Pyruvate kinase M2 sustains cardiac mitochondrial quality surveillance in septic cardiomyopathy by regulating prohibitin 2 abundance via S91 phosphorylation.

The endogenous mitochondrial quality control (MQC) system serves to protect mitochondria against cellular stressors. Although mitochondrial dysfunction contributes to cardiac damage during many pathological conditions, the regulatory signals influencing MQC disruption during septic cardiomyopathy (SC) remain unclear. This study aimed to investigate the involvement of pyruvate kinase M2 (PKM2) and prohibitin 2 (PHB2) interaction followed by MQC impairment in the pathogenesis of SC. We utilized LPS-induced SC models in PKM2 transgenic (PKM2TG) mice, PHB2S91D-knockin mice, and PKM2-overexpressing HL-1 cardiomyocytes. After LPS-induced SC, cardiac PKM2 expression was significantly downregulated in wild-type mice, whereas PKM2 overexpression in vivo sustained heart function, suppressed myocardial inflammation, and attenuated cardiomyocyte death. PKM2 overexpression relieved sepsis-related mitochondrial damage via MQC normalization, evidenced by balanced mitochondrial fission/fusion, activated mitophagy, restored mitochondrial biogenesis, and inhibited mitochondrial unfolded protein response. Docking simulations, co-IP, and domain deletion mutant protein transfection experiments showed that PKM2 phosphorylates PHB2 at Ser91, preventing LPS-mediated PHB2 degradation. Additionally, the A domain of PKM2 and the PHB domain of PHB2 are required for PKM2-PHB2 binding and PHB2 phosphorylation. After LPS exposure, expression of a phosphorylation-defective PHB2S91A mutant negated the protective effects of PKM2 overexpression. Moreover, knockin mice expressing a phosphorylation-mimetic PHB2S91D mutant showed improved heart function, reduced inflammation, and preserved mitochondrial function following sepsis induction. Abundant PKM2 expression is a prerequisite to sustain PKM2-PHB2 interaction which is a key element for preservation of PHB2 phosphorylation and MQC, presenting novel interventive targets for the treatment of septic cardiomyopathy.

A broadband multi-frequency microwave combined biological exposure setup.

With the rapid popularization of wireless electronic devices, there has been an increasing concern about the impacts of the electromagnetic environment on health. However, most research reports on the biological effects of microwaves have focused on a single frequency point. In reality, people are exposed to complex electromagnetic environments that consist of multiple frequency microwave signals in their daily lives. It is important to investigate whether multi-frequency combined microwave energies have different biological effects compared with single frequency microwave energy. Unfortunately, there are limited reports on this topic due to the lack of suitable platforms for research on multi-frequency microwave energy combined with biological exposure. To address this issue, this study presents a setup that has a very wide working frequency bandwidth and can be compatible with single frequency and multi-frequency microwave combined exposure. Moreover, it can achieve relatively equal exposure to multiple biological samples at any frequency point in the working frequency range, which is crucial for electromagnetic biology research. The experimental results are in good agreement with the simulation results, confirming its capability to facilitate the study of complex electromagnetic environment effects on organisms.

The endocannabinoid system is involved in the anxiety-like behavior induced by dual-frequency 2.65/0.8 GHz electromagnetic radiation in mice.

As wireless communication devices gain popularity, concerns about the potential risks of environmental exposure to complex frequency electromagnetic radiation (EMR) on mental health have become a public health issue. Historically, EMR research has predominantly focused on single- frequency electromagnetic waves, neglecting the study of multi-frequency electromagnetic waves, which more accurately represent everyday life. To address these concerns, our study compared the emotional effects of single-frequency and dual-frequency EMR while exploring potential molecular mechanisms and intervention targets. Our results revealed that single-frequency EMR at 2.65 or 0.8 GHz did not induce anxiety-like behavior in mice. However, exposure to dual-frequency EMR at 2.65/0.8 GHz significantly led to anxiety-like behavior in mice. Further analysis of mouse sera revealed substantial increases in corticosterone and corticotrophin releasing hormone levels following exposure to 2.65/0.8 GHz EMR. Transcriptome sequencing indicated a significant decrease in the expression of Cnr1, encoding cannabinoid receptor 1 Type (CB1R), in the cerebral. This finding was consistently verified through western blot analysis, revealing a substantial reduction in CB1R content. Additionally, a significant decrease in the endocannabinoid 2-arachidonoylglycerol was observed in the cerebral cortex. Remarkably, administering the cannabinoid receptor agonist Win55-212-2 significantly alleviated the anxiety-like behavior, and the cannabinoid receptor antagonist AM251 effectively counteracted the anti-anxiety effects of Win55-212-2. In summary, our research confirmed that dual-frequency EMR is more likely to induce anxiety-like behavior in mice than single-frequency EMR, with implications for the hypothalamic-pituitary-adrenal axis and the endocannabinoid system. Furthermore, our findings suggest that Win55-212-2 may represent a novel avenue for researching and developing anti-EMR drugs.

Nuclear Receptor FTZ-F1 Controls Locust Molt by Regulating the Molting Process of Locusta migratoria.

Fushi-tarazu factor 1 (FTZ-F1) is a class of transcription factors belonging to the nuclear receptor superfamily and an important molting regulator in insects; however, its detailed function in the molting process of Locusta migratoria is still unclear. This study identified two FTZ-F1 transcripts (LmFTZ-F1-X1 and LmFTZ-F1-X2) in L. migratoria. The classical domains of FTZ-F1 were present in their protein sequences and distinguished based on their variable N-terminal domains. Reverse-transcription quantitative polymerase chain reaction analysis revealed that LmFTZ-F1-X1 and LmFTZ-F1-X2 were highly expressed in the integument. RNA interference (RNAi) was used to explore the function of LmFTZ-F1s in the molting of the third-instar nymph. Separate LmFTZ-F1-X1 or LmFTZ-F1-X2 silencing did not affect the normal development of third-instar nymphs; however, the simultaneous RNAi of LmFTZ-F1-X1 and LmFTZ-F1-X2 caused the nymphs to be trapped in the third instar stage and finally die. Furthermore, the hematoxylin-eosin and chitin staining of the cuticle showed that the new cuticles were thickened after silencing the LmFTZ-F1s compared to the controls. RNA-seq analysis showed that genes encoding four cuticle proteins, two chitin synthesis enzymes, and cytochrome P450 303a1 were differentially expressed between dsGFP- and dsLmFTZ-F1s-injected groups. Taken together, LmFTZ-F1-X1 and LmFTZ-F1-X2 are involved in the ecdysis of locusts, possibly by regulating the expression of genes involved in cuticle formation, chitin synthesis, and other key molting processes.

Ano1 regulates embryo transport by modulating intracellular calcium levels in oviduct smooth muscle.

Oviductal smooth muscle exhibits spontaneous rhythmic contraction (SRC) and controls the passage of the ova at the exact time, but its mechanistic regulation remains to be determined. In this study, female mice with Ano1SMKO (smooth muscle-specific deletion of Ano1) had reduced fertility. Deficiency of Ano1 in mice resulted in impaired oviductal SRC function and reduced calcium signaling in individual smooth muscle cells in the oviduct. The Ano1 antagonist T16Ainh-A01 dose-dependently inhibited SRCs and [Ca2+]i in the oviducts of humans and mice. A similar inhibitory effect of SRCs and [Ca2+]i was observed after treatment with nifedipine. In our study, ANO1 acted primarily as an activator or amplifier in [Ca2+]i and contraction of tubal smooth muscle cells. We found that tubal SRC was markedly attenuated in patients with ectopic pregnancy. Then, our study was designed to determine whether chloride channel Ano1-mediated smooth muscle motility is associated with tubal SRC. Our findings reveal a new mechanism for the regulation of tubal motility that may be associated with abnormal pregnancies such as ectopic pregnancies.

Cholesterol-Mediated Anchoring of Phospholipids onto Proteinosomes for Switching Membrane Permeability.

Modulated membrane functionalization is a necessary and overarching step for hollow microcompartments toward their application as nanoreactors or artificial cells. In this study, we show a way to generate phospholipid hybrid proteinosomes that could show superposed virtues of liposomes and proteinosomes. In comparison to pure proteinosomes, both the membrane fluidity and permeability are improved obviously after forming the phospholipid hybrid proteinosomes. Specifically, the integration of phospholipids also endows the hybrid proteinosomes demonstrating a stepwise release of the encapsulants of FITC-dextran (70 and 150 kDa) triggered sequentially by phospholipase and protease, and then a modulated cascaded enzymatic reaction between two different populations of proteinosomes are achieved. Therefore, it is anticipated that such constructed phospholipid hybrid proteinosomes could be employed as an improved microcompartmental model for further advanced artificial cell design toward achieving logic signal communication within the various artificial cellular populations as well as potential applications in the field of microreactors.

Mitoguardin 1 and 2 promote granulosa cell proliferation by activating AKT and regulating the Hippo-YAP1 signaling pathway.

Mitochondria have been identified to be involved in oxidative phosphorylation, lipid metabolism, cell death, and cell proliferation. Previous studies have demonstrated that mitoguardin (Miga), a mitochondrial protein that governs mitochondrial fusion, mitochondria-endoplasmic reticulum (ER) contacts, lipid formation, and autophagy, is crucial for ovarian endocrine and follicular development. Nevertheless, whether mammalian MIGA1 or MIGA2 (MIGA1,-2) regulates ovarian granulosa cell proliferation remains unclear. This study revealed that mammalian MIGA1,-2 promotes cell proliferation and regulates the phosphorylation and localization of Yes-associated protein 1 (YAP1) in ovarian granulosa cells. MIGA2 upregulation resulted in reduced YAP1 activity, while MIGA2 removal led to increased YAP1 activity. Further analysis indicated that MIGA1,-2 regulated YAP1 via the Hippo signaling pathway and regulated protein kinase B (AKT) activity in collaboration with YAP1. In addition, lysophosphatidic acid (LPA) regulated MIGA2 expression and AKT activity by activating YAP1. Briefly, we demonstrated that the mitochondrial MIGA1 and MIGA2, especially MIGA2, promoted cellular proliferation by activating AKT and regulating the Hippo/YAP1 signaling pathway in ovarian granulosa cells, which may contribute to the molecular pathogenesis of reproductive endocrine diseases, such as polycystic ovary syndrome (PCOS).

Comparative Efficacy and Safety of Neoadjuvant Immunotherapy with Chemotherapy versus Chemotherapy Alone in Non-Small Cell Lung Cancer: A Propensity Score and Inverse Probability Treatment Weighting Analysis.

Purpose: This study aimed to compare the efficacy and safety of neoadjuvant chemotherapy (NCT) and neoadjuvant immunotherapy combined with chemotherapy (NICT) combined with radical lung cancer resection for the treatment of patients with resectable non-small cell lung cancer (NSCLC). To adjust for confounding factors, we innovatively adopted two matching methods: propensity score (PS) and inverse probability of treatment weighting (IPTW). Patients and Methods: We conducted a retrospective analysis of the clinicopathological features and prognosis of patients with resectable NSCLC treated with NCT or NICT combined with radical lung cancer resection using propensity score matching (PSM) at a ratio of 1:1 and IPTW to balance potential bias. Results: After PSM, 116 pairs of patients who had undergone NCT or NICT were selected for the final analysis. The pathological complete remission (pCR) and major pathological remission (MPR) rates were significantly better in the NICT group than in the NCT group (pCR rate of 44.8% vs 2.6%, P< 0.001; MPR rate of 66.4% vs 20.7%, P< 0.001). No significant difference was seen between the NICT and NCT groups in terms of postoperative complications (12.1% vs 9.5%, P=0.182). Patients in the NICT group had significantly better disease-free survival (DFS) and overall survival(OS) than those in the NCT group ([3-year DFS: 75.2% vs 43.3%, P< 0.001] and [3-year OS: 91.5% vs 58.0%, P< 0.001]). Among all patients, those with postoperative pathology of pCR had better DFS (P< 0.001) and OS (P= 0.009). Patients with postoperative pathology of MPR had better DFS (P< 0.001) and OS (P< 0.001). The IPTW method yielded similar pathologic and prognostic results. Conclusion: Patients with resectable NSCLC treated with NICT had better pathological responses and prognosis, than those treated with NCT, and the safety profiles of NICT and NCT were similar.

Highly Hydrophobic Gelatin Nanocomposite Film Assisted by Nano-ZnO/(3-Aminopropyl) Triethoxysilane/Stearic Acid Coating for Liquid Food Packaging.

Biodegradable gelatin (G) food packaging films are in increasing demand as the substitution of petroleum-based preservative materials. However, G packaging films universally suffer from weak hydrophobicity in practical applications. Constructing a hydrophobic micro/nanocoating with low surface energy is an effective countermeasure. However, the poor compatibility with the hydrophilic G substrate often leads to the weak interfacial adhesion and poor durability of the hydrophobic coating. To overcome this obstacle, we used (3-aminopropyl) triethoxysilane (APS) as an interfacial bridging agent to prepare a highly hydrophobic, versatile G nanocomposite film. Specifically, tannic acid (TA)-modified nanohydroxyapatite (n-HA) particles (THA) were introduced in G matrix (G-THA) to improve the mechanical properties. Micro/nanostructure with low surface energy composed of nanozinc oxide (Nano-ZnO)/APS/stearic acid (SA) (NAS) was constructed on the surface of G-THA film (G-THA/NAS) through one-step spray treatment. Consequently, as-prepared G-THA/NAS film presented excellent mechanics (tensile strength: 7.6 MPa, elongation at break: 292.7%), water resistance ability (water contact angle: 150.4°), high UV-shielding (0% transmittance at 200 nm), degradability (100% degradation rate after buried in the natural soil for 15 days), antioxidant (78.8% of 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity), and antimicrobial (inhibition zone against Escherichia coli: 15.0 mm and Staphylococcus aureus: 16.5 mm) properties. It should be emphasized that the bridging function of APS significantly improves the interfacial adhesion ability of the NAS coating with more than 95% remaining area after the cross-cut adhesion test. Meanwhile, the G-THA/NAS film could maintain stable and long-lasting hydrophobic surfaces against UV radiation, high temperature, and abrasion. Based on these multifunctional properties, the G-THA/NAS film was successfully applied as a liquid packaging material. To sum up, we provide a feasible and effective method to prepare high-performance green packaging films.

High-fructose corn syrup aggravates colitis via microbiota dysbiosis-mediated Th17/Treg imbalance.

Dietary fructose is widely used in beverages, processed foods, and Western diets as food additives, and is closely related to the increased prevalence of multiple diseases, including inflammatory bowel disease (IBD). However, the detailed mechanism by which high fructose disrupts intestinal homeostasis remains elusive. The present study showed that high-fructose corn syrup (HFCS) administration exacerbated intestinal inflammation and deteriorated barrier integrity. Several in vivo experimental models were utilized to verify the importance of gut microbiota and immune cells in HFCS-mediated dextran sulfate sodium (DSS)-induced colitis. In addition, untargeted metabolomics analysis revealed the imbalance between primary bile acids (PBAs) and secondary bile acids (SBAs) in feces. Hence, high fructose was speculated to modulate gut microbiota community and reduced the relative abundance of Clostridium and Clostridium scindens at genus and species level respectively, followed by a decrease in SBAs, especially isoalloLCA, thereby affecting Th17/Treg cells equilibrium and promoting intestinal inflammation. These findings provide novel insights into the crosstalk between gut flora, bile acids, and mucosal immunity, and highlight potential strategies for precise treatment of IBD.

Magnesium accelerates changes in the fruit ripening and carotenoid accumulation in Satsuma Mandarin pulp.

This study aims to further examine the effect of Magnesium (Mg) application on fruit quality and carotenoid metabolism in Satsuma mandarin pulp. For this, a field experiment was using 20-year-old Satsuma mandarin (C. unshiu Marc.) for two treatment; (1) CK treatment (without Mg), (2) Mg fertilizer treatment (200 g MgO plant-1). Compared with CK, Mg treatment substantially raised the Mg content in pulp at 90 to 150 DAF (the fruit expansion period), increasing by 15.69%-21.74%. Mg treatment also increased fruit TSS content by 15.84% and 9.88%, decreased fruit TA content in by 34.25% and 33.26% at 195 DAF and 210 DAF (the fruit ripening period). Moreover, at 120 to 195 DAF, Mg treatment significantly increased the levels of lutein, ß-cryptoxanthin, zeaxanthin and violaxanthin in the pulp. This can be explained by the increased expression of important biosynthetic genes, including CitPSY, CitPDS, CitLCYb1, CitLCYb2, CitLCYe, CitHYb, and CitZEP, that played a role in altering the carotenoid composition. The findings of this research offer a novel approach for augmenting both the economic and nutritional worth of citrus fruits.

Catalytic metal-nucleotide coordinative cytoskeleton on algae cell towards photosynthetic hydrogen production under air.

A metal-nucleotide coordinative cytoskeleton with ascorbate oxidase-like catalytic behavior was constructed on an individual algae cell wall, which endows the engineered cells with the capability of self-generating a localized hypoxic microenvironment around the cell surface, and thus allows the functionality switching from photosynthetic oxygen production to efficient hydrogen evolution for over one month.

Construction of spidroin coacervate microdroplets and regulation of their morphology.

In recent years, developing artificial cells of higher complexity has emerged as being key to simulating advanced life behaviors, among which coacervate microdroplets are a promising kind of model artificial cell. Constructing simple coacervate systems in vitro which can subsequently achieve specific responses to environmental stimuli to form coacervate microdroplet communities are fundamental for studying the interactions between liquid-liquid phase separated molecules and the way such interactions determine material properties, composition and phase behavior. Herein, we propose a membrane-free artificial cell based on recombinant spidroin, NT2RepCT, which utilizes the complex structure of spidroin to provide coacervate microdroplets with a unique population morphology in response to environmental stimuli. By changing the environmental conditions such as protein concentration, pH and temperature, the coacervate microdroplets of single-type, regular adhesion-type and irregular adhesion-type were statistically generalized, and it is highlighted that the adhesion-type of coacervate microdroplets depended on the α-helical percentage, complex folding degree of spidroin and internally hydrophobic environment of the coacervate, while it was inversely proportional to the surface hydrophobic environment. Much more interesting, regulation of the non-enzymatic polymerization reaction of oligonucleotides was successfully achieved by adjusting the population morphology of coacervate microdroplets.

Tyrosine residues initiated photopolymerization in living organisms.

Towards intracellular engineering of living organisms, the development of new biocompatible polymerization system applicable for an intrinsically non-natural macromolecules synthesis for modulating living organism function/behavior is a key step. Herein, we find that the tyrosine residues in the cofactor-free proteins can be employed to mediate controlled radical polymerization under 405 nm light. A proton-coupled electron transfer (PCET) mechanism between the excited-state TyrOH* residue in proteins and the monomer or the chain transfer agent is confirmed. By using Tyr-containing proteins, a wide range of well-defined polymers are successfully generated. Especially, the developed photopolymerization system shows good biocompatibility, which can achieve in-situ extracellular polymerization from the surface of yeast cells for agglutination/anti-agglutination functional manipulation or intracellular polymerization inside yeast cells, respectively. Besides providing a universal aqueous photopolymerization system, this study should contribute a new way to generate various non-natural polymers in vitro or in vivo to engineer living organism functions and behaviours.

Photosynthesis-Mediated Intracellular Biomineralization of Gold Nanoparticles inside Chlorella Cells towards Hydrogen Boosting under Green Light.

Engineering living microorganisms to enhance green biomanufacturing for the development of sustainable and carbon-neutral energy strategies has attracted the interest of researchers from a wide range of scientific communities. In this study, we develop a method to achieve photosynthesis-mediated biomineralization of gold nanoparticles (AuNPs) inside Chlorella cells, where the photosynthesis-dominated reduction of Au3+ to Au0 allows the formed AuNPs to locate preferentially around the thylakoid membrane domain. In particular, we reveal that the electrons generated by the localized surface plasmon resonance of AuNPs could greatly augment hypoxic photosynthesis, which then promotes the generation and transferring of photoelectrons throughout the photosynthetic chain for augmented hydrogen production under sunlight. We demonstrate that the electrons from AuNPs could be directly transferred to hydrogenase, giving rise to an 8.3-fold enhancement of Chlorella cells hydrogen production independent of the cellular photosynthetic process under monochromatic 560 nm light irradiation. Overall, the photosynthesis-mediated intracellular biomineralization of AuNPs could contribute to a novel paradigm for functionalizing Chlorella cells to augment biomanufacturing.

Interaction between dual specificity phosphatase-1 and cullin-1 attenuates alcohol-related liver disease by restoring p62-mediated mitophagy.

Besides abstinence, no effective treatment exists for alcohol-related liver disease (ALD), a dreaded consequence of alcohol abuse. In this study, we assessed the roles on ALD of dual specificity phosphatase-1 (DUSP1), an hepatoprotective enzyme, and Cullin-1 (CUL1), a member of the E3 ubiquitin ligase complex that exerts also transcriptional suppression of mitochondrial genes. Alcohol treatment downregulated hepatic DUSP1 expression in wild-type mice. Notably, DUSP1 transgenic (Dusp1Tg ) mice showed resistance to alcohol-mediated hepatic dysfunction, as evidenced by decreased AST/ALT activity, improved alcohol metabolism, and suppressed liver fibrosis, inflammation, and oxidative stress. Functional experiments demonstrated that DUSP1 overexpression prevents alcohol-mediated mitochondrial damage in hepatocytes through restoring mitophagy. Accordingly, pharmacological blockade of mitophagy abolished the hepatoprotective actions of DUSP1. Molecular assays showed that DUSP1 binds cytosolic CUL1 and prevents its translocation to the nucleus. Importantly, CUL1 silencing restored the transcription of p62 and Parkin, resulting in mitophagy activation, and sustained mitochondrial integrity and hepatocyte function upon alcohol stress. These results indicate that alcohol-mediated DUSP1 downregulation interrupts DUSP1/CUL1 interaction, leading to CUL1 nuclear translocation and mitophagy inhibition via transcriptional repression of p62 and Parkin. Thus, targeting the DUSP1/CUL1/p62 axis will be a key approach to restore hepatic mitophagy as well as alleviate symptoms of ALD.

Respiratory muscle ultrasonography evaluation and its clinical application in stroke patients: A review.

Background: Respiratory muscle ultrasound is a widely available, highly feasible technique that can be used to study the contribution of the individual respiratory muscles related to respiratory dysfunction. Stroke disrupts multiple functions, and the respiratory function is often significantly decreased in stroke patients. Method: A search of the MEDLINE, Web of Science, and PubMed databases was conducted. We identified studies measuring respiratory muscles in healthy and patients by ultrasonography. Two reviewers independently extracted and documented data regarding to the criteria. Data were extracted including participant demographics, ultrasonography evaluation protocol, subject population, reference values, etc. Result: A total of 1954 participants from 39 studies were included. Among them, there were 1,135 participants from 19 studies on diaphragm, 259 participants from 6 studies on extra-diaphragmatic inspiratory muscles, and 560 participants from 14 studies on abdominal expiratory muscles. The ultrasonic evaluation of diaphragm and abdominal expiratory muscle thickness had a relatively typically approach, while, extra-diaphragmatic inspiratory muscles were mainly used in ICU that lack of a consistent paradigm. Conclusion: Diaphragm and expiratory muscle ultrasound has been widely used in the assessment of respiratory muscle function. On the contrary, there is not enough evidence to assess extra-diaphragmatic inspiratory muscles by ultrasound. In addition, the thickness of the diaphragm on the hemiplegic side was lower than that on the non-hemiplegic side in stroke patients. For internal oblique muscle (IO), rectus abdominis muscle (RA), transversus abdominis muscle (TrA), and external oblique muscle (EO), most studies showed that the thickness on the hemiplegic side was lower than that on the non-hemiplegic side.Clinical Trial Registration: The protocol of this review was registered in the PROSPERO database (CRD42022352901).

Algal cell bionics as a step towards photosynthesis-independent hydrogen production.

The engineering and modulation of living micro-organisms is a key challenge in green bio-manufacturing for the development of sustainable and carbon-neutral energy technologies. Here, we develop a cellular bionic approach in which living algal cells are interfaced with an ultra-thin shell of a conductive polymer along with a calcium carbonate exoskeleton to produce a discrete cellular micro-niche capable of sustained photosynthetic and photosynthetic-independent hydrogen production. The surface-augmented algal cells induce oxygen depletion, conduct photo-induced extracellular electrons, and provide structural and chemical stability that collectively give rise to localized hypoxic conditions and concomitant hydrogenase activity under daylight in air. We show that assembly of the living cellular micro-niche opens a direct extracellular photoelectron pathway to hydrogenase resulting in photosynthesis-independent hydrogen evolution for 200 d. In addition, surface-conductive dead algal cells continue to produce hydrogen for up to 8 d due to their structural stability and retention of functional hydrogenases. Overall, the integration of artificial biological hydrogen production pathways and natural photosynthesis in surface-augmented algal cells provides a cellular bionic approach to enhanced green hydrogen production under environmentally benign conditions and could pave the way to new opportunities in sustainable energy production.

Pharmacokinetics of Voriconazole in Peritoneal Fluid of Critically Ill Patients.

Data on the distribution of voriconazole (VRC) in the human peritoneal cavity are sparse. This prospective study aimed to describe the pharmacokinetics of intravenous VRC in the peritoneal fluid of critically ill patients. A total of 19 patients were included. Individual pharmacokinetic curves, drawn after single (first dose on day 1) and multiple (steady-state) doses, displayed a slower rise and lower fluctuation of VRC concentrations in peritoneal fluid than in plasma. Good but variable penetration of VRC into the peritoneal cavity was observed, and the median (range) peritoneal fluid/plasma ratios of the area under the concentration-time curve (AUC) were 0.54 (0.34 to 0.73) and 0.67 (0.63 to 0.94) for single and multiple doses, respectively. Approximately 81% (13/16) of the VRC steady-state trough concentrations (Cmin,ss) in plasma were within the therapeutic range (1 to 5.5 µg/mL), and the corresponding Cmin,ss (median [range]) in peritoneal fluid was 2.12 (1.39 to 3.72) µg/mL. Based on the recent 3-year (2019 to 2021) surveillance of the antifungal susceptibilities for Candida species isolated from peritoneal fluid in our center, the aforementioned 13 Cmin,ss in peritoneal fluid exceeded the MIC90 of C. albicans, C. glabrata, and C. parapsilosis (0.06, 1.00, and 0.25 µg/mL, respectively), which supported VRC as a reasonable choice for initial empirical therapies against intraabdominal candidiasis caused by these three Candida species, prior to the receipt of susceptibility testing results.

Serine/threonine kinase 3 promotes oxidative stress and mitochondrial damage in septic cardiomyopathy through inducing Kelch-like ECH-associated protein 1 phosphorylation and nuclear factor erythroid 2-related factor 2 degradation.

Serine/threonine kinases (STK3) is a core component of the Hippo pathway and modulates oxidative stress and inflammatory responses in cardiovascular diseases. However, its potential role in septic cardiomyopathy remains undefined. STK3-mediated phosphorylation of Kelch-like ECH-associated protein 1 (KEAP1) was shown to suppress antioxidant gene transcription controlled by nuclear factor erythroid 2-related factor 2 (Nrf2) in macrophages. To explore whether STK3 induces KEAP1-mediated suppression of Nrf2 in septic cardiomyopathy, wild-type and global STK3 knockout (STK3 -/- ) mice were treated with LPS. LPS treatment upregulated cardiac STK3 expression. STK3 deletion attenuated myocardial inflammation and cardiomyocyte death, and improved myocardial structure and function. In LPS-challenged HL-1 cardiomyocytes, shRNA-mediated STK3 knockdown normalized mitochondrial membrane potential and ATP production, attenuated apoptosis, and rescued antioxidant gene expression by preventing Nrf2 downregulation. Co-IP, docking analysis, western blotting, and immunofluorescence assays further showed that STK3 binds and phosphorylates KEAP1, promoting Nrf2 downregulation. Accordingly, transfection of phosphodefective KEAP1 mutant protein in cardiomyocyte restored Nrf2 expression and mitochondrial performance upon LPS, while expression of a phosphomimetic KEAP1 mutant abolished the mitochondria-protective and pro-survival effects of STK3 deletion. These findings suggest that STK3 upregulation contributes to septic cardiomyopathy by phosphorylating KEAP1 to promote Nrf2 degradation and suppression of the antioxidant response.