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ObjectiveThe objective of this research is to scrutinize adverse events (AEs) linked to Trifluridine/Tipiracil (TFTD/TPI), using data from the FDA Adverse Event Reporting System (FAERS) database.MethodsThe AEs data related to TFTD/TPI were collected from the fourth quarter of 2015 through the fourth quarter of 2023. After normalizing the data, multiple signal quantification techniques including Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian approaches such as Bayesian Confidence Propagation Neural Network (BCPNN) and the Multi-item Gamma Poisson Shrinker (MGPS) were used for overall and subgroup analysis and visualization analyses were performed.ResultsFrom the FAERS database, we analyzed 13,520,073 reports, identifying 8,331 as primary suspect (PS) AEs for TFTD/TPI, occurring across 27 organ systems. The study retained 99 significant disproportionality Preferred Terms (PTs) across four algorithms and unveiled unexpected serious AEs such as iron deficiency and intestinal perforation, hepatic failure, cholangitis and so on. The median onset of TFTD/TPI-associated AEs was 44 days (IQR 20-97 days), with most occurring within the first 30 days of treatment.ConclusionThis research uncovers critical new safety signals for TFTD/TPI, supporting its clinical monitoring and risk identification.

Summary: The high infiltration of tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment prominently attenuates the efficacy of immune checkpoint blockade (ICB) therapies, yet the underlying mechanisms are not fully understood. Here, we investigate the metabolic profile of TAMs and identify S-2-hydroxyglutarate (S-2HG) as a potential immunometabolite that shapes macrophages into an antitumoral phenotype. Blockage of L-2-hydroxyglutarate dehydrogenase (L2HGDH)-mediated S-2HG catabolism in macrophages promotes tumor regression. Mechanistically, based on its structural similarity to α-ketoglutarate (α-KG), S-2HG has the potential to block the enzymatic activity of 2-oxoglutarate-dependent dioxygenases (2-OGDDs), consequently reshaping chromatin accessibility. Moreover, S-2HG-treated macrophages enhance CD8+ T cell-mediated antitumor activity and sensitivity to anti-PD-1 therapy. Overall, our study uncovers the role of blockage of L2HGDH-mediated S-2HG catabolism in orchestrating macrophage antitumoral polarization and, further, provides the potential of repolarizing macrophages by S-2HG to overcome resistance to anti-PD-1 therapy.

The rapid development of the shipping industry has made energy consumption and environmental problems of traditional ships increasingly prominent. Hydrogen-powered ships are one of the development directions for waterway transportation vehicles and will play a significant part in achieving the carbon peak and carbon neutralization goals in the waterway transportation field. Therefore, it is urgent to research the innovative developmental mode of hydrogen-powered ships in China. The development status of hydrogen-powered ships is summarized in this article, and the layout of the hydrogen-powered ship industry is analyzed from the perspectives of industrial chain development trend and coordinated development layout. The technical and economic feasibility of developing hydrogen-powered ships is analyzed from the aspects of hydrogen and ammonia fuel, hydrogen fuel cell, hydrogen internal combustion engine, infrastructure, and total cost of ownership. Moreover, the key links of the industry chain of hydrogenpowered ships are analyzed, including hydrogen production, hydrogen transportation, large-capacity hydrogen storage, safe fueling, fuel cell, hydrogen internal combustion engine, multi-energy collaborative control, and safety in hydrogen application. Based on national conditions, we proposed multi-stage development goals, a development roadmap for hydrogen-powered ships, and a construction path for the hydrogen fuel supply system. To promote the rapid and high-quality development of hydrogen-powered ships, China needs to clarify application scenarios, develop key technologies, improve infrastructure facilities, and innovate operation systems.

The demand of energy saving and loss mitigation in modern industry gives rise to drag reduction techniques such as micro groove/riblet ever since the last century. Plenty of studies are conducted under straight flow condition showing relevance between drag reduction and flow features. However, the same issue has not been studied adequately for rotational flows, which is typical in turbopumps. In this paper, two-dimensional numerical simulations of rotating disks are performed together with verification experiments to investigate drag reduction effect of micro riblet under rotational flow condition. The numerical results show that riblets with certain dimensions can lessen the resistant torque by a maximum of 8.46% and the drag reduction efficiency depends on rotational Reynolds number and riblet dimensions. Meanwhile, the distributions of static pressure and swirl velocity on surfaces are changed and near-wall turbulence intensity is tranquilized by riblets which are considered as the main reasons to the diminish of drag. Finally, the relevance of vortexes inside riblets to swirl wall shear stress and torque is demonstrated revealing that the configuration of riblets plays an important role in cutting resistance. The results of this paper can be a supplement for the investigation of micro groove/riblet drag reduction mechanism.

Abstract To investigate the efficacy of 125I seed implantation in the treatment regimen of pelvic recurrence after early cervical cancer surgery and to analyse prognostic factors. To evaluate efficacy and analyse prognostic factors of 125I seed implantation for pelvic recurrence after early cervical cancer surgery. A prospective study was conducted on 62 patients who experienced pelvic recurrence after early cervical cancer surgery between August 2005 and September 2015. The 62 patients were treated and assessed in 2 groups (n = 30). All 62 patients were randomized into two groups that received two different treatment regimens: the treatment group (n = 30), which received 125I particle implantation therapy, and the control group (n = 32), which received whole-pelvic irradiation using the anteroposterior/posteroanterior field and cisplatin-based concurrent chemoradiation therapy. The efficacy/efficiency of 125I seed implantation and prognostic factors were analysed by logistic regression. Overall survival was determined by Kaplan–Meier analysis. Multivariate analysis results were obtained by the Cox proportional hazards regression model. The effective control rates at 1, 3, 6 and 12 months were 76.7%, 80.0%, 83.3%, and 86.7% in the 125I particle implantation group. The total effective control rates at 1, 3, 6 and 12 months were 65.6%, 65.5%, 62.5%, and 71.9% in the chemoradiotherapy group. Significant differences were observed between the two groups. The overall survival rates at 1, 2, 3, 4, and 5 years and the median overall were 96.7%, 93.3%, 86.7%, 71.9%, 65.6% and 4.34 years, respectively, in the 125I seed implantation group and 81.3%, 71.9%, 62.5%, 56.3%, 53.1% and 3.59 years, respectively, in the control group. There were statistically significant differences in survival rates depending on the diameter of the largest recurrent pelvic tumour (χ2 = 6.611, P = 0.010). The multivariate analysis showed that the survival rates were related to the diameter of the largest recurrent pelvic tumour (χ2 = 4.538, P = 0.033). 125I implantation is an effective, safe, and promising method for the treatment of pelvic recurrence after early cervical cancer surgery. The diameter of the recurrent pelvic tumour was identified as a significant independent prognostic factor in patients who received 125I implantation.

A new type of indexing cam-planetary gear composite mechanism is designed and studied. The input shaft is coaxial with the output shaft， the input shaft is fixedly connected to the swing rod， the swing rod is hinged to the planetary gear shaft， and the planetary gear， the two swing arms and the planetary gear shaft are fixedly connected. The swinging rod rotates with the input shaft， and the rollers on the two swinging rods are kept in contact with the two cams respectively. The contact point changes continuously with the rotation of the swinging rod， and the swinging arm rotates relative to the swinging rod to drive the planetary wheel connected thereto to swing. Finally， the intermittent movement of the center wheel is realized， that is， the indexing movement. The working condition parameters of the mechanism motion are defined. According to the specific parameters， the actual contour equation of the cam is designed， and the 3D modeling and motion simulation of the mechanism are completed， which verifies the correctness of the design modeling process.

Many organism behaviors are innate or instinctual and have been "hard-coded" through evolution. Current approaches to understanding these behaviors model evolution as an optimization problem in which the traits of organisms are assumed to optimize an objective function representing evolutionary fitness. Here, we use a mechanistic birth-death dynamics approach to study the evolution of innate behavioral strategies in a simulated population of organisms. In particular, we performed agent-based stochastic simulations and mean-field analyses of organisms exploring random environments and competing with each other to find locations with plentiful resources. We find that when organism density is low, the mean-field model allows us to derive an effective objective function, predicting how the most competitive phenotypes depend on the exploration-exploitation trade-off between the scarcity of high-resource sites and the increase in birth rate those sites offer organisms. However, increasing organism density alters the most competitive behavioral strategies and precludes the derivation of a well-defined objective function. Moreover, there exists a range of densities for which the coexistence of many phenotypes persists for evolutionarily long times.

Statistical gene detection plays an important role in biostatistics and bioinformatics. So far, many gene loci associated with human complex disease have been found by statistical methods. However, it is difficult to find all the mutation genes that are associated with a certain disease. Researchers need to detect more associated genes aiming at a disease so that human will conquer the disease one day. In this paper, we considered a real and big data set and study the detection problem of genes associated with the PIK3C2B gene on lung disease. 168 significant genes associated with the PIK3C2B gene were detected at nominal significance level 0.001 by using statistical multiple testing method. The detected genes will provide some reference to further study the function of the PIK3C2B gene to lung disease for biologists and medical scientists.

A new concave shaped high refractive index plasmonic sensor with a micro-channel is proposed in this work, which comprises an analyte channel in the core hole. The sensor is elaborately designed to reduce the interference effect from the metal coating. Furthermore, the impact of the proposed structure on the sensitivity is also investigated by engineering the geometric parameters using the finite element method. We select gold as the plasmonic material in this theoretical study because it is widely used to fabricate plasmonic and metamaterial devices due to its chemical stability and compatibility. According to wavelength interrogation technique, simulations results show that this sensor can obtain maximal wavelength sensitivity of 10,050 nm/refractive index unit. In view of the excellent indicators of this device, it has important development potential in chemical and biological research fields.

To investigate the effect of gardenia pomace (GP) as an unconventional feed of antioxidants, 180 Xiangcun pigs were randomly divided into 3 groups during the finishing period, with 6 replicates per group and 10 pigs per replicate. During the 47-day feeding period, the pigs were fed either a control diet based on corn and soybean meal (control group), or the control diet added with 50 g/kg or 100 g/kg GP (groups GP5 and GP10, respectively). Feed and water were provided ad libitum. One pig per replicate was slaughtered and sampled. The effects on growth performance, meat quality, digestibility, metabolism, and immunity and antioxidant properties of the pigs were investigated. The results showed that GP had no significant effect on the growth performance of Xiangcun pigs. Compared with the control group, the digestibility of crude ash, phosphorus, and crude fibre of pigs in the GP groups improved (p < 0.01), and the content of inosinic acid in the longissimus dorsi muscle increased (p < 0.05). The addition of GP to the diet significantly increased superoxide dismutase (SOD) levels in the liver and spleen, and glutathione peroxidase (GSH-Px) activity in the longissimus dorsi muscle and spleen (p < 0.05). Additionally, it significantly reduced the contents of malondialdehyde (MDA) in the liver and spleen (p < 0.05). The GP5 group had a higher inosinic acid content in the longissimus dorsi and lower levels of the inflammatory factor interleukin-2 and interleukin-8 than those in the other groups (p < 0.05). The GP10 group had a higher IgA level (p < 0.05). Adding different proportions of GP to the diet improved the a* and b* of the longissimus dorsi muscles of Xiangcun pigs (p < 0.05). In summary, GP, as an unconventional feed, improved the apparent digestibility of the diet and body antioxidant capacity in Xiangcun pigs during the finishing period and did not negatively affect the growth performance or meat quality.

In order to build a scientific pre-evaluation system for the industrialization of local science and technology (sci-tech) achievements, based on the analysis of the characteristics and laws of the industrialization projects of sci-tech achievements, the pre-evaluation of the industrialization projects of sci-tech achievements at home and abroad, the importance of the pre-evaluation of the industrialization projects of local sci-tech achievements and the research methods, the pre-evaluation index system of industrialization projects of local sci-tech achievements has been established from six aspects: policy environment, technical performance, economic benefits, resource guarantee, organizational guarantee, and social benefits. The research took the smart manufacturing project in Xiqing District of Tianjin as the object of empirical analysis and applied the fuzzy analytic hierarchy process (FAHP) to comprehensively evaluate the project. The overall score of the smart manufacturing project was 87.639, and the evaluation result was good and in accordance with the actual situation. The feasibility and validity of the evaluation index system and the evaluation model are verified, the risks of economy and policy in the industrialization of sci-tech achievements are reduced, and the optimization rate of the industrialization project is improved, which provide a reliable basis for local governments to realize the industrialization of sci-tech achievements.

Rice is one of the major staple cereals in the world, but heat stress is increasingly threatening its yield. Analyzing the thermotolerance mechanism from new thermotolerant germplasms is very important for rice improvement. Here, physiological and transcriptome analyses were used to characterize the difference between two germplasms, heat-sensitive MH101 and heat-tolerant SDWG005. Two genotypes exhibited diverse heat responses in pollen viability, pollination characteristics, and antioxidant enzymatic activity in leaves and spikelets. Through cluster analysis, the global transcriptomic changes indicated that the ability of SDWG005 to maintain a steady-state balance of metabolic processes played an important role in thermotolerance. After analyses of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, we found that the thermotolerance mechanism in SDWG00 was associated with reprogramming the cellular activities, such as response to abiotic stress and metabolic reorganization. In contrast, the down-regulated genes in MH101 that appeared to be involved in DNA replication and DNA repair proofreading, could cause serious injury to reproductive development when exposed to high temperature during meiosis. Furthermore, we identified 77 and 11 differentially expressed genes (DEGs) involved in lignin and flavonoids biosynthetic pathways, respectively. Moreover, we found that more lignin deposition and flavonoids accumulation happened in SDWG005 than in MH101 under heat stress. The results indicated that lignin and flavonoid biosynthetic pathways might play important roles in rice heat resistance during meiosis.

The vehicle semi-active suspension system plays an important role in improving the driving safety and ride comfort by adjusting the coefficients of the damping and spring. The main contribution of this paper is the proposal of a PPO-based vibration control strategy for a vehicle semi-active suspension system, in which the designed reward function realizes the dynamic adjustment according to the road condition changes. More specifically, for the different suspension performances caused by different road conditions, the three performances of the suspension system, body acceleration, suspension deflection, and dynamic tire load, were taken as the state space of the PPO algorithm, and the reward value was set according to the numerical results of the passive suspension, so that the corresponding damping force was selected as the action space, and the weight matrix of the reward function was dynamically adjusted according to different road conditions, so that the agent could have a better improvement effect at different speeds and road conditions. In this paper, a quarter–car semi-active suspension model was analyzed and simulated, and numerical simulations were performed using stochastic road excitation for different classes of roads, vehicle models, and continuously changing road conditions. The simulation results showed that the body acceleration was reduced by 46.93% under the continuously changing road, which proved that the control strategy could effectively improve the performance of semi-active suspension by combining the dynamic changes of the road with the reward function.

A new type of eccentric cylindrical gear rack mechanism is introduced. The gear is normal cylindrical gear which is eccentrically installed and the pitch curve of the rack is plane curve. The gear and rack are engaged with each other so that a special request of movements can be achieved. According to the fundamental law of mating profile,the equations of the pitch curve of the rack can be deduced. And further,the tooth profile equations of the rack are calculated based on the concept of the counterpart rack. Eventually,the3-dimentional modeling and motion simulation of the mechanism are carried out,through which the correctness of the design and modeling is preliminarily confirmed.