Model test study of bridge pile horizontal bearing behavior under landslide deformation.

Pile is a common foundation on the slope, which poses a serious threat to the construction and operation if the slope deformation and causes landslide. In this study, a model device of pile foundation on landslide was independently developed by relative displacement loading between pile and soil to explore the influence of landslide deformation on pile and analysis the soil failure rule and the deformation characteristics of pile in different stages of landslide deformation, a few model tests were completed including the relative displacement between soil and pile from 1 to 17 cm, and the pile diameter and the modulus of slide bed were also considered. The results indicated that: the evolution process of landslide deformation with pile foundation on could be divided into four stages including soil compaction, cracks growth, yield stage, and failure stage; ratios of the maximum soil pressure and bending moment growth from the soil compaction stage to the cracks growth stage to the total growth in these four stages are both exceeding 60%; the soil pressure increases with the increase of pile diameter and sliding bed modulus. Therefore, it is best to effectively monitor and control the landslide in the initial soil compression stage that in soil compaction stage and methods such as increasing pile foundations or reinforcing the sliding bed can be used for protection.

Novel MRI-Based Pedicle Bone Quality Score Independently Predicts Pedicle Screw Loosening after Degenerative Lumbar Fusion Surgery.

Pedicle screw loosening after posterior lumbar fusion is associated with poor bone quality, which often determines screw pull-out strength, insertion torque, and vertebral body loading characteristics. Magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score were associated with poor bone quality. Current evidence suggests that pedicle bone quality (PBQ) has a greater impact on screw stability. However, the correlation between MRI-based PBQ score and screw loosening has not been reported. PURPOSE: To introduce and evaluate an MRI-based PBQ score to determine its effectiveness in predicting pedicle screw loosening following lumbar fusion surgery. METHODS: The retrospective study analyzed 244 patients who underwent posterior lumbar interbody fusion (PLIF) with pedicle screws between December 2017 and December 2021, with CT and MRI imaging before surgery. Data collected included patient demographics and preoperative radiological data. Radiographic screw loosening was measured at 12 months postoperatively. Clinical assessments included pain visual analog scale (VAS) and Oswestry Disability Index (ODI) scores. The PBQ score was measured using MRI scans. We use univariate analysis for preliminary screening of the risk factors of screw loosening. Subsequent analysis involved multivariate logistic regression to identify independent predictive factors for screw loosening. We constructed the receiver operating characteristic (ROC) curve to ascertain the discriminative capacity of the PBQ score. The area under the curve (AUC) quantified its predictive accuracy. Additionally, we evaluated the association between PBQ score and screw loosening using Spearman's correlation analysis. RESULTS: Overall, 244 patients who underwent PLIF with pedicle screw fixation participated in this study, including 35 in the loosening group and 209 in the non-loosening group. PBQ score in the loosening group was significantly higher than that in the non-loosening group. On multivariate logistic regression, the higher PBQ score (OR = 8.481, 95% CI: 3.158-22.774; p < 0.001) and the lower mean Hounsfield unit (HU) value of L1-4 (OR = 0.967, 95% CI 0.951-0.984; p < 0.001) were the variables that significantly predicted screw loosening. The AUC for the PBQ score and HU value were 0.751 (95% CI: 0.673-0.828) and 0.702 (95% CI: 0.612-0.791). The PBQ score optimal cutoff to differentiate patients with loosening and with non-loosening was calculated as 3.045 with a sensitivity of 85.7% and specificity of 76.9%, while the optimal cutoff of the HU value was 151.5 with a sensitivity of 64.6% and specificity of 89.5%. CONCLUSIONS: The association between the PBQ score and the propensity for lumbar pedicle screw loosening was found to be substantial. As a predictive measure, the PBQ score outperformed the HU value in forecasting the likelihood of screw loosening post-posterior lumbar fusion.

The role of radiotherapy in patients with refractory Hodgkin's lymphoma after treatment with brentuximab vedotin and/or immune checkpoint inhibitors.

Background: Approximately 10%-30% of patients with Hodgkin's lymphoma (HL) experience relapse or refractory (R/R) disease after first-line standard therapy. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) have important roles in the salvage treatment of R/R HL. However, subsequent treatment for HL refractory to BV and/or ICI treatment is challenging. Methods: We retrospectively analyzed patients in two institutions who had R/R HL, experienced BV or ICI treatment failure, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Overall, 19 patients were enrolled. First-line systemic therapy comprised doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD, 84.2%); AVD plus ICIs (10.5%); and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP, 5.3%). After first-line therapy, 15 (78.9%) and four patients (21.1%) had refractory disease and relapsed, respectively. After R/R HL diagnosis, six (31.6%), two (10.5%), and 11 (57.9%) patients received BV and ICIs concurrently, BV monotherapy, and ICI monotherapy, respectively. All patients received intensity-modulated RT (n = 12, 63.2%) or volumetric modulated arc therapy (VMAT; n = 7, 36.8%). The ORR as well as the complete response (CR) rate was 100%; the median DOR to RT was 17.2 months (range, 7.9-46.7 months). Two patients showed progression outside the radiation field; one patient had extensive in-field, out-of-field, nodal, and extranodal relapse. With a median follow-up time of 16.2 months (range, 9.2-23.2 months), the 1-year PFS and OS were 84.4% and 100%, respectively. PFS was associated with extranodal involvement (P = 0.019) and gross tumor volume (P = 0.044). All patients tolerated RT well without adverse events of grade ≥ 3. Conclusion: RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

CD4+ T-Cell Senescence in Neurodegenerative Disease: Pathogenesis and Potential Therapeutic Targets.

With the increasing proportion of the aging population, neurodegenerative diseases have become one of the major health issues in society. Neurodegenerative diseases (NDs), including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neurodegeneration associated with aging, leading to a gradual decline in cognitive, emotional, and motor functions in patients. The process of aging is a normal physiological process in human life and is accompanied by the aging of the immune system, which is known as immunosenescence. T-cells are an important part of the immune system, and their senescence is the main feature of immunosenescence. The appearance of senescent T-cells has been shown to potentially lead to chronic inflammation and tissue damage, with some studies indicating a direct link between T-cell senescence, inflammation, and neuronal damage. The role of these subsets with different functions in NDs is still under debate. A growing body of evidence suggests that in people with a ND, there is a prevalence of CD4+ T-cell subsets exhibiting characteristics that are linked to senescence. This underscores the significance of CD4+ T-cells in NDs. In this review, we summarize the classification and function of CD4+ T-cell subpopulations, the characteristics of CD4+ T-cell senescence, the potential roles of these cells in animal models and human studies of NDs, and therapeutic strategies targeting CD4+ T-cell senescence.

Formation and Structure of Gas-Phase Lanthanide(III) Cyanobenzyne Complex (η2-4-CNC6H3)LnCl2-, Obtained via Both the Single- and Dual-Ligand Strategies.

The lanthanide(III) cyanobenzyne complexes (η2-4-CNC6H3)LnCl2- (Ln = La-Lu except Eu; Pm was not examined) were generated in the gas phase using an electrospray ionization mass spectrometry coupled with collision-induced dissociation (CID) technique. For all lanthanides except Sm, Eu, and Yb, (4-CNC6H3)LnCl2- can be generated either via a single-ligand strategy through consecutive CO2 and HCl losses of (4-CNC6H4CO2)LnCl3- or via a dual-ligand strategy through successive CO2/C6H5CN or 4-CNC6H4CO2H and CO2 losses of (4-CNC6H4CO2)2LnCl2-. For Sm and Yb, although only reduction products LnCl3- were formed upon CID of (4-CNC6H4CO2)LnCl3-, (4-CNC6H3)LnCl2- were obtained via the dual-ligand strategy without the appearances of other products. CID of (4-CNC6H4CO2)EuCl3- and (4-CNC6H4CO2)2EuCl2- gave EuCl3- and the cyanophenyl complex (4-CNC6H4)EuCl2-, respectively, in both of which the +III oxidation state of Eu was reduced to +II. Density functional theory (DFT) calculations reveal that (4-CNC6H3)LnCl2- are formally described as Ln(III) cyanobenzyne complexes, (η2-4-CNC6H3)LnCl2-, with the dianionic cyanobenzyne ligand (4-CNC6H32-) coordinating to the Ln(III) centers through two Ln-C σ bonds, which is in accordance with their reactivities toward water. Benzyne and substituted benzyne complexes (XC6H3)LuCl2- (X = H, 3-CN, 4-F, 4-Cl, and 4-CH3) were also synthesized in the gas phase via the single- and dual-ligand strategies.

Myricetin ameliorates polycystic ovary syndrome in mice by brown adipose tissue activation.

In brief: Brown adipose tissue impaired in polycystic ovary syndrome (PCOS) plays a crucial role in the treatment of PCOS. This study shows that myricetin potently improves PCOS by activating brown adipose tissue (BAT). Abstract: PCOS is a complex endocrine disease characterized by hyperandrogenism, anovulation and polycystic ovary, and is often accompanied by metabolic disorder such as insulin resistance. BAT has been considered as a promising target for the treatment of obesity and other metabolic disease. In this study, we showed that 3 weeks of myricetin (a compound from natural product) treatment improved metabolic capacity and insulin sensitivity by activating BAT in dehydroepiandrosterone (DHEA)-induced PCOS mice. Furthermore, increased number of corpus luteum and decreased cystic formation were observed in PCOS mice. With the hormone levels such as luteinizing hormone (LH) were reversed, estrous cycle was also normalized after myricetin treatment. Eventually, myricetin markedly improved reproductive defects in PCOS mice. In short, our results suggest that myricetin treatment dramatically ameliorates ovarian dysfunction and metabolic disturbances in PCOS and provides a novel perspective for the treatment of PCOS.

Hypofractionated radiotherapy for refractory or relapsed aggressive B-cell lymphoma in the rituximab era.

BACKGROUND: Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. METHODS: We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. RESULTS: A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3-5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2-27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P < 0.001). No serious non-hematological adverse effects (≥ grade 3) associated with RT were reported. CONCLUSION: These data suggest that hypofractionated RT was effective and tolerable for patients with R/R aggressive B-cell lymphoma, especially for those that exhibited localized residual disease.

Effect of oxide impurities on the dissolution behavior of Th4+, Be2+ and U4+ in fluoride salts.

Oxides are one of the most important impurities in the fuel salt of molten salt reactors (MSRs), and excessive oxide impurities pose a risk to the safe operation of MSRs. This study focused on investigating the precipitation behavior between Th4+, U4+, and Be2+ with O2- in the 2LiF-BeF2 (FLiBe) eutectic salt system. The results showed that the solubility of UO2 was 5.52 × 10-3 mol kg-1, and the solubility product (Ksp) of UO2 was 6.14 × 10-7 mol3 kg-3 in FLiBe salt at 650 °C. It was also found that the O2- ion would firstly react with U4+ to form UO2, and then the excessive O2- would react with Be2+ to generate BeO in the FLiBe system. Despite conducting the solubility experiment of ThO2 and titration experiment of FLiBe-ThF4, the system failed to achieve the solubility and the Ksp of ThO2. The main reason for this was that O2- preferentially reacted with Be2+ over Th4+ to form precipitates, in other words, Be2+ exerted a protective effect against Th4+. Above all, this work experimentally demonstrated that in the FLiBe system, O2- preferentially combines with U4+ to form a precipitate, followed by Be2+, while Th4+ is relatively inert.

LATS1 Promotes B-ALL Tumorigenesis by Regulating YAP1 Phosphorylation and Subcellular Localization.

OBJECTIVE: YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors; differentiating between these roles may depend on the YAP1 phosphorylation pattern. The specific function of YAP1 in B cell acute lymphoblastic leukemia (B-ALL), however, is currently unclear. Thus, in the present study, the role of YAP1 in B-ALL was investigated using relevant cell lines and patient datasets. METHODS: The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting, quantitative real-time polymerase chain reaction, flow cytometry, immunostaining, and nude mouse subcutaneous tumorigenesis experiments. Gene expression levels of Hippo pathway-related molecules before and after verteporfin (VP) treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 cells. RESULTS: Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation levels. YAP1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells; YAP1 was distributed in the nuclei in NALM6 cells. Knockdown of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 phase. Before and after VP treatment, the expression of the upstream gene LATS1 was upregulated; its overexpression promoted YAP1-Ser127 phosphorylation. Further, YAP1 was distributed in the plasma. CONCLUSION: LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function; thus, VP, which targets this axis, may serve as a new therapeutic method for improving the outcomes for B-ALL patients.