Meibomian glands segmentation in infrared images with limited annotation.

AIM: To investigate a pioneering framework for the segmentation of meibomian glands (MGs), using limited annotations to reduce the workload on ophthalmologists and enhance the efficiency of clinical diagnosis. METHODS: Totally 203 infrared meibomian images from 138 patients with dry eye disease, accompanied by corresponding annotations, were gathered for the study. A rectified scribble-supervised gland segmentation (RSSGS) model, incorporating temporal ensemble prediction, uncertainty estimation, and a transformation equivariance constraint, was introduced to address constraints imposed by limited supervision information inherent in scribble annotations. The viability and efficacy of the proposed model were assessed based on accuracy, intersection over union (IoU), and dice coefficient. RESULTS: Using manual labels as the gold standard, RSSGS demonstrated outcomes with an accuracy of 93.54%, a dice coefficient of 78.02%, and an IoU of 64.18%. Notably, these performance metrics exceed the current weakly supervised state-of-the-art methods by 0.76%, 2.06%, and 2.69%, respectively. Furthermore, despite achieving a substantial 80% reduction in annotation costs, it only lags behind fully annotated methods by 0.72%, 1.51%, and 2.04%. CONCLUSION: An innovative automatic segmentation model is developed for MGs in infrared eyelid images, using scribble annotation for training. This model maintains an exceptionally high level of segmentation accuracy while substantially reducing training costs. It holds substantial utility for calculating clinical parameters, thereby greatly enhancing the diagnostic efficiency of ophthalmologists in evaluating meibomian gland dysfunction.

Exploring the Localization of Siderophore-Mediated Cargo Delivery in Gram-Negative Bacteria Using 3-Hydroxypyridin-4(1H)-one-Fluorescein Probes.

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1H)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo. By monitoring changes in the fluorescence intensity of FAM conjugate 20 in bacteria, the translocation of the conjugate across the outer membranes of Gram-negative pathogens was confirmed. Further, the use of the fluorogen activating protein(FAP)/MG system revealed that 3-hydroxypyridin-4(1H)-one-MG conjugate 26 was ultimately distributed mainly in the periplasm rather than being translocated into the cytosol of Escherichia coli and Pseudomonas aeruginosa PAO1. Additional mechanistic studies suggested that the uptake of the conjugate involved the siderophore-dependent iron transport pathway and the 3-hydroxypyridin-4(1H)-ones siderophore receptor-dependent mechanism. Meanwhile, we demonstrated that the conjugation of 3-hydroxypyridin-4(1H)-ones to the fluorescein 5-FAM can reduce the possibility of the conjugates crossing the membrane layers of mammalian Vero cells by passive diffusion, and the advantages of the mono-3-hydroxypyridin-4(1H)-ones as a delivery vehicle in the design of conjugates compared to the tri-3-hydroxypyridin-4(1H)-ones. Overall, this work reveals the localization rules of 3-hydroxypyridin-4(1H)-ones as siderophores to deliver the cargo into Gram-negative bacteria. It provides a theoretical basis for the subsequent design of siderophore-antibiotic conjugates, especially based on 3-hydroxypyridin-4(1H)-ones as siderophores.

Berberine inhibits the malignant cell phenotype by inactivating PI3K/AKT/mTOR signaling in laryngeal squamous cell carcinoma.

BACKGROUND: Berberine is an active compound found in different herbs used in Chinese medicine and is well-known for its potential anticancer properties. The study aimed to figure out the role of berberine in regulating the malignant behavior of laryngeal squamous cell carcinoma (LSCC) cells. METHODS: LSCC cell lines (SNU-899 and AMC-HN-8) were treated with different concentrations of berberine (0-200 µM) to determine its cytotoxicity. The migration, invasion, and apoptosis of LSCC cells were measured by wound healing assays, Transwell assays, and flow cytometry. Western blot was performed for the quantification of proteins involved in PI3K/AKT/mTOR signaling. RESULTS: The viability of LSCC cells was dose-dependently reduced by berberine. Berberine dampened LSCC cell migration and invasion while augmenting cell apoptosis, as evidenced by a reduced wound closure rate, a decrease in invaded cell number, and a surge in cell apoptosis in the context of berberine stimulation. Importantly, the effects of berberine on the cancer cell process were enhanced by LY294002 (an inhibitor for PI3K) treatment. Moreover, the protein levels of phosphorylated PI3K, AKT, and mTOR were markedly reduced in response to berberine treatment. CONCLUSION: Berberine inhibits cell viability, migration, and invasion but augments cell apoptosis by inactivating PI3K/AKT/mTOR signaling in LSCC.

How culture shapes Chinese teacher's compassionate love.

BACKGROUND: Love could play a role in motivating teachers to help students and is closely related to students' achievement and prosocial behaviour. Though influenced by culture, teachers' love is not adequately studied. PURPOSE: This study explores how Chinese teachers' compassionate love is expressed and how situational factors such as Chinese culture and history influence or motivate teachers to perceive and express compassionate love for students. METHOD: This study adopted a qualitative approach of narrative study by describing and investigating the experience of a Chinese middle school teacher and two middle school students and their parents during COVID-19 pandemic. FINDINGS: Chinese teacher's compassionate love demonstrates some universal features in terms of emotional response, cognitive understanding and behaviour. Furthermore some Chinese culture-related features are also found: Chinese teachers behave in a caring and supporting way at the cost of sacrificing their own free time and comfort; an enduring long-term teacher-student relationship is valued; the Chinese culture encourages, sustains and motivates Chinese teacher's compassionate love. DISCUSSION: Teacher's compassionate love is a multi-dimensional concept entailing some universal traits in cognition, emotion and behaviour. The perception and enactment of teacher's love is subject to situational factors. Some measures for compassionate love could be built into teacher's education programme.

Rare Earth Nanoprobes for Targeted Delineation of Triple Negative Breast Cancer and Enhancement of Radioimmunotherapy.

Radiotherapy demonstrates a synergistic effect with immunotherapy by inducing a transformation of "immune cold" tumors into "immune hot" tumors in triple negative breast cancer (TNBC). Nevertheless, the effectiveness of immunotherapy is constrained by low expression of tumor-exposed antigens, inadequate inflammation, and insufficient tumor infiltrating lymphocyte (TILs). To address this predicament, novel lutecium-based rare earth nanoparticles (RENPs) are synthesized with the aim of amplifying radiation effect and tumor immune response. The nanoprobe is characterized by neodymium-based down-conversion fluorescence, demonstrating robust photostability, biocompatibility, and targetability. The conjugation of RENPs with a CXCR4 targeted drug enables precise delineation of breast tumors using a near-infrared imaging system and improves radiation efficacy via lutetium-based radio-sensitizer in vivo. Furthermore, the study shows a notable enhancement of immune response through the induction of immunogenic cell death and recruitment of TILs, resulting in the inhibition of tumor progression both in vitro and in vivo models following the administration of nanoparticles. Hence, the novel multifunctional nanoprobes incorporating various lanthanide elements offer the potential for imaging-guided tumor delineation, radio-sensitization, and immune activation post-radiation, thus presenting an efficient radio-immunotherapeutic approach for TNBC.

Functional extracellular vesicles from SHEDs combined with gelatin methacryloyl promote the odontogenic differentiation of DPSCs for pulp regeneration.

BACKGROUND: Pulp regeneration is a novel approach for the treatment of immature permanent teeth with pulp necrosis. This technique includes the combination of stem cells, scaffolds, and growth factors. Recently, stem cell-derived extracellular vesicles (EVs) have emerged as a new methodology for pulp regeneration. Emerging evidence has proven that preconditioning is an effective scheme to modify EVs for better therapeutic potency. Meanwhile, proper scaffolding is of great significance to protect EVs from rapid clearance and destruction. This investigation aims to fabricate an injectable hydrogel loaded with EVs from pre-differentiated stem cells from human exfoliated deciduous teeth (SHEDs) and examine their effects on pulp regeneration. RESULTS: We successfully employed the odontogenic induction medium (OM) of SHEDs to generate functional EV (OM-EV). The OM-EV at a concentration of 20 µg/mL was demonstrated to promote the proliferation and migration of dental pulp stem cells (DPSCs). The results revealed that OM-EV has a better potential to promote odontogenic differentiation of DPSCs than common EVs (CM-EV) in vitro through Alizarin red phalloidin, alkaline phosphatase staining, and assessment of the expression of odontogenic-related markers. High-throughput sequencing suggests that the superior effects of OM-EV may be attributed to activation of the AMPK/mTOR pathway. Simultaneously, we prepared a photocrosslinkable gelatin methacryloyl (GelMA) to construct an OM-EV-encapsulated hydrogel. The hydrogel exhibited sustained release of OM-EV and good biocompatibility for DPSCs. The released OM-EV from the hydrogel could be internalized by DPSCs, thereby enhancing their survival and migration. In tooth root slices that were subcutaneously transplanted in nude mice, the OM-EV-encapsulated hydrogel was found to facilitate dentinogenesis. After 8 weeks, there was more formation of mineralized tissue, as well as higher levels of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1). CONCLUSIONS: The effects of EV can be substantially enhanced by preconditioning of SHEDs. The functional EVs from SHEDs combined with GelMA are capable of effectively promoting dentinogenesis through upregulating the odontogenic differentiation of DPSCs, which provides a promising therapeutic approach for pulp regeneration.

LRG1 promotes the apoptosis of pulmonary microvascular endothelial cells through KLK10 in chronic obstructive pulmonary disease.

INTRODUCTION: Cigarette smoking is one of the most important causes of COPD and could induce the apoptosis of pulmonary microvascular endothelial cells (PMVECs). The conditional knockout of LRG1 from endothelial cells reduced emphysema in mice. However, the mechanism of the deletion of LRG1 from endothelial cells rescued by cigarette smoke (CS) induced emphysema remains unclear. This research aimed to demonstrate whether LRG1 promotes the apoptosis of PMVECs through KLK10 in COPD. METHODS: Nineteen patients were divided into three groups: control non-COPD (n=7), smoker non-COPD (n=7), and COPD (n=5). The emphysema mouse model defined as the CS exposure group was induced by CS exposure plus cigarette smoke extract (CSE) intraperitoneal injection for 28 days. Primary PMVECs were isolated from the mouse by magnetic bead sorting method via CD31-Dynabeads. Apoptosis was detected by western blot and flow cytometry. RESULTS: LRG1 was increased in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. KLK10 was over-expressed in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. LRG1 promoted apoptosis in PMVECs. LRG1 knockdown reversed CSE-induced apoptosis in PMVECs. The mRNA and protein expression of KLK10 were increased after over-expressed LRG1 in PMVECs isolated from mice. Similarly, both the mRNA and protein levels of KLK10 were decreased after LRG1 knockdown in PMVECs. The result of co-immunoprecipitation revealed a protein-protein interaction between LRG1 and KLK10 in PMVECs. KLK10 promoted apoptosis via the down-regulation of Bcl-2/Bax in PMVECs. KLK10 knockdown could reverse CSE-induced apoptosis in PMVECs. CONCLUSIONS: LRG1 promotes apoptosis via up-regulation of KLK10 in PMVECs isolated from mice. KLK10 promotes apoptosis via the down-regulation of Bcl-2/Bax in PMVECs. There was a direct protein-protein interaction between LRG1 and KLK10 in PMVECs. Our novel findings provide insights into the understanding of LRG1/KLK10 function as a potential molecule in COPD.

Understanding the Relationship Between Vascular Smooth Muscle Cell Function and the Efficacy of Acupuncture in Treating Cerebral Ischemic Stroke: A Preclinical Meta-Analysis and Systematic Review.

Background: Cerebral blood flow and vascular structures serve as the fundamental components of brain metabolism and circulation. Acupuncture, an alternative and complementary medical approach, has demonstrated efficacy in treating cerebral ischemic stroke (CIS). Nevertheless, the mechanisms underlying the impact of acupuncture on vascular smooth muscle cell (VSMC) function remain uncertain. The objective of this systematic review and meta-analysis is to assess the alterations in VSMC function following acupuncture stimulation in CIS models. Methods: The databases PubMed, Web of Science, SCOPUS, and EMBASE were queried until November 2022 using a predetermined search strategy. The FORMAT BY SYRCLE guidelines were adhered to, and the risk of bias of the included studies was evaluated using the Risk of Bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation. The random-effects model was employed to estimate the standardized mean difference (SMD). Results: Eighteen articles are included in this review. Acupuncture showed significant positive effects on the region cerebral blood flow (SMD=8.15 [95% CI, 4.52 to 11.78]) and neurological deficiency (SMD=-3.75 [95% CI, -5.54 to -1.97]). Descriptive analysis showed a probable mechanism of acupuncture stimulation in CIS rats related to VSMC function. Limitations and publication bias were presented in the studies. Conclusion: In this systematic review and meta-analysis, our findings indicate that acupuncture stimulation has the potential to improve regional cerebral blood flow and alleviate neurological deficits, possibly by regulating VSMC function. However, it is important to exercise caution when interpreting these results due to the limitations of animal experimental design and methodological quality.

Comparing fine motor performance among young children with autism spectrum disorder, intellectual disability, attention-deficit/hyperactivity disorder, and specific developmental disorder of motor function.

Objective: The acquisition of fine motor skills is considered to be a crucial developmental milestone throughout early childhood. This study aimed to investigate the fine motor performance of young children with different disability diagnoses. Methods: We enrolled a sample of 1,897 young children under the age of 6 years who were at risk of developmental delays and were identified by a transdisciplinary team. A series of standardized developmental assessments included the Bayley Scales of Infant Development-Third Edition, Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition, Peabody Developmental Motor Scale-Second Edition, and Movement Assessment Battery for Children-Second Edition were used. Retrospective chart reviews were conducted on all children to identify specific developmental disorders. The number of autism spectrum disorder (ASD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), comorbidity, motor dysfunction, and unspecified developmental delays (DD) were 363 (19.1%), 223 (11.8%), 234 (12.3%), 285 (15.0%), 128 (6.7%), and 590 (31.1%), respectively. Results: Young children with ID, comorbidity, and motor dysfunction demonstrated significant difficulty in performing manual dexterity and visual motor integration tasks and scored significantly lower in these areas than children with ASD, ADHD, and unspecified DD. In addition, fine motor performance was associated with cognitive ability in children with different disability diagnoses, indicating that young children showed better fine motor performance when they demonstrated better cognitive ability. Conclusion: Our findings support that differences in fine motor performance differ by disability type. Close links between fine motor performance and cognitive ability in children under the age of 6 years were seen in all disability types.

Protein crotonylation: Basic research and clinical diseases.

Crotonylation is an importantly conserved post-translational modification, which is completely different from acetylation. In recent years, it has been confirmed that crotonylation occurs on histone and non-histone. Crotonylated Histone primarily affects gene expression through transcriptional regulation, while non-histone Crotonylation mainly regulates protein functions including protein activity, localization, and stability, as well as protein-protein interactions. The change in protein expression and function will affect the physiological process of cells and even cause disease. Reviewing previous studies, this article summarizes the mechanisms of histone and non-histone crotonylation in regulating diseases and cellular physiological processes to explore the possibility of precise regulation of crotonylation sites as potential targets for disease treatment.

Endothelial mesenchymal transition promotes pannus formation in ankylosing spondylitis by activation of TGF-ß/SMAD signalling pathway.

OBJECTIVES: To explore the role of endothelial-mesenchymal transition (EndMT) mediated by the TGF-ß/SMAD signalling pathway in the pathogenesis of ankylosing spondylitis (AS). METHODS: Serum levels of TGF-ß1 were measured by enzyme-linked immunosorbent assay (ELISA) in 48 patients with AS and 15 healthy subjects. The expression levels of TGF-ß1, SMAD7, CTGF, CD34 and EndMT-related markers (α-SMA, vimentin, FSP-1, VE-cadherin) in the sacroiliac joint (SIJ) of three AS patients were detected by immunohistochemistry, and three non-spondyloarthritis (SpA) autopsy samples were used as controls. RESULTS: Serum TGF-ß1 level of AS patients was significantly higher than that of healthy controls (22971 ± 7667 pg/ml vs. 14837±4653 pg/ml, p<0.01). Compared with the non-SpA control group, the microvascular density (MVD) at the pannus formation site of SIJ in AS patients was significantly increased, accompanied by respectively increased expressions of TGF-ß1, CTGF, α-SMA, vimentin, and FSP-1 (all p<0.05), whereas respectively decreased expressions of VE-cadherin and SMAD7 (p<0.01). The expression level of FSP-1 was positively correlated with levels of TGF-ß1 and MVD, and negatively correlated with SMAD7. CONCLUSIONS: Our findings show that EndMT is involved in the promotion of pannus formation by TGF-ß/SMAD signalling pathway activation in AS.

Efficacy and safety of GST-HG171 in adult patients with mild to moderate COVID-19: a randomised, double-blind, placebo-controlled phase 2/3 trial.

Background: GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C like protease inhibitor that has demonstrated greater potency and efficacy compared to Nirmatrelvir in pre-clinical studies. We aimed to evaluate the efficacy and safety of orally administered GST-HG171 plus Ritonavir in patients with coronavirus disease 2019 (COVID-19) infected with emerging XBB and non-XBB variants. Methods: This randomised, double-blind, placebo-controlled phase 2/3 trial was conducted in 47 sites in China among adult patients with mild-to-moderate COVID-19 with symptoms onset ≤72 h. Eligible patients were randomised 1:1 to receive GST-HG171 (150 mg) plus Ritonavir (100 mg) or corresponding placebo tablets twice daily for 5 days, with stratification factors including the risk level of disease progression and vaccination status. The primary efficacy endpoint was time to sustained recovery of clinical symptoms within 28 days, defined as a score of 0 for 11 COVID-19-related target symptoms for 2 consecutive days, assessed in the modified intention-to-treat (mITT) population. This trial was registered at ClinicalTrials.gov (NCT05656443) and Chinese Clinical Trial Registry (ChiCTR2200067088). Findings: Between Dec 19, 2022, and May 4, 2023, 1525 patients were screened. Among 1246 patients who underwent randomisation, most completed basic (21.2%) or booster (74.9%) COVID-19 immunization, and most had a low risk of disease progression at baseline. 610 of 617 who received GST-HG171 plus Ritonavir and 603 of 610 who received placebo were included in the mITT population. Patients who received GST-HG171 plus Ritonavir showed shortened median time to sustained recovery of clinical symptoms compared to the placebo group (13.0 days [95.45% confidence interval 12.0-15.0] vs. 15.0 days [14.0-15.0], P = 0.031). Consistent results were observed in both SARS-CoV-2 XBB (45.7%, 481/1053 of mITT population) and non-XBB variants (54.3%, 572/1053 of mITT population) subgroups. Incidence of adverse events was similar in the GST-HG171 plus Ritonavir (320/617, 51.9%) and placebo group (298/610, 48.9%). The most common adverse events in both placebo and treatment groups were hypertriglyceridaemia (10.0% vs. 14.7%). No deaths occurred. Interpretation: Treatment with GST-HG171 plus Ritonavir has demonstrated benefits in symptom recovery and viral clearance among low-risk vaccinated adult patients with COVID-19, without apparent safety concerns. As most patients were treated within 2 days after symptom onset in our study, confirming the potential benefits of symptom recovery for patients with a longer duration between symptom onset and treatment initiation will require real-world studies. Funding: Fujian Akeylink Biotechnology Co., Ltd.

Paradoxical herniation associated with hyperbaric oxygen therapy after decompressive craniectomy: A case report.

BACKGROUND: Whether hyperbaric oxygen therapy (HBOT) can cause paradoxical herniation is still unclear. CASE SUMMARY: A 65-year-old patient who was comatose due to brain trauma underwent decompressive craniotomy and gradually regained consciousness after surgery. HBOT was administered 22 d after surgery due to speech impairment. Paradoxical herniation appeared on the second day after treatment, and the patient's condition worsened after receiving mannitol treatment at the rehabilitation hospital. After timely skull repair, the paradoxical herniation was resolved, and the patient regained consciousness and had a good recovery as observed at the follow-up visit. CONCLUSION: Paradoxical herniation is rare and may be caused by HBOT. However, the underlying mechanism is unknown, and the understanding of this phenomenon is insufficient. The use of mannitol may worsen this condition. Timely skull repair can treat paradoxical herniation and prevent serious complications.

Spatiotemporal expression of AP-2/myosin â ¥ in mouse cochlear IHCs and correlation with auditory function.

BACKGROUND: Recycling of synaptic vesicles plays an important role in vesicle pool replenishment, neurotransmitter release and synaptic plasticity. Clathrin-mediated endocytosis (CME) is considered to be the main mechanism for synaptic vesicle replenishment. AP-2 (adaptor-related protein complex 2) and myosin Ⅵ are known as key proteins that regulate the structure and dynamics of CME. OBJECTIVE: This study aims to reveal the spatiotemporal expression of AP-2/myosin Ⅵ in inner hair cells (IHCs) of the mouse cochlea and its correlation with auditory function. MATERIAL AND METHODS: Immunofluorescence was used to detect the localization and expression of AP-2 and myosin Ⅵ in cochlear hair cells (HCs) of CBA/CaJ mice of various ages. qRT-PCR was used to verify the differential expression of AP-2 and myosin Ⅵ mRNA in the mouse cochlea, and ABR tests were administered to mice of various ages. A preliminary analysis of the correlation between AP-2/myosin Ⅵ levels and auditory function was conducted. RESULTS: AP-2 was located in the cytoplasmic region of IHCs and was mainly expressed in the basal region of IHCs and the area near ribbon synapses, while myosin Ⅵ was expressed in the cytoplasmic region of IHCs and OHCs. Furthermore, AP-2 and myosin Ⅵ were not significant detected in the cochleae of P7 mice; the expression level reached a peak at P35 and then decreased significantly with age. The expression patterns and expression levels of AP-2 and myosin Ⅵ in the cochleae of the mice were consistent with the development of the auditory system. CONCLUSIONS AND SIGNIFICANCE: AP-2 and myosin Ⅵ protein expression may differ in mice of different ages, and this variation probably leads to a difference in the efficiency in CME; it may also cause a defect in IHC function.

LectoScape: A Highly Multiplexed Imaging Platform for Glycome Analysis and Biomedical Diagnosis.

Glycosylation, a fundamental biological process, involves the attachment of glycans to proteins, lipids, and RNA, and it plays a crucial role in various biological pathways. It is of great significance to obtain the precise spatial distribution of glycosylation modifications at the cellular and tissue levels. Here, we introduce LectoScape, an innovative method enabling detailed imaging of tissue glycomes with up to 1 µm resolution through image mass cytometry (IMC). This method utilizes 12 distinct, nonoverlapping lectins selected via microarray technology, enabling the multiplexed detection of a wide array of glycans. Furthermore, we developed an efficient labeling strategy for these lectins. Crucially, our approach facilitates the concurrent imaging of diverse glycan motifs, including N-glycan and O-glycan, surpassing the capabilities of existing technologies. Using LectoScape, we have successfully delineated unique glycan structures in various cell types, enhancing our understanding of the glycan distribution across human tissues. Our method has identified specific glycan markers, such as α2,3-sialylated Galß1, 3GalNAc in O-glycan, and terminal GalNAc, as diagnostic indicators for cervical intraepithelial neoplasia. This highlights the potential of LectoScape in cancer diagnostics through the detection of abnormal glycosylation patterns.

Phosphorus starvation response genes and function coupling: A mechanism to regulate phosphorus availability in a subtropical estuary.

Phosphorus (P) plays an important role in regulating primary production in estuarine environments. However, knowledge of the P-functional gene composition of microbial communities and the mechanisms of microbial adaptation to changes in available P in estuaries remain limited. This study coupling 16 s rDNA and metagenomics sequencing was conducted to reveal the relationship between P cycling functional genes, microbial interactions, and P availability in the Jiulong River Estuary. The results showed that the relative abundance of P cycling functions genes was highest in winter, and lowest in summer. Spatially, the total relative abundance of P cycling functions genes was higher in the riverward than that in the seaward. P cycling functional microbial interactions and P cycling gene coupling were strongest in summer and in the seaward. Changes in both temperature and salinity had significant direct and indirect effects on P cycling function, and the influence of salinity on P cycling function was greater than that on the microbial community in the estuary. Salinity had significant direct negative effects on inorganic P-solubilization (IP), organic P-mineralization (OP), and P uptake and transport functions (PT). Whereas, salinity had a significant positive effect on P-starvation response regulation (PR) function. Thus, salinity and microbial communities regulate the soluble reactive phosphate concentrations in estuarine environments by strengthening internal coupling among P cycling functions, promoting PR function, and facilitating PT gene expression. PR is the most important predictors, PR, PT, and PR-PT together explained 38.56 % of the overall soluble reactive phosphorus (SRP) variation. Over 66 % of the explained SRP variations can be predicted by the PR, PT, and PR-PT functional genes. This finding improves the knowledge base of the microbial processes for P cycling and provides a foundation for eutrophication management strategies in the estuary.

DPP: deep phase prior for parallel imaging with wave encoding.

Objective.In Magnetic Resonance (MR) parallel imaging with virtual channel-expanded Wave encoding, limitations are imposed on the ability to comprehensively and accurately characterize the background phase. These limitations are primarily attributed to the calibration process relying solely on center low-frequency Auto-Calibration Signals (ACS) data for calibration.Approach.To tackle the challenge of accurately estimating the background phase in wave encoding, a novel deep neural network model guided by deep phase priors is proposed with integrated virtual conjugate coil (VCC) extension. Concretely, within the proposed framework, the background phase is implicitly characterized by employing a carefully designed decoder convolutional neural network, leveraging the inherent characteristics of phase smoothness and compact support in the transformed domain. Furthermore, the proposed model with wave encoding benefits from additional priors, which incorporate transmission sparsity of the latent image and coil sensitivity smoothness.Main results.Ablation experiments were conducted to ascertain the proposed method's capability to implicitly represent CSM and the background phase. Subsequently, the superiority of the proposed method is demonstrated through confidence comparisons with competing methods, employing 4-fold and 5-fold acceleration experiments. In achieving 4-fold and 5-fold acceleration, the optimal quantitative metrics (PSNR/SSIM/NMSE) are 44.1359 dB/0.9863/0.0008 (4-fold) and 41.2074/0.9846/0.0017 (5-fold), respectively. Furthermore, the generalizability of the proposed method is further validated by conducting acceleration experiments with T1, T2, T2*, and various undersampling patterns. In addition, the DPP delivered much better performance than the conventional methods by exploring accelerated phase-sensitive SWI imaging. In SWI accelerated imaging, it also surpasses the optimal competing method in terms of (PSNR/SSIM/NMSE) with 0.096%/0.009%/0.0017%.Significance.The proposed method enables precise characterization of the background phase in the integrated VCC and wave encoding framework, supported via theoretical analysis and empirical findings. Our code is available at:https://github.com/sober235/DPP.

Comparative analysis of sipeimine content, metabolome and chloroplast genome in cultivated and wild varieties of Fritillaria taipaiensis.

BACKGROUND: The wild variety Fritillaria taipaiensis E.B (EB) is known for its superior therapeutic effects, but its limited production cannot meet demand. As a result, the cultivated variety F. taipaiensis P. Y. Li (PY) has been widely grown. In this study, we conducted a comprehensive analysis comparing EB and PY in terms of external features, sipeimine content, metabolome and chloroplast genome to differentiate these two varieties. RESULTS: Our research revealed that the petals and pods of EB are green, while those of PY have purple markings. The bulbs of EB contain significantly higher levels of sipeimine compared to those of PY. Metabolomic analysis identified 56 differentially expressed metabolites (DMs), with 23 upregulated and 33 downregulated in EB bulbs. Particularly, 3-hydroxycinnamic acid and secoxyloganin may serve as distinctive DMs. These DMs were associated with 17 KEGG pathways, including pyrimidine metabolism, alanine, aspartate and glutamate metabolism, and galactose metabolism. Differences in the length of the chloroplast genome were primarily observed in the large single-copy (LSC) region, with the largest variation in the trnH-GUC-psbA region. The placement of the trnH gene and the rps gene in proximity to the LSC/IRb boundary differs between EB and PY. CONCLUSION: The results of this study provide valuable insights for the introduction and comprehensive development of wild F. taipaiensis from a scientific perspective. © 2024 Society of Chemical Industry.

A numerical study on the siphonic effect of enhanced external counterpulsation at lower extremities with a coupled 0D-1D closed-loop personalized hemodynamics model.

Enhanced external counterpulsation (EECP) is a treatment and rehabilitation approach for ischemic diseases, including coronary artery disease. Its therapeutic benefits are primarily attributed to the improved blood circulation achieved through sequential mechanical compression of the lower extremities. However, despite the crucial role that hemodynamic effects in the lower extremity arteries play in determining the effectiveness of EECP treatment, most studies have focused on the diastole phase and ignored the systolic phase. In the present study, a novel siphon model (SM) was developed to investigate the interdependence of several hemodynamic parameters, including pulse wave velocity, femoral flow rate, the operation pressure of cuffs, and the mean blood flow changes in the femoral artery throughout EECP therapy. To verify the accuracy of the SM, we coupled the predicted afterload in the lower extremity arteries during deflation using SM with the 0D-1D patient-specific model. Finally, the simulation results were compared with clinical measurements obtained during EECP therapy to verify the applicability and accuracy of the SM, as well as the coupling method. The precision and reliability of the previously developed personalized approach were further affirmed in this study. The average waveform similarity coefficient between the simulation results and the clinical measurements during the rest state exceeded 90%. This work has the potential to enhance our understanding of the hemodynamic mechanisms involved in EECP treatment and provide valuable insights for clinical decision-making.

Reducing the length of stay for patients stranded in the emergency department: A single-center prospective study of 18,631 patients in China.

The purpose of this study was to reduce the length of stay (LOS) for patients stranded in the emergency department (ED) of a Grade III A hospital in China, and to improve patient flow and increase bed capacity. We utilized a pre-/postintervention design and employed the Six Sigma methodology, which is based on the DMAIC cycle (define, measure, analyze, improve, and control), to evaluate and improve the existing process. Data from 18,631 patients who were stranded in the ED were collected and analyzed. The median LOS for stranded patients decreased from 17.21 (6.22, 27.36) hours to 13.45 (5.56, 25.85) hours (P < .05). Similarly, the median LOS for admitted patients decreased from 19.64 (7.77, 27.68) hours to 15.92 (6.19, 26.24) hours (P < .05). The median LOS for patients with an ED triage Level IV decreased from 16.15 (5.80, 26.62) hours to 12.59 (5.20, 24.97) hours (P < .05). In addition, the average hospitalization days of hospitalized patients decreased from 0.92 days to 0.82 days (P < .05). Furthermore, the bed utilization rate increased from 66.79% to 72.29% (P < .05). The number of bed turnovers in the ED resuscitation room increased from 20.30 to 21.96 (P < .05). We had effectively met our goal of minimizing ED patient LOS. Six Sigma method can effectively shorten patient LOS by measuring and analyzing the key factors affecting patient LOS, and by implementing measures such as strict implementation of emergency classification and triage system, establishment of multidisciplinary cooperative team, reasonable allocation of human resources, information management of bed resources, and improvement of performance appraisal scheme to improve and control the effectiveness of patient LOS.