π Phase Interlayer Shift and Stacking Fault in the Kagome Superconductor CsV_{3}Sb_{5}.

The stacking degree of freedom is a crucial factor in tuning material properties and has been extensively investigated in layered materials. The kagome superconductor CsV_{3}Sb_{5} was recently discovered to exhibit a three-dimensional CDW phase below T_{CDW}∼94 K. Despite the thorough investigation of in-plane modulation, the out-of-plane modulation has remained ambiguous. Here, our polarization- and temperature-dependent Raman measurements reveal the breaking of C_{6} rotational symmetry and the presence of three distinct domains oriented at approximately 120° to each other. The observations demonstrate that the CDW phase can be naturally explained as a 2c staggered order phase with adjacent layers exhibiting a relative π phase shift. Further, we discover a first-order structural phase transition at approximately 65 K and suggest that it is a stacking order-disorder phase transition due to stacking fault, supported by the thermal hysteresis behavior of a Cs-related phonon mode. Our findings highlight the significance of the stacking degree of freedom in CsV_{3}Sb_{5} and offer structural insights to comprehend the entanglement between superconductivity and CDW.

FKBP51 regulates decidualization through Ser473 dephosphorylation of AKT.

Defective decidualization of human endometrial stromal cells (ESCs) has recently been highlighted as an underlying cause of implantation failure. FK-506-binding protein 51 (FKBP51) has been shown to participate in the steroid hormone response and the protein kinase B (AKT) regulation process, both of which are important pathways involved in decidualization. The objective of the present study was to investigate the potential effects and mechanisms of FKBP51 in the regulation of ESC decidualization. By performing immunohistochemical staining on an endometrial tissue microarray (TMA) derived from normal females, we found that FKBP51 expression was much higher in the luteal phase than in the follicular phase in ESCs. Primary ESCs were isolated from patients to build an in vitro decidualization model through co-culture with medroxyprogesterone acetate (MPA) and 8-bromoadenosine (cAMP). SC79, a specific AKT activator in various physiological and pathological conditions, and shRNA-FKBP51 were used to examine the roles of AKT and FKBP51 in decidualization. The Western blot and RT-PCR results showed that FKBP51, insulin-like growth factor-binding protein 1 (IGFBP1) and prolactin (PRL) expression increased in ESCs treated with MPA + cAMP; meanwhile, the level of p-Ser473 AKT (p-S473 AKT) decreased and forkhead box protein O1 (FOXO1A) expression increased. Decidualization was inhibited by the AKT activator SC79 and the transfection of FKBP51-shRNA by affecting protein synthesis, cell morphology, cell growth and cell cycle. Furthermore, this inhibition was rescued by FKBP51-cDNA transfection. The results supported that FKBP51 promotes decidualization by reducing the Ser473 phosphorylation levels in AKT.

Supercritical CH3OH-Triggered Isotype Heterojunction and Groups in g-C3N4 for Enhanced Photocatalytic H2 Evolution.

The structure tuning of bulk graphitic carbon nitride (g-C3N4) is a critical way to promote the charge carriers dynamics for enhancing photocatalytic H2-evolution activity. Exploring feasible post-treatment strategies can lead to effective structure tuning, but it still remains a great challenge. Herein, a supercritical CH3OH (ScMeOH) post-treatment strategy (250-300 °C, 8.1-11.8 MPa) is developed for the structure tuning of bulk g-C3N4. This strategy presented advantages of time-saving (less than 10 min), high yield (over 80%), and scalability due to the enhanced mass transfer and high reactivity of ScMeOH. During the ScMeOH post-treatment process, CH3OH molecules diffused into the interlayers of g-C3N4 and subsequently participated in N-methylation and hydroxylation reactions with the intralayers, resulting in a partial phase transformation from g-C3N4 into carbon nitride with a poly(heptazine imide)-like structure (Q-PHI) as well as abundant methyl and hydroxyl groups. The modified g-C3N4 showed enhanced photocatalytic activity with an H2-evolution rate 7.2 times that of pristine g-C3N4, which was attributed to the synergistic effects of the g-C3N4/Q-PHI isotype heterojunction construction, group modulation, and surface area increase. This work presents a post-treatment strategy for structure tuning of bulk g-C3N4 and serves as a case for the application of supercritical fluid technology in photocatalyst synthesis.

Base- or acid-assisted polystyrene plastic degradation in supercritical CO2.

Plastic has caused serious "white pollution" to the environment, and the highly inert characteristics of plastic bring a major challenge for degradation. Supercritical fluids have unique physical properties and have been widely used in various fields. In this work, supercritical CO2 (Sc-CO2) with mild conditions was selected and assisted by NaOH/HCl solution to degrade polystyrene (PS) plastic, and the reaction model was designed using response surface methodology (RSM). It was found that, regardless of the types of assistance solutions, the factors affecting PS degradation efficiencies were reaction temperature, reaction time, and NaOH/HCl concentration. At the temperature of 400 °C, time of 120 min, and base/acid concentration of 5% (in weight), 0.15 g PS produced 126.88/116.99±5 mL of gases with 74.18/62.78±5 mL of H2, and consumed 81.2/71.5±5 mL of CO2. Sc-CO2 created a homogeneous environment, which made PS highly dispersed and uniformly heated, thus promoting the degradation of PS. Moreover, Sc-CO2 also reacted with the degradation products to produce new CO and more CH4 and C2Hx (x=4, 6). Adding NaOH/HCl solution not only improved the solubility of PS in Sc-CO2, but also provided a base/acid environment that reduced the activation energy of the reaction, and effectively improved the degradation efficiencies of PS. In short, degrading PS in Sc-CO2 is feasible, and better results are obtained with the assistance of base/acid solution, which can provide a reference for the disposal of waste plastics in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s42768-023-00139-1.

Value of AFP and PIVKA-II in diagnosis of HBV-related hepatocellular carcinoma and prediction of vascular invasion and tumor differentiation.

BACKGROUND: To explore the value of alpha fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in diagnosis of HBV-related hepatocellular carcinoma (HCC) and their relationship with vascular invasion, tumor differentiation and size. METHODS: A total of 433 participants were enrolled in this study including 266 cases with HBV-related HCC, 87 cases with HBV DNA positive benign liver disease and 80 healthy individuals. Then we explored the correlation between AFP, PIVKA-II serum level and several pathological features such as vascular invasion, tumor differentiation and size. The value of these two markers used singly or jointly in diagnosing HBV-related HCC was evaluated by receiver operating characteristic (ROC) curve. The ROC curve was also plotted to identify AFP, PIVKA-II serum cut-off values that would best distinguish HBV-related HCC patients with and without vascular invasion. RESULTS: The level of AFP and PIVKA-II in HBV-related HCC group was significantly higher (Z was 7.428, 11.243 respectively, all P < 0.01). When AFP and PIVKA-II were used as the individual tumor marker, the areas under the ROC curve (AUC) of HBV-related HCC diagnosis were 0.765 (95% CI, 0.713 ~ 0.8170) for AFP, 0.901 (95% CI, 0.868 ~ 0.935) for PIVKA-II, and 0.917 (95% CI, 0.886 ~ 0.948) for AFP and PIVKA-II simultaneously. The serum levels of AFP and PIVKA-II were positively correlated with tumor differentiation and size. High AFP and PIVKA-II expression was significantly associated with the presence of vascular invasion (P was 0.007 and 0.014 respectively). The AFP level > 64.4 ng/ml or PIVKA-II level > 957.61mAU/ml was the best critical value to predict the presence of vascular invasion. CONCLUSION: Our results validate that AFP and PIVKA-II play a significant role in the diagnosis of HBV-related HCC. The diagnostic value of AFP and PIVKA-II combined detection or single assay of PIVKA-II is higher than that of separate assay of AFP. Moreover, their concentration has important clinical value in judging tumor size, tumor cell differentiation and vascular invasion.

LncRNA H19/microRNA-675/PPARα axis regulates liver cell injury and energy metabolism remodelling induced by hepatitis B X protein via Akt/mTOR signalling.

Emerging evidence indicates that the lncRNAs/microRNA/mRNA axis plays important roles in a variety of diseases. This study was aimed to investigate the potential roles and underlying molecular mechanisms of lncRNA H19 and H19-derived miR-675 in regulating hepatitis B virus (HBV)-associated liver injury. mRNA and miR-675 levels were determined by quantitative real-time PCR (qRT-PCR), protein levels were determined by western blot, cell viability was measured by the MTT assay, cell apoptosis was measured by flow cytometry, inflammatory cytokine production was determined by ELISA, oxidative stress and energy metabolism were assessed by commercial kits, and the target relationship between PPARα and miR-675 was confirmed by the dual-luciferase reporter assay. The results showed that the expression of lncRNA H19 and miR-675 was up-regulated in patients with chronic hepatitis B (n = 20). Inhibition of lncRNA H19 or miR-675 in L02 cells increased cell viability, suppressed hepatitis B X protein (HBx)-induced cell apoptosis, inflammatory cytokine production, and oxidative stress, and remodelled energy metabolism. Furthermore, PPARα was found to be a target gene of miR-675. The expression of PPARα was down-regulated in patients with chronic hepatitis B, and there was a negative correlation between the expression of lncRNA H19 and PPARα, or between miR-675 and PPARα. Moreover, by knocking down the expression of PPARα, the actions (apoptosis, inflammatory factors, oxidative stress, and energy metabolism) of lncRNA H19 or miR-675 inhibition in HBx-induced L02 cells were at least partially reversed. In addition, HBx-induced elevated levels of p-AktSer473, p-AktThr308 and p-mTORSer2448 were down-regulated by lncRNA H19 or miR-675 inhibition. Furthermore, PPARα knockdown partly reversed the down-regulated effects of H19 or miR-675 inhibition. Taken together, these data indicate that the lncRNA H19/miR-675/PPARα axis regulates liver cell injury and energy metabolism remodelling induced by HBx, which may be related to the modulation of Akt/mTOR signalling.

Hepatitis B Virus e Antigen Regulates Monocyte Function and Promotes B Lymphocyte Activation.

Hepatitis B virus (HBV) e (HBe) antigen is a nonstructural virus component with great immune regulation roles. It regulates adaptive immunity response and participates in persistent infection development. However, its roles on monocytes and B lymphocytes were rarely studied. Herein, we studied HBe roles on U937 and Hmy2.CIR by creating HBe stably transfected cells using lentivirus. We detected the motility of HBe-U937 through transwell migration assay. Cytokines that primarily produced by monocytes, including BAFF, B-cell activating factor (BAFF), interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and A proliferation inducing ligand (APRIL), were measured in culture supernatants of transfected U937, and serum BAFF, IL-6, and IL-10 were detected in HBe-positive and HBe-negative HBV-infected patients. Among these, BAFF mRNA and membrane-bound BAFF were further detected. Activation and inhibition markers of B lymphocytes on HBe-Hmy2.CIR and proliferation of transfected Hmy2.CIR after coculture with transfected U937 were also detected. We found that U937 migration was inhibited by HBe. BAFF expression was increased in HBe-U937, however, membrane-bound BAFF on HBe-U937 was decreased. In addition, Serum BAFF in HBe-positive patients was higher than in HBe-negative patients. IL-6 and IL-10 were increased in HBe-U937 after being stimulated by lipopolysaccharide (LPS), however, serum IL-6 and IL-10 were not associated with HBe status in patients. Besides, TNF-α and APRIL expression were basically the same in GV166-U937 and HBe-U937. B lymphocyte activation markers CD86 and Tspan33 were raised in HBe-Hmy2.CIR. However, inhibition markers Lyn and CD32b had no differences between HBe-Hmy2.CIR and control. Proliferation of transfected Hmy2.CIR was not affected by coculture with transfected U937, however, HBe transfection itself enhanced Hmy2.CIR proliferation. Altogether, these revealed that HBe can inhibit U937 migration and promote cytokines, including BAFF, IL-6, and IL-10, production in U937. Besides, HBe enhances BAFF release from U937 and increases BAFF concentration in vivo. In addition, HBe antigen facilitates Hmy2.CIR activation and proliferation through direct induction.

A FKBP5 mutation is associated with Paget's disease of bone and enhances osteoclastogenesis.

Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c.163G>C (p.Val55Leu) mutation in FKBP5 (encodes FK506-binding protein 51, FKBP51) associated with PDB using whole-exome sequencing. Mutant FKBP51 enhanced the Akt phosphorylation and kinase activity in cells. A study of osteoclast function using FKBP51V55L KI transgenic mice proved that osteoclast precursors from FKBP51V55L mice were hyperresponsive to RANKL, and osteoclasts derived from FKBP51V55L mice displayed more intensive bone resorbing activity than did FKBP51WT controls. The osteoclast-specific molecules tartrate-resistant acid phosphatase, osteoclast-associated receptor and transcription factor NFATC1 were increased in bone marrow-derived monocyte/macrophage cells (BMMs) from FKBP51V55L mice during osteoclast differentiation. However, c-fos expression showed no significant difference in the wild-type and mutant groups. Akt phosphorylation in FKBP51V55L BMMs was elevated in response to RANKL. In contrast, IκB degradation, ERK phosphorylation and LC3II expression showed no difference in wild-type and mutant BMMs. Micro-CT analysis revealed an intensive trabecular bone resorption pattern in FKBP51V55L mice, and suspicious osteolytic bone lesions were noted in three-dimensional reconstruction of distal femurs from mutant mice. These results demonstrate that the mutant FKBP51V55L promotes osteoclastogenesis and function, which could subsequently participate in PDB development.

FKBP51 decreases cell proliferation and increases progestin sensitivity of human endometrial adenocarcinomas by inhibiting Akt.

In this study, we investigated the role of FK506 binding protein 51 (FKBP51) in human endometrial adenocarcinoma progression. Immunohistochemical analysis showed decreased FKBP51 expression in endometrial adenocarcinoma tissues. Moreover, higher FKBP51 expression was observed in the normal secretory phase than in proliferative-phase endometrial tissues. FKBP51-shRNA transfected KLE cells showed high Ser473-phospho Akt with decreased p21 and p27 levels, which promoted S-G2/M phase cell cycle progression and proliferation. Conversely, FKBP51 overexpressing Ishikawa cells showed low Ser473-phospho Akt, which led to increased p21 and p27 levels and, in turn, G0/G1 cell cycle arrest and decreased cell proliferation. FKBP51 overexpression in progesterone receptor-positive Ishikawa cells sensitized them to medroxyprogesterone acetate (MPA; progestin) treatment by repressing Akt signaling. Conversely, FKBP51-shRNA knockdown in RL95-2 cells attenuated progestin sensitivity. These findings indicate FKBP51 inhibits cell proliferation and promotes progestin sensitivity in endometrial adenocarcinoma by decreasing Akt signaling.