical tissue samples indicated that CDK3 and miR-1205 levels were inversely correlated in lymph node metastasis-positive primary tumors. This study demonstrated the pro-metastatic role of miR-1205 in breast cancer, mediated via a novel miR-1205/CDK3/Snail axis. Moreover, we identified miR-1205 and CDK3 as potential markers of invasion and progression in breast cancer.

4,4'-methylenediphenol reduces Aß-induced toxicity in a Caenorhabditis elegans model of Alzheimer's disease.

Introduction: Gastrodia elata Blume is a widely used medicinal and edible herb with a rich chemical composition. Moreover, prescriptions containing Gastrodia elata are commonly used for the prevention and treatment of cardiovascular, cerebrovascular, and aging-related diseases. Recent pharmacological studies have confirmed the antioxidant and neuroprotective effects of Gastrodia elata, and, in recent years, this herb has also been used in the treatment of Alzheimer's disease (AD) and other neurodegenerative disorders. We have previously shown that 4,4'-methylenediphenol, a key active ingredient of Gastrodia elata, can mitigate amyloid-ß (Aß)-induced paralysis in AD model worms as well as prolong the lifespan of the animals, thus displaying potential as a treatment of AD. Methods: We investigated the effects of 4,4'-methylenediphenol on AD and aging through paralysis, lifespan, and behavioral assays. In addition, we determined the anti-AD effects of 4,4'-methylenediphenol by reactive oxygen species (ROS) assay, lipofuscin analysis, thioflavin S staining, metabolomics analysis, GFP reporter gene worm assay, and RNA interference assay and conducted in-depth studies on its mechanism of action. Results: 4,4'-Methylenediphenol not only delayed paralysis onset and senescence in the AD model worms but also enhanced their motility and stress tolerance. Meanwhile, 4,4'-methylenediphenol treatment also reduced the contents of reactive oxygen species (ROS) and lipofuscin, and decreased Aß protein deposition in the worms. Broad-spectrum targeted metabolomic analysis showed that 4,4'-methylenediphenol administration had a positive effect on the metabolite profile of the worms. In addition, 4,4'-methylenediphenol promoted the nuclear translocation of DAF-16 and upregulated the expression of SKN-1, SOD-3, and GST-4 in the respective GFP reporter lines, accompanied by an enhancement of antioxidant activity and a reduction in Aß toxicity; importantly, our results suggested that these effects of 4,4'-methylenediphenol were mediated, at least partly, via the activation of DAF-16. Conclusion: We have demonstrated that 4,4'-methylenediphenol can reduce Aß-induced toxicity in AD model worms, suggesting that it has potential for development as an anti-AD drug. Our findings provide ideas and references for further research into the anti-AD effects of Gastrodia elata and its active ingredients.

Copper Difluorocarbene Enables Catalytic Difluoromethylation.

Despite the synthetic versatility of difluorocarbene, its high reactivity severely regulates widespread applications of difluorocarbene in organic synthesis. Here, we report a copper difluorocarbene-involved catalytic coupling, representing a new mode of the difluoromethylation reaction. This method allows difluoromethylation of a wide range of readily available allyl/propargyl electrophiles with NaBH3CN and low-cost difluorocarbene precursor BrCF2CO2K, featuring high cost-efficiency, high stereo- and regioselectivities, and high functional group tolerance, even with complex drug-like molecules. Applying the method led to the efficient synthesis of deuterated difluoromethylated compounds of medicinal interest. The resulting difluoromethylated allyl and allenyl products can serve as versatile synthons for diverse transformations, rendering the approach attractive for synthesizing complex fluorinated structures. Experimental mechanistic studies and computational calculations reveal that the formation of a difluoromethylcopper(I) intermediate through the nucleophilic attack of boron hydride on the copper(I) difluorocarbene is the key step in the reaction.

Screening of active components of Ganoderma lucidum and decipher its molecular mechanism to improve learning and memory disorders.

Learning and memory impairment (LMI), a common degenerative central nervous system disease. Recently, more and more studies have shown that Ganoderma lucidum (GL) can improve the symptoms of LMI. The active ingredients in GL and their corresponding targets were screened through TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and BATMAN-TCM (Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine) databases, and the potential LMI targets were searched for through GeneCard (GeneCards Human Gene Database) and DrugBank. Then, we construct a "main active ingredient-target" network and a protein-protein interaction (PPI) network diagram.The GO (Gene Ontology) functional enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotation analysis were performed on the common targets through DAVID (Database for Annotation Visualization and Integrated Discovery) to clarify the potential molecular mechanism of action of active ingredients in GL. The TNF protein was verified by western blot;Twenty one active ingredients in GL and 142 corresponding targets  were screened out, including 59 targets shared with LMI. The 448 biological processes shown by the GO functional annotation results and 55 signal pathways shown by KEGG enrichment analysis were related to the improvement of LMI by GL, among which the correlation of Alzheimer disease pathway is the highest, and TNF was the most important protein; TNF can improve LMI.GL can improve LMI mainly by 10 active ingredients in it, and they may play a role by regulating Alzheimer disease pathway and TNF protein.

P-hydroxybenzaldehyde protects Caenorhabditis elegans from oxidative stress and ß-amyloid toxicity.

Introduction: Gastrodia elata is the dried tuber of the orchid Gastrodia elata Bl. It is considered a food consisting of a source of precious medicinal herbs, whose chemical composition is relatively rich. Gastrodia elata and its extracted fractions have been shown to have neuroprotective effects. P-hydroxybenzaldehyde (p-HBA), as one of the main active components of Gastrodia elata, has anti-inflammatory, antioxidative stress, and cerebral protective effects, which has potential for the treatment of Alzheimer's disease (AD). The aim of this study was to verify the role of p-HBA in AD treatment and to investigate its mechanism of action in depth based using the Caenorhabditis elegans (C. elegans) model. Methods: In this study, we used paralysis, lifespan, behavioral and antistress experiments to investigate the effects of p-HBA on AD and aging. Furthermore, we performed reactive oxygen species (ROS) assay, thioflavin S staining, RNA-seq analysis, qPCR validation, PCR Array, and GFP reporter gene worm experiment to determine the anti-AD effects of p-HBA, as well as in-depth studies on its mechanisms. Results: p-HBA was able to delay paralysis, improve mobility and resistance to stress, and delay aging in the AD nematode model. Further mechanistic studies showed that ROS and lipofuscin levels, Aß aggregation, and toxicity were reduced after p-HBA treatment, suggesting that p-HBA ameliorated Aß-induced toxicity by enhancing antioxidant and anti-aging activity and inhibiting Aß aggregation. p-HBA had a therapeutic effect on AD by improving stress resistance, as indicated by the down-regulation of NLP-29 and UCR-11 expression and up-regulation of PQN-75 and LYS-3 expression. In addition, the gene microarray showed that p-HBA treatment played a positive role in genes related to AD, anti-aging, ribosomal protein pathway, and glucose metabolism, which were collectively involved in the anti-AD mechanism of p-HBA. Finally, we also found that p-HBA promoted nuclear localization of DAF-16 and increased the expression of SKN-1, SOD-3, and GST-4, which contributed significantly to inhibition of Aß toxicity and enhancement of antioxidative stress. Conclusion: Our work suggests that p-HBA has some antioxidant and anti-aging activities. It may be a viable candidate for the treatment and prevention of Alzheimer's disease.

Establishment of homotrimer collagen type I signature and its association with clinical manifestation and tertiary lymphoid structures formation in liver cancer.

Background: collagen type I is a fundamental composition of extracellular matrix. Typically it exists in the form of a heterotrimer, consisting of two α1 chains encoded by COL1A1 and one α2 chain encoded by COL1A2. However, in cancer a homotrimeric form of collagen type I comprises three α1 chains encoded by COL1A1 was founded. There is still a lack of transcriptional and histologic methods for detecting homotrimeric collagen type I. Furthermore, a comprehensive analysis of the pan-cancer distribution pattern and clinical relevance of homotrimeric collagen type I is conspicuously absent. Method: Using transcriptional and immunoflourance method, we established homocol signature, which is able to transcriptionally and histologically detect homotrimeric collagen type I. We investigated the diagnostic and prognostic potential of homocol as a novel cancer biomarker in a pan-cancer cohort. Furthermore, we assessed its association with clinical manifestations in a liver cancer cohort undergoing treatment at our institute. Result: Homotrimer Collagen Type I is predominantly expressed by cancer cells and is linked to several critical cancer hallmarks, particularly inflammatory response and proliferation. Survival analyses have indicated that a high Homocol expression is correlated with poor outcomes in most types of cancer studied. In terms of cancer detection, Homocol demonstrated strong performance in Receiver Operating Characteristic (ROC) analysis, with an Area Under Curve (AUC) of 0.83 for pan-cancer detection and between 0.72 and 0.99 for individual cancers.In cohorts undergoing PD1 treatment, we noted a higher presence of Homocol in the response group. In a Hepatocellular Carcinoma (HCC) clinical set, high Homocol expression was associated with an increased formation of intra-tumor tertiary lymphoid structures (TLS), larger tumor sizes, more advanced Barcelona Clinic Liver Cancer (BCLC) stages, higher microvascular invasion (MVI) grades, absence of a capsule, and an enriched para-tumor collagen presence. Conclusion: our research has led to the development of a novel gene signature that facilitates the detection of Homotrimer Collagen Type I. This may greatly assist efforts in cancer detection, prognosis, treatment response prediction, and further research into Homotrimer Collagen Type I.

Historic dog furs unravel the origin and artificial selection of modern Nordic Lapphund and Elkhound dog breeds.

The origins and extreme morphological evolution of the modern dog breeds are poorly studied because the founder populations are extinct. Here, we analyse eight 100-200 years old dog fur samples obtained from traditional North Swedish clothing, to explore the origin and artificial selection of the modern Nordic Lapphund and Elkhound dog breeds. Population genomic analysis confirmed the Lapphund and Elkhound breeds to originate from the local dog population, and showed a distinct decrease in genetic diversity in agreement with intense breeding. We identified eleven genes under positive selection during the breed development. In particular, the MSRB3 gene, associated with breed-related ear morphology, was selected in all Lapphund and Elkhound breeds, and functional assays showed that a SNP mutation in the 3'UTR region suppresses its expression through miRNA regulation. Our findings demonstrate analysis of near-modern dog artifacts as an effective tool for interpreting the origin and artificial selection of the modern dog breeds.

Chemo-, Regio- and Stereoselective Preparation of (Z)-2-Butene-1,4-Diol Monoesters via Pd-Catalyzed Decarboxylative Acyloxylation.

(Z)-alkenes are useful synthons but thermodynamically less stable than their (E)-isomers and typically more difficult to prepare. The synthesis of 1,4-hetero-bifunctionalized (Z)-alkenes is particularly challenging due to the inherent regio- and stereoselectivity issues. Herein we demonstrate a general, chemoselective and direct synthesis of (Z)-2-butene-1,4-diol monoesters. The protocol operates within a Pd-catalyzed decarboxylative acyloxylation regime involving vinyl ethylene carbonates (VECs) and various carboxylic acids as the reaction partners under mild and operationally attractive conditions. The newly developed process allows access to a structurally diverse pool of (Z)-2-butene-1,4-diol monoesters in good yields and with excellent regio- and stereoselectivity. Various synthetic transformations of the obtained (Z)-2-butene-1,4-diol monoesters demonstrate how these synthons are of great use to rapidly diversify the portfolio of these formal desymmetrized (Z)-alkenes.

The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis.

To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.

Acupoint Autohemotherapy Attenuates DNCB-Induced Atopic Dermatitis and Activates Regulatory T Cells in BALB/c Mice.

Purpose: Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown. Methods: This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10+, IFN-γ+ and FoxP3+CD4+T cells in murine spleen. Results: It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3+, IL-10+ and IFN-γ+ CD4+T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation. Conclusion: These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.

The Role of the Tissue Perfusion Index in Predicting Disease Severity and Prognosis in Patients with Severe and Critical COVID-19.

OBJECTIVES: The study investigated whether percutaneous partial pressure of oxygen (PtcO2), percutaneous partial pressure of carbon dioxide (PtcCO2), and the derived tissue perfusion index (TPI) can predict the severity and short-term outcomes of severe and critical COVID-19. DESIGN: Prospective observational study conducted from January 1, 2023 to February 10, 2023. SETTING: A teaching hospital specializing in tertiary care in Nanjing City, Jiangsu Province, China. PARTICIPANTS: Adults (≥18 years) with severe and critical COVID-19. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The general information and vital signs of the patients were collected. The PtcO2 and PtcCO2 were monitored in the left dorsal volar. The ratio of TPI was defined as the ratio of PtcO2/fraction of inspired oxygen (FiO2) to PtcCO2. Mortality at 28 was recorded. The ability of the TPI to assess disease severity and predict prognosis was determined. ENDPOINT: Severity of the disease on the enrollment and mortality at 28. RESULTS: A total of 71 patients with severe and critical COVID-19, including 40 severe and 31 critical cases, according to the COVID-19 treatment guidelines published by WHO, were recruited. Their median age was 70 years, with 56 (79%) males. The median SpO2/FiO2, PtcO2, PtcCO2, PtcO2/ FiO2, and TPI values were 237, 61, 42, 143, and 3.6 mm Hg, respectively. Compared with those for severe COVID-19, the TPI, PtcO2/ FiO2, SpO2/FiO2, and PtcO2 were significantly lower in critical COVID-19, while the PtcCO2 was significantly higher. After 28 days, 26 (37%) patients had died. TPI values < 3.5 were correlated with more severe disease status (AUC 0.914; 95% CI: 0.847-0.981, P < 0.001), and TPI < 3.3 was associated with poor outcomes (AUC 0.937; 95% CI 0.880-0.994, P < 0.001). CONCLUSIONS: The tissue perfusion index (TPI), PtcCO2, and PtcO2/ FiO2 can predict the severity and outcome of severe and critical COVID-19.

Efficacy of Huangma Ding or autologous platelet-rich gel for the diabetic lower extremity arterial disease patients with foot ulcers.

BACKGROUND: Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability, traditional treatment has poor efficacy and there is an urgent need to develop a practical treatment method. AIM: To investigate whether Huangma Ding or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers. METHODS: A total of 155 diabetic LEAD patients with foot ulcers were enrolled and divided into three groups: Group A (62 patients; basal treatment), Group B (38 patients; basal treatment and APG), and Group C (55 patients; basal treatment and Huangma Ding). All patients underwent routine follow-up visits for six months. After follow-up, we calculated the changes in all variables from baseline and determined the differences between groups and the relationships between parameters. RESULTS: The infection status of the three groups before treatment was the same. Procalcitonin (PCT) improved after APG and Huangma Ding treatment more than after traditional treatment and was significantly greater in Group C than in Group B. Logistic regression analysis revealed that PCT was positively correlated with total amputation, primary amputation, and minor amputation rates. The ankle-brachial pressure and the transcutaneous oxygen pressure in Groups B and C were greater than those in Group A. The major amputation rate, minor amputation rate, and total amputation times in Groups B and C were lower than those in Group A. CONCLUSION: Our research indicated that diabetic foot ulcers (DFUs) lead to major amputation, minor amputation, and total amputation through local infection and poor microcirculation and macrocirculation. Huangma Ding and APG were effective attreating DFUs. The clinical efficacy of Huangma Ding was better than that of autologous platelet gel, which may be related to the better control of local infection by Huangma Ding. This finding suggested that in patients with DFUs combined with coinfection, controlling infection is as important as improving circulation.

Chromosome-level genome assemblies of Musa ornata and Musa velutina provide insights into pericarp dehiscence and anthocyanin biosynthesis in banana.

Musa ornata and Musa velutina are members of the Musaceae family and are indigenous to the South and Southeast Asia. They are very popular in the horticultural market, but the lack of genomic sequencing data and genetic studies has hampered efforts to improve their ornamental value. In this study, we generated the first chromosome-level genome assemblies for both species by utilizing Oxford Nanopore long reads and Hi-C reads. The genomes of M. ornata and M. velutina were assembled into 11 pseudochromosomes with genome sizes of 427.85 Mb and 478.10 Mb, respectively. Repetitive sequences comprised 46.70% and 50.91% of the total genomes for M. ornata and M. velutina, respectively. Differentially expressed gene (DEG) and Gene Ontology (GO) enrichment analyses indicated that upregulated genes in the mature pericarps of M. velutina were mainly associated with the saccharide metabolic processes, particularly at the cell wall and extracellular region. Furthermore, we identified polygalacturonase (PG) genes that exhibited higher expression level in mature pericarps of M. velutina compared to other tissues, potentially being accountable for pericarp dehiscence. This study also identified genes associated with anthocyanin biosynthesis pathway. Taken together, the chromosomal-level genome assemblies of M. ornata and M. velutina provide valuable insights into the mechanism of pericarp dehiscence and anthocyanin biosynthesis in banana, which will significantly contribute to future genetic and molecular breeding efforts.

Testing plastomes and nuclear ribosomal DNA sequences as the next-generation DNA barcodes for species identification and phylogenetic analysis in Acer.

BACKGROUND: Acer is a taxonomically intractable and speciose genus that contains over 150 species. It is challenging to distinguish Acer species only by morphological method due to their abundant variations. Plastome and nuclear ribosomal DNA (nrDNA) sequences are recommended as powerful next-generation DNA barcodes for species discrimination. However, their efficacies were still poorly studied. The current study will evaluate the application of plastome and nrDNA in species identification and perform phylogenetic analyses for Acer. RESULT: Based on a collection of 83 individuals representing 55 species (c. 55% of Chinese species) from 13 sections, our barcoding analyses demonstrated that plastomes exhibited the highest (90.47%) species discriminatory power among all plastid DNA markers, such as the standard plastid barcodes matK + rbcL + trnH-psbA (61.90%) and ycf1 (76.19%). And the nrDNA (80.95%) revealed higher species resolution than ITS (71.43%). Acer plastomes show abundant interspecific variations, however, species identification failure may be due to the incomplete lineage sorting (ILS) and chloroplast capture resulting from hybridization. We found that the usage of nrDNA contributed to identifying those species that were unidentified by plastomes, implying its capability to some extent to mitigate the impact of hybridization and ILS on species discrimination. However, combining plastome and nrDNA is not recommended given the cytonuclear conflict caused by potential hybridization. Our phylogenetic analysis covering 19 sections (95% sections of Acer) and 128 species (over 80% species of this genus) revealed pervasive inter- and intra-section cytonuclear discordances, hinting that hybridization has played an important role in the evolution of Acer. CONCLUSION: Plastomes and nrDNA can significantly improve the species resolution in Acer. Our phylogenetic analysis uncovered the scope and depth of cytonuclear conflict in Acer, providing important insights into its evolution.