Complete miRNA-15/16 loss in mice promotes hematopoietic progenitor expansion and a myeloid-biased hyperproliferative state.

Dysregulated apoptosis and proliferation are fundamental properties of cancer, and microRNAs (miRNA) are critical regulators of these processes. Loss of miR-15a/16-1 at chromosome 13q14 is the most common genomic aberration in chronic lymphocytic leukemia (CLL). Correspondingly, the deletion of either murine miR-15a/16-1 or miR-15b/16-2 locus in mice is linked to B cell lymphoproliferative malignancies. However, unexpectedly, when both miR-15/16 clusters are eliminated, most double knockout (DKO) mice develop acute myeloid leukemia (AML). Moreover, in patients with CLL, significantly reduced expression of miR-15a, miR-15b, and miR-16 associates with progression of myelodysplastic syndrome to AML, as well as blast crisis in chronic myeloid leukemia. Thus, the miR-15/16 clusters have a biological relevance for myeloid neoplasms. Here, we demonstrate that the myeloproliferative phenotype in DKO mice correlates with an increase of hematopoietic stem and progenitor cells (HSPC) early in life. Using single-cell transcriptomic analyses, we presented the molecular underpinning of increased myeloid output in the HSPC of DKO mice with gene signatures suggestive of dysregulated hematopoiesis, metabolic activities, and cell cycle stages. Functionally, we found that multipotent progenitors (MPP) of DKO mice have increased self-renewing capacities and give rise to significantly more progeny in the granulocytic compartment. Moreover, a unique transcriptomic signature of DKO MPP correlates with poor outcome in patients with AML. Together, these data point to a unique regulatory role for miR-15/16 during the early stages of hematopoiesis and to a potentially useful biomarker for the pathogenesis of myeloid neoplasms.

Effect of lanthanum nitrate on adipogenesis in mice.

Lanthanum (La) is widely used in modern industry and agriculture because of its unique physicochemical properties and is broadly exposed in the population. Some studies have shown that La may have some effects on adipogenesis, but there is a lack of related in vivo evidence. In this study, the effects of La(NO3 )3 on adipogenesis and its associated mechanism were studied using C57BL/6J mouse model. The results showed that La(NO3 )3 exposure caused a decrease in body weight and the percentage of fat content in mice. In addition, the adipose marker molecules and specific adipogenic transcription factors decreased in both white adipose tissue (WAT) and brown adipose tissue (BAT). Detection of signaling pathway-related molecules revealed that canonical wnt/ß-catenin pathway-related molecules were upregulated in both adipose tissues. In summary, in vivo exposure to La(NO3 )3 might inhibited adipogenesis in mice, possibly through upregulation of the canonical Wnt/ß-catenin signaling pathway.

A Novel Family of Stable Polyelectrolyte Complexes Based on Mixed Olefins-Maleic Anhydride Copolymer.

In the present study, the copolymer of mixed olefins included in unetherified gasoline and maleic anhydride (PUGM) was prepared by self-stabilized precipitation polymerization (2SP) and employed for the synthesis of a new family of stable polyelectrolyte complexes (PECs). Polyanionic saponified PUGM partially grafted with methoxy poly(ethylene glycol) (PUGMS-g-mPEG) and polycationic quaternized PUGM (PUGMQ) were both derived from PUGM via the facile modification of anhydride groups. The particle size, zeta potential, morphology, and stability of self-assembled PEC particles were investigated thoroughly. Strikingly, the introduction of long mPEG side chains (Mn = 4000) had a remarkable effect on the self-assembled particles, which displayed a constant particle size of ∼200 nm regardless of varying n+/n-. Moreover, it also enhanced the salt tolerance and long-term stability of PEC particles significantly. Our work not only provides an effective approach to PECs from petroleum resources with low cost but also deepens the understanding of the relationship between the chain structure of polyelectrolytes and the stability of PECs.

UV-Induced Thiol-Ene "Click" Surface Grafting Polymerization on BOPP Substrate and Its Postmodifying for Hydrophilic and Antibacterial Applications.

This paper proposed a novel and versatile surface modification route by integrating UV light-mediated thiol-ene "click" surface grafting polymerization and postmodification via the reactions of the surface thiol groups. At first, poly(thiol ether) layers with tunable thiol group density, up to 8.2 × 102 ea/nm3 for cross-linked grafting layers, were grafted from biaxially oriented polypropylene (BOPP) film. Then, the surface -SH groups reacted with epoxy compounds to introduce quaternary ammonium salt. With the immobilized quaternary ammonium salt and coordinated Zn2+ ions, the modified film demonstrated 99.98% antibacterial rate against Staphylococcus aureusafter soaking in DI water for 21 days and in a highly alkaline environment (0.1 M NaOH aqueous solution) for 3 days, and the surface water contact angle decreased to 39°. At last, the polymethacrylate chains were also successfully grafted from the surface thiol groups of the cross-linked poly(thiol ether) under visible light irradiation. With 2-(dimethyldodecylammonium) ethyl methacrylate as the grafting monomer, the modified BOPP film had shown a 99.99% antibacterial rate against both Escherichia coliand S. aureus. Meanwhile, with 2-methacryloxyethyl phosphoryl choline as grafting monomer, the modified surface showed an excellent antibioadhesion of living S. aureus, and the surface water contact angle was as low as 48°.

Yolk-Shell Encapsulation of Cells by Biomimetic Mineralization and Visible Light-Induced Surface Graft Polymerization.

The pursuit of low-cytotoxicity modification strategies represents a prominent avenue in cell coating research, holding immense significance for the advancement of practical living cell-related technologies. Here, we presented a novel method to fabricate encapsulated yeast cells with a yolk-shell structure by biomimetic mineralization and visible-light-induced surface graft polymerization. In this approach, an amorphous calcium carbonate (ACC) shell was first deposited on the surface of a yeast cell (cell@ACC) modified with 4 layers of self-assembled poly(diallyl dimethylammonium chloride) (PDADMAC)/poly(acrylic acid) (PAA) film using a biomimetic mineralization technique. Subsequently, polyethylenimine (PEI) was absorbed on the surface of cell@ACC by electrostatic interaction. Then, a cross-linked shell was introduced by surface-initiated graft polymerization of poly(ethylene glycol) diacrylate (PEGDA) on cell@ACC under irradiation of visible light using thioxanthone catechol-O,O'-diacetic acid as the photosensitizer. After the removal of the inner ACC shell, the yolk-shell-structured yeast cells (cell@PHS) were obtained. Due to the mild conditions of the strategy, the cell@PHS could retain 98.81% of its original viability. The introduction of the shell layer significantly prolonged the lag phase of yeast cells, which could be tuned between 5 and 25 h by regulating the thickness of the shell. Moreover, the cell@PHS showed improved resistance against lyticase due to the presence of a protective shell. After 30 days of storage, the viability of cell@PHS was 81.09%, which is significantly higher than the 19.89% viability of native yeast cells.

Visible-Light-Induced Tandem Radical Brominative Addition/Cyclization of Activated Alkynes with CBr4 for the Synthesis of 3-Bromocoumarins.

A visible-light-induced tandem radical brominative addition/spiro-cyclization/1,2-ester migration of activated alkynes with CBr4 is developed. This protocol features good functional group tolerance, operational simplicity, and mild reaction conditions without the use of catalysts and external additives, providing easy access to valuable 3-bromocoumarins in generally high yields.

Recent progress in photoinduced direct desulfurization of thiols.

The reduction of mercaptans plays an important role in diverse areas such as protein synthesis, polymer science, environmental study, and pharmaceutical chemistry. Despite significant advancements in this area, particularly in light-induced transformations, review articles have rarely been reported on this topic. Thus, this review article emphasizes the direct photoinduced desulfurization and functionalization of thiols to alkanes or coupling products, with a focus on significant advancements made in the last decade. The progress is discussed according to the types of bonds formed from the cleavage of Csp3-SH bonds.

Single Nickel Atom Catalysts Enable Fast Polysulfide Redox for Safe and Long-Cycle Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries have attracted great interest due to their low cost, high theoretical energy density, and environmental friendliness. However, the sluggish conversion of lithium polysulfides (LiPS) to S and Li2 S during the charge/discharge process leads to unsatisfactory rate performance of lower to 0.1 C (1 C = 1675 mA g-1 ) especially for Li-S pouch batteries, thus hindering their practical applications in high power batteries. Here, well-defined and monodispersed Ni single-atom catalysts (SACs) embedded in highly porous nitrogen-doped graphitic carbons (NiSA-N-PGC) are designed and synthesized to form Ni-N4 catalytic sites at the atomic level. When serving as a bifunctional electrocatalyst, the Ni-N4 catalytic sites cannot only promote the interfacial conversion redox of LiPS by accelerating the transformation kinetics, but also suppress the undesirable shuttle effect by immobilizing LiPS. These findings are verified by both experimental results and DFT theoretical calculations. Furthermore, Li ions show low diffusion barrier on the surface of Ni-N4 sites, resulting in enhanced areal capacity of batteries. As a result, the Li-S battery delivers stable cycling life of more than 600 cycles with 0.069% capacity decay per cycle at a rate of 0.5 C. More importantly, the Li-S pouch cells with NiSA-N-PGC show an initial capacity of 1299 mAh g-1 at a rate of 0.2 C even with high sulfur loading of 6 mg cm-2 . This work opens up an avenue for developing single-atom catalysts to accelerate the kinetic conversion of LiPS for highly stable Li-S batteries.

Covalently Attaching Hollow Silica Nanoparticles on a COC Surface for the Fabrication of a Three-Dimensional Protein Microarray.

Compared to traditional two-dimensional (2D) biochips, three-dimensional (3D) biochips exhibit the advantages of higher probe density and detection sensitivity due to their designable surface microstructure as well as enlarged surface area. In the study, we proposed an approach to prepare a 3D protein chip by deposition of a monolayer of functionalized hollow silica nanoparticles (HSNs) on an activated cyclic olefin copolymer (COC) substrate. First, the COC substrate was chemically modified through the photografting technique to tether poly[3-(trimethoxysilyl) propyl methacrylate] (PTMSPMA) brushes on it. Then, a monolayer of HSNs was deposited on the modified COC and covalently attached via a condensation reaction between the hydrolyzed pendant siloxane groups of PTMSPMA and the Si-OH groups of HSNs. The roughness of the COC substrate significantly increased to 50.3 nm after depositing a monolayer of HSNs (ranging from 100 to 700 nm), while it only caused a negligible reduction in the light transmittance of COC. The HSN-modified COC was further functionalized with epoxide groups by a silane coupling agent for binding proteins. Immunoglobulin G could be effectively immobilized on this substrate with the highest immobilization efficiency of 75.2% and a maximum immobilization density of 1.236 µg/cm2, while the highest immobilization efficiency on a 2D epoxide group-modified glass slide was only 57.4%. Moreover, immunoassay results confirmed a competitive limit of detection (LOD) (1.06 ng/mL) and a linear detection range (1-100 ng/mL) of the 3D protein chip. This facile and effective approach for fabricating nanoparticle-based 3D protein microarrays has great potential in the field of biorelated detection.

PPh3-Triggered Tandem Synthesis of 2,3-Disubstituted Benzofuran Derivatives from o-Quinone Methides with Acyl Chlorides.

A PPh3-triggered tandem strategy for the efficient synthesis of valuable 2,3-disubstituted benzofuran derivatives in generally good to high yields from aryl or alkyl acyl chlorides and o-quinone methides has been developed. This method features mild reaction conditions, simple operation, and a broad substrate scope.

Highly Conductive, Transparent, Adhesive, and Self-Healable Ionogel Based on a Deep Eutectic Solvent with Widely Adjustable Mechanical Strength.

Ionogels have attracted intensive attentions as promising flexible conductive materials. However, simultaneous integration of excellent mechanical properties, high conductivity, outstanding self-healing ability, and strong adhesiveness is still challenging. Here, an ingenious composition design is proposed to address this long-standing challenge of ionogels. High-performance PEI/PAA/CMC ionogels, consist of a loosely cross-linked poly(acrylic acid) (PAA) network, dynamically cross-linked network based on polycationic polyethyleneimine (PEI) and polyanionic PAA, and carboxymethyl cellulose (CMC) reinforcing filler, are formed in a deep eutectic solvent (DES) composed of choline chloride and urea. Benefiting from the loose PAA network and dynamic noncovalent interactions, ionogels with both highly enhanced mechanical robustness and excellent conductivity are obtained at high loading of DES, overcoming the strength-ductility/conductivity trade-off dilemma. By adjusting PEI/PAA mass ratio, the tensile strength and strain of PEI/PAA/CMC ionogels are effectively controlled in a wide range of 0.15-7.9 MPa and 232-1161%, respectively, while maintaining the desirable conductivity of ≈10-4 S cm-1 . Besides, healed tensile strength over 2.1 MPa and adhesion strength up to 0.2 MPa are achieved for the PEI0.06 /PAA0.25 /CMC0.01 ionogel. The delicate design strategy provides a feasible approach to prepare ionogels with outstanding comprehensive performance, which have potential for applications in flexible electronics.

Evaluating the long-term survival benefits of high intensity focused ultrasound ablation for hepatocellular carcinoma with portal vein tumor thrombus: a single center retrospective study.

AIMS: To evaluate the long-term survival benefits of high intensity focused ultrasound (HIFU) ablation in patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombus (PVTT). METHODS: The data of patients with HCC-PVTT treated with HIFU from January 2014 to December 2019 were retrospectively analyzed. All patients received HIFU ablation for both PVTT and liver tumor in one session. Perioperative adverse events (AEs) were recorded, and follow-up was performed postoperatively. The Kaplan-Meier method was used for survival analysis. RESULTS: Median follow-up was 13.75 ± 1.31 months. A total of 144 patients (male/female: 122/22, age: 54.15 ± 11.84 years old) were included in the study. A total of 267 liver tumors (tumor number: 1.87 ± 1.65, range 1-10) were treated with HIFU. The mean ± SD diameter of viable liver tumors was 100.98 ± 61.65 mm. The reported postoperative AEs of HIFU were skin edema (93.75%), local pain (69.44%) and fever (7.64%). There was no liver failure, gastrointestinal bleeding or perioperative death. The median overall survival (OS) time was 14 months, while the cumulative survival rates of 0.5, 1, 2 and 3 years were 79.0%, 58.6%, 33.3% and 5.9%, respectively. The median OS of PVTT types I, II and III was 22, 13 and 14 months, respectively, and the difference was not statistically significant (p > 0.05). CONCLUSION: HIFU is a minimally invasive method for HCC-PVTT with fewer complications, which could prolong the OS. Patients with PVTT type III could benefit more from HIFU, compared to types I and II.

Identification of three new microsatellites and their effects on body measurement traits in pigs using time of flight-mass spectrometry (TOF-MS).

The body status of livestock affects their physiological function and productive performances. Microsatellites, one of the most used DNA markers, have been found to be associated with pig productive traits. However, their identifications and effects on body measurement traits of the Chinese Qinghai Bamei pig still uncovered. According to our previous sequencing data, in this study, three novel microsatellites were found in this breed. Using time of flight-mass spectrometry (TOF-MS) method, these microsatellites were further identified in a large Bamei pig population. TOF-MS spectra showed that there are three microsatellites loci, named P1, P2 and P3. These microsatellites were linkage equilibrium based on the values of D' and r2 tests. Association results demonstrated that P1 locus was associated with the body length, body height and chest width and the beneficial genotype was 150-/150-bp (p < 0.05); and P2 locus was associated with the body height (p < 0.05), and the 145-/145-bp, 145-/147-bp and 145-/149-bp were claimed as favorable genotypes and 145-bp allele was considered as the favorable allele. These findings suggested that P1 and P2 microsatellites might be considered as the candidate genetic markers to select pigs with superior body sizes, especially in local breed.

UV-Assisted Li+-Catalyzed Radical Grafting Polymerization of Vinyl Ethers: A New Strategy for Creating Hydrolysis-Resistant and Long-Lived Polymer Brushes as a "Smart" Surface Coating.

A facile synthetic route was developed to prepare a surface-grafted brush layer of poly(vinyl ethers) (PVEs) directly by a radical mechanism, with the "naked" Li+ acting as a catalyst. Density functional theory calculations suggested that complexation of naked Li+ to VEs significantly reduced the highest unoccupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gap from 5.08 to 0.68 eV, providing a better prospect for electron transfer. The structure, morphology, and surface properties of grafted polymer layers were characterized using attenuated total reflection Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, atomic force microscopy, and dynamic water contact angle (DCA). Moreover, ellipsometry data indicated that the thickness of the polymer brushes was in the range of 20-60 nm, which corresponds to the grafting densities of 0.65-1.15 chain/nm2, and DCA decreased from 84.4 to 45.3°. Most importantly, no hydrolysis was observed for the modified surface after 30 days of exposure to phosphate-buffered saline solution, 0.1 mol/L NaOH(eq) and 0.1 mol/L HCl(eq), demonstrating excellent hydrolysis resistance with long service life. In addition, as a proof of concept, the side hydroxyl groups of grafted PVEs provide active sites for efficient fixation of bioactive molecules, e.g., glycosaminoglycan and serum protein.

Hepatitis B virus-triggered PTEN/ß-catenin/c-Myc signaling enhances PD-L1 expression to promote immune evasion.

Hepatitis B virus (HBV) exploits multiple strategies to evade host immune surveillance. Programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling plays a critical role in regulating T cell homeostasis. However, it remains largely unknown as to how HBV infection elevates PD-L1 expression in hepatocytes. A mouse model of HBV infection was established by hydrodynamic injection with a vector containing 1.3-fold overlength HBV genome (pHBV1.3) via the tail vein. Coculture experiments with HBV-expressing hepatoma cells and Jurkat T cells were established in vitro. We observed significant decrease in the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and increase in ß-catenin/PD-L1 expression in liver tissues from patients with chronic hepatitis B and mice subjected to pHBV1.3 hydrodynamic injection. Mechanistically, decrease in PTEN enhanced ß-catenin/c-Myc signaling and PD-L1 expression in HBV-expressing hepatoma cells, which in turn augmented PD-1 expression, lowered IL-2 secretion, and induced T cell apoptosis. However, ß-catenin disruption inhibited PTEN-mediated PD-L1 expression, which was accompanied by decreased PD-1 expression, and increased IL-2 production in T cells. Luciferase reporter assays revealed that c-Myc stimulated transcriptional activity of PD-L1. In addition, HBV X protein (HBx) and HBV polymerase (HBp) contributed to PTEN downregulation and ß-catenin/PD-L1 upregulation. Strikingly, PTEN overexpression in hepatocytes inhibited ß-catenin/PD-L1 signaling and promoted HBV clearance in vivo. Our findings suggest that HBV-triggered PTEN/ß-catenin/c-Myc signaling via HBx and HBp enhances PD-L1 expression, leading to inhibition of T cell response, and promotes HBV immune evasion.NEW & NOTEWORTHY This study demonstrates that during HBV infection, HBV can increase PD-L1 expression via PTEN/ß-catenin/c-Myc signaling pathway, which in turn inhibits T cell response and ultimately promotes HBV immune evasion. Targeting this signaling pathway is a potential strategy for immunotherapy of chronic hepatitis B.

Orexin A associates with inflammation by interacting with OX1R/OX2R receptor and activating prepro-Orexin in cancer tissues of gastric cancer patients.

OBJECTIVE: Gastric cancer (GC) has been become the second leading cause for cancer-associated death. This study aimed to investigate Orexin A levels and associated receptors in tumor tissues of GC patients. PATIENTS AND METHODS: Forty-six consecutive gastric cancer patients (GC, n=46) and 13 chronic atrophic gastritis patients (CAG, n=13) were recruited. Meanwhile, 18 health individuals visiting Medical Examination Department were involved as control (N group, n=18). ELISA was used to examine Orexin A concentration. Immunohistochemistry assay was used to examine OX1R and OX2R. HE staining was applied to evaluate inflammation. qRT-PCR was employed to detect OX1R, OX2R, prepro-Orexin mRNAs. Serum Helicobacter pylori (H. pylori) infection was measured. RESULTS: Orexin A expression in GC patients was significantly up-regulated compared to N group and CAG group (p<0.05). Orexin A expression was increased in CAG group compared to N group (p<0.05). Gastric cancer tissues exhibited significantly obvious inflammation compared to N group and CAG group (p<0.05). OX1R and OX2R expressions were significantly down-regulated in GC group compared to N group and CAG group (p<0.05). OX1R and OX2R were lower significantly in GC group compared to CAG group (p<0.05). Prepro-Orexin was significantly depleted in tumor tissues of GC group compared to N group and CAG group (p<0.05). Orexin A expression was un-associated with gender, age and differential grades (p>0.05). CAG and GC patients demonstrated higher H. pylori infection rates. CONCLUSION: Orexin A was associated with inflammation by interacting with OX1R/OX2R receptor and activating prepro-Orexin in tumor tissues of gastric cancer patients.

Comparison of diabetic nephropathy between male and female eNOS-/-db/db mice.

Sex is an important biological variable that impacts diverse physiological and pathological processes, including the progression of diabetic nephropathy. Diabetic nephropathy is one of the most common complications of diabetes mellitus and is the leading cause of end-stage renal disease. The endothelial nitric oxide synthase-deficient (eNOS-/-) db/db mouse is an appropriate and valuable model to study mechanisms in the development of diabetic nephropathy because of the similarities of the features of diabetic kidney disease in this model to those in humans. The aim of the present study was to determine whether there was a sex difference in renal injury in eNOS-/-db/db mice. Both male and female eNOS-/-db/db mice showed hyperglycemia, obesity, and renal hypertrophy. However, there was no significant difference in those variables between male and female mice. Furthermore, both male and female diabetic mice showed progressive albuminuria and significantly greater levels of serum creatinine and blood urea nitrogen compared with the same sex of wild-type mice (nondiabetic controls). Although all three variables in female eNOS-/-db/db mice had a tendency to be greater than those in male eNOS-/-db/db mice, those sex differences were not statistically significant. Moreover, both male and female eNOS-/-db/db mice showed significant mesangial expansion, higher glomerular injury scores, profound renal fibrosis, and substantial accumulation of fibronectin and collagen type IV proteins. However, sex differences in those structural changes were not observed. Similarly, survival rates of male and female eNOS-/-db/db mice were comparable. Taken together, the results from the present study suggest no sex difference in renal structural and functional damage in eNOS-/-db/db mice.

Efficacy and safety of high-intensity focused ultrasound ablation for hepatocellular carcinoma by changing the acoustic environment: microbubble contrast agent (SonoVue) and transcatheter arterial chemoembolization.

OBJECTIVE: To compare efficacy and safety of microbubble contrast agent (SonoVue) and transcatheter arterial chemoembolization (TACE) in combination with high-intensity focused ultrasound (HIFU) for treatment of patients with hepatocellular carcinoma (HCC). METHODS: According to our inclusion criteria, we retrospectively reviewed 52 patients with HCCs, and divided them into SonoVue group and TACE group. Tumors were examined by enhanced magnetic resonance imaging. Change of lesions, alpha-fetoprotein values, hepatic and renal function were measured pre- and postoperatively. Then, adverse events were observed and clinical follow-up was performed. RESULTS: Clinical efficacy and the majority of treatment parameters were similar, except for time and energy required for the first massive grey-scale changes in SonoVue group, which were significantly lower than those in TACE group (p < .05). For adverse events, only rate of fever (3.85%) in SonoVue group was significantly lower than that in TACE group (50.00%, p < .05). The 'diagnosis and treatment cycle' in SonoVue group (11.5 ± 2.9) was remarkably shorter than TACE group (22.7 ± 6.3, p < .05). Energy efficiency factor was positively correlated with distance from the deepest layer of lesion to the hepatic capsule or to the abdominal wall in SonoVue group, while that was negatively correlated with iodized oil deposition in TACE group. CONCLUSION: Using microbubble (SonoVue) in HIFU procedure has a similar therapeutic effect compared with TACE, and does not increase the risk of treatment. It might present a new strategy in clinical treatment, especially for patients with a smaller diameter of HCC.

Postoperative Serum Levels of Interleukin-1ß (IL-1ß), Interleukin-17 (IL-17), and Tumor Necrosis Factor-α (TNF-α) in Patients Following Hip Replacement Surgery for Traumatic Fractured Femoral Neck: A Retrospective Study.

BACKGROUND This study aimed to investigate the clinical significance of postoperative serum levels of interleukin-1ß (IL-1ß), interleukin-17 (IL-17), and tumor necrosis factor-alpha (TNF-alpha) in patients who required hip replacement surgery for traumatic fractured neck of femur. MATERIAL AND METHODS A retrospective study included 180 patients who had hip replacement surgery for traumatic fractured neck of femur and a control group of 100 patients. Differences between the two groups were compared for serum levels of IL-1ß, IL-17, and TNF-alpha, and the Harris Hip Score (HHS) (maximum 100 points) using Pearson's correlation. RESULTS Serum levels of IL-1ß, IL-17, and TNF-alpha in the control group were significantly lower than those in the study group (P<0.05). According to the HHS, there were 53 patients in the excellent group, 65 patients in the good group, 43 patients in the fair group and 19 patients in the poor group. Postoperative indicator analysis showed significant differences in IL-1ß, IL-17, and TNF-alpha levels between the four groups (P<0.05). Clinical indicators increased from the excellent group to the poor group, with significant differences between the four groups (P<0.05). Postoperative levels of IL-1ß, IL-17, and TNF-alpha were significantly decreased (P<0.05). Pearson's correlation analysis showed a significant correlation with the clinical indicators (P<0.05). CONCLUSIONS In patients with hip replacement surgery for traumatic fractured neck of femur, measurement of postoperative serum levels of IL-1ß, IL-17, and TNF-alpha were shown to be potential prognostic indicators.

ABIN1 inhibits HDAC1 ubiquitination and protects it from both proteasome- and lysozyme-dependent degradation.

ABIN1, an important immune regulator, has been shown to be involved in various cellular functions, such as immunity, development, tissue homeostasis, and tumor progression. It inhibits TNF- and TLR-induced NF-κB signaling activation and the consequent gene expression. Despite its functional significance, the mechanism of ABIN1 in the regulation of various cellular functions remains unclear. In this study, we identified HDAC1, a key regulator of eukaryotic gene expression and many important cellular events, including cell proliferation, differentiation, cancer and immunity, as an interacting partner of ABIN1. The results showed that ABIN1 acted as a modulator to down-regulate HDAC1 ubiquitination via three different linkages, thereby stabilizing HDAC1 by inhibiting its lysosomal and proteasomal degradation. Interestingly, the inhibitory function of ABIN1 required direct binding with HDAC1. Moreover, the level of p53, which was a tumor suppressor and a well-studied substrate of HDAC1, was under the regulation of ABIN1 via the modulation of HDAC1 levels, suggesting that ABIN1 was physiologically significant in tumor progression. This study has revealed a new function of ABIN1 in mediating HDAC1 modification and stability.