OTULIN deficiency: focus on innate immune system impairment.

OTULIN deficiency is a complex disease characterized by a wide range of clinical manifestations, including skin rash, joint welling, lipodystrophy to pulmonary abscess, and sepsis shock. This disease is mechanistically linked to mutations in the OTULIN gene, resulting in an immune disorder that compromises the body's ability to effectively combat pathogens and foreign stimuli. The OTULIN gene is responsible for encoding a deubiquitinating enzyme crucial for hydrolyzing Met1-poly Ub chains, and its dysfunction leads to dysregulated immune responses. Patients with OTULIN deficiency often exhibit an increase in monocytes, including neutrophils and macrophages, along with inflammatory clinical features. The onset of symptoms typically occurs at an early age. However, individuals with OTULIN haploinsufficiency are particularly susceptible to life-threatening staphylococcal infections. Currently, the most effective treatment for patients with OTULIN biallelic mutations involves the use of TNF-blocking agents, which target the dysregulated immune response. In conclusion, OTULIN deficiency presents a complex clinical picture with diverse manifestations, attributed to mutations in the OTULIN gene. Understanding the underlying mechanisms is crucial for developing targeted therapeutic interventions to address this challenging condition. Further research into the pathophysiology of OTULIN deficiency is essential for improving clinical management and outcomes for affected individuals.

[Treatment of Tile type C pelvic ring fracture using orthopedic robot combined with Starr pelvis reduction frame].

OBJECTIVE: To investigate the clinical effect of orthopedic robot combined with Starr pelvic reduction frame in the treatment of Tile type C pelvic ring fracture. METHODS: From October 2019 to May 2021, 14 patients with type C pelvic ring fracture were treated with robotic combined with Starr pelvic reduction frame, including 9 males and 5 females. The age ranged from 33 to 69 years. All the 14 patients had fresh closed fractures without femur, tibia and fibula fracture. Surgery was completed from 4 to 7 d after hospital admission. During the operation, the X-ray carbon bed was used, the pelvic ring was reduced by Starr pelvis reduction frame, and pelvic ring fracture was treated by orthopedic robot. Operation time, bleeding volume, fluoroscopy times of single screw placement, fracture reduction quality, affected limb function and complications were observed. Radiological reduction was evaluated using Matta scoring standard, and clinical efficacy was evaluated by Majeed pelvic function scoring system at the final follow-up. RESULTS: All of 14 patients successfully completed the operation, the operation time was 84 to 141 min, the bleeding volume was 20 to 50 ml, and the fluoroscopy times of single screw insertion was 4 to 9 times. All of 14 patients were followed up for 12 to 24 months. The healing time was 3 to 7 months. No complications such as fracture of internal fixation, screw loosening, infection and nerve injury were found. According to the evaluation criteria of Matta imaging reduction, 9 cases were excellent, 4 cases were good, and 1 case was fair. At the final follow-up, Majeed pelvic function scoring system was used:10 cases were excellent, 4 cases were good. CONCLUSION: The treatment of type C pelvic ring fracture with robotic combined Starr pelvis reduction frame is simple, time-saving, less trauma, less complications and effective.

Ether-Water Co-Solvent Electrolytes Enhanced Vanadium Oxide Cathode Cyclic Behaviors for Zinc Batteries.

Vanadium-based compounds are fantastic cathodes for aqueous zinc metal batteries due to the high specific capacity and excellent rate capability. Nevertheless, the practical application has been hampered by the dissolution of vanadium in traditional aqueous electrolytes owing to the strong polarity of water molecules. Herein, we propose a hybrid electrolyte made of Zn(ClO4)2 salt in tetraethylene glycol dimethyl ether (G4) and H2O solvents to upgrade the cycle life of Zn//K0.486V2O5 battery. The G4 jointly solvates with Zn2+ ions and replaces a portion of the H2O molecules in the Zn2+ solvation sheath. It forms a strong bond with H2O, reducing its activity, and significantly inhibiting vanadium dissolution and water-induced parasitic reaction. Consequently, the optimized electrolyte with H2O and G4 volume ratio of 5 : 5 enhances the cycling stability of Zn//K0.486V2O5 battery, enabling it to reach up to 600 cycles. In addition, the battery demonstrates a satisfactory reversible capacity of 475.7 mAh g-1 and excellent rate performance attributed to the moderate ionic conductivity (28.8 mS cm-1) of the hybrid electrolyte. Last but not least, in the optimized electrolyte, the symmetric Zn//Zn cells deliver a long cycling performance of 400 h, while the asymmetric Zn//Cu cells shows a high average coulombic efficiency of 97.4 %.

Improved Double Deep Q-Network Algorithm Applied to Multi-Dimensional Environment Path Planning of Hexapod Robots.

Detecting transportation pipeline leakage points within chemical plants is difficult due to complex pathways, multi-dimensional survey points, and highly dynamic scenarios. However, hexapod robots' maneuverability and adaptability make it an ideal candidate for conducting surveys across different planes. The path-planning problem of hexapod robots in multi-dimensional environments is a significant challenge, especially when identifying suitable transition points and planning shorter paths to reach survey points while traversing multi-level environments. This study proposes a Particle Swarm Optimization (PSO)-guided Double Deep Q-Network (DDQN) approach, namely, the PSO-guided DDQN (PG-DDQN) algorithm, for solving this problem. The proposed algorithm incorporates the PSO algorithm to supplant the traditional random selection strategy, and the data obtained from this guided approach are subsequently employed to train the DDQN neural network. The multi-dimensional random environment is abstracted into localized maps comprising current and next level planes. Comparative experiments were performed with PG-DDQN, standard DQN, and standard DDQN to evaluate the algorithm's performance by using multiple randomly generated localized maps. After testing each iteration, each algorithm obtained the total reward values and completion times. The results demonstrate that PG-DDQN exhibited faster convergence under an equivalent iteration count. Compared with standard DQN and standard DDQN, reductions in path-planning time of at least 33.94% and 42.60%, respectively, were observed, significantly improving the robot's mobility. Finally, the PG-DDQN algorithm was integrated with sensors onto a hexapod robot, and validation was performed through Gazebo simulations and Experiment. The results show that controlling hexapod robots by applying PG-DDQN provides valuable insights for path planning to reach transportation pipeline leakage points within chemical plants.

Identification and characterization of the Dmrt1B gene in the oriental river prawn, Macrobrachium nipponense.

Dmrt (doublesex and mab-3 related transcription factor) is a protein family of transcription factors implicated in sexual regulation. Dmrt proteins are widely conserved and known for their involvement in sex determination and differentiation across species, from invertebrates to humans. In this study, we identified a novel gene with a DM (doublesex/Mab-3)-domain gene in the river prawn, Macrobrachium nipponense, which we named MniDmrt1B due to its similarities and close phylogenetic relationship with Dmrt1B in Macrobrachium rosenbergii. Through amino acid alignments and structural predictions, we observed conservation and identified putative active sites within the DM domain. qRT-PCR analysis revealed that MniDmrt1B exhibited high expression levels in the testis, with consistently higher expression in males compared to females during development. Additionally, similar to other sex-regulated genes, the MniDmrt1B gene exhibited high expression levels during the sex differentiation-sensitive periods in M. nipponense. These results strongly indicated that MniDmrt1B probably plays an important role in testis development and sex differentiation in M. nipponense.

Transition metal single-atoms supported on hexagonal ZnIn2S4 monolayers for the hydrogen evolution reaction.

Herein, we report a series of 5d transition metal (TM) single atoms supported on ZIS as promising catalysts for the hydrogen evolution reaction using first-principles calculations. The binding behaviors of TMs with the ZIS surface in single-atom catalyst formation are analysed using the adsorption energy (Eads), partial density of states (PDOS), charge density difference (CDD), and crystal orbital Hamilton population (COHP). The TM@ZIS (TM = Ta, W, Re, Os, Ir, and Pt) shows excellent hydrogen evolution performance with the Gibbs free energy (ΔGH*) values from -0.120 to 0.128 eV. The Tafel and Heyrovsky reaction mechanisms to drive H2 formation are also identified.

Activation of the p62-Keap1-Nrf2 pathway improves pulmonary arterial hypertension in MCT-induced rats by inhibiting autophagy.

Autophagy is implicated in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to investigate whether the p62-Keap1-Nrf2 pathway affects the development of PAH by mediating autophagy. A PAH rat model was established using monocrotaline (MCT). Pulmonary artery smooth muscle cells (PASMCs) were extracted, and the changes in proliferation, migration, autophagy, and oxidative stress were analyzed following overexpression or knockdown of p62. The impact of p62 on the symptoms of PAH rats was assessed by the injection of an adenovirus overexpressing p62. We found that the knockdown of p62 increased the proliferation and migration of PASMCs, elevating the oxidative stress of PASMCs and upregulating gene expression of NADPH oxidases. Co-IP assay results demonstrated that p62 interacted with Keap1. p62 knockdown enhanced Keap1 protein stability and Nrf2 ubiquitination. LC3II/I and ATG5 were expressed more often when p62 was knocked down. Treating with an inhibitor of autophagy reversed the impact of p62 knockdown on PASMCs. Nrf2 inhibitor treatment reduced the expression of Nrf2 and p62, while increasing the expression of Keap1, LC3II/I, and ATG5 in PASMCs. However, overexpressing p62 diminished mRVP, SPAP, and Fulton index in PAH rats and attenuated pulmonary vascular wall thickening. Overexpression of p62 also decreased the expression of Keap1, LC3II/I, and ATG5 and increased the nuclear expression of Nrf2 in PAH rats. Importantly, overexpression of p62 reduced oxidative stress and the NADPH oxidase expression in PAH rats. Overall, activation of the p62-Keap1-Nrf2 positive feedback signaling axis reduces the proliferation and migration of PASMCs and alleviates PAH by inhibiting autophagy and oxidative stress.

Effectiveness and economic evaluation of rhTPO and rhIL-11 in the treatment of cancer therapy induced thrombocytopenia based on real-world research.

Objective: Based on real-world research, we aimed to evaluate the effectiveness and economy of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin 11 (rhIL-11) in the treatment of cancer therapy induced thrombocytopenia (CTIT). Methods: We retrospectively collected clinical data of patients with CTIT who were treated with rhTPO or rhIL-11 in a single cancer hospital from January 2020 to December 2021. Propensity score matching (PSM) was applied to eliminate confounding factors. The measurements of effectiveness analysis were the platelet compliance rate, days of medication, days of compliance, highest platelet count after medication, platelet count elevation before and after medication, and the lowest platelet count after next-cycle cancer therapy. The economic evaluation was performed according to the results of the effectiveness evaluation. At the same time, patients were stratified according to type of tumor and grade of thrombocytopenia for subgroup analysis. Results: A total of 262 patients were collected and 174 patients were enrolled after PSM, 87 in the rhTPO group and 87 in the rhIL-11 group. In all patients, there were no significant differences in the platelet compliance rate, mean days of medication, median days of compliance, median highest platelet count after medication, and the median platelet count elevation before and after medication between the two groups (p > 0.05), but the median lowest platelet count after next-cycle cancer therapy in the rhTPO group was lower than that in the rhIL-11 group (p = 0.014). The subgroup analysis showed that the rhTPO group had longer mean days of medication than the rhIL-11 group in patients with hematological malignancies (p = 0.042), and a lower median lowest platelet count after next-cycle cancer therapy in patients with grade I/II thrombocytopenia than rhIL-11 group (p = 0.022), with no significant difference in other outcome indicators (p > 0.05). As there was no statistically significant difference in platelet compliance rate between the two groups, the cost-minimization analysis showed that the rhIL-11 group had lower treatment costs than the rhTPO group. Conclusion: RhTPO and rhIL-11 showed similar effectiveness in the treatment of CTIT, but rhIL-11 was more advantageous in economic cost.

Paeoniflorin loaded liposomes modified with glycyrrhetinic acid for liver-targeting: preparation, characterization, and pharmacokinetic study.

OBJECTIVE: To enhance the retention times and therapeutic efficacy of paeoniflorin (PF), a liver-targeted drug delivery system has been developed using glycyrrhetinic acid (GA) as a ligand. SIGNIFICANCE: The development and optimization of GA-modified PF liposomes (GPLs) have shown promising potential for targeted delivery to the liver, opening up new possibilities for liver disease treatment. METHODS: This study aimed to identify the best prescriptions using single-factor experiments and response surface methodology. The formulation morphology was determined using transmission electron microscopy. Tissue distribution was observed through in vivo imaging, and pharmacokinetic studies were conducted. RESULTS: The results indicated that GPLs, prepared using the thin film dispersion method and response surface optimization, exhibited well-dispersed and uniformly sized particles. The in vitro release rate of GPLs was slower compared to PF monomers, suggesting a sustained release effect. The liver-targeting ability of GA resulted in stronger fluorescence signals in the liver for targeted liposomes compared to non-targeted liposomes. Furthermore, pharmacokinetic studies demonstrated that GPLs significantly prolonged the residence time of PF in the bloodstream, thereby contributing to prolonged efficacy. CONCLUSION: These findings suggest that GPLs are more effective than PF monomers in terms of controlling drug release and delivering drugs to specific targets, highlighting the potential of PF as a liver-protective drug.

Correlation between in vitro starch digestibility and starch structure/physicochemical properties in rice.

Natural resistant starch (RS) in rice provides human health benefits, and its concentration in rice is influenced by the structure and physicochemical properties of starch. The native starch structures and physicochemical properties of three rice varieties, QR, BR58, and BR50, and their relationships to in vitro digestibility were studied. The starch granules in all three varieties were irregular or polyhedral in shape. There were a few oval granules and a few pinhole structures in QR, no oval granules but a higher number of pinholes in BR58, and no oval granules and pinholes in BR50. QR is a low-amylose (13.8 %), low-RS (0.2 %) variety. BR58 is a low-amylose (15.3 %), high-RS (6.5 %) variety. BR50 is a high-amylose (26.7 %), high-RS (8.3 %) variety. All three starches exhibited typical A-type diffraction patterns. Starch molecular weight, chain length distribution, starch branching degree, pasting capabilities, and thermal properties differed considerably between the rice starches. The RS contents of the rice starch varieties were positively correlated with AAC, Mw/Mn, Mz/Mn, peak 3, B, PTime, and Tp and negatively correlated with Mn, peak 2, DB, PV, and BD, according to Pearson's correlation analysis. These findings may be helpful for the breeding and development of high-RS rice varieties.

Characterization of a novel γ-type carbonic anhydrase, Sjγ-CA2, in Saccharina japonica: Insights into carbon concentration mechanism in macroalgae.

Carbonic anhydrase (CA) is a crucial component of CO2-concentrating mechanism (CCM) in macroalgae. In Saccharina japonica, an important brown seaweed, 11 CAs, including 5 α-, 3 ß-, and 3 γ-CAs, have been documented. Among them, one α-CA and one ß-CA were localized in the periplasmic space, one α-CA was found in the chloroplast, and one γ-CA was situated in mitochondria. Notably, the known γ-CAs have predominantly been identified in mitochondria. In this study, we identified a chloroplastic γ-type CA, Sjγ-CA2, in S. japonica. Based on the reported amino acid sequence of Sjγ-CA2, the epitope peptide for monoclonal antibody production was selected as 165 Pro-305. After purification and specificity identification, anti-SjγCA2 monoclonal antibody was employed in immunogold electron microscopy. The results illustrated that Sjγ-CA2 was localized in the chloroplasts of both gametophytes and sporophytes of S. japonica. Subsequently, immunoprecipitation coupled with LC-MS/MS analysis revealed that Sjγ-CA2 mainly interacted with photosynthesis-related proteins. Moreover, the first 65 amino acids at N-terminal of Sjγ-CA2 was identified as the chloroplast transit peptide by the transient expression of GFP-SjγCA2 fused protein in tabacco. Real-time PCR results demonstrated an up-regulation of the transcription of Sjγ-CA2 gene in response to high CO2 concentration. These findings implied that Sjγ-CA2 might contribute to minimizing the leakage of CO2 from chloroplasts and help maintaining a high concentration of CO2 around Rubisco.

Temperature-Induced Sex Differentiation in River Prawn (Macrobrachium nipponense): Mechanisms and Effects.

Macrobrachium nipponense is gonochoristic and sexually dimorphic. The male prawn grows faster and usually has a larger size than the female. Therefore, a higher male proportion in stock usually results in higher yield. To investigate the impact of temperature on sexual differentiation in M. nipponense, two temperature treatments (26 °C and 31 °C) were conducted. The results showed that compared to the 31 °C treatment (3.20 ± 0.12), the 26 °C treatment displayed a lower female/male ratio (2.20 ± 0.11), which implied that a lower temperature could induce masculinization in M. nipponense. The temperature-sensitive sex differentiation phase was 25-35 days post hatching (DPH) at 26 °C while 15-20 DPH at 31 °C. Transcriptome and qPCR analysis revealed that a lower temperature up-regulated the expression of genes related to androgen secretion, and down-regulated the expressions of genes related to oogonia differentiation. Thirty-one temperature-regulated sex-differentiation genes were identified and the molecular mechanism of temperature-regulated sex differentiation was suggested. The finding of this study indicates that temperature regulation can be proposed as an innovative strategy for improving the culture yield of M. nipponense.

Engineering of heterointerface of ultrathin carbon nanosheet-supported CoN/MnO enhances oxygen electrocatalysis for rechargeable Zn-air batteries.

Designing bifunctional electrocatalysts with outstanding reactivity and durability towards the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) has remained a long-term aim for metal-air batteries. Achieving the high level of fusion between two distinct metal components to form bifunctional catalysts with optimized heterointerfaces and well-defined morphology holds noteworthy implications in the enhancement of electrocatalytic activity yet challenging. Herein, the fabrication of numerous heterointerfaces of CoN/MnO is successfully realized within ultrathin carbon nanosheets via a feasible self-templating synthesis strategy. Experimental results and theoretic calculations verify that the interfacial electron transfer from CoN to MnO at the heterointerface engenders an ameliorated charge transfer velocity, finely tuned energy barriers concerning reaction intermediates and ultimately accelerated reaction kinetics. The as-prepared CoN/MnO@NC demonstrates exceptional bifunctional catalytic performance, excelling in both OER and ORR showcasing a low reversible overpotential of 0.69 V. Furthermore, rechargeable liquid and quasi-solid-state flexible Zn-air batteries employing CoN/MnO@NC as the air-cathode deliver remarkable endurance and elevated power density, registering values of 153 and 116 mW cm-2 respectively and exceeding Pt/C + RuO2 counterparts and those reported in literature. Deeply exploring the effect of electron-accumulated heterointerfaces on catalytic activity would contribute wisdom to the development of bifunctional electrocatalysts for rechargeable metal-air batteries.

Effects of Dietary Folic Acid Supplementation on Sex Differences in Oriental River Prawn, Macrobrachium nipponense.

To better understand the sex differences in the utilization of folic acid for male and female prawns, Macrobrachium nipponense, three experimental diets with graded folic acid contents (A: 1.22 mg/kg, B: 5.44 mg/kg, and C: 10.09 mg/kg) were provided to prawns for 8 weeks. The experimental study demonstrated that prawns fed diets containing 1.22 mg/kg showed the best values on body weight gain (BWG), specific growth rate (SGR), and individual weight for both males and females. Male prawns fed above 1.22 mg/kg of dietary folic acid significantly decreased the crude protein contents in their bodies (p < 0.05), while no significant differences were observed in females among all treatments (p > 0.05). The protease activity of the hepatopancreas in females was significantly (p < 0.05) improved by a dietary level of 10.09 mg/kg of folic acid. However, the opposite trend was observed in males, with the highest protease activity observed at a dietary level of 1.22 mg/kg folic acid. Increasing dietary folic acid levels did not suppress early maturation but led to an increase in the fecundity of females. Furthermore, prawns fed with 10.09 mg/kg of folic acid exhibited improved tolerance against thermal stress in both males and females. Transcriptome analysis revealed that during thermal stress, the "Oxidative phosphorylation" and "Pantothenate and CoA biosynthesis" signaling pathways were significantly enriched in females, and the "Fatty acid biosynthesis" signaling pathway was significantly enriched in males. The results of this study preliminarily evaluate the differences between male and female M. nipponense in response to different dietary folic acid levels and are helpful in promoting the health and growth of aquaculture production of this species.

A Vehicle Simulation Study Examining the Effects of System Interface Design Elements on Performance in Different Vibration Environments Below 3 Hz.

OBJECTIVE: This study aimed to explore the relationship between system interface elements' design features and interaction performance in simulated vehicle vibration environments. BACKGROUND: Touch screens have been widely used in vehicle information systems, but few studies have focused on the decline of touchscreen interaction performance and task load increase when driving on unpaved roads. METHOD: The interaction performance (reaction time and task accuracy rate) with vibration frequencies below 3 Hz (1.5, 2.0, and 2.5 Hz) and different interface design elements was investigated employing a touch screen computer and E-prime software. RESULTS: The results indicate that vehicle vibration (below 3 Hz) can significantly reduce interaction performance with a vehicle information system interface. CONCLUSION: An appropriate increase in the physical size of the interface design features (visual stimulus materials and touch buttons) can help to mitigate this negative effect of vibration. APPLICATION: The results and findings of this study can be utilized for the design of information system interfaces as it relates to the vibration scenario of unpaved roads.

High Coordination Numbers of Actinides (An) in AnC13+ Rings (An = Th and U).

An intriguingly high abundance of both ThC13+ and UC13+ cluster cations was observed in a previous mass spectrometry experiment; however, the structural identification of these cations has not yet been completed. In this study, we determined the lowest lying structures of ThC13+ and UC13+ clusters using an unbiased structural search method. The 13-coordinate planar ring configuration was the most stable for both ThC13+ and UC13+ cluster cations. The C-An bonds in ThC13+ and UC13+ show a small degree of covalency, originating from the overlap of the s, d, and f orbitals of the An atoms with C 2p orbitals of both π and σ characteristics. The infrared and electronic absorption spectra of the most favorable planar ring configurations were theoretically simulated to facilitate the identification of the molecular structures in future experiments. This study provides an in-depth understanding of the experimental mass spectra.

Adsorption and diffusion of actinyls on the basal gibbsite (001) surface: a theoretical perspective.

Actinides are an important component of nuclear fuel for nuclear power and affect human health, and a key process in the transport of radionuclides in the environment is adsorption on mineral surfaces. In this work, we have used density functional theory (DFT) to investigate the microscopic adsorption and diffusion mechanisms of actinyls, U(V), U(VI), Np(V), Np(VI) Pu(V), and Pu(VI), on the gibbsite (001) surface. Actinyls(VI) are attached to the gibbsite surface through two An-Os bonds, which results in a bidentate inner sphere mode, while actinyls(V) favor a monodentate inner sphere adsorption mode with the gibbsite (001) surface. The solvent effects were considered through an explicit water cluster model. All the actinyls studied can be efficiently adsorbed on the gibbsite (001) surface with binding energies ranging from -113.9 kJ mol-1 to -341.2 kJ mol-1. Electronic structure analyses indicate that the cooperation of the An-Os bonds and hydrogen bonds leads to high adsorption stability of the actinyls with the gibbsite surface. The diffusion barriers of the actinyls on the gibbsite surface were determined, and the high energy barriers indicate that this type of gas-phase diffusion process is not likely to take place.

Ficolin A knockout alleviates sepsis-induced severe lung injury in mice by restoring gut Akkermansia to inhibit S100A4/STAT3 pathway.

Acute lung injury (ALI) is a life-threatening disease with high morbidity and mortality. Our previous results demonstrated that Ficolin A (FcnA) protected against lipopolysaccharide (LPS)-induced mild ALI via activating complement, however the mechanism of severe lung damage caused by sepsis remains unclear. This study aimed to investigate whether FcnA modulated gut microbiota to affect the progression of sepsis-induced severe ALI. Fcna-/- and Fcnb-/- C57BL/6 mice were applied to establish the ALI model by injection of LPS intraperitoneally. Mice were treated with antibiotics, fecal microbiota transplantation (FMT), and intratracheal administration of recombinant protein S100A4. Changes in body weight of mice were recorded, and lung injury were assessed. Then lung tissue wet/dry weight was calculated. We found knockout of FcnA, but not FcnB, alleviated sepsis-induced severe ALI evidenced by increased body weight change, decreased wet/dry weight of lung tissue, reduced inflammatory infiltration, decreased lung damage score, decreased Muc-2, TNF-α, IL-1ß, IL-6, and Cr levels, and increased sIgA levels. Furthermore, knockout of FcnA restored gut microbiota homeostasis in mice. Correlation analysis showed that Akkermansia was significantly negatively associated with TNF-α, IL-1ß, and IL-6 levels in serum and bronchoalveolar lavage fluid (BALF). Moreover, knockout of FcnA regulated gut microbiota to protect ALI through S100A4. Finally, we found knockout of FcnA alleviated ALI by inhibiting S100A4 via gut Akkermansia in mice, which may provide further insights and new targets into treating sepsis-induced severe lung injury.

Screening and in vitro Biological Evaluation of Novel Multiple Tyrosine Kinases Inhibitors as Promising Anticancer Agents.

BACKGROUND: Tyrosine kinases have emerged as key stimulatory drivers in several cancer-related pathways. This is particularly evident in non-small cell lung cancer with regulating cell growth and apoptosis and so on. Tyrosine kinase inhibitors (TKI) are one breakthrough option that could improve the life quality of cancer patients. INTRODUCTION: This study aims to find more effective tyrosine kinase inhibitors. METHODS: In this study, natural products from TargetMol that may be the potential TKI for lung cancer were screened through structure-based virtual screening and experimental validation. Moreover, the binding between the hit compounds and tyrosine kinase was explored. RESULTS: From the study findings, Gramicidin and Tannic acid have strong interactions with the four tyrosine kinases (ALK, TRK, MET, and ABL), and this could significantly inhibit the viability of A549 cells in a concentration-dependent manner. CONCLUSION: These findings indicated that Gramicidin and Tannic acid might be potential multiple TKI and are promising anticancer agents that call for further study.