Evaluation of hemostatic, anti-inflammatory, wound healing, skin irritation and allergy, and antimicrobial properties of active fraction from the ethanol extract of Chromolaena odorata (L.) R.M. King & H. Rob.

ETHNOPHARMACOLOGICAL RELEVANCE: Chromolaena odorata (L.) R.M. King & H. Rob, a perennial herb, has been traditionally utilized as a herbal remedy for treating leech bites, soft tissue wounds, burn wounds, skin infections, and dento-alveolitis in tropical and subtropical regions. AIM OF THE STUDY: The present study was to analyze the active fraction of C. odorata ethanol extract and investigate its hemostatic, anti-inflammatory, wound healing, and antimicrobial properties. Additionally, the safety of the active fraction as an external preparation was assessed through skin irritation and allergy tests. MATERIALS AND METHODS: The leaves and stems of C. odorata were initially extracted with ethanol, followed by purification through AB-8 macroporous adsorption resin column chromatography to yield different fractions. These fractions were then screened for hemostatic activity in mice and rabbits to identify the active fraction. Subsequently, the hemostatic effect of the active fraction was assessed through the bleeding time of the rabbit ear artery in vivo and the coagulant time of rabbit blood in vitro. The anti-inflammatory activity of the active fraction was tested on mice ear edema induced by xylene and rat paw edema induced by carrageenin. Furthermore, the active fraction's promotion effect on wound healing was evaluated using a rat skin injury model, and skin safety tests were conducted on rabbits and guinea pigs. Lastly, antimicrobial activities against two Gram-positive bacteria (G+, Staphylococcus aureus and S. epidermidis) and three Gram-negative bacteria (G-, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were determined using the plate dilution method. RESULTS: The ethanol extract of C. odorata leaves and stems was fractionated into 30%, 60%, and 90% ethanol eluate fractions. These fractions demonstrated hemostatic activity, with the 30% ethanol eluate fraction (30% EEF) showing the strongest effect, significantly reducing bleeding time (P<0.05). A concentration of 1.0 g/mL of the 30% EEF accelerated cutaneous wound healing in rats on the 3rd, 6th, and 9th day post-operation, with the healing effect increasing over time. No irritation or allergy reactions were observed in rabbits and guinea pigs exposed to the 30% EEF. Additionally, the 30% EEF exhibited mild inhibitory effect on mice ear and rat paw edema, as well as antimicrobial activity against tested bacteria, with varying minimal inhibitory concentration (MIC) values. CONCLUSIONS: The 30% EEF demonstrated a clear hemostatic effect on rabbit bleeding time, a slight inhibitory effect on mice ear edema and rat paw edema, significant wound healing activity in rats, and no observed irritation or allergic reactions. Antibacterial activity was observed against certain clinically isolated bacteria, particularly the G- bacteria. This study lays the groundwork for the potential development and application of C. odorata in wound treatment.

Treatment ideas of acupuncture and moxibustion for adenomyosis based on "etiology, location, nature and development of disease". / 基于"ç— å› ã€ç— ä½ã€ç— æ€§ã€ç— åŠ¿"æµ æžå­å®«è ºè‚Œç—‡çš„é’ˆç¸æ²»ç–—æ€è·¯.

Focusing on the syndrome/pattern differentiation to determine treatment, the approaches to the diagnosis and treatment of acupuncture and moxibustion for adenomyosis are explored by identifying the etiology, location, nature and development of disease. The syndromes/patterns of adenomyosis are differentiated in view of both zangfu and meridian theories. The treatment is delivered complying with the menstrual cycle and the basic rule of treatment, "treating the symptoms in the acute stage, while the root causes in the recovery stage". During menstrual period, stopping pain and eliminating stasis are dominant; while during the other days of menstrual cycle, regulating zangfu dysfunction (excess or deficiency) is emphasized. In general, the functions of the thoroughfare vessel and the conception vessel should be specially considered and adjusted, and the principles of treatment include strengthening the spleen, regulating the kidney and soothing the liver. Acupoints are selected mainly from the spleen meridian of foot-taiyin, the kidney meridian of foot-shaoyin and the conception vessel. Ciliao (BL 32), Shiqizhui (EX-B 8), Zigong (EX-CA 1), Diji (SP 8) and four-gate points (bilateral Hegu [LI 4] and Taichong [LR 3]) are used in menstrual period; Zusanli (ST 36), Sanyinjiao (SP 6) and Taixi (KI 3) in postmenstrual phase; Guanyuan (CV 4), Luanchao (Ovary, Extra) and Qihai (CV 6) in intermenstrual phase; while, Guanyuan (CV 4), Qihai (CV 6) and Shenque (CV 8), combined with Gongsun (SP 4), Neiguan (PC 6) and Jianshi (PC 5) in premenstrual phase. According to the dynamic development of patient's conditions, the reinforcing or reducing techniques of acupuncture and moxibustion are feasibly applied in treatment of adenomyosis.

scDAC: deep adaptive clustering of single-cell transcriptomic data with coupled autoencoder and Dirichlet process mixture model.

MOTIVATION: Clustering analysis for single-cell RNA sequencing (scRNA-seq) data is an important step in revealing cellular heterogeneity. Many clustering methods have been proposed to discover heterogenous cell types from scRNA-seq data. However, adaptive clustering with accurate cluster number reflecting intrinsic biology nature from large-scale scRNA-seq data remains quite challenging. RESULTS: Here, we propose a single-cell Deep Adaptive Clustering (scDAC) model by coupling the Autoencoder (AE) and the Dirichlet Process Mixture Model (DPMM). By jointly optimizing the model parameters of AE and DPMM, scDAC achieves adaptive clustering with accurate cluster numbers on scRNA-seq data. We verify the performance of scDAC on five subsampled datasets with different numbers of cell types and compare it with 15 widely used clustering methods across nine scRNA-seq datasets. Our results demonstrate that scDAC can adaptively find accurate numbers of cell types or subtypes and outperforms other methods. Moreover, the performance of scDAC is robust to hyperparameter changes. AVAILABILITY AND IMPLEMENTATION: The scDAC is implemented in Python. The source code is available at https://github.com/labomics/scDAC.

Analysis of Immune and Prognostic-Related lncRNA PRKCQ-AS1 for Predicting Prognosis and Regulating Effect in Sepsis.

Background: Sepsis was a high mortality and great harm systemic inflammatory response syndrome caused by infection. lncRNAs were potential prognostic marker and therapeutic target. Therefore, we expect to screen and analyze lncRNAs with potential prognostic markers in sepsis. Methods: Transcriptome sequencing and limma was used to screen dysregulated RNAs. Key RNAs were screened by correlation analysis, lncRNA-mRNA co-expression and weighted gene co-expression network analysis. Immune infiltration, gene set enrichment analysis and gene set variation analysis were used to analyze the immune correlation. Kaplan-Meier curve, receiver operator characteristic curve, Cox regression analysis and nomogram were used to analyze the correlation between key RNAs and prognosis. Sepsis model was established by lipopolysaccharide-induced HUVECs injury, and then cell viability and migration ability were detected by cell counting kit-8 and wound healing assay. The levels of apoptosis-related proteins and inflammatory cytokines were detected by RT-qPCR and Western blot. Reactive Oxygen Species and superoxide dismutase were detected by commercial kit. Results: Fourteen key differentially expressed lncRNAs and 663 key differentially expressed genes were obtained. And these lncRNAs were closely related to immune cells, especially T cell activation, immune response and inflammation. Subsequently, Subsequently, lncRNA PRKCQ-AS1 was identified as the regulator for further investigation in sepsis. RT-qPCR results showed that PRKCQ-AS1 expression was up-regulated in clinical samples and sepsis model cells, which was an independent prognostic factor in sepsis patients. Immune correlation analysis showed that PRKCQ-AS1 was involved in the immune response and inflammatory process of sepsis. Cell function tests confirmed that PRKCQ-AS1 could inhibit sepsis model cells viability and promote cell apoptosis, inflammatory damage and oxidative stress. Conclusion: We constructed immune-related lncRNA-mRNA regulatory networks in the progression of sepsis and confirmed that PRKCQ-AS1 is an important prognostic factor affecting the progression of sepsis and is involved in immune response.

miR-19a may function as a biomarker of oral squamous cell carcinoma (OSCC) by regulating the signaling pathway of miR-19a/GRK6/GPCRs/PKC in a Chinese population.

BACKGROUND: In this study, we aimed to investigate the potential of miR-19a as a biomarker of OSCC and its underlying molecular mechanisms. METHODS: We collected serum and saliva samples from 66 OSCC patients and 66 healthy control subjects. Real-time PCR analysis, bioinformatic analysis and luciferase assays were performed to establish a potential signaling pathway of miR-19a/GRK6/GPCRs/PKC. Flowcytometry and Transwell assays were performed to observe the changes in cell apoptosis, metastasis and invasion. RESULTS: We found that miR-19a, GPR39 mRNA and PKC mRNA were upregulated while GRK6 mRNA was downregulated in the serum and saliva samples collected from OSCC patients. Moreover, in silico analysis confirmed a potential binding site of miR-19a on the 3'UTR of GRK6 mRNA, and the subsequent luciferase assays confirmed the molecular binding between GRK6 and miR-19a. We further identified that the over-expression of miR-19a could regulate the signaling between GRK6, GPR39 and PKC via the signaling pathway of miR-19a/GRK6/GPR39/PKC, which accordingly resulted in suppressed cell apoptosis and promoted cell migration and invasion. CONCLUSION: Collectively, the findings of our study propose that miR-19a is a crucial mediator in the advancement of OSCC, offering a potential avenue for the development of innovative therapeutic interventions aimed at regulating GRK6 and its downstream signaling pathways.

Single-cell multi-omics sequencing of human spermatogenesis reveals a DNA demethylation event associated with male meiotic recombination.

Human spermatogenesis is a highly ordered process; however, the roles of DNA methylation and chromatin accessibility in this process remain largely unknown. Here by simultaneously investigating the chromatin accessibility, DNA methylome and transcriptome landscapes using the modified single-cell chromatin overall omic-scale landscape sequencing approach, we revealed that the transcriptional changes throughout human spermatogenesis were correlated with chromatin accessibility changes. In particular, we identified a set of transcription factors and cis elements with potential functions. A round of DNA demethylation was uncovered upon meiosis initiation in human spermatogenesis, which was associated with male meiotic recombination and conserved between human and mouse. Aberrant DNA hypermethylation could be detected in leptotene spermatocytes of certain nonobstructive azoospermia patients. Functionally, the intervention of DNA demethylation affected male meiotic recombination and fertility. Our work provides multi-omics landscapes of human spermatogenesis at single-cell resolution and offers insights into the association between DNA demethylation and male meiotic recombination.

An interval water demand prediction method to reduce uncertainty: A case study of Sichuan Province, China.

Effective prediction of water demand is a prerequisite for decision makers to achieve reliable management of water supply. Currently, the research on water demand prediction focuses on point prediction method. In this study, we constructed a GA-BP-KDE hybrid interval water demand prediction model by combining non-parametric estimation and point prediction. Multiple metaheuristic algorithms were used to optimize the Back-Propagation Neural Network (BP) and Kernel Extreme Learning Machine (KELM) network structures. The performance of the water demand point prediction models was compared by the Root Mean Squared Error (RMSE), Mean Absolute Percentage Error (MAPE), Kling-Gupta Efficiency (KGE), computation time, and fitness convergence curves. The kernel density estimation method (KDE) and the normal distribution method were used to fit the distribution of errors. The probability density function with the best fitting degree was selected based on the index G. The shortest confidence interval under 95% confidence was calculated according to the asymmetry of the error distribution. We predicted the impact indicator values for 2025 using the exponential smoothing method, and obtained water demand prediction intervals for various water use sectors. The results showed that the GA-BP model was the optimal model as it exhibited the highest computational efficiency, algorithmic stability, and prediction accuracy. The three prediction intervals estimated after adjusting the KDE bandwidth parameter covered most of the sample points in the test set. The prediction intervals of the four water use sectors were evaluated as F values of 1.6845, 1.3294, 1.6237, and 1.3600, which indicates high accuracy and quality of the prediction intervals. The mixed water demand interval prediction based on GA-BP-KDE reduces the uncertainty of the point prediction results and can provide a basis for water resource management by decision makers.

Gelatin-Functionalized Carbon Nanotubes Loaded with Cisplatin for Anti-Cancer Therapy.

Cisplatin (Cp), a chemotherapeutic agent, interacts with purines on tumor DNA, causing tumor cell apoptosis. However, cisplatin has the characteristics of non-specific distribution and lack of selectivity, resulting in systemic toxicity. Moreover, it cannot maintain the drug's high concentration in the tumor-weak acid environment. These flaws of cisplatin restrict its use in clinical applications. Therefore, a pH-responsive carbon nanotube-modified nano-drug delivery system (CNTs/Gel/Cp) was constructed in this study using gelatin (Gel)-modified carbon nanotubes (CNTs/Gel) loaded with cisplatin to release drugs precisely and slowly, preventing premature inactivation and maintaining an effective concentration. When MCp:MCNTs/Gel = 1:1, the drug reaches the highest loading rate and entrapment efficiency. To achieve the sustained-release effect, CNTs/Gel/Cp can release the medicine steadily for a long time in a pH environment of 6.0. Additionally, CNTs/Gel/Cp display antitumor properties comparable to cisplatin in a manner that varies with the dosage administered. These findings indicate that CNTs/Gel/Cp have an effective, sustained release of cisplatin and a good antitumor effect, providing a theoretical and experimental basis for the clinical application of modified carbon nanotubes (CNTs) as a new drug delivery system.

Inhibition of SIRT1 promotes ultraviolet B induced cataract via downregulation of the KEAP1/NFE2L2 signaling pathway.

Due to continuous exposure to ultraviolet B(UVB) radiation, eye lenses are constantly subjected to oxidative stress that induces lens epithelial cell (LEC) apoptosis, which has been associated with the inactivation of Sirtuin1 (SIRT1). It is well-established that NFE2L2 has a major protective effect on UVB-induced oxidative stress and damage. However, whether UVB radiation affects oxidative/antioxidative imbalance and damages LECs by inactivating the protective NFE2L2-mediated antioxidative stress pathway through inhibition of SIRT1 is unknown. In our research, we established in vivo and in vitro UVB exposure models in Sprague Dawley rats and SRA01/04 cells, respectively, to investigate the effect of UVB radiation on the NFE2L2/ KEAP1 pathway and the role of SIRT1 in this process. The in vivo findings revealed that UVB radiation exposure decreased Sirt1 and Nfe2l2 levels, upregulated Keap1 expression, led to an oxidative/antioxidative imbalance and increased LEC apoptosis in the eye lens. Sirt1 downregulated Keap1 expression levels, but activated Nfe2l2 and its downstream target proteins. The in vitro findings showed that UVB inhibited the deacetylation of SIRT1 target proteins and increased the acetylation levels of KEAP1 and NFE2L2. We also found that UVB radiation exposure led to a significant decrease in both co-localization levels and protein interaction between SIRT1 and KEAP1. In addition, the inhibition of SIRT1 increased KEAP1 levels, inhibited the activity of NFE2L2 and decreased co- localization levels and protein interactions between NFE2L2 and KEAP1. These results suggested that UVB radiation decreased SIRT1 levels and inhibited the KEAP1/NFE2L2 pathway, thereby reducing its antioxidant effect, which might be an important mechanism of UVB-induced cataract.

An acquired BMF with FANCL gene heterozygous mutation: Case report.

RATIONALE: Bone marrow failure (BMF) includes inherited and acquired BMFs. Acquired BMF can be secondary to various factors, such as autoimmune dysfunction, benzene, drugs, radiation, viral infection and so on. Fanconi anemia (FA) complementation group L (FANCL) is an E3 ubiquitin ligase that participates in the repair of DNA damage. Homozygous or compound heterozygous mutations of FANCL can lead to the onset of FA, which is one of the most common inherited BMFs. PATIENT CONCERNS AND DIAGNOSES: Here, we report a case of acquired BMF. This patient had a history of benzene exposure for half a year before the onset of the disease, and presented with progressive pancytopenia, especially the reduction of erythrocytes and megakaryocyte, without malformation. Interestingly, this patient and his brother/father had a heterozygous (non-homozygous/compound heterozygous) mutation (Exon9, c.745C > T, p.H249Y) in the FANCL gene. INTERVENTIONS AND OUTCOMES: The patient successfully underwent unrelated and fully compatible umbilical cord blood hematopoietic stem cell transplantation. LESSONS SUBSECTIONS: We report for the first time an acquired BMF case with FANCL gene heterozygous mutation, and the mutation site (Exon9, c.745C > T, p.H249Y) has never been reported. This case suggests that heterozygous mutations in FANCL gene may be associated with increased susceptibility to acquired BMF. Based on current reports and this case, we speculate that heterozygous mutations in the FA complementation gene may exist in a certain proportion of tumor and acquired BMF patients, but have not been detected. We recommend routine screening for FA complementation gene mutations in tumor and acquired BMF patients in clinical practice. If positive results are found, further screening can be conducted on their families.

Determining Reaction Paths by Evaluating Kinetic Isotopic Effects with Density Functional Theory: Example of Methane Thermogenesis.

This study demonstrates the determination of reaction pathways by evaluating the carbon kinetic isotopic effect and interpreting isotopic fractionations based on quantum chemical calculations. The reaction under investigation is methane thermogenesis from the decomposition of kerogen, which is a geochemical reaction under temperatures below 150 °C and lasts for tens of millions of years. Investigating its mechanism requires theoretical simulations because lab experiments at practical time-lengths require elevated temperatures, which introduce unwanted side reactions. Density functional theory and kinetic simulations were conducted on isotopic fractionations with the use of two possible pathways (free-radical versus carbonium), and the results were compared to field data sets. Different molecular sizes of kerogen were investigated to account for the hindrance of translation and rotation in modeling a reactant in the solid phase. Both pathways have low reaction barriers, implying that the reaction rates are limited by the concentration of active species (hydrated protons and free radicals). The results support the carbonium pathway and rule out the free-radical pathway as the 13CH4 from the latter would be 30‰ more depleted than the observed data. Additionally, simulations were conducted on hydrocarbon isotope fractionation of the carbonium pathway with consideration of hydrogen exchange between methane and water, successively reproducing the observed abundances of deuterium-containing isotopologues (13CH3D, 13CH3D, and 12CH2D2).

Ablation of porcine subcutaneous fat and porcine aorta tissues by a burst-mode nanosecond-pulsed laser at 355 nm.

High-energy laser pulses used in laser angioplasty are challenging the laser cost, delivery system damage, efficiency, and laser catheter operating time. 355 nm nanosecond-pulsed laser in burst mode has shown potentials in reducing the system complexity and selective ablation of tissues. In this paper, burst mode laser ablation of porcine subcutaneous fat and porcine aorta is investigated. A histopathological analysis demonstrates that porcine subcutaneous fat can be ablated at a rate of greater than 0.2 mm/s when the number of pulses per burst is 1500 (corresponding to a fluence of 0.12 mJ/mm2 per pulse and 180 mJ/mm2 per burst), and the temperature of tissue during lasing is lower than 45°C. The porcine aorta remains nearly unaffected at the same laser parameter, and the tissue temperature during lasing is lower than 35°C. It shows the feasibility of using a burst-mode laser for selective ablation of tissue.

Clinical characteristics of antithyroid drug-induced aplastic anemia cases over the past 30 years.

Objective: The authors aimed to investigate the clinical characteristics of antithyroid drug-induced aplastic anemia cases over the past 30 years. Methods: The data of patients with antithyroid drug-induced aplastic anemia were retrieved from PubMed and Wanfang Medical Network databases from 1992 to August 2022. The clinical characteristics, such as age distribution, gender tendency, common symptoms, blood cell count, bone marrow features, treatment strategy, and prognosis, were analyzed. Results: A total of 17 cases (male:female = 1:16) had been retrieved. Patients' age ranged from 16 to 74 years (median 50 years). Among them, 82.3% (14/17) of the patients were administered methimazole (MMI), and 78.6% of them had MMI ≥30 mg/day. In addition, 88.2% (15/17) of the patients had sore throat and fever, and 47.1% (8/17) of the patients had hemorrhagic symptoms. Aplastic anemia occurred within 6 months after initiation of the antithyroid therapy in 94.1% of the patients. Agranulocytosis (94.1%) was the most common and earliest blood cell change, and 47.1% of the patients experienced progressive platelet decline during the treatment process. The treatments include timely withdrawal of antithyroid drugs, broad-spectrum antibiotics, granulocyte colony-stimulating factor (G-CSF)/granulocyte-macrophage colony-stimulating factor (GM-CSF), glucocorticoids and other immunosuppressive agents, and supportive treatments such as erythrocyte transfusion and platelet transfusion. Moreover, 70.6% of the patients had complete or near-complete remission within 8 days to 6 weeks. Conclusion: Aplastic anemia is a rare and serious adverse reaction of antithyroid drugs, which is more common in women. It usually occurs during early treatment with high-dose antithyroid drugs. Most patients have a good prognosis after timely drug ceasing and appropriate treatment.

The Palmitoylation/Depalmitoylation Cycle is Involved in the Inhibition of AMPA Receptor Trafficking Induced by Aluminum In Vitro.

To study the effect of the palmitoylation/depalmitoylation cycle on the inhibition of ɑ-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) receptor trafficking induced by aluminum (Al) in vitro. Five different doses of aluminum-maltolate complex (Al(mal)3) were administered to rat adrenal pheochromocytoma cells (PC12 cells) for three exposure time durations, and the cell activity was measured by the CCK-8 method to obtain the optimal doses and time of Al(mal)3 exposure. Following Al(mal)3 exposure, membrane protein (M) and total protein (T) were extracted. The expression levels of GluR1 and GluR2, which are AMPA receptor subunits, were determined by Western blot analysis, and the levels with respect to membrane and total protein were calculated. The ratio of membrane protein to total protein (M/T) was used to measure the rate of AMPA receptor transport. The palmitoylation levels of GluR1 and GluR2 were detected by immunoprecipitation-acyl-biotin exchange (IP-ABE) assay. Western blotting was performed to detect the protein expression of acyltransferase (zDHHC3) and palmitoyl protein thioesterase 1 (PPT1). Following depalmitoylation inhibitor (palmostatin B) treatment of PC12 cells, the effect of aluminum on AMPA receptor trafficking was detected through the aforementioned methods. With increasing Al(mal)3 doses administered to PC12 cells, a gradual decrease in the trafficking of AMPA receptor subunits GluR1 and GluR2 and in the palmitoylation levels of GluR1 and GluR2 was found; the expression of zDHHC3 was decreased; and the expression of PPT1 was increased. In addition, palmostatin B reduced the effects of Al(mal)3 on AMPA receptor palmitoylation and trafficking. Al can inhibit the trafficking of the AMPA receptor in vitro, and a decrease in the palmitoylation level of the AMPA receptor may be a mechanism of Al action. The palmitoylation/depalmitoylation cycle of the AMPA receptor is influenced by Al through the actions of zDHHC3 and PPT1.

Targeting APLN/APJ restores blood-testis barrier and improves spermatogenesis in murine and human diabetic models.

Type 2 diabetes mellitus is one of the most prevalent metabolic diseases presenting with systemic pathologies, including reproductive disorders in male diabetic patients. However, the molecular mechanisms that contributing to spermatogenesis dysfunction in diabetic patients have not yet been fully elucidated. Here, we perform STRT-seq to examine the transcriptome of diabetic patients' testes at single-cell resolution including all major cell types of the testis. Intriguingly, whereas spermatogenesis appears largely preserved, the gene expression profiles of Sertoli cells and the blood-testis barrier (BTB) structure are dramatically impaired. Among these deregulate pathways, the Apelin (APLN) peptide/Apelin-receptor (APJ) axis is hyper-activated in diabetic patients' testes. Mechanistically, APLN is produced locally by Sertoli cells upon high glucose treatment, which subsequently suppress the production of carnitine and repress the expression of cell adhesion genes in Sertoli cells. Together, these effects culminate in BTB structural dysfunction. Finally, using the small molecule APLN receptor antagonist, ML221, we show that blocking APLN/APJ significantly ameliorate the BTB damage and, importantly, improve functional spermatogenesis in diabetic db/db mice. We also translate and validate these findings in cultured human testes. Our findings identify the APLN/APJ axis as a promising therapeutic target to improve reproduction capacity in male diabetic patients.

Effect of brewing conditions on the chemical and sensory profiles of milk tea.

The brewing conditions of beverage milk tea determine the taste of milk tea. This study investigated the changes in sensory characteristics and small molecule compounds in milk tea made from large-leaf yellow tea under different brewing conditions by sensory analysis, colorimeter, and LC-MS. The results show that the tea to milk ratio is the most important process affecting the taste, and the color values of b* (+yellow, - blue) can be used to evaluate the taste of milk tea made from large leaf yellow tea. The composition of small molecular compounds is affected by tea to milk ratio, which can change the taste of milk tea. l-cysteine and 8-methylsulfinyloctyl glucosinolate are significantly positively correlated with taste by metabolomics analysis. l-cysteine was used to verify the analysis results by LC-MS. The total acceptance of milk tea is improved by adding l-cysteine at a low level (0.025-0.035 mM).

Bovine Lactoferrin Alleviates Pulmonary Lipid Peroxidation and Inflammatory Damage in Heat Stroke Rats.

Lung injury occurring in the early stage of heat stroke (HS) leads to hypoxia and further aggravation of other organic damage. Lactoferrin (LF) is an iron binding protein with anti-inflammatory and antioxidant effects. This study focuses on the protection of preadministration of bovine lactoferrin (BLF) against lung injury in rats with HS. Sixty-four Sprague-Dawley male rats were divided into four groups randomly: control (CON)+phosphate-buffered saline (PBS) (n = 16), HS+PBS (n = 16), HS+low-dose BLF (LBLF) (n = 16), and HS+high-dose BLF (HBLF) (n = 16). CON+PBS and HS+PBS were preadministered 10 mL/kg PBS for 1 week. HS+LBLF and HS+HBLF were preadministered 100 and 200 mg/kg BLF for 1 week, respectively. The HS onset time and the survival rate were recorded, and bronchoalveolar lavage fluid was obtained to measure protein concentration. Lung was obtained for pathological analysis and wet/dry weight ratio measurement; later, the content of malondialdehyde (MDA), activity of myeloperoxidase (MPO), and superoxide dismutase (SOD) were measured in lung tissue homogenate. The results indicated that BLF preadministration could delay the HS onset time, enhance the survival rate, the levels of serum inflammatory cytokine and MDA content in HS+LBLF and HS+HBLF showed significant reduction compared with HS+PBS, while a significant elevation of SOD activity and reduction of MPO activity in HS+HBLF. Our results demonstrate that BLF preadministration could relieve lung injury in HS rats by enhancing thermal endurance, and alleviating serum inflammatory response and pulmonary oxidative stress damage.

Identification of the hormetic dose-response and regulatory network of multiple metals co-exposure-related hypertension via integration of metallomics and adverse outcome pathways.

Environmental stressors, including heavy metals, can be associated with hypertension development. However, little information regarding the dose-response relationship and toxicity mechanisms of metal mixtures with hypertension development is currently available. Therefore, we recruited 940 participants from six factories in northeastern China and measured the urinary concentrations of 19 metals. Then, we used Bayesian kernel machine regression (BKMR) to explore associations between metals co-exposure and hypertension. The BKMR model indicated a hermetic dose-response relationship between eight urinary metals (Co, Cr, Ni, Cd, As, Fe, Zn, and Pb) and hypertension risk. Moreover, heterogeneous and non-linear association patterns were detected across different metals/metalloids concentrations. Next, for the first time, we analyzed data of chemicals containing specific metal elements in the Comparative Toxicogenomics Database (CTD) from a disease perspective and provided insights from various biological levels to explain heavy metal co-exposure-related hypertension. On the molecular scale, 43 chemical components and 112 potential target genes were detected for metal exposure-related hypertension. Further, the network topology analysis indicated that target genes such as insulin (INS, degree = 78), albumin (ALB, degree = 74), renin (REN, degree = 71), interleukin-6 (IL6, degree = 70), endothelin 1 (EDN1, degree = 70), and endothelial nitric oxide synthase (NOS3, degree = 69) have a strong correlation with heavy metals co-exposure. Finally, we used integrative analyses in the adverse outcome pathway (AOP) wiki to analyze the co-exposure of heavy metals and hypertension and support an integrated metallomics approach. We selected the AOP 149 as the framework and found that the molecular initiating events (MIEs) of hypertension stems from the oxidation of AA residues on critical peptides of the NO pathway. The NOS3 was particularly promising since its subunit has three metal ion cross-linking domains with Zn2+, Fe2+, and Ga3+, which might serve as a binding site for heavy metal ions.

Methane from microbial hydrogenolysis of sediment organic matter before the Great Oxidation Event.

Methane, along with other short-chain alkanes from some Archean metasedimentary rocks, has unique isotopic signatures that possibly reflect the generation of atmospheric greenhouse gas on early Earth. We find that alkane gases from the Kidd Creek mines in the Canadian Shield are microbial products in a Neoarchean ecosystem. The widely varied hydrogen and relatively uniform carbon isotopic compositions in the alkanes infer that the alkanes result from the biodegradation of sediment organic matter with serpentinization-derived hydrogen gas. This proposed process is supported by published geochemical data on the Kidd Creek gas, including the distribution of alkane abundances, stable isotope variations in alkanes, and CH2D2 signatures in methane. The recognition of Archean microbial methane in this work reveals a biochemical process of greenhouse gas generation before the Great Oxidation Event and improves the understanding of the carbon and hydrogen geochemical cycles.

Engineering aluminum hydroxyphosphate nanoparticles with well-controlled surface property to enhance humoral immune responses as vaccine adjuvants.

Aluminum phosphate adjuvants play a critical role in human inactivated and subunit prophylactic vaccines. However, a major challenge is that the underlying mechanism of immune stimulation remains poorly understood, which impedes the further optimal design and application of more effective adjuvants in vaccine formulations. To address this, a library of amorphous aluminum hydroxyphosphate nanoparticles (AAHPs) is engineered with defined surface properties to explore the specific mechanism of adjuvanticity at the nano-bio interface. The results demonstrate that AAHPs could induce cell membrane perturbation and downstream inflammatory responses, with positively-charged particles showing the most significantly enhanced immunostimulation potentials compared to the neutral or negatively-charged particles. In a vaccine using Staphylococcus aureus (S. aureus) recombinant protein as antigens, the positively-charged particles elicit long-lasting and enhanced humoral immunity, and provide protection in S. aureus sepsis mice models. In addition, when formulated with human papillomavirus type 18 virus-like particles, it is demonstrated that particles with positive charges outperform in promoting serum antigen-specific antibody productions. This study shows that engineering AAHPs with well-controlled physicochemical properties enable the establishment of a structure-activity relationship that is critical to instruct the design of suitable engineered nanomaterial-based adjuvants within vaccine formulations for the benefits of human health.