Stenotrophomonas maltophilia contributes to smoking-related emphysema through IRF1-triggered PANoptosis of alveolar epithelial cells.

Cigarette smoke (CS), the main source of indoor air pollution and the primary risk factor for respiratory diseases, contains chemicals that can perturb microbiota through antibiotic effects. Although smoking induces a disturbance of microbiota in the lower respiratory tract, whether and how it contributes to initiation or promotion of emphysema are not well clarified. Here, we demonstrated an aberrant microbiome in lung tissue of patients with smoking-related COPD. We found that Stenotrophomonas maltophilia (S. maltophilia) was expanded in lung tissue of patients with smoking-related COPD. We revealed that S. maltophilia drives PANoptosis in alveolar epithelial cells and represses formation of alveolar organoids through IRF1 (interferon regulatory factor 1). Mechanistically, IRF1 accelerated transcription of ZBP1 (Z-DNA Binding Protein 1) in S. maltophilia-infected alveolar epithelial cells. Elevated ZBP1 served as a component of the PANoptosome, which triggered PANoptosis in these cells. By using of alveolar organoids infected by S. maltophilia, we found that targeting of IRF1 mitigated S. maltophilia-induced injury of these organoids. Moreover, the expansion of S. maltophilia and the expression of IRF1 negatively correlated with the progression of emphysema. Thus, the present study provides insights into the mechanism of lung dysbiosis in smoking-related COPD, and presents a potential target for mitigation of COPD progression.

Foliar Application of Nanoparticles Reduced Cadmium Content in Wheat (Triticum aestivum L.) Grains via Long-Distance "Leaf-Root-Microorganism" Regulation.

Foliar application of beneficial nanoparticles (NPs) exhibits potential in reducing cadmium (Cd) uptake in crops, necessitating a systematic understanding of their leaf-root-microorganism process for sustainable development of efficient nano-enabled agrochemicals. Herein, wheat grown in Cd-contaminated soil (5.23 mg/kg) was sprayed with different rates of four commonly used NPs, including nano selenium (SeNPs)/silica (SiO2NPs)/zinc oxide/manganese dioxide. SeNPs and SiO2NPs most effectively reduced the Cd concentration in wheat grains. Compared to the control, Cd concentration in grains was significantly decreased by 35.0 and 33.3% by applying 0.96 mg/plant SeNPs and 2.4 mg/plant SiO2NPs, and the grain yield was significantly increased by 33.9% with SeNPs application. Down-regulated gene expression of Cd transport proteins (TaNramp5 and TaLCT1) and up-regulated gene expression of vacuolar Cd fixation proteins (TaHMA3 and TaTM20) were observed with foliar SeNPs and SiO2NPs use. SeNPs increased the levels of leaf antioxidant metabolites. Additionally, foliar spray of SeNPs resulted in lower abundances of rhizosphere organic acids and reduced Cd bioavailability in rhizosphere soil, and soil microorganisms related to carbon and nitrogen (Solirubrobacter and Pedomicrobium) were promoted. Our findings underscore the potential of the foliar application of SeNPs and SiO2NPs as a plant and rhizosphere soil metabolism-regulating approach to reduce Cd accumulation in wheat grains.

Hollow Layered Iron-Based Prussian Blue Cathode with Reduced Defects for High-Performance Sodium-Ion Batteries.

Fe-based Prussian blue (Fe-PB) analogues have emerged as promising cathode materials for sodium-ion batteries, owing to their cost-effectiveness, high theoretical capacity, and environmental friendliness. However, their practical application is hindered by [Fe(CN)6] defects, negatively impacting capacity and cycle stability. This work reports a hollow layered Fe-PB composite material using 1,3,5-benzenetricarboxylic acid (BTA) as a chelating and etching agent by the hydrothermal method. Compared to benzoic acid, our approach significantly reduces defects and enhances the yield of Fe-PB. Notably, the hollow layered structure shortens the diffusion path of sodium ions, enhances the activity of low-spin Fe in the Fe-PB lattice, and mitigates volume changes during Na-ion insertion/extraction into/from Fe-PB. As a sodium-ion battery cathode, this hollow layered Fe-PB exhibits an impressive initial capacity of 95.9 mAh g-1 at a high current density of 1 A g-1. Even after 500 cycles, it still maintains a considerable discharge capacity of 73.1 mAh g-1, showing a significantly lower capacity decay rate (0.048%) compared to the control sample (0.089%). Moreover, the full cell with BTA-PB-1.6 as the cathode and HC as the anode provides a considerable energy density of 312.2 Wh kg-1 at a power density of 291.0 W kg-1. This research not only enhances the Na storage performance of Fe-PB but also increases the yield of products obtained by hydrothermal methods, providing some technical reference for the production of PB materials using the low-yield hydrothermal method.

Deletion of Luzp2 Does Not Cause Hearing Loss in Mice.

Deafness is the prevailing sensory impairment among humans, impacting every aspect of one's existence. Half of congenital deafness cases are attributed to genetic factors. Studies have shown that Luzp2 is expressed in hair cells (HCs) and supporting cells of the inner ear, but its specific role in hearing remains unclear. To determine the importance of Luzp2 in auditory function, we generated mice deficient in Luzp2. Our results revealed that Luzp2 has predominant expression within the HCs and pillar cells. However, the loss of Luzp2 did not result in any changes in auditory threshold. HCs or synapse number and HC stereocilia morphology in Luzp2 knockout mice did not show any notable distinctions. This was the first study of the role of Luzp2 in hearing in mice, and our results provide important guidance for the screening of deafness genes.

ZNF554 Inhibits Endometrial Cancer Progression via Regulating RBM5 and Inactivating WNT/ß-Catenin Signaling Pathway.

OBJECTIVE: Uterine corpus endometrial carcinoma (UCEC), a kind of gynecologic malignancy, poses a significant risk to women's health. The precise mechanism underlying the development of UCEC remains elusive. Zinc finger protein 554 (ZNF554), a member of the Krüppel-associated box domain zinc finger protein superfamily, was reported to be dysregulated in various illnesses, including malignant tumors. This study aimed to examine the involvement of ZNF554 in the development of UCEC. METHODS: The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay. Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection. CCK-8, wound healing, and Transwell invasion assays were employed to assess cell proliferation, migration, and invasion. Propidium iodide (PI) staining combined with fluorescence-activated cell sorting (FACS) flow cytometer was utilized to detect cell cycle distribution. qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels. Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5 (RBM5). RESULTS: The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines. Decreased expression of ZNF554 was associated with higher tumor stage, decreased overall survival, and reduced disease-free survival in UCEC. ZNF554 overexpression suppressed cell proliferation, migration, and invasion, while also inducing cell cycle arrest. In contrast, a decrease in ZNF554 expression resulted in the opposite effect. Mechanistically, ZNF554 transcriptionally regulated RBM5, leading to the deactivation of the Wingless (WNT)/ß-catenin signaling pathway. Moreover, the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression on ß-catenin and p-glycogen synthase kinase-3ß (p-GSK-3ß). Similarly, the deliberate activation of RBM5 reduced the increase in ß-catenin and p-GSK-3ß caused by the suppression of ZNF554. In vitro experiments showed that ZNF554 overexpression-induced decreases in cell proliferation and migration were counteracted by RBM5 knockdown. Additionally, when RBM5 was overexpressed, it hindered the improvements in cell proliferation and migration caused by reducing the ZNF554 levels. CONCLUSION: ZNF554 functions as a tumor suppressor in UCEC. Furthermore, ZNF554 regulates UCEC progression through the RBM5/WNT/ß-catenin signaling pathway. ZNF554 shows a promise as both a prognostic biomarker and a therapeutic target for UCEC.

Nucleophilic Aromatic Substitution (SNAr) as an Approach to Challenging Nitrogen-Bridged BODIPY Oligomers.

A series of nitrogen-bridged BODIPY oligomers were synthesized via nucleophilic aromatic substitution (SNAr) as a convenient approach. Further transformations achieved novel α,α-aryl BODIPY dimers as well as a BODIPY hexamer efficiently. These BODIPY oligomers showed good photophysical properties, such as apparent absorption and emission both in visible and near-infrared regions. Interestingly, the high air and photothermal stability, strong NIR absorption, and high photothermal conversion rates of hexamer B6 suggest potential applications in photothermal therapy.

Protocol for evaluating the effects of the Reducing Cardiometabolic Diseases Risk dietary pattern in the Chinese population with dyslipidaemia: a single-centre, open-label, dietary intervention study.

INTRODUCTION: Cardiometabolic disease (CMD) is the leading cause of mortality in China. A healthy diet plays an essential role in the occurrence and development of CMD. Although the Chinese heart-healthy diet is the first diet with cardiovascular benefits, a healthy dietary pattern that fits Chinese food culture that can effectively reduce the risk of CMD has not been found. METHODS/DESIGN: The study is a single-centre, open-label, randomised controlled trial aimed at evaluating the effect of the Reducing Cardiometabolic Diseases Risk (RCMDR) dietary pattern in reducing the risk of CMDs in people with dyslipidaemia and providing a reference basis for constructing a dietary pattern suitable for the prevention of CMDs in the Chinese population. Participants are men and women aged 35-45 years with dyslipidaemia in Tianjin. The target sample size is 100. After the run-in period, the participants will be randomised to the RCMDR dietary pattern intervention group or the general health education control group with a 1:1 ratio. The intervention phases will last 12 weeks, with a dietary intervention of 5 working days per week for participants in the intervention group. The primary outcome variable is the cardiometabolic risk score. The secondary outcome variables are blood lipid, blood pressure, blood glucose, body composition indices, insulin resistance and 10-year risk of cardiovascular diseases. ETHICS AND DISSEMINATION: The study complies with the Measures for Ethical Review of Life Sciences and Medical Research Involving Human Beings and the Declaration of Helsinki. Signed informed consent will be obtained from all participants. The study has been approved by the Medical Ethics Committee of the Second Hospital of Tianjin Medical University (approval number: KY2023020). The results from the study will be disseminated through publications in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2300072472).

NIR-absorbing and emitting α,α-nitrogen-bridged BODIPY dimers with strong excitonic coupling.

Three new distinct NIR α,α-NH-bridged BODIPY dimers were prepared by a direct nucleophilic substitution reaction. The synergistic effects of the nitrogen bridges and strong excitonic coupling between each BODIPY unit play major roles in enhancing the delocalization of an electron spin over the entire BODIPY dimers. The in situ formed aminyl radical dimer showed an absorption maximum at 1040 nm.

Dual Nonradical Catalytic Pathways Mediated by Nanodiamond-Derived sp2/sp3 Hybrids for Sustainable Peracetic Acid Activation and Water Decontamination.

Peracetic acid (PAA) oxidation catalyzed by metal-free carbons is promising for advanced water decontamination. Nevertheless, developing reaction-oriented and high-performance carbocatalysts has been limited by the ambiguous understanding of the intrinsic relationship between carbon chemical/molecular structure and PAA transformation behavior. Herein, we comprehensively investigated the PAA activation using a family of well-defined sp2/sp3 carbon hybrids from annealed nanodiamonds (ANDs). The activity of ANDs displays a volcano-type trend, with respect to the sp2/sp3 ratio. Intriguingly, sp3-C-enriched AND exhibits the best catalytic activity for PAA activation and phenolic oxidation, which is different from persulfate chemistry in which the sp2 network normally outperforms sp3 hybridization. At the electron-rich sp2-C site, PAA undergoes a reduction reaction to generate a reactive complex (AND-PAA*) and induces an electron-transfer oxidation pathway. At the sp3-C site adjacent to C═O, PAA is oxidized to surface-confined OH* and O* successively, which ultimately evolves into singlet oxygen (1O2) as the primary reactive species. Benefiting from the dual nonradical regimes on sp2/sp3 hybrids, AND mediates a sustainable redox recycle with PAA to continuously generate reactive species to attack water contaminants, meanwhile maintaining structural/chemical integrity and exceptional reusability in cyclic runs.

[Multi-index evaluation of different parts of Amomum villosum].

To investigate the quality differences between the seeds and husks of Amomum villosum and explore the rationality of using the seeds without husks, this study determined the content of protocatechuic acid, vanillic acid, epicatechin, quercitrin, volatile oil, water extract, and ethanol extract. The 2,2-diphenyl-1-picrylhydrazyl(DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), and hydroxyl radical scavenging activities were determined to evaluate the antioxidant activities of seeds and husks. The quality differences between the seeds and husks were assessed through orthogonal partial least squares-discriminant analysis(OPLS-DA) and analytic hierarchy process(AHP) combined with the entropy weight method(EWM). Significant differences(P<0.05) were observed in all 10 indicators between the seeds and husks. The levels of epicatechin, quercetin, and volatile oil were higher in the seeds, whereas those of protocatechuic acid, vanillic acid, water extract, and ethanol extract were higher in the husks. The seeds showed stronger scavenging ability against DPPH and ABTS radicals, while the husks showed a stronger scavenging effect on hydroxyl radicals. OPLS-DA significantly discriminated between the seeds and husks. Furthermore, volatile oil, water extract, DPPH radical scavenging rate, quercitrin, ABTS radical scavenging rate, hydroxyl radical scavenging rate, and vanillic acid were selected as the main differential indicators by variable importance in projection(VIP). Comprehensive scores calculated by AHP combined with EWM indicated that the seeds were superior to husks in terms of overall quality. However, there are still some dominant components and a certain antioxidant effect in the husks. Therefore, it is suggested to using Amomi Fructus with a certain amount of husks or utilizing the husks for other purposes.

Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis.

Objective: To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis (EPTB). Methods: This study was conducted at the Shanghai Public Health Clinical Center. A total of 115 patients underwent ultrasound-guided puncture biopsy, followed by MGIT 960 culture (culture), smear, GeneXpert MTB/RIF (Xpert), and histopathological examination. These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria: liquid culture and composite reference standard (CRS). Results: When CRS was used as the reference standard, the sensitivity and specificity of culture, smear, Xpert, and histopathological examination were (44.83%, 89.29%), (51.72%, 89.29%), (70.11%, 96.43%), and (85.06%, 82.14%), respectively. Based on liquid culture tests, the sensitivity and specificity of smear, Xpert, and pathological examination were (66.67%, 72.60%), (83.33%, 63.01%), and (92.86%, 45.21%), respectively. Histopathological examination showed the highest sensitivity but lowest specificity. Further, we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80% and a specificity of 89.29%. Conclusion: Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB. Compared with culture, smear, and Xpert, histopathological examination showed higher sensitivity but lower specificity. The combination of histopathology with Xpert showed the best performance characteristics.

Nitrate-dependent anaerobic methane oxidation coupled to Fe(III) reduction as a source of ammonium and nitrous oxide.

'Candidatus Methanoperedens nitroreducens' is an archaeal methanotroph with global importance that links carbon and nitrogen cycles and great potential for sustainable operation of wastewater treatment. It has been reported to mediate the anaerobic oxidation of methane through a reverse methanogenesis pathway while reducing nitrate to nitrite. Here, we demonstrate that 'Ca. M. nitroreducens' reduces ferric iron forming ammonium (23.1 %) and nitrous oxide (N2O, 46.5 %) from nitrate. These results are supported with the upregulation of genes coding for proteins responsible for dissimilatory nitrate reduction to ammonium (nrfA), N2O formation (norV, cyt P460), and multiple multiheme c-type cytochromes for ferric iron reduction. Concomitantly, an increase in the N2O-reducing SJA-28 lineage and a decrease in the nitrite-reducing 'Candidatus Methylomirabilis oxyfera' are consistent with the changes in 'Ca. M. nitroreducens' end products. These findings demonstrate the highly flexible physiology of 'Ca. M. nitroreducens' in anaerobic ecosystems with diverse electron acceptor conditions, and further reveals its roles in linking methane oxidation to global biogeochemical cycles. 'Ca. M. nitroreducens' could significantly affect the bioavailability of nitrogen sources as well as the emission of greenhouse gas in natural ecosystems and wastewater treatment plants.

Dextromethorphan moderates reward deficiency associated with central serotonin transporter availability in 3,4-methylenedioxy-methamphetamine-treated animals.

BACKGROUND: The neurotoxicity of 3,4-methylenedioxy-methamphetamine (MDMA) to the serotonergic system is well-documented. Dextromethorphan (DM), an antitussive drug, decreased morphine- or methamphetamine (MA)-induced reward in rats and may prevent MDMA-induced serotonergic deficiency in primates, as indicated by increased serotonin transporter (SERT) availability. We aimed to investigate the effects of DM on reward, behavioral sensitization, and neurotoxicity associated with loss of SERT induced by chronic MDMA administration in rats. METHODS: Conditioned place preference (CPP) and locomotor activity tests were used to evaluate drug-induced reward and behavioral sensitization; 4-[18F]-ADAM/animal-PET and immunohistochemistry were used to explore the effects of DM on MDMA-induced loss of SERT. RESULTS: MDMA significantly reduced SERT binding in the rat brain; however, co-administration of DM significantly restored SERT, enhancing the recovery rate at day 14 by an average of ~23% compared to the MDMA group. In confirmation of the PET findings, immunochemistry revealed MDMA reduced SERT immunoactivity in all brain regions, whereas DM markedly increased the serotonergic fiber density after MDMA induction. CONCLUSION: Behavioral tests and in vivo longitudinal PET imaging demonstrated the CPP indexes and locomotor activities of the reward system correlate negatively with PET 4-[18F]ADAM SERT activity in the reward system. Our findings suggest MDMA induces functional abnormalities in a network of brain regions important to decision-making processes and the motivation circuit. DM may exert neuroprotective effects to reverse MDMA-induced neurotoxicity.

Subtracting-adding strategy for necrotic lesion segmentation in osteonecrosis of the femoral head.

PURPOSE: Osteonecrosis of the femoral head (ONFH) is a severe bone disease that can progressively lead to hip dysfunction. Accurately segmenting the necrotic lesion helps in diagnosing and treating ONFH. This paper aims at enhancing deep learning models for necrosis segmentation. METHODS: Necrotic lesions of ONFH are confined to the femoral head. Considering this domain knowledge, we introduce a preprocessing procedure, termed the "subtracting-adding" strategy, which explicitly incorporates this domain knowledge into the downstream deep neural network input. This strategy first removes the voxels outside the predefined volume of interest to "subtract" irrelevant information, and then it concatenates the bone mask with raw data to "add" anatomical structure information. RESULTS: Each of the tested off-the-shelf networks performed better with the help of the "subtracting-adding" strategy. The dice similarity coefficients increased by 10.93%, 9.23%, 9.38% and 1.60% for FCN, HRNet, SegNet and UNet, respectively. The improvements in FCN and HRNet were statistically significant. CONCLUSIONS: The "subtracting-adding" strategy enhances the performance of general-purpose networks in necrotic lesion segmentation. This strategy is compatible with various semantic segmentation networks, alleviating the need to design task-specific models.

Pyrimethamine upregulates BNIP3 to interfere SNARE-mediated autophagosome-lysosomal fusion in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

Differential Effects of JAK1 vs. JAK2 Inhibition in Mouse Models of Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) comprises a severe hyperinflammatory phenotype driven by the overproduction of cytokines, many of which signal via the JAK/STAT pathway. Indeed, the JAK1/2 inhibitor ruxolitinib has demonstrated efficacy in pre-clinical studies and early-phase clinical trials in HLH. Nevertheless, concerns remain for ruxolitinib-induced cytopenias, which are postulated to result from the blockade of JAK2-dependent hematopoietic growth factors. To explore the therapeutic effects of selective JAK inhibition in mouse models of HLH, we carried out studies incorporating the JAK1 inhibitor itacitinib, the JAK2 inhibitor fedratinib and the JAK1/2 inhibitor ruxolitinib. All three drugs were well-tolerated and at the doses tested, they suppressed interferon-gamma (IFNg)-induced STAT1 phosphorylation in vitro and in vivo. Itacitinib, but not fedratinib, significantly improved survival and clinical scores in CpG-induced secondary HLH. Conversely, in primary HLH, where perforin-deficient (Prf1-/-) mice are infected with lymphocytic choriomeningitis virus (LCMV), itacitinib and fedratinib performed suboptimally. Ruxolitinib demonstrated excellent clinical efficacy in both HLH models. RNA-sequencing of splenocytes from LCMV-infected Prf1-/- mice revealed that itacitinib targeted inflammatory and metabolic pathway genes in CD8 T cells, while fedratinib targeted genes regulating cell proliferation and metabolism. In monocytes, neither drug conferred major transcriptional impacts. Consistent with its superior clinical effects, ruxolitinib exerted the greatest transcriptional changes in CD8 T cells and monocytes, targeting more genes across several biologic pathways, most notably JAK-dependent pro-inflammatory signaling. We conclude that JAK1 inhibition is sufficient to curtail CpG-induced disease, but combined inhibition of JAK1 and JAK2 is needed to best control LCMV-induced immunopathology.

Catalytic Asymmetric Construction of Chiral Amines with Three Nonadjacent Stereocenters via Trifunctional Catalysis.

Pharmaceuticals and biologically active natural products usually contain multiple stereocenters. The development of catalytic asymmetric reactions for the direct construction of complex motifs containing three nonadjacent stereocenters is a particularly important and formidable challenge. In this paper, we report an unprecedented method for the direct asymmetric construction of complex chiral amines with 1,3,5- or 1,3,4-stereocenters from readily available achiral and racemic starting materials. The reaction was made possible by the development of highly efficient chiral ammonium catalysts that serve three distinct functions: promoting efficient kinetic resolution by chiral recognition of racemic electrophiles, promoting asymmetric C-C bond forming reactions by recognizing enantiotropic faces of achiral nucleophiles, and mediating a highly stereoselective protonation of carbanions. Using these trifunctional catalysts, the reaction of imines and tulipane derivatives proceeded in a highly regio-, chemo-, and stereoselective manner to produce synthetically useful yields of complex chiral amines. We believe that trifunctional catalysis can be applied in a variety of asymmetric transformations for the streamlined asymmetric synthesis of complex chiral molecules with multiple stereocenters.

[Primary Structure Characterization and Biosynthesis of Spider Silk Proteins for Multifunctional Biomaterials].

Spider silk is a natural fiber known as "biosteel" with the strongest composite performance, such as high tensile strength and toughness. It is also equipped with excellent biocompatibility and shape memory ability, thus shows great potential in many fields such as biomedicine and tissue engineering. Spider silk is composed of macromolecular spidroin with rich structural diversity. The characteristics of the primary structure of natural spidroin, such as the high repeatability of amino acids in the core repetitive region, the high content of specific amino acids, the large molecular weight, and the high GC content of the spidroin gene, have brought great difficulties in heterologous expression. This review discusses focuses on the relationship between the featured motifs of the microcrystalline region in the repetitive unit of spidroin and its structure, as well as the spinning performance and the heterologous expression. The optimization design for the sequence of spidroin combined with heterologous expression strategy has greatly promoted the development of the biosynthesis of spider silk proteins. This review may facilitate the rational design and efficient synthesis of recombinant spidroin.

MitoQ protects against carbon tetrachloride-induced hepatocyte ferroptosis and acute liver injury by suppressing mtROS-mediated ACSL4 upregulation.

Ferroptosis has been shown to be involved in carbon tetrachloride (CCl4)-induced acute liver injury (ALI). The mitochondrion-targeted antioxidant MitoQ can eliminate the production of mitochondrial reactive oxygen species (mtROS). This study investigated the role of MitoQ in CCl4-induced hepatocytic ferroptosis and ALI. MDA and 4HNE were elevated in CCl4-induced mice. In vitro, CCl4 exposure elevated the levels of oxidized lipids in HepG2 cells. Alterations in the mitochondrial ultrastructure of hepatocytes were observed in the livers of CCl4-evoked mice. Ferrostatin-1 (Fer-1) attenuated CCl4-induced hepatic lipid peroxidation, mitochondrial ultrastructure alterations and ALI. Mechanistically, acyl-CoA synthetase long-chain family member 4 (ACSL4) was upregulated in CCl4-exposed human hepatocytes and mouse livers. The ACSL4 inhibitor rosiglitazone alleviated CCl4-induced hepatic lipid peroxidation and ALI. ACSL4 knockdown inhibited oxidized lipids in CCl4-exposed human hepatocytes. Moreover, CCl4 exposure decreased the mitochondrial membrane potential and OXPHOS subunit levels and increased the mtROS level in HepG2 cells. Correspondingly, MitoQ pretreatment inhibited the upregulation of ACSL4 in CCl4-evoked mouse livers and HepG2 cells. MitoQ attenuated lipid peroxidation in vivo and in vitro after CCl4 exposure. Finally, MitoQ pretreatment alleviated CCl4-induced hepatocytic ferroptosis and ALI. These findings suggest that MitoQ protects against hepatocyte ferroptosis in CCl4-induced ALI via the mtROS-ACSL4 pathway.

Analysis of changes in high-mobility group box 1, receptor for advanced glycation endproducts, and T helper 17/regulatory T balance in severe preeclampsia with acute heart failure.

We measured the levels of High-Mobility Group Box 1 (HMGB1), Receptor for Advanced Glycation Endproducts (RAGE), T Helper 17 cells (Th17), Regulatory T cells (Treg), and related cytokines in the peripheral blood of patients with severe preeclampsia (SPE) complicated with acute heart failure (AHF) to explore the expression changes in these indicators. In total, 96 patients with SPE admitted to Gansu Provincial Maternity and Child-care Hospital between June 2020 and June 2022 were included in the study. The patients were divided into SPE+AHF (40 patients) and SPE (56 patients) groups based on whether they suffered from AHF. Additionally, 56 healthy pregnant women who either received prenatal examinations or were admitted to our hospital for delivery during the same period were selected as the healthy control group. An enzyme-linked immunosorbent assay was performed to detect the expression levels of HMGB1, RAGE, interleukin (IL)-17, IL-6, transforming growth factor ß (TGF-ß), IL-10, and NT-proBNP in plasma. Flow cytometry was employed to determine the percentages of Th17 and Treg cells. Compared to the healthy control group, the SPE+AHF and SPE groups had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage. Compared to the SPE group, the SPE+AHF group had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage (P < .05). In patients with SPE with AHF, plasma HMGB1 was positively correlated with RAGE, Th17, Th17/Treg, IL-17, and IL-6 and was negatively correlated with TGF-ß and IL-10 (P < .05). Our findings revealed that patients with SPE with AHF had elevated levels of HMGB1 and RAGE while exhibiting Th17/Treg immune imbalance, suggesting that the abnormal expression of these indicators may be involved in the pathogenesis of SPE with AHF.