The past decade has witnessed ongoing progress in immune therapy to ameliorate human health. As an emerging technique, chimeric antigen receptor (CAR) T-cell therapy has the advantages of specific ...killing of cancer cells, a high remission rate of cancer-induced symptoms, rapid tumor eradication, and long-lasting tumor immunity, opening a new window for tumor treatment. However, challenges remain in CAR T-cell therapy for solid tumors due to target diversity, tumor heterogeneity, and the complex microenvironment. In this review, we have outlined the development of the CAR T-cell technique, summarized the current advances in tumor-associated antigens (TAAs), and highlighted the importance of tumor-specific antigens (TSAs) or neoantigens for solid tumors. We also addressed the challenge of the TAA binding domain in CARs to overcome off-tumor toxicity. Moreover, we illustrated the dominant tumor microenvironment (TME)-induced challenges and new strategies based on TME-associated antigens (TMAs) for solid tumor CAR T-cell therapy.
Heart failure (HF) is a common disease and a major public health problem. HF mortality prediction is critical for developing individualized prevention and treatment plans. However, due to their lack ...of interpretability, most HF mortality prediction models have not yet reached clinical practice. We aimed to develop an interpretable model to predict the mortality risk for patients with HF in intensive care units (ICUs) and used the SHapley Additive exPlanation (SHAP) method to explain the extreme gradient boosting (XGBoost) model and explore prognostic factors for HF. In this retrospective cohort study, we achieved model development and performance comparison on the eICU Collaborative Research Database (eICU-CRD). We extracted data during the first 24 hours of each ICU admission, and the data set was randomly divided, with 70% used for model training and 30% used for model validation. The prediction performance of the XGBoost model was compared with three other machine learning models by the area under the curve. We used the SHAP method to explain the XGBoost model. A total of 2798 eligible patients with HF were included in the final cohort for this study. The observed in-hospital mortality of patients with HF was 9.97%. Comparatively, the XGBoost model had the highest predictive performance among four models with an area under the curve (AUC) of 0.824 (95% CI 0.7766-0.8708), whereas support vector machine had the poorest generalization ability (AUC=0.701, 95% CI 0.6433-0.7582). The decision curve showed that the net benefit of the XGBoost model surpassed those of other machine learning models at 10%~28% threshold probabilities. The SHAP method reveals the top 20 predictors of HF according to the importance ranking, and the average of the blood urea nitrogen was recognized as the most important predictor variable. The interpretable predictive model helps physicians more accurately predict the mortality risk in ICU patients with HF, and therefore, provides better treatment plans and optimal resource allocation for their patients. In addition, the interpretable framework can increase the transparency of the model and facilitate understanding the reliability of the predictive model for the physicians.
Adsorption stands as an economically viable, efficient, recyclable, operationally straightforward, cost-effective, and low-sludge method extensively employed for phosphorus removal. In an effort to ...enhance the adsorption capabilities of the adsorbent, this study employs the rare-earth metal lanthanum in conjunction with the group’s previously researched high-efficiency composite industrial residue phosphorus removal materials (EPRC) for modification, thereby generating lanthanum-modified reinforced composite phosphorus removal materials (La-EPRC). Subsequently, the novel material undergoes static modification, followed by experimental investigations into static and dynamic adsorption for phosphorus removal. Static adsorption experiments reveal optimal phosphorus removal efficiency when the initial phosphorus solution concentration is 20 mgP/L, with a La-EPRC particle dosage of 3 g/250 mL and a temperature of 25 °C. The removal efficiency of phosphorus particles is above 90% within the pH range of 4 to 10. Common coexisting anions in water, including Cl−, SO42−, HCO3−, and CO32−, demonstrate minimal impact on the efficacy of phosphorus removal. La-EPRC demonstrates a robust adsorption stability in both water and hot water environments. In a 2.5 mol/L NaOH solution, effective desorption of La-EPRC particles is observed, facilitating material regeneration. The raw materials for La-EPRC are easily accessible and cost-effective, imparting significant potential for widespread applications.
Sugarcane bagasse was pyrolyzed under oxygen-limited conditions from 100 to 600 °C and used for the adsorptive removal of oxidation intermediate p-benzoquinone, tetracycline, and polyvinyl alcohol. ...The three organic pollutants have different polarities and solubilities. The carbon content increased from 57.7% of the raw bagasse to 75.3% of the biochar pyrolyzed at 600 °C, while the O content decreased from 13.2% to 6.1%. Accordingly, the biochar surface became more hydrophobic with increasing pyrolytic temperature. Interestingly, the adsorption affinity of biochars towards the three pollutants improved with an increase in the pyrolytic temperature. The adsorption of tetracycline molecules was almost unaffected by its being negatively charged with increasing solution pH. A mechanism of
π
-
π
electron-donor-acceptor interaction might contribute to the adsorption of tetracycline and p-benzoquinone, while H-bond interaction between polyvinyl alcohol and the biochar might be dominant during adsorption. The Elovich model fitted the kinetic model well, indicating that the diffusional rate-determining step was more pronounced. An isotherm study indicated that the contribution of partitioning was also dominant in the adsorption processes. Wide application of the prepared biochars is expected for the efficient adsorptive removal of organic pollutants.
Propionic acid (PA) is widely used in the food, agricultural, and pharmaceutical industries. Since the petrochemical PA is unsustainable, biological production of PA from renewable substrates is ...gaining attention. In this study, we engineered the strain
Pseudomonas putida
KT2440 to transform
l
-threonine to PA with only CO
2
released as by-product. The cell factory was created by chromosomal incorporation of heterologous
l
-threonine deaminase, permease, and acyl-CoA thioesterase, deletion of branch pathways as well as overproduction of the endogenous branched-chain alpha-keto acid dehydrogenase complex. The final engineered strain could produce 399 mM PA from 400 mM
l
-threonine in a batch biotransformation process, with a molar yield of 99.8% under the optimized conditions in 48 h. The PA titer further reached to 50.3 g/L (679 mM) with a productivity of 0.6 g/L/h in a fed-batch conversion process. No obvious by-products, such as acetate and succinate, were detected in the broth, which would significantly facilitate downstream purification steps. Thus, this study offers an alternative route for biological production of PA.
Flexible tactile sensors have been utilized in intelligent robotics for human-machine interaction and healthcare monitoring. The relatively low flexibility, unbalanced sensitivity and sensing range ...of the tactile sensors are hindering the accurate tactile information perception during robotic hand grasping of different objects. This paper developed a fully flexible tactile pressure sensor, using the flexible graphene and silver composites as the sensing element and stretchable electrodes, respectively. As for the structural design of the tactile sensor, the proposed bilayer interlaced bumps can be used to convert external pressure into the stretching of graphene composites. The fabricated tactile sensor exhibits a high sensing performance, including relatively high sensitivity (up to 3.40% kPa
), wide sensing range (200 kPa), good dynamic response, and considerable repeatability. Then, the tactile sensor has been integrated with the robotic hand finger, and the grasping results have indicated the capability of using the tactile sensor to detect the distributed pressure during grasping applications. The grasping motions, properties of the objects can be further analyzed through the acquired tactile information in time and spatial domains, demonstrating the potential applications of the tactile sensor in intelligent robotics and human-machine interfaces.
An organizational ethical climate enhances the degree of collaboration and cohesion among employees and facilitates the development and interests of organizations. Such roles lead to organizational ...sustainable development and survival. Therefore, the importance of ethical climate in organizations is becoming increasingly apparent. In this background, this study aims to explore whether an organizational ethical climate can improve whistleblowing behavior and the mediating role of organizational identification in promoting whistleblowing behavior. Most previous studies have only focused on the mediating or moderating role of the model. This study expands the research field, adds the dual moderation of person-organization value congruence and leader ethical behavior, and verifies two moderated mediation models. Overall, the purpose of this study is to determine the behavior of employees under the influence of an organizational ethical climate and, on this basis, propose suggestions for strengthening organizational ethical climate, expanding the scope of research on organizational climate and providing a theoretical basis for related research. In order to achieve the research goals, the data were collected from 344 Chinese SMEs for empirical analysis. The results showed that an organizational ethical climate has no direct impact on whistleblowing behavior but could have a positive effect on whistleblowing formation through the mediating variable of organizational identification. In addition, person-organization value congruence and leader ethical behavior significantly moderated the mediating role of organizational identification between organizational ethical climate and whistleblowing behavior. Finally, the directions that can contribute to future research were suggested.
ClpX and ClpP are involved in many important functions, including stress responses and energy metabolism, in microorganisms. However, the ClpX and ClpP of microbes used in industrial scale have ...rarely been studied. Industrial bacterial fermentation experiences a variety of stresses, and energy metabolism is extremely important for industrial bacteria. Thus, the role played by the ClpX and ClpP of industrial bacteria in fermentation should be investigated. Most microorganisms have a single
clpP
gene, while
Corynebacterium crenatum
AS 1.542 possesses two
clpPs.
Herein, the
clpX
,
clpP1
, and
clpP2
of
C. crenatum
were cloned, and its fusion protein was expressed and characterized. We also constructed
clpX
deletion mutant and complementation strain. Results indicate that ClpX serves an important function in thermal, pH, and ethanol stresses. It is also involved in NADPH synthesis and glucose consumption during fermentation.
The organizational system is directly associated with overall organizational management and sustainability. The reason is that the organizational system has a strong relationship with organizational ...performance. One of the most important functions of the organizational system is the high-performance work system, which is the system that manages the employees so that they can maximize their functions, this study focuses on the importance of a high-performance work system in order to achieve organizational goals and increase performance. In particular, a high-performance work system is directly related to innovation performance that secures the competitive advantage of organizations. Based on such background, this study focused on how a high-performance system improves innovation performance. Unlike previous studies, rather than simply focusing on variables exploration or main effect verification, we provided and verified the research model related to the process by which innovation performance occurs. Specifically, this study aimed to investigate whether high-performance work systems in organizations enhance employees’ innovation performance and examined the mediating role of employees’ intrinsic motivation in enhancing innovation performance. In addition, we investigated the moderating role of employee person–organization fit in high-performance work systems and employee intrinsic ation directly. To validate this model, we collected data from 309 members of Chinese SMEs. We found that high-performance work systems positively affect employees’ innovation performance through a person–organization fit and that employees’ person–organization fit significantly moderates the relationship between high-performance work systems and employees’ intrinsic motivation directly. Overall, this study expands the scope of research on the enhancement of employee innovation performance and provides a theoretical basis for related research, which is also a contribution of this study.
Purpose We compared the perioperative and postoperative characteristics of prostate PlasmaKinetic™ enucleation and bipolar transurethral resection for large volume benign prostatic hyperplasia. ...Materials and Methods In this prospective, randomized, controlled trial 80 patients with benign prostatic hyperplasia and a prostate of larger than 70 ml were randomly assigned to prostate bipolar transurethral resection or PlasmaKinetic enucleation. Operative time, resected adenoma weight, changes in hemoglobin, catheterization time and postoperative hospital stay were recorded and compared. Patients were followed 1, 6, 12, 24, 36, 48 and 60 months after surgery. Results Greater resected prostate weight (mean ± SD 64.2 ± 19.0 vs 50.6 ± 20.0 gm, p = 0.03), less blood loss (mean 0.87 ± 0.42 vs 1.74 ± 0.63 gm, p <0.01), and shorter catheterization time (mean 35.5 ± 5.8 vs 60.1 ± 5.8 hours, p <0.01) and postoperative hospital stay (mean 3.2 ± 0.9 vs 4.4 ± 1.1 days, p <0.01) were recorded in the enucleation group than in the resection group. The postoperative improvement in International Prostate Symptom Score, quality of life, maximal flow rate and post-void residual urine volume was similar in the 2 groups at 1, 6, 12 and 24 months but significantly better in the enucleation group at 36, 48 and 60 months. During the 5-year followup no patient in the enucleation group but 2 in the resection group experienced recurrence. Conclusions For large volume benign prostatic hyperplasia PlasmaKinetic enucleation of the prostate is associated with less blood loss, shorter hospital stay and catheterization time than bipolar transurethral resection of the prostate. Moreover, PlasmaKinetic enucleation seems to be superior at long-term followup with fewer reoperations necessary.
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