Multiple myeloma exosomal miRNAs suppress cGAS-STING antiviral immunity.

DNA virus infection is a significant cause of morbidity and mortality in patients with multiple myeloma (MM). Monocyte dysfunction in MM patients plays a central role in infectious complications, but the precise molecular mechanism underlying the reduced resistance of monocytes to viruses in MM patients remains to be elucidated. Here, we found that MM cells were able to transfer microRNAs (miRNAs) to host monocytes/macrophages via MM cell-derived exosomes, resulting in the inhibition of innate antiviral immune responses. The screening of miRNAs enriched in exosomes derived from the bone marrow (BM) of MM patients revealed five miRNAs that negatively regulate the cGAS-STING antiviral immune response. Notably, silencing these miRNAs with antagomiRs in MM-bearing C57BL/KaLwRijHsd mice markedly reduced viral replication. These findings identify a novel mechanism whereby MM cells possess the capacity to inhibit the innate immune response of the host, thereby rendering patients susceptible to viral infection. Consequently, targeting the aberrant expression patterns of characteristic miRNAs in MM patients is a promising avenue for therapeutic intervention. Considering the miRNA score and relevant clinical factors, we formulated a practical and efficient model for the optimal assessment of susceptibility to DNA viral infection in patients with MM.

Clarifying the Direct Generation of •OH Radicals in Photocatalytic O2 Reduction: Theoretical Prediction Combined with Experimental Validation.

This work systematically studied thermocatalytic and photocatalytic pathways of formaldehyde degradation and H-assisted O2 reduction over a Pt13/anatase-TiO2(101) composite via DFT calculations together with constrained molecular dynamics (MD) simulations. We show that photocatalytic O2 reduction on Pt/TiO2 can directly generate •OH radicals (*O2 → *OOH → •OH) via two hydrogenation steps with small barriers, and the product selectivity (*H2O2 or •OH) is decided by the relative position between catalyst Fermi level and •OH/*H2O2 redox potential (theoretical determination of 0.07 V referencing to the SHE). Such a novel reaction channel was furthermore validated at the liquid-solid interface via constrained MD simulations and experimental electron paramagnetic resonance detections, and a wide range of H resources, e.g., *HCHO, *HCO, *H (H+ + e-), can always drive the direct •OH generation. The additional portion of e--triggered •OH radicals are prone to diffuse into solution or the TiO2 surface and furthermore cooperate with the conventional h+-driven photooxidations.

Full-color biomass carbon dots for high-level information encryption and multi-color light emitting diode applications.

Six biomass carbon dots (BCDs) with adjustable emission from 450 to 680 nm under a single wavelength excitation were successfully synthesized from spinach via solvent control strategy. The obtained BCDs show blue, green, yellow, violet, pink, and red emission with high photoluminescence quantum yield (PLQY = 12.68 ~ 30.77%). Detailed characterizations disclose that the tunable-emission mechanism is caused by the synergistic effect of carbon conjugate and surface oxidation degree. Meanwhile, full-color photoluminescence BCDs/PVP powder and BCDs/PVP/PVA films were fabricated by utilizing the prepared BCDs combined with polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA), respectively, which presented excellent high-level information encryption application. Importantly, multi-color and white light-emitting diode (LED) with Commission Internationale de L' Eclairage (CIE) of blue (0.25, 0.29); green (0.25, 0.31); yellow (0.42, 0.45); red (0.52, 0.31); and white (0.32, 0.31) were achieved by only using our prepared BCDs. This work provides a valuable strategy of preparing multi-color BCDs using readily available biomass materials and paves a way for high-level information encryption and LED applications.

Chemical Vapor Deposition Toward Efficient Bimetallic Atomically Dispersed Oxygen Reduction Catalysts.

Non-precious metal-based nitrogen-doped carbon (M-Nx/C) shows great potential as a substitute for precious metal Pt-based catalysts. However, the conventional pyrolytic methods for forming M-Nx/C active sites are prone to issues such as the lack of synergistic interactions among bimetallic atoms and the potential encasement of active sites, leading to compromised catalytic efficiency and hindered mass transfer. In this work, a highly active FeCo-N-C@U-AC electrocatalyst is developed with a high density of active sites, adequate exposure of catalytic sites, and robust mass transfer capability using the chemical vapor-phase deposition (CVD) technique. The resulting catalyst demonstrates impressive oxygen reduction reaction (ORR) catalytic performance and stability, with half-wave potentials of 0.820 V (0.1 M HClO4) and 0.911 V (0.1 M KOH), respectively. It also exhibits significantly enhanced stability, retaining 93.25% and 98.38% of current after continuous 50 000 s of durability testing, surpassing the retention rates of Pt/C (80.31% in HClO4 and 84.96% in KOH electrolytes). Notably, when employed as a cathode catalyst in proton exchange membrane fuel cells (PEMFCs) and zinc-air flow batteries (ZAFBs), the FeCo-N-C@U-AC catalyst delivers peak power densities of 859 and 162 mW·cm-2, respectively, showcasing competitive performance comparable to benchmark Pt/C.

Vonoprazan-associated Clostridioides difficile infection: an analysis of the Japanese Adverse Drug Event Report and the FDA Adverse Event Reporting System.

Background: Prolonged or excessive use of acid suppressants may increase the risk of Clostridioides difficile infection (CDI) by altering the intestinal microecosystem. Vonoprazan, a novel potassium-competitive acid blocker, exhibits a faster and more sustained acid-suppressive effect than proton pump inhibitors (PPIs). Therefore, vonoprazan may have a greater impact on the gut microbiota, potentially resulting in CDI. Objectives: This study aimed to explore the potential relationship between acid suppressants and CDI by the Japan Adverse Drug Event Report (JADER) and the FDA Adverse Event Reporting System (FAERS) databases. Design: A retrospective analysis of the JADER and FAERS databases was examined by disproportionality analysis. Methods: We performed signal detection analyses of CDI induced by vonoprazan and PPIs using the JADER and FAERS databases. The association between acid suppressants and CDI was calculated using the reporting odds ratio (ROR) and corresponding 95% confidence interval (95% CI). When the lower limit of the 95% CI is exceeded by 1, the association is considered statistically significant. Results: In the JADER database, the ROR (95% CI) for vonoprazan and PPIs based on suspect drug reports was 15.84 (12.23-20.50) and 2.51 (1.92-3.28), respectively. In the FAERS database, the ROR (95% CI) for vonoprazan and PPIs based on primary and secondary suspect drug reports was 11.50 (6.36-20.82) and 1.42 (1.34-1.51), respectively. Subgroup analysis showed that elderly patients aged 60 years and older were more strongly associated with CDI. The ROR (95% CI) for vonoprazan and PPIs in patients aged 60 years and older in the JADER database was 15.35 (11.59-20.33) and 1.65 (1.14-2.39), respectively. Similarly, the ROR (95% CI) for vonoprazan and PPIs in the FAERS database was 12.56 (6.26-25.20) and 1.43 (1.31-1.57), respectively. Excluding the effect of Helicobacter pylori (H. pylori) infection, the use of acid suppressants was still associated with CDI. Conclusion: While signal detection analysis based on the JADER and FAERS databases could not establish causality, our study demonstrated that both vonoprazan and PPIs were significantly associated with CDI. Vonoprazan showed a stronger association with CDI in both databases.

Introduction: Vonoprazan is a new type of acid suppressant, which has a stronger effect on acid inhibition than traditional proton pump inhibitors (PPIs). Vonoprazan may have a greater impact on the gut microbiota, which may increase the risk of Clostridioides difficile infection (CDI). The FDA created the FDA Adverse Event Reporting System (FAERS) database to support the post-market surveillance program. The PMDA created the Japan Adverse Drug Reaction Event Report (JADER) database to specifically collect adverse reaction reports in Japan. To further understand the potential relationship between acid suppressants and CDI, this study was analyzed using the JADER and FAERS databases. Methods: This study analyzed cases of CDI reported after the use of acid suppressants in the JADER and FAERS databases. Results: The analysis revealed that vonoprazan and PPIs are significantly associated with CDI in both databases. Notably, vonoprazan exhibited a stronger association compared to PPIs. Subgroup analysis indicated that this association was more pronounced in elderly patients aged 60 years and older. Additionally, excluding the influence of Helicobacter pylori (H. pylori) did not diminish the association between acid suppressants and CDI. Conclusion: Although signal detection analysis based on the JADER and FAERS databases could not establish causality, the results showed that both vonoprazan and PPIs were significantly associated with CDI. Vonoprazan was also more strongly associated with CDI than PPIs, which could be a potential safety concern, and further clinical studies are needed to confirm this finding.

Vonoprazan and Clostridioides difficile infection risk.

Analysis of Changes and Diagnostic Value of Doppler Ultrasound Parameters in Patients with Acute Kidney Injury after Laparoscopic Radical Prostatectomy.

BACKGROUND: Early diagnosis of postoperative acute kidney injury (AKI) is crucial. This study investigated the changes and early diagnostic value of Doppler ultrasound parameters in patients with AKI after laparoscopic radical prostatectomy (LRP). METHODS: This study retrospectively analysed the clinical data of 198 patients with LRP undergoing Doppler ultrasound from May 2020 to May 2022. The incidence of AKI after LRP was measured based on diagnostic criteria of AKI developed by Kidney Disease: Improving Global Outcomes. The patients were divided into AKI group (n = 12) and non-AKI group (n = 186) in accordance with the presence or absence of AKI. This study compared changes in Doppler ultrasound parameters between two groups, and evaluated the clinical efficacy of single and combined diagnosis of ultrasound parameters using receiver operating characteristic (ROC) curve and area under the curve (AUC). RESULTS: Twelve patients experienced postoperative AKI, with an incidence rate of 6.06%. No significant difference was found in baseline data, serum creatinine (Scr), urinary output and blood potassium levels of both groups (p > 0.05). The urinary output 1 day after surgery was significantly lower than that before surgery (p < 0.05). The AKI group demonstrated higher pulsatility index (PI) and resistive index (RI) of the renal interlobar artery than the non-AKI group (p < 0.05), with no significant difference in peak systolic velocity (PSV) in both groups (p > 0.05). No significant difference was observed in the Doppler ultrasound parameters of renal segmental artery and main renal artery (p > 0.05). The AUCs in the PI of the renal interlobar artery, the RI of the renal interlobar artery, and the combined diagnosis were 0.720, 0.704 and 0.724, respectively. ROC curve showed that the above two Doppler ultrasound parameters had good diagnostic efficacy for AKI after LRP (p < 0.05). CONCLUSIONS: The PI and RI of renal interlobar artery in the AKI group after LRP were significantly different from those in the non-AKI group. These two Doppler ultrasound parameters had good diagnostic efficacy in the early identification of AKI after LRP. Thus, they could provide reference and guidance for clinical practice.

Orally administrated liquid metal agents for inflammation-targeted alleviation of inflammatory bowel diseases.

Rapid drug clearance and off-target effects of therapeutic drugs can induce low bioavailability and systemic side effects and gravely restrict the therapeutic effects of inflammatory bowel diseases (IBDs). Here, we propose an amplifying targeting strategy based on orally administered gallium (Ga)-based liquid metal (LM) nano-agents to efficiently eliminate reactive oxygen and nitrogen species (RONS) and modulate the dysregulated microbiome for remission of IBDs. Taking advantage of the favorable adhesive activity and coordination ability of polyphenol structure, epigallocatechin gallate (EGCG) is applied to encapsulate LM to construct the formulations (LM-EGCG). After adhering to the inflamed tissue, EGCG not only eliminates RONS but also captures the dissociated Ga to form EGCG-Ga complexes for enhancive accumulation. The detained composites protect the intestinal barrier and modulate gut microbiota for restoring the disordered enteral microenvironment, thereby relieving IBDs. Unexpectedly, LM-EGCG markedly decreases the Escherichia_Shigella populations while augmenting the abundance of Akkermansia and Bifidobacterium, resulting in favorable therapeutic effects against the dextran sulfate sodium-induced colitis.

Interaction of a non-axisymmetric artificial single spatula with rough surfaces.

Hair-like attachment structures are frequently used by animals to create stable contact with rough surfaces. Previous studies focused primarily on axisymmetric biomimetic models of artificial spatulas, such as those with a mushroom-shaped and cylinder-shaped geometry, in order to simulate the so-called gecko effect. Here, two geometric prototypes of artificial adhesive structures with non-axisymmetric properties were designed. The investigation of the prototype's interactions with rough surfaces was carried out using the finite element software ABAQUS. Under increasing vertical displacement, the effect of asperity size on the contact pressure evolution of the spatula was investigated. It has been demonstrated that the contact behaviour is greatly affected by the flexibility of the spatula, which is caused by its variable thickness. The thinner spatula shows a higher nominal contact area and attaches more strongly to various rough surfaces. Although a thicker spatula is more susceptible to the 'leverage' phenomenon, which occurs when excessively applied displacements prematurely reduce the nominal contact area, it obtains the ability to regulate attachment during unidirectional loading. Two non-axisymmetric prototypes provide different design concepts for the artificial adhesives. It is hoped that this study will provide fresh viewpoints and innovations that contribute to the development of biologically inspired adhesives.

Characterization of biomass burning tracers in particulate matter at 12 sites in China: Significant increase of coal combustion emitted levoglucosan in northern China during winter.

Biomass burning (BB) is the largest contributor to carbonaceous aerosols globally. Specific organic tracers can track BB particles and identify BB types. At present, there is limited information on the composition of BB tracers on a continental scale. In this study, we conducted year-round sampling of particulate matter (PM) at 12 sites in China. Nine BB tracers were measured in PM with aerodynamic diameters <1.1 µm (PM<1.1), in the range of 1.1-3.3 µm (PM1.1-3.3), and > 3.3 µm (PM>3.3). The annual average concentration of these nine BB tracers (∑9 BB tracers) in the total PM was 366 ng m-3 with the majority of levoglucosan (66 %). The concentration of ∑9 BB tracers was higher in northern China than in southern China, especially in winter. ∑9 BB tracers were most enriched in PM<1.1 (50-61 % in mass), followed by PM1.1-3.3 and PM>3.3. The highest concentrations of ∑9 BB tracers were observed in winter, while satellite-recorded fire spots were intensive in autumn and spring. The mismatch of seasonal trends between them indicated that the high levels of BB tracers in winter was not due to open BB. The composition of 4-hydroxybenzoic acid, syringic acid and vanillic acid suggested that the burning of crop residues and softwoods were the major BB types in China. The ratio of levoglucosan to mannosan could neither identify the major BB types in China nor distinguish between BB and coal combustion. Correlation analysis and the PMF model demonstrated that non-BB sources contributed 7 %-58 % to levoglucosan at the 12 sites, with coal combustion being the predominant non-BB source in China, especially in northern urban sites during winter. Our findings suggest that caution should be taken in application of these organic tracers to identify BB types and estimate BB aerosols.

Jujuboside A through YY1/CYP2E1 signaling alleviated type 2 diabetes-associated fatty liver disease by ameliorating hepatic lipid accumulation, inflammation, and oxidative stress.

Non-alcoholic fatty liver disease (NAFLD) was a chronic complication of type 2 diabetes mellitus (T2DM), and this comorbid disease lacked therapeutic drugs. Semen Ziziphi Spinosae (SZS) was the seed of Ziziphus jujuba var. Spinosa (Bunge) Hu ex H.F. Chow, and it could alleviate the symptoms of T2DM patients. As a triterpene saponin, Jujuboside A (Ju A) was the main active substance isolated from SZS and could improve hyperglycemia of diabetic mice. However, it was still unknown whether Ju A has protective effects on T2DM-associated NAFLD. Our study showed that Ju A attenuated T2DM-associated liver damage by alleviating hepatic lipid accumulation, inflammatory response, and oxidative stress in the liver of db/db mice, and high glucose (HG) and free fatty acid (FFA) co-stimulated human hepatocellular carcinomas (HepG2) cells. Along with the improved hyperglycemia and liver injury, Ju A restrained Yin Yang 1 (YY1)/cytochrome P450 2E1 (CYP2E1) signaling in vivo and in vitro. YY1 overexpression intercepted the protective effects of Ju A on T2DM-induced liver injury via promoting hepatic lipid accumulation, inflammatory response, and oxidative stress. While, the blocking effect of YY1 overexpression on Ju A's hepatoprotective effect was counteracted by further treatment of CYP2E1 specific inhibitor diethyldithiocarbamate (DDC) in vitro. In-depth mechanism research showed that Ju A through YY1/CYP2E1 signaling promoted hepatic fatty acid ß-oxidation, and inhibited inflammatory response and oxidative stress by activating peroxisome proliferator-activated receptor alpha (PPARα), leading to the improvement of T2DM-associated NAFLD. Ju A might be a potential agent in the treatment and health care of T2DM-associated liver disease, especially NAFLD.

Ultra-Wide Interlayered WxMo2xSy Alloy Electrode Patterning through High-Precision Controllable Photonic-Synthesis.

Ultra-thin 2D materials have great potential as electrodes for micro-supercapacitors (MSCs) because of their facile ion transport channels. Here, a high-precision controllable photonic-synthesis strategy that provided 1 inch wafer-scale ultra-thin film arrays of alloyed WxMo2xSy with sulfur vacancies and expanded interlayer (13.2 Å, twice of 2H MoS2) is reported. This strategy regulates the nucleation and growth of transition metal dichalcogenides (TMDs) on the picosecond or even femtosecond scale, which induces Mo-W alloying, interlayer expansion, and sulfur loss. Therefore, the diffusion barrier of WxMo2xSy is reduced, with charge transfer and ion diffusion enhancing. The as-prepared symmetric MSCs with the size of 100 × 100 µm2 achieve ultrahigh specific capacitance (242.57 mF cm-2 and 242567.83 F cm-3), and energy density (21.56 Wh cm-3 with power density of 485.13 W cm3). The established synthesis strategy fits numerous materials, which provides a universal method for the flexible synthesis of electrodes in microenergy devices.

TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA.

Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically. In an Alzheimer's disease model, we demonstrate silencing of mutant APPswe mRNA without altering the wild-type APP mRNA. Notably, due to the compact size of TaqTth, we are able to combine with APOE2 overexpression in a single AAV vector, which results in stronger inhibition of pathologies.

A disproportionality analysis of adverse events caused by GnRHas from the FAERS and JADER databases.

Background: Gonadotrophin-releasing hormone analogs (GnRHas) play a significant role in addressing gynecological diseases, central precocious puberty, and cancer. However, ensuring the safety of GnRHas in real-world applications requires continuous vigilance. In light of this, we undertook a disproportionality analysis focused on adverse events (AEs) associated with GnRHas using data from both the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER). We evaluated GnRHas-associated AEs and characterized the clinical priority of unlisted AEs caused by each GnRHa from the different databases. Methods: In the disproportionality analysis, we applied two adjusted algorithms to identify signals related to GnRHas in the FAERS and JADER databases from 2004 to 2023. Additionally, we utilized the Statistical Analysis System (SAS, 9.4) to examine potential and high-aROR (adjusted reporting odds ratio) signals associated with GnRHas. We performed clinical priority assessment for suspicious PTs and an analysis of serious/non-serious outcomes. We also gathered information on the onset times of AEs linked with GnRHas from both databases. Results: From January 2004 to September 2023, FAERS and JADER recorded a total of 50,360,413 and 1,440,200 AEs, respectively. Employing two algorithms, the suspicious preferred terms (PTs) related to leuprolide (Leu) were 562 potential PTs (44 unlisted in specifications), followed by goserelin (Gos) with 189 PTs (28 unlisted), triptorelin (Tri) with 172 PTs (28 unlisted), and Leu-JADER with 85 PTs (10 unlisted). At the same PT level, the differences in GnRHas between the two databases were observed, such as cardiac failure, diabetes mellitus, liver disorder, dementia, suicidal ideation, interstitial lung disease, urinary disorders, and hypertensive crisis. In an analysis of serious vs. non-serious outcomes, a total of 43 AEs of Leu were more likely to be reported as serious AEs with p < 0.05 (such as asthenia, urinary retention, diabetes mellitus, interstitial lung disease, gait disturbance, and so on), following by Tri (6 AEs), and Gos (4 AEs). Based on the clinical priority score, 41 PTs of Leu, 26 PTs of Tri, 24 PTs of Gos, and 8 PTs of Leu-JADER were graded as weak. There were 3 PTs of Leu, 2 PTs of Tri, 4 PTs of Gos, and 2 PTs of Leu-JADER that were graded as moderate. Notably, in the assessment of the relevant evidence, 2 PTs (loss of libido and urinary tract toxicity caused by Leu), 1 PT (electrolyte imbalance caused by Tri), and 2 PTs (anorexia and suicidal ideation caused by Gos) showed a strong level of evidence with "++." The differences in the signal strength of the same PTs from two databases were also worth noting. Moreover, the median onset time for GnRHas (Leu, Tri, and Gos) was 23 days (0, 298), 22 days (0, 181), and 217 days (29, 706), respectively, as median (Q1, Q3). Conclusion: An examination of two databases revealed suspicious AEs associated with GnRHas. Our study found potential new AE signals of GnRHas and supported continuous clinical monitoring, pharmacovigilance, regional differences, and further studies of GnRHas.

Comparative Efficacy and Safety of Potassium-Competitive Acid Blockers vs. Proton Pump Inhibitors for Peptic Ulcer with or without Helicobacter pylori Infection: A Systematic Review and Network Meta-Analysis.

Novel potassium-competitive acid blockers (P-CABs) have emerged as effective acid-suppressive drugs in recent years, replacing proton pump inhibitors (PPIs). We aim to compare the efficacy and safety of P-CABs versus PPIs in the treatment of peptic ulcers with or without Helicobacter pylori (H. pylori) infection. We searched in PubMed, Embase, WOS, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases (all years up to January 2024). Efficacy and safety outcomes were evaluated using odds ratio (OR) and 95% confidence intervals (CI). The Surface Under the Cumulative Ranking (SUCRA) probabilities were used to rank each intervention. Among 14,056 studies screened, 56 studies involving 9792 participants were analyzed. Vonoprazan demonstrated the best efficacy in ulcer healing rate and H. pylori eradication rate (SUCRA = 86.4% and 90.7%, respectively). Keverprazan ranked second in ulcer healing rates (SUCRA = 76.0%) and was more effective in pain remission rates (SUCRA = 91.7%). The risk of adverse events was low for keverprazan (SUCRA = 11.8%) and tegoprazan (SUCRA = 12.9%), and moderate risk for vonoprazan (SUCRA = 44.3%) was demonstrated. Compared to lansoprazole, vonoprazan exhibited a higher risk of drug-related adverse events (OR: 2.15; 95% CI: 1.60-2.89) and serious adverse events (OR: 2.22; 95% CI: 1.11-4.42). Subgroup analysis on patients with H. pylori-positive peptic ulcers showed that vonoprazan was at the top of the SUCRA rankings, followed by keverprazan. Vonoprazan showed superior performance in peptic ulcers, especially for patients with H. pylori-positive peptic ulcers. However, the risk of adverse events associated with vonoprazan should be noted. Keverprazan has also shown good therapeutic outcomes and has performed better in terms of safety.

Oral microsphere formulation of M2 macrophage-mimetic Janus nanomotor for targeted therapy of ulcerative colitis.

Oral medication for ulcerative colitis (UC) is often hindered by challenges such as inadequate accumulation, limited penetration of mucus barriers, and the intricate task of mitigating excessive ROS and inflammatory cytokines. Here, we present a strategy involving sodium alginate microspheres (SAMs) incorporating M2 macrophage membrane (M2M)-coated Janus nanomotors (denominated as Motor@M2M) for targeted treatment of UC. SAM provides a protective barrier, ensuring that Motor@M2M withstands the harsh gastric milieu and exhibits controlled release. M2M enhances the targeting precision of nanomotors to inflammatory tissues and acts as a decoy for the neutralization of inflammatory cytokines. Catalytic decomposition of H2O2 by MnO2 in the oxidative microenvironment generates O2 bubbles, propelling Motor@M2M across the mucus barrier into inflamed colon tissues. Upon oral administration, Motor@M2M@SAM notably ameliorated UC severity, including inflammation mitigation, ROS scavenging, macrophage reprogramming, and restoration of the intestinal barrier and microbiota. Consequently, our investigation introduces a promising oral microsphere formulation of macrophage-biomimetic nanorobots, providing a promising approach for UC treatment.

Scorpion venom heat-resistant synthesized peptide ameliorates epileptic seizures and imparts neuroprotection in rats mediated by NMDA receptors.

Finding new and effective natural products for designing antiepileptic drugs is highly important in the scientific community. The scorpion venom heat-resistant peptide (SVHRP) was purified from Buthus martensii Karsch scorpion venom, and subsequent analysis of the amino acid sequence facilitated the synthesis of a peptide known as scorpion venom heat-resistant synthesis peptide (SVHRSP) using a technique for peptide synthesis. Previous studies have demonstrated that the SVHRSP can inhibit neuroinflammation and provide neuroprotection. This study aimed to investigate the antiepileptic effect of SVHRSP on both acute and chronic kindling seizure models by inducing seizures in male rats through intraperitoneal administration of pentylenetetrazole (PTZ). Additionally, an N-methyl-D-aspartate (NMDA)-induced neuronal injury model was used to observe the anti-excitotoxic effect of SVHRSP in vitro. Our findings showed that treatment with SVHRSP effectively alleviated seizure severity, prolonged latency, and attenuated neuronal loss and glial cell activation. It also demonstrated the prevention of alterations in the expression levels of NMDA receptor subunits and phosphorylated p38 MAPK protein, as well as an improvement in spatial reference memory impairment during Morris water maze (MWM) testing in PTZ-kindled rats. In vitro experiments further revealed that SVHRSP was capable of attenuating neuronal action potential firing, inhibiting NMDA receptor currents and intracellular calcium overload, and reducing neuronal injury. These results suggest that the antiepileptic and neuroprotective effects of SVHRSP may be mediated through the regulation of NMDA receptor function and expression. This study provides new insight into therapeutic strategies for epilepsy.

The ArgR-Regulated ADI Pathway Facilitates the Survival of Vibrio fluvialis under Acidic Conditions.

Vibrio fluvialis is an emerging foodborne pathogenic bacterium that can cause severe cholera-like diarrhea and various extraintestinal infections, posing challenges to public health and food safety worldwide. The arginine deiminase (ADI) pathway plays an important role in bacterial environmental adaptation and pathogenicity. However, the biological functions and regulatory mechanisms of the pathway in V. fluvialis remain unclear. In this study, we demonstrate that L-arginine upregulates the expression of the ADI gene cluster and promotes the growth of V. fluvialis. The ADI gene cluster, which we proved to be comprised of two operons, arcD and arcACB, significantly enhances the survival of V. fluvialis in acidic environments both in vitro (in culture medium and in macrophage) and in vivo (in mice). The mRNA level and reporter gene fusion analyses revealed that ArgR, a transcriptional factor, is necessary for the activation of both arcD and arcACB transcriptions. Bioinformatic analysis predicted the existence of multiple potential ArgR binding sites at the arcD and arcACB promoter regions that were further confirmed by electrophoretic mobility shift assay, DNase I footprinting, or point mutation analyses. Together, our study provides insights into the important role of the ArgR-ADI pathway in the survival of V. fluvialis under acidic conditions and the detailed molecular mechanism. These findings will deepen our understanding of how environmental changes and gene expression interact to facilitate bacterial adaptations and virulence.

A study on the morphology of iliac crest based on the objectives of jaw bone defect reconstruction.

OBJECTIVES: to understand the morphological characteristics of iliac crest and provide advice and assistance for jaw bone reconstruction with iliac bone flap by evaluating the thickness and curvature of iliac crest. MATERIALS AND METHODS: 100 patients who had taken Spiral CT of the Abdominal region before surgeries between 2020 and 2022 were included in this study. 3D reconstruction images of the iliac bones were created. 5 vertical planes perpendicular to the iliac crest were made every 2 cm along the centerline of the iliac crest (VP2 ~ VP10). On these vertical planes, 4 perpendicular lines were made every 1 cm along the long axis of the iliac crest (D1 ~ D4). The thicknesses at these sites, horizontal angle (HA) of iliac crest and the distance between inflection point and the central point of anterior superior iliac spine (DIA) were measured. RESULTS: The thickness of iliac bone decreased significantly from D1 ~ D4 on VP6 ~ VP10 and from VP2 ~ VP10 on D3 and D4 level (P<0.05). HA of iliac crests was 149.13 ± 6.92°, and DIA was 7.36 ± 1.01 cm. Iliac bone thickness, HA and DIA had very weak or weak correlation with patient's age, height and weight. CONCLUSIONS: The average thicknesses of iliac crest were decreased approximately from front to back, from top to bottom. The thickness and curvature of the iliac crest were difficult to predict by age, height and weight. CLINICAL RELEVANCE: Virtual surgical planning is recommended before jaw bone reconstruction surgery with iliac bone flap, and iliac crest process towards alveolar process might be a better choice.

Integrative analysis reveals different feature of intrahepatic cholangiocarcinoma subtypes.

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) has two main histological subtypes: large and small duct-type iCCA, which are characterized by different clinicopathological features. This study was conducted with the purpose of expanding our understanding of their differences in molecular features and immune microenvironment. METHODS: We selected 132 patients who underwent radical surgery at our department between 2015 and 2021 for clinical and survival analyses. Whole-exome sequencing was performed to analyse mutational landscapes. Bulk RNA sequencing and single-cell RNA sequencing data were used for pathway enrichment and immune infiltration analyses based on differentially expressed genes. The function of PPP1R1B was analysed both in vitro and in vivo and the gene mechanism was further investigated. RESULTS: We found that large duct-type iCCA had worse overall survival and recurrence-free survival rates than small duct-type iCCA. Mutations in ARID1A, DOT1L and ELF3 usually occur in large duct-type iCCA, whereas mutations in IDH1 and BAP1 occur in small duct-type iCCA. Among the differentially expressed genes, we found that PPP1R1B was highly expressed in large duct-type iCCA tumour tissues. Expression of PPP1R1B promoted cell proliferation, migration and invasion and indicated a worse prognosis. A combination of USF2 with the promoter of PPP1R1B can enhance gene expression in iCCA, which may further affect the expression of genes such as AHNAK, C4BPA and activating the PI3K/AKT pathway. CONCLUSIONS: Our findings extend our understanding of large and small duct-type iCCA. In addition, PPP1R1B may serve as a potential marker and therapeutic target for large duct-type iCCA.