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Abstract To investigate effects of agomelatine and mirtazapine on sleep disturbances in patients with major depressive disorder. A total of 30 depressed patients with sleep disturbances, 27 of which completed the study, took agomelatine or mirtazapine for 8 weeks. Subjective scales were administered, and polysomnography was performed at baseline and at the end of week 1 and 8. Functional magnetic resonance imaging was performed at baseline and at the end of week 8. Compared with baseline, scores on the Hamilton Depression Scale, Hamilton Anxiety Scale, Pittsburgh Sleep Quality Index, Sleep Dysfunction Rating Scale, and Insomnia Severity Index after 8 weeks of treatment significantly decreased in both groups, with no significant differences between groups, accompanied by significant increases in total sleep time, sleep efficiency, and rapid eye movement (REM) sleep and significant decrease in wake after sleep onset. Mirtazapine treatment increased N3 sleep at week 1 compared with agomelatine treatment, but this difference disappeared at week 8. The increases in the percentage and duration of N3 sleep were positively correlated with increases in connectivity between right dorsal lateral prefrontal cortex (dlPFC) and right precuneus and between left posterior cingulate cortex and right precuneus in both groups, respectively. Functional connectivity (FC) between right dlPFC and left precuneus in mirtazapine group was higher compared with agomelatine group after 8 weeks of treatment. These findings indicated that both agomelatine and mirtazapine improved sleep in depressed patients, and the effect of mirtazapine was greater than agomelatine with regard to rapidly increasing N3 sleep and gradually improving FC in the brain.

Toludesvenlafaxine hydrochloride sustained‐release tablets, as China’s first independently developed chemical Class 1 innovative drug with independent intellectual property rights for the treatment of depression and a new molecular entity, represent a novel triple reuptake inhibitor (TRI) with specific target selectivity for serotonin (5‐HT), norepinephrine (NE), and dopamine (DA). This single‐arm, multicenter clinical study aimed to evaluate the efficacy and safety of toludesvenlafaxine in alleviating anhedonia symptoms in patients with major depressive disorder (MDD). A total of 123 patients aged 18–65 years were enrolled between April 2023 and April 2024 and received an 8‐week treatment with toludesvenlafaxine sustained‐release tablets (80–160 mg/day). The primary efficacy endpoint was the change in the total score of the Dimensional Anhedonia Rating Scale (DARS) at weeks 2, 4, and 8. Significant improvements in DARS scores were observed, with mean changes from baseline of 8.4 (95% CI [6.4, 10.4], p < 0.0001), 14.1 (95% CI [12.0, 16.2], p < 0.0001), and 20.4 (95% CI [18.0, 22.9], p < 0.0001), respectively. Additionally, after 8 weeks of treatment, plasma levels of neurotrophic factors, including mature brain‐derived neurotrophic factor (mBDNF) ( t = 28.78, p < 0.0001), pro‐BDNF ( t = 27.71, p < 0.0001), and vascular endothelial growth factor (VEGF) ( t = 31.07, p < 0.0001), were significantly increased, and the plasma level of IGF‐1 was not significantly changed ( t = 0.35, p = 0.7269). No association was found between the percentage of changes in neurotrophic factors and the percentage of symptom improvements. Toludesvenlafaxine was generally well‐tolerated, with treatment‐emergent adverse events (AEs) (TEAEs) reported in 83.7% of participants and treatment‐related AEs (TRAEs) in 76.4%. These findings indicate that toludesvenlafaxine hydrochloride sustained‐release tablets are safe, well‐tolerated, and effective in alleviating anhedonia symptoms in patients with depression. Trial Registration: http://www.chictr.org.cn (No.: ChiCTR2300070331).

We establish the global well-posedness for the multidimensional Chemotaxis model with some classes of large initial data, especially the case when the rate of variation of ln v 0 ( v 0 is the chemical concentration) contains high oscillation and the initial density near the equilibrium is allowed to have large oscillation in 3D. Besides, we show the optimal time-decay rates of the strong solutions under an additional perturbation assumption, which include specially the situations of d = 2, 3 and improve the previous time-decay rates. Our method mainly relies on the introduce of the effective velocity and the application of the localization in Fourier spaces.

Background： Th9 cells are a newly discovered CD4＋ T helper cell subtype, characterized by high interleukin （IL）-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis （MS）. Mast cells are multifunctional innate imnmne cells, which are perhaps best known for their role as dominant effector cells in allergies and asthma. Several lines of evidence point to an important role lbr mast cells in MS and its animal models. Simultaneously, there is dynamic ＂＇cross-talk＂ between Th9 and mast cells. The aim of the present study was to examine the IL-9-mast cell axis in experimental autoimmune encephalomyelitis （EAE） and deternaine its interaction alter neutralizing anti-lL-9 antibody treatment. Methods： Female C57BL/6 mice were randomly divided into three groups （#1 = 5 in each group）： mice with myelin oligodendrocyte glycoprotein （MOG）-induced EAE （EAE group）, EAE mice treated with anti-lL-9 antibody （anti-lL-9 Abs group）, and EAE mice treated with IgG isotype control （lgG group）. EAE clinical score was evaluated. Mast cells from central nervous system （CNS） were detected by flow cytometry. The production of chemokine recruiting mast cells in the CNS was explored by reverse transcription-polymerase chain reaction （RT-PCR）. In mice with MOG-induced EAE, the expression of IL-9 receptor （IL-9R） complexes in CNS and spleen mast cells was also explored by RT-PCR, and then was repeating validated by immunocytochemistry. In vitro, spleen cells from EAE mice were cultured with anti-lL-9 antibody, and quantity of mast cells was counted by flow cytoinetry alter co-culture. Results： Compared with IgG group, IL-9 blockade delayed clinical disease onset and ameliorated EAE severity （t = -2.217, P- 0.031 ）, accompany with mast cells infiltration decreases （day 5： t = -8.005, P 〈 0.001; day 15： t = -11.857, P 〈 0.001; day 20： t- 5.243, P = 0.001 ） in anti-lL-9 Abs group. The messenger RNA expressions of C-C motif chemokine ligand 5 （t = -5.932, P = 0.003） and vascular cell adhesion molecule-I （t = -4.029, P 0.004） were significantly decreased alter 1L-9 neutralization in anti-lL-9 Abs group, compared with lgG group. In MOG-induced EAE, the 1L-9R complexes were expressed in CNS and spleen mast cells. 1#7 vitro, splenocyles cultured with anti-lL-9 antibody showed significantly lower levels of mast cells in a dose-dependent manner, compared with splenocytes cultured with anti-mouse lgG （5 μg/ml： t = -0.894, P = 0.397; 10 p-g/ml： t = -3.348, P - 0.019：20 μg/ml： I - -7.639, P 〈 0.001 ）.Conclusions： This study revealed that 1L-9 neutralization reduced mast cell infiltration in CNS and ameliorated EAE, which might be relate to the interaction between IL-9 and mast cells.

Accurate runoff forecasting is of great significance for water resource allocation flood control and disaster reduction. However, due to the inherent strong randomness of runoff sequences, this task faces significant challenges. To address this challenge, this study proposes a new SMGformer runoff forecast model. The model integrates Seasonal and Trend decomposition using Loess (STL), Informer’s Encoder layer, Bidirectional Gated Recurrent Unit (BiGRU), and Multi-head self-attention (MHSA). Firstly, in response to the nonlinear and non-stationary characteristics of the runoff sequence, the STL decomposition is used to extract the runoff sequence’s trend, period, and residual terms, and a multi-feature set based on ‘sequence-sequence’ is constructed as the input of the model, providing a foundation for subsequent models to capture the evolution of runoff. The key features of the input set are then captured using the Informer’s Encoder layer. Next, the BiGRU layer is used to learn the temporal information of these features. To further optimize the output of the BiGRU layer, the MHSA mechanism is introduced to emphasize the impact of important information. Finally, accurate runoff forecasting is achieved by transforming the output of the MHSA layer through the Fully connected layer. To verify the effectiveness of the proposed model, monthly runoff data from two hydrological stations in China are selected, and eight models are constructed to compare the performance of the proposed model. The results show that compared with the Informer model, the 1th step MAE of the SMGformer model decreases by 42.2% and 36.6%, respectively; RMSE decreases by 37.9% and 43.6% respectively; NSE increases from 0.936 to 0.975 and from 0.487 to 0.837, respectively. In addition, the KGE of the SMGformer model at the 3th step are 0.960 and 0.805, both of which can maintain above 0.8. Therefore, the model can accurately capture key information in the monthly runoff sequence and extend the effective forecast period of the model.

The accurate modeling of carbohydrates is challenged by conformational flexibility, hydration, and many-body electrostatics. In this work, a polarizable bond dipole potential for carbohydrates (PBDPC25) is presented, in which C–O, O–H, and C–H bonds are represented as intrinsically polarizable dipoles. Electrostatic interactions are described through bond dipole coupling, with an orbital overlap contribution introduced to account for hydrogen bonding. For carbohydrate monomers, PBDPC25 reproduces conformational energies with a root-mean-square error (RMSE) of 2.13 kcal/mol. This accuracy exceeds that of GLYCAM06 (2.87 kcal/mol) and CHARMM36 (3.74 kcal/mol). It is also slightly better than the polarizable AMOEBA force field (2.82 kcal/mol). Optimized geometries are maintained within 0.15 Å of benchmark reference structures. This level of agreement is comparable to GLYCAM06 (0.21 Å) and close to CHARMM36 and AMOEBA (both 0.14 Å). Molecular dipole moments show excellent agreement with the reference data. Correlation coefficients exceed R2 > 0.98. For carbohydrate–water clusters, hydration energies, including many-body contributions, are predicted with an RMSE of 3.50 kcal/mol. This represents a substantial improvement over GLYCAM06, CHARMM36, and AMOEBA. These results demonstrate that PBDPC25 provides a reliable framework for modeling carbohydrate conformations and local hydration effects.

Fullerene-supported single-atom catalysts (SACs) have emerged as a promising class of materials for electrocatalytic overall water splitting, offering a route to reduce reliance on scarce and costly precious metals. This review systematically summarizes recent advances in the design, synthesis, and application of fullerene-based SACs, with an emphasis on their unique structural, electronic, and catalytic properties. The exceptional stability, conductivity, and surface chemistry of fullerenes enable strong interactions with metal atoms, allowing high dispersion and enhanced catalytic performance for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Recent studies demonstrate that C60- and C24-based materials, when combined with transition metals such as Pt, Ru, and V, exhibit superior HER/OER activity, bifunctionality, and spin-selective catalytic pathways. The vast structural space of fullerene–metal combinations presents new opportunities, which can be efficiently explored using machine learning and high-throughput simulations. By integrating density functional theory, transition state modeling, and data-driven techniques, this emerging research frontier is paving the way for rational catalyst design. The review concludes by proposing a machine learning-assisted framework to predict and screen high-performance fullerene-based SACs, ultimately accelerating the development of efficient, stable, and scalable electrocatalysts for sustainable hydrogen production.

is an apicomplexan parasite that causes toxoplasmosis, a widespread zoonotic disease leading to serious public health concerns and economic losses to animal husbandry. Currently, highly effective vaccines against toxoplasmosis remain unavailable. This study aimed to investigate the safety, immunogenicity, and protective efficacy of the -deficient mutant strain PruΔ as a live-attenuated vaccine candidate. We evaluated the virulence of PruΔ in a mouse model, determined the optimal immunization dose, and measured serum antibody levels and cytokine profiles. Then, mice immunized with PruΔ were challenged with different strains to assess protection against acute and chronic infection. PruΔ displayed significantly attenuated virulence and its ability to form cysts was weakened. Vaccination with 5 × 10 tachyzoites elicited predominantly Th1-skewed immune responses. Immunization with PruΔ provided complete protection against challenge infection with relatively low-virulent PYS strain and homologous Pru strain, prolonged survival against the highly virulent RH strain, and achieved a 90% survival rate with reduced brain cyst burden under chronic challenge. In conclusion, PruΔ is relatively safe and immunogenic in the murine model, and is worth being evaluated in food-producing animals and cats.

Dermacentor is the most widely distributed tick genus in China. Dermacentor nuttalli, a predominant tick species in Inner Mongolia, can carry and transmit pathogenic microorganisms. Here, D. nuttalli were collected from Ordos (O-D) and Hinggan League (H-D) in the Inner Mongolia. D. nuttalli specimens at different developmental stages were subsequently reared under identical laboratory conditions. Sample processing, nucleic acid extraction, high-throughput sequencing, and microbial community analyses were conducted. Bacterial communities in O-D and H-D were annotated to 8 phyla, 145 genera and 16 phyla, 141 genera, respectively, with Proteobacteria showing the highest relative abundance. Differences in dominant bacterial genera were observed across developmental stages between the two regions. The most abundant bacterial species were Arsenophonus_uncultured_bacterium in O-D and Rickettsia japonica in H-D. Viral communities were annotated to 4 orders, 25 families, 61 genera, and 126 species in O-D and 6 orders, 28 families, 49 genera, 135 species in H-D. Notable difference in the viral genera with >1% abundance were identified at different developmental stages in the two regions. To our knowledge, this is the first study to compare microbial community compositions of D. nuttalli across developmental stages in two Inner Mongolian regions under under identical rearing conditions and to report the presence of R. japonica, Tacheng Tick Virus-2, and bovine viral diarrhea virus in D. nuttalli.