The RNA binding protein Arid5a drives IL-17-dependent autoantibody-induced glomerulonephritis.

Autoantibody-mediated glomerulonephritis (AGN) arises from dysregulated renal inflammation, with urgent need for improved treatments. IL-17 is implicated in AGN and drives pathology in a kidney-intrinsic manner via renal tubular epithelial cells (RTECs). Nonetheless, downstream signaling mechanisms provoking kidney pathology are poorly understood. A noncanonical RNA binding protein (RBP), Arid5a, was upregulated in human and mouse AGN. Arid5a-/- mice were refractory to AGN, with attenuated myeloid infiltration and impaired expression of IL-17-dependent cytokines and transcription factors (C/EBPß, C/EBPδ). Transcriptome-wide RIP-Seq revealed that Arid5a inducibly interacts with conventional IL-17 target mRNAs, including CEBPB and CEBPD. Unexpectedly, many Arid5a RNA targets corresponded to translational regulation and RNA processing pathways, including rRNAs. Indeed, global protein synthesis was repressed in Arid5a-deficient cells, and C/EBPs were controlled at the level of protein rather than RNA accumulation. IL-17 prompted Arid5a nuclear export and association with 18S rRNA, a 40S ribosome constituent. Accordingly, IL-17-dependent renal autoimmunity is driven by Arid5a at the level of ribosome interactions and translation.

Formation of NifA-PII complex represses ammonium-sensitive nitrogen fixation in diazotrophic proteobacteria lacking NifL.

Biological nitrogen fixation catalyzed by nitrogenase contributes greatly to the global nitrogen cycle. Nitrogenase expression is subject to regulation in response to nitrogen availability. However, the mechanism through which the transcriptional activator NifA regulates nitrogenase expression by interacting with PII nitrogen regulatory proteins remains unclear in diazotrophic proteobacteria lacking NifL. Here, we demonstrate that in Rhodopseudomonas palustris grown with ammonium, NifA bound deuridylylated PII proteins to form an inactive NifA-PII complex, thereby inhibiting the expression of nitrogenase. Upon nitrogen limitation, the dissociation of uridylylated PII proteins from NifA resulted in the full restoration of NifA activity, and, simultaneously, uridylylation of the significantly up-regulated PII protein GlnK2 led to the increased expression of NifA in R. palustris. This insight into how NifA interacts with PII proteins and controls nitrogenase expression sets the stage for creating highly efficient diazotrophs, reducing the need for energy-intensive chemical fertilizers and helping to diminish carbon emissions.

Disruption of BACH1 Protects AC16 Cardiomyocytes Against Hypoxia/Reoxygenation-Evoked Injury by Diminishing CDKN3 Transcription.

Reperfusion after myocardial infarction (MI) can lead to myocardial ischemia/reperfusion (I/R) damage. The transcription factor (TF) broad-complex, tramtrack, and bric-a-brac (BTB) and cap'n'collar (CNC) homology 1 (BACH1) is implicated in the injury. However, the downstream mechanisms of BACH1 in affecting myocardial hypoxia/reoxygenation (H/R) damage are still fully understood. AC16 cells were stimulated with H/R conditions to model cardiomyocytes under H/R. mRNA analysis was performed by quantitative real-time PCR. Protein levels were gauged by immunoblot analysis. The effect of BACH1/cyclin-dependent kinase inhibitor 3 (CDKN3) on H/R-evoked injury was assessed by measuring cell viability via Cell Counting Kit-8 (CCK-8), apoptosis (flow cytometry and caspase 3 activity), ferroptosis via Fe2+, glutathione (GSH), reactive oxygen species (ROS) and malondialdehyde (MDA) markers and inflammation cytokines interleukin-1beta (IL-1ß) and tumor necrosis factor alpha (TNF-α). The BACH1/CDKN3 relationship was examined by chromatin immunoprecipitation (ChIP) experiment and luciferase assay. BACH1 was increased in MI serum and H/R-stimulated AC16 cardiomyocytes. Functionally, disruption of BACH1 mitigated H/R-evoked in vitro apoptosis, ferroptosis and inflammation of AC16 cardiomyocytes. Mechanistically, BACH1 activated CDKN3 transcription and enhanced CDKN3 protein expression in AC16 cardiomyocytes. Our rescue experiments validated that BACH1 disruption attenuated H/R-evoked AC16 cardiomyocyte apoptosis, ferroptosis and inflammation by downregulating CDKN3. Additionally, BACH1 disruption could activate the adenosine monophosphate-activated protein kinase (AMPK) signaling by downregulating CDKN3 in H/R-stimulated AC16 cardiomyocytes. Our study demonstrates that BACH1 activates CDKN3 transcription to induce H/R-evoked damage of AC16 cardiomyocytes partially via AMPK signaling.

Ball billing induced highly dispersed nano-MgO in biochar for glucose isomerization at low temperatures.

The isomerization of glucose is a crucial step for biomass valorization to downstream chemicals. Herein, highly dispersed MgO doped biochar (BM-0.5@450) was prepared from rice straw via a solvent-free ball milling pretreatment and pyrolysis under nitrogen conditions. The nano-MgO doped biochar demonstrated enhanced conversion of glucose in water at low temperatures. A 31 % yield of fructose was obtained from glucose over BM-0.5@450 at 50 °C with 80.0 % selectivity. At 60 °C for 140 min, BM-0.5@450 achieved a 32.5 % yield of fructose. Compared to catalyst synthesized from conventional impregnation method (IM@450), the BM-0.5@450 catalyst shows much higher fructose yields (32.5 % vs 25.9 %), which can be attributed to smaller crystallite size of MgO (11.32 nm vs 19.58 nm) and homogenous distribution. The mechanism study shows that the activated MgOH+·OH- group by water facilitated the deprotonation process leading to the formation of key intermediate enediol.

The mysteries of pharmacokinetics and in vivo metabolism of Oroxylum indicum (L.) Kurz: A new perspective from MSOP method.

The pharmacological effects of flavonoids in Oroxylum indicum (L.) Kurz against inflammation, bacterial, and oxidation have been well-documented. Additionally, it is commonly consumed as tea. However, the in vivo mechanism of its main compounds has not been well elucidated. In this study, a highly selective and sensitive UHPLC-Q-TOF-MS method combined with Mass Spectrum-based Orthogonal Projection (MSOP) theory and four-step analytical strategy was established and validated to identify metabolites in rats following oral administration Oroxylum indicum (L.) Kurz extract. Furthermore, a sensitive LC-MS/MS method was developed and validated for the first time to analyze the pharmacokinetics of ten main flavonoids in rats. Notably, a total of 47 metabolites were identified in blood, bile, urine, and feces samples. The maximum plasma concentration (Cmax) values for oroxin A, oroxin B, baicalin, chrysin, baicalein, scutellarein, apigenin, quercetin oroxylin A and isorhamnetin were 2945.1 ± 11.23 ng/mL, 3123.9 ± 16.37 ng/mL, 130.40 ± 27.52 ng/mL, 117.20 ± 28.54 ng/mL, 64.12 ± 19.33 ng/mL, 97.22 ± 24.27 ng/mL, 145.22 ± 29.92 ng/mL, 45.19 ± 18.84 ng/mL, 67.32 ± 15.78 ng/mL and 128.44 ± 26.42 ng/mL. A double peak was observed in the drug-time curve of apigenin, due to enterohepatic recirculation. This study demonstrated that MSOP method provided more technical support for the identification of flavonoid metabolites in complex system than traditional methods.

Electrochemical oscillation during galvanostatic charging and discharging of Zr-modified Li4Ti5O12 in Li-ion batteries.

The electrochemical oscillation in Li-ion batteries has been reported for two-phase electrode materials of Li4Ti5O12 and LiCrTiO4, which is originated from the group-by-group phase transition in a multi-particle electrode. For both Li4Ti5O12 and LiCrTiO4, the electrochemical oscillation exhibits usually during charging, while rarely for discharging. Herein, a series of Zr-modified Li4Ti5O12 samples are prepared by using the spray-drying combined with high-temperature sintering method, and the electrochemical oscillation is observed during not only the charging process, but also the discharging process, which gradually grows up and then disappears by increasing the Li content. Compared with Li4Ti5O12, the specific capacity of Zr-modified Li4Ti5O12 decreases gradually by increasing the Zr/Ti ratio, owing to the impurity phases. According to the XRD, XPS and STEM results, the Zr element tends to accumulate on the surface to form ZrO2 nanoparticles, rather than dope into the bulk phase of Li4Ti5O12, which makes Li4Ti5O12 particles well dispersive. In contrast to the Li deficiency for only charging, the electrochemical oscillation during both charging and discharging should be attributed to the Li excess, but too much Li2TiO3 phase will suppress the electrochemical oscillation. Therefore, the Li excess can induce the electrochemical oscillation during both charging and discharging of Zr-modified Li4Ti5O12, which can be adopted to investigate the electrochemical oscillation of other materials in LIBs.

MOF-Derived Zn/N-Doped Porous Carbon Film on a Carbon Nanotube for High-Performance Supercapacitors.

Designing high-performance binder-free electrochemical electrodes is crucially important toward supercapacitors. In this paper, a Zn/N-doped porous carbon film coating on flexible carbon nanotubes (ZIF-8@CT-800) derived from the epitaxial Zn-MOF film growth on cotton textile was successfully fabricated via a combination of the liquid-phase epitaxial (LPE) method and calcination treatments. The ZIF-8@CT-800 serves directly as a self-supported electrode for supercapacitors and exhibits a high areal capacitance of 930 mF·cm-2 at a current density of 1 mA·cm-2 and a good recyclability of 86% after 2000 cycles. The excellent supercapacitor property is ascribed to the unique structural design of ZIF-8@CT-800, which provides appropriate channels for enhanced electronic and ionic transport as well as increased surface area for accessing more electrolyte ions. This work will provide significant guidance for designing MOF-derived porous carbon to construct flexible binder-free electrode materials with high electrochemical performance.

New options for endoscopic treatment of gastric varices.

BACKGROUND: Gastric venous bleeding is one of the most common adverse events in liver cirrhosis. The therapeutic effect of isolated gastric varices is relatively clear. However, there is no appropriate clinical and endoscopic treatment for extensive variceal bleeding in the gastric fundus and body. METHODS: In this patient with non-isolated gastric varices, we decided to perform endoscopic multi-point ligation of the obvious varices in the gastric fundus and body. RESULTS: In this patient, endoscopic treatment of gastric varices with bleeding after surgery achieved a significant therapeutic effect. Reexamination of gastroscopy at 3 months after operation showed that multiple scars were formed in the gastric fundus and fundus, and no obvious varices were found. CONCLUSIONS: For patients with non-isolated gastric varices, endoscopic multi-point ligation is a safe and effective treatment option for the varices with obvious gastric fundus and body.

Mechanism of discoloration of Antarctic krill oil upon storage: A study based on model systems.

The reddish-orange color of Antarctic krill oil fades during storage, and the mechanism remains unclear. Model systems containing different combinations of astaxanthin (ASTA), phosphatidylethanolamine (PE), and tocopherol were subjected to accelerated storage. Among all groups containing ASTA, only the ones with added PE showed significant fading. Meanwhile, the specific UV-visible absorption (A470 and A495) showed a similar trend. Peroxide value and thiobarbituric acid reactive substances increased during storage, while ASTA and PE contents decreased. Correlation analysis suggested that oxidized PE promoted fading by accelerating the transformation of ASTA. PE content exceeded the critical micelle concentration (1µg/g) indicating the formation of reverse micelles. Molecular docking analysis indicated that PE also interacted with ASTA in an anchor-like manner. Therefore, it is speculated that amphiphilic ASTA is more readily distributed at the oil-water interface of reverse micelles and captured by oxidized PE, which facilitates oxidation transfer, leading to ASTA oxidation and color fading.

Early detection of pancreatic cancer in patients with recurrent pancreatitis: A case report.

BACKGROUND: Pancreatic cancer presents a challenge with its low early diagnosis and treatment rates, leading to high metastasis and mortality rates. The median survival time for advanced pancreatic cancer is a mere 3 months. However, there's hope: small pancreatic cancers diagnosed at an early stage (T1) or those less than or equal to 1 cm in diameter boast an impressive 5-year survival rate of nearly 100%. This underscores the critical importance of early pancreatic cancer detection for significantly improving prognosis. CASE SUMMARY: Pancreatic cancer, a malignant tumor of the digestive tract, poses challenges in both diagnosis and treatment due to its occult and atypical clinical symptoms. Clinically, patients with recurrent pancreatitis should be vigilant, as it may be indicative of pancreatic cancer, particularly in middle-aged and elderly patients. Here, we presented the case of a patient who experienced recurrent acute pancreatitis within a span of 2 months. During the initial episode of pancreatitis, routine imaging failed to identify the cause of pancreatic cancer. However, upon recurrence of acute pancreatitis, endoscopic ultrasonography (EUS) revealed a space-occupying lesion approximately 1 cm in size in the pancreatic body. Subsequent EUS coupled with fine-needle aspiration examination demonstrated atypical pancreatic gland epithelium. Ultimately, the patient underwent surgery and was diagnosed with an intraductal papillary mucinous tumor of the pancreas (severe epithelial dysplasia, focal cancer). CONCLUSION: We recommend EUS for patients with recurrent pancreatitis of unknown etiology to exclude early pancreatic cancer.

Humoral and cellular immune responses following Omicron BA.2.2 breakthrough infection and Omicron BA.5 reinfection.

The emergence of novel Omicron subvariants has raised concerns regarding the efficacy of immunity induced by prior Omicron subvariants breakthrough infection (BTI) or reinfection against current circulating Omicron subvariants. Here, we prospectively investigated the durability of antibody and T cell responses in individuals post Omicron BA.2.2 BTI, with or without subsequent Omicron BA.5 reinfection. Our findings reveal that the emerging Omicron subvariants, including CH.1.1, XBB, and JN.1, exhibit extensive immune evasion induced by previous infections. Notably, the level of IgG and neutralizing antibodies were found to correlate with subsequent Omicron BA.5 reinfection. Fortunately, T cell responses recognizing both Omicron BA.2 and CH.1.1 peptides were observed. Furthermore, Omicron BA.5 reinfection may alleviate immune imprinting induced by WT-vaccination, bolster virus-specific ICS+ T cell responses, and promote the phenotypic differentiation of virus-specific memory CD8+ T cells. Antigen-updated or T cell-conserved vaccines are needed to control the transmission of diverse emerging SARS-CoV-2 variants.

Gut microbiota modulation: a narrative review on a novel strategy for prevention and alleviation of ovarian aging.

The global rise in life expectancy corresponds with a delay in childbearing age among women. Ovaries, seen as the chronometers of female physiological aging, demonstrate features of sped up aging, evidenced by the steady decline in both the quality and quantity of ovarian follicles from birth. The multifaceted pathogenesis of ovarian aging has kindled intensive research interest from the biomedical and pharmaceutical sectors. Novel studies underscore the integral roles of gut microbiota in follicular development, lipid metabolism, and hormonal regulation, forging a nexus with ovarian aging. In this review, we outline the role of gut microbiota in ovarian function (follicular development, oocyte maturation, and ovulation), compile and present gut microbiota alterations associated with age-related ovarian aging. We also discuss potential strategies for alleviating ovarian aging from the perspective of gut microbiota, such as fecal microbiota transplantation and probiotics.

Fine-YOLO: A Simplified X-ray Prohibited Object Detection Network Based on Feature Aggregation and Normalized Wasserstein Distance.

X-ray images typically contain complex background information and abundant small objects, posing significant challenges for object detection in security tasks. Most existing object detection methods rely on complex networks and high computational costs, which poses a challenge to implement lightweight models. This article proposes Fine-YOLO to achieve rapid and accurate detection in the security domain. First, a low-parameter feature aggregation (LPFA) structure is designed for the backbone feature network of YOLOv7 to enhance its ability to learn more information with a lighter structure. Second, a high-density feature aggregation (HDFA) structure is proposed to solve the problem of loss of local details and deep location information caused by the necked feature fusion network in YOLOv7-Tiny-SiLU, connecting cross-level features through max-pooling. Third, the Normalized Wasserstein Distance (NWD) method is employed to alleviate the convergence complexity resulting from the extreme sensitivity of bounding box regression to small objects. The proposed Fine-YOLO model is evaluated on the EDS dataset, achieving a detection accuracy of 58.3% with only 16.1 M parameters. In addition, an auxiliary validation is performed on the NEU-DET dataset, the detection accuracy reaches 73.1%. Experimental results show that Fine-YOLO is not only suitable for security, but can also be extended to other inspection areas.

Study on the photosynthetic growth characters in Cimicifuga dahurica (Turcz.) Maxim under different supplemental light environments.

Cimicifuga dahurica (C. dahurica) is an important medicinal plant in the northern region of China. The best supplemental light environment helps plant growth, development, and metabolism. In this study, we used two-year-old seedlings as experimental materials. The white light as the control (CK). The different ratios of red (R) and blue (B) combined light were supplemented (T1, 2R: 1B, 255.37 µmol m-2·s-1; T2, 3R: 1B, 279.69 µmol m-2·s-1; T3, 7R: 1B, 211.16 µmol m-2·s-1). The growth characteristics, photosynthetic pigment content, photosynthesis and chlorophyll fluorescence parameters, and primary metabolite content were studied in seedlings. The results showed that: 1) The fresh weight from shoot, root, and total fresh weight were significantly (P < 0.05) increased under T2 and T3 treatment. 2) The contents of chlorophyll a (Chl a), chlorophyll b (Chl b), and total chlorophyll (Chl) were significantly (P < 0.05) increased under T2 treatment, and carotenoid (car) content was reduced. 3) The photochemical quenching (qP), the actual photosynthetic efficiency of PSII (Y(II)), and the photosynthetic electron transfer rate (ETR) from leaves were significantly (P < 0.05) increased under T1 treatment. The Net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) were significantly (P < 0.05) increased under T2 and T3 treatments. 4) A total of 52 primary metabolites were detected in C. dahurica leaves. Compared with CK, 14, 15, and 18 differential metabolites were screened under T1, T2, and T3 treatments. In addition, D-xylose, D-glucose, glycerol, glycolic acid, and succinic acid were significantly (P < 0.05) accumulated under the T2 treatment, which could regulate the TCA cycle metabolism pathway. The correlation analysis suggested that plant growth was promoted by regulating the change of D-mannose content in galactinol metabolism and amino sugar and nucleotide sugar metabolism. In summary, the growth of C. dahurica was improved under T2 treatment.

Inhibiting AGTR1 reduces AML burden and protects the heart from cardiotoxicity in mouse models.

Clinical treatment of acute myeloid leukemia (AML) largely relies on intensive chemotherapy. However, the application of chemotherapy is often hindered by cardiotoxicity. Patient sequence data revealed that angiotensin II receptor type 1 (AGTR1) is a shared target between AML and cardiovascular disease (CVD). We found that inhibiting AGTR1 sensitized AML to chemotherapy and protected the heart against chemotherapy-induced cardiotoxicity in a human AML cell-transplanted mouse model. These effects were regulated by the AGTR1-Notch1 axis in AML cells and cardiomyocytes from mice. In mouse cardiomyocytes, AGTR1 was hyperactivated by AML and chemotherapy. AML leukemogenesis increased the expression of the angiotensin-converting enzyme and led to increased production of angiotensin II, the ligand of AGTR1, in an MLL-AF9-driven AML mouse model. In this model, the AGTR1-Notch1 axis regulated a variety of genes involved with cell stemness and chemotherapy resistance. AML cell stemness was reduced after Agtr1a deletion in the mouse AML cell transplant model. Mechanistically, Agtr1a deletion decreased γ-secretase formation, which is required for transmembrane Notch1 cleavage and release of the Notch1 intracellular domain into the nucleus. Using multiomics, we identified AGTR1-Notch1 signaling downstream genes and found decreased binding between these gene sequences with Notch1 and chromatin enhancers, as well as increased binding with silencers. These findings describe an AML/CVD association that may be used to improve AML treatment.

Sphingobium sp. SJ10-10 encodes a not-yet-reported chromate reductase and the classical Rieske dioxygenases to simultaneously degrade PAH and reduce chromate.

Both polycyclic aromatic hydrocarbons (PAHs) and heavy metals persist in the environment and are toxic to organisms. Their co-occurrence makes any of them difficult to remove during bioremediation and poses challenges to environmental management and public health. Microorganisms capable of effectively degrading PAHs and detoxifying heavy metals concurrently are required to improve the bioremediation process. In this study, we isolated a new strain, Sphingobium sp. SJ10-10, from an abandoned coking plant and demonstrated its capability to simultaneously degrade 92.6 % of 75 mg/L phenanthrene and reduce 90 % of 3.5 mg/L hexavalent chromium [Cr(VI)] within 1.5 days. Strain SJ10-10 encodes Rieske non-heme iron ring-hydroxylating oxygenases (RHOs) to initiate PAH degradation. Additionally, a not-yet-reported protein referred to as Sphingobium chromate reductase (SchR), with low sequence identity to known chromate reductases, was identified to reduce Cr(VI). SchR is distributed across different genera and can be classified into two classes: one from Sphingobium members and the other from non-Sphingobium species. The widespread presence of SchR in those RHO-containing Sphingobium members suggests that they are excellent candidates for bioremediation. In summary, our study demonstrates the simultaneous removal of PAHs and Cr(VI) by strain SJ10-10 and provides valuable insights into microbial strategies for managing complex pollutant mixtures.

Maleic anhydride-functionalized cellulose nanocrystal-stabilized high internal phase Pickering emulsion for pesticide delivery.

The salt-responsiveness of Pickering emulsions has significantly influenced their applications due to the large amount of salt on the surface of plant leaves. The present study provided a maleic anhydride-functionalized cellulose nanocrystal-stabilized high internal phase Pickering emulsion (MACNCs-HIPPEs) that was stable to high-concentration salt and used for pesticide delivery. The stability of MACNCs-HIPPEs was investigated by adjusting the oil-phase volume fraction (φ), the MACNCs concentration, NaCl dosages, and the rheological properties. The high internal phase Pickering emulsion was obtained at φ of 0.8 and MACNCs concentration of 2wt% and showed excellent salt stability (NaCl, 1200 mM) and significant storage stability (60 days). The sustained release of imidacloprid (IMI) from imidacloprid-loaded MACNCs-HIPPEs (IMI@MACNCs-HIPPEs) showed a positive correlation to the temperature (15°C, 25°C, 35°C), indicating clear thermo-responsiveness of the prepared pesticide formulation. The test of spread and retention of IMI@MACNCs-HIPPEs on the leaf surface showed a significant advantage compared with the commercial IMI water dispersible granules (CG). All the advantages mentioned above showed the excellent potential of the MACNCs-HIPPEs in delivering lipophilic pesticides.

Ectoine Enhances Mucin Production Via Restoring IL-13/IFN-γ Balance in a Murine Dry Eye Model.

Purpose: This study aimed to explore protective effects and potential mechanism of ectoine, a natural osmoprotectant, on ocular surface mucin production in dry eye disease. Methods: A dry eye model was established in C57BL/6 mice exposed to desiccating stress (DS) with untreated (UT) mice as controls. DS mice were topically treated with 2.0% ectoine or PBS vehicle. Corneal epithelial defects were assessed by Oregon Green Dextran (OGD) fluorescent staining. Conjunctival goblet cells, ocular mucins, and T help (Th) cytokines were evaluated by immunofluorescent staining or ELISA, and RT-qPCR. Results: Compared with UT mice, corneal epithelial defects were detected as strong punctate OGD fluorescent staining in DS mice with vehicle, whereas ectoine treatment largely reduced OGD staining to near-normal levels. Conjunctival goblet cell density and cell size decreased markedly in DS mice, but was significantly recovered by ectoine treatment. The protein production and mRNA expression of two gel-forming secreted MUC5AC and MUC2, and 4 transmembrane mucins, MUC1, MUC4, MUC16, and MUC15, largely decreased in DS mice, but was restored by ectoine. Furthermore, Th2 cytokine IL-13 was inhibited, whereas Th1 cytokine IFN-γ was stimulated at protein and mRNA levels in conjunctiva and draining cervical lymph nodes (CLNs) of DS mice, leading to decreased IL-13/IFN-γ ratio. Interestingly, 2.0% ectoine reversed their alternations and restored IL-13/IFN-γ balance. Conclusions: Our findings demonstrate that topical ectoine significantly reduces corneal damage, and enhances goblet cell density and mucin production through restoring imbalanced IL-13/IFN-γ signaling in murine dry eye model. This suggests therapeutic potential of natural osmoprotectant ectoine for dry eye disease.