Determination of succinic acid and lactic acid in pigs' serum, intestinal contents, and meat by ultrahigh-performance liquid chromatography-tandem mass spectrometry.

RATIONALE: Succinic acid and lactic acid have been associated with diarrhea in weaned piglets. The level of succinic acid and lactic acid in serum, meat, and intestinal contents is important to elucidate the mechanism of diarrhea in weaned piglets. METHODS: A facile method was developed for the quantification of succinic acid and lactic acid in pigs' serum, intestinal contents, and meat using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS). The serum samples underwent protein precipitation with methanol. The meat and intestinal contents were freeze-dried and homogenized using a tissue grinding apparatus. Methanol-water mixture (80:20, v/v) was used for homogenizing the meat, while water was used for homogenizing the intestinal contents. An additional step of protein precipitation with acetonitrile was required for the intestinal contents. The resulting solution was diluted with water before being analyzed by UHPLC/MS/MS. Separation of succinic acid and lactic acid could be achieved within 3 min using a Kinetic XB-C18 column. RESULTS: The coefficients of variation for peak areas of succinic acid and lactic acid were less than 5.0%. The established method demonstrated good linearity as indicated by correlation coefficients exceeding 0.996. Additionally, satisfactory recoveries ranging from 88.58% to 108.8% were obtained. The detection limits (RS/N = 3) for succinic acid and lactic acid were determined to be 0.75 ng/mL and 0.02 µg/mL, respectively. CONCLUSION: This method exhibited high sensitivity, simplicity in operation, and small sample weight, making it suitable for quantitative determination of succinic acid and lactic acid in pigs' serum, intestinal contents, and meat. The method developed will provide valuable technical support in studying the metabolic mechanisms of succinic acid and lactic acid in pigs.

CD22-targeted glyco-engineered natural killer cells offer a further treatment option for B-cell acute lymphoblastic leukemia.

Not available.

Efficiency of Protective Interventions on Irinotecan-Induced Diarrhea: A Systematic Review and Meta-Analysis.

BACKGROUND: Irinotecan is widely used in the treatment of various solid tumors, but the adverse effects from it, especially diarrhea, limit its use. Several clinical trials of prophylactic treatment of irinotecan-induced diarrhea (IID) have been ongoing, and some of the data are controversial. This encouraged us to conduct a meta-analysis of the effects of interventions on preventing IID. METHOD: This systematic review was conducted based on the PRISMA statement. We performed literature searches from PubMed, Web of Science, Embase, and Cochrane Library. The number registered in PROSPERO is CRD42022368633. After searching 1034 articles in the database and references, 8 studies were included in this meta-analysis. RESULT: The RR of high-grade diarrhea and all-grade diarrhea were 0.31 (I2 = 51%, 95% CI: 0.14-0.69; P = .004) and .76 (I2 = 65%, 95% CI: 0.62-0.93; P < .008) respectively, thus the use of intervention measures for preventing IID is effective, and the risk reduction of high-grade diarrhea was more significant. Subgroup analysis revealed that the monotherapy group (RR: 0.48, 95% CI: 0.21-1.13, I2 = 0%) and combination therapy group (RR: 0.14, 95% CI: 0.06-0.32, I2 = 0%) in the risk of high-grade diarrhea had no significant heterogeneity within the groups, and traditional herbal medicines (Kampo medicine Hangeshashin-to, PHY906 and hot ironing with Moxa Salt Packet on Tianshu and Shangjuxu) were effective preventive measures (RR:0.20, 95% CI: 0.07-0.60, I2 = 0%). The Jadad scores for traditional herbal medicines studies were 3, and the follow-up duration was only 2 to 6 weeks. CONCLUSION: This systematic review and meta-analysis suggest that preventive treatments significantly reduced the risk of high-grade and all-grade diarrhea, confirming the efficacy in the incidence and severity of IID, among which traditional herbal medicines (baicalin-containing) provided a protective effect in reducing the severity of IID. However, the traditional herbal medicines studies were of low quality. Combined irinotecan therapy can obtain better preventive effects than monotherapy of IID. These would be helpful for the prevention of IID in clinical practice.

Facile fabrication of a novel, photodetachable salecan-based hydrogel dressing with self-healing, injectable, and antibacterial properties based on metal coordination.

Achieving the controllable detachment of polysaccharide-based wound dressings is challenging. In this study, a novel, photodetachable salecan-based hydrogel dressing with injectable, self-healing, antibacterial, and wound healing properties was developed using a green and facile approach. A salecan hydrogel with a uniform porous structure and water content of 90.4 % was prepared by simply mixing salecan and an Fe3+-citric acid complexing solution in an acidic D-(+)-glucono-1,5-lactone environment. Metal coordinate interactions were formed between the released Fe3+ ions and carboxyl groups on the salecan polysaccharide, inducing homogeneous gelation. Benefiting from this dynamic and reversible crosslinking, the salecan hydrogel exhibited self-healing and injectable behavior, facilitating the formation of the desired shapes in situ. The exposure of Fe3+-citric acid to UV light (365 nm) resulted in the reduction of Fe3+ to Fe2+ through photochemical reactions, enabling phototriggered detachment. Moreover, the hydrogel exhibited excellent biocompatibility and satisfactory antibacterial efficacy against Escherichia coli and Staphylococcus aureus of 72.5 % and 85.3 %, respectively. The adhesive strength of the salecan hydrogel to porcine skin was 1.06 ± 0.12 kPa. In vivo wound healing experiments further highlighted the advantages of the prepared hydrogel in alleviating the degree of wound inflammation and promoting tissue regeneration within 12 days.

Gut microbiota and its metabolic products in acute respiratory distress syndrome.

The prevalence rate of acute respiratory distress syndrome (ARDS) is estimated at approximately 10% in critically ill patients worldwide, with the mortality rate ranging from 17% to 39%. Currently, ARDS mortality is usually higher in patients with COVID-19, giving another challenge for ARDS treatment. However, the treatment efficacy for ARDS is far from satisfactory. The relationship between the gut microbiota and ARDS has been substantiated by relevant scientific studies. ARDS not only changes the distribution of gut microbiota, but also influences intestinal mucosal barrier through the alteration of gut microbiota. The modulation of gut microbiota can impact the onset and progression of ARDS by triggering dysfunctions in inflammatory response and immune cells, oxidative stress, cell apoptosis, autophagy, pyroptosis, and ferroptosis mechanisms. Meanwhile, ARDS may also influence the distribution of metabolic products of gut microbiota. In this review, we focus on the impact of ARDS on gut microbiota and how the alteration of gut microbiota further influences the immune function, cellular functions and related signaling pathways during ARDS. The roles of gut microbiota-derived metabolites in the development and occurrence of ARDS are also discussed.

A novel NIR fluorescent probe inhibits melanoma progression through apoptosis and ERK/DRP1-mediated mitochondrial fission.

Melanoma, a highly metastatic malignant tumour, necessitated early detection and intervention. This study focuses on a hemicyanine fluorescent probe activated by near-infrared (NIR) light for bioimaging and targeted mitochondrial action in melanoma cells. IR-418, our newly designed hemicyanine-based NIR fluorescent probe, demonstrated effective targeting of melanoma cell mitochondria for NIR imaging. In vitro and in vivo experiments revealed IR-418's inhibition of melanoma growth through the promotion of mitochondrial apoptosis (Bax/Bcl-2/Cleaved Caspase pathway). Moreover, IR-418 inhibited melanoma metastasis by inhibiting mitochondrial fission through the ERK/DRP1 pathway. Notably, IR-418 mitigated abnormal ATL and ASL elevations caused by tumours without inflicting significant organ damage, indicating its high biocompatibility. In conclusion, IR-418, a novel hemicyanine-based NIR fluorescent probe targeting the mitochondria, exhibits significant fluorescence imaging capability, anti-melanoma proliferation, anti-melanoma lung metastasis activities and high biosafety. Therefore, it has significant potential in the early diagnosis and treatment of melanoma.

Amino acids in piglet diarrhea: Effects, mechanisms and insights.

Piglet diarrhea is among one of the most serious health problems faced by the pig industry, resulting in significant economic losses. Diarrheal disease in piglets has a multifactorial etiology that is affected by physiology, environment, and management strategy. Diarrhea is the most apparent symptom of intestinal dysfunction. As a key class of essential nutrients in the piglet diet, amino acids confer a variety of beneficial effects on piglets in addition to being used as a substrate for protein synthesis, including maintaining appropriate intestinal integrity, permeability and epithelial renewal, and alleviating morphological damage and inflammatory and oxidative stress. Thus, provision of appropriate levels of amino acids could alleviate piglet diarrhea. Most amino acid effects are mediated by metabolites, gut microbes, and related signaling pathways. In this review, we summarize the current understanding of dietary amino acid effects on gut health and diarrhea incidence in piglets, and reveal the mechanisms involved. We also provide ideas for using amino acid blends and emphasize the importance of amino acid balance in the diet to prevent diarrhea in piglets.

Enhanced Efficiency and Stability of Inverted CsPbI2Br Perovskite Solar Cells via Fluorinated Organic Ammonium Salt Surface Passivation.

All-inorganic perovskite solar cells (PSCs) have recently received increasing attention due to their outstanding thermal stability. However, the performance of these devices, especially for the devices with a p-i-n structure, is still inferior to that of the typical organic-inorganic counterparts. In this study, we introduce phenylammonium iodides with different side groups on the surface of the CsPbI2Br perovskite film and investigate their passivation effects. Our studies indicate that the 4-trifluoromethyl phenylammonium iodide (CFPA) molecule with the -CF3 side group effectively decreases the trap density of the perovskite film by forming interactions with the undercoordinated Pb2+ ions and significantly inhibits the nonradiative recombination in the derived PSC, leading to an enhanced open-circuit voltage (Voc) from 0.96 to 1.10 V after passivation. Also, the CFPA post-treatment enables better energy-level alignment between the conduction band minimum of CsPbI2Br perovskite and [6,6]-phenyl C61 butyric acid methyl ester, thereby enhancing the charge extraction from the perovskite to the charge transport layer. These combined benefits result in a significant enhancement of the power conversion efficiency from 11.22 to 14.37% for inverted CsPbI2Br PSCs. The device without encapsulation exhibits a degradation of only ≈4% after 1992 h in a N2 glovebox.

The adjuvant treatment role of ω-3 fatty acids by regulating gut microbiota positively in the acne vulgaris.

Objectives:We aimed to explore the potential role of omega-3 (ω-3) fatty acids on acne vulgaris by modulating gut microbiota.Materials and Methods:We randomly divided the untreated acne patients into two groups with or without ω-3 fatty acids intervention for 12 weeks. The Sprague Dawley (SD) rats with acne model were given isotretinoin, ω-3 fatty acids or their combination respectively. Then the colonic contents samples of the drug intervention SD rats were transferred to the pseudo sterile rats with acne model. The severity of the disease was assessed by the Global Acne Grading System (GAGS) score of the patients, and the swelling rate of auricle and the pathological section of the rat with acne model. The 16S rDNA gene sequencing was performed to detect the alteration of the gut microbiota.Results:ω-3 fatty acids could increase the diversity of the gut microbiota and regulate the flora structure positively both in the patients and rats, increase the abundance of butyric acid producing bacteria and GAGS score in the patients, and alleviate the inflammation and comedones of rats.Conclusion:Supplementation of ω-3 fatty acids could alleviate the inflammation of acne vulgaris by increasing the abundance of butyric acid producing bacteria.

Transcriptome Sequencing and Mass Spectrometry Reveal Genes Involved in the Non-mendelian Inheritance-Mediated Feather Growth Rate in Chicken.

The feather growth rate in chickens included early and late feathering. We attempted to characterize the genes and pathways associated with the feather growth rate in chickens that are not in agreement with Mendelian inheritance. Gene expression profiles in the hair follicle tissues of late-feathering cocks (LC), early-feathering cocks (EC), late-feathering hens (LH), and early-feathering hens (EH) were acquired using RNA sequencing (RNA-seq), mass spectrometry (MS), and quantitative reverse transcription PCR (qRT­PCR). A total of 188 differentially expressed genes (DEGs) were ascertained in EC vs. LC and 538 DEGs were identified in EH vs. LH. We observed that 14 up-regulated genes and 9 down-regulated genes were screened both in EC vs. LC and EH vs. LH. MS revealed that 41 and 138 differentially expressed proteins (DEPs) were screened out in EC vs. LC and EH vs. LH, respectively. Moreover, these DEGs and DEPs were enriched in multiple feather-related pathways, including JAK-STAT, MAPK, WNT, TGF-ß, and calcium signaling pathways. qRT-PCR assay showed that the expression of WNT8A was decreased in LC compared with EC, while ALK and GRM4 expression were significantly up-regulated in EH relative to LH. This study helps to elucidate the potential mechanism of the feather growth rate in chickens that do not conform to genetic law.

Promising role of protein arginine methyltransferases in overcoming anti-cancer drug resistance.

Drug resistance remains a major challenge in cancer treatment, necessitating the development of novel strategies to overcome it. Protein arginine methyltransferases (PRMTs) are enzymes responsible for epigenetic arginine methylation, which regulates various biological and pathological processes, as a result, they are attractive therapeutic targets for overcoming anti-cancer drug resistance. The ongoing development of small molecules targeting PRMTs has resulted in the generation of chemical probes for modulating most PRMTs and facilitated clinical treatment for the most advanced oncology targets, including PRMT1 and PRMT5. In this review, we summarize various mechanisms underlying protein arginine methylation and the roles of specific PRMTs in driving cancer drug resistance. Furthermore, we highlight the potential clinical implications of PRMT inhibitors in decreasing cancer drug resistance. PRMTs promote the formation and maintenance of drug-tolerant cells via several mechanisms, including altered drug efflux transporters, autophagy, DNA damage repair, cancer stem cell-related function, epithelial-mesenchymal transition, and disordered tumor microenvironment. Multiple preclinical and ongoing clinical trials have demonstrated that PRMT inhibitors, particularly PRMT5 inhibitors, can sensitize cancer cells to various anti-cancer drugs, including chemotherapeutic, targeted therapeutic, and immunotherapeutic agents. Combining PRMT inhibitors with existing anti-cancer strategies will be a promising approach for overcoming anti-cancer drug resistance. Furthermore, enhanced knowledge of the complex functions of arginine methylation and PRMTs in drug resistance will guide the future development of PRMT inhibitors and may help identify new clinical indications.

Integrated CO2 capture and conversion via H2-driven CO2 biomethanation: Cyclic performance and microbial community response.

This study investigated the use of H2-driven CO2 biomethanation for integrated CO2 capture and conversion (iCCC). Anaerobic chambers containing Na2CO3-amended microbial growth medium provided with H2 were inoculated with anaerobic granular sludge. Microorganisms were enriched that could regenerate carbonate by using the bicarbonate formed from CO2 absorption to generate methane. Multiple absorption-regeneration cycles were performed and effective restoration of CO2 absorption capacity and stable carbonate recycling via CO2 biomethanation were observed for CO2 absorbents adjusted to three different pH values (9.0, 9.5, and 10.0). The pH = 10.0 group had the highest CO2 absorption capacity; 65.3 mmol/L in the 5th cycle. A slight alkaline inhibition of acetoclastic methanogenesis occurred near the end of regeneration, but had limited impact on the cyclic performance of the iCCC process. Microbial communities were dominated by H2-utilizing and alkali-tolerant species that could participate in CO2 biomethanation and survive under alternating neutral and alkaline conditions.

Improving gut functions and egg nutrition with stevia residue in laying hens.

This study aimed to investigate the effect of stevia residue (STER) on the production performance, egg quality and nutrition, antioxidant ability, immune responses, gut morphology and microbiota of laying hens during the peak laying period. A total of 270 Yikoujingfen NO. 8 laying hens (35 wk of age) were randomly divided into 5 treatments. The control group fed a basal diet and groups supplemented with 2, 4, 6, and 8% STER. The results showed that STER significantly increased egg production, the content of amino acids (alanine, proline, valine, ornithine, asparagine, aspartic acid, and cysteine) in egg whites, and decreased the yolk color (P < 0.05). Additionally, STER significantly increased acetate, HOMOγ linolenic acid and cis-13, 16-docosadienoic acid levels in egg yolk (P < 0.05). IL-2, IL-4, and IL-10 levels in serum significantly increased by STER (P < 0.05), while IL-1ß significantly decreased (P < 0.05). STER also increased total antioxidant activity (T-AOC) in the liver and estradiol level in the oviduct (P < 0.05), but decreased the cortisol level in the oviduct (P < 0.05). For the intestinal morphology, the jejunal villus height and crypt-to-villus (V:C) significantly increased by STER (P < 0.05). STER increased the relative abundance of Actinobacteriota (P < 0.05), while deceased Proteobacteria, Desulfobacterota, and Synergistota (P < 0.05). In conclusion, STER improved egg production, quality and nutrition, improved the immune responses, antioxidant capabilities, estrogen level, gut morphology, and increased the relative abundance of beneficial bacteria while decreased the harmful bacteria. Among all treatments, 4 and 6% STER supplementation yielded the most favorable results in terms of enhancing production performance, egg nutrition, gut health, and immune capabilities in laying hens.

Retraction Notice to: miR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT/p70S6K and JNK Pathways through ABHD2.

[This retracts the article DOI: 10.1016/j.omto.2020.03.009.].

Peppermint extract improves egg production and quality, increases antioxidant capacity, and alters cecal microbiota in late-phase laying hens.

Introduction: Peppermint contains substantial bioactive ingredients belonging to the phytoestrogens, and its effects on the production of late-laying hens deserve more attention. This study evaluated the effects of dietary peppermint extract (PE) supplementation on egg production and quality, yolk fatty acid composition, antioxidant capacity, and cecal microbiota in late-phase laying hens. Method: PE powder was identified by UPLC-MS/MS analysis. Two hundred and sixteen laying hens (60 weeks old) were randomly assigned to four treatments, each for 28 days: (i) basal diet (control group, CON); (ii) basal diet + 0.1% PE; (iii) basal diet + 0.2% PE; and (iv) basal diet + 0.4% PE. Egg, serum, and cecal samples were collected for analysis. Results: Dietary PE supplementation increased the laying rate, serum triglyceride, immunoglobulin G, and total antioxidant capacity, while 0.2 and 0.4% PE supplementation increased eggshell thickness, serum total protein level, and superoxide dismutase activity of laying hens compared with the CON group (P < 0.05). PE addition in diets increased the C14:0, C18:3n3, C18:3n6, C23:0, C24:0, and C24:1n9 contents in the yolk. In addition, the egg yolk saturated fatty acid content was higher (P < 0.05) in the 0.2 and 0.4% PE groups compared with the CON and 0.1% PE groups. The microbiota analysis revealed that the cecal phylum Proteobacteria was decreased (P < 0.05) in the PE-supplemented groups. A total of 0.4% PE supplementation increased the cecal richness of gram-positive bacteria and decreased the richness of gram-negative and potentially pathogenic bacteria compared with the 0.1% PE group (P < 0.05). Microbial function prediction analysis showed that the cecal microbiota of the PE group was mainly enriched by fatty acid degradation, fatty acid metabolism, amino sugar metabolism, nucleotide sugar metabolism, and other pathways. Regression analysis suggested that 0.28-0.36% PE supplementation was the optimal level for improving egg production and quality, antioxidant capacity, and yolk fatty acid in late-phase laying hens. Discussion: Dietary PE supplementation improved egg production and quality (including yolk fatty acid composition) by increasing serum IgG and antioxidant capacity and modulating the intestinal microbiota in late-phase laying hens.

An Accurate Estimate of the Amino Acid Content of Human Milk Collected from Chinese Women Adjusted for Differences in Amino Acid Digestibility.

BACKGROUND: The amino acid (AA) composition of human milk is used to define the AA requirements of the infant. Thus, it is important that estimates of composition be as complete and accurate as possible. When determining AA composition using standard hydrolysis methods, some AAs are progressively destroyed while others are incompletely released. For accuracy, AA composition needs to be determined using multiple hydrolysis times. The true ileal digestibility of AAs also needs to be taken into consideration. OBJECTIVE: The objective was to bring together AA compositional (determined using multiple hydrolysis intervals) and digestibility data determined using the piglet to give an estimate of the absorbed AA profile of human milk with reference in particular to Asian females. METHODS: Mature milk was collected from Chinese females. AA analysis using multiple hydrolysis intervals and a nonlinear regression model was used to accurately estimate AA composition. Human milk, as well as a protein-free diet, were fed to piglets (n = 6), and ileal digesta were collected (piglet age, 21 d) to determine the true ileal AA digestibility of AAs in human milk. RESULTS: True ileal AA digestibility coefficients ranged from (mean ± standard error of the mean) 0.61 ± 0.081 for tyrosine to 1.01 ± 0.030 for tryptophan, with a digestibility for total nitrogen of 0.90 ± 0.013. Convergence criteria were met for the modeling for each AA, and the model had a level of significance of P < 0.0001 for each AA. The amount of available AAs (total AA content as per the model prediction multiplied by the true ileal AA digestibility coefficient determined in the piglet) are reported. CONCLUSIONS: An estimate of the absorbed AA profile of mature milk collected from Chinese females is provided. For the first time, data is presented for cysteine.

Characteristics of a ceftadine/avibatam resistance KPC-33-producing Klebsiella Pneumoniae strain with capsular serotype K19 belonging to ST15.

OBJECTIVES: The aim of this study was to characterize the blaKPC-33 in a ST15-K19 ceftazidime-avibactam (CAZ-AVI)-resistant Klebsiella pneumoniae strain after the antibiotic CAZ-AVI was approved for use in Wuxi No. 2 People's Hospital, China. METHODS: Antimicrobial susceptibility testing was performed by the microdilution broth method. Whole genome sequencing (WGS) was performed using PacBio II and MiSeq sequencers. High-quality reads were assembled using the SOAPdenovo and GapCloser v1.12, and genome annotation was performed using the NCBI Prokaryotic Genome Annotation Pipeline (PGAP). Genomic characteristics were analysed by using bioinformatics methods. RESULTS: K. pneumoniae strain KPHRJ showed resistance to CAZ-AVI. WGS analysis showed that strain KPHRJ had one 5 536 506 bp chromosome (57.25% G+C content) and one plasmid (133 451 bp, G+C 54.29%). KPHRJ was classified as ST15 and K19 serotype. Resistome analysis showed that KPHRJ carries seven antimicrobial resistance genes (ARGs). WGS analysis and conjugation experiments demonstrated that the blaKPC-33 gene was carried by plasmid pKPHRJ, flanked by two copies of IS26 mobile elements (IS26-ISKpn27-blaKPC-33-ISKpn6-korC-TnAs1-tetR-tetA-Tn3-IS26). Besides these acquired resistance genes, mutations in porin protein-coding genes, such as OmpK36 and OmpK37, which may reduce susceptibility to the CAZ-AVI, were also identified from the genome. CONCLUSION: Here, we present the WGS of a CAZ-AVI resistant K. pneumoniae isolate, strain KPHRJ, with capsular serotype K19 and belonging to ST15. CAZ-AVI resistance is likely conferred by a KPC-2 variant, blaKPC-33 and mutations in porin-coding genes. We speculate that the approval of the CAZ-AVI in hospital could contribute to the emergence of these genomic features by providing a selective pressure leading to the emergence of CAZ-AVI resistant bacteria.

Multifunctional Near-Infrared Dye IR-817 Encapsulated in Albumin Nanoparticles for Enhanced Imaging and Photothermal Therapy in Melanoma.

Background: Near-infrared cyanine dyes have high sensitivity and spatial resolution imaging capabilities, but they also have unavoidable drawbacks such as photobleaching, low water solubility, fluorescence quenching, and toxic side effects. As an effective biologic drug carrier, albumin combines with cyanine dyes to form albumin@dye nanoparticles. These nanoparticles can alleviate the aforementioned issues and are widely used in tumor imaging and photothermal therapy. Methods: Herein, a newly synthesized near-infrared dye IR-817 was combined with bovine serum albumin (BSA) to create BSA@IR-817 nanoparticles. Through the detection of fluorescence emission and absorption, the optimal concentration and ratio of BSA and IR-817 were determined. Subsequently, dynamic light scattering (DLS) measurements and scanning electron microscopy (SEM) were used for the physical characterization of the BSA@IR-817 nanoparticles. Finally, in vitro and in vivo experiments were conducted to assess the fluorescence imaging and photothermal therapeutic potential of BSA@IR-817 nanoparticles. Results: IR-817 was adsorbed onto the BSA carrier by covalent conjugation and supramolecular encapsulation, resulting in the formation of dispersed, homogeneous, and stable nanoparticles with a particle size range of 120-220 nm. BSA@IR-817 not only improved the poor water solubility, fluorescence quenching, and toxic side effects of IR-817 but also enhanced the absorption and fluorescence emission peaks in the near-infrared region, as well as the fluorescence in the visible spectrum. In addition, BSA@IR-817 combined with laser 808 irradiation was able to convert light energy into heat energy with temperatures exceeding 50 °C. By creating a mouse model of subcutaneous melanoma, it was discovered that the tumor inhibition rate of BSA@IR-817 was greater than 99% after laser irradiation and that it achieved nearly complete tumor ablation without causing significant toxicity. Conclusion: Our research, therefore, proposes the use of safe and effective photothermal nanoparticles for the imaging, diagnosis, and treatment of melanoma, and offers a promising strategy for future biomedical applications.

Downregulated BIRC5 inhibits proliferation and metastasis of melanoma through the ß-catenin/HIF-1α/VEGF/MMPs pathway.

PURPOSE: Melanoma is a malignant skin tumor caused by melanocytes and associated with high mortality rates. This study aims to investigate the specific mechanism of ZWZ-3 in melanoma proliferation and metastasis. METHODS: RNA sequencing was performed to identify the effect of ZWZ-3 on gene expression. siRNA was used to inhibit BIRC5 gene expression in the B16F10 cell line. A zebrafish tumor model was used to assess the therapeutic effect of ZWZ-3 in vivo. Mechanistic insights into the inhibition of tumor metastasis by ZWZ-3 were obtained through analysis of tumor tissue sections in mice. RESULTS: Our findings demonstrated that ZWZ-3 suppressed melanoma cell proliferation and migration. We performed RNA sequencing in melanoma cells after the treatment with ZWZ-3 and found that Birc5, which is closely associated with tumor metastasis, was significantly down-regulated. Bioinformatics analysis and the immuno-histochemical results of tissue chips for melanoma further confirmed the high expression of BIRC5 in melanoma and its effect on disease progression. Moreover, Birc5 knock-down significantly inhibited melanoma cell proliferation and metastasis, which was correlated with the ß-catenin/HIF-1α/VEGF/MMPs pathway. Additionally, ZWZ-3 significantly inhibited tumor growth in the zebrafish tumor model without any evident side effects. Histological and immuno-histochemical analyses revealed that ZWZ-3 inhibited tumor cell metastasis by down-regulating HIF-1α, VEGF, and MMP9. CONCLUSION: Our findings revealed that ZWZ-3 could downregulate BIRC5 and inhibit melanoma proliferation and metastasis through the ß-catenin/HIF-1α/VEGF/MMPs pathway. Therefore, BIRC5 represents a promising therapeutic target for the treatment of melanoma.

Untargeted metabolomics analysis of plasma metabolic characteristics in patients with acne and insulin resistance.

Acne vulgaris is a chronic inflammatory disease with high incidence, diverse clinical manifestations, poor clinical efficacy, and easy recurrence. Recent studies have found that the occurrence of acne is related to metabolic factors such as insulin resistance; however, the specific mechanism of action remains unclear. This study aimed to identify significantly different metabolites and related metabolic pathways in the serum of acne vulgaris patients with or without insulin resistance. LC-MS/MS was used to analyze serum samples from patients about acne with insulin resistance (n = 51) and acne without insulin resistance (n = 69) to identify significant metabolites and metabolic pathways. In this study, 18 significant differential metabolites were screened for the first time. In the positive-ion mode, the upregulated substances were creatine, sarcosine, D-proline, uracil, Phe-Phe, L-pipecolic acid, and DL-phenylalanine; the downregulated substances were tridecanoic acid (tridecylic acid), L-lysine, cyclohexylamine, sphingomyelin (d18:1/18:0), gamma-L-Glu-epsilon-L-Lys, and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine. In the negative-ion mode, the upregulated substance was cholesterol sulfate, and the downregulated substances were D(-)-beta-hydroxybutyric acid, myristic acid, D-galacturonic acid, and dihydrothymine. Cholesterol sulfate showed the most significant expression among all differential metabolites (VIP = 7.3411). Based on the KEGG database, necroptosis and ABC transporters were the most significantly enriched metabolic pathways in this experiment. The differential metabolites and pathways identified in this study may provide new possibilities for the clinical diagnosis and development of targeted drugs for acne patients with insulin resistance.