4-Nitrophenol at environmentally relevant concentrations mediates reproductive toxicity in Caenorhabditis elegans via metabolic disorders-induced estrogen signaling pathway.

4-Nitrophenol (4-NP), as a toxic and refractory pollutant, has generated significant concern due to its adverse effects. However, the potential toxic effects and mechanism remained unclear. In this study, the reproduction, development, locomotion and reactive oxygen species (ROS) production of Caenorhabditis elegans were investigated to evaluate the 4-NP toxicity. We used metabolomics to assess the potential damage mechanisms. The role of metabolites in mediating the relationship between 4-NP and phenotypes was examined by correlation and mediation analysis. 4-NP (8 ng/L and 8 µg/L) caused significant reduction of brood size, ovulation rate, total germ cells numbers, head thrashes and body bends, and an increase in ROS. However, the oosperm numbers in uterus, body length and body width were decreased in 8 µg/L. Moreover, 36 differential metabolites were enriched in the significant metabolic pathways, including lysine biosynthesis, ß-alanine metabolism, tryptophan metabolism, pentose phosphate pathway, pentose and glucuronate interconversions, amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, galactose metabolism, propanoate metabolism, glycerolipid metabolism, and estrogen signaling pathway. The mechanism of 4-NP toxicity was that oxidative stress caused by the perturbation of amino acid, which had effects on energy metabolism through disturbing carbohydrate and lipid metabolism, and finally affected the estrogen signaling pathway to exert toxic effects. Moreover, correlation and mediation analysis showed glycerol-3P, glucosamine-6P, glucosamine-1P, UDP-galactose, L-aspartic acid, and uracil were potential markers for the reproduction and glucose-1,6P2 for developmental toxicity. The results provided insight into the pathways involved in the toxic effects caused by 4-NP and developed potential biomarkers to evaluate 4-NP toxicity.

Recycling Fe and improving organic pollutant removal via in situ forming magnetic core-shell Fe3O4@CaFe-LDH in Fe(II)-catalyzed oxidative wastewater treatment.

Due to its high efficiency, Fe(II)-based catalytic oxidation has been one of the most popular types of technology for treating growing organic pollutants. A lot of chemical Fe sludge along with various refractory pollutants was concomitantly produced, which may cause secondary environmental problems without proper disposal. We here innovatively proposed an effective method of achieving zero Fe sludge, reusing Fe resources (Fe recovery = 100%) and advancing organics removal (final TOC removal > 70%) simultaneously, based on the in situ formation of magnetic Ca-Fe layered double hydroxide (Fe3O4@CaFe-LDH) nano-material. Cations (Ca2+ and Fe3+) concentration (≥ 30 mmol/L) and their molar ratio (Ca:Fe ≥ 1.75) were crucial to the success of the method. Extrinsic nano Fe3O4 was designed to be involved in the Fe(II)-catalytic wastewater treatment process, and was modified by oxidation intermediates/products (especially those with COO- structure), which promoted the co-precipitation of Ca2+ (originated from Ca(OH)2 added after oxidation process) and by-produced Fe3+ cations on its surface to in situ generate core-shell Fe3O4@CaFe-LDH. The oxidation products were further removed during Fe3O4@CaFe-LDH material formation via intercalation and adsorption. This method was applicable to many kinds of organic wastewater, such as bisphenol A, methyl orange, humics, and biogas slurry. The prepared magnetic and hierarchical CaFe-LDH nanocomposite material showed comparable application performance to the recently reported CaFe-LDHs. This work provides a new strategy for efficiently enhancing the efficiency and economy of Fe(II)-catalyzed oxidative wastewater treatment by producing high value-added LDHs materials.

Abiotic aerobic oxidation pathways of stibnite revealed by oxygen and sulfur isotope systematics of sulfate.

The environmental threat posed by stibnite is an important geoenvironmental issue of current concern. To better understand stibnite oxidation pathways, aerobic abiotic batch experiments were conducted in aqueous solution with varying δ18OH2O value at initial neutral pH for different lengths of time (15-300 days). The sulfate oxygen and sulfur isotope compositions as well as concentrations of sulfur and antimony species were determined. The sulfur isotope fractionation factor (Δ34SSO4-stibnite) values decreased from 0.8‰ to -2.1‰ during the first 90 days, and increased to 2.6‰ at the 180 days, indicating the dominated intermediate sulfur species such as S2O32-, S0, and H2S (g) involved in Sb2S3 oxidation processes. The incorporation of O into sulfate derived from O2 (∼100%) indicated that the dissociated O2 was only directly adsorbed on the stibnite-S sites in the initial stage (0-90 days). The proportion of O incorporation into sulfate from water (27%-52%) increased in the late stage (90-300 days), which suggested the oxidation mechanism changed to hydroxyl attack on stibnite-S sites promoted by nearby adsorbed O2 on stibnite-Sb sites. The exchange of oxygen between sulfite and water may also contributed to the increase of water derived O into SO42-. The new insight of stibnite oxidation pathway contributes to the understanding of sulfide oxidation mechanism and helps to interpret field data.

Immunoglobulin G4 -related gastrointestinal disease associated with type 1 autoimmune pancreatitis: A case report.

Immunoglobulin G4 (IgG4)-related diseaseis a systemic inflammatory condition of unknown etiology characterized by increases in serum IgG4 and in the number of IgG4-positive cells in affected tissues. One of the commonly involved locations is the pancreas; this condition is known as type 1 autoimmune pancreatitis (AIP). Type 1 AIP, which shows a biliary stricture in the intrapancreatic bile duct, can be misdiagnosed as a malignancy due to similar cholangiography findings and clinical presentation. In rare cases complicated by post-bulbar duodenal ulcers, differentiating between type 1 AIP and malignancies is even more difficult. An 81-year-old male was referred to our hospital for the treatment of a pancreatic head mass and obstructive jaundice. Serological and radiological findings were consistent with both type 1 AIP and a malignancy. Gastroduodenoscopy revealed a post-bulbar duodenal ulcer with endoscopic features that evoked malignant duodenal invasion. Although biopsies were negative for malignant cells, subsequent bleeding from the lesion suggested the progression of malignancy, which led to surgical resection. Pancreatoduodenectomy and pathological examination indicated that type 1 AIP was present. Simultaneously, the involvement of IgG4-related disease in the ulcerative lesion was suggested. To our knowledge, this is the first reported case of type 1 AIP complicated by post-bulbar duodenal ulcers, which was misdiagnosed as malignancy and considered an IgG4-related gastrointestinal disease associated with type 1 AIP.

Efficient photodegradation of perfluoroalkyl substances under visible light by hexagonal ZnIn2S4 nanosheets.

Perfluoroalkyl substances (PFASs) are typical persistent organic pollutants, and their removal is urgently required but challenging. Photocatalysis has shown potential in PFASs degradation due to the redox capabilities of photoinduced charge carriers in photocatalysts. Herein, hexagonal ZnIn2S4 (ZIS) nanosheets were synthesized by a one-pot oil bath method and were well characterized by a series of techniques. In the degradation of sodium p-perfluorous nonenoxybenzenesulfonate (OBS), one kind of representative PFASs, the as-synthesized ZIS showed activity superior to P25 TiO2 under both simulated sunlight and visible-light irradiation. The good photocatalytic performance was attributed to the enhanced light absorption and facilitated charge separation. The pH conditions were found crucial in the photocatalytic process by influencing the OBS adsorption on the ZIS surface. Photogenerated e- and h+ were the main active species involved in OBS degradation in the ZIS system. This work confirmed the feasibility and could provide mechanistic insights into the degradation and defluorination of PFASs by visible-light photocatalysis.

Sensitive visual detection of norfloxacin in water by smartphone assisted colorimetric method based on peroxidase-like active cobalt-doped Fe3O4 nanozyme.

Norfloxacin is widely used owing to its strong bactericidal effect on Gram-negative bacteria. However, the residual norfloxacin in the environment can be biomagnified via food chain and may damage the human liver and delay the bone development of minors. Present work described a reliable and sensitive smartphone colorimetric sensing system based on cobalt-doped Fe3O4 magnetic nanoparticles (Co-Fe3O4 MNPs) for the visual detection of norfloxacin. Compared with Fe3O4, Co-Fe3O4 MNPs earned more remarkably peroxidase-like activity and TMB (colorless) was rapidly oxidized to oxTMB (blue) with the presence of H2O2. Interestingly, the addition of low concentration of norfloxacin can accelerate the color reaction process of TMB, and blue deepening of the solution can be observed with the naked eye. However, after adding high concentration of norfloxacin, the activity of nanozyme was inhibited, resulting in the gradual fading of the solution. Based on this principle, a colorimetric sensor integrated with smartphone RGB mode was established. The visual sensor exhibited good linearity for norfloxacin monitoring in the range of 0.13-2.51 µmol/L and 17.5-100 µmol/L. The limit of visual detection was 0.08 µmol/L. In the actual water sample analysis, the spiked recoveries of norfloxacin were over the range of 95.7%-104.7 %. These results demonstrated that the visual sensor was a convenient and fast method for the efficient and accurate detection of norfloxacin in water, which may have broad application prospect.

A comparison increasing the photodegradation power of a Ag/g-C3N4 /CoNi-LDH nanocomposite: Photocatalytic activity toward water treatment.

For environmental applications, it is crucial to rationally design and synthesize photocatalysts with positive exciton splitting and interfacial charge transfer. Here, a novel Ag-bridged dual Z-scheme Ag/g-C3N4/CoNi-LDH plasmonic heterojunction was successfully synthesized using a simple method, with the goal of overcoming the common drawbacks of traditional photocatalysts such as weak photoresponsivity, rapid combination of photo-generated carriers, and unstable structure. These materials were characterized by XRD, FT-IR, SEM, TEM UV-Vis/DRS, and XPS to verify the structure and stability of the heterostructure. The pristine LDH, g-C3N4, and Ag/g-C3N4/CoNi-LDH composite were investigated as photocatalysts for water remediation, an environmentally motivated process. Specifically, the photocatalytic degradation of tetracycline was studied as a model reaction. The performance of the supports and composite catalyst were determined by evaluating both the degradation and adsorption phenomenon. The influence of several experimental parameters such as catalyst loading, pH, and tetracycline concentration were evaluated. The current study provides important data for water treatment and similar environmental protection applications.

Autophagic degradation of CDK4 is responsible for G0/G1 cell cycle arrest in NVP-BEZ235-treated neuroblastoma.

BACKGROUND: CDK4 is highly expressed and associated with poor prognosis and decreased survival in advanced neuroblastoma (NB). Targeting CDK4 degradation presents a potentially promising therapeutic strategy compared to conventional CDK4 inhibitors. However, the autophagic degradation of the CDK4 protein and its anti-proliferation effect in NB cells has not been mentioned. RESULTS: We identified autophagy as a new pathway for the degradation of CDK4. Firstly, autophagic degradation of CDK4 is critical for NVP-BEZ235-induced G0/G1 arrest, as demonstrated by the overexpression of CDK4, autophagy inhibition, and blockade of autophagy-related genes. Secondly, we present the first evidence that p62 binds to CDK4 and then enters the autophagy-lysosome to degrade CDK4 in a CTSB-dependent manner in NVP-BEZ235 treated NB cells. Similar results regarding the interaction between p62 and CDK4 were observed in the NVP-BEZ235 treated NB xenograft mouse model. CONCLUSIONS: Autophagic degradation of CDK4 plays a pivotal role in G0/G1 cell cycle arrest in NB cells treated with NVP-BEZ235.

ß-d-N4-hydroxycytidine, a metabolite of molnupiravir, exhibits in vitro antiviral activity against rabies virus.

Rabies is a fatal neurological disorder caused by rabies virus (RABV) infection. Approximately 60,000 patients die from rabies annually, and there are no effective treatments for this disease. Nucleoside analogs are employed as antiviral drugs based on their broad antiviral spectrum, and certain nucleoside analogs have been reported to exhibit anti-RABV activity. The nucleoside analog ß-d-N4-hydroxycytidine (NHC) has antiviral effects against a range of RNA viruses. Molnupiravir (MPV), a prodrug of NHC, is clinically used as an oral antiviral drug for coronavirus infections. Despite its broad-spectrum activity, the antiviral activity of NHC against RABV remains unclear. In this study, we reveal that NHC exhibits comparable in vitro anti-RABV activity as ribavirin and favipiravir (also known as T-705) with a 90% effective concentration of 6 µM in mouse neuroblastoma cells. NHC reduced viral loads in neuronal and nonneuronal cells in a dose-dependent manner. Both laboratory and field RABVs (fixed and street strains, respectively) were susceptible to NHC. However, no increase in survival or reduction in viral titers in the brain was observed in RABV-infected mice treated prophylactically with MPV. These findings highlight the potential and challenges of NHC in the treatment of RABV infection.

NAT10 promotes osteoclastogenesis in inflammatory bone loss by catalyzing Fos mRNA ac4C modification and upregulating MAPK signaling pathway.

INTRODUCTION: Excessive osteoclastogenesis is a key driver of inflammatory bone loss. Suppressing osteoclastogenesis has always been considered essential for the treatment of inflammatory bone loss. N-acetyltransferase 10 (NAT10) is the sole enzyme responsible for N4-acetylcytidine (ac4C) modification of mRNA, and is involved in cell development. However, its role in osteoclastogenesis and inflammatory bone loss remained elusive. OBJECTIVES: We aimed to clarify the regulatory mechanism of NAT10 and ac4C modification in osteoclastogenesis and inflammatory bone loss. METHODS: NAT10 expression and ac4C modification during osteoclastogenesis were determined by quantitative real-time PCR (qPCR), western blotting, dot blot and immunofluorescent staining, and the effect of NAT10 inhibition on osteoclast differentiation in vitro was measured by the tartrate-resistant acid phosphatase staining, podosome belts staining assay and bone resorption pit assay. Then, acRIP-qPCR and NAT10RIP-qPCR, ac4C site prediction, mRNA decay assay and luciferase reporter assay were performed to further study the underlying mechanisms. At last, mice models of inflammatory bone loss were applied to verify the therapeutic effect of NAT10 inhibition in vivo. RESULTS: NAT10 expression was upregulated during osteoclast differentiation and highly expressed in alveolar bone osteoclasts from periodontitis mice. Inhibition of NAT10 notably reduced osteoclast differentiation in vitro, as indicated by great reduction of tartrated resistant acid phosphatse positive multinuclear cells, osteoclast-specific gene expression, F-actin ring formation and bone resorption capacity. Mechanistically, NAT10 catalyzed ac4C modification of Fos (encoding AP-1 component c-Fos) mRNA and maintained its stabilization. Besides, NAT10 promoted MAPK signaling pathway and thereby activated AP-1 (c-Fos/c-Jun) transcription for osteoclastogenesis. Therapeutically, administration of Remodelin, the specific inhibitor of NAT10, remarkably impeded the ligature-induced alveolar bone loss and lipopolysaccharide-induced inflammatory calvarial osteolysis. CONCLUSIONS: Our study demonstrated that NAT10-mediated ac4C modification is an important epigenetic regulation of osteoclast differentiation and proposed a promising therapeutic target for inflammatory bone loss.

Experimental and first-principles investigation on how support morphology determines the performance of the Ziegler-Natta catalyst during ethylene polymerization.

One class of the Ziegler-Natta catalysts (ZNC) - the TiCl4/MgCl2 having triethyl aluminum (AlEt3), has been widely utilized during ethylene polymerization. Although the Ti species plays the role of a major active site, an increase of Ti species does not always improve the activity of ZNC. Herein, investigations of experiments and density functional theory (DFT) elucidate this inverse effect of the increased amount of TiCl4 deposition in ZNC because of the pretreatment process. However, the activity of ZNC on pretreated MgCl2 dropped to 60% of the unpretreated one. The DFT demonstrates that the pretreatment strengthened the interaction between TiCl4 and ZNC, especially on the (104) surface, forming the TiCl4-TiCl4 cluster. The existence of this TiCl4-TiCl4 cluster found on the ZNC (104) surface weakens the adsorption of the first AlEt3 molecule and obstructs further alkylation process, making another Ti site of the alkylated TiCl4-TiCl4 cluster inactive. However, the difficult formation of the TiCl4-TiCl4 cluster found on the ZNC (110) is an important key point that enables the activation of all adsorbed TiCl4 on this surface by facilitating the alkylation process. Moreover, the existence of the MgCl2 (110) surface prevents the formation of the TiCl4-TiCl4 cluster significantly. Hence, it is suggested that the existence of the (110) plane on ZNC plays a key role in controlling the performance of the ZNC, especially the stability via the prevention of deactivation caused by the clustering of TiCl4.

Machine learning-assisted substrate binding pocket engineering based on structural information.

Engineering enzyme-substrate binding pockets is the most efficient approach for modifying catalytic activity, but is limited if the substrate binding sites are indistinct. Here, we developed a 3D convolutional neural network for predicting protein-ligand binding sites. The network was integrated by DenseNet, UNet, and self-attention for extracting features and recovering sample size. We attempted to enlarge the dataset by data augmentation, and the model achieved success rates of 48.4%, 35.5%, and 43.6% at a precision of ≥50% and 52%, 47.6%, and 58.1%. The distance of predicted and real center is ≤4 Å, which is based on SC6K, COACH420, and BU48 validation datasets. The substrate binding sites of Klebsiella variicola acid phosphatase (KvAP) and Bacillus anthracis proline 4-hydroxylase (BaP4H) were predicted using DUnet, showing high competitive performance of 53.8% and 56% of the predicted binding sites that critically affected the catalysis of KvAP and BaP4H. Virtual saturation mutagenesis was applied based on the predicted binding sites of KvAP, and the top-ranked 10 single mutations contributed to stronger enzyme-substrate binding varied while the predicted sites were different. The advantage of DUnet for predicting key residues responsible for enzyme activity further promoted the success rate of virtual mutagenesis. This study highlighted the significance of correctly predicting key binding sites for enzyme engineering.

A Novel Liver Fibrosis Marker FIB-5 Index Predicted Response to Cardiac Resynchronization Therapy and Prognostic Outcomes in Patients With Heart Failure.

BACKGROUND: The fibrosis-5 (FIB-5) index is a noninvasive marker for assessing the progression of liver fibrosis and predictor in patients with heart failure (HF). This study investigated the association between the FIB-5 index and response to cardiac resynchronization therapy (CRT) and evaluated its predictive value for prognosis. METHODS: In total, 203 patients who underwent CRT/CRT-defibrillator (CRT-D) implantation were retrospectively included. The FIB-5 index was calculated using blood samples obtained before and after CRT/CRT-D. Response to CRT was defined as a relative reduction in left ventricular end-systolic volume of ≥15% 6 months after CRT/CRT-D. We compared the prognosis after CRT/CRT-D between the groups according to the FIB-5 index. RESULTS: One hundred and twenty-three patients (61%) responded to CRT. The responder group demonstrated a significantly higher FIB-5 index than the nonresponder group (-2.76 ± 3.85 vs. -4.67 ± 3.29, p < 0.001). Receiver-operating characteristic analysis demonstrated that the area under the curve of the FIB-5 index was 0.660 with a cutoff value of -4.00 for responders. In multivariate analysis, FIB-5 index ≥ -4.00 was an independent predictor for CRT response (odds ratio: 3.665, p = 0.003), in addition to QRS duration ≥ 150 ms and echocardiographic dysynchrony. The FIB-5 index increased significantly after 6 months in the responder group but not in the nonresponder group. The FIB-5 index ≥ -4.00 group showed a significantly better prognosis for cardiac death, HF hospitalization, and composite endpoint than the FIB-5 index < -4.00 group. CONCLUSION: The FIB-5 index in addition to classical predictors may be a useful marker for predicting response to CRT.

Inhibition of mitophagy via the EIF2S1-ATF4-PRKN pathway contributes to viral encephalitis.

INTRODUCTION: Mitophagy, a selective form of autophagy responsible for maintaining mitochondrial homeostasis, regulates the antiviral immune response and acts as viral replication platforms to facilitate infection with various viruses. However, its precise role in herpes simplex virus 1 (HSV-1) infection and herpes simplex encephalitis (HSE) remains largely unknown. OBJECTIVES: We aimed to investigate the regulation of mitophagy by HSV-1 neurotropic infection and its role in viral encephalitis, and to identify small compounds that regulate mitophagy to affect HSV-1 infection. METHODS: The antiviral effects of compounds were investigated by Western blot, RT-PCR and plaque assay. The changes of Parkin (PRKN)-mediated mitophagy and Nuclear Factor kappa B (NFKB)-mediated neuroinflammation were examined by TEM, RT-qPCR, Western blot and ELISA. The therapeutic effect of taurine or PRKN-overexpression was confirmed in the HSE mouse model by evaluating survival rate, eye damage, neurodegenerative symptoms, immunohistochemistry analysis and histopathology. RESULTS: HSV-1 infection caused the accumulation of damaged mitochondria in neuronal cells and in the brain tissue of HSE mice. Early HSV-1 infection led to mitophagy activation, followed by inhibition in the later viral infection. The HSV-1 proteins ICP34.5 or US11 deregulated the EIF2S1-ATF4 axis to suppress PRKN/Parkin mRNA expression, thereby impeding PRKN-dependent mitophagy. Consequently, inhibition of mitophagy by specific inhibitor midiv-1 promoted HSV-1 infection, whereas mitophagy activation by PRKN overexpression or agonists (CCCP and rotenone) attenuated HSV-1 infection and reduced the NF-κB-mediated neuroinflammation. Moreover, PRKN-overexpressing mice showed enhanced resistance to HSV-1 infection and ameliorated HSE pathogenesis. Furthermore, taurine, a differentially regulated gut microbial metabolite upon HSV-1 infection, acted as a mitophagy activator that transcriptionally promotes PRKN expression to stimulate mitophagy and to limit HSV-1 infection both in vitro and in vivo. CONCLUSION: These results reveal the protective function of mitophagy in HSE pathogenesis and highlight mitophagy activation as a potential antiviral therapeutic strategy for HSV-1-related diseases.

An Optimized Peptide Antagonist of CXCR4 Limits Survival of BCR-ABL1-Transformed Cells in Philadelphia-Chromosome-Positive B-Cell Acute Lymphoblastic Leukemia.

Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is characterized by reciprocal chromosomal translocation between chromosome 9 and 22, leading to the expression of constitutively active oncogenic BCR-ABL1 fusion protein. CXC chemokine receptor 4 (CXCR4) is essential for the survival of BCR-ABL1-transformed mouse pre-B cells, as the deletion of CXCR4 induces death in these cells. To investigate whether CXCR4 inhibition also effectively blocks BCR-ABL1-transformed cell growth in vitro, in this study, we explored an array of peptide-based inhibitors of CXCR4. The inhibitors were optimized derivatives of EPI-X4, an endogenous peptide antagonist of CXCR4. We observed that among all the candidates, EPI-X4 JM#170 (referred to as JM#170) effectively induced cell death in BCR-ABL1-transformed mouse B cells but had little effect on untransformed wild-type B cells. Importantly, AMD3100, a small molecule inhibitor of CXCR4, did not show this effect. Treatment with JM#170 induced transient JNK phosphorylation in BCR-ABL1-transformed cells, which in turn activated the intrinsic apoptotic pathway by inducing cJun, Bim, and Bax gene expressions. Combinatorial treatment of JM#170 with ABL1 kinase inhibitor Imatinib exerted a stronger killing effect on BCR-ABL1-transformed cells even at a lower dose of Imatinib. Surprisingly, JM#170 actively killed Sup-B15 cells, a BCR-ABL1+ human ALL cell line, but had no effect on the BCR-ABL1- 697 cell line. This suggests that the inhibitory effect of JM#170 is specific for BCR-ABL1+ ALL. Taken together, JM#170 emerges as a potent novel drug against Ph+ ALL.

Absence of Aquaporin-4 (AQP4) Prolongs the Presence of a CD11c+ Microglial Population during Postnatal Corpus Callosum Development.

Aquaporin-4 (AQP4) expression is associated with the development of congenital hydrocephalus due to its structural role in the ependymal membrane. Gene expression analysis of periaqueductal tissue in AQP4-knockout (KO) mice at 11 days of age (P11) showed a modification in ependymal cell adhesion and ciliary protein expression that could alter cerebrospinal fluid homeostasis. A microglial subpopulation of CD11c+ cells was overexpressed in the periaqueductal tissue of mice that did not develop hydrocephalus, suggesting a possible protective effect. Here, we verified the location of this CD11c+ expression in the corpus callosum (CC) and cerebellum of AQP4-KO mice and analysed its time course. Immunofluorescence labelling of the CD11c protein in the CC and cerebellum of WT and KO animals at P3, P5, P7 and P11 confirmed an expanded presence of these cells in both tissues of the KO animal; CD11c+ cells appeared at P3 and reached a peak at P11, whereas in the WT animal, they appeared at P5, reached their peak at P7 and were undetectable by P11. The gene expression analysis in the CC samples at P11 confirmed the presence of CD11c+ microglial cells in this tissue. Among the more than 4000 overexpressed genes, Spp1 stood out with the highest differential gene expression (≅600), with other genes, such as Gpnmb, Itgax, Cd68 and Atp6v0d2, also identified as overexpressed. Therefore, CD11c+ cells appear to be necessary for normal corpus callosum development during postnatal life, and the absence of AQP4 prolonged its expression in this tissue.

Comparison of renal prognosis between dipeptidyl peptidase-4 inhibitor users and non-users.

AIM: To evaluate the renal prognosis of dipeptidyl peptidase-4 inhibitor (DPP-4i) users and non-users using real-world Asian data. METHODS: Using databases from DeSC Healthcare, Inc., patients aged 30 years or older who used antidiabetic drugs from 2014 to 2021 were identified. Propensity score matching analyses were used to compare renal prognosis between DPP-4i users and non-users. The primary outcomes were estimated glomerular filtration rate (eGFR) decline and end-stage kidney disease (ESKD) development in the eGFR of 45 mL/min/1.73m2 or higher and eGFR of less than 45 mL/min/1.73m2 groups, respectively. RESULTS: In total, 65 375 and 9866 patients were identified in the eGFR of 45 mL/min/1.73m2 or higher and eGFR of less than 45 mL/min/1.73m2 groups, respectively. In the eGFR of 45 mL/min/1.73m2 or higher group, propensity score matching created 16 002 pairs. A significant difference was observed in the primary outcome of eGFR decline between DPP-4i users and non-users at 2 years (-2.31 vs. -2.56 mL/min/1.73m2: difference, 0.25 mL/min/1.73m2; 95% confidence interval [CI], 0.06-0.44) and 3 years (-2.75 vs. -3.41 mL/min/1.73m2: difference, 0.66 mL/min/1.73m2; 95% CI, 0.39-0.93). In the eGFR less than 45 mL/min/1.73m2 group, propensity score matching created 2086 pairs. After a mean of 2.2 years of observation, ESKD development was 1.15% and 2.30% in users and non-users, respectively, and Kaplan-Meier analysis revealed a significant difference (log rank P = .005). CONCLUSIONS: This retrospective real-world study revealed that patients using DPP-4is had a better renal prognosis than those not using DPP-4is.

(+)-Catechin attenuates CCI-induced neuropathic pain in male rats by promoting the Nrf2 antioxidant pathway to inhibit ROS/TLR4/NF-κB-mediated activation of the NLRP3 inflammasome.

The objective of this study was to investigate the potential mechanisms by which (+)-catechin alleviates neuropathic pain. Thirty-two male Sprague-Dawley rats were divided into four groups: the sham group, the chronic constriction injury (CCI)group, the CCI+ ibuprofen group, and the CCI+ (+)-catechin group. CCI surgery induces thermal hyperalgesia in rats and (+)-catechin ameliorated CCI-induced thermal hyperalgesia and repaired damaged sciatic nerve in rats. CCI decreased SOD levels in male rat spinal cord dorsal horn and promoted MDA production, induced oxidative stress by increasing NOX4 levels and decreasing antioxidant enzyme HO-1 levels, and also increased protein levels of TLR4, p-NF-κB, NLRP3 inflammasome components, and IL-1ß. In contrast, (+)-catechin reversed the above results. In i vitro experiments, (+)-catechin reduced the generation of reactive oxygen species (ROS) in GMI-R1 cells after LPS stimulation and attenuated the co-expression of IBA-1 and NLRP3. It also showed significant inhibition of the NF-κB and NLRP3 inflammatory pathways and activation of the Nrf2-mediated antioxidant system. Overall, these findings suggest that (+)-catechin inhibits the activation of the NLRP3 inflammasome through the triggering of the Nrf2-induced antioxidant system, the inhibition of the TLR4/NF-κB pathway, and the production of ROS to alleviate CCI-induced neuropathic pain in male rats.

Emerging Roles of Graphitic Carbon Nitride-based Materials in Biomedical Applications.

Graphite carbon nitride (g-C3N4) is a two-dimensional conjugated polymer with a unique energy band structure similar to graphene. Due to its outstanding analytical advantages, such as relatively small band gap (2.7 eV), low-cost synthesis, high thermal stability, excellent photocatalytic ability, and good biocompatibility, g-C3N4 has attracted the interest of researchers and industry, especially in the medical field. This paper summarizes the latest research on g-C3N4-based composites in various biomedical applications, including therapy, diagnostic imaging, biosensors, antibacterial, and wearable devices. In addition, the application prospects and possible challenges of g-C3N4 in nanomedicine are also discussed in detail. This review is expected to inspire emerging biomedical applications based on g-C3N4.

Architectural Decoration of Bioleached NiFeP Surfaces by Co3O4 Flowers for Efficient Electrocatalytic Hydrogen Generation.

In the quest for sustainable hydrogen production via water electrolysis, the development of high-performance, noble-metal-free catalytic systems is highly desired. Herein, we proposed an innovative strategy for the development of an electrocatalyst by refining the surface characteristics of a NiFeP alloy through microbiological techniques and subsequent enrichment of active sites by tailoring 3D hierarchical flower-like structures with intact and interconnected two-dimensional (2D) Co3O4. The resultant 3D Co3O4@NiFeP-5/24h has a porous structure comprised of intercrossed nanoparticles covering the entirety of the catalytic surface. This design ensures comprehensive electrolyte ion penetration and facilitates the release of gas bubbles while reducing bubble adhesion rates. Remarkably, the Co3O4@NiFeP-5/24h electrode demonstrates superior hydrogen evolution (HER) performance in an alkaline medium, characterized by its high stability, low overpotential (106 mV at a current density of 10 mA cm-2), and reduced Tafel slope (98 mV dec-1). Besides, the minimized interfacial contact resistance among the phases of electrode and electrolyte emphasizes the high HER performance of the 3D Co3O4@NiFeP-5/24h electrode. The innovative design and fabrication strategy employed herein holds significant potential for advancing the field of water-splitting electrocatalysis, offering a promising path toward the rational design and development of noble-metal-free electrocatalysts.