Abstract Ingestion of specific probiotics, namely “psychobiotics”, produces psychotropic effects on behavior and affects the hypothalamic–pituitary–adrenal axis and neurochemicals in the brain. We ...examined the psychotropic effects of a potential psychobiotic bacterium, Lactobacillus plantarum strain PS128 (PS128), on mice subjected to early life stress (ELS) and on naïve adult mice. Behavioral tests revealed that chronic ingestion of PS128 increased the locomotor activities in both ELS and naïve adult mice in the open field test. In the elevated plus maze, PS128 significantly reduced the anxiety-like behaviors in naïve adult mice but not in the ELS mice; whereas the depression-like behaviors were reduced in ELS mice but not in naïve mice in forced swimming test and sucrose preference test. PS128 administration also reduced ELS-induced elevation of serum corticosterone under both basal and stressed states but had no effect on naïve mice. In addition, PS128 reduced inflammatory cytokine levels and increased anti-inflammatory cytokine level in the serum of ELS mice. Furthermore, the dopamine level in the prefrontal cortex (PFC) was significantly increased in PS128 treated ELS and naïve adult mice whereas serotonin (5-HT) level was increased only in the naïve adult mice. These results suggest that chronic ingestion of PS128 could ameliorate anxiety- and depression-like behaviors and modulate neurochemicals related to affective disorders. Thus PS128 shows psychotropic properties and has great potential for improving stress-related symptoms.
Four new iridium biscarbene complexes with different N⁁N ligands showing very different emission colors from deep‐blue to red are synthesized. The emission colors are mainly controlled by the N⁁N ...ligands. The electroluminescent devices using these complexes as dopant emitters exhibit extremely high efficiencies.
Vacuum‐sublimed inorganic cesium lead halide perovskite thin films are prepared and integrated in all‐vacuum‐deposited solar cells. Special care is taken to determine the stoichiometric balance of ...the sublimation precursors, which has great influence on the device performance. The mixed halide devices exhibit exceptional stabilized power conversion efficiency (11.8%) and promising thermal and long‐term stabilities.
MicroRNA-122 (miR-122), which accounts for 70% of the liver's total miRNAs, plays a pivotal role in the liver. However, its intrinsic physiological roles remain largely undetermined. We demonstrated ...that mice lacking the gene encoding miR-122a (Mir122a) are viable but develop temporally controlled steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). These mice exhibited a striking disparity in HCC incidence based on sex, with a male-to-female ratio of 3.9:1, which recapitulates the disease incidence in humans. Impaired expression of microsomal triglyceride transfer protein (MTTP) contributed to steatosis, which was reversed by in vivo restoration of Mttp expression. We found that hepatic fibrosis onset can be partially attributed to the action of a miR-122a target, the Klf6 transcript. In addition, Mir122a(-/-) livers exhibited disruptions in a range of pathways, many of which closely resemble the disruptions found in human HCC. Importantly, the reexpression of miR-122a reduced disease manifestation and tumor incidence in Mir122a(-/-) mice. This study demonstrates that mice with a targeted deletion of the Mir122a gene possess several key phenotypes of human liver diseases, which provides a rationale for the development of a unique therapy for the treatment of chronic liver disease and HCC.
The gut microbiota plays a role in nonalcoholic fatty liver disease (NAFLD), but data about gut dysbiosis in Asians with NAFLD remains scarce. We analyzed the differences in fecal microbiota between ...adults with and without NAFLD. This cross-sectional study examined adults with histology-proven NAFLD (25 nonalcoholic fatty liver (NAFL) patients, 25 nonalcoholic steatohepatitis (NASH) patients, and 25 living liver donors (healthy controls)). The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The NAFL and NASH groups showed lower total bacterial diversity and richness than the controls. NAFLD patients had higher levels of the phylum Bacteroidetes and lower levels of Firmicutes than controls. The genus
, family
, order
, and class
were less abundant in patients with NAFL or NASH than healthy individuals. The lipopolysaccharide biosynthesis pathway was differentially enriched in the NASH group. This study examined the largest number of Asian patients with biopsy-proven NAFL and NASH in terms of dysbiosis of the gut microbiota in NAFLD patients. NAFLD patients had higher levels of Bacteroidetes and lower levels of Firmicutes
These results are different from research from western countries and could provide different targets for therapies by region.
The nucleotide‐binding and oligomerization domain, leucine‐rich repeats, and pyrin domain‐containing protein 3 (NLRP3) inflammasome plays a crucial role in innate immunity and is involved in the ...pathogenesis of autoinflammatory diseases. Glycolysis regulates NLRP3 inflammasome activation in macrophages. However, how lactic acid fermentation and pyruvate oxidation controlled by the mitochondrial pyruvate carrier (MPC) affect NLRP3 inflammasome activation and autoinflammatory disease remains elusive. We found that the inactivation of MPC with genetic depletion or pharmacological inhibitors, MSDC‐0160 or pioglitazone, increased NLRP3 inflammasome activation and IL‐1β secretion in macrophages. Glycolytic reprogramming induced by MPC inhibition skewed mitochondrial ATP‐associated oxygen consumption into cytosolic lactate production, which enhanced NLRP3 inflammasome activation in response to monosodium urate (MSU) crystals. As pioglitazone is an insulin sens MSDC‐itizer used for diabetes, its MPC inhibitory effect in diabetic individuals was investigated. The results showed that MPC inhibition exacerbated MSU‐induced peritonitis in diabetic mice and increased the risk of gout in patients with diabetes. Altogether, we found that glycolysis controlled by MPC regulated NLRP3 inflammasome activation and gout development. Accordingly, prescriptions for medications targeting MPC should consider the increased risk of NLRP3‐related autoinflammatory diseases.
Inactivation of mitochondrial pyruvate carrier (MPC) with genetic depletion or pharmacological inhibitors pioglitazone or MSDC‐0160 blocks mitochondrial pyruvate import, thus reducing oxidative phosphorylation (OXPHOS) in macrophages. To compensate for energy demand, an increase in lactic fermentation maintains glycolysis through the NAD+ cycle to make glycolytic ATP but is also accompanied by lactate production. When combined with insulin therapy, insulin enables cells to take up glucose to promote lactate fermentation, maximizing lactate production. Cellular lactate controlled by MPC contributes to upgrading NOD, LRR, and pyrin domain‐containing protein 3 (NLRP3) inflammasome hyperactivation and exacerbating gout development. Downregulation of lactate production by the lactate dehydrogenase (LDH) inhibitor GSK2837808A efficiently prevented NLRP3 inflammasome activation.
Asymmetric three‐component, 1,2‐aminoxy‐trifluoromethylation of styrenes with N‐hydroxy‐1,3‐benz/naphthoxazine‐2,4‐diones (i. e., N‐OH‐(B/Np)OxzOn) catalysed by chiral vanadyl complexes derived from ...N‐salicylidene‐L‐t‐leucinate were explored. Among 14 different solvents and 13 different catalysts screened, the best reaction scenarios were in 2‐propanol with 3‐(2,5‐dimethyl)phenyl‐5‐bromo (DMP), or 3‐t‐butyl‐5‐bromo substituted catalysts that led to the corresponding complementary (R)‐ and (S)‐products with potential biological activities in 45–91% yields and up to 85 and 75% ee, respectively. Further optimisation with the DMP catalyst led to the best combination of 3‐halo/3,5‐dihalo‐styrenes with 6‐/7‐Br−N−OH‐(B/Np)OxzOn as the trapping agents. The corresponding eight different products were isolated in 52–75% yields with ees in a range of 88–93% (R). Based on Density Functional Theory (DFT) calculations with conformational searches, the origin of enantiocontrol and the working mechanism were proposed by resorting to a bidentate‐chelation between the amide or carbamate C=O group and N−OH group in the trapping agent to the vanadyl center followed by asymmetric benzylic radical trapping in an SH2 fashion. Subsequent Fragment Molecular Orbital (FMO)/Pair Interaction Energy Decomposition Analysis (PIEDA) calculations with the DMP catalyst were carried out to rationalize the extent of asymmetric induction. One representative product derived from p‐methyl‐styrene and NpOxzOn was hydrolyzed in basic MeOH with decarboxylation to unmask its carbamate moiety. The resulting chiral (R)‐N‐benzoxy‐3‐hydroxy‐2‐naphthamide was subjected to aerobic, oxidative homo‐coupling catalysed by the DMP catalyst in CCl4. The corresponding 2,2‐binaphthol product was isolated in 90% (brsm) yield with nearly complete diastereo‐control at the created (M)‐axial chirality, allowing for sequential, bi‐functional asymmetric cross‐coupling applications.
The albumin-bilirubin (ALBI) grade has been validated as a significant predictor for hepatocellular carcinoma (HCC). However, there is little information about the impact of postoperative ALBI grade ...in patients with HCC who are undergoing liver resection. We enrolled 525 HCC patients who received primary resection from April 2001 to March 2017. The impact of the pre- and post-operative ALBI grades on overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. During the follow-up period (mean, 65 months), 253 (48.1%) patients experienced recurrence, and 85 (16.2%) patients died. Multivariate analysis revealed that diabetes mellitus (DM) (p = 0.011), alpha-fetoprotein levels (AFP) (p < 0.001), low platelet count (p = 0.008), liver cirrhosis (p < 0.001), and the first year of ALBI grade after resection (p < 0.001) were independent predictors for RFS. Additionally, old age (p = 0.006), DM (p = 0.002), AFP (p = 0.027), and ALBI grade at the first year after resection (p < 0.001) were independent risk factors for poor liver-related survival. Patients with post-operative ALBI grades II/III had older age (p = 0.019), hypoalbuminemia (p = 0.038), DM (p = 0.043), and high stages of pTNM (p = 0.021). The post-operative ALBI grade is better for predicting the outcomes in HCC patients after curative hepatectomy than the pre-operative ALBI grade.
Electronic device versions of the neural functions of the human retina have high potential for use in artificial vision. This study demonstrates halide perovskite artificial human photoreceptors with ...specific photoresponses to red, green, and blue colors, which are consistent with human retinal photoreceiving cones and rods. In contrast to the current programmable spectral‐response technologies, a novel microcavity structure is combined in this study with a perovskite absorber to achieve a targeted spectrum without using external optical filters. The fabricated artificial photoreceptors exhibit excellent performance including a high detectivity of more than 1013 Jones, a large linear dynamic range of 154 dB, and a short response time of 580 ns. These values are equal to or better than those of the natural human retina. These devices can easily be monolithically integrated on a single flexible substrate by using vacuum deposition, and a true proof‐of‐concept full‐color image reconstruction is demonstrated.
Microcavity‐integrated monolithic flexible perovskite artificial human photoreceptors are demonstrated. The artificial cones and rods exhibit a true similarity with the natural human retina and exhibit excellent specific detectivity, large linear dynamic range, short response time, and low noise current. The potential of these versatile structures is manifested by reproducing a realistic full‐color image.
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