Molecular alterations and prognosis of breast cancer with cutaneous metastasis.

PURPOSE: Cutaneous metastasis (CM) accounts for 5-30% of patients with breast cancer (BC) and presents unfavorable response to treatment and poor prognosis. A better understanding of the molecular alterations involved in metastasis is essential, which would help identify diagnostic and efficacy biomarkers for CM. MATERIALS: We retrospectively reviewed a total of 13 patients with histological or cytological diagnosis of breast cancer and CM. Clinical information was extracted from the medical records. The mutational landscape of matched primary tumors with their lymph nodes or CM tissues were analyzed using next-generation sequencing (NGS) of 425 cancer-relevant genes. All tissues were also analyzed by immunohistochemistry (IHC). The association of prognosis with various clinical and molecular factors was also evaluated. RESULTS: More than half of the patients were Ki67 low (< 50%, 53.7%). Most patients (12, 92.3%) had other metastasis sites other than skin. The median time from diagnosis to the presentation of CM (T1) was 15 months (range: 0-94 months) and the median time from CM to death (T2) was 13 months (range 1-78). The most frequently altered genes across the three types of tissues were TP53 (69.6%, 16/23), PIK3CA (34.8%, 8/23), and MYC (26.1%). The number of alterations in CM tends to be higher than in primary tumors (median 8 vs. 6, P = 0.077). Copy number loss in STK11, copy number gain in FGFR4, TERT, AR, FLT4 and VEGFA and mutations in ATRX, SRC, AMER1 and RAD51C were significantly enriched in CM (all P < 0.05). Ki67 high group (> 50%) showed significantly shorter T1 than the Ki67 low group (≤ 50%) (median 12.5 vs. 50.0 months, P = 0.036). TP53, PIK3CA mutations, and TERT amplification group were associated with inferior T2 (median 11 vs. 36 months, P = 0.065; 8 vs. 36 months, P = 0.013, 7 vs. 36 months, P = 0.003, respectively). All p values were not adjusted. CONCLUSION: We compared the genomic features of primary breast cancer tissues with their corresponding CM tissues and discussed potential genes and pathways that may contribute to the skin metastasis of advanced breast cancers patients. TP53, PIK3CA mutant, and TERT amplification may serve as biomarkers for poor prognosis for CM patients.

Simulating liquefaction-induced resuspension flux in a sediment transport model.

Wave-induced liquefaction is a geological hazard under the action of cyclic wave load on seabed. Liquefaction influences the suspended sediment concentration (SSC), which is essential for sediment dynamics and marine water quality. Till now, the identification of liquefaction state and the effect of liquefaction on SSC have not been sufficiently accounted for in the sediment model. In this study, we introduced a method for simulating the liquefaction-induced resuspension flux into an ocean model. We then simulated a storm north of the Yellow River Delta, China, and validated the results using observational data, including significant wave heights, water levels, excess pore water pressures, and SSCs. The liquefaction areas were mainly distributed in coastal zones with water depths less than 12 m, and the simulated maximum potential soil liquefaction depth was 1.39 m. The liquefaction-induced SSC was separated from the total SSC of both liquefaction- and shear-induced SSCs by the model, yielding a maximum liquefaction-induced SSC of 1.07 kg·m-3. The simulated maximum proportion of liquefaction-induced SSC was 26.2% in regions with water depths of 6-12 m, with a maximum significant wave height of 3.4 m along the 12 m depth contour. The erosion zone at water depths of 8-12 m was reproduced by the model. Within 52.5 h of the storm, the maximum erosion thickness along the 10 m depth contour was enhanced by 33.9%. The model is applicable in the prediction of liquefaction, and provides a new method to simulate the SSC and seabed erosion influenced by liquefaction. Model results show that liquefaction has significant effects on SSC and seabed erosion in the coastal area with depth of 6-12 m. The validity of this method is confined to certain conditions, including a fully saturated seabed exhibiting homogeneity and isotropic properties, small liquefaction depth, residual liquefaction dominating the development of pore pressures, no influence by structures, and the sediment composed of silt and mud that experiences frequent wave-induced liquefaction.

Radical-Chain Hydrosilylation of Alkenes Enabled by Triplet Energy Transfer.

Development of mild, robust and metal-free catalytic approach for the hydrosilylation of alkenes is critical to the advancement of modern organosilicon chemistry given their powerful capacity in the construction of various C-Si bonds. Herein, we wish to disclose a visible light-triggered organophotocatalytic strategy, which proceeds via a triplet energy transfer (EnT)-enabled radical chain pathway. Notably, this redox-neutral protocol is capable of accommodating a broad spectrum of electron-deficient and -rich alkenes with excellent functional group compatibility. Electron-deficient alkenes are more reactive and the reaction could be finished within a couple of minutes even in PBS solution with extremely low concentration, which suggests its click-like potential in organic synthesis. The preparative power of the transformations has been further highlighted in a number of complex settings, including the late-stage functionalization and scale-up experiments. Furthermore, although only highly reactive (TMS)3SiH is suitable hydrosilane substrate, our studies revealed the great reactivity and versatility of (TMS)3Si- group in diverse C-Si and Si-Si bond cleavage-based transformations, enabling the rapid introduction of diverse functional groups and the facile construction of valuable quaternary silicon architectures.

Iron-Catalyzed Photoredox Alcohol α-C-H Alkylation and Tandem Intramolecular Cyclization: Facile Access to Multisubstituted 2,3-Dihydrofurans and γ-Butyrolactones.

Multisubstituted furans occupy a pivotal position within the realms of synthetic chemistry and pharmacological science due to their distinctive chemical configurations and inherent properties. We herein introduce a tandem difunctionalization protocol of alcohols for the efficient synthesis of multisubstituted 2,3-dihydrofurans and γ-butyrolactones through the combination of photocatalysis and iron catalysis under mild conditions. Photoredox alcohol α-C(sp3)-H activation and Pinner-type intramolecular cyclization are two key processes. This method features significant convenience, economic benefits, and environmental friendliness.

A crosslinked and percolation network alginate coating for litchi prevention.

The short shelf life of Litchi is due to its rapid metabolism after being harvested. Refrigeration is not a suitable method for preserving litchi, as the browning process of litchi that has been cryogenic will accelerate when it is brought to room temperature. This study introduces an alginate-based coating as a solution to control the post-harvest metabolism of litchi. The coating achieves this by simultaneously establishing crosslink and percolation networks, both of which act as barriers. The percolation network is created using rod-like cellulose nanocrystals, which possess excellent percolation properties. This network effectively reduces moisture loss. Compared to the control group, the coated litchi exhibited a 38.1 % lower browning index and a 62.5 % lower decay rate. Additionally, the soluble solid content increased by 107.1 %. The inclusion of cellulose nanocrystals and the crosslinking of calcium ions enhanced the mechanical properties of the composite membrane. Specifically, the tensile strength and elongation at break increased by 70 % and 366 % respectively. As all the components in the coating are edible, it is environmentally friendly and safe for human consumption.

Outcomes Following a False-Positive Multi-Cancer Early Detection Test: Results from DETECT-A, the First Large, Prospective, Interventional MCED Study.

Guideline recommended standard of care screening is available for four cancer types; most cancer-related deaths are caused by cancers without standard of care screening. DETECT-A is the first prospective interventional trial evaluating a multi-cancer early detection (MCED) blood test (CancerSEEK) in women without a history of cancer, providing the first opportunity to assess the long-term outcomes of individuals with false-positive (FP) MCED results. This prospective analysis of DETECT-A participants with FP results evaluates the performance of an imaging-based diagnostic workflow and examines cancer risk following a FP result. This analysis included all DETECT-A participants with a positive CancerSEEK test and subsequent flourine-18 fluorodeoxyglucose positron emission tomography-IV contrast-enhanced computed tomography (18-F-FDG PET-CT) imaging and clinical workup indicating no evidence of cancer within 1 year of enrollment (n = 98). Medical records, study interactions, and study surveys were used to assess cancer incidence, treatments, and clinical outcomes through August 2023. Ninety-five of 98 participants with a FP result remained cancer-free with a median follow-up of 3.6 years (IQR: 2.5-4.1) from determination of FP status. Three incident cancers were observed over the follow-up period. One bilateral stage IIIC ovarian cancer was diagnosed 1.9 years after determination of FP status; two stage I breast cancers were diagnosed 0.1 and 1.6 years from determination of FP status. The annual incidence rate of cancer during follow-up from FP determination was 1.0% (95% confidence interval, 0.2%-2.8%). Participants with a positive CancerSEEK test who underwent 18-F-FDG PET-CT and clinical workup without cancer findings had low risk for cancer over the following several years. Prevention Relevance: This study provides multiyear clinical outcomes data following a false-positive multi-cancer early detection test for individuals participating in a prospective interventional trial. It provides a preliminary performance assessment of an imaging-based diagnostic workflow following a false-positive multi-cancer early detection test.

Establishment of a RAA-CRISPR Cas12a based diagnostic method for peste des petits ruminants virus N gene and M gene.

Peste des petis ruminants (PPR) is an acute, highly contagious fatal disease affecting both domestic and wild small ruminants, caused by Morbillivirus caprinae (also known as peste des petis ruminants virus (PPRV)). Herein, a rapid method based on recombinase aided amplification-clustered regularly interspaced short palindromic repeats-Cas12a (RAA-CRISPR Cas12a) to detect PPRV was developed. CRISPR RNAs and RAA primers for PPRV-N (nucleocapsid) and PPRV-M (matrix) fragments were designed. The reaction system was constructed following screening and optimization. Detection could be completed within in 50 minutes at 37°C. Detection of gradient dilutions of plasmids carrying of PPRV N and M gene fragments indicated a minimum limit of detection of 10 copies/µL. There were no cross-reactions with related viruses and all tested lineages of PPRV were detected successfully. The method also showed good repeatability. The detection of clinical samples (previously detected using reverse transcription polymerase chain reaction (RT-PCR)) indicated good consistency between the RAA-CRISPR Cas12a method and RT-PCR. Thus, the RAA-CRISPR Cas12a method for rapid PPRV diagnosis has strong specificity, high sensitivity, and stable repeatability. Moreover, the results can be observed visually under blue or UV light or using lateral flow strips without complex instruments.

Comparative Study on Passive Film Formation Mechanism of Cast and PBF-LB/M-TC4 in Simulated Physiological Solution.

Personalized laser powder bed fusion (PBF-LB/M) Ti-6Al-4V (TC4) has a broader application prospect than that of traditional casting. In this paper, the composition and corrosion resistance of the passive film formation mechanism of TC4 prepared by optimization of PBF-LB/M techniques and traditional casting were systematically studied in 0.9 wt.% NaCl at 37 °C by electrochemical technique and surface analysis. The rates of the passive film formation process, corrosion resistance and composition of TC4 show different characteristics for the different preparation processes. Although the rate of passive film formation of cast-TC4 was higher at the initial immersion, the open circuit potential was more positive, and the film thickness was larger after stabilization, those facts show no positive correlation with corrosion resistance. On the contrary, with no obvious defects on the optimized PBF-LB/M-TC4, the passive film resistance is 2.5 times more, the defect concentration is reduced by 30%, and the TiO2 content is higher than that of the cast-TC4, making the martensitic-based PBF-LB/M-TC4 exhibit excellent corrosion resistance. This also provides good technical support for the further clinical application of PBF-LB/M-TC4.

[Anti-tumor mechanism of total saponins of Paridis Rhizoma on inducing ferroptosis of breast cancer MCF-7 cells].

This study aims to investigate the mechanism of total saponins of Paridis Rhizoma in inducing the ferroptosis of MCF-7 cells and provide a theoretical basis for the clinical treatment of breast cancer with total saponins of Paridis Rhizoma. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the effects of different concentrations of total saponins of Paridis Rhizoma on the proliferation of MCF-7 cells. A phase contrast inverted microscope was used to observe the morphological changes of MCF-7 cells. The colony formation assay was employed to test the colony formation of MCF-7 cells. The lactate dehydrogenase(LDH) release test was conducted to determine the cell membrane integrity of MCF-7 cells. The cell scratch assay was employed to examine the migration of MCF-7 cells. After that, the level of reactive oxygen species(ROS) in MCF-7 cells was observed by an inverted fluorescence microscope, and the content of Fe~(2+) in MCF-7 cells was detected by the corresponding kit. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of MCF-7 cells. Western blot was employed to determine the expression of ferroptosis-related proteins, such as p53, solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long-chain family member 4(ACSL4), and transferrin receptor protein 1(TFR1) in MCF-7 cells. The results showed that 1.5, 3, 4.5, 6, 7.5, and 9 µg·mL~(-1) total saponins of Paridis Rhizoma significantly inhibited the proliferation of MCF-7 cells, with the IC_(50) of 4.12 µg·mL~(-1). Total saponins of Paridis Rhizoma significantly damaged the morphology of MCF-7 cells, leading to the formation of vacuoles and the gradual shrinkage and detachment of cells. Meanwhile, total saponins of Paridis Rhizoma inhibited the colony formation of MCF-7 cells, destroyed the cell membrane(leading to the release of LDH), and shortened the migration distance of MCF-7 cells. Total saponins of Paridis Rhizoma treatment significantly increased the content of ROS, induced oxidative damage, and led to the accumulation of Fe~(2+) in MCF-7 cells. Furthermore, total saponins of Paridis Rhizoma changed the mitochondrial structure, increased the mitochondrial membrane density, led to the decrease or even disappear of ridges, promoted the expression of p53 protein, down-regulated the expression of SLC7A11 and GPX4, and up-regulated the expression of ACSL4 and TFR1. In summary, total saponins of Paridis Rhizoma can significantly inhibit the proliferation and migration of MCF-7 cells and destroy the cell structure by inducing ferroptosis.

[Sinomenine inhibits PDGF/PDGFR signaling pathway to reduce RA-FLS migration induced by NETs].

This study aims to decipher the mechanism of sinomenine in inhibiting platelet-derived growth factor/platelet-derived growth factor receptor(PDGF/PDGFR) signaling pathway in rheumatoid arthritis-fibroblast-like synoviocyte(RA-FLS) migration induced by neutrophil extracellular traps(NETs). RA-FLS was isolated from the synovial tissue of 3 RA patients and cultured. NETs were extracted from the peripheral venous blood of 4 RA patients and 4 healthy control(HC). RA-FLS was classified into control group, HC-NETs group, RA-NETs group, RA-NETs+sinomenine group and RA-NETs+sinomenine+CP-673451 group. RNA-sequencing(RNA-seq) was conducted to identify the differentially expressed genes between HC-NETs and RA-NETs groups. Sangerbox was used to perform the Gene Ontology(GO) function and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape was employed to build the protein-protein interaction(PPI) network. AutoDock Vina and PyMOL were used for molecular docking of sinomenine with PDGFß and PDGFRß. The cell proliferation and migration were determined by the cell counting kit-8(CCK-8) and cell scratch assay, respectively. Western blot was employed to determine the protein level of PDGFRß. Real-time quantitative polymerase chain reaction(RT-qPCR) was carried out to determine the mRNA levels of matrix metalloproteinases(MMPs). The results revealed that neutrophils in RA patients were more likely to produce NETs. Compared with HC-NETs group, RA-NETs group showed up-regulated expression of PDGFß and PDGFRß. Compared with control group, RA-NETs group showed increased cell proliferation and migration and up-regulated protein level of PDGFRß and mRNA levels of PDGFß, PDGFRß, MMP1, MMP3, and MMP9(P<0.05). Compared with RA-NETs group, RA-NETs+sinomenine group presented decreased cell proliferation and migration and down-regulated protein and mRNA level of PDGFRß and mRNA levels of MMP1, MMP3, and MMP9(P<0.05). Compared with RA-NETs+sinomenine group, the proliferation ability of RA-NETs+sinomenine+CP-673451 group decreased(P<0.05). The findings prove that sinomenine reduces the RA-NETs-induced RA-FLS migration by inhibiting PDGF/PDGFR signaling pathway, thus mitigating RA.

Dynamics of solar-induced chlorophyll fluorescence (SIF) and its response to meteorological drought in the Yellow River Basin.

Solar-induced chlorophyll fluorescence (SIF) has been used since its discovery to characterize vegetation photosynthesis and is an effective tool for monitoring vegetation dynamics. Its response to meteorological drought enhances our comprehension of the ecological consequences and adaptive mechanisms of plants facing water scarcity, informing more efficient resource management and efforts in mitigating climate change. This study investigates the spatial and temporal patterns of SIF and examines how vegetation SIF in the Yellow River Basin (YRB) responds to meteorological drought. The findings reveal a gradual southeast-to-northwest decline in SIF across the Yellow River Basin, with an overall increase-from 0.1083 W m-2µm-1sr-1 in 2001 to 0.1468 W m-2µm-1sr-1 in 2019. Approximately 96% of the YRB manifests an upward SIF trend, with 75% of these areas reaching statistical significance. The Standardized Precipitation Evapotranspiration Index (SPEI) at a time scale of 4 months (The SPEI-4), based on the Liang-Kleeman information flow method, is identified as the most suitable drought index, adeptly characterizing the causal relationship influencing SIF variations. As drought intensified, the SPEI-4 index markedly deviated from the baseline, resulting in a decrease in SIF values to their lowest value; subsequently, as drought lessened, it gravitated towards the baseline, and SIF values began to gradually increase, eventually recovering to near their annual maximum. The key finding is that the variability of SIF with SPEI is relatively pronounced in the early growing season, with forests demonstrating superior resilience compared to grasslands and croplands. The responsiveness of vegetation SIF to SPEI can facilitate the establishment of effective drought early warning systems and promote the rational planning of water resources, thereby mitigating the impacts of climate change.

Activation of GPR55 Ameliorates Maternal Separation-Induced Learning and Memory Deficits by Augmenting 5-HT Synthesis in the Dorsal Raphe Nucleus of Juvenile Mice.

Maternal separation (MS) represents a profound early life stressor with enduring impacts on neuronal development and adult cognitive function in both humans and rodents. MS is associated with persistent dysregulations in neurotransmitter systems, including the serotonin (5-HT) pathway, which is pivotal for mood stabilization and stress-coping mechanisms. Although the novel cannabinoid receptor, GPR55, is recognized for its influence on learning and memory, its implications on the function and synaptic dynamics of 5-HT neurons within the dorsal raphe nucleus (DRN) remain to be elucidated. In this study, we sought to discern the repercussions of GPR55 activation on 5-HT synthesis within the DRN of adult C57BL/6J mice that experienced MS. Concurrently, we analyzed potential alterations in excitatory synaptic transmission, long-term synaptic plasticity, and relevant learning and memory outcomes. Our behavioral assessments indicated a marked amelioration in MS-induced learning and memory deficits following GPR55 activation. In conjunction with this, we noted a substantial decrease in 5-HT levels in the MS model, while GPR55 activation stimulated tryptophan hydroxylase 2 synthesis and fostered the release of 5-HT. Electrophysiological patch-clamp analyses highlighted the ability of GPR55 activation to alleviate MS-induced cognitive deficits by modulating the frequency and magnitude of miniature excitatory postsynaptic currents within the DRN. Notably, this cognitive enhancement was underpinned by the phosphorylation of both NMDA and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. In summary, our findings underscore the capacity of GPR55 to elevate 5-HT synthesis and modify synaptic transmissions within the DRN of juvenile mice, positing GPR55 as a promising therapeutic avenue for ameliorating MS-induced cognitive impairment.

Plasmapheresis combined with rituximab treatment of a case of thrombotic thrombocytopenic purpura with Sjögren syndrome and renal impairment: A case report.

RATIONALE: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy caused by reduced activity of the von Willebrand factor-cleaving protease (ADAMTS13), which can be life-threatening. The patient reported in this case study also had concurrent Sjögren syndrome and renal impairment, presenting multiple symptoms and posing a great challenge in treatment. PATIENT CONCERNS: A 25-year-old woman in the postpartum period visited the hospital due to indifference in consciousness for more than 1 day following cesarean section 8 days prior. DIAGNOSIS: Notable decreases were observed in platelets, hemoglobin, creatinine, and ADAMTS13 levels. After a consultative examination by an ophthalmologist, she was diagnosed with retinal hemorrhage in the right eye and dry eye syndrome in both eyes. INTERVENTIONS: Having been diagnosed with TTP with Sjögren syndrome and renal impairment, she received repeated treatments with plasmapheresis combined with rituximab. OUTCOMES: Following treatment and during the follow-up period, the patient's platelet counts and bleeding symptoms significantly improved. LESSONS: TTP has a high mortality rate, and when combined with Sjögren syndrome and renal impairment, it poses an even greater challenge in treatment. However, after administering standard plasmapheresis combined with rituximab treatment, the treatment outcome is favorable.

Dinuclear Titanium(III)-Catalyzed Radical-Type Kinetic Resolution of Epoxides for the Enantioselective Synthesis of cis-Glycidic Esters.

Glycidic esters represent pivotal constituents in synthetic chemistry, offering enhanced versatility for tailoring toward a diverse array of molecular targets in comparison with simple epoxides. While considerable progress has been made in the asymmetric synthesis of trans- and trisubstituted glycidic esters, achieving enantioselective preparation of cis-glycidic esters has remained a long-standing challenge. Here, we demonstrate a selectivity-predictable modular platform for the asymmetric synthesis of cis-glycidic esters via a novel dinuclear (salen)titanium(III)-catalyzed radical-type kinetic resolution (KR) approach. This radical KR protocol operates under mild conditions and demonstrates a wide substrate scope, facilitating the synthesis of alkyl- and aryl-substituted cis-glycidic esters with high levels of regioselectivity and enantioselectivity, along with hydroxy ester byproducts representing synthetically valuable motifs as well. This study presents a unique exploration of radical-type KR applied to epoxides, effectively overcoming the steric challenges inherent in conventional nucleophilic-type methodologies typically employed in epoxide chemistry.

Polysaccharides from Dendrobium officinale delay diabetic kidney disease interstitial fibrosis through LncRNA XIST/TGF-ß1.

PURPOSE: Renal interstitial fibrosis is a pathological manifestation of the progression of diabetic kidney disease (DKD). Dendrobium officinale polysaccharides (DOP), one of the major active components of Dendrobium officinale, have hypoglycemic and hypolipidemic effects and are used clinically to treat diabetes. However, the role of DOP in delaying DKD progression remains unclear. This study aimed to explore the potential mechanisms by which DOP delays DKD renal interstitial fibrosis. METHODS: Using db/db mice as a model of DKD, we administered DOP by gavage and observed its therapeutic effectiveness. Employing ASO technology, we knocked down lncRNA XIST expression in kidney tissues and detected the expression of lncRNA XIST, TGF-ß1, and renal interstitial fibrosis-related molecules. RESULTS: DOP was primarily composed of monosaccharides, with 91.57% glucose and 1.41% mannose, forming a spheroid-like structure. It has a high polydispersity index with an Mw/Mn of 6.146, and the polysaccharides are mainly connected by 4-Man(p) and 4-Glc(p) linkages. In the kidneys of db/db mice, lncRNA XIST and TGF-ß1 are highly expressed; however, their expression is significantly reduced after gastric infusion with DOP, and upon knockdown of lncRNA XIST, it might delay the progression of renal interstitial fibrosis in DKD. CONCLUSION: DOP may delay the progression of DKD renal interstitial fibrosis through the regulation of the LncRNA XIST/TGF-ß1 related fibrotic pathway. This provides a new perspective for clinical strategies to delay the progression of DKD renal interstitial fibrosis.

MiR-132-3p suppresses peritoneal fibrosis induced by peritoneal dialysis via targeting TGF-ß1/Smad2/3 signaling pathway.

BACKGROUND: Peritoneal fibrosis (PF) is the main complication of peritoneal dialysis (PD) and the most common cause of cessation from PD. There is still no effective therapeutic approach to reserve PF. We aimed to investigate the role of miR-132-3p and underlying potential mechanisms in PF. METHODS: A total of 18 Sprague-Dawley (SD) rats were divided randomly into three groups (n = 6): (i)Control group (ii)PF group (iii)PF+Losartan group; Rats in the PF group and PF+Losartan group received daily intraperitoneal injections of 3 mg/kg chlorhexidine for 14 days, and rats in the PF+Losartan group simultaneously received daily intraperitoneal injections of 2 mg/kg losartan for 14 days. The control group was injected with saline in the same volume. Met-5A cells were treated for 24h with TGF-ß1 dissolved in recombinant buffered saline at a concentration of 10 ng/ml, meanwhile, PBS solution as a negative control. The human peritoneal solution was collected for the detection of miR-132-3p. RESULTS: In vivo, SD rats were infused with chlorhexidine to establish PF model, and we found that miR-132-3p significantly decreased and the expressions of transforming growth factor-ß1 (TGF-ß1), and Smad2/3 were up-regulated in PF. In vitro, miR-132-3p mimics suppressed TGF-ß1/Smad2/3 activity, whereas miR-132-3p inhibition activated the pathway. In human peritoneal solution, we found that the expression of miR-132-3p decreased in a time-dependent model and its effect became more pronounced with longer PD duration. CONCLUSION: MiR-132-3p ameliorated PF by suppressing TGF-ß1/Smad2/3 activity, suggesting that miR-132-3p represented a potential therapeutic approach for PF.

Microstructure and Mechanical Properties of Powder Metallurgy Superalloy Joints Welded by Inertia Friction Welding.

In recent years, for the structural characteristics and design requirements of the integral rotor and disc shaft of the integrated engine, the welding quality and mechanical properties of superalloy weldments have received increasing attention. In this paper, inertia friction welding (IFW) of FGH96 alloy was carried out using different welding parameters, and the homogeneous connection of FGH96 alloy hollow bars was successfully realized. The microstructure evolution, mechanical properties and fracture failure of the welded joints at room and high temperatures were investigated. The FGH96 alloy IFW joints were divided into the weld nugget zone (WNZ), the thermo-mechanically affected zone (TMAZ), the heat-affected zone (HAZ) and the base metal (BM), and there were significant differences in grain structure and distribution of the γ' phase in each of the characteristic zones. The microhardness and tensile properties of the IFW joints were investigated, and the results showed an "M"-shaped curve in the microhardness distribution, with the lowest point of hardness observed in the HAZ. The tensile test results indicated that the fracture position moved from the BM to the WNZ with the increase in temperature, the microstructure at the fracture changed significantly and the tensile strength decreased from 1512.0 MPa at room temperature to 1201.3 MPa at 750 °C. The difference in the mechanical properties of the joints was mainly attributed to the changes in the dissolution and precipitation of the γ' phase.

Polycyclic aromatic compounds (PACs) in industrial soils from northwestern of China: occurrence, distribution, exposure risk, and implications on risk-based controls.

Some Polycyclic Aromatic Compounds (PACs) such as nitrated-PAHs (NPAHs), oxygenated-PAHs (OPAHs) and methyl-PAHs (MPAHs) have attracted significant concern due to derivatives have greater potential to be more toxic at low environmental concentrations compared to their PPAHs, particularly in petrochemical industrial region and its surrounding areas surface soils in China. Hence, this article provides an insight into the fate, sources, impacts, and relevance to the external environment of PAH-derivatives based on important emissions source. Moreover, prospective health risk due to their exposure has also been discussed. In this study, the concentration (10-3 ng/g) of Æ©18PPAHs, Æ©11MPAHs, Æ©12NPAHs, and Æ©4OPAHs in the park were 9.67 ± 1.40, 3.24 ± 0.54, 0.03 ± 0.02 and 0.19 ± 0.65, respectively, which were 4.47, 3.89, 2.04 and 1.17 times than of them surrounding the region. A decreasing trend of the low molecular weight (2-4Rings) contribution to the total amount of PAHs, while the fraction of high molecular weight (5-6Rings) species showed the opposite trend. According to the principal component analysis (PCA) and diagnostic ratios indicated PAHs in the soil samples have mixed sources from industrial activities, solid fuel combustion, and heavy traffic. Despite the high concentrations of MPAHs and OPAHs, the toxicity equivalency quotients (TEQs) of them were not calculated due to the lack of toxic equivalent factors (TEF), thus current studies on PAH and derivatives could have underestimated their exposure risks. The quality and sustainable management of soils are crucial for human health and sustainable development, while there is lack of public awareness of the severe issue of soil pollution. It is recommended to conduct more intensive monitoring and regional assessments in the future.

Fabrication and properties of PLA/ß-TCP scaffolds using liquid crystal display (LCD) photocuring 3D printing for bone tissue engineering.

Introduction: Bone defects remain a thorny challenge that clinicians have to face. At present, scaffolds prepared by 3D printing are increasingly used in the field of bone tissue repair. Polylactic acid (PLA) has good thermoplasticity, processability, biocompatibility, and biodegradability, but the PLA is brittle and has poor osteogenic performance. Beta-tricalcium phosphate (ß-TCP) has good mechanical properties and osteogenic induction properties, which can make up for the drawbacks of PLA. Methods: In this study, photocurable biodegradable polylactic acid (bio-PLA) was utilized as the raw material to prepare PLA/ß-TCP slurries with varying ß-TCP contents (ß-TCP dosage at 0%, 10%, 20%, 30%, 35% of the PLA dosage, respectively). The PLA/ß-TCP scaffolds were fabricated using liquid crystal display (LCD) light-curing 3D printing technology. The characterization of the scaffolds was assessed, and the biological activity of the scaffold with the optimal compressive strength was evaluated. The biocompatibility of the scaffold was assessed through CCK-8 assays, hemocompatibility assay and live-dead staining experiments. The osteogenic differentiation capacity of the scaffold on MC3T3-E1 cells was evaluated through alizarin red staining, alkaline phosphatase (ALP) detection, immunofluorescence experiments, and RT-qPCR assays. Results: The prepared scaffold possesses a three-dimensional network structure, and with an increase in the quantity of ß-TCP, more ß-TCP particles adhere to the scaffold surface. The compressive strength of PLA/ß-TCP scaffolds exhibits a trend of initial increase followed by decrease with an increasing amount of ß-TCP, reaching a maximum value of 52.1 MPa at a 10% ß-TCP content. Degradation rate curve results indicate that with the passage of time, the degradation rate of the scaffold gradually increases, and the pH of the scaffold during degradation shows an alkaline tendency. Additionally, Live/dead staining and blood compatibility experiments suggest that the prepared PLA/ß-TCP scaffold demonstrates excellent biocompatibility. CCK-8 experiments indicate that the PLA/ß-TCP group promotes cell proliferation, and the prepared PLA/ß-TCP scaffold exhibits a significant ability to enhance the osteogenic differentiation of MC3T3-E1 cells in vitro. Discussion: 3D printed LCD photocuring PLA/ß-TCP scaffolds could improve surface bioactivity and lead to better osteogenesis, which may provide a unique strategy for developing bioactive implants in orthopedic applications.