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The eutectoid Ti–Cu alloy has the advantages of high strength and hardness. However, the pearlite eutectoid structures with coupled α + Ti2Cu lamellae result in low plasticity. In this study, a Zr alloying method is proposed to suppress the formation of lamellar pearlite and promote a bainite-like morphology. Increasing the Zr content can transform the α lamellae into rod-like laths and the Ti2Cu lamellae into dispersed particles, thereby reducing their embrittlement effect. The α laths are further refined to about 0.27 and 0.37 μm with 30% and 50% Zr addition, resulting in strong grain boundary strengthening effects. As a result, the mechanical properties are enhanced after Zr alloying. The best combination of compressive yield strength, maximum strength, and plasticity is achieved with 30% Zr addition, which is about 1040 MPa, 2505 MPa, and 33%, respectively. The results in this study can offer valuable insights into microstructure optimization and performance enhancement in active eutectoid Ti–Cu systems.

The limited mechanical properties of Al–Si alloys hinder their application in demanding and extreme conditions. The cracking tendency of high-strength aluminum alloys and high-cost of rare-earth elements pose challenges for the large-scale application of aluminum alloys in additive manufacturing. The novel and practical high-speed scanning remelting proposed in this study enables Al–Si alloys to exhibit significant proportion of fine microstructures and nano-precipitates, surpassing the mechanical properties of aluminum alloys fabricated by normal methods with exceptional strength (496.1 ± 5.8 MPa) and plasticity (21.4 ± 0.9%). This in-situ microstructure control method opens new pathways for the application in demanding engineering contexts.

The inferior creep ductility of Inconel 718 (IN718) fabricated by selective laser melting (SLM), which is unable to meet aerospace material specification (≥4%), limits its engineering application. Despite persistent optimization efforts in the SLM process and post-heat treatment, this issue remains unresolved. This study involved SLM fabrication of the modified IN718 with trace amounts of LaB6 and/or P, followed by homogenization and double aging heat treatment. The addition of trace LaB6 notably influenced the recrystallized grain structure and carbide precipitation at grain boundaries, while trace P addition had minimal impact. All samples exhibited similar γ′ and γ″ strengthening precipitates. Creep tests conducted at 650°C/690 MPa revealed that the individual modification of LaB6 showed limited improvement in creep performance and P showed no improvement, but the combined addition of LaB6 and P led to a substantial enhancement in creep performance, especially reaching as high as 8.6% creep strain. This remarkable improvement in creep ductility is unlikely to arise from the altered grain structure and grain boundary precipitates induced by LaB6 but predominantly arises from the synergistic effect of P and B in enhancing resistance to crack propagation during the third stage of creep.

Abstract Cytokine-mediated STAT5 protein activation is vital for lymphocyte development and function. In vitro tyrosine phosphorylation of a C-terminal tyrosine is critical for activation of STAT5A and STAT5B; however, the importance of STAT5 tyrosine phosphorylation in vivo has not been assessed. Here we generate Stat5a and Stat5b tyrosine-to-phenylalanine mutant knockin mice and find they have greatly reduced CD8+ T-cell numbers and profoundly diminished IL-2-induced proliferation of these cells, and this correlates with reduced induction of Myc, pRB, a range of cyclins and CDKs, and a partial G1→S phase-transition block. These mutant CD8+ T cells also exhibit decreased IL-2-mediated activation of pERK and pAKT, which we attribute in part to diminished expression of IL-2Rβ and IL-2Rγ. Our findings thus demonstrate that tyrosine phosphorylation of both STAT5A and STAT5B is essential for maximal IL-2 signaling. Moreover, our transcriptomic and proteomic analyses elucidate the molecular basis of the IL-2-induced proliferation of CD8+ T cells.

Abstract The X-rays emitted during CT scans can increase solid cancer risks by damaging DNA, with the risk tied to patient-specific organ doses. This study aims to establish a new method to predict patient specific abdominal organ doses from CT examinations using minimized computational resources at a fast speed. The CT data of 247 abdominal patients were selected and exported to the auto-segmentation software named DeepViewer to generate abdominal regions of interest (ROIs). Radiomics feature were extracted based on the selected CT data and ROIs. Reference organ doses were obtained by GPU-based Monte Carlo simulations. The support vector regression (SVR) model was trained based on the radiomics features and reference organ doses to predict abdominal organ doses from CT examinations. The prediction performance of the SVR model was tested and verified by changing the abdominal patients of the train and test sets randomly. For the abdominal organs, the maximal difference between the reference and the predicted dose was less than 1 mGy. For the body and bowel, the organ doses were predicted with a percentage error of less than 5.2%, and the coefficient of determination (R2) reached up to 0.9. For the left kidney, right kidney, liver, and spinal cord, the mean absolute percentage error ranged from 5.1 to 8.9%, and the R2 values were more than 0.74. The SVR model could be trained to achieve accurate prediction of personalized abdominal organ doses in less than one second using a single CPU core.

Abstract High frequencies of stem-like memory T cells in infusion products correlate with superior patient outcomes across multiple T cell therapy trials. Herein, we analyzed a published CRISPR activation screening to identify transcriptional regulators that could be harnessed to augment stem-like behavior in CD8+ T cells. Using IFN-γ production as a proxy for CD8+ T cell terminal differentiation, LMO4 emerged among the top hits inhibiting the development of effectors cells. Consistently, we found that Lmo4 was downregulated upon CD8+ T cell activation but maintained under culture conditions facilitating the formation of stem-like T cells. By employing a synthetic biology approach to ectopically express LMO4 in antitumor CD8+ T cells, we enabled selective expansion and enhanced persistence of transduced cells, while limiting their terminal differentiation and senescence. LMO4 overexpression promoted transcriptional programs regulating stemness, increasing the numbers of stem-like CD8+ memory T cells and enhancing their polyfunctionality and recall capacity. When tested in syngeneic and xenograft tumor models, LMO4 overexpression boosted CD8+ T cell antitumor immunity, resulting in enhanced tumor regression. Rather than directly modulating gene transcription, LMO4 bound to JAK1 and potentiated STAT3 signaling in response to IL-21, inducing the expression of target genes (Tcf7, Socs3, Junb, and Zfp36) crucial for memory responses. CRISPR/Cas9-deletion of Stat3 nullified the enhanced memory signature conferred by LMO4, thereby abrogating the therapeutic benefit of LMO4 overexpression. These results establish LMO4 overexpression as an effective strategy to boost CD8+ T cell stemness, providing a new synthetic biology tool to bolster the efficacy of T cell-based immunotherapies.

Abstract Deep learning has made significant advancements in speech enhancement, which plays a crucial role in improving the quality of speech signals in noisy conditions. In this paper, we propose a new approach called M-DGAN, which introduces a time (T)-domain encoder-decoder structure with rich channel representations into the time-frequency (TF)-domain generator framework, resulting in a new generator structure with mixed magnitude and phase representations in the T and TF-domains. The proposed mixed T-domain and TF-domain generator, incorporating the cascaded reworked conformer (CRC) structure, exhibits improved modeling capability and adaptability. Test results on the Voice Bank + DEMAND public dataset show that our method achieves the highest score with $$PSEQ=3.52$$ P S E Q = 3.52 and performs well on all the remaining metrics when compared to the current state-of-the-art methods. In addition, tests on the NISQA_TEST_LIVETALK real dataset of the NISQA Corpus show the breadth and robustness of our model on speech enhancement tasks.

Mg-Gd-Y-Zn-Zr alloy is an important lightweight material in the aerospace field. Wire arc additive manufacturing (WAAM) provides a new route to fabricate large Mg alloy components. Here, a Mg-8Gd-4Y–1Zn-0.5Zr (wt.%) alloy was fabricated using WAAM based on the cold metal transfer (CMT) process. Subsequently, a short-time solid solution + aging treatment was designed to tailor the microstructure. In the as-fabricated condition, the microstructure mainly consisted of fine α-Mg, network (Mg,Zn)3(Gd,Y) eutectic phase, and lamellar γ′ basal precipitate. After 500 °C-1 h short-time solid solution, the eutectic phase rapidly dissolved, the long-period stacking ordered (LPSO) phase formed, and the fine grain was maintained. Due to the good deformation capacity of the fine grains and the kinking deformation capacity of the LPSO phase, the ductility was significantly improved from 5.2 ± 0.4% to 15.5 ± 1.1%. After further 200 °C-64 h artificial aging, dense β′ prismatic precipitates formed. Thanks to the synergistic strengthening of the fine grains and β′ prismatic precipitates, a yield strength of 242 ± 4 MPa was achieved. However, the kinking deformation of the LPSO phase was inhibited, resulting in a drastic decrease of ductility to 6.1 ± 0.5%. Overall, the combination of strength and ductility of the CMT-based WAAM-processed Mg-Gd-Y-Zn-Zr alloy under an optimized heat treatment regime can be superior to those of the cast Mg-Gd-Y-Zn-Zr alloys with similar contents of Gd and Y elements. This work can guide further performance optimization for WAAM-processed Mg-Gd-Y-Zn-Zr alloys.

The high yield ratio and low strain hardening ability of titanium alloys significantly limit their engineering applications. In this work, a Ti65Zr30Cu5 (at.%) alloy with nanoscale α laths was additively manufactured and achieved a high yield strength of 1274 MPa and a high strain hardening rate up to 40% of the shear modulus. Results show that universal basal/pyramidal dislocation reactions occur during the tensile deformation process. This triggers high-density sessile 〈c 〉 dislocation junctions, which accumulate and pin other mobile dislocations. Consequently, abundant dislocation walls are induced, leading to a strong hetero-deformation-induced strain hardening effect.

【Objective】The study was carried out to explore the effects of acute hypoxia on the survival of juvenile Eleutheronema tetradactylum and their spleen and heart tissue structure, with a view to providing technical support and theoretical references for the breeding and production of this species.【Method】Filling water with nitrogen to quickly overflow oxygen and reduce the content of dissolved oxygen in the water. Different levels of dissolved oxygen treatment were set in the experiment: normal oxygen group (6.33 ± 0.15 mg/L), moderate hypoxia group (3.99 ± 0.18 mg/L), and severe hypoxia group (2.05 ± 0.15 mg/L). Each treatment group was set up with 3 parallel devices. During the experiment, the flowing water was turned off, and the dissolved oxygen level in the water was monitored in real time by using a dissolved oxygen measuring instrument. The corresponding dissolved oxygen level was maintained by adjusting the size of the inflation valve. Using paraffin embedding, sectioning and hematoxylin eosin (HE) staining methods were used to observe the changes in tissue structure of the heart and spleen of juvenile E. tetradactylum.【Result】In terms of mortality rate, there was no mortality observed in the E. tetradactylum in the normal oxygen group; the mortality rates of juvenile fish under the stress in the moderate and severe hypoxia groups were 10.0%-13.3% at 23 hours, 30.0%-40.0% at 26 hours, and 43.3%-53.3% at 29 hours. In terms of spleen tissue structure, compared with the normal oxygen group, the moderate hypoxia group showed an increase in white pulp and the number of lymphocyte in juvenile fish, sparse distribution of peripheral red pulp, and a decrease in the number of melanin macrophages; the red pulp area of juvenile fish in the severe hypoxia group expanded, with a decrease in the white pulp area and the number of lymphocytes, and melanin macrophages rarely appearing. In terms of heart tissue structure, the compact layer of heart tissue in juvenile fish in the moderate hypoxia group became thinner, the myocardial fibers in the sponge layer became thinner, and the spacing became wider, and partial myocardial fiber rupture phenomenon occurred; the degree of thinning of the compact layer and thinning of the myocardial fibers in the sponge layer of juvenile fish in the severely hypoxic group increased, and the degree of expansion of the interstitial space increased compared to the hypoxic group, with partial myocardial cell rupture, nucleus protrusion, myocardial fiber rupture, and disordered arrangement.【Conclusion】The study has shown that acute hypoxia stress can affect the survival rate of juvenile E. tetradactylum. The lower the dissolved oxygen level, the higher the mortality rate, and the degree of tissue structure damage increases with the level of hypoxia.

Abstract Due to the advanced studies on stem cells in developmental biology, the roles of stem cells in the body and their phenotypes in related diseases have not been covered clearly. Meanwhile, with the intensive research on the mechanisms of stem cells in regulating various diseases, stem cell therapy is increasingly being attention because of its effectiveness and safety. As one of the most widely used stem cell in stem cell therapies, hematopoietic stem cell transplantation shows huge advantage in treatment of leukemia and other blood-malignant diseases. Besides, due to the effect of anti-inflammatory and immunomodulatory, mesenchymal stem cells could be a potential therapeutic strategy for variety infectious diseases. In this review, we summarized the effects of Staphylococcus aureus (S. aureus) and its components on different types of adult stem cells and their downstream signaling pathways. Also, we reviewed the roles of different kinds of stem cells in various disease models caused by S. aureus, providing new insights for applying stem cell therapy to treat infectious diseases.

Abstract Facial features are important sources of information about perceived trustworthiness. Masks and protective clothing diminish the visibility of facial cues by either partially concealing the mouth and nose or covering the entire face. During the pandemic, the use of personal protective equipment affected and redefined who trusts whom in society. This study used the classical investment game of interpersonal trust with Chinese participants to explore the impact of occlusion on interpersonal trust. Faces with moderate initial trustworthiness were occluded by a mask or protective clothing in Experiment 1 and were digitally occluded by a square in Experiment 2, and faces with three levels of initial trustworthiness were occluded by a mask in Experiment 3. Results showed that both undergraduates (Experiment 1a) and non-student adults (Experiment 1b) perceived the faces with protective clothing as more trustworthy than faces wearing standard masks and faces not wearing masks. Faces with the top halves showing were perceived as trustworthy as full faces, while faces with the bottom halves showing were perceived as less trustworthy. The effect of masks is weak and complex. Masks reduced participants’ trust in faces with high initial trustworthiness, had no effect on faces with low and moderate initial trustworthiness, and only slightly increased the trust of undergraduates in faces with moderate initial trustworthiness. Our findings indicate that the lack of information caused by occlusion and the social significance associated with occlusion collectively affect people’s trust behavior in Chinese society. We believe the findings of this study will be useful in elucidating the effects of personal protective equipment usage on perceptions of trustworthiness.

【Objective】The effects of different mass concentrations of MS-222 and eugenol stresses on gill and liver tissue damage in juvenile Eleutheronema tetradactylum were studied.【Method】Seven different mass concentrations of MS-222 (20, 30, 35, 40, 45, 50 and 60 mg/L) and seven different mass concentrations of eugenol (5, 10, 20, 25, 30, 40 and 50 mg/L) were set to analyze the static anaesthesia effects of different treatments on juvenile E. tetradactylum with an average length of 4.5 (±0.5) cm and an average body weight of 1.5 (±0.5) g.【Result】When the concentration of MS-222 was not less than 35 mg/ L, the juvenile fish began to show stress reactions after 467 s of anesthesia. When the concentration was 50 mg/L, some juvenile fish could be induced into the anesthesia period. When the concentration was 60 mg/L, all juvenile fish could be induced into the anesthesia period after 293 s. When the concentration of eugenol was not less than 25 mg/L, the juvenile fish began to exhibit stress reactions after 291 s of anaesthesia; when the concentration was 30 mg/L, some juvenile fish could be induced into the anaesthesia period; when the concentrations were 40 and 50 mg/L, all juvenile fish could be induced into the anaesthesia period at 194 s and 102 s, respectively. With the increase of MS-222 and eugenol concentrations, the time for juvenile fish to enter the same anaesthesia period was significantly shortened (P < 0.05). At high concentrations, the time for juvenile fish to enter the anaesthesia period was too fast, which exceeded the tolerance value and may have a certain toxic effect on the fish body, leading to fish death. By observing the pathological sections of juvenile fish tissues, it was found that, with the increase of MS-222 and eugenol concentrations, the liver cells of juvenile fish showed vacuoles, disordered arrangement, nuclear dissolution visible in the nucleus and unclear liver plate structure. The gill lamellae were curved with enlarged ends, and they may burst or fall off in severe cases.【Conclusion】A moderate dosage of anaesthetic can reduce the stress response of fish to the external environment and reduce oxygen consumption. Different concentrations of MS-222 and eugenol (except for 5 mg/L) have a sedative effect on E. tetradactylum within 3 minutes. When the concentrations of the two anaesthetics are too high, the anaesthesia time is too long, and the juvenile fish are in a state of stress for a long time, the fish will die.

Abstract Background The purpose of this study was to explore the relevant risk factors associated with biliary complications (BCs) in patients with end-stage hepatic alveolar echinococcosis (HAE) following ex vivo liver resection and autotransplantation (ELRA) and to establish and visualize a nomogram model. Methods This study retrospectively analysed patients with end-stage HAE who received ELRA treatment at the First Affiliated Hospital of Xinjiang Medical University between August 1, 2010 and May 10, 2023. The least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize the feature variables for predicting the incidence of BCs following ELRA. Multivariate logistic regression analysis was used to develop a prognostic model by incorporating the selected feature variables from the LASSO regression model. The predictive ability, discrimination, consistency with the actual risk, and clinical utility of the candidate prediction model were evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Internal validation was performed by the bootstrapping method. Results The candidate prediction nomogram included predictors such as age, hepatic bile duct dilation, portal hypertension, and regular resection based on hepatic segments. The model demonstrated good discrimination ability and a satisfactory calibration curve, with an area under the ROC curve (AUC) of 0.818 (95% CI 0.7417–0.8958). According to DCA, this prediction model can predict the risk of BCs occurrence within a probability threshold range of 9% to 85% to achieve clinical net benefit. Conclusions A prognostic nomogram with good discriminative ability and high accuracy was developed and validated to predict BCs after ELRA in patients with end-stage HAE.

Abstract Objective This study aimed to explore the effect of CD276 expression on the sunitinib sensitivity of clear cell renal cell carcinoma (ccRCC) cell and animal models and the potential mechanisms involved. Methods CD276 expression levels of ccRCC and normal samples were analyzed via online databases and real-time quantitative PCR (RT-qPCR). CD276 was knocked down in ccRCC cell models (sunitinib-resistant 786-O/R cells and sunitinib-sensitive 786-O cells) using shRNA transfection, and the cells were exposed to a sunitinib (2 µM) environment. Cells proliferation was then analyzed using MTT assay and colony formation experiment. Alkaline comet assay, immunofluorescent staining, and western blot experiments were conducted to assess the DNA damage repair ability of the cells. Western blot was also used to observe the activation of FAK-MAPK pathway within the cells. Finally, a nude mouse xenograft model was established and the nude mice were orally administered sunitinib (40 mg/kg/d) to evaluate the in vivo effects of CD276 knockdown on the therapeutic efficacy of sunitinib against ccRCC. Results CD276 was significantly upregulated in both ccRCC clinical tissue samples and cell models. In vitro experiments showed that knocking down CD276 reduced the survival rate, IC50 value, and colony-forming ability of ccRCC cells. Knocking down CD276 increased the comet tail moment (TM) values and γH2AX foci number, and reduced BRCA1 and RAD51 protein levels. Knocking down CD276 also decreased the levels of p-FAK, p-MEK, and p-ERK proteins. Conclusion Knocking down CD276 effectively improved the sensitivity of ccRCC cell and animal models to sunitinib treatment.

Abstract Immune evasion contributes to cancer growth and progression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) and programmed cell death ligands (PD-Ls) are considered to be the major immune checkpoint molecules. The interaction of PD-1 and PD-L1 negatively regulates adaptive immune response mainly by inhibiting the activity of effector T cells while enhancing the function of immunosuppressive regulatory T cells (Tregs), largely contributing to the maintenance of immune homeostasis that prevents dysregulated immunity and harmful immune responses. However, cancer cells exploit the PD-1/PD-L1 axis to cause immune escape in cancer development and progression. Blockade of PD-1/PD-L1 by neutralizing antibodies restores T cells activity and enhances anti-tumor immunity, achieving remarkable success in cancer therapy. Therefore, the regulatory mechanisms of PD-1/PD-L1 in cancers have attracted an increasing attention. This article aims to provide a comprehensive review of the roles of the PD-1/PD-L1 signaling in human autoimmune diseases and cancers. We summarize all aspects of regulatory mechanisms underlying the expression and activity of PD-1 and PD-L1 in cancers, including genetic, epigenetic, post-transcriptional and post-translational regulatory mechanisms. In addition, we further summarize the progress in clinical research on the antitumor effects of targeting PD-1/PD-L1 antibodies alone and in combination with other therapeutic approaches, providing new strategies for finding new tumor markers and developing combined therapeutic approaches.

Abstract In this study, we aimed to investigate the risk factors associated with in-hospital mortality in patients with cirrhosis and sepsis, establish and validate the nomogram. This retrospective study included patients diagnosed with liver cirrhosis and sepsis in the Medical Information Mart for Intensive Care IV (MIMIC-IV). Models were compared by the area under the curve (AUC), integrated discriminant improvement (IDI), net reclassification index (NRI) and decision curve analysis (DCA). A total of 1,696 patients with cirrhosis and sepsis were included in the final cohort. Our final model included the following 9 variables: age, heartrate, total bilirubin (TBIL), glucose, sodium, anion gap (AG), fungal infections, mechanical ventilation, and vasopressin. The nomogram were constructed based on these variables. The AUC values of the nomograms were 0.805 (95% CI 0.776–0.833), which provided significantly higher discrimination compared to that of SOFA score [0.684 (95% CI 0.647–0.720)], MELD-Na [0.672 (95% CI 0.636–0.709)] and ABIC [0.674(95% CI 0.638–0.710)]. We established the first nomogram for predicting in-hospital mortality in patients with liver cirrhosis and sepsis based on these factors. This nomogram can performs well and facilitates clinicians to identify people at high risk of in-hospital mortality.

Abstract Starting from the molecular picture for the $$D_{s1}(2460)$$ D s 1 ( 2460 ) and $$D_{s1}(2536)$$ D s 1 ( 2536 ) resonances, which are dynamically generated by the interaction of coupled channels, the most important of which are the $$D^*K$$ D ∗ K for the $$D_{s1}(2460)$$ D s 1 ( 2460 ) and $$DK^*$$ D K ∗ for the $$D_{s1}(2536)$$ D s 1 ( 2536 ) , we evaluate the ratio of decay widths for the $$\bar{B}_s^0 \rightarrow D_{s1}(2460)^+ K^-$$ B ¯ s 0 → D s 1 ( 2460 ) + K - and $$\bar{B}_s^0 \rightarrow D_{s1}(2536)^+ K^-$$ B ¯ s 0 → D s 1 ( 2536 ) + K - decays, the latter of which has been recently investigated by the LHCb collaboration, and we obtain a ratio of the order of unity. The present results should provide an incentive for the related decay into the $$D_{s1}(2460)$$ D s 1 ( 2460 ) resonance to be performed, which would provide valuable information on the nature of these two resonances.

Abstract As traditional energy reserves continue to decline, the importance of new energy sources increases. However, the current traditional power system often fails to consider new energy sources, particularly in power supply systems that integrate multiple new energy sources. The cost, efficiency, and environmental factors seriously affect the energy system’s efficiency. Therefore, this proposal presents a multi-objective optimization discrete assignment pathfinder algorithm. The algorithm can handle multi-objective optimization problems and adapt to various constraints, providing a more precise optimization scheme for new energy systems. The experimental results indicated that the proposed research method exhibits better performance compared to other algorithms of the same type. Compared with the multi-objective multivariate universe optimization algorithm and the multi-objective sparrow search algorithm, the research method was ahead in terms of fitness value by 9.54% and 14.67%, respectively. Meanwhile, in the grid simulation, the research method achieved an average efficiency of 96.16%, which is better than the comparative algorithms by 6.57–14.02%. The study not only improves the optimization efficiency of new energy consumption, but also provides a powerful decision support tool for the planning and operation of wind farms. It is of great significance for the improvement of power system efficiency and decarbonization, and helps to promote the large-scale integration and sustainable development of new energy.

Background: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have become integral elements within the current landscape of breast cancer treatment modalities; however, they are associated with interstitial lung disease (ILD), which is rare but potentially fatal. Notably, only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors. Therefore, this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors. We also reported three cases of ILD after PD-1 inhibitor treatment. Methods: We comprehensively searched PubMed, EMBASE, and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer. Pooled overall estimates of incidence and risk ratio (RR) were calculated with a 95% confidence interval (CI), and a mirror group analysis was performed using eligible studies. Results: This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment. A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors (0.05 vs. 0.02). The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors (RR = 2.34, 95% CI, 1.13–4.82, P = 0.02). Conclusion: Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors. These findings are instrumental for clinicians in treatment deliberations, and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.

Nitrogen oxides (NOx), significant contributors to air pollution and climate change, form aerosols and ozone in the atmosphere. Accurate, timely, and transparent information on NOx emissions is essential for decision-making to mitigate both haze and ozone pollution. However, a comprehensive understanding of the trends and drivers behind anthropogenic NOx emissions from China—the world's largest emitter—has been lacking since 2020 due to delays in emissions reporting. Here we show a consistent decline in China's NOx emissions from 2020 to 2022, despite increased fossil fuel consumption, utilizing satellite observations as constraints for NOx emission estimates through atmospheric inversion. This reduction is corroborated by data from two independent spaceborne instruments: the TROPOspheric Monitoring Instrument (TROPOMI) and the Ozone Monitoring Instrument (OMI). Notably, a reduction in transport emissions, largely due to the COVID-19 lockdowns, slightly decreased China's NOx emissions in 2020. In subsequent years, 2021 and 2022, reductions in NOx emissions were driven by the industry and transport sectors, influenced by stringent air pollution controls. The satellite-based inversion system developed in this study represents a significant advancement in the real-time monitoring of regional air pollution emissions from space.

Abstract Tropical wetlands account for ∼20% of the global total methane (CH4) emissions, but uncertainties remain in emission estimation due to the inaccurate representation of wetland spatiotemporal variations. Based on the latest satellite observational inundation data, we constructed a model to map the long‐term time series of wetland extents over the Sudd floodplain, which has recently been identified as an important source of wetland CH4 emissions. Our analysis reveals an annual, total wetland extent of 5.73 ± 2.05 × 104 km2 for 2003–2022, with a notable accelerated expansion rate of 1.19 × 104 km2 yr−1 during 2019–2022 driven by anomalous upstream precipitation patterns. We found that current wetland products generally report smaller wetland areas, resulting in a systematic underestimation of wetland CH4 emissions from the Sudd wetland. Our study highlights the pivotal role of comprehensively characterizing the seasonal and interannual dynamics of wetland extent to accurately estimate CH4 emissions from tropical floodplains.

The spatial and temporal variation of submarine groundwater discharge (SGD) has been a topic of interest for researchers in recent years. However, the study of SGD is limited within the scope of Zhanjiang Bay. The Zhanjiang Bay is located in western Guangdong Province, known for its high temperatures and typhoon vulnerability. The present study examined the fluctuation patterns of seawater 222Rn in Zhanjiang Bay during the period from June 2021 to March 2022. This investigation employs the 222Rn tracing technique to establish a mass balance model to compute the SGD rate, and assess the significance of SGD in translocating nutrients into the bay. We conducted a four-month sampling, observing the differences between the rainy and dry seasons. Precipitation exerts a significant influence on the seasonal variations of SGD. The SGD rates of Zhanjiang Bay ranged from 7.14 to 10.75 cm·d-1 in the dry season and from 13.38 to 14.61 cm·d-1 in the rainy season. SGD-derived nutrients also exhibited seasonal fluctuations, the annual input of nutrients it supplies may be comparable to the quantity delivered by rivers, which significantly impacted the trophic status of the bay.

In order to address the issue of metering inaccuracies in charging stations that directly affect the development of electric vehicles, a prediction method for the relative error of charging stations based on the ConvFormer model is proposed. The model combines Convolutional Neural Networks (CNN) with Transformer models in parallel, significantly improving the prediction accuracy. First, charging station data is preprocessed using forward interpolation and normalization methods, and the dataset is transformed into a dataset of input relative errors. Then, a neural network with an improved unidirectional convolutional and attention combination for time-series forecasting is constructed, and common regression performance evaluation metrics, MAE (Mean Absolute Error) and MSE (Mean Squared Error), are selected for evaluation. Finally, based on seven days of charging station data, the relative error of charging stations for the next 24 h is predicted, and compared to traditional Transformer and LSTM (Long Short-Term Memory) time-series models. The results show that the improved model yields the lowest values for both MAE and MSE, with a 47.30 % reduction in MAE compared to the Transformer model and a 38.06 % reduction compared to LSTM, and a 66.94 % reduction in MSE compared to the Transformer model and approximately 62.32 % reduction compared to LSTM.

BackgroundPancreatic hamartoma, a rare benign non-neoplastic condition, presents challenges in differentiating from other pancreatic diseases due to its atypical imaging and unreliable biopsy results. In this study, we present a case of pancreatic hamartoma and conduct a comprehensive review of relevant literature to outline its characteristic features, aiming to underscore its clinical relevance and implications.Case presentationA 63-year-old man presented with a pancreatic mass, discovered during evaluation of abdominal pain and distension. Laboratory tests were largely unremarkable. Ultrasound revealed a hypoechoic mass in the head of the pancreas. Subsequent computed tomography and magnetic resonance imaging demonstrated an inhomogeneous mass with a clear boundary in the uncinate process of the pancreas. Furthermore, a distinct delayed enhancement pattern was noted on imaging. Histopathological examination confirmed the diagnosis of pancreatic hamartoma.ConclusionsPreoperative diagnosis of pancreatic hamartoma remains challenging. Imaging modalities can play a crucial role in facilitating accurate diagnosis and potentially avoiding unnecessary surgical intervention in patients with this condition.

Summary: Leptomeningeal metastases (LMs) remain a devastating complication of non-small cell lung cancer (NSCLC), particularly following osimertinib resistance. We conducted single-cell RNA sequencing on cerebrospinal fluid (CSF) from EGFR-mutant NSCLC with central nervous system metastases. We found that macrophages of LMs displayed functional and phenotypic heterogeneity and enhanced immunosuppressive properties. A population of lipid-associated macrophages, namely RNASE1_M, were linked to osimertinib resistance and LM development, which was regulated by Midkine (MDK) from malignant epithelial cells. MDK exhibited significant elevation in both CSF and plasma among patients with LMs, with higher MDK levels correlating to poorer outcomes in an independent cohort. Moreover, MDK could promote macrophage M2 polarization with lipid metabolism and phagocytic function. Furthermore, malignant epithelial cells in CSF, particularly after resistance to osimertinib, potentially achieved immune evasion through CD47-SIRPA interactions with RNASE1_M. In conclusion, we revealed a specific subtype of macrophages linked to osimertinib resistance and LM development, providing a potential target to overcome LMs.

How the spacetime evolved non-perturbatively in a landscape with multiple anti-de Sitter (AdS) vacua, which is theoretically well-motivated, has always been a matter of concern. As a step towards this issue, we perform (3+1)D numerical relativity simulations for the inhomogeneous universe in an AdS landscape, and find that large inhomogeneity of scalar field can develop into not only sphere-like bubbles, but also novel tube-like structures. It is observed that the bubble or tube wall (across the potential barrier) likely inflates as a quasi-dS space, while the different regions separated by the walls are in different AdS vacua and will collapse towards singularity.

Introduction: Osteochondral repair poses a significant challenge due to its unique pathological mechanisms and complex repair processes, particularly in bacterial tissue conditions resulting from open injuries, infections, and surgical contamination. This study introduces a biomimetic honeycomb-like scaffold (Zn-AlgMA@Mg) designed for osteochondral repair. The scaffold consists of a dicalcium phosphate dihydrate (DCPD)-coated porous magnesium scaffold (DCPD Mg) embedded within a dual crosslinked sodium alginate hydrogel (Zn-AlgMA). This combination aims to synergistically exert antibacterial and osteochondral integrated repair properties.Methods: The Zn-AlgMA@Mg scaffold was fabricated by coating porous magnesium scaffolds with DCPD and embedding them within a dual crosslinked sodium alginate hydrogel. The structural and mechanical properties of the DCPD Mg scaffold were characterized using scanning electron microscopy (SEM) and mechanical testing. The microstructural features and hydrophilicity of Zn-AlgMA were assessed. In vitro studies were conducted to evaluate the controlled release of magnesium and zinc ions, as well as the scaffold’s osteogenic, chondrogenic, and antibacterial properties. Proteomic analysis was performed to elucidate the mechanism of osteochondral integrated repair. In vivo efficacy was evaluated using a rabbit full-thickness osteochondral defect model, with micro-CT evaluation, quantitative analysis, and histological staining (hematoxylin-eosin, Safranin-O, and Masson’s trichrome).Results: The DCPD Mg scaffold exhibited a uniform porous structure and superior mechanical properties. The Zn-AlgMA hydrogel displayed consistent microstructural features and enhanced hydrophilicity. The Zn-AlgMA@Mg scaffold provided controlled release of magnesium and zinc ions, promoting cell proliferation and vitality. In vitro studies demonstrated significant osteogenic and chondrogenic properties, as well as antibacterial efficacy. Proteomic analysis revealed the underlying mechanism of osteochondral integrated repair facilitated by the scaffold. Micro-CT evaluation and histological analysis confirmed successful osteochondral integration in the rabbit model.Discussion: The biomimetic honeycomb-like scaffold (Zn-AlgMA@Mg) demonstrated promising results for osteochondral repair, effectively addressing the challenges posed by bacterial tissue conditions. The scaffold’s ability to release magnesium and zinc ions in a controlled manner contributed to its significant osteogenic, chondrogenic, and antibacterial properties. Proteomic analysis provided insights into the scaffold’s mechanism of action, supporting its potential for integrated osteochondral regeneration. The successful in vivo results highlight the scaffold’s efficacy, making it a promising biomaterial for future applications in osteochondral repair.

Abstract Background The elderly, especially those with physical disabilities, often encounter barriers that prevent them from accessing outdoor activities. Their perceptions of the convenience of accessing outdoor activities may be influenced by various factors including their health, the social context, and/or planned behavior. This study aimed to develop predictive models that identify the principal determinants of perceived convenience among this demographic, and it also examined the disparities observed between genders. Methods This was a cross-sectional survey of 1216 community-dwelling older people with physical disabilities in rural China. Grounded on the rehabilitation concepts and the theory of planned behavior, structural equation models integrated health and social behavior factors were constructed to predict perceived convenience of accessing outdoor activities. The standardized coefficients explained the contributions of various factors to the variance. Results The final structural models demonstrated good fit for both female and male participants. Perceptions of the convenience of accessing outdoor activities among both women and men were directly impacted by their physical functioning and their intention to participate, and indirectly by medical expenditure, subjective norms, pain, and role limitation in emotional interactions. Positive mental health was more influential for women, while men were more influenced by subjective norms. Conclusions Structural equation models have effectively predicted the self-reported convenience of accessing outdoor activities, underscoring the importance of functional and behavioral rehabilitation. Furthermore, gender-sensitive rehabilitation programs are advised to promote engagement in outdoor activities among elderly individuals with physical disabilities.

With the development of aerospace, Mg-Gd-Y-Zn-Zr alloy as a high-performance light alloy has attracted much attention. In this paper, the Mg-8.8Gd-3.9Y-0.85Zn-0.45Zr (wt%, GWZ941) alloy single-pass multilayer components fabricated by cold metal transfer wire and arc additive manufacturing (CMT-WAAM) in CMT mode, CMT-P mode and CMT-Advance mode. Studying the effects of the three CMT characteristics on voltage and current waveforms and metal transfer behaviors of the deposition processes for the GWZ941 alloy. The macro morphology, defect distribution, microstructure, and mechanical properties of the three as-deposited samples were compared. The GWZ941 alloy deposit fabricated by CMT-WAAM exhibits a uniform equiaxed grain structure whose average grain size of the three samples was 11.9 μm, 13.9 μm, and 7.9 μm, with the porosity less than 0.01%. The UTS and EL of the three GWZ941 alloy samples were 257 ± 4 MPa and 7.5 ± 1%, 230 ± 8 MPa and 3.5 ± 1%, 253 ± 2 MPa and 7.0 ± 0.3%, respectively. In the presence of oxide particles in the GWZ941 alloy formed by CMT-WAAM, the oxide content is less than 0.08%, which is the main influencing factor for the reduced strength and plasticity of the GWZ941 alloy.

Abstract Background Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators. Methods A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects’ blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records. Results After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with − 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (

Mg-Gd-Y-Zr is an important lightweight material in the aerospace field. However, the engineering applications of large-scale Mg-Gd-Y-Zr alloy components are significantly limited by macrosegregation and microstructure coarsening during the casting process. In recent years, wire-arc directed energy deposition (DED), which has high design and manufacturing freedom, provides a new route to manufacture large-scale metal parts. In this work, a dilute Mg-3.2Gd-0.6Y-0.5Zr (wt.%) alloy, which had a degree of alloying comparable to AZ31 commercial alloys, was fabricated using a wire-arc DED process based on tungsten inert gas (TIG) welding, the microstructure evolution, tensile properties, and impact toughness were investigated. Due to the multiple grain refinement effects, the DED sample displayed a fine-grain structure (12.3 ± 7.4 μm), which was comparable to that of the wrought counterpart. Combined with the ductilizing effects of the fine grain and the Gd/Y solutes, the DED sample achieved a high ductility, which was better than most reported additive-manufactured Mg alloys as well as wrought Mg alloys. The good plastic deformation capacity also endowed the DED sample with good crack propagation resistance under dynamic impact load. We hope this work can help guide the further development of high-performance Mg alloys that are specially designed for the wire-arc DED additive manufacturing process.

Inconel 625 superalloy coatings were prepared on 12CrMoV steel plates by CMT process and MIG process respectively. The microstructures, the mechanical properties and oxidation resistance of the coatings were tested and analyzed. The results show that the heat input of CMT process is obviously lower than that of MIG process, and the forming quality of the coating is better, with smooth surface, no splash, no internal porosity and no other defects. The average weld penetration depth of CMT process coating is 0.51 mm and the dilution ratio is 6.8 %, which are much lower than that of the MIG process. Both coatings are mainly composed of coarse columnar crystals, however, the dendrites in the CMT process coating are finer and have better alignment consistency. The microstructure of two process coatings shows significant differences, and a large amount of Laves phase presents in the coating of the MIG process. The presence of Laves phase was not found in the coating of CMT process, but was replaced by element segregation region. In terms of mechanical properties, the CMT process coating has a higher hardness of about 221 HV and it is higher than the MIG process coating which is about 204 HV. Oxidation resistance testing of the coatings shows that the outer Cr2O3 film plays key role to the oxidation resistance. More compact and stable outer oxide film is formed in the oxidation process of the coating prepared by CMT process, which resulted in a better oxidation resistance.

This paper introduces a novel method for accurately estimating the 2D coordinates of hand keypoints from single static images, utilizing a sequential convolutional neural network optimized with Maximum Likelihood Estimation Loss. Unlike traditional heatmap-based techniques, our approach eliminates the need to generate label heatmaps and sidesteps the direct optimization of model parameters based on noisy labels. Instead, it concentrates on modeling the distribution of the discrepancies between predicted results and ground truth, rather than the potential presence of noisy labels, thus enabling the direct prediction of hand keypoint coordinates. Furthermore, we propose a sequential training and inference framework that consists of a deep convolutional backbone network and a multi-stage sequential network. Each stage of this network features similar structures, facilitating the progressive and precise prediction of hand keypoint coordinates. Our extensive experimental results demonstrate that our approach is both highly accurate and robust, outperforming mainstream methods under the experimental conditions detailed in this paper.

Abstract Background Gut microbiota alterations have been implicated in sepsis and related infectious diseases, but the causal relationship and underlying mechanisms remain unclear. Methods We evaluated the association between gut microbiota composition and sepsis using two-sample Mendelian randomization (MR) analysis based on published genome-wide association study (GWAS) summary statistics. Sensitivity analyses were conducted to validate the robustness of the results. Reverse MR analysis and integration of GWAS and expression quantitative trait loci (eQTL) data were performed to identify potential genes and therapeutic targets. Results Our analysis identified 11 causal bacterial taxa associated with sepsis, with increased abundance of six taxa showing positive causal relationships. Ten taxa had causal effects on the 28-day survival outcome of septic patients, with increased abundance of six taxa showing positive associations. Sensitivity analyses confirmed the robustness of these associations. Reverse MR analysis did not provide evidence of reverse causality. Integration of GWAS and eQTL data revealed 76 genes passing the summary data-based Mendelian randomization (SMR) test. Differential expression of these genes was observed between sepsis patients and healthy individuals. These genes represent potential therapeutic targets for sepsis. Molecular docking analysis predicted potential drug-target interactions, further supporting their therapeutic potential. Conclusion Our study provides insights for the development of personalized treatment strategies for sepsis and offers preliminary candidate targets and drugs for future drug development.

Objective: To explore the efficacy and potential mechanisms of the ethanol extract of Abelmoschus manihot (L.) Medic in contrast-induced nephropathy (CIN). Methods: CIN rat models and human renal proximal tubular cells (HK-2) with iopromide-induced injury were employed to mimic CIN conditions. The effect of Abelmoschus manihot extract on the rat models and HK-2 cells was evaluated. In rat models, kidney function, histology, oxidative stress and apoptosis were determined. In HK-2 cells, cell viability, apoptosis, mitochondrial membrane potential, and endoplasmic reticulum stress were assessed. Results: Abelmoschus manihot extract significantly improved structural and functional impairments in the kidneys of CIN rats. Additionally, the extract effectively mitigated the decline in cellular viability and reduced iopromide-induced oxidative stress and lipid peroxidation. Mechanistic investigations revealed that Abelmoschus manihot extract prominently attenuated acute endoplasmic reticulum stress-mediated apoptosis by downregulating GRP78 and CHOP protein levels. Conclusions: Abelmoschus manihot extract can be used as a promising therapeutic and preventive agent in the treatment of CIN.

Abstract We perform a theoretical study of the $$J/\psi \rightarrow \omega (\phi ) K^* \bar{K} + c.c. \rightarrow \omega (\phi ) K^0 \pi ^+ K^-$$ J / ψ → ω ( ϕ ) K ∗ K ¯ + c . c . → ω ( ϕ ) K 0 π + K - reactions with the assumption that the $$f_1(1285)$$ f 1 ( 1285 ) is dynamically generated from a single channel $$K^* \bar{K} + c.c$$ K ∗ K ¯ + c . c interaction in the chiral unitary approach. Two peaks in the $$K^0 \pi ^+ K^-$$ K 0 π + K - invariant mass distribution are observed, one clear peak locates at the $$f_1(1285)$$ f 1 ( 1285 ) nominal mass, the other peak locates at around $$1420 \text {MeV}$$ 1420 MeV with about $$70 \text {MeV}$$ 70 MeV width. We conclude that the former peak is associated with the $$f_1(1285)$$ f 1 ( 1285 ) and the latter peak is not a genuine resonance but a manifestation of the kinematic effect in the higher energy region caused by the $$K^* \bar{K} + c.c.$$ K ∗ K ¯ + c . c . decay mode of the $$f_1(1285)$$ f 1 ( 1285 ) .

Abstract Emissions from fossil fuel exploitation are a leading contributor to global anthropogenic methane emissions, but are highly uncertain. The lack of reliable estimates hinders monitoring of the progress on pledges towards methane reductions. Here we analyze methane emissions from exploitation of coal, oil and gas for major producing nations across a suite of bottom-up inventories and global inversions. Larger disagreement in emissions exists for the oil/gas sector across the inventories compared to coal, arising mostly from disparate data sources for emission factors. Moreover, emissions reported to the United Nations Framework Convention on Climate Change are lower than other bottom-up and inversion estimates, with many countries lacking reporting in the past decades. Finally, comparison with previous global inversions, revealed a strong influence of the prior inventory on the inferred sub-sectoral emissions magnitude. This study highlights the need to improve consensus on the methodological inputs among the bottom-up inventories in order to obtain more consistent inverse modelling results at the sub-sectoral level.

FengYun-3E (FY3E) is the world's first dust-dawn orbiting meteorological satellite for civil use, which has filled the vacancy of global early-morning-orbit satellite observation by working together with FengYun-3C and FengYun-3D satellites. The Medium Resolution Spectral Imager-Low Light (MERSI-LL) sensor carried by FY3E can detect surface temperature variation. The radiometric calibration conditions of MERSI-LL thermal infrared bands were evaluated using the collected field measurements and atmospheric transfer simulations during 5–23 December, 2022, at Lake Erhai. A thermal infrared radiometer equipped on an unmanned surface vehicle was used to continuously collect surface-emitted radiance and water temperature. Atmospheric conditions, surface emissivity, and aerosol optical depth measured near-field experiment site were adopted by atmospheric radiative transfer code to calculate the influence of atmosphere on long-wave radiation during the propagation from land surface to satellite aperture. The good in-orbit operational status could be detected according to our calibration experiments, and the calibration analysis suggested that the differences between the simulated brightness temperature and satellite-based brightness temperature are 0.71 K with an RMSE of 0.79 K and 0.11 K with an RMSE of 0.47 K for channels 6 and 7, respectively, which achieved better or similar calibration accuracy by comparing with TIR channels of other FengYun satellites.

The preparation of biodegradable pure Zn porous scaffolds using additive manufacturing technology has great potential for application. However, the mechanical properties of pure Zn are not sufficient for the clinical application of stents. An object of this paper was to investigate the effect of laser power on microstructural evolution and tensile properties of pure Zn fabricated via laser powder bed fusion (LPBF). The results demonstrated that the temperature gradient and heat storage were the main factors determining the microstructure. The formation of columnar grains was due to the high temperature gradient in the early printing stage, and the equiaxed grains in the middle and top region were attributed to the heat storage induced recrystallization and columnar-to-equiaxed transition (CET), respectively. In addition, as the laser power increased from 40 W to 60 W, the recrystallization degree increased, and the Kernel average misorientation value and Taylor factor decreased gradually, resulting in a significant increase in the ductility. The mechanical properties were maximized at the laser power of 60 W and the scanning rate of 150 mm/s (yield strength, tensile strength and elongation of samples can reach 82.02 MPa, 116.20 MPa and 37.16 %, respectively). This work provides theoretical support for optimizing the mechanical properties of LPBF Zn-based materials by microstructural regulation.

Most metallic structural materials possess an intrinsic inverse relationship between strength and ductility. Heterostructured materials are expected to address this issue. Through composition regulation, TC4/TC4+2.5Ni layered heterostructures with exceptional strength and ductility were fabricated by direct laser deposition (DLD), exhibiting a significant increase in strength compared to that of TC4 while retaining excellent ductility. The mechanism of strength–ductility synergy was investigated under different alternating interlayer design conditions. The addition of nickel refined the microstructure of TC4, promoting the transformation of coarse columnar grains into nearly equiaxed grains. The DLD-fabricated TC4/TC4+2.5Ni layered heterostructure comprised alternating regions of columnar and near-equiaxed grains. By appropriately adjusting the thickness of alternating components (three to four DLD-deposited layers), a significant compositional and microstructural heterogeneity was achieved, resulting in a synergistic effect on strength and ductility in TC4-TC42.5Ni layered heterostructures. Moreover, strength–ductility synergy was achieved under the combined effect of hetero-deformation-induced stress, crack deflection near the component interface, and inhibition of strain localization by alternating soft and hard regions. This study provides a theoretical foundation and key evidence for designing DLD-deposited heterostructured titanium alloys with improved strength–ductility synergy, offering novel insights and contributions to improving the performance of titanium alloys.

Wire arc additive manufacturing (WAAM) technology is expected to be used for the fabrication of large and complex magnesium alloy components. In this work, Mg-9.54Gd-1.82Y-0.44Zr (wt.%, GW92) alloy thin-walled components were fabricated by cold metal transfer (CMT) arc in CMT-Advance mode. The microstructure of the WAAMed GW92 alloy consists of fine equiaxed ɑ-Mg grains with an average size of ∼17 μm, eutectic phases, β" phase, cubic phases, and Zr particles. The short-term high-temperature solution treatment at 525 ℃ for 25 minutes significantly reduced the content of the eutectic phase, resulting in a significant increase in elongation (EL) (13.5 ± 0.3%). The peak aging time of the solution-treated GW92 alloy at 225 ℃ for 12 h. The WAAM-T6 sample showed a significant increase in strength while maintaining good ductility, with a yield strength (YS) of 235 ± 3 MPa, ultimate tensile strength (UTS) of 360 ± 7 MPa, and elongation of 10.8 ± 1.7%. The synergistic strength and ductility properties of Mg-Gd-Y-Zr alloys fabricated by the WAAM process were significantly impacted by the short-term high-temperature solution + aging treatments to preserve the fine grain and high-density.

ABSTRACTLaser powder bed fusion (LPBF) of multi-scaled structures is a prominent direction pursued by innovative designs and engineering applications. However, understanding the impact of scale effect on the effectiveness of actual structures is a pressing challenge. This work investigates the influence of structure scale on surface morphology and mechanical property by fabricating tensile samples with gauge diameters ranging from 0.2 mm to 5.0 mm. For the hatching scanning strategy, the surface roughness drastically reduces by ∼51% as the diameter increases. This appears to be the coupling results of heat accumulation, molten pool morphology at the end of single-track, overlap between multi-tracks within a layer, and successive rotational buildup between layers. Moreover, decreasing the diameter substantially reduces the tensile strength. Fortunately, a hatching-contour scanning strategy is proposed to eliminate the scale effect of surface morphology and strength. These efforts provide essential guidance for the broader application of multi-scaled structures.

ABSTRACTUnintended end-of-process depression (EOPD) commonly occurs in laser powder bed fusion (LPBF), leading to poor surface quality and lower fatigue strength, especially for many implants. In this study, a high-fidelity multi-physics meso-scale simulation model is developed to uncover the forming mechanism of this defect. A defect-process map of the EOPD phenomenon is obtained using this simulation model. It is found that the EOPD formation mechanisms are different under distinct regions of process parameters. At low scanning speeds in keyhole mode, the long-lasting recoil pressure and the large temperature gradient easily induce EOPD. While at high scanning speeds in keyhole mode, the shallow molten pool morphology and the large solidification rate allow the keyhole to evolve into an EOPD quickly. Nevertheless, in the conduction mode, the Marangoni effects along with a faster solidification rate induce EOPD. Finally, a ‘step’ variable power strategy is proposed to optimise the EOPD defects for the case with high volumetric energy density at low scanning speeds. This work provides a profound understanding and valuable insights into the quality control of LPBF fabrication.

Background: Bronchobiliary fistulas (BBFs), primarily stemming from choledocholithiasis, present considerable diagnostic and treatment challenges. Their prolonged nature can lead to life-threatening situations without timely management, often complicated by lung abscesses. Case presentation: A 64-year-old man, presenting with fever, chills, and a cough initially misdiagnosed as a common cold, developed severe respiratory distress and delirium upon admission. Urgent intensive care unit (ICU) admission was prompted by a computed tomography (CT) scan revealing a right lung abscess. Enhanced CT scans and elevated bilirubin levels confirmed the biliary origin of the BBFs. Comprehensive treatment included laparoscopic partial hepatectomy, choledochojejunostomy, stone extraction, choledochoscopy, T-tube drainage, and BBFs closure. The patient was discharged with a T-tube. Follow-up CT after two months showed no recurrence. Conclusions: Managing BBFs, especially with concurrent lung abscesses in choledocholithiasis patients, remains challenging but feasible. Early diagnosis and intervention are crucial to improving survival rates and quality of life, highlighting the need for vigilance. This case underscores the importance of early detection and comprehensive treatment for successful outcomes in such complex conditions.

Underground rail transit has become one of the most popular transportation modes because of its advantages such as fast running speed, large passenger flow and punctuality. This mode of transportation can alleviate urban traffic congestion to a certain extent, so underground rail transit has been vigorously developed, and the number of rail lines has increased exponentially. However, with the continuous development of underground rail transit, the energy consumption of train operation is also increasing, resulting in a waste of energy. To solve this problem, this paper proposes to improve the energy-saving technology of train operation by using train autopilot control strategy. Firstly, a train operation optimization model considering train position and speed limit is established by using automatic train driving strategy, and the nonlinear problem of the optimization model is solved by genetic algorithm. The micro-field theory is introduced into the control strategy of automatic train driving, and the energy-saving model of underground rail transit is established. The energy consumption is optimized from three aspects: train energy-saving technology, line planning and overall operation planning of rail transit. The simulation results show that the average impact rate and energy consumption of trains under the proposed energy-saving model are significantly reduced compared with the other two groups of trains, and the average impact rate and energy consumption are significantly reduced compared with the other two groups of trains. The running time and energy consumption of the energy-saving model are lower than those of the experimental group. To sum up, the energy-saving model of underground rail transit proposed in this paper not only reduces the operating energy consumption, but also improves the passenger comfort, which can provide low-cost energy-saving technology for underground transportation field, and has positive significance for urban low-carbon development.

Multiple myeloma (MM) remains an incurable hematological malignancy. Despite tremendous advances in the treatment, about 10% of patients still have very poor outcomes with median overall survival less than 24 months. Our study aimed to underscore the critical mechanisms pertaining to the rapid disease progression and provide novel therapeutic selection for these ultra-high-risk patients. We utilized single-cell transcriptomic sequencing to dissect the characteristic bone marrow niche of patients with survival of less than two years (EM24). Notably, an enrichment of LILRB4high pre-matured plasma-cell cluster was observed in the patients in EM24 compared to patients with durable remission. This cluster exhibited aggressive proliferation and drug-resistance phenotype. High-level LILRB4 promoted MM clonogenicity and progression. Clinically, high expression of LILRB4 was correlated with poor prognosis in both newly diagnosed MM patients and relapsed/refractory MM patients. The ATAC-seq analysis identified that high chromosomal accessibility caused the elevation of LILRB4 on MM cells. CRISPR-Cas9 deletion of LILRB4 alleviated the growth of MM cells, inhibited the immunosuppressive function of MDSCs, and further rescued T cell dysfunction in MM microenvironment. The more infiltration of myeloid-derived suppressive cells (MDSCs) was observed in EM24 patients as well. Therefore, we innovatively generated a TCR-based chimeric antigen receptor (CAR) T cell, LILRB4-STAR-T. Cytotoxicity experiment demonstrated that LILRB4-STAR-T cells efficaciously eliminated tumor cells and impeded MDSCs function. In conclusion, our study elucidates that LILRB4 is an ideal biomarker and promising immunotherapy target for high-risk MM. LILRB4-STAR-T cell immunotherapy is promising against tumor cells and immunosuppressive tumor microenvironment in MM.

Introduction Breast cancer (BC) is a common cancer characterized by a high molecular heterogeneity. Therefore, understanding its biological properties and developing effective treatments for patients with different molecular features is imperative. Calcium-sensing receptor (CaSR) has been implicated in several regulatory functions in various types of human cancers. However, its underlying pathological mechanism in BC progression remains elusive. Methods We utilized The Cancer Genome Atlas and Gene Expression Omnibus databases to explore the function of CaSR in the metastasis of BC. Gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and Gene Set Enrichment Analysis of biological processes and cell signaling pathways revealed that CaSR could be activated or inhibited. Importantly, quantitative reverse transcriptase-polymerase chain reaction and western blotting were used to verify the gene expression of the CaSR. Wound healing and transwell assays were conducted to assess the effect of CaSR on the migration of BC cells. Results We demonstrated that CaSR expression in metastatic BC was higher than that in non-metastatic BC. It is the first time that database information has been used to reveal the biological process and molecular mechanism of CaSR in BC. Moreover, the CaSR expression in normal breast epithelial cells was notably less compared to that in BC cells. The activation of CaSR by Cinacalcet (a CaSR agonist) significantly enhanced the migration of BC cells, whereas NPS-2143 (a CaSR antagonist) treatment dramatically inhibited these effects. Conclusion and future perspective Bioinformatics techniques and experiments demonstrated the involvement of CaSR in BC metastasis. Our findings shed new light on the receptor therapy and molecular pathogenesis of BC, and emphasize the crucial function of CaSR, facilitating the metastasis of BC.

ObjectiveEpilepsy is a common neurological disorder characterized by recurrent epilepsy episodes. As a non-pharmacological treatment, the ketogenic diet has been widely applied in treating epilepsy. However, the exact therapeutic mechanism of the ketogenic diet for epilepsy remains unclear. This study investigates the molecular mechanisms of the ketogenic diet in regulating fatty acid metabolism and activating the ADCY3-initiated cAMP signaling pathway to enhance neuronal inhibition and thereby treat epilepsy.Methods and resultsMeta-analysis reveals that the ketogenic diet is superior to the conventional diet in treating epilepsy. Animal experiments demonstrate that the ketogenic diet is more effective than the conventional diet in treating epilepsy, with the best results achieved using the classic ketogenic diet. Transcriptome sequencing analysis identifies six essential genes, among which ADCY3 shows increased expression in the ketogenic diet. In vivo experiments confirm that the activation of the cAMP-PKA signaling pathway by ADCY3 enhances neuronal inhibition and improves epilepsy control.ConclusionClinical observations indicate that the ketogenic diet improves patient epilepsy episodes by regulating the ADCY3-initiated cAMP signaling pathway.

Abstract It is important to directly characterize the modulus of objects through wearable systems, which can further develop electronic skin and human‐computer interaction. In this work, a modulus sensing system based on a pressure sensor and vibration module is developed. This resistive pressure sensor exhibits good linearity and sensitivity. Combined with the vibration module to adjust the applied stress and strain, the modulus value of the objects can be directly calculated. The modulus sensing system demonstrates excellent modulus monitoring capabilities in the range of 60‒3000 kPa modulus and high linearity. In addition, it is used to detect modulus values for different parts of the human body and integrate a concept eye mask to prevent and monitor migraine. The system shows the potential to be further applied to wearable devices for human health monitoring and disease prevention.