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• Temperature exposure during pregnancy may increase risk of preeclampsia. • High pre-pregnancy BMI may increase sensitivity to temperature exposure. • Gestational weeks 1 – 8 of pregnancy are vulnerable to temperature exposure. Environmental exposures during pregnancy have been associated with adverse obstetric outcomes. However, limited and inconsistent evidence exists regarding the association between air temperature exposure and the risk of preeclampsia (PE). This study aimed to evaluate the correlation between ambient temperature exposure during pregnancy and PE risk, as well as identify the specific time window of temperature exposure that increases PE risk. A population-based cohort study was conducted from January 2012 to April 2022 in Guangzhou, China. Pregnant women were recruited in early pregnancy and followed until delivery. A total of 3,314 PE patients and 114,201 normal pregnancies were included. Ambient temperature exposures at different gestational weeks were recorded for each participant. Logistic regression models were used to evaluate the correlation between ambient temperature exposure and PE risk. Stratified analyses were conducted based on maternal age and pre-pregnancy BMI. Distributed lag models were employed to identify the time window of temperature exposure related to PE. Exposure to extreme high temperature (aOR = 1.24, 95 % CI 1.12 – 1.38) and moderate high temperature (aOR = 1.22, 95 % CI 1.10 – 1.35) during early pregnancy was associated with an increased risk of PE. Furthermore, women with higher pre-pregnancy BMI had a higher risk of developing PE when exposed to high temperature during early pregnancy compared to normal-weight women. The time window of temperature exposure related to PE was identified as pregnancy weeks 1 to 8. This study provides evidence for the association of high temperature exposure during early pregnancy with the risk of PE, as well as identifies the specific time window of temperature exposure related to PE. These findings have implications for developing potential strategies to protect pregnant women, particularly those with higher pre-pregnancy BMI, from the adverse effects of extreme temperatures during early pregnancy. [ABSTRACT FROM AUTHOR]

• Probiotic-derived selenium (Se) nanoparticles acted as the immune adjuvant. • HBO effectively promoted the Se-mediated O 2 – generation to boost tumor CDT. • HBO largely ameliorated the immunosuppressive tumor microenvironment. Chemodynamic therapy (CDT) was a promising approach to enhance the immunogenicity of tumor cells for potentiating immune checkpoint blockade (ICB) therapy, but usually suffered from hypoxia and immunosuppressive tumor microenvironment. Herein, we developed a hyperbaric oxygen (HBO)-strengthened CDT-nanoadjuvants platform (Se@OMV-GOx-HA) by modifying probiotic-derived selenium (Se) nanoparticles with glucose oxidase (GOx) and hyaluronic acid (HA) to boost αPD-L1-medaited ICB therapy against breast cancer. In the presence of H 2 O 2 and glutathione (GSH), Se@OMV acted as nanoenzyme to mediate the electron transfer from GSH to O 2 giving O 2 –, while GOx catalyzed the production of H 2 O 2. Synergistically, HBO effectively improved tumor hypoxia to foster GOx-catalyzed oxidation of glucose to H 2 O 2 , then provided the essential fuels including H 2 O 2 and O 2 for Se-mediated O 2 – generation, causing strong immunogenic cell death (ICD) effect to enhance the immunogenicity of tumor cells. Under co-stimulation by Se@OMV acting as immunoadjuvants, maturation of dendritic cells and priming of cytotoxic T cells were largely promoted. Assisted by HBO, infiltration of cytotoxic T cells in mice tumor was significantly improved, which not only generated long-term antitumor immune memory, but largely boosted αPD-L1-medaited ICB therapy. Given the clinical available of HBO, this nanosystem has great clinical translation potential for cancer CDT/immunotherapy. [ABSTRACT FROM AUTHOR]

A-kinase interacting protein 1 (AKIP1) has previously been demonstrated to be overexpressed in clear cell renal cell carcinoma (ccRCC) tissues and is associated with patient prognosis. The aim of the present study was to explore whether AKIP1 can affect the proliferation, invasion, migration and angiogenesis of ccRCC cells via its interaction with Rac1. Furthermore, the influence of AKIP1 and therefore Rac1 on the expression of the downstream ERK/cellular (c)-Myc signaling pathway was explored. The interaction between AKIP1 and Rac1 was determined using co-immunoprecipitation. The mRNA and protein expression levels of AKIP1 and Rac1 in normal renal epithelial cell lines and ccRCC cell lines were detected using reverse transcription-quantitative PCR (RT-qPCR) and western blotting, respectively. The transfection efficiency of small interfering RNA-AKIP1 and the Rac1 overexpression vector were also confirmed using RT-qPCR and western blotting. The viability, proliferation, invasion and migration of ccRCC cells following transfection were analyzed using the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, Transwell and wound healing assays, respectively. The tube formation ability of HUVECs was assessed using the tube formation assay. The protein expression levels of proliferation, invasion, migration and tube-formation-associated proteins as well as proteins associated with the ERK/c-Myc signaling pathway, were detected via western blotting. The results demonstrated that AKIP1 expression levels were increased in ccRCC cell lines. AKIP1 knockdown inhibited the proliferation, invasion and migration of ccRCC cells and HUVEC tube-formation. In addition, AKIP1 was demonstrated to bind to Rac1 in ccRCC cells and AKIP1 downregulation inhibited Rac1 expression. Furthermore, Rac1 overexpression reversed the effects of AKIP1 knockdown on ccRCC cells. AKIP1 knockdown also suppressed the ERK/c-Myc signaling pathway, which was reversed by Rac1 overexpression. In conclusion, AKIP1 knockdown potentially suppressed the proliferation, invasion, migration and angiogenesis of ccRCC cells and inhibited the ERK/c-Myc signaling pathway by binding to Rac1. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) occurs in the urinary system which has high incidence and mortality. During past decades, lots of long noncoding RNAs (lncRNAs) have been identified to function in cancer progression, including BC. In our research, we targeted at investigating the functions and mechanisms of lncRNA pro-transition associated RNA (PTAR) in BC. Functional assays were implemented to access the changes of BC cell phenotype. Mechanistic assays were applied for confirming the interaction between RNAs. Based on the collected data, PTAR expression was high in BC cells and silenced PTAR repressed BC cell proliferative, migratory and invasive abilities but improved cell apoptotic ability. In vivo study also verified PTAR depletion inhibited BC tumor growth. Furthermore, miR-299–3p was confirmed to bind with PTAR and its overexpression suppressed malignant behaviors of BC cells. Cluster of differentiation 164 (CD164) was proved to be miR-299–3p target. Rescue experiments implied overexpressed CD164 offset the inhibitory function of PTAR depletion on BC cell phenotype. Additionally, CD164 was uncovered to combine with C-X-C motif chemokine receptor 4 (CXCR4) to switch on PI3K/AKT pathway. To conclude, PTAR facilitates BC development via regulating miR-299–3p/CD164 axis and activating PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Three-dimensional numerical simulations are carried out to investigate the temperature field in the contact zone due to the thermal loading of the workpiece in surface grinding. This technique considers that the thermophysical properties of the workpiece material are non-linear according to temperature, the contact zone between the wheel and the workpiece is assumed as an arc surface, and the heat flux entering the workpiece is assumed as proportional to the local undeformed chip thickness. A good agreement is found between the simulated results and the experimental observations. The high grinding temperature leads to the thermal expansion of the workpiece material, which causes the thickness of the actual material removal layer to be larger than the cutting depth. The grinding temperature at the central portion is higher than that on the side of the workpiece during the wet grinding, thus the material removal layer in the central zone is thicker than that on the side zone, and the workpiece surface is concave across the grinding width. [ABSTRACT FROM AUTHOR]

Cytotoxic T lymphocyte (CTL), a key effector cell in aplastic anemia (AA) immune injury, is shown to be a potential target for AA drug therapy. However, there is no candidate for this target till now. Oriented by the inhibition activity of CTL and macrophage derived nitric oxide (NO), a series of novel sinomenine derivatives on rings A and C are designed, synthesized and screened. Among them, compound 3a demonstrates the best inhibitory activity on CTL with an IC 50 value of 2.3 μM, and a 97.1% inhibiton rate on macrophage NO production without significant cytotoxicity. Further, compound 3a exhibits substantial therapeutic efficacy on immune-mediated BM failure in AA model mice by improving the symptoms of anemia and the function of BM hematopoiesis, and shows more advantages in life quality improving than cyclosporine A (CsA). Its efficacy on AA at least partly comes from targeting on activated cluster of differentiation (CD)8+ T cell. Additionally, 3a also shows much less toxicity (LD 50 > 10.0 g/kg) than sinomenine (LD 50 = 1.1 g/kg) in preliminary acute toxicity assessment in mice, and has a low risk to inhibit hERG to cause cardiotoxicity. These results indicate that compound 3a merits further investigation for AA treatment by targeting on CTL. [Display omitted] • A series of novel sinomenine derivatives are designed and synthesized. • 3a shows the best in vitro inhibitory activity. • 3a shows substantial therapeutic efficacy on mice model of aplastic anemia. • The efficacy of 3a at least partly comes from targeting on activated CD8+ T cell. • 3a shows good safety in vivo. [ABSTRACT FROM AUTHOR]

• Ten new compounds were isolated from the roots of Stephania tetrandra. • Compounds 1 , 2 , and 12 were unambiguously determined by X-ray crystallography. • Compound 3 was a partial racemate and was discovered by chiral HPLC. • Compounds 1 – 4 and 14 – 16 showed anti-inflammatory activities. Ten new bisbenzylisoquinoline alkaloids (1 – 10) and eight known analogues (11 – 18) were obtained from the roots of Stephania tetrandra. The structures of these compounds were determined by spectroscopic methods, single-crystal X-ray diffraction, electronic circular dichroism analyses, and chemical method. Compounds 1 , 15 , and 16 showed the better anti-inflammatory activities with IC 50 values of 15.26 ± 2.99, 6.12 ± 0.25, and 5.92 ± 1.89 μM, respectively. Compound 18 possessed cytotoxic activities against MCF-7, HCT-116, and HepG2 cell lines with IC 50 values of 2.81 ± 0.06, 3.66 ± 0.26, and 2.85 ± 0.15 μM, respectively. [ABSTRACT FROM AUTHOR]