High-Throughput Metabolite Analysis of Unicellular Microalgae by Orthogonal Hybrid Ionization Label-Free Mass Cytometry.

Microalgae metabolite analysis is fundamental for the rational design of metabolic engineering strategies for the biosynthesis of high-value products. Mass spectrometry (MS) has been utilized for single-cell microalgae analysis. However, limitations in the detection throughput and polarities of detectable substances make it difficult to realize high-throughput screening of high-performance microalgae. Herein, a plasma-assisted label-free mass cytometry, named as PACyESI-MS, was proposed combining the advantages of orthogonal hybrid ionization and high-throughput MS analysis, which realized rapid metabolite detection of single microalgae. The cell detection throughput of PACyESI-MS was up to 52 cells/min. Dozens of the critical primary and secondary metabolites within single microalgae were detected simultaneously, including pigments, lipids, and energy metabolites. Furthermore, metabolite changes of Chlamydomonas reinhardtii and Haematococcus pluvialis under nitrogen deficiency stress were studied. Discrimination of Chlamydomonas under different nutrient conditions was realized using single-cell metabolite profiles obtained by PACyESI-MS. The relationships between the accumulation of bioactive astaxanthin and changes in functional primary metabolites of Haematococcus were investigated. It was demonstrated that PACyESI-MS can detect the flexible change of metabolites in single microalgae cells under different nutritional conditions and during the synthesis of high-value products, which is expected to become an important tool for the design of metabolic engineering-based high-performance microalgae factories.

IGF2 promotes the differentiation of chicken embryonic myoblast by regulating mitochondrial remodeling.

Skeletal muscle is crucial for animal movement and posture maintenance, and it serves as a significant source of meat in the livestock and poultry industry. The number of muscle fibers differentiated from myoblast in the embryonic stage is one of the factors determining the content of skeletal muscle. Insulin-like growth factor 2 (IGF2), a well-known growth-promoting hormone, is crucial for embryonic and skeletal muscle growth and development. However, the specific molecular mechanism underlying its impact on chicken embryonic myoblast differentiation remains unclear. To elucidate the molecular mechanism by which IGF2 regulates chicken myoblast differentiation, we manipulated IGF2 expression in chicken embryonic myoblast. The results demonstrated that IGF2 was upregulated during chicken skeletal muscle development and myoblast differentiation. On the one hand, we found that IGF2 promotes mitochondrial biogenesis through the PGC1/NRF1/TFAM pathway, thereby enhancing mitochondrial membrane potential, oxidative phosphorylation, and ATP synthesis during myoblast differentiation. This process is mediated by the PI3K/AKT pathway. On the other hand, IGF2 regulates BNIP3-mediated mitophagy, clearing dysfunctional mitochondria. Collectively, our findings confirmed that IGF2 cooperatively regulates mitochondrial biogenesis and mitophagy to remodel the mitochondrial network and enhance mitochondrial function, ultimately promoting myoblast differentiation.

Ultrasound assessment of diaphragmatic dysfunction in non-critically ill patients: relevant indicators and update.

Diaphragm dysfunction (DD) can be classified as mild, resulting in diaphragmatic weakness, or severe, resulting in diaphragmatic paralysis. Various factors such as prolonged mechanical ventilation, surgical trauma, and inflammation can cause diaphragmatic injury, leading to negative outcomes for patients, including extended bed rest and increased risk of pulmonary complications. Therefore, it is crucial to protect and monitor diaphragmatic function. Impaired diaphragmatic function directly impacts ventilation, as the diaphragm is the primary muscle involved in inhalation. Even unilateral DD can cause ventilation abnormalities, which in turn lead to impaired gas exchange, this makes weaning from mechanical ventilation challenging and contributes to a higher incidence of ventilator-induced diaphragm dysfunction and prolonged ICU stays. However, there is insufficient research on DD in non-ICU patients, and DD can occur in all phases of the perioperative period. Furthermore, the current literature lacks standardized ultrasound indicators and diagnostic criteria for assessing diaphragmatic dysfunction. As a result, the full potential of diaphragmatic ultrasound parameters in quickly and accurately assessing diaphragmatic function and guiding diagnostic and therapeutic decisions has not been realized.

Determination of multi-residue pesticides in dairy products using single-step emulsification/demulsification clean-up strategy combined with low-pressure gas chromatography-tandem mass spectrometry.

In this study, a simple, sensitive, and rapid method was developed for the simultaneous determination of 99 kinds of pesticides in fatty milk samples. This novel emulsification-demulsification clean-up approach, coupled with an automatic demulsification-dehydration cartridge, allowed rapid single-step clean-up operation and high throughput. It also achieved effective and selective removal of lipids. The analysis was performed using low-pressure gas chromatography-tandem mass spectrometry (LPGC-MS/MS). Based on the optimal conditions, the targeted pesticides showed good linearity in the range of 5-250 µg/kg, with recoveries of 70-120% at spiking levels of 5, 10, and 20 µg/kg in cow milk, goat milk, and almond milk, respectively. The limit of quantification for most pesticides was 5 µg/kg, and the RSDs were lower than 20%. Analysis of real dairy products obtained from local markets revealed a potential risk in plant-derived almond milk, but no significant risks were found for cow and goat milk.

Evaluating the Efficacy of Chinese Patent Medicine Paiteling in Treating Vaginal Stump Disease VaIN: An Analysis of 67 Clinical Cases.

Background: Vaginal Intraepithelial Neoplasia (VaIN) is a prevalent condition that can progress to invasive carcinoma if left untreated. Despite its significance, effective treatments for VaIN remain limited. Objective: This study aimed to analyze the efficacy of Paiteling in treating VaIN among patients who have undergone total hysterectomy due to high cervical lesions or invasive cervical cancer. Design: This study employed a retrospective design. Settings: The study was conducted at Ningxia General Hospital of Medical University from January 2019 to January 2023. Participants: A total of 67 cases diagnosed with VaIN were included in the study. Inclusion criteria comprised patients who had undergone total hysterectomy for high cervical lesions or invasive cervical cancer and had confirmed VaIN diagnosis through abnormal ThinPrep Cytology Test (TCT) and/or High-risk Human Papillomavirus (HR-HPV) results with colposcopy biopsy. Intervention: Patients were treated with Chinese patent medicines Paiteling and patulin according to their specific VaIN classification: VaIN1, VaIN2, and VaIN3. Primary Outcome Measures: The primary outcome measures included complete negative conversion rates for VaIN1, VaIN2, and VaIN3, as well as overall effective rate and complete negative rate across all VaIN cases. Statistical analysis was performed using IBM SPSS 24.0, with significance set at P < .05. Results: Patients with VaIN1, VaIN2, and VaIN3 were treated with Chinese patent medicines Paiteling, and patulin, respectively. Complete negative conversion rates were 100% for VaIN1, 72.73% for VaIN2, and 75.67% for VaIN3, resulting in an overall effective rate of 88.89% and a complete negative rate of 72.22% across all VaIN cases. Conclusion: This study underscores the efficacy of Chinese patent medicine Paiteling in managing post-total hysterectomy VaIN. It presents a conservative treatment option for vaginal stump diseases, addressing a crucial gap in therapeutic strategies. The findings advocate for further exploration of Paiteling's potential in VaIN management.

Efficacy and Safety of Ganyushu Granule in Treatment of Premenstrual Syndrome with Gan (Liver) Depression and Qi Stagnation Syndrome: A Randomized, Double-Blind, Multi-Center, Phase-II Clinical Trial.

OBJECTIVE: To confirm the efficacy and safety of Ganyushu Granule (GYSG) in treating premenstrual syndrome (PMS) in patients with Gan (Liver) depression and qi stagnation syndrome (GDQSS) and determine its effective dosage. METHODS: From June 2018 to March 2021, a total of 240 PMS women with GDQSS were included and randomly divided into 3 groups in a 1:1:1 ratio using central block randomization: high-dose GYSG group (n=78, GYSG 2 packs/time), low-dose GYSG group (n=82, GYSG and its simulant 1 pack/time), and placebo group (n=80, GYSG simulant 2 packs/time). Treatment with GYSG or placebo was given thrice daily and for up to 3 menstrual cycles. Primary outcomes were PMS diary (PMSD) score and premenstrual tension syndrome self-rating scale (PMTS). Secondary outcomes were Chinese medicine (CM) syndrome efficacy. PMSD, PMTS, and efficacy of CM were evaluated with menstrual cycles during the treatment period. Outcome indicators were analyzed after each menstrual cycle. All analyses were performed using an intention-to-treat method, and clinical safety was assessed. RESULTS: Of the 216 patients included in the effectiveness analysis, 70, 75, and 71 patients were in the high-, low-dose GYSG, and placebo groups, respectively. From the 2nd treatment cycle, the change in PMSD scores in the high- and low-dose groups was lower than that in the placebo group (P<0.05). PMTS scores in the high-dose GYSG group after the 1st treatment cycle was lower than that in the placebo group (P<0.05), while after the 3rd treatment cycle, that in the low-dose group was lower than that in the placebo group (P<0.05). After the 2nd treatment cycle, the high-dose GYSG group had the best CM syndrome efficacy (P<0.05). No serious adverse reactions were reported. CONCLUSIONS: GYSG was safe and well-tolerated at both doses for treating PMS patients with GDQSS. High-dose GYSG might be the optimal dose for a phase III trial. (Registration No. ChiCTR1800016595).

Evaluation of the flavor profiles of Yanbian-style sauced beef from differently treated raw beef samples.

In this study, we investigated the volatile flavor compounds and sensory perceptions of Yanbian-style sauced beef prepared from raw meats subjected to different treatments (hot fresh, chilled, and frozen beef). The results indicated that the treatment of raw beef significantly impacted the quality and flavor of sauced beef. Sauced chilled beef (CRSB) exhibited the highest content of fatty acids and total amino acids. A total of 48 volatile compounds were identified. Moreover, a relative odor activity value analysis identified hexanal, nonanal, heptanal, 1-octen-3-ol, and 2,3-octanedione as the characteristic flavor compounds in Yanbian-style sauced beef. The sensory evaluation demonstrated that CRSB was the most palatable and flavorful. Additionally, correlation loading plot analysis indicated strong correlations between sensory evaluation, fatty acids, amino acids, and volatile flavor compounds. These results suggest that chilled beef meat is the best raw material for the production of Yanbian-style sauced beef.

Comparative mitochondrial genomics in Nematoda reveal astonishing variation in compositional biases and substitution rates indicative of multi-level selection.

BACKGROUND: Nematodes are the most abundant and diverse metazoans on Earth, and are known to significantly affect ecosystem functioning. A better understanding of their biology and ecology, including potential adaptations to diverse habitats and lifestyles, is key to understanding their response to global change scenarios. Mitochondrial genomes offer high species level characterization, low cost of sequencing, and an ease of data handling that can provide insights into nematode evolutionary pressures. RESULTS: Generally, nematode mitochondrial genomes exhibited similar structural characteristics (e.g., gene size and GC content), but displayed remarkable variability around these general patterns. Compositional strand biases showed strong codon position specific G skews and relationships with nematode life traits (especially parasitic feeding habits) equal to or greater than with predicted phylogeny. On average, nematode mitochondrial genomes showed low non-synonymous substitution rates, but also high clade specific deviations from these means. Despite the presence of significant mutational saturation, non-synonymous (dN) and synonymous (dS) substitution rates could still be significantly explained by feeding habit and/or habitat. Low ratios of dN:dS rates, particularly associated with the parasitic lifestyles, suggested the presence of strong purifying selection. CONCLUSIONS: Nematode mitochondrial genomes demonstrated a capacity to accumulate diversity in composition, structure, and content while still maintaining functional genes. Moreover, they demonstrated a capacity for rapid evolutionary change pointing to a potential interaction between multi-level selection pressures and rapid evolution. In conclusion, this study helps establish a background for our understanding of the potential evolutionary pressures shaping nematode mitochondrial genomes, while outlining likely routes of future inquiry.

Overview of the current procedures in synthesis of heparin saccharides.

Natural heparin, a glycosaminoglycan consisting of repeating hexuronic acid and glucosamine linked by 1 â†’ 4 glycosidic bonds, is the most widely used anticoagulant. To subvert the dependence on animal sourced heparin, alternative methods to produce heparin saccharides, i.e., either heterogenous sugar chains similar to natural heparin, or structurally defined oligosaccharides, are becoming hot subjects. Although the success by chemical synthesis of the pentasaccharide, fondaparinux, encourages to proceed through a chemical approach generating homogenous product, synthesizing larger oligos is still cumbersome and beyond reach so far. Alternatively, the chemoenzymatic pathway exhibited exquisite stereoselectivity of glycosylation and regioselectivity of modification, with the advantage to skip the tedious protection steps unavoidable in chemical synthesis. However, to a scale of drug production needed today is still not in sight. In comparison, a procedure of de novo biosynthesis in an organism could be an ultimate goal. The main purpose of this review is to summarize the current available/developing strategies and techniques, which is expected to provide a comprehensive picture for production of heparin saccharides to replenish or eventually to replace the animal derived products. In chemical and chemoenzymatic approaches, the methodologies are discussed according to the synthesis procedures: building block preparation, chain elongation, and backbone modification.

Comprehensive performance domain tolerance analysis methodology for freeform imaging spectrometers.

In recent years, attention has been directed towards cost-effective and compact freeform Schwarzschild imaging spectrometers with plane gratings. The utilization of tolerance analysis serves as a potent approach to facilitate the development of prototypes. Conventional tolerance analysis methods often rely solely on the modulation transfer function (MTF) criterion. However, for a spectrometer system, factors such as the keystone/smile distortion and spectral resolution performance also require consideration. In this study, a tailored comprehensive performance domain tolerance analysis methodology for freeform imaging spectrometers was developed, considering vital aspects such as the MTF, keystone/smile distortion, and spectral resolution. Through this approach, meticulous tolerance analysis was conducted for a freeform Schwarzschild imaging spectrometer, providing valuable insights for the prototype machining and assembly processes. Emphasis was placed on the necessity of precise control over the tilt and decenter between the first and third mirrors, whereas the other fabrication and assembly tolerances adhered to the standard requirements. Finally, an alignment computer-generated hologram (CGH) was employed for the preassembly of the first and third mirrors, enabling successful prototype development. The congruence observed between the measured results and tolerance analysis outcomes demonstrates the effectiveness of the proposed method.

Exploring the use of metabarcoding to reveal eukaryotic associations with mononchids nematodes.

Nematodes play a vital ecological role in soil and marine ecosystems, but there is limited information about their dietary diversity and feeding habits. Due to methodological challenges, the available information is based on inference rather than confirmed observations. The lack of correct dietary requirements also hampers rearing experiments. To achieve insight into the prey of mononchid nematodes, this study employed high-throughput Illumina paired-end sequencing using universal eukaryotic species 18S primers on 10 pooled mononchid nematode species, namely Mylonchulus brachyuris, M. brevicaudatus, Mylonchulus sp., Clarkus parvus, Prionchulus sp. M. hawaiiensis, M. sigmaturellus, M. vulvapapillatus, Anatonchus sp. and Miconchus sp. The results indicate that mononchids are associated with a remarkable diversity of eukaryotes, including fungi, algae, and protists. While the metabarcoding approach, first introduced here for mononchids, proved to be a simple and rapid method, it has several limitations and crucial methodological challenges that should be addressed in future studies. Ultimately, such methods should be able to evaluate the dietary complexity of nematodes and provide a valuable avenue for unraveling the dietary requirements of previously unculturable nematodes. This can contribute to the methodology of understanding their feeding habits and contributions to ecosystem dynamics.

Development and characterization of a novel specific monoclonal antibody against mink enteritis virus and its antigen epitope analysis.

This study prepared a novel monoclonal antibody (MAb) against mink enteritis parvovirus (MEV) and identified its antigen epitope. The antibody subclass is identified as IgG1, the titers of the MAb is up to 1:1 × 106 and keeps stably after low-temperature storage for 9 months or 11 passages of the MAb cells. The MAb can specifically recognize MEV in the cells in IFA, but not Aleutian disease virus (ADV) or canine distemper virus (CDV). Its antigen epitope was identified as a polypeptide containing 5 key amino acids (378YAFGR382) and the homology in 20 MEV strains, 4 canine parvovirus strains, and 4 feline panleukopenia virus strains was 100%. This study supplies a biological material for developing new methods to detect MEV.

[Evaluation of efficacy of Dihuang Baoyuan Granules for diabetes mellitus and composition and in vivo distribution analysis based on UHPLC-LTQ-Orbitrap MS].

Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 µm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.

Discovery of novel biphenyl derivatives as androgen receptor degraders for the treatment of enzalutamide-resistant prostate cancer.

Second-generation AR antagonists, such as enzalutamide, are the primary therapeutic agents for advanced prostate cancer. However, the development of both primary and secondary drug resistance leads to treatment failures and patient mortality. Bifunctional agents that simultaneously antagonize and degrade AR block the AR signaling pathway more completely and exhibit excellent antiproliferative activity against wild-type and drug-resistant prostate cancer cells. Here, we reported the discovery and optimization of a series of biphenyl derivatives as androgen receptor antagonists and degraders. These biphenyl derivatives exhibited potent antiproliferative activity against LNCaP and 22Rv1 cells. Our discoveries enrich the diversity of small molecule AR degraders and offer insights for the development of novel AR degraders for the treatment of enzalutamide-resistant prostate cancer.

Efficacy of post-surgery family-based participatory cluster pain care in children with developmental dislocation of hip.

BACKGROUND: Developmental dislocation of the hip (DDH) is a common congenital deformity of the skeletal system in children. OBJECTIVE: To investigate the efficacy of post-surgery cluster nursing in children with DDH. METHODS: A total of 60 children with DDH who underwent hip joint orthopedic surgery in our hospital from September 2021 to September 2022 were enrolled as the research participants in this prospective study, and divided into the control group and the observation group according to the numerical table method, with 30 patients in each group. The control group was given routine pain care, and the observation group was given cluster pain care. The hip joint function scores, pain scores, self-rating anxiety score (SAS) were compared between the two groups and between before intervention and after intervention in the two groups. RESULTS: The pain score of the children and the SAS of the primary caregivers after the intervention in the observation group were lower than those in the control group (P< 0.05), and the hip joint function score and family satisfaction degree were higher than those in the control group (P< 0.05). CONCLUSION: Family-based cluster pain care can reduce pain in children with DDH after surgery, promote hip joint functional recovery, reduce the negative emotions of caregivers, and improve family satisfaction, and has clinical popularization value.

Real-world experience of Fuzheng Yiqing granule as chemoprophylaxis against COVID-19 infection among close contacts: A prospective cohort study.

BACKGROUND: The objective of the current study was to evaluate whether the use of traditional Chinese medicine, Fuzheng Yiqing granule (FZYQG), was associated with a reduced infection risk of COVID-19 in close contacts. RESEARCH DESIGN AND METHODS: This was a prospective cohort study across 203 quarantine centres for close contacts and secondary contacts of COVID-19 patients in Yangzhou city. FZYQG group was defined as quarantined individuals who voluntarily took FZYQG; control group did not take FZYQG. The primary outcome was the coronavirus test positive rate during quarantine period. Logistic regression with propensity score inverse probability weighting was used for adjusted analysis to evaluate independent association between FZYQG and test positive rate. RESULTS: From July 13, 2021 to September 30, 2021, 3438 quarantined individuals took FZYQG and 2248 refused to take the granule. Test positive rate was significantly lower among quarantined individuals who took FZYQG (0.29% vs. 1.73%, risk ratio 0.17, 95% confidence interval (CI): 0.08-0.34, p < 0.001). On logistic regression, odds for test positive were decreased in FZYQG group (odds ratio: 0.16, 95% CI: 0.08-0.32, p < 0.001). CONCLUSIONS: Close and secondary contacts of COVID-19 patients who received FZYQG had a lower test positive rate than control individuals in real-world experience. TRIAL REGISTRATION: This study has been registered on Chinese Clinical Trial Registry (ChiCTR2100049590) on August 5, 2021.

Environmentally relevant concentrations of benzophenones exposure disrupt intestinal homeostasis, impair the intestinal barrier, and induce inflammation in mice.

The aim of this study is to investigate the adverse effects of benzophenones (BPs) on the intestinal tract of mice and the potential mechanism. F1-generation ICR mice were exposed to BPs (benzophenone-1, benzophenone-2, and benzophenone-3) by breastfeeding from birth until weaning, and by drinking water after weaning until maturity. The offspring mice were executed on postnatal day 56, then their distal colons were sampled. AB-PAS staining, HE staining, immunofluorescence, Transmission Electron Microscope, immunohistochemistry, Western Blot and RT-qPCR were used to study the effects of BPs exposure on the colonic tissues of offspring mice. The results showed that colonic microvilli appeared significantly deficient in the high-dose group, and the expression of tight junction markers Zo-1 and Occludin was significantly down-regulated and the number of goblet cells and secretions were reduced in all dose groups, and the expression of secretory cell markers MUC2 and KI67 were decreased, as well as the expression of intestinal stem cell markers Lgr5 and Bmi1, suggesting that BPs exposure caused disruption of intestinal barrier and imbalance in the composition of the intestinal stem cell pool. Besides, the expression of cellular inflammatory factors such as macrophage marker F4/80 and tumor necrosis factor TNF-α was elevated in the colonic tissues of all dose groups, and the inflammatory infiltration was observed, which means the exposure of BPs caused inflammatory effects in the intestinal tract of F1-generation mice. In addition, the contents of Notch/Wnt signaling pathway-related genes, such as Dll-4, Notch1, Hes1, Ctnnb1and Sfrp2 were significantly decreased in each high-dose group (P < 0.05), suggesting that BPs may inhibit the regulation of Notch/Wnt signaling pathway. In conclusion, exposure to BPs was able to imbalance colonic homeostasis, disrupt the intestinal barrier, and trigger inflammation in the offspring mice, which might be realized through interfering with the Notch/Wnt signaling pathway.

ENDOGENOUS ß 3 -ADRENERGIC RECEPTOR ACTIVATION ALLEVIATES SEPSIS-INDUCED CARDIOMYOCYTE APOPTOSIS VIA PI3K/AKT SIGNALING PATHWAY.

ABSTRACT: ß 3 -adrenergic receptor (ß 3 -AR) has been proposed as a new therapy for several myocardial diseases. However, the effect of ß 3 -AR activation on sepsis-induced myocardial apoptosis is unclear. Here, we investigated the effect of ß 3 -AR activation on the cardiomyocyte apoptosis and cardiac dysfunction in cecal ligation and puncture (CLP)-operated rats and lipopolysaccharide (LPS)-treated cardiomyocytes. We found that ß 3 -AR existed both in adult rat ventricular myocytes (ARVMs) and H9c2 cells. The expression of ß 3 -AR was upregulated in LPS-treated ARVMs and the heart of CLP rats. Pretreatment with ß 3 -AR agonist, BRL37344, inhibited LPS-induced cardiomyocyte apoptosis and caspase-3, -8, and -9 activation in ARVMs. BRL37344 also reduced apoptosis and increased the protein levels of PI3K, p-Akt Ser473 and p-eNOS Ser1177 in LPS-treated H9c2 cells. Inhibition of PI3K using LY294002 abolished the inhibitory effect of BRL37344 on LPS-induced caspase-3, -8, and -9 activation in H9c2 cells. Furthermore, administration of ß 3 -AR antagonist, SR59230A (5 mg/kg), significantly decreased the maximum rate of left ventricular pressure rise (+dP/dt) in CLP-induced septic rats. SR59230A not only increased myocardial apoptosis, reduced p-Akt Ser473 and Bcl-2 contents, but also increased mitochondrial Bax, cytoplasm cytochrome c, cleaved caspase-9, and cleaved caspase-3 levels of the myocardium in septic rats. These results suggest that endogenous ß 3 -AR activation alleviates sepsis-induced cardiomyocyte apoptosis via PI3K/Akt signaling pathway and maintains intrinsic myocardial systolic function in sepsis.

Hydrolysis of Beef Sarcoplasmic Protein by Dry-Aged Beef-Isolated Penicillium oxalicum and Its Associated Metabolic Pathways.

Yanbian cattle have a unique meat flavor, and high-grade meat is in short supply. Therefore, in this study, we aimed to improve the added value of Yanbian cattle low-fat meat and provide a theoretical reference for the subsequent development of an excellent starter. Rump meat from Yanbian cattle was dry-aged and then screened for protease-producing fungi. Three protease-producing fungi (Yarrowia hollandica (D4 and D11), Penicillium oxalicum (D5), and Meesziomyces ophidis (D20)) were isolated from 40 d dry-aged beef samples, and their ability to hydrolyze proteins was determined using bovine sarcoplasmic protein extract. SDS-PAGE showed that the ability of Penicillium oxalicum (D5) to degrade proteins was stronger than the other two fungi. In addition, the volatile component content of sarcoplasmic proteins in the D5 group was the highest (45.47%) and comprised the most species (26 types). Metabolic pathway analysis of the fermentation broth showed that phenylalanine, tyrosine, and tryptophan biosynthesis was the most closely related metabolic pathway in sarcoplasmic protein fermentation by Penicillium oxalicum (D5). Dry-aged beef-isolated Penicillium oxalicum serves as a potential starter culture for the fermentation of meat products.

Coupling Nano and Atomic Electric Field Confinement for Robust Alkaline Oxygen Evolution.

The alkaline oxygen evolution reaction (OER) is a promising avenue for producing clean fuels and storing intermittent energy. However, challenges such as excessive OH- consumption and strong adsorption of oxygen-containing intermediates hinder the development of alkaline OER. In this study, we propose a cooperative strategy by leveraging both nano-scale and atomically local electric fields for alkaline OER, demonstrated through the synthesis of Mn single atom doped CoP nanoneedles (Mn SA-CoP NNs). Finite element method simulations and density functional theory calculations predict that the nano-scale local electric field enriches OH- around the catalyst surface, while the atomically local electric field improves *O desorption. Experimental validation using in situ attenuated total reflection infrared and Raman spectroscopy confirms the effectiveness of the nano-scale and atomically electric fields. Mn SA-CoP NNs exhibit an ultra-low overpotential of 189 mV at 10 mA cm-2 and stable operation over 100 hours at ~100 mA cm-2 during alkaline OER. This innovative strategy provides new insights for enhancing catalyst performance in energy conversion reactions.