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Diabetic neuropathy (DN) represents a common and debilitating complication of diabetes, affecting a significant proportion of patients. Despite available treatments focusing on symptom management, there remains an unmet need for therapies that address the underlying pathophysiology. In pursuit of novel interventions, this study evaluated the therapeutic effects of caffeic acid—a natural phenolic compound prevalent in various foods—on diabetic neuropathy using a mouse model, particularly examining its interaction with the Insulin-like Growth Factor 1 (IGF-1) signaling pathway. Caffeic acid was administered orally at two dosages (5 mg/kg and 10 mg/kg), and a comprehensive set of outcomes including fasting blood glucose levels, body weight, sensory behavior, spinal cord oxidative stress markers, inflammatory cytokines, and components of the IGF-1 signaling cascade were assessed. Additionally, to determine the specific contribution of IGF-1 signaling to the observed benefits, IGF1R inhibitor Picropodophyllin (PPP) was co-administered with caffeic acid. Our results demonstrated that caffeic acid, at both dosages, effectively reduced hyperglycemia and alleviated sensory behavioral deficits in diabetic mice. This was accompanied by a marked decrease in oxidative stress markers and an increase in antioxidant enzyme activities within the spinal cord. Significantly lowered microglial activation and inflammatory cytokine expression highlighted the potent antioxidative and anti-inflammatory effects of caffeic acid. Moreover, increases in both serum and spinal levels of IGF-1, along with elevated phosphorylated IGF1R, implicated the IGF-1 signaling pathway as a mediator of caffeic acid's neuroprotective actions. The partial reversal of caffeic acid's benefits by PPP substantiated the pivotal engagement of IGF-1 signaling in mediating its effects. Our findings delineate the capability of caffeic acid to mitigate DN symptoms, particularly through reducing spinal oxidative stress and inflammation, and pinpoint the integral role of IGF-1 signaling in these protective mechanisms. The insights gleaned from this study not only position caffeic acid as a promising dietary adjunct for managing diabetic neuropathy but also highlight the therapeutic potential of targeting spinal IGF-1 signaling as part of a strategic treatment approach.

Optical flow estimation captures the motion information of objects in a scene through analyzing the displacement of pixels in an image over time. This technology provides a powerful tool for vision systems, allowing them to understand and perceive changes in dynamic environments. Optical flow estimation has a wide range of applications in fields such as military, medicine, traffic regulation, and intelligent robotics. This study systematically explores two key directions in the field of optical flow estimation—traditional methods and emerging strategies based on deep learning—aiming to provide a comprehensive and in-depth perspective to help scholars gain a deeper understanding of the development of the optical flow estimation field. First, the core principles and constraints of conventional optical flow estimation are briefly analyzed, focusing on reviewing the faced challenges and associated solutions based on differential, variational, and matching optical flow estimation principles. Then, we discuss the backbone networks and training strategies used in deep learning approaches in depth, with a particular focus on the current challenges faced under supervised and unsupervised conditions, as well as existing solutions. In addition, to evaluate the performance of these methods, existing datasets and evaluation indicators are analyzed and comprehensive comparisons on several publicly available datasets are conducted. Finally, we discuss prospects related to various application fields and future research directions in the field of optical flow estimation.

As an effective non-thermal sterilization method, ultrasound remains at the level of passive bacterial death despite the initial understanding of its sterilization mechanism. Here, we present the perspective that bacteria can choose to actively enter an apoptosis-like death state in response to external ultrasonic stress. In this study, Vibrio parahaemolyticus exhibited apoptotic markers such as phosphatidylserine ectropion and activated caspases when subjected to ultrasound stress. Additionally, the accumulation of reactive oxygen species (ROS) and enhanced calcium signaling were observed. Further transcriptomic analysis was conducted to investigate the regulatory mechanism of the SOS response in Vibrio parahaemolyticus during an apoptosis-like state. The results showed that the genes encoding the citrate cycle were down-regulated in Vibrio parahaemolyticus cells adapted to ultrasonic stress, leading to an apoptosis-like state and a decrease in production capacity and ability to catabolize carbon dioxide. Furthermore, the level of oxidized glutathione increased, suggesting that the bacteria were engaged in various anti-oxidative stress responses, ultimately leading to apoptosis. Moreover, the ultrasound field activated the regulatory factor CsrA, which facilitates stress survival as cells transition from rapid growth to an apoptotic state through a stringent response and catabolic inhibition system. Parallel reaction monitoring (PRM) revealed that the expression of certain key SOS proteins in Vibrio parahaemolyticus was up-regulated following ultrasound treatment, resulting in a gradual adaptation of the cells to external stress and ultimately leading to active cell death. In conclusion, the biological lethal effect of ultrasound treatment is not solely a mechanical cell necrosis process as traditionally viewed, but also a programmed cell death process regulated by cellular adaptation. This enriched the biological effect pathway of ultrasound sterilization.

Polygonati rhizoma (known as Huangjing in Chinese), an edible medicinal herb with homology of medicine and food, was also commonly used as food additives in Asian countries to provide many health benefits. Currently, the amelioration of fatigue induced by excessive exercise has become a health concern. In the present study, we studied the anti-fatigue effect of P. rhizoma polysaccharides (PRP) and also explored its potential mechanism by gut flora regulation. The molecular weight, monosaccharide composition, morphology, and FT-IR analysis of PRP were performed. Following intragastric administration of PRP, the exhaustive swimming model mice demonstrated increased swimming time, creatine kinase and malondialdehyde level, decreased lactic acid and blood urine nitrogen levels. Furthermore, the abundance of Akkermansia, Lactobacillus, and Faecalibacterium was remarkably enhanced, while the abundance of Streptococcus and Bacteroides was decreased, compared to model group. In summary, our findings offer compelling evidence supporting the beneficial effects of PRP on exercise-induced fatigue.

Aims: Altered lipid, energy metabolism and sleep disorders had been linked with coronary heart disease (CHD), however, the metabolic signatures and sleep rhythm in non-obstructive coronary atherosclerosis-CHD remain unclear. This pilot study aims to investigate the lipidome and central carbon metabolites profiles and associated sleep characteristics among CHD patients without traditional risk factors. Methods: From January to July 2021, 15 CHD patients and 15 healthy controls were randomly selected from the cardiology unit of Zhongshan Hospital, Shanghai. A total of 464 lipids and 45 central carbon metabolites (CCM) were quantified in blood plasma. Metabolic signatures were selected through orthogonal projections to latent structures discriminant analysis (OPLS-DA) and principal component analysis (PCA) was conducted to link the profiles of identified metabolites with CHD risk, sleep patterns, cardiometabolic traits and cardiac electrophysiologic parameters. Results: Using OPLS-DA, we identified 40 metabolites (variable influence on projection >1) that were altered in CHD patients, with 38 lipids, including 25 triacylglycerols (TAGs), 8 diacylglycerols (DAGs), being elevated and two CCM metabolites (i.e., succinic acid and glycolic acid) being reduced. Using PCA, four principal components (PCs) were identified and associated with increased risk of CHD. Specifically, one standard unit increasement in the PC that was characterized by high levels of DAG (18:1) and low succinic acid and the PC that was characterized by high levels of two sphingomyelins [SM (26:0) and SM (24:0)] was associated with 21% [odds ratio (OR) = 1.21, 95% CI: 1.02,1.43] and 14% (OR = 1.14,1.02,1.29) increased risk of CHD, respectively. Further regression analyses confirmed that the identified metabolites and the four PCs were positively associated with TG and ALT. Interestingly, glycolic acid was negatively associated with sleep quality and PSQI. Participants with night sleep mode tended to have a high level of the identified lipids, especially FFA (20:4). Conclusion: In the present pilot study, our findings provide clues on alterations of lipid and energy metabolism in CHD patients without traditional risk factors, with multiple triacylglycerols and diacylglycerols metabolites seemingly elevated and certain nonlipids metabolites (e.g., succinic acid and glycolic acid) decreased in cases. Considering the limit sample size, further studies are warranted to confirm our results.

Although nano-systems can promote the cellular internalization, polymeric nanoparticles (NPs) are easily to be destroyed or eliminated in the gastrointestinal tract, which leads to premature drug release or insufficient colonic accumulation. A novel oral nano-in-micro system for the efficient colonic delivery of curcumin (Cur) was developed in this study, in which the hyaluronic acid (HA)/zein complex NPs loading Cur were embedded in alginate/chitosan hydrogel microparticles (Cur@NMPs) with the electrospray technology. The Cur@NMPs showed uniform-sized sphere with an average size of 218.36 ± 10 μm, encapsulating Cur@HA/zein NPs with the average size of 148.64 ± 3.21 nm. Cur in NMPs showed the sustained drug-release profiles in simulated gastric fluid, whereas it showed the rapid release in simulated colonic fluid. Mediated by the HA-CD44 receptor recognition, Cur@HA/zein NPs had the increased cellular uptake efficiency in macrophages. Furthermore, NMPs had the significant colon-retention and bio-adhesiveness capacity in colon tissues. As expected, the oral administration of Cur@NMPs significantly mitigated colitis symptoms in DSS-induced UC mice by inhibiting TLR4/NF-κB pathway. The above results can provide a useful drug delivery strategy for Cur in the treatment of UC by retaining the advantages of nano- and micro-scaled carriers.

Summary: Defining factors that govern CD8+ T cell immunodominance is critical for the rational design of vaccines for viral pathogens. Here, we assess the contribution of human leukocyte antigen (HLA) class-I-peptide stability for 186 optimal HIV epitopes across 18 HLA alleles using transporter associated with antigen processing (TAP)-deficient mono-allelic HLA-expressing cell lines. We find that immunodominant HIV epitopes increase surface stabilization of HLA class-I molecules in comparison to subdominant epitopes. HLA class-I-peptide stability is also strongly correlated with overall immunodominance hierarchies, particularly for epitopes from high-abundance proteins (e.g., Gag). Moreover, HLA alleles associated with HIV protection are preferentially stabilized by epitopes derived from topologically important viral regions at a greater frequency than neutral and risk alleles. These findings indicate that relative stabilization of HLA class-I is a key factor for CD8+ T cell epitope immunodominance hierarchies, with implications for HIV control and the design of T-cell-based vaccines.