Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction.

An efficient protocol for the synthesis of polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine-3,4b,5,6,7(1H)-pentacarboxylates was developed by a three-component reaction. In the absence of any catalyst, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile afforded polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine-3,4b,5,6,7(1H)-pentacarboxylates in high yields and with high diastereoselectivity. The reaction was finished by in situ generation of activated 5-(alkylimino)cyclopenta-1,3-dienes from addition of alkyl isocyanide to two molecules of but-2-ynedioates and sequential formal [3 + 2] cycloaddition reaction with 5,6-unsubstituted 1,4-dihydropyridine.

PD-L2 Expression in Breast Cancer Promotes Tumor Development and Progression.

Background: This work focused on investigating the role of programmed death ligand 2 (PD-L2) in the progression of breast cancer by utilizing breast cancer specimens and cells. Materials and Methods: The serum levels of soluble PD-L2 (sPD-L2) in breast cancer patients and healthy individuals were analyzed by means of the enzyme-linked immunosorbent assay, and the PD-L2 levels within 416 resected breast cancer specimens were assessed through immunohistochemistry. Concurrently, in vitro cell experiments and in vivo animal experiments were carried out to analyze the relationship between PD-L2 and the invasion and migration of breast cancer. Results: The concentration of sPD-L2 in breast cancer patients significantly increased compared to that in the control groups. Additionally, breast cancer patients with high concentrations of sPD-L2 had higher Ki67 values (≥30%) and tumor grades. PD-L2 was expressed in 79.09% of the cancer samples, which exhibited a positive correlation with the progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2). Furthermore, we discovered that knockdown of PD-L2 inhibited the migratory and invasive abilities of both MCF-7 and MDA-MB231 cells. Conclusion: Our findings demonstrated that knockdown of PD-L2 suppressed tumor growth, providing novel insights into important biological functions.

Vedolizumab plus basiliximab as second-line therapy for steroid-refractory lower gastrointestinal acute graft-versus-host disease.

Background: Steroid-resistant (SR) lower gastrointestinal (LGI) tract graft-versus-host disease (GVHD) is the predominant cause of morbidity and mortality from GVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The role of vedolizumab in the treatment of SR-LGI acute GVHD (aGVHD) remains uncertain. We aimed to assess the efficacy and safety of vedolizumab combined with basiliximab as second-line therapy for SR-LGI-aGVHD. Methods: This study aimed to explore the efficacy of vedolizumab combined with basiliximab for SR-LGI-aGVHD. The primary endpoint was the overall response (OR) on day 28. Secondary and safety endpoints included durable OR at day 56, overall survival (OS), chronic GVHD (cGVHD), non-relapse mortality (NRM), failure-free survival (FFS), and adverse events. Results: Twenty-eight patients with SR-LGI-aGVHD were included. The median time to start of combination therapy after SR-LGI-aGVHD diagnosis was 7 (range, 4-16) days. The overall response rate (ORR) at 28 days was 75.0% (95% CI: 54.8%-88.6%), and 18 achieved a complete response (CR) (64.3%, 95% CI: 44.1%-80.7%). The durable OR at day 56 was 64.3% (95% CI: 44.1%-80.7%). The 100-day, 6-month, and 12-month OS rates for the entire cohort of patients were 60.7% (95% CI: 45.1%-81.8%), 60.7% (95% CI: 45.1%-81.8%), and 47.6% (95% CI: 31.4%-72.1%), respectively. The median failure-free survival was 276 days; (95% CI: 50-not evaluable) 12-month NRM was 42.9% (95% CI: 24.1%-60.3%). The 1-year cumulative incidence of cGVHD was 35.7%. Within 180 days after study treatments, the most common grade 3 and 4 adverse events were infections. Nine (32.1%) patients developed cytomegalovirus (CMV) reactivation complicated with bacterial infections (25.0%, CMV infection; 7.1%, CMV viremia). Epstein-Barr virus (EBV) reactivation occurred in five patients (17.9%, 95% CI: 6.8%-37.6%). Only three patients (10.7%, 95% CI: 2.8%-29.4%) in our study developed pseudomembranous colitis. Conclusions: Vedolizumab plus basiliximab demonstrated efficacy in severe SR-LGI-aGVHD and was well-tolerated. Vedolizumab plus basiliximab may be considered a potential treatment option for patients with LGI-aGVHD.

Multicolor Tuning of Perylene Diimides Dyes for Targeted Organelle Imaging In Vivo.

The adjustment of the emission wavelengths and cell permeability of the perylene diimides (PDI) for multicolor cell imaging is a great challenge. Herein, based on a bay-region substituent engineering strategy, multicolor perylene diimides (MCPDI) were rationally designed and synthesized by introducing azetidine substituents on the bay region of PDIs. With the fine-tuned electron-donating ability of the azetidine substituents, these MCPDI showed high brightness, orange, red, and near infrared (NIR) fluorescence along with Stokes shifts increasing from 35 to 110 nm. Interestingly, azetidine substituents distorted to the plane of the MCPDI dyes, and the twist angle of monosubstituted MCPDI was larger than that of disubstituted MCPDI, which might efficiently decrease their π-π stacking. Moreover, all of these MCPDI dyes were cell-permeable and selectively stained various organelles for multicolor imaging of multiple organelles in living cells. Two-color imaging of lipid droplets (LDs) and other organelles stained with MCPDI dyes was performed to reveal the interaction between the LDs and other organelles in living cells. Furthermore, a NIR-emitting MCPDI dye with a mitochondria-targeted characteristic was successfully applied for tumor-specific imaging. The facile synthesis, excellent stability, high brightness, tunable fluorescence emission, and Stokes shifts make these MCPDI promising fluorescent probes for biological applications.

The role of Phafin proteins in cell signaling pathways and diseases.

Membrane-associated proteins are important membrane readers that mediate and facilitate the signaling and trafficking pathways in eukaryotic membrane-bound compartments. The protein members in the Phafin family are membrane readers containing two phosphoinositide recognition domains: the Pleckstrin Homology domain and the FYVE (Fab1, YOTB, Vac1, and early endosome antigen 1) domain. Phafin proteins, categorized into two subfamilies, Phafin1 and Phafin2, associate with cellular membranes through interactions involving membrane-embedded phosphoinositides and phosphoinositide-binding domains. These membrane-associated Phafin proteins play pivotal roles by recruiting binding partners and forming complexes, which contribute significantly to apoptotic, autophagic, and macropinocytotic pathways. Elevated expression levels of Phafin1 and Phafin2 are observed in various cancers. A recent study highlights a significant increase in Phafin1 protein levels in the lungs of idiopathic pulmonary fibrosis patients compared to normal subjects, suggesting a crucial role for Phafin1 in the pathogenesis of pulmonary fibrosis. Additionally, phosphatidylinositol-3-phosphate-binding 2 (Pib2), a close relative of the Phafin1 protein, functions as an amino acid sensor activating the TOCR1 pathway in yeasts. This review focuses on delineating the involvement of Phafin proteins in cellular signaling and their implications in diseases and briefly discusses the latest research findings concerning Pib2.

Investigating the therapeutic mechanism of Jiedu-Quyu-Ziyin Fang on systemic lupus erythematosus through the ERα-miRNA-TLR7 immune axis.

Jiedu-Quyu-Ziyin Fang (JQZF) is a formula that has been empirically used for the treatment of SLE in clinical practice. JQZF has become an approved hospital prescription in China. Fifteen MRL/lpr mice were randomly divided into three groups: Model, JQZF, and JQZF + GC, with five mice in each group. Five MRL/MPJ mice were used as the Blank group. After 8 weeks of administration, peripheral blood serum was collected to detect anti-dsDNA antibodies and complement C3 levels. Spleen B cells were collected to detect the expression of TLR7 and NF-κBp65 mRNA, and correlation analysis was performed. Transcriptome sequencing analysis was also performed on spleen B cells. Further, key miRNA and key gene mRNA expression were detected by RT-qPCR, and key protein expression levels were detected by Western blot method. Bioinformatics methods predicted that ESR1 is a key target of JQZF action on SLE, hsa-miR-146a-5p is one of the key miRNAs, and KEGG pathway analysis showed that NF-κB signaling pathway is its key signaling pathway. Transcriptome sequencing of MRL/lpr mouse spleen B cells revealed that the differential genes between the JQZF and Model groups were enriched in Toll-like receptor signaling pathway, NF-κB signaling pathway, Estrogen signaling pathway, etc. Animal studies show that JQZF treatment significantly boosts serum C3 and lowers anti-dsDNA antibodies (P < 0.01). On the molecular level, JQZF suppresses TLR7 and NF-κBp65 mRNA in spleen B cells, with TLR7 mRNA positively linked to anti-dsDNA titers and negatively to serum C3. Further cellular work demonstrates that JQZF reverses the increased IRAK1 and TRAF6 expression seen after miR146a inhibition. Additionally, post-ERα inhibition, JQZF continues to upregulate miR146a and more significantly reduces TLR7 mRNA expression (P < 0.01), pointing to ERα's pivotal role in the miR146a-TLR7 axis. These results indicate JQZF alleviates SLE by adjusting the ERα-miR146a-TLR7 loop, showcasing its mechanism and therapeutic potential for SLE.

Brain network functional connectivity changes in long illness duration chronic schizophrenia.

Introduction: Chronic schizophrenia has a course of 5 years or more and has a widespread abnormalities in brain functional connectivity. This study aimed to find characteristic functional and structural changes in a long illness duration chronic schizophrenia (10 years or more). Methods: Thirty-six patients with a long illness duration chronic schizophrenia and 38 healthy controls were analyzed by independent component analysis of brain network functional connectivity. Correlation analysis with clinical duration was performed on six resting state networks: auditory network, default mode network, dorsal attention network, fronto-parietal network, somatomotor network, and visual network. Results: The differences in the resting state network between the two groups revealed that patients exhibited enhanced inter-network connections between default mode network and multiple brain networks, while the inter-network connections between somatomotor network, default mode network and visual network were reduced. In patients, functional connectivity of Cuneus_L was negatively correlated with illness duration. Furthermore, receiver operating characteristic curve of functional connectivity showed that changes in Thalamus_L, Rectus_L, Frontal_Mid_R, and Cerebelum_9_L may indicate a longer illness duration chronic schizophrenia. Discussion: In our study, we also confirmed that the course of disease is significantly associated with specific brain regions, and the changes in specific brain regions may indicate that chronic schizophrenia has a course of 10 years or more.

Gingipain and oncostatin M synergistically disrupt kidney tight junctions in periodontitis-associated acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is characterized by rapid renal decline. Periodontitis, a chronic oral inflammatory disease, is increasingly associated with renal dysfunction. Although periodontitis is recognized as a contributor to kidney damage, the mechanisms linking it to AKI remain unclear. METHODS: This study explored the effects of Porphyromonas gingivalis (P. gingivalis) W83-infected periodontitis on AKI in C57BL/6J mice, using ischemia-reperfusion injury 55 days post-infection. Gingipain inhibitors, KYT-1 and KYT-36, were applied. Detection of P. gingivalis was performed using quantitative real-time polymerase chain reaction (qRT-PCR) and PCR, while transcriptome sequencing, qRT-PCR, immunohistochemistry, and immunofluorescence staining assessed renal damage. In vitro, HK-2 cells were exposed to P. gingivalis at a multiplicity of infection of 10 for 48 h, with inhibition by gingipain or oncostatin M (OSM). Disruption of tight junctions (TJs) was quantified using qRT-PCR, transepithelial electrical resistance, and cell counting kit-8 assays. RESULTS: Periodontitis worsened AKI, linked to P. gingivalis infection and renal TJ disruption in the kidney. P. gingivalis infection activated OSM expression, which correlated positively with gingipain. Significantly, OSM and gingipain might collaboratively contribute to the damage of renal TJs, with the reduced expression of TJ proteins. Suppressing gingipain activity presented itself as a protective strategy against the destruction of TJs and the attendant worsening of AKI due to periodontitis. CONCLUSIONS: Our study enhances the understanding of the interplay between periodontitis and AKI, highlighting the harmful impact of P. gingivalis in AKI.

Zona incerta mediates early life isoflurane-induced fear memory deficits.

The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments.

Metagenomic profiling uncovers microbiota and antibiotic resistance patterns across human, chicken, pig fecal, and soil environments.

The ongoing and progressive evolution of antibiotic resistance presents escalating challenges for the clinical management and prevention of bacterial infections. Understanding the makeup of resistance genomes and accurately quantifying the current abundance of antibiotic resistance genes (ARGs) are crucial for assessing the threat of antimicrobial resistance (AMR) to public health. This comprehensive study investigated the distribution and diversity of bacterial community composition, ARGs, and virulence factors (VFs) across human, chicken, pig fecal, and soil microbiomes in various provinces of China. As a result, multidrug resistance was identified across all samples. Core ARGs primarily related to multidrug, MLS (Macrolides-Lincosamide-Streptogramins), and tetracycline resistance were characterized. A significant correlation between ARGs and bacterial taxa was observed, especially in soil samples. Probiotic strains such as Lactobacillus harbored ARGs, potentially contributing to the dissemination of antibiotic resistance. We screened subsets of ARGs from samples from different sources as indicators to assess the level of ARGs contamination in samples, with high accuracy. These results underline the complex relationship between microbial communities, resistance mechanisms, and environmental factors, emphasizing the importance of continued research and monitoring to better understand these dynamics.

Comparison of Polygonatum sibiricum Polysaccharides Found in Young and Mature Rhizomes.

The main active component of Polygonatum sibiricum (P. sibiricum) rhizome is Polygonatum sibiricum Polysaccharide (PsP) with antioxidant function. At present, only the mature rhizome of P. sibiricum is used to extract PsP, while the young rhizome of by-product is discarded directly as waste, resulting in significant wastage of P. sibiricum resources. We used ultrasound-assisted extraction-deep eutectic solvents (UAE-DESs) method to extract PsP of young and mature rhizomes, respectively. The extraction rate, structure composition and antioxidant ability of PsP between young and mature rhizomes were compared, so as to provide references for comprehensive utilization of P. sibiricum resources. The PsP extraction rate (33.88 ± 1.95%) of young rhizome was close to that (45.08 ± 1.92%) of mature rhizomes. The main component (PsP-2) of the PsP in young rhizome contained six kinds of monosaccharides, which belonged to acidic polysaccharides. The above characteristics of the PsP of young rhizome were similar to those of mature rhizome. The PsP of young rhizome also exhibited similar biological activity to that of the mature rhizome, which indicated even more advantages in DPPH free radical scavenging ability. The results of this study support the utility of the young rhizome, consequently helping to avoid unnecessary waste and provide reference for comprehensive utilization of P. sibiricum.

Sex ratio and age of onset in AQP4 antibody-associated NMOSD: a review and meta-analysis.

BACKGROUND: Aquaporin-4 (AQP4) antibody-associated neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated inflammatory disease of the central nervous system. We have undertaken a systematic review and meta-analysis to ascertain the sex ratio and mean age of onset for AQP4 antibody associated NMOSD. We have also explored factors that impact on these demographic data. METHODS: A systematic search of databases was conducted according to the PRISMA guidelines. Articles reporting sex distribution and age of onset for AQP4 antibody-associated NMSOD were reviewed. An initially inclusive approach involving exploration with regression meta-analysis was followed by an analysis of just AQP4 antibody positive cases. RESULTS: A total of 528 articles were screened to yield 89 articles covering 19,415 individuals from 88 population samples. The female:male sex ratio was significantly influenced by the proportion of AQP4 antibody positive cases in the samples studied (p < 0.001). For AQP4 antibody-positive cases the overall estimate of the sex ratio was 8.89 (95% CI 7.78-10.15). For paediatric populations the estimate was 5.68 (95% CI 4.01-8.03) and for late-onset cases, it was 5.48 (95% CI 4.10-7.33). The mean age of onset was significantly associated with the mean life expectancy of the population sampled (p < 0.001). The mean age of onset for AQP4 antibody-positive cases in long-lived populations was 41.7 years versus 33.3 years in the remainder. CONCLUSIONS: The female:male sex ratio and the mean age of onset of AQP4 antibody-associated NMOSD are significantly higher than MS. The sex ratio increases with the proportion of cases that are positive for AQP4 antibodies and the mean age of onset increases with population life expectancy.

Optic nerve compression associated with visual cortex functional alteration in dysthyroid optic neuropathy: A combined orbital and brain imaging study.

AIMS: To investigate the alterations of the optic nerve and visual cortex in dysthyroid optic neuropathy (DON), a subgroup of thyroid eye disease (TED). METHODS: Multiple orbital imaging biomarkers related to optic nerve compression and the amplitude of low-frequency fluctuations (ALFF) of the brain were obtained from 47 patients with DON, 56 TED patients without DON (nDON), and 37 healthy controls (HC). Correlation analyses and diagnostic tests were implemented. RESULTS: Compared with HC, the nDON group showed alterations in orbital imaging biomarkers related to optic nerve compression in posterior segments, as well as ALFF of the right inferior temporal gyrus and left fusiform gyrus. DON differed from nDON group mainly in the modified muscle index of the posterior segment of optic nerve, and ALFF of orbital part of right superior frontal gyrus, right hippocampus, and right superior temporal gyrus. Orbital and brain imaging biomarkers were significantly correlated with each other. Diagnostic models attained an area under a curve of 0.80 for the detection of DON. CONCLUSION: The combined orbital and brain imaging study revealed alterations of the visual pathway in patients with TED and DON as well as provided diagnostic value. The initiation of alterations in the visual cortex in TED may precede the onset of DON.

A review of the polysaccharides against fatigue and the underlying mechanism.

Fatigue is a common physiological state that affects normal human activities. Prolonged fatigue induces a variety of diseases and seriously affects human health, so it is imperative to discover nutritional dietary supplements and treatments without side effects, among which natural anti-fatigue polysaccharides have shown great potential. Polysaccharides, a class of biomolecules produced by a variety of organisms such as plants, animals, bacteria and algae, have attracted much attention in recent years due to their anti-fatigue activity and fewer side effects. This review summarizes the classification, dosage and experimental models of polysaccharides with anti-fatigue activity obtained from different natural sources. We also review the fatigue-relieving effects of these polysaccharides through mechanisms such as modulating oxidative damage, regulating energy metabolism and influencing intestinal flora, as well as the effects of molecular weights, monosaccharide compositions, structural features and chemical modifications of the polysaccharides on their anti-fatigue activities to support their potential application value in functional foods and pharmaceuticals. New valuable insights for future research on natural polysaccharides are also presented in the field of natural production of bio-based functional materials, functional foods and therapeutic agents.

Evaluation of preoperative difficult airway prediction methods for adult patients without obvious airway abnormalities: a systematic review and meta-analysis.

BACKGROUND: This systematic review aims to assist clinical decision-making in selecting appropriate preoperative prediction methods for difficult tracheal intubation by identifying and synthesizing literature on these methods in adult patients undergoing all types of surgery. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. Comprehensive electronic searches across multiple databases were completed on March 28, 2023. Two researchers independently screened, selected studies, and extracted data. A total of 227 articles representing 526 studies were included and evaluated for bias using the QUADAS-2 tool. Meta-Disc software computed pooled sensitivity (SEN), specificity (SPC), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Heterogeneity was assessed using the Spearman correlation coefficient, Cochran's-Q, and I2 index, with meta-regression exploring sources of heterogeneity. Publication bias was evaluated using Deeks' funnel plot. RESULTS: Out of 2906 articles retrieved, 227 met the inclusion criteria, encompassing a total of 686,089 patients. The review examined 11 methods for predicting difficult tracheal intubation, categorized into physical examination, multivariate scoring system, and imaging test. The modified Mallampati test (MMT) showed a SEN of 0.39 and SPC of 0.86, while the thyromental distance (TMD) had a SEN of 0.38 and SPC of 0.83. The upper lip bite test (ULBT) presented a SEN of 0.52 and SPC of 0.84. Multivariate scoring systems like LEMON and Wilson's risk score demonstrated moderate sensitivity and specificity. Imaging tests, particularly ultrasound-based methods such as the distance from the skin to the epiglottis (US-DSE), exhibited higher sensitivity (0.80) and specificity (0.77). Significant heterogeneity was identified across studies, influenced by factors such as sample size and study design. CONCLUSION: No single preoperative prediction method shows clear superiority for predicting difficult tracheal intubation. The evidence supports a combined approach using multiple methods tailored to specific patient demographics and clinical contexts. Future research should focus on integrating advanced technologies like artificial intelligence and deep learning to improve predictive models. Standardizing testing procedures and establishing clear cut-off values are essential for enhancing prediction reliability and accuracy. Implementing a multi-modal predictive approach may reduce unanticipated difficult intubations, improving patient safety and outcomes.

Phosphoribosylpyrophosphate synthetase as a metabolic valve advances Methylobacterium/Methylorubrum phyllosphere colonization and plant growth.

The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive. In the present study, we investigate the significance of methanol assimilation in shaping the success of mutualistic relationships between methylotrophs and plants. A set of strains originating from Methylorubrum extorquens AM1 are subjected to evolutionary pressures to thrive under low methanol conditions. A mutation in the phosphoribosylpyrophosphate synthetase gene is identified, which converts it into a metabolic valve. This valve redirects limited C1-carbon resources towards the synthesis of biomass by up-regulating a non-essential phosphoketolase pathway. These newly acquired bacterial traits demonstrate superior colonization capabilities, even at low abundance, leading to increased growth of inoculated plants. This function is prevalent in Methylobacterium/Methylorubrum strains. In summary, our findings offer insights that could guide the selection of Methylobacterium/Methylorubrum strains for advantageous agricultural applications.

Accuracy of Automatic Processing of Speech-Language Pathologist and Child Talk During School-Based Therapy Sessions.

PURPOSE: This study examines the accuracy of Interaction Detection in Early Childhood Settings (IDEAS), a program that automatically transcribes audio files and estimates linguistic units relevant to speech-language therapy, including part-of-speech units that represent features of language complexity, such as adjectives and coordinating conjunctions. METHOD: Forty-five video-recorded speech-language therapy sessions involving 27 speech-language pathologists (SLPs) and 56 children were used. The F measure determines the accuracy of IDEAS diarization (i.e., speech segmentation and speaker classification). Two additional evaluation metrics, namely, median absolute relative error and correlation, indicate the accuracy of IDEAS for the estimation of linguistic units as compared with two conditions, namely, Oracle (manual diarization) and Voice Type Classifier (existing diarizer with acceptable accuracy). RESULTS: The high F measure for SLP talk data suggests high accuracy of IDEAS diarization for SLP talk but less so for child talk. These differences are reflected in the accuracy of IDEAS linguistic unit estimates. IDEAS median absolute relative error and correlation values for nine of the 10 SLP linguistic unit estimates meet the accuracy criteria, but none of the child linguistic unit estimates meet these criteria. The type of linguistic units also affects IDEAS accuracy. CONCLUSIONS: IDEAS was tailored to educational settings to automatically convert audio recordings into text and to provide linguistic unit estimates in speech-language therapy sessions and classroom settings. Although not perfect, IDEAS is reliable in automatically capturing and returning linguistic units, especially in SLP talk, that are relevant in research and practice. The tool offers a way to automatically measure SLP talk in clinical settings, which will support research seeking to understand how SLP talk influences children's language growth.

Batch Fabrication of Flexible Strain Sensors with High Linearity and Low Hysteresis for Health Monitoring and Motion Detection.

In recent years, flexible strain sensors have gradually come into our lives due to their superiority in the field of biomonitoring. However, these sensors still suffer from poor durability, high hysteresis, and difficulty in calibration, resulting in great hindrance of practical application. Herein, starting with interfacial interaction regulation and structure-induced cracking, flexible strain sensors with high performance are successfully fabricated. In this strategy, dopamine treatment is used to enhance the bonding between flexible substrates and carbon nanotubes (CNT). The combination within the conductive networks is then controlled by substituting the CNT type. Braid-like fibers are employed to achieve controllable expansion of the conductive layer cracks. Finally, we obtain strain sensors that possess high linearity (R2 = 0.997) with low hysteresis (5%), high sensitivity (GF = 60) and wide sensing range (0-50%), short response time (62 ms), outstanding stability, and repeatability (>10,000 cycles). Flexible strain sensors with all performances good are rarely reported. Static and dynamic respiration and pulse signal monitoring by the fiber sensor are demonstrated. Moreover, a knee joint monitoring system is constructed for the monitoring of various walking stances, which is of great value to the diagnosis and rehabilitation of many diseases.

Evidence of synergistic mechanisms of hepatoprotective botanical herbal preparation of Pueraria montana var. lobata and Schisandra sphenanthera.

Background: Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) and Schisandra sphenanthera Rehder & E.H. Wilson are traditional edible and medicinal hepatoprotective botanical drugs. Studies have shown that the combination of two botanical drugs enhanced the effects of treating acute liver injury (ALI), but the synergistic effect and its action mechanisms remain unclear. This study aimed to investigate the synergistic effect and its mechanism of the combination of Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) (PM) and Schisandra sphenanthera Rehder & E.H. Wilson (SS) in the treatment of ALI. Methods: High performance liquid chromatography (HPLC) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of botanical hybrid preparation of PM-SS (BHP PM-SS) against ALI were comprehensively evaluated by the CCl4 induced ALI mice model. Afterwards, symptom-oriented network pharmacology, transcriptomics and metabolomics were applied to reveal the underlying mechanism of action. Finally, the key target genes were experimentally by RT-qPCR. Results: Chemical analysis and pharmacodynamic experiments revealed that BHP PM-SS was superior to the single botanical drug, especially at 2:3 ratio, with a better dissolution rate of active ingredients and synergistic anti-ALI effect. Integrated symptom-oriented network pharmacology combined with transcriptomics and metabolomics analyses showed that the active ingredients of BHP PM-SS could regulate Glutathione metabolism, Pyrimidine metabolism, Arginine biosynthesis and Amino acid sugar and nucleotide sugar metabolism, by acting on the targets of AKT1, TNF, EGFR, JUN, HSP90AA1 and STAT3, which could be responsible for the PI3K-AKT signaling pathway, MAPK signaling pathway and Pathway in cancer to against ALI. Conclusion: Our study has provided compelling evidence for the synergistic effect and its mechanism of the combination of BHP PM-SS, and has contributed to the development and utilization of BHP PM-SS dietary supplements.