Motion/force coordinated trajectory tracking control of nonholonomic wheeled mobile robot via LMPC-AISMC strategy.

Nonholonomic constrained wheeled mobile robot (WMR) trajectory tracking requires the enhancement of the ground adaptation capability of the WMR while ensuring its attitude tracking accuracy, a novel dual closed-loop control structure is developed to implement this motion/force coordinated control objective in this paper. Firstly, the outer-loop motion controller is presented using Laguerre functions modified model predictive control (LMPC). Optimised solution condition is introduced to reduce the number of LMPC solutions. Secondly, an inner-loop force controller based on adaptive integral sliding mode control (AISMC) is constructed to ensure the desired velocity tracking and output driving torques by combining second-order nonlinear extended state observer (ESO) with the estimation of dynamic uncertainties and external disturbances during WMR travelling process. Then, Lyapunov stability theory is utilised to guarantee the consistent final boundedness of the designed controller. Finally, the system is numerically simulated and practically verified. The results show that the double-closed-loop control strategy devised in this paper has better control performance in terms of complex trajectory tracking accuracy, system resistance to strong interference and computational timeliness, and is able to realise effective coordinated control of WMR motion/force.

Electrophysiological activity pattern of mouse hippocampal CA1 and dentate gyrus under isoflurane anesthesia.

General anesthesia can impact a patient's memory and cognition by influencing hippocampal function. The CA1 and dentate gyrus (DG), serving as the primary efferent and gateway of the hippocampal trisynaptic circuit facilitating cognitive learning and memory functions, exhibit significant differences in cellular composition, molecular makeup, and responses to various stimuli. However, the effects of isoflurane-induced general anesthesia on CA1 and DG neuronal activity in mice are not well understood. In this study, utilizing electrophysiological recordings, we examined neuronal population dynamics and single-unit activity (SUA) of CA1 and DG in freely behaving mice during natural sleep and general anesthesia. Our findings reveal that isoflurane anesthesia shifts local field potential (LFP) to delta frequency and reduces the firing rate of SUA in both CA1 and DG, compared to wakefulness. Additionally, the firing rates of DG neurons are significantly lower than CA1 neurons during isoflurane anesthesia, and the recovery of theta power is slower in DG than in CA1 during the transition from anesthesia to wakefulness, indicating a stronger and more prolonged impact of isoflurane anesthesia on DG. This work presents a suitable approach for studying brain activities during general anesthesia and provides evidence for distinct effects of isoflurane anesthesia on hippocampal subregions.

Astrocyte-derived lactate aggravates brain injury of ischemic stroke in mice by promoting the formation of protein lactylation.

Aim: Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether the role of accumulated lactate at the ischemia phase is neuroprotection or not remains largely unknown. Thus, in this study, we aimed to investigate the roles and mechanisms of accumulated brain lactate at the ischemia stage in regulating brain injury of ischemic stroke. Methods and Results: Pharmacological inhibition of lactate production by either inhibiting LDHA or glycolysis markedly attenuated the mouse brain injury of ischemic stroke. In contrast, additional lactate supplement further aggravates brain injury, which may be closely related to the induction of neuronal death and A1 astrocytes. The contributing roles of increased lactate at the ischemic stage may be related to the promotive formation of protein lysine lactylation (Kla), while the post-treatment of lactate at the reperfusion stage did not influence the brain protein Kla levels with neuroprotection. Increased protein Kla levels were found mainly in neurons by the HPLC-MS/MS analysis and immunofluorescent staining. Then, pharmacological inhibition of lactate production or blocking the lactate shuttle to neurons showed markedly decreased protein Kla levels in the ischemic brains. Additionally, Ldha specific knockout in astrocytes (Aldh1l1 CreERT2; Ldha fl/fl mice, cKO) mice with MCAO were constructed and the results showed that the protein Kla level was decreased accompanied by a decrease in the volume of cerebral infarction in cKO mice compared to the control groups. Furthermore, blocking the protein Kla formation by inhibiting the writer p300 with its antagonist A-485 significantly alleviates neuronal death and glial activation of cerebral ischemia with a reduction in the protein Kla level, resulting in extending reperfusion window and improving functional recovery for ischemic stroke. Conclusion: Collectively, increased brain lactate derived from astrocytes aggravates ischemic brain injury by promoting the protein Kla formation, suggesting that inhibiting lactate production or the formation of protein Kla at the ischemia stage presents new therapeutic targets for the treatment of ischemic stroke.

Homeostatic Shrinkage of Dendritic Spines Requires Melatonin Type 3 Receptor Activation During Sleep.

High-frequency oscillatory activity in cognition-related neural circuits during wakefulness consistently induces the growth of dendritic spines and axonal terminals. Although these structural changes are essential for cognitive functions, it is hypothesized that if these newly expanded structures fail to establish functional connections, they may become superfluous. Sleep is believed to facilitate the reduction of such redundant structures to maintain neural homeostasis. However, the mechanisms underlying this pruning process during sleep remain poorly understood. In this study, that melatonin type 3 receptors (MT3Rs) are selectively expressed in the stellate neurons of the medial entorhinal cortex (MEC) is demonstrated, an area where high melatonin levels are detected during sleep. Activation of MT3Rs during sleep initiates the shrinkage of dendritic spines in stellate neurons by downregulating neural network activity and dephosphorylating synaptic proteins in the MEC. This process is disrupted when MT3R expression is knocked down or when MT3Rs are blocked during sleep. Notably, interference with MT3Rs in the MEC during sleep impairs the acquisition of spatial memory but does not affect object memory acquisition following sleep. These findings reveal novel molecular mechanisms involving melatonin and MT3Rs in the regulation of dendritic spine shrinkage during sleep, which is crucial for the acquisition and consolidation of spatial memory.

Baitouweng decoction suppresses growth of esophageal carcinoma cells through miR-495-3p/BUB1/STAT3 axis.

BACKGROUND: Esophageal carcinoma (EC) is one of the most prevalent cancers in human populations worldwide. Baitouweng decoction is one of the most important Chinese medicine formulas, with the potential to treat cancer. AIM: To investigate the role and mechanism of Baitouweng decoction on EC cells. METHODS: Differentially expressed genes (DEGs) in EC tissues and normal tissues were screened by the cDNA microarray technique and by bioinformatics methods. The target genes of microRNAs were predicted based on the TargetScan database and verified by dual luciferase gene reporter assay. We used Baitouweng decoction to intervene EC cells, and detected the activity of EC9706 and KYSE150 cells by the MTT method. Cell cycle and apoptosis were measured by flow cytometry. The expression of BUB1 mRNA and miR-495-3p was measured by qRT-PCR. The protein levels of BUB1, STAT3, p-STAT3, CCNB1, CDK1, Bax, Caspase3, and Caspase9 were measured by Western blot analysis. The migration and invasion abilities of the cells were measured by wound-healing assay and Transwell invasion assay, respectively. RESULTS: DEGs identified are involved in biological processes, signaling pathways, and network construction, which are mainly related to mitosis. BUB1 was the key hub gene, and it is also a target gene of miR-495-3p. Baitouweng decoction could upregulate miR-495-3p and inhibit BUB1 expression. In vitro experiments showed that Baitouweng decoction significantly inhibited the migration and invasion of EC cells and induced apoptosis and G2/M phase arrest. After treatment with Baitouweng decoction, the expression of Bax, Caspase 3, and Caspase 9 in EC cells increased significantly, while the expression of BUB1, CCNB1, and CDK1 decreased significantly. Moreover, the STAT3 signaling pathway may play an important role in this process. CONCLUSION: Baitouweng decoction has a significant inhibitory effect on EC cell growth. BUB1 is a potential therapeutic target for EC. Further analysis showed that Baitouweng decoction may inhibit the growth of EC cells by upregulating miR-495-3p targeting the BUB1-mediated STAT3 signal pathway.

Induced-aggregates in photocatalysis: An unexplored approach to reduce the noble metal co-catalyst content.

Photocatalysis has emerged as a promising and environmentally sustainable solution to produce high-purity hydrogen through ethanol photoreforming. It is commonly accepted that adding co-catalysts, especially noble metals, significantly enhances the catalytic activity of semiconductors. However, the high cost of noble metals such as Pt may limit the real application of this emerging technology. Here we evaluate the possibility of reducing the noble metal loading by creating the appropriate interface between pre-formed semiconductor nanoparticles. Commercial titania (P25) was selected as the semiconductor due to its commercial availability, facilitating the straightforward validation and corroboration of our results. Pt was selected as co-catalyst because one of the most efficient photocatalysts for the ethanol photo-reforming is still based on the use of P25 in combination with Pt. We report that the creation of induced aggregates dramatically improves the total hydrogen produced when very low loadings (≤0.05 wt%) of Pt are used. We have developed a pioneering reactor designed for conducting photoluminescence studies under authentic operational conditions of nanoparticle suspensions in the liquid phase. This approach allows us to obtain the average photoluminescence emission from the P25 agglomerates what it would be impossible to obtain by using standard solid samples holders. Thanks to this equipment, we can conclude that this remarkable improvement of the activity is mainly due to creation of an interface that favors the charge transfer between the particles of the aggregates. According to this, the titania nanoparticles of the agglomerates act as an antenna to collect the photons of the sun-light and produce the photo-excited electrons that will be transferred to the platinum nanoparticles located in the same agglomeration. In contrast, raw P25 with low loadings of Pt would have a high number of titania nanoparticles without platinum, and therefore, inactive. This result would be especially relevant in the case of immobilized photocatalytic systems for real future photocatalytic reactors because the immobilization of the semiconductors would generate similar interactions to the one created by our method. Consequently, the initial semiconductor immobilization followed by the subsequent photo-deposition of the co-catalyst emerges as a promising approach for a substantial reduction of the co-catalyst content.

A rapid quarantine approach for the pathogenic and invasive Phytophthora species associated with imported fruits in China.

BACKGROUND: Phytophthora spp. represent a pivotal genus of plant pathogens with a global distribution, exerting significant deleterious effects on food safety and forestry ecosystems. Numerous pathogenic and invasive Phytophthora species, introduced through imported fruits, have been frequently detected at Chinese ports. With the rise in global trade activities, the plant quarantine of imported fruits is becoming increasingly important but challenging. Fast, simple, and labor-saving techniques are necessary and anticipated. RESUITS: A polymerase chain reaction restriction fragment length polymorphism capillary electrophoresis (PCR-RFLP-CE) technology-based quarantine approach was developed for 16 Phytophthora species associated with the imported fruits in China. The Ypt1 gene, exhibiting abundant interspecific variations, was selected as the marker gene for PCR. The restriction endonuclease AluI was proven to be capable and compatible in simultaneously separating different Phytophthora species during CE. By combining with a fast and efficient DNA extraction kit, the developed PCR-RFLP-CE technique was successfully applied to identify Phytophthora species in artificially infested fruits. CONCLUSION: We provide a quick, practical, and high-throughput detection approach for hazardous and invasive Phytophthora species associated with imported fruits in China. This strategy can give good convenience and technological support for carrying out massive quarantine activities at Chinese ports. © 2024 Society of Chemical Industry.

Translating metabolic and cardiovascular research into effective treatments: What's next?

The future of healthcare for cardiovascular diseases holds immense promise, not only based in new discoveries in cardiac metabolism but also in translating them to solutions for critical challenges faced by society. Here, ten scientists share their insights, shedding light on the future that lies ahead for this field.

Unraveling pathogenesis, biomarkers and potential therapeutic agents for endometriosis associated with disulfidptosis based on bioinformatics analysis, machine learning and experiment validation.

BACKGROUND: Endometriosis (EMs) is an enigmatic disease of yet-unknown pathogenesis. Disulfidptosis, a novel identified form of programmed cell death resulting from disulfide stress, stands a chance of treating diverse ailments. However, the potential roles of disulfidptosis-related genes (DRGs) in EMs remain elusive. This study aims to thoroughly explore the key disulfidptosis genes involved in EMs, and probe novel diagnostic markers and candidate therapeutic compounds from the aspect of disulfidptosis based on bioinformatics analysis, machine learning, and animal experiments. RESULTS: Enrichment analysis on key module genes and differentially expressed genes (DEGs) of eutopic and ectopic endometrial tissues in EMs suggested that EMs was closely related to disulfidptosis. And then, we obtained 20 and 16 disulfidptosis-related DEGs in eutopic and ectopic endometrial tissue, respectively. The protein-protein interaction (PPI) network revealed complex interactions between genes, and screened nine and ten hub genes in eutopic and ectopic endometrial tissue, respectively. Furthermore, immune infiltration analysis uncovered distinct differences in the immunocyte, human leukocyte antigen (HLA) gene set, and immune checkpoints in the eutopic and ectopic endometrial tissues when compared with health control. Besides, the hub genes mentioned above showed a close correlation with the immune microenvironment of EMs. Furthermore, four machine learning algorithms were applied to screen signature genes in eutopic and ectopic endometrial tissue, including the binary logistic regression (BLR), the least absolute shrinkage and selection operator (LASSO), the support vector machine-recursive feature elimination (SVM-RFE), and the extreme gradient boosting (XGBoost). Model training and hyperparameter tuning were implemented on 80% of the data using a ten-fold cross-validation method, and tested in the testing sets which determined the excellent diagnostic performance of these models by six indicators (Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, Accuracy, and Area Under Curve). And seven eutopic signature genes (ACTB, GYS1, IQGAP1, MYH10, NUBPL, SLC7A11, TLN1) and five ectopic signature genes (CAPZB, CD2AP, MYH10, OXSM, PDLIM1) were finally identified based on machine learning. The independent validation dataset also showed high accuracy of the signature genes (IQGAP1, SLC7A11, CD2AP, MYH10, PDLIM1) in predicting EMs. Moreover, we screened 12 specific compounds for EMs based on ectopic signature genes and the pharmacological impact of tretinoin on signature genes was further verified in the ectopic lesion in the EMs murine model. CONCLUSION: This study verified a close association between disulfidptosis and EMs based on bioinformatics analysis, machine learning, and animal experiments. Further investigation on the biological mechanism of disulfidptosis in EMs is anticipated to yield novel advancements for searching for potential diagnostic biomarkers and revolutionary therapeutic approaches in EMs.

Linguistic network in early deaf individuals: A neuroimaging meta-analysis.

This meta-analysis summarizes evidence from 44 neuroimaging experiments and characterizes the general linguistic network in early deaf individuals. Meta-analytic comparisons with hearing individuals found that a specific set of regions (in particular the left inferior frontal gyrus and posterior middle temporal gyrus) participates in supramodal language processing. In addition to previously described modality-specific differences, the present study showed that the left calcarine gyrus and the right caudate were additionally recruited in deaf compared with hearing individuals. In addition, this study showed that the bilateral posterior superior temporal gyrus is shaped by cross-modal plasticity, whereas the left frontotemporal areas are shaped by early language experience. Although an overall left-lateralized pattern for language processing was observed in the early deaf individuals, regional lateralization was altered in the inferior temporal gyrus and anterior temporal lobe. These findings indicate that the core language network functions in a modality-independent manner, and provide a foundation for determining the contributions of sensory and linguistic experiences in shaping the neural bases of language processing.

FBLN2 is associated with Goldenhar syndrome and is essential for cranial neural crest cell development.

Goldenhar syndrome, a rare craniofacial malformation, is characterized by developmental anomalies in the first and second pharyngeal arches. Its etiology is considered to be heterogenous, including both genetic and environmental factors that remain largely unknown. To further elucidate the genetic cause in a five-generation Goldenhar syndrome pedigree and exploit the whole-exome sequencing (WES) data of this pedigree, we generated collapsed haplotype pattern markers based on WES and employed rare variant nonparametric linkage analysis. FBLN2 was identified as a candidate gene via analysis of WES data across the significant linkage region. A fbln2 knockout zebrafish line was established by CRISPR/Cas9 to examine the gene's role in craniofacial cartilage development. fbln2 was expressed specifically in the mandible during the zebrafish early development, while fbln2 knockout zebrafish exhibited craniofacial malformations with abnormal chondrocyte morphologies. Functional studies revealed that fbln2 knockout caused abnormal chondrogenic differentiation, apoptosis, and proliferation of cranial neural crest cells (CNCCs), and downregulated the bone morphogenic protein (BMP) signaling pathway in the zebrafish model. This study demonstrates the role of FBLN2 in CNCC development and BMP pathway regulation, and highlights FBLN2 as a candidate gene for Goldenhar syndrome, which may have implications for the selection of potential screening targets and the development of treatments for conditions like microtia-atresia.

Circulating tumor DNA as prognostic markers of relapsed breast cancer: a systematic review and meta-analysis.

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognosis biomarker in patients of breast cancer. This review aims to assess the clinical value of ctDNA in outcome prediction in breast cancer patients throughout the whole treatment cycle. Methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov were searched from January 2016 to May 2022. Conference abstracts published in last three years were also included. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English languages were included. The following pre-specified criteria should be met for inclusion: (1) observational studies (prospective or retrospective), randomized control trials, case-control studies and case series studies; (2) patients with breast cancer; (3) ctDNA measurement; (4) clinical outcome data such as objective response rate (ORR), pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS), and so on. The random-effect model was preferred considering the potential heterogeneity across studies. The primary outcomes included postoperative short-term outcomes (ORR and pCR) and postoperative long-term outcomes (RFS, OS, and relapse). Secondary outcomes focused on ctDNA detection rate. Results: A total of 30 studies, comprising of 19 cohort studies, 2 case-control studies and 9 case series studies were included. The baseline ctDNA was significantly negatively associated with ORR outcome (Relative Risk [RR] = 0.65, 95% confidence interval [CI]: 0.50-0.83), with lower ORR in the ctDNA-positive group than ctDNA-negative group. ctDNA during neoadjuvant therapy (NAT) treatment was significantly associated with pCR outcomes (Odds Ratio [OR] = 0.15, 95% CI: 0.04-0.54). The strong association between ctDNA and RFS or relapse outcome was significant across the whole treatment period, especially after the surgery (RFS: Hazard Ratio [HR] = 6.74, 95% CI: 3.73-12.17; relapse outcome: RR = 7.11, 95% CI: 3.05-16.53), although there was heterogeneity in these results. Pre-operative and post-operative ctDNA measurements were significantly associated with OS outcomes (pre-operative: HR = 2.03, 95% CI: 1.12-3.70; post-operative: HR = 6.03, 95% CI: 1.31-27.78). Conclusions: In this review, ctDNA measurements at different timepoints are correlated with evaluation indexes at different periods after treatment. The ctDNA can be used as an early potential postoperative prognosis biomarker in breast cancer, and also as a reference index to evaluate the therapeutic effect at different stages.

Clinical features and management strategies concerning auditory canal duplication anomalies in children with congenital first branchial cleft anomalies.

OBJECTIVE: This study aimed to summarise the clinical features and management strategies concerning auditory canal duplication anomalies in children with congenital first branchial cleft anomalies (CFBCAs), and to provide guidance for precise treatment. METHODS: We retrospectively analysed 84 children with CFBCAs who had complete data, diagnosed between December 2018 and February 2024. RESULTS: All the lesions identified were located around the external auditory canal or near the mandibular angle, manifested as pinhead-sized perforations in 10 cases, painless masses in 18 cases, recurrent swelling and pain with purulent discharge in 52 cases, and otorrhea in 4 cases. Otoscopy examinations revealed external auditory canal swelling in seven children, fistulas within the auditory canal in four children, and a myringa web in three children. Fifty-six children had a preoperative history of infection. Using Work's classification system, Work I and II in 70 (87.5%) and 14 (12.5%) children, respectively. Intraoperatively, 80 (95.2%) children had auditory canal duplication anomalies at the base of the lesion, closely associated with the cartilage of the inferior wall of external auditory canal(EAC), We then classified auditory canal duplication anomalies into three types: Type A (duplication anomalies of epithelial tissue structure between the skin of the EAC and the cartilage of the inferior wall, n = 16 children), Type B (duplication anomalies of the epithelial and/or skin tissue structure, sharing a wall with the cartilage of the inferior wall, n = 40), and Type C (duplication anomalies of the skin and cartilage tissue structure, connected to the cartilage of the inferior wall of EAC, n = 24). Sixty-eight children had lesions superficial to the facial nerve, 12 had lesions deep to the facial nerve, and four had lesions between branches. There were two cases of transient postoperative facial paralysis, three cases of CFBCA recurrence, and two cases of transient auditory canal stenosis. CONCLUSION: Auditory canal duplication anomalies are an important feature of first branchial cleft anomalies in children. Precise staging and accurate identification of the base of the lesion facilitate complete removal, thereby increasing the cure rate.

Simulator Verification Is Potentially Beneficial for the Fitting of Softband Bone Conduction Hearing Devices in Young Children.

HYPOTHESIS: The current study employed a skull-simulator verification method to assess whether the output of softband bone conduction hearing devices (BCHDs) at the manufacturer's default settings deviated widely from the target determined by the fitting formula. BACKGROUND: Real ear analysis is utilized for the verification of the fitting of air conduction hearing devices (ACHDs) in a variety of institutions. This procedure, however, has not been used in the fitting of BCHDs, largely due to the difficulty of testing the output of these devices to temporal bones. Despite the availability of skull simulators, they have not been utilized clinically to measure BCHD output. MATERIALS AND METHODS: This prospective, single-center study enrolled 42 subjects, aged 3 months to 10 years, with microtia-atresia-associated mild-to-severe bilateral conductive hearing loss. Hearing sensitivity was evaluated behaviorally by pure tone audiometry (PTA) in 22 subjects 4 years or older (the PTA group), and by auditory brainstem response (ABR) in 20 subjects younger than 4 years (the ABR group). Following 6 months of subjects wearing the prescribed softband BCHDs, their dial level (DL) thresholds were reassessed while using their own BCHDs, configured with zero gain across all frequencies, functioning solely as a bone vibrator. These DL thresholds were inputted into the fitting formula, desired sensation level-bone conduction devices (DSL-BCD) for children, to obtain the target values of BCHD output. The simulator output of the BCHD programmed at the manufacturer's default setting was measured in response to speech presented at 55, 65, and 80 dB SPL, followed by gain adjustment based on the differences between the simulator output and the target. Aided speech intelligibility index (SII) was measured before and after the gain adjustment. RESULTS: The softband BCHDs at the manufacturer's settings generally had lower output than the prescribed target values. This difference was larger at low frequencies and low levels. Across the 12 points tested (four frequencies from 500 to 4000 Hz multiplied by three levels), 22 (52.3%) and 42 (100%) BCHDs had deviations of +7 and +5 dB, respectively, at one point or more. The gain adjustments reduced the deviation and improved the SII values at the two lower levels of speech presented. CONCLUSION: The simulator output of softband bone conduction hearing devices (BCHDs) with the manufacturer's settings may exhibit significant deviations from the formula. Objective output verification should be considered a beneficial step in BCHD fitting and is recommended when applicable.

Zearalenone degrading enzyme evolution to increase the hydrolysis efficiency under acidic conditions by the rational design.

Based on rational design, zearalenone degrading enzyme was evolved to improve the hydrolysis efficiency under acidic conditions. At pH 4.2 and 37 °C, the activity of the zearalenone degrading enzyme evolved with 8 mutation sites increased from 7.69 U/mg to 38.67 U/mg. Km of the evolved zearalenone degrading enzyme decreased from 283.61 µM to 75.33 µM. The evolved zearalenone degrading enzyme was found to effectively degrade zearalenone in pig stomach chyme. Molecular docking revealed an increase in the number of hydrogen bonds and π-sigma interactions between the evolved zearalenone degrading enzyme and zearalenone. The evolved zearalenone degrading enzyme was valuable for hydrolyzing zearalenone under acidic conditions.

NeuroSeg-III: efficient neuron segmentation in two-photon Ca2+ imaging data using self-supervised learning.

Two-photon Ca2+ imaging technology increasingly plays an essential role in neuroscience research. However, the requirement for extensive professional annotation poses a significant challenge to improving the performance of neuron segmentation models. Here, we present NeuroSeg-III, an innovative self-supervised learning approach specifically designed to achieve fast and precise segmentation of neurons in imaging data. This approach consists of two modules: a self-supervised pre-training network and a segmentation network. After pre-training the encoder of the segmentation network via a self-supervised learning method without any annotated data, we only need to fine-tune the segmentation network with a small amount of annotated data. The segmentation network is designed with YOLOv8s, FasterNet, efficient multi-scale attention mechanism (EMA), and bi-directional feature pyramid network (BiFPN), which enhanced the model's segmentation accuracy while reducing the computational cost and parameters. The generalization of our approach was validated across different Ca2+ indicators and scales of imaging data. Significantly, the proposed neuron segmentation approach exhibits exceptional speed and accuracy, surpassing the current state-of-the-art benchmarks when evaluated using a publicly available dataset. The results underscore the effectiveness of NeuroSeg-III, with employing an efficient training strategy tailored for two-photon Ca2+ imaging data and delivering remarkable precision in neuron segmentation.

Possible adverse events of imidazole antifungal drugs during treatment of vulvovaginal candidiasis: analysis of the FDA Adverse Event Reporting System.

Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been systematically analyzed in the real world. We used the FDA Adverse Event Reporting System (FAERS) to investigate the adverse events (AEs) associated with imidazole therapy for VVC. FAERS data (from quarter 1 2004 to quarter 3 2022) were retrieved using OpenVigil 2.1, and AEs were retrieved and standardized according to the Medical Dictionary for Regulatory Activities (MedDRA). In the top 10 System Organ Class (SOC), all four drugs have been found to have kidney and urinary system diseases and pregnancy. We found significant signals, including clotrimazole [bladder transitional cell carcinoma, (report odds ratio, ROR = 291.66)], [fetal death, (ROR = 10.28)], ketoconazole[nephrogenic anemia (ROR = 22.1)], [premature rupture of membranes (ROR = 22.91 46.45, 11, 3)], Miconazole[hematuria (ROR = 19.03)], [neonatal sepsis (ROR = 123.71)], [spontaneous abortion (ROR = 5.98)], Econazole [acute kidney injury (ROR = 4.41)], [spontaneous abortion (ROR = 19.62)]. We also discovered new adverse reactions that were not reported. Therefore, when using imidazole drugs for treatment, it is necessary to closely monitor the patient's renal function, pay attention to the developmental toxicity of the fetus during pregnancy, and be aware of potential adverse reactions that may occur.

Effects of the Interaction between Rumen Microbiota Density-VFAs-Hepatic Gluconeogenesis on the Adaptability of Tibetan Sheep to Plateau.

During the adaptive evolution of animals, the host and its gut microbiota co-adapt to different elevations. Currently, there are few reports on the rumen microbiota-hepato-intestinal axis of Tibetan sheep at different altitudes. Therefore, the purpose of this study was to explore the regulatory effect of rumen microorganism-volatile fatty acids (VFAs)-VFAs transporter gene interactions on the key enzymes and genes related to gluconeogenesis in Tibetan sheep. The rumen fermentation parameters, rumen microbial densities, liver gluconeogenesis activity and related genes were determined and analyzed using gas chromatography, RT-qPCR and other research methods. Correlation analysis revealed a reciprocal relationship among rumen microflora-VFAs-hepatic gluconeogenesis in Tibetan sheep at different altitudes. Among the microbiota, Ruminococcus flavefaciens (R. flavefaciens), Ruminococcus albus (R. albus), Fibrobactersuccinogenes and Ruminobacter amylophilus (R. amylophilus) were significantly correlated with propionic acid (p < 0.05), while propionic acid was significantly correlated with the transport genes monocarboxylate transporter 4 (MCT4) and anion exchanger 2 (AE2) (p < 0.05). Propionic acid was significantly correlated with key enzymes such as pyruvate carboxylase, phosphoenolpyruvic acid carboxylase and glucose (Glu) in the gluconeogenesis pathway (p < 0.05). Additionally, the expressions of these genes were significantly correlated with those of the related genes, namely, forkhead box protein O1 (FOXO1) and mitochondrial phosphoenolpyruvate carboxykinase 2 (PCK2) (p < 0.05). The results showed that rumen microbiota densities differed at different altitudes, and the metabolically produced VFA contents differed, which led to adaptive changes in the key enzyme activities of gluconeogenesis and the expressions of related genes.

[Cardiovascular safety of sitagliptin added to metformin in real world patients with type 2 diabetes].

OBJECTIVE: To assess the safety of sitagliptin added to metformin on cardiovascular adverse events in real world patients with type 2 diabetes mellitus (T2DM). METHODS: Real world data from Yinzhou Regional Health Care Database were used to select T2DM patients with diagnosis and treatment records in the platform from January 1, 2017 to December 31, 2022. According to drug prescription records, the patients were divided into metformin plus sitagliptin group (combination group) and metformin monotherapy group(monotherapy group). A series of retrospective cohorts were constructed according to the index date.Finally, full retrospective cohorts were constructed according to propensity score model, including baseline covariates that might be related to outcomes, to match the subjects in the combination group and monotherapy group for the purpose of increasing the comparability of baseline characteristics. The participants were followed up from the index date until the first occurrence of the following events: Diagnosis of outcomes, death, or the end of the study period (December 31, 2022). Cox proportional risk model was used to estimate the hazard ratio(HR)and 95% confidence interval (CI) of sitagliptin added to metformin on 3-point major adverse cardiovascular events (3P-MACE) combination outcome and secondary cardiovascular outcomes. RESULTS: Before propensity score matching, the proportion of the patients in combination group using insulin, α glucosidase inhibitors, sodium-glucose transporter 2 inhibitors (SGLT-2I) and glienides at baseline was higher than that in monotherapy group, and the baseline fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels in combination group were higher than those in monotherapy group. After propensity score matching, 5 416 subjects were included in the combination group and the monotherapy group, and baseline characteristics were effectively balanced between the groups. The incidence densities of 3P-MACE were 6.41/100 person years and 6.35/100 person years, respectively. Sitagliptin added to metformin did not increase or decrease the risk of 3P-MACE compared with the metformin monotherapy (HR=1.00, 95% CI: 0.91-1.10). In secondary outcomes analysis, the incidence of cardiovascular death was lower in the combination group than in the monotherapy group (HR=0.59, 95% CI: 0.41-0.85), and no association was found between sitagliptin and the risk of myocardial infarction and stroke (HR=1.12, 95% CI: 0.89-1.41; HR=0.99, 95% CI: 0.91-1.12). CONCLUSION: In T2DM patients in Yinzhou district of Ningbo, compared with metformin alone, sitagliptin added to metformin may reduce the risk of cardiovascular death, and do not increase the incidence of overall cardiovascular events. The results of this study can provide real-world evidence for post-marketing cardiovascular safety evaluation of sitagliptin.

Effect of task-oriented training assisted by force feedback hand rehabilitation robot on finger grasping function in stroke patients with hemiplegia: a randomised controlled trial.

BACKGROUND: Over 80% of patients with stroke experience finger grasping dysfunction, affecting independence in activities of daily living and quality of life. In routine training, task-oriented training is usually used for functional hand training, which may improve finger grasping performance after stroke, while augmented therapy may lead to a better treatment outcome. As a new technology-supported training, the hand rehabilitation robot provides opportunities to improve the therapeutic effect by increasing the training intensity. However, most hand rehabilitation robots commonly applied in clinics are based on a passive training mode and lack the sensory feedback function of fingers, which is not conducive to patients completing more accurate grasping movements. A force feedback hand rehabilitation robot can compensate for these defects. However, its clinical efficacy in patients with stroke remains unknown. This study aimed to investigate the effectiveness and added value of a force feedback hand rehabilitation robot combined with task-oriented training in stroke patients with hemiplegia. METHODS: In this single-blinded randomised controlled trial, 44 stroke patients with hemiplegia were randomly divided into experimental (n = 22) and control (n = 22) groups. Both groups received 40 min/day of conventional upper limb rehabilitation training. The experimental group received 20 min/day of task-oriented training assisted by a force feedback rehabilitation robot, and the control group received 20 min/day of task-oriented training assisted by therapists. Training was provided for 4 weeks, 5 times/week. The Fugl-Meyer motor function assessment of the hand part (FMA-Hand), Action Research Arm Test (ARAT), grip strength, Modified Ashworth scale (MAS), range of motion (ROM), Brunnstrom recovery stages of the hand (BRS-H), and Barthel index (BI) were used to evaluate the effect of two groups before and after treatment. RESULTS: Intra-group comparison: In both groups, the FMA-Hand, ARAT, grip strength, AROM, BRS-H, and BI scores after 4 weeks of treatment were significantly higher than those before treatment (p < 0.05), whereas there was no significant difference in finger flexor MAS scores before and after treatment (p > 0.05). Inter-group comparison: After 4 weeks of treatment, the experimental group's FMA-Hand total score, ARAT, grip strength, and AROM were significantly better than those of the control group (p < 0.05). However, there were no statistically significant differences in the scores of each sub-item of the FMA-Hand after Bonferroni correction (p > 0.007). In addition, there were no statistically significant differences in MAS, BRS-H, and BI scores (p > 0.05). CONCLUSION: Hand performance improved in patients with stroke after 4 weeks of task-oriented training. The use of a force feedback hand rehabilitation robot to support task-oriented training showed additional value over conventional task-oriented training in stroke patients with hand dysfunction. CLINICAL TRIAL REGISTRATION INFORMATION: NCT05841108.