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Postural disorder is a common disabling movement complication of Parkinson's disease (PD), in which camptocormia is the most common disabling postural disorder, which further aggravates the movement disorder of PD, and seriously reduces the activities of daily living and quality of life of patients. This paper reviews the pathogenesis and treatment progress of PD with camptocormia, providing theoretical basis for further investigation of the pathogenesis of camptocormia in PD, and assisting the clinical diagnosis and treatment of the disease.

Abstract Neuro-inspired vision systems hold great promise to address the growing demands of mass data processing for edge computing, a distributed framework that brings computation and data storage closer to the sources of data. In addition to the capability of static image sensing and processing, the hardware implementation of a neuro-inspired vision system also requires the fulfilment of detecting and recognizing moving targets. Here, we demonstrated a neuro-inspired optical sensor based on two-dimensional NbS2/MoS2 hybrid films, which featured remarkable photo-induced conductance plasticity and low electrical energy consumption. A neuro-inspired optical sensor array with 10 × 10 NbS2/MoS2 phototransistors enabled highly integrated functions of sensing, memory, and contrast enhancement capabilities for static images, which benefits convolutional neural network (CNN) with a high image recognition accuracy. More importantly, in-sensor trajectory registration of moving light spots was experimentally implemented such that the post-processing could yield a high restoration accuracy. Our neuro-inspired optical sensor array could provide a fascinating platform for the implementation of high-performance artificial vision systems.

A key property of the circadian clock is that it is reset by light to remain synchronized with the day-night cycle. An attractive model to explore light input to the circadian clock in vertebrates is the zebrafish. Circadian clocks in zebrafish peripheral tissues and even zebrafish-derived cell lines are entrainable by direct light exposure thus providing unique insight into the function and evolution of light regulatory pathways. Our previous work has revealed that light-induced gene transcription is a key step in the entrainment of the circadian clock as well as enabling the more general adaptation of zebrafish cells to sunlight exposure. However, considerable evidence points to post-transcriptional regulatory mechanisms, notably microRNAs (miRNAs), playing an essential role in shaping dynamic changes in mRNA levels. Therefore, does light directly impact the function of miRNAs? Are there light-regulated miRNAs and if so, which classes of mRNA do they target? To address these questions, we performed a complete sequencing analysis of light-induced changes in the zebrafish transcriptome, encompassing small non-coding RNAs as well as mRNAs. Importantly, we identified sets of light-regulated miRNAs, with many regulatory targets representing light-inducible mRNAs including circadian clock genes and genes involved in redox homeostasis. We subsequently focused on the light-responsive miR-204-3-3p and miR-430a-3p which are predicted to regulate the expression of cryptochrome genes (cry1a and cry1b). Luciferase reporter assays validated the target binding of miR-204-3-3p and miR-430a-3p to the 3′UTRs of cry1a and cry1b, respectively. Furthermore, treatment with mimics and inhibitors of these two miRNAs significantly affected the dynamic expression of their target genes but also other core clock components (clock1a, bmal1b, per1b, per2, per3), as well as the rhythmic locomotor activity of zebrafish larvae. Thus, our identification of light-responsive miRNAs reveals new intricacy in the multi-level regulation of the circadian clockwork by light. Author summary: Our study explored how light affects the biological clock of zebrafish, with a particular focus on the role of miRNAs, small molecules that regulate gene expression. Zebrafish provide a unique model for this research because their internal clocks can be directly reset by light. Through RNA-sequencing, we identified 1365 genes and 66 miRNAs that respond to light exposure, and constructed light-responsive mRNA-miRNA interaction networks, highlighting their roles in various biological processes including circadian clock regulation. We particularly focused on two miRNAs, miR-204-3-3p and miR-430a-3p, which can target core clock genes cry1a and cry1b, respectively and significantly impact the rhythmic gene expression and behavioral patterns of zebrafish larvae. This study not only advances our understanding of the mechanisms governing biological rhythms in zebrafish, but also provides new insight that could be relevant to other organisms, including humans. Ultimately, this work may contribute to developing better strategies for managing circadian rhythm disorders and improving overall health. [ABSTRACT FROM AUTHOR]

Simple Summary: In livestock farming, oxidative stress is common and hurts animal growth and product quality. Curcumin, a natural compound, can help fight oxidative stress and cell death. This study used cells from cow fat to create an oxidative stress model and tested curcumin's effects. The results show that curcumin reduces oxidative stress and cell death in these cells, possibly by triggering a cellular cleanup process called autophagy. The study suggests that curcumin could be useful in protecting livestock from oxidative stress, improving their health and production. In livestock production, oxidative stress (OS) is ubiquitous, reducing animal productivity and product quality. Hence, investigating the mechanisms of oxidative stress in livestock and inhibiting oxidative stress-induced damage is crucial. Curcumin, a plant-derived bioactive compound, exhibits antioxidant and anti-apoptotic properties. Adipose-derived stem cells (ADSCs) from animal adipose tissue are easily accessible and possess multilineage differentiation potential. Therefore, this work utilized bovine ADSCs to establish an oxidative stress model and investigated the effects of curcumin on oxidative stress and apoptosis. Firstly, bovine ADSCs were isolated and cultured from fetal calf subcutaneous adipose tissue. Their surface markers were identified by immunofluorescence, confirming the expression of CD29, CD44, CD73, CD90, CD105 and Vimentin, but not CD34, indicative of mesenchymal stem/progenitor cell characteristics. Secondly, to explore the effects of curcumin on oxidative damage and apoptosis in bovine ADSCs, an oxidative stress model was induced using H2O2. CCK-8 assays showed significantly reduced cell viability and SOD activity, along with increased malondialdehyde (MDA) and reactive oxygen species (ROS) levels, indicating successful modeling. RT-qPCR further confirmed that 500 μM of H2O2 treatment for 24 h promoted apoptosis. Herein, CCK-8 assays indicated a significant reduction in cell viability at >8 μM of curcumin. Thirdly, using 4 μM and 8 μM of curcumin for pre-protection, 8 μM maintained SOD activity, reduced MDA and ROS, inhibited apoptosis-related gene changes (Bcl-2, Bax, Caspase-3), and suppressed apoptosis according to a TUNEL assay. Fourthly, curcumin's autophagy-inducing potential was hypothesized, which was confirmed by increased LC3-II and decreased P62 expression upon co-treatment with 3-MA. 3-MA inhibited curcumin's antioxidant and anti-apoptotic effects, suggesting that curcumin's antioxidant and anti-apoptotic roles may involve autophagy induction. In conclusion, bovine ADSCs are abundant, easily accessible, and multipotent, making them suitable for in vitro expansion. Curcumin alleviated H2O2-induced oxidative stress in bovine ADSCs, with curcumin also inhibiting apoptosis, likely through autophagy induction. This study validates the protective role of curcumin in bovine ADSCs, with potential applications in livestock production. [ABSTRACT FROM AUTHOR]

A Ni-catalyzed cascade cyclization of N-acrylamides and unactivated alkyl bromides to synthesize 3,3-disubstituted oxindoles was reported. Up to 22 different oxindole derivatives were synthesized by this method and all the synthesized molecules were tested for inhibitory activity of nitric oxide release. The results show that 3,3-disubstituted oxindole is a potential scaffold to design new nitric oxide release inhibition drugs. [ABSTRACT FROM AUTHOR]

The Nuclear receptor subfamily 5 group A member 2 (NR5A2) gene plays a pivotal role in ovarian development, ovulation, and reproductive traits. There is a lack of studies on its impact on ovarian traits and reproductive traits in cattle. This study aimed to explore NR5A2 gene polymorphisms associations with reproductive traits and investigate the distribution of NR5A2 gene polymorphisms across diverse bovine breeds worldwide. We identified a novel 17-bp deletion within the NR5A2 gene specifically in Chinese Holstein cows (n = 1033) leading to the observation of two genotypes DD and ID. Subsequent association analysis revealed a significant correlation between the 'ID' genotype at this locus and a larger number of corpus albicans (p = 0.042) in diestrus, as well as a higher number of mature follicles (p = 0.038) in estrus. In addition, we also found that the distribution of this deletion exhibits strong regionality across different cattle breeds globally. These findings indicate that the 17-bp deletion mutation within the NR5A2 gene is significantly associated with an increased corpus luteum diameter and a greater number of mature follicles, suggesting its potential utility as a valuable DNA marker for enhancing cow fertility. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC).Methods3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites.ResultsA total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07).ConclusionMolecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients.

Daprodustat is the first oral hypoxia‐inducible factor prolyl hydroxylase inhibitor approved recently for the treatment of anemia caused by chronic kidney disease (CKD) in adults receiving dialysis. We evaluated the role of organic anion transporting polypeptide (OATP)1B‐mediated hepatic uptake transport in the pharmacokinetics (PKs) of daprodustat using in vitro and in vivo studies, and physiologically‐based PK (PBPK) modeling of its drug–drug interactions (DDIs) with inhibitor drugs. In vitro, daprodustat showed specific transport by OATP1B1/1B3 in the transfected cell systems and primary human and monkey hepatocytes. A single‐dose oral rifampin (OATP1B inhibitor) reduced daprodustat intravenous clearance by a notable 9.9 ± 1.2‐fold (P < 0.05) in cynomolgus monkeys. Correspondingly, volume of distribution at steady‐state was also reduced by 5.0 ± 1.1‐fold, whereas the half‐life change was minimal (1.5‐fold), corroborating daprodustat hepatic uptake inhibition by rifampin. A PBPK model accounting for OATP1B‐CYP2C8 interplay was developed, which well described daprodustat PK and DDIs with gemfibrozil (CYP2C8 and OATP1B inhibitor) and trimethoprim (weak CYP2C8 inhibitor) within 25% error of the observed data in healthy subjects. About 18‐fold increase in daprodustat area under the curve (AUC) following gemfibrozil treatment was found to be associated with strong CYP2C8 inhibition and moderate OATP1B inhibition. Moreover, PK modulation in hepatic dysfunction and subjects with CKD, in comparison to healthy control, was well‐captured by the model. CYP2C8 and/or OATP1B inhibitor drugs (e.g., gemfibrozil, clopidogrel, rifampin, and cyclosporine) were predicted to perpetrate moderate‐to‐strong DDIs in healthy subjects, as well as, in target CKD population. Daprodustat can be used as a sensitive CYP2C8 index substrate in the absence of OATP1B modulation. [ABSTRACT FROM AUTHOR]