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Physics-informed neural networks (PINNs) commonly use the mean squared error (MSE) as the loss function. However, this MSE is sensitive to high-residual regions and noise, often causing nonconvergence, overfitting, and loss imbalance during training. To address these challenges, we propose a Huber+ that combines the robustness of the Huber loss with a residual-driven weighting mechanism. The Huber loss transitions smoothly from the MSE for small residuals to the mean absolute error for large residuals, enhancing robustness and accuracy. Furthermore, the dynamic weighting mechanism adaptively adjusts loss weights on the basis of residual variations at each training point, effectively mitigating loss imbalance and enabling PINNs to focus on high-residual regions. To validate the effectiveness of the proposed method, we conduct comparative experiments, ablation studies, and noise sensitivity tests on the Allen–Cahn equation, the Burgers equation, and the Helmholtz equation. The experimental results show that the proposed strategy improves both accuracy and convergence speed.

Background Conditioned place preference (CPP) is a common behavioral paradigm for studying the association of unconditioned stimulus reward memory with context. Generalization is a flexible memory recall pattern developed on the basis of original memory. Drug‐seeking behaviors in substance use disorders (SUDs) exhibit diversity, which we generally attribute to the highly generalized features of SUD memory. However, to date, there are no animal models for SUD generalization studies. Methods We design the generalization box (G‐box) and the generalization retrieval process based on the conditioned place preference (CPP) model. In the memory retrieval stage, we replaced the conditioning CPP box (T‐box) with a generalization box (G‐box) to study drug generalization memory. For appearance, the generalized boxes have different angles and numbers of sides compared to the conditioning boxes. For the visual cues, the shapes of the symbols are different (triangle icons for the hexagonal chamber and dot icons for the round chamber), but the orientation information remains the same. To establish CPP generalization, the mice received morphine on the vertical or horizontal side of a conditioning box (T‐box) and saline on the other side. Then, after CPP conditioning, the generalization test was performed in a generalization box (G‐box: hexagonal chamber and Gr‐box: round chamber) 21 days later. Results CPP‐conditioned mice still displayed a clear preference for similar visual information in the G‐box. CPA‐conditioned mice behaved similarly to CPP, with mice consistently avoiding similar visual information in the G‐box. We further observed that the generalization results are similar using two generalization boxes (G‐box and Gr‐box). Conclusion In this study, we succeeded in creating a simple and effective generalization model for morphine reward. The establishment of this model provides a new tool for generalization studies of SUD and therapy in humans. We use a behavioral paradigm based on conditional place preference to explore the generalization of drug memory. It provides a new approach for substance use disorders research.

Star-like nano-ZrO2 has been synthesized using Zr(NO3)4·5H2O as zirconium source by a hydrothermal process without any template and surfactant. The structure of the as-prepared ZrO2 powder was investigated by multiple advanced analytical methods. The results showed that CH3COO− and NO3− had great effects on the formation of star-like ZrO2 nanostructures. The as-prepared ZrO2 had a superior catalytic activity, and the reason for it was analyzed by UV-Vis diffuse reflectance spectroscopy. The effect of raw material ratios on the photocatalytic property of ZrO2 was studied. The synthesized ZrO2 showed a narrow bandgap (3.50–3.85 eV) and an excellent photocatalytic activity, and the degradation of RhB was up to nearly 100% in 30 min with this photocatalyst.

An obvious reason for substance uses disorders (SUDs) is drug craving and seeking behavior induced by conditioned context, which is an abnormal solid context memory. The relationship between susceptibility to SUD and learning ability remains unclear in humans and animal models. In this study, we found that susceptibility to morphine use disorder (MUD) was negatively correlated with learning ability in conditioned place preference (CPP) in C57 mice. By using behavioral tests, we identified the FVB mouse as learning impaired. In addition, we discovered that learning-relevant proteins, such as the glutamate receptor subunits GluA1, NR1, and NR2A, were decreased in FVB mice. Finally, we assessed the context learning ability of FVB mice using the CPP test and priming. We found that FVB mice had lower learning performance with respect to normal memory but higher performance of morphine-reinstatement memory. Compared to C57 mice, FVB mice are highly sensitive to MUDs. Our results suggest that SUD susceptibility is predicted by impaired learning ability in mice; therefore, learning ability can play a simple and practical role in identifying high-risk SUD groups.

Star‐like nano‐ZrO 2 has been synthesized using Zr(NO 3 ) 4 ·5H 2 O as zirconium source by a hydrothermal process without any template and surfactant. The structure of the as‐prepared ZrO 2 powder was investigated by multiple advanced analytical methods. The results showed that CH 3 COO − and NO 3 − had great effects on the formation of star‐like ZrO 2 nanostructures. The as‐prepared ZrO 2 had a superior catalytic activity, and the reason for it was analyzed by UV‐Vis diffuse reflectance spectroscopy. The effect of raw material ratios on the photocatalytic property of ZrO 2 was studied. The synthesized ZrO 2 showed a narrow bandgap (3.50–3.85 eV) and an excellent photocatalytic activity, and the degradation of RhB was up to nearly 100% in 30 min with this photocatalyst.

Aim： Dominant negative mutant G proteins have provided critical insight into the mechanisms of G protein-coupled receptor （GPCR） signaling, but the mechanisms underlying the dominant negative characteristics are not completely understood. The aim of this study was to determine the structure of the dominant negative Gαi1β1Y2 G203A/A326S complex （Gi-DN） and to reveal the structural basis of the mutation-induced phenotype of Gαi1β1Y2. Methods： The three subunits of the Gi-DN complex were co-expressed with a baculovirus expression system. The Gi-DN heterotrimer was purified, and the structure of its complex with GDP was determined through X-ray crystallography. Results： The Gi-DN heterotrimer structure revealed a dual mechanism underlying the dominant negative characteristics. The mutations weakened the hydrogen bonding network between GDP/GTP and the binding pocket residues, and increased the interactions in the Gα-GβY interface. Concomitantly, the Gi-DN heterotrimer adopted a conformation, in which the C-terminus of Gai and the N-termini of both the Gβ and Gy subunits were more similar to the GPCR-bound state compared with the wild type complex. From these structural observations, two additional mutations （T48F and D272F） were designed that completely abolish the GDP binding of the Gi-DN heterotrimer. Conclusion： Overall, the results suggest that the mutations impede guanine nucleotide binding and Gα-GβY protein dissociation and favor the formation of the G protein/GPCR complex, thus blocking signal propagation. In addition, the structure provides a rationale for the design of other mutations that cause dominant negative effects in the G protein, as exemplified by the T48F and D272F mutations.

Aim： To evaluate the pharmacokinetics （PK）, pharmacodynamics （PD） and primary tolerability of an anti-CD11a monoclonal antibody （CMABO01） in Chinese healthy volunteers and psoriatic patients. Methods： Two open-label studies were conducted. One was a parallel-group, single-center, dose-escalation test, including 24 healthy adult volunteers from 18 to 45 years in age. All subjects randomly received a single subcutaneous injection dose of 0.5, 1.0, or 2.0 mg/kg. The other was a multiple-dose study： 10 adult psoriatic patients were administered weekly subcutaneous injections of 1.0 mg/kg for 7 weeks. Results： CMABO01 was well tolerated in the single-and multiple-dose studies. Slow absorption was observed in both studies. In the single-dose study, the concentration of CMABO01 reached its highest level 2 d later after the injection, and the Cmax increased in an approximate dose-proportionate manner, while the area under curve （AUC） showed much greater than dose-proportionate increase. In the multiple-dose study, the steady-state serum concentration level was attained following the 4th injection. Conclusion： CMABO01 exhibited a nonlinear pharmacokinetic profile over the dose range from 0.5 to 2.0 mg/kg, and was well tolerated in healthy volunteers and psoriatic patients.

Myocardial ischemia/reperfusion injury can lead to severe brain injury.Glycogen synthase kinase 3 beta is known to be involved in myocardial ischemia/reperfusion injury and diabetes mellitus.However,the precise role of glycogen synthase kinase 3 beta in myocardial ischemia/reperfusion injury-induced brain injury is unclear.In this study,we observed the effects of glycogen synthase kinase 3 beta on brain injury induced by myocardial ischemia/reperfusion injury in diabetic rats.Rat models of diabetes mellitus were generated via intraperitoneal injection of streptozotocin.Models of myocardial ischemia/reperfusion injury were generated by occluding the anterior descending branch of the left coronary artery.Post-conditioning comprised three cycles of ischemia/reperfusion.Immunohistochemical staining and western blot assays demonstrated that after 48 hours of reperfusion,the structure of the brain was seriously damaged in the experimental rats compared with normal controls.Expression of Bax,interleukin-6,interleukin-8,terminal deoxynucleotidyl transferase d UTP nick end labeling,and cleaved caspase-3 in the brain was significantly increased,while expression of Bcl-2,interleukin-10,and phospho-glycogen synthase kinase 3 beta was decreased.Diabetes mellitus can aggravate inflammatory reactions and apoptosis.Ischemic post-conditioning with glycogen synthase kinase 3 beta inhibitor lithium chloride can effectively reverse these changes.Our results showed that myocardial ischemic post-conditioning attenuated myocardial ischemia/reperfusion injury-induced brain injury by activating glycogen synthase kinase 3 beta.According to these results,glycogen synthase kinase 3 beta appears to be an important factor in brain injury induced by myocardial ischemia/reperfusion injury.