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During the laser cladding repair, the heat accumulation effect is produced due to the continuous input of energy, which leads to the increase of dilution rate under the same process parameters. In order to get the appropriate dilution rate, an accurate finite element model was established based on the experiment, and the variation of dilution rates under different power functions was analyzed. According to the results of finite element analysis, different power functions and dilution rates at different times were collected, and the dilution rate was optimized through deep learning, and the ideal power function was obtained. The results show that the dilution rate of the whole cladding layer fluctuates around the ideal value all the time by adjusting the laser power in real time, and the results are satisfactory. The maximum error of dilution rate is 21.75%, the minimum error is 0, and the average error is 5.79%.

Gear fault diagnosis (GFD) based on vibration signals is a popular research topic in industry and academia. This paper provides a comprehensive summary and systematic review of vibration signal‐based GFD methods in recent years, thereby providing insights for relevant researchers. The authors first introduce the common gear faults and their vibration signal characteristics. The authors overview and compare the common feature extraction methods, such as adaptive mode decomposition, deconvolution, mathematical morphological filtering, and entropy. For each method, this paper introduces its idea, analyses its advantages and disadvantages, and reviews its application in GFD. Then the authors present machine learning‐based methods for gear fault recognition and emphasise deep learning‐based methods. Moreover, the authors compare different fault recognition methods. Finally, the authors discuss the challenges and opportunities towards data‐driven GFD.

Background B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR T-cell) therapy has exhibited remarkable efficacy in refractory or relapsed multiple myeloma (R/R MM), but recurrence and rapid progression of disease are still observed within a short time after treatment. Long-term pomalidomide therapy, which potentiates T-cell functionality, might enhance the efficacy of BCMA CAR T-cell therapy. Methods We performed a single-center retrospective clinical study. Patients with relapsed or refractory multiple myeloma who received BCMA CAR T-cell infusion were enrolled in our study, and were followed by long-term pomalidomide treatment (4 mg/day) or not one month after infusion. The response and adverse events were assessed after infusion. The effect of pomalidomide on BCMA CAR T-cells was assessed in vitro. Results The objective response rate (ORR) of BCMA-CART was 100%. Three months following CAR T-cell infusion, of the 8 patients receiving pomalidomide, except for 2 patients who stopped maintenance therapy and were lost to follow-up, all patients (6/6) achieved VGPR (very good partial response) or CR (complete response), while only 5 patients (5/8) who did not receive pomalidomide treatment achieved VGPR or better. At a median follow-up of 27 months, for the 8 patients who did not receive pomalidomide administration, the median TTP (time to progression) was 5.85 (1–14) months, while the OS (overall survival) was 10.7 (1.2–16) months. Of the 8 patients who received pomalidomide therapy after CAR T-cell infusion, the median TTP was 13 (7–13) months, while the OS was not reached. Moreover, neither long-term hematological toxicity nor drug-induced liver damage was observed during the follow-up period. Mechanistically, pomalidomide promotes antimyeloma efficacy of BCMA CAR T-cells by inhibiting cell apoptosis and enhancing cytoxicity. Conclusions Our results confirmed that BCMA CAR T-cell therapy combined with long-term pomalidomide had a low recurrence rate and manageable therapy-related side effects, providing a promising option for treating R/R MM. Graphical Abstract

The complexity and specificity of the three-cylinder crankshaft lead to under-filling in the balance slider. Normally, way of the precision of the crankshaft is to increase the blank diameter or the bridge size of flash, which result in high forging load, low service life of die, and material utilization. Therefore, a preformed dressing is designed in the balance slider of the pre-forging die. During the pre-forging period, a dressing will be formed in the balance slider, which is used to ensure the precision of the three-cylinder crankshaft in the final forging period. First, CAD models of the die and billet are established, then which are simulated by the Deform-3D software. The forging load and die wear depth are analyzed, and the area of the balance slider is under-filling. Second, a new pre-forging die is designed with a preformed dressing by the CAD software. Third, response surface analysis (RSA) and finite element technology are combined to optimize the pre-forging die of the three-cylinder crankshaft. According to variance analysis, the preformed dressing is not a significant influence factor on the die wear depth and load. Optimized factors’ R , D , H of the pre-forging die are 19 mm, 84 mm, and 6 mm, respectively. Fourth, the flash height of the final forging die is optimized, and the balance slider is filled well, and the die wear depth is reduced. Finally, physical experiment and practice forging are carried out to verify the optimal scheme of the finite element method (FEM), and the results of the experimental and finite element have a good consistency.

Background Cognitive dysfunction caused by infection frequently emerges as a complication in sepsis survivor patients. However, a comprehensive understanding of its pathogenesis remains elusive. Methods In our in vivo experiments, an animal model of endotoxemia was employed, utilizing the Novel Object Recognition Test and Morris Water Maze Test to assess cognitive function. Various techniques, including immunofluorescent staining, Western blotting, blood‒brain barrier permeability assessment, Limulus Amebocyte Lysate (LAL) assay, and Proximity-ligation assay, were employed to identify brain pathological injury and neuroinflammation. To discern the role of Caspase-11 (Casp11) in hematopoietic or non-hematopoietic cells in endotoxemia-induced cognitive decline, bone marrow chimeras were generated through bone marrow transplantation (BMT) using wild-type (WT) and Casp11-deficient mice. In vitro studies involved treating BV2 cells with E. coli-derived outer membrane vesicles to mimic in vivo conditions. Results Our findings indicate that the deficiency of Casp11-GSDMD signaling pathways reverses infection-induced cognitive dysfunction. Moreover, cognitive dysfunction can be ameliorated by blocking the IL-1 effect. Mechanistically, the absence of Casp11 signaling significantly mitigated blood‒brain barrier leakage, microglial activation, and synaptic damage in the hippocampal CA3 region, ultimately leading to improved cognitive function. Conclusion This study unveils the crucial contribution of Casp11 and GSDMD to cognitive impairments and spatial memory loss in a murine sepsis model. Targeting Casp11 signaling emerges as a promising strategy for preventing or treating cognitive dysfunction in patients with severe infections.

Acute leukemia (AL) is an aggressive hematologic malignancy that often causes serious complications and requires intensive care unit (ICU) treatment. Identifying risk factors for mortality in AL patients during and post-ICU admission can improve prognosis. This retrospective study enrolled AL patients first admitted to the ICU of the Third Xiangya Hospital, Central South University, from November 2008 to October 2023. It analyzed risk factors associated with ICU mortality, 1-month mortality and 6-month mortality, and conducted a subgroup analysis of the prognosis of ICU survivors. A total of 126 patients were included in this study, with a median age of 42 years. Acute respiratory failure (46%) and sepsis (23%) were the main reasons for ICU admission. Overall, the mortality rates were 57.9% in the ICU, 67.5% at 1 month, and 69% at 6 months. Notably, among the ICU survivors, 26.4% (14/53) died within 6 months, with 85.7% (12/14) occurring within the first month. The time from hospital admission to ICU transfer >10 days and invasive mechanical ventilation were independent risk factors for ICU mortality, 1-month mortality and 6-month mortality. Relapsed or refractory leukemia (OR = 20.715) and low albumin levels (OR = 34.428) were independent risk factors for death within one month among ICU survivors. The risk factors for mortality in AL patients admitted to the ICU exhibit dynamic changes across different stages. For ICU survivors, optimizing nutritional support and initiating anti-tumor treatment as early as possible after discharge are crucial for improving prognosis.

As a kind of self-excited vibrations, chatter vibration is extremely common in end milling, especially in high-speed cutting processes. It affects the machining accuracy of products and decreases the processing efficiency of machine tools. Thus it is very crucial to develop an effective condition monitoring system to extract the chatter feature before chatter vibration grows. In this paper, a hybrid chatter detection method (HCDM) is proposed for chatter feature extraction and classification in end milling. Firstly, wavelet packet decomposition is employed to decompose cutting vibration signals into a series of wavelet coefficients, and the signals of each frequency band are reconstructed. Secondly, fast Fourier transform and singular spectrum analysis are chosen to obtain the chatter features. Furthermore, the support vector machine model is optimized by particle swarm optimization to recognize the cutting states in end milling. At last, cutting experiments of 300 M steel under different machining conditions are conducted, and the results indicate that the proposed HCDM can distinguish the stable, transition, and chatter states accurately and rapidly in end milling.

Immune checkpoint inhibitors (ICIs) have transformed the treatment of many solid tumors. Still, their effectiveness in multiple myeloma (MM) remains underwhelming, highlighting the need to explore alternative approaches beyond conventional ICIs. Here, CD161 is identified as a novel inhibitory receptor on bone marrow (BM) tissue resident memory CD8+ T cells (CD8+ TRM), known for their sustained presence and vital role in local immune surveillance in MM BM tumor microenvironments. The CD161–CLEC2D axis, where CD161 interacts with CLEC2D on MM cells, mediates immune suppression and TRM dysfunction. Blocking CD161 enhances TRM function, including tissue residency, proliferation, and antitumor activity. CD161 blockade significantly alleviates chimeric antigen receptor T‐cell (CAR‐T) exhaustion and enhances their antimyeloma function ex vivo. These findings identified the CD161–CLEC2D pathway as a potential novel target for immunotherapy of MM. CD161 is identified as a novel inhibitory receptor on bone marrow (BM)‐resident CD8⁺ T cells in multiple myeloma (MM). Through interaction with its ligand CLEC2D, CD161 impairs T‐cell function and promotes immune suppression. Blockade of CD161 restores tissue residency and cytotoxicity of CD8⁺ T cells and enhances chimeric antigen receptor T‐cell (CAR‐T) activity, providing a potential immunotherapeutic target in MM.

Patients with peripheral T cell lymphoma (PTCL) who achieved tumor response with first-line standard therapy were at high risk of disease relapse. We explored golidocitinib (150 mg once daily) as maintenance therapy for this group of patients (JACKPOT26, NCT06511869). This study included two cohorts: patients achieving a complete response (Cohort 1 (CR), N  = 30) and a partial response (Cohort 2 (PR), N  = 18) during induction stage. All enrolled patients were transplant ineligible or did not have a transplant plan. All dosed patients were included in the efficacy and safety analysis. In Cohort 1, the 24-month disease free survival (DFS) rate was 74.2% with golidocitinib treatment. In nodal subtypes (AITL, NOS, ALK- ALCL), the 24-month DFS rate was 62.7%. In Cohort 2, median progression free survival (PFS) was 17.4 months, and 24-month PFS rate was 48.6%. Nine out of 18 patients with initial PR achieved complete response, leading to a complete response rate of 50.0%, and median duration of response of 23.9 months. The most common ≥grade 3 treatment-related treatment-emergent adverse events (TRAEs) were hematological adverse events in nature, including neutrophil count decreased (47.9%), white blood cell count decreased (31.3%), lymphocyte count decreased (14.6%) and leukopenia (12.5%). The majority of these TRAEs were reversible and clinically manageable. TRAEs leading to treatment interruption and discontinuation occurred in 60.4% and 10% of patients, respectively. No TRAEs leading to fatal outcomes were reported. This study suggests the potential of golidocitinib as maintenance therapy for patients with PTCL.