Genetically modified indigenous Pseudomonas aeruginosa drove bacterial community to change positively toward microbial enhanced oil recovery applications.

AIMS: Microbial enhanced oil recovery (MEOR) is cost-effective and eco-friendly for oil exploitation. Genetically modified biosurfactants-producing high-yield strains are promising for ex-situ MEOR. However, can they survive and produce biosurfactants in petroleum reservoirs for in-situ MEOR? What is their effect on the native bacterial community? METHODS AND RESULTS: A genetically modified indigenous biosurfactants-producing strain Pseudomonas aeruginosa PrhlAB was bioaugmented in simulated reservoir environments. Pseudomonas aeruginosa PrhlAB could stably colonize in simulated reservoirs. Biosurfactants (200 mg l-1) were produced in simulated reservoirs after bio-augmenting strain PrhlAB. The surface tension of fluid was reduced to 32.1 mN m-1. Crude oil was emulsified with an emulsification index of 60.1%. Bio-augmenting strain PrhlAB stimulated the MEOR-related microbial activities. Hydrocarbon-degrading bacteria and biosurfactants-producing bacteria were activated, while the hydrogen sulfide-producing bacteria were inhibited. Bio-augmenting P. aeruginosa PrhlAB reduced the diversity of bacterial community, and gradually simplified the species composition. Bacteria with oil displacement potential became dominant genera, such as Shewanella, Pseudomonas, and Arcobacter. CONCLUSIONS: Culture-based and sequence-based analyses reveal that genetically modified biosurfactants-producing strain P. aeruginosa PrhlAB are promising for in-situ MEOR as well.

Nutritional improvement status of primary and secondary school students in the pilot nutrition improvement areas of Hainan, China from 2014 to 2021.

OBJECTIVE: By meticulously tracking the evolving growth, development, and nutritional status of primary and secondary school students in Qiongzhong County from 2014 to 2021 post-implementation of the "Nutrition Improvement Program for Rural Compulsory Education Students"(NIPRCES, This project provides a supplementary food allowance of at least ï¿¥4 per person per day for primary and secondary school students. The project area undergoes annual routine monitoring.), this study aims to offer a scientific basis for enhancing and promoting the project. Through thorough monitoring of students' nutritional status changes influenced by this program, we strive to establish a comprehensive and evidence-based framework for its future advancement. METHODS: From 2014 to 2021, this study employed a multi-stage sampling method utilizing cluster sampling to select six primary and six secondary schools in Qiongzhong County, Hainan Province. Data on the growth and development of respondents were collected. This cohort was a dynamic cohort with a total of 18,762 final data recovered. The prevalence of malnutrition was evaluated using the Cochran Armitage Trend Test (CATT) to assess year-to-year changes. Furthermore, height/weight and the prevalence of malnutrition between groups were compared using the t-test, χ2 test, and Bonferroni's corrected analysis. RESULTS: The average height of both boys and girls has increased. In 2021, boys and girls of all ages showed an average height increase of 2.31 cm and 1.98 cm, respectively, compared to 2014. Nevertheless, the growth and development levels, and rate of improvement of these students remain comparatively lower than their rural counterparts across China, who are of the same age. From 2014 to 2021, the prevalence of undernutrition (mainly wasting) showed a significant downward trend (P < 0.05) from 29.30% to 22.19%, and the prevalence of overnutrition showed an upward trend (both P < 0.05). The prevalence of undernutrition was higher among boys, students in grades 1-3 and those of Li nationality. Meanwhile, the prevalence of overnutrition was higher among boys, students in grades 1-3 and those of Han nationality. CONCLUSIONS: Over the 8-year period of NIPRCES, there has been progress in the growth and development of students, yet levels still lag behind the national average for rural students of the same age. While malnutrition prevalence have decreased, they remain high, with a concerning rise in overnutrition prevalence. Undernutrition and overweight/obesity are more prevalent among boys and younger students. Li students show higher prevalence of undernutrition, while overnutrition is a growing issue among Han students. Simultaneously, local education and health care departments must acknowledge the disparities in growth and nutritional status among primary and secondary school students residing in rural areas within the tropics and those in rural areas across the entire nation. Nutritional improvement measures should be tailored to local conditions.

Manipulating the Rate and Overpotential for Electrochemical Water Oxidation: Mechanistic Insights for Cobalt Catalysts Bearing Noninnocent Bis(benzimidazole)pyrazolide Ligands.

Electrochemical water oxidation is known as the anodic reaction of water splitting. Efficient design and earth-abundant electrocatalysts are crucial to this process. Herein, we report a family of catalysts (1-3) bearing bis(benzimidazole)pyrazolide ligands (H 2 L1-H 2 L3). H 2 L3 contains electron-donating substituents and noninnocent components, resulting in catalyst 3 exhibiting unique performance. Kinetic studies show first-order kinetic dependence on [3] and [H2O] under neutral and alkaline conditions. In contrast to previously reported catalyst 1, catalyst 3 exhibits an insignificant kinetic isotope effect of 1.25 and zero-order dependence on [NaOH]. Based on various spectroscopic methods and computational findings, the L3Co2 III(µ-OH) species is proposed to be the catalyst resting state and the nucleophilic attack of water on this species is identified as the turnover-limiting step of the catalytic reaction. Computational studies provided insights into how the interplay between the electronic effect and ligand noninnocence results in catalyst 3 acting via a different reaction mechanism. The variation in the turnover-limiting step and catalytic potentials of species 1-3 leads to their catalytic rates being independent of the overpotential, as evidenced by Eyring analysis. Overall, we demonstrate how ligand design may be utilized to retain good water oxidation activity at low overpotentials.

Prevalence and Patterns of Drug-Resistant Mycobacterium tuberculosis in Newly Diagnosed Patients in China: A Systematic Review and Meta-Analysis.

BACKGROUND: Tuberculosis (TB), one of the deadliest infectious diseases globally, is increasingly exacerbated in China by the emergence of resistant Mycobacterium tuberculosis (MTB) strains. Drug-resistant TB, including mono-drug resistant TB, multidrug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB), presents significant public health challenges. METHODS: We conducted a systematic literature review from January 2010 to February 2024 using databases such as PubMed, Embase, Web of Science, and Google Scholar. Our focus was on empirical data related to drug resistance patterns in newly diagnosed TB cases. Non-empirical studies were excluded through meticulous filtering. For meta-analysis, we used Review Manager (RevMan) 5.2 and assessed evidence quality using the Newcastle-Ottawa Scale (NOS). RESULTS: Our search strategy identified 40 studies that met the inclusion criteria, encompassing a total sample size of 87,667 participants. Among new TB cases, the estimated prevalence of MDR-TB in China was 6.9% (95% CI: 5.6-8.1%). Prevalence rates for mono-drug resistance to first-line anti-TB medications were as follows: isoniazid at 18.2% (95% CI: 16.4-20.6%), rifampicin at 10.5% (95% CI: 8.6-12.8%), and ethambutol at 5.7% (95% CI: 4.1-7.3%). The prevalence of streptomycin resistance, a former first-line anti-TB drug, was 17.1% (95% CI: 14.6-19.1%). The prevalence of other types of mono-drug resistance was 15.2% (95% CI: 13.9-17.3%), and for XDR-TB, it was 0.9% (95% CI: 0.6-1.4%). CONCLUSIONS: The high prevalence of drug-resistant TB in China poses a significant public health challenge. There is an urgent need for targeted interventions and continued surveillance to combat the spread of drug-resistant TB.

Prognosis and diagnosis of prostate cancer based on hypergraph regularization sparse least partial squares regression algorithm.

BACKGROUND: Prostate cancer (PCa) is a malignant tumor of the male reproductive system, and its incidence has increased significantly in recent years. This study aimed to further identify candidate biomarkers with prognostic and diagnostic significance by integrating gene expression and DNA methylation data from PCa patients through association analysis. MATERIAL AND METHODS: To this end, this paper proposes a sparse partial least squares regression algorithm based on hypergraph regularization (HR-SPLS) by integrating and clustering two kinds of data. Next, module 2, with the most significant weight, was selected for further analysis according to the weight of each module related to DNA methylation and mRNAs. Based on the DNA methylation sites in module 2, this paper uses multiple machine learning methods to construct a PCa diagnosis-related model of 10-DNA methylation sites. RESULTS: The results of Receiver Operating Characteristic (ROC) analysis showed that the DNA methylation-related diagnostic model we constructed could diagnose PCa patients with high accuracy. Subsequently, based on the mRNAs in module 2, we constructed a prognostic model for 7-mRNAs (MYH11, ACTG2, DDR2, CDC42EP3, MARCKSL1, LMOD1, and MYLK) using multivariate Cox regression analysis. The prognostic model could predict the disease free survival of PCa patients with moderate to high accuracy (area under the curve (AUC) =0.761). In addition, Gene Set EnrichmentAnalysis (GSEA) and immune analysis indicated that the prognosis of patients in the risk group might be related to immune cell infiltration. CONCLUSIONS: Our findings may provide new methods and insights for identifying disease-related biomarkers by integrating DNA methylation and gene expression data.

Blood-supplementing effect of low molecular weight peptides of E-Jiao on chemotherapy-induced myelosuppression: evaluation of pharmacological activity and identification of bioactive peptides released in vivo.

Background: Equus asinus L. [Equidae; Asini Corri Colla] (donkey-hide gelatin, E-Jiao) is a traditional Chinese medicine renowned for its exceptional blood-supplementing effect. However, the specific components that contribute to its efficacy remain elusive. This study aimed to demonstrate that peptides are responsible for E-Jiao's blood-supplementing effect and to explore the specific peptides contributing to its efficacy. Methods: The low molecular weight peptides of E-Jiao (LMEJ) were obtained using an in vitro digestion method. LMEJ and peptides in the rat bloodstream were characterized by peptidomics analysis. The blood-supplementing effect of LMEJ was assessed using blood-deficient zebrafish and mouse models. The effect of the peptides detected in rat blood was evaluated using the same zebrafish model, and network pharmacology analysis was performed to investigate the underlying mechanisms. Results: A total of 660 unique peptides were identified within LMEJ. Both E-Jiao and LMEJ significantly alleviated myelosuppression in mice but only LMEJ attenuated myelosuppression in zebrafish. After the administration of E-Jiao to rats, 67 E-Jiao-derived peptides were detected in the bloodstream, 41 of which were identical to those identified in LMEJ. Out of these 41 peptides, five were synthesized. Subsequent verification of their effects revealed that two of them were able to alleviate myelosuppression in zebrafish. Network pharmacology study suggested that E-Jiao may exert a blood-supplementing effect by regulating signaling pathways such as JAK-STAT, IL-17 and others. These results indicated that peptides are at least partially responsible for E-Jiao's efficacy. Conclusion: This study provides a crucial foundation for further exploration of the bioactive components of E-Jiao.

Manipulating the tumour immune microenvironment by N6-methyladenosine RNA modification.

N6-methyladenosine (m6A), a posttranscriptional regulatory mechanism, is the most common epigenetic modification in mammalian mRNA. M6A modifications play a crucial role in the developmental network of immune cells. The expression of m6A-related regulators often affects carcinogenesis and tumour suppression networks. In the tumour microenvironment, m6A-modified enzymes can affect the occurrence and progression of tumours by regulating the activation and invasion of tumour-associated immune cells. Immunotherapy, which utilises immune cells, has been demonstrated to be a powerful weapon in tumour treatment and is increasingly being used in the clinic. Here, we provide an updated and comprehensive overview of how m6A modifications affect invasive immune cells and their potential role in immune regulation. In addition, we summarise the regulation of epigenetic regulators associated with m6A modifications in tumour cells on the antitumour response of immune cells in the tumour immune microenvironment. These findings provide new insights into the role of m6A modifications in the immune response and tumour development, leading to the development of novel immunotherapies for cancer treatment.

NinaB and BCO Collaboratively Participate in the ß-Carotene Catabolism in Crustaceans: A Case Study on Chinese Mitten Crab Eriocheir sinensis.

Carotenoid cleavage oxygenases can cleave carotenoids into a range of biologically important products. Carotenoid isomerooxygenase (NinaB) and ß, ß-carotene 15, 15'-monooxygenase (BCO1) are two important oxygenases. In order to understand the roles that both oxygenases exert in crustaceans, we first investigated NinaB-like (EsNinaBl) and BCO1-like (EsBCO1l) within the genome of Chinese mitten crab (Eriocheir sinensis). Their functions were then deciphered through an analysis of their expression patterns, an in vitro ß-carotene degradation assay, and RNA interference. The results showed that both EsNinaBl and EsBCO1l contain an RPE65 domain and exhibit high levels of expression in the hepatopancreas. During the molting stage, EsNinaBl exhibited significant upregulation in stage C, whereas EsBCO1l showed significantly higher expression levels at stage AB. Moreover, dietary supplementation with ß-carotene resulted in a notable increase in the expression of EsNinaBl and EsBCO1l in the hepatopancreas. Further functional assays showed that the EsNinaBl expressed in E. coli underwent significant changes in its color, from orange to light; in addition, its ß-carotene cleavage was higher than that of EsBCO1l. After the knockdown of EsNinaBl or EsBCO1l in juvenile E. sinensis, the expression levels of both genes were significantly decreased in the hepatopancreas, accompanied by a notable increase in the redness (a*) values. Furthermore, a significant increase in the ß-carotene content was observed in the hepatopancreas when EsNinaBl-mRNA was suppressed, which suggests that EsNinaBl plays an important role in carotenoid cleavage, specifically ß-carotene. In conclusion, our findings suggest that EsNinaBl and EsBCO1l may exhibit functional co-expression and play a crucial role in carotenoid cleavage in crabs.

Enhancement of Upconversion Luminescence through Three-Dimensional Design of Plasma Ti3O5-Coupled Structural Domain-Limiting Effects.

Upconversion luminescence plays a crucial role in various technological applications, and among the various valence states of lanthanide elements, Ln3+ has the highest stability. The 4f orbitals of these elements are in a fully empty, semifull, or full state. This special 4f electron configuration allows them to exhibit rich discrete energy levels. However, the 4f-4f transition of Ln3+ rare earth ions itself is prohibited, resulting in a lower luminescence efficiency. This limitation greatly hinders the practical application of upconversion luminescence. In this study, we report nanostructured luminescence-enhanced substrate platforms with both semiconductive local surface plasmons and spatially confined domain effects on a single defect semiconductor substrate. By coupling NaYF4:Yb-Er nanoparticle emitters to the surface of Ti3O5 NC-arrays plasmonic nanostructures, an ultrabright luminescence with a 32-fold increase in green emission and a 40-fold increase in red emission was achieved. Furthermore, the fluorescence resonance energy transfer characteristics observed in the R6G/NaYF4/Ti3O5 NC-array composite film enable accurate detection of fluorescent molecules. The results provide an innovative and intelligent approach to enhance the upconversion luminescence intensity of rare-doped nanoparticles and develop highly sensitive molecular detection systems based on the above luminescence enhancement.

Protective effects of Wenqingyin on sepsis-induced acute lung injury through regulation of the receptor for advanced glycation end products pathway.

BACKGROUND: Wenqingyin (WQY), an ancient Chinese medicinal agent, has been extensively used in treating infectious ailments throughout history. However, the anti-sepsis mechanism remains unknown. PURPOSE: This study investigated the diverse mechanisms of WQY in mitigating sepsis-induced acute lung injury (ALI). Additionally, the effects of WQY were validated using biological experiments. METHODS: This study combined UHPLC-Orbitrap-HRMS analysis and network pharmacology to predict the potential anti-sepsis mechanism of WQY. Sepsis-induced ALI models were established in vivo via intraperitoneal lipopolysaccharide (LPS) administration and in vitro by LPS-stimulated RAW 264.7 macrophages. Various techniques, including hematoxylin-eosin staining, TUNEL, qPCR, and ELISA, were used to assess lung damage and quantify inflammatory cytokines. Inflammatory cell infiltration was visualized through immunohistochemistry. Hub targets and signaling pathways were identified using Western blotting, immunohistochemistry, and immunofluorescence staining. RESULTS: Seventy-five active components and 237 associated targets were acquired, with 145 of these targets overlapping with processes related to sepsis. Based on the comprehensive protein-protein interaction network analysis, JUN, AKT1, TP53, IL-6, HSP90AA1, CASP3, VEGFA, IL-1ß, RELA, and EGFR may be targets of WQY for sepsis. Analysis of the Kyoto Gene and Genome Encyclopedia revealed that WQY is implicated in the advanced glycation end products/receptor for advanced glycation end products (AGE/RAGE) signaling pathway. In vivo, WQY alleviated sepsis-induced ALI, suppressing proinflammatory cytokines and inhibiting macrophage/neutrophil infiltration. In vitro, WQY reduced TNF-α, IL-6, and IL-1ß in LPS-induced RAW 264.7 macrophages. Furthermore, we verified that WQY protected against sepsis-induced ALI by regulating the RAGE pathway for the first time. Baicalin, coptisine, and paeoniflorin may be the effective components of WQY that inhibit RAGE. CONCLUSION: The primary mechanism of WQY in combating sepsis-induced ALI involves controlling RAGE levels and the PI3K/AKT pathway, suppressing inflammation, and mitigating lung damage. This study establishes a scientific foundation for understanding the mechanism of WQY and its clinical use in treating sepsis.

Use of plasma induced modification of biomolecules (PLIMB) to evaluate hemin dissociation from fish and bovine methemoglobins.

Hemin dissociation occurs much faster from fish methemoglobin (metHb) compared to mammalian metHb yet the mechanism remains poorly understood. This may involve enhanced solvent access to His(E7) of fish metHbs by a protonation mechanism. Plasma induced modification of biomolecules (PLIMB) produces free radicals that covalently modify solvent accessible residues of proteins, and so can provide insight regarding accessibility of hydronium ions to protonate His(E7). PLIMB-induced modifications to heme crevice sites of trout IV and bovine metHb were determined using tandem mass spectrometry after generating peptides with Trypsin/Lys-C. αHis(CE3) was more modified in trout attributable to the more dynamic nature of bovine αHis(CE3) from available crystal structures. Although His(E7) was not found to be more modified in trout, aspects of trout peptides containing His(E7) hampered modification determinations. An existing computational structure-based approach was also used to estimate protonation tendencies, suggesting His(E7) of metHbs with low hemin affinity are more protonatable.

Exportin XPO6 upregulation activates the TLR2/MyD88/NF-κB signaling by facilitating TLR2 mRNA nuclear export in COPD pulmonary monocytes.

Chronic obstructive pulmonary disease (COPD) poses a significant health threat characterized by lung inflammation primarily triggered by pulmonary monocytes. Despite the centrality of inflammation in COPD, the regulatory mechanisms governing this response remain elusive, presenting a challenge for anti-inflammatory interventions. In this study, we assessed the expression of exportins in COPD mouse models, revealing a notable upregulation of XPO6 in the mouse lung (P = 0.0011). Intriguingly, we observed a consistent upregulation of XPO6 in pulmonary monocytes from both human and mouse COPD subjects (P < 0.0001). Furthermore, in human lung tissue, XPO6 expression exhibited a positive correlation with TLR2 expression (P = 0). In vitro investigations demonstrated that XPO6 enhances TLR2 expression, activating the MyD88/NF-κB inflammatory signaling pathway. This activation, in turn, promotes the secretion of pro-inflammatory cytokines such as TNFα, IL-6, and IL-1ß in monocytes. Mechanistically, XPO6 facilitates the nuclear export of TLR2 mRNA, ensuring its stability and subsequent protein expression in monocytes. In conclusion, our findings unveil that the upregulation of XPO6 in COPD pulmonary monocytes activates the MyD88/NF-κB inflammatory signaling pathway by facilitating the nuclear export of TLR2 mRNA, thereby identifying XPO6 as a promising therapeutic target for anti-inflammatory interventions in COPD.

Community Assembly Processes of Deadwood Mycobiome in a Tropical Forest Revealed by Long-Read Third-Generation Sequencing.

Despite the importance of wood-inhabiting fungi on nutrient cycling and ecosystem functions, their ecology, especially related to their community assembly, is still highly unexplored. In this study, we analyzed the wood-inhabiting fungal richness, community composition, and phylogenetics using PacBio sequencing. Opposite to what has been expected that deterministic processes especially environmental filtering through wood-physicochemical properties controls the community assembly of wood-inhabiting fungal communities, here we showed that both deterministic and stochastic processes can highly contribute to the community assembly processes of wood-inhabiting fungi in this tropical forest. We demonstrated that the dynamics of stochastic and deterministic processes varied with wood decomposition stages. The initial stage was mainly governed by a deterministic process (homogenous selection), whereas the early and later decomposition stages were governed by the stochastic processes (ecological drift). Deterministic processes were highly contributed by wood physicochemical properties (especially macronutrients and hemicellulose) rather than soil physicochemical factors. We elucidated that fine-scale fungal-fungal interactions, especially the network topology, modularity, and keystone taxa of wood-inhabiting fungal communities, strongly differed in an initial and decomposing deadwood. This current study contributes to a better understanding of the ecological processes of wood-inhabiting fungi in tropical regions where the knowledge of wood-inhabiting fungi is highly limited.

Analytical strategies to identify multicomponent quality markers for commercial Hua-ju-hong using multidimensional chemical analysis.

Hua-ju-hong (HJH) is a Chinese medicinal material obtained from Citrus grandis 'Tomentosa' (CGT) and Citrus grandis (L.) Osbeck (CG) with various commercial specifications. It is known for relieving cough and dispelling phlegm. To reveal the quality marker for distinguishing the various HJH, 215 batches of commercial HJH were studied systematically using multidimensional chemical analysis. Ten major components were identified by high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry and quantified via high-performance liquid chromatography coupled with diode array detection. In this study, a rapid, efficient, and low-cost chromatographic method was established. Total coumarin-hemiterpene and total coumarin-monoterpene were first classified and analyzed in HJH. The result indicated that the main component, naringin, was not the quality marker for differentiating CGT from CG. For reflecting the unique medicinal and food value of HJH, coumarins should be the more potential quality markers. Flavonoids were the possible quality markers for distinguishing two growth stages of fruit-exocarp and young fruit. For the first time, two chemotypes of HJH were identified in CG. This study provides a convenient yet reliant chromatographic method and novel yet systematic strategies for overall quality control of commercial HJH.

Non-linear effects of meteorological factors on COVID-19: An analysis of 440 counties in the americas.

Background: In the last three years, COVID-19 has caused significant harm to both human health and economic stability. Analyzing the causes and mechanisms of COVID-19 has significant theoretical and practical implications for its prevention and mitigation. The role of meteorological factors in the transmission of COVID-19 is crucial, yet their relationship remains a subject of intense debate. Methods: To mitigate the issues arising from short time series, large study units, unrepresentative data and linear research methods in previous studies, this study used counties or districts with populations exceeding 100,000 or 500,000 as the study unit. The commencement of local outbreaks was determined by exceeding 100 cumulative confirmed cases. Pearson correlation analysis, generalized additive model (GAM) and distributed lag nonlinear model (DLNM) were used to analyze the relationship and lag effect between the daily new cases of COVID-19 and meteorological factors (temperature, relative humidity, solar radiation, surface pressure, precipitation, wind speed) across 440 counties or districts in seven countries of the Americas, spanning from January 1, 2020, to December 31, 2021. Results: The linear correlations between daily new cases and meteorological indicators such as air temperature, relative humidity and solar radiation were not significant. However, the non-linear correlations were significant. The turning points in the relationship for temperature, relative humidity and solar radiation were 5 °C and 23 °C, 74 % and 750 kJ/m2, respectively. Conclusion: The influence of meteorological factors on COVID-19 is non-linear. There are two thresholds in the relationship with temperature: 5 °C and 23 °C. Below 5 °C and above 23 °C, there is a positive correlation, while between 5 °C and 23 °C, the correlation is negative. Relative humidity and solar radiation show negative correlations, but there is a change in slope at about 74 % and 750 kJ/m2, respectively.

Salvia miltiorrhiza suppresses cardiomyocyte ferroptosis after myocardial infarction by activating Nrf2 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferroptosis, a recently identified non-apoptotic form of cell death reliant on iron, is distinguished by an escalation in lipid reactive oxygen species (ROS) that are iron-dependent. This phenomenon has a strong correlation with irregularities in iron metabolism and lipid peroxidation. Salvia miltiorrhiza Bunge (DS), a medicinal herb frequently utilized in China, is highly esteemed for its therapeutic effectiveness in enhancing blood circulation and ameliorating blood stasis, particularly during the treatment of cardiovascular diseases (CVDs). Numerous pharmacological studies have identified that DS manifests antioxidative stress effects as well as inhibits lipid peroxidation. However, ambiguity persists regarding the potential of DS to impede ferroptosis in cardiomyocytes and subsequently improve myocardial damage post-myocardial infarction (MI). AIM OF THE STUDY: The present work focused on investigating whether DS could be used to prevent the ferroptosis of cardiomyocytes and improve post-MI myocardial damage. MATERIALS AND METHODS: In vivo experiments: Through ligation of the left anterior descending coronary artery, we constructed both a wild-type (WT) and NF-E2 p45-related factor 2 knockout (Nrf2-/-) mouse model of MI. Effects of DS and ferrostatin-1 (Fer-1) on post-MI cardiomyocyte ferroptosis were examined through detecting ferroptosis and myocardial damage-related indicators as well as Nrf2 signaling-associated protein levels. In vitro experiments: Erastin was used for stimulating H9C2 cardiomyocytes to construct an in vitro ferroptosis cardiomyocyte model. Effects of DS and Fer-1 on cardiomyocyte ferroptosis were determined based on ferroptosis-related indicators and Nrf2 signaling-associated protein levels. Additionally, inhibitor and activator of Nrf2 were used for confirming the impact of Nrf2 signaling on DS's effect on cardiomyocyte ferroptosis. RESULTS: In vivo: In comparison to the model group, DS suppressed ferroptosis in cardiomyocytes post-MI and ameliorated myocardial damage by inducing Nrf2 signaling-related proteins (Nrf2, xCT, GPX4), diminishing tissue ferrous iron and malondialdehyde (MDA) content. Additionally, it enhanced glutathione (GSH) levels and total superoxide dismutase (SOD) activity, effects that are aligned with those of Fer-1. Moreover, the effect of DS on alleviating cardiomyocyte ferroptosis after MI could be partly inhibited through Nrf2 knockdown. In vitro: Compared with the erastin group, DS inhibited cardiomyocyte ferroptosis by promoting the expression of Nrf2 signaling-related proteins, reducing ferrous iron, ROS, and MDA levels, but increasing GSH content and SOD activity, consistent with the effect of Fer-1. Additionally, Nrf2 inhibition increased erastin-mediated ferroptosis of cardiomyocytes through decreasing Nrf2 signaling-related protein expressions. Co-treatment with DS and Nrf2 activator failed to further enhance the anti-ferroptosis effect of DS. CONCLUSION: MI is accompanied by cardiomyocyte ferroptosis, whose underlying mechanism is probably associated with Nrf2 signaling inhibition. DS possibly suppresses ferroptosis of cardiomyocytes and improves myocardial damage after MI through activating Nrf2 signaling.

Development and Improvement of a Piezoelectrically Driven Miniature Robot.

In this paper, we proposed a miniature quadrupedal piezoelectric robot with a mass of 1.8 g and a body length of 4.6 cm. The robot adopts a novel spatial parallel mechanism as its transmission. Each leg of the robot has two degrees of freedom (DOFs): swing and lift. The trajectory necessary for walking is achieved by the appropriate phasing of these two DOFs. A new manufacturing method for piezoelectric actuators was developed. During the stacking process, discrete patterned PZT pieces are used to avoid dielectric failure caused by laser cutting. Copper-clad FR-4 is used as the solder pad instead of copper foil, making the connection between the pad and the actuator more reliable. The lift powertrain of the robot was modeled and the link length of the powertrain was optimized based on the model. The maximum output force of each leg can reach 26 mN under optimized design parameters, which is 1.38 times the required force for successful walking. The frequency response of the powertrain was measured and fitted to the second-order system, which enabled increased leg amplitudes near the powertrain resonance of approximately 70 Hz with adjusted drive signals. The maximum speed of the robot without load reached 48.66 cm/s (10.58 body lengths per second) and the payload capacity can reach 5.5 g (3.05 times its mass) near the powertrain resonance.

Synthesis of 3,4,5-Trisubstituted 1,2,4-Triazoles via I2-Catalyzed Cycloaddition of Amidines with Hydrazones.

A general and practical method for the construction of various 3,4,5-trisubstituted 1,2,4-triazoles via I2-catalyzed cycloaddition of N-functionalized amidines with hydrazones is reported. This strategy features cheap and readily available catalyst and starting materials, broader substrate scope, and moderate-to-good yields. The mechanism study shows that the existence of hydrogen on the nitrogen of hydrazones is crucial for this transformation.

Efficient reduction of vanadium (V) with biochar and experimental parameters optimized by response surface methodology.

Water pollution deteriorates ecosystems and has a great threaten to the environment. The environmental benefits of wastewater treatment are extremely important to minimize pollutants. Here, the biochar purchased from the related industry was used to treat the wastewater which contained high concentration of vanadium (V). The concentration of vanadium was measured by the IC-OES and the results showed that 96.1% vanadium (V) was reduced at selected reaction conditions: the mass ratio of biochar to vanadium of 5.4, reaction temperature of 90 °C, reaction time at 60 min and concentration of H2SO4 of 10 g/L, respectively. Response surface methodology confirmed that all the experimental parameters had positive effect on the reduction of vanadium (V), which could improve the reduction efficiency of vanadium (V) as increased. The influence of each parameter on the reduction process followed the order: A (Concentration of H2SO4) > C (mass ratio of biochar to vanadium) > B (mass ratio of biochar to vanadium). Especially, the mass ratio of biochar to vanadium and concentration of H2SO4 had the greatest influence on the reduction process. This paper provides a versatile strategy for the treatment of wastewater containing vanadium (V) and shows a bright tomorrow for wastewater treatment.

Targeting dysregulated lipid metabolism for the treatment of Alzheimer's disease and Parkinson's disease: Current advancements and future prospects.

Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aß deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.