Lactate modulates RNA splicing to promote CTLA-4 expression in tumor-infiltrating regulatory T cells.

RNA splicing is involved in cancer initiation and progression, but how it influences host antitumor immunity in the metabolically abnormal tumor microenvironment (TME) remains unclear. Here, we demonstrate that lactate modulates Foxp3-dependent RNA splicing to maintain the phenotypic and functional status of tumor-infiltrating regulatory T (Treg) cells via CTLA-4. RNA splicing in Treg cells was correlated with the Treg cell signatures in the TME. Ubiquitin-specific peptidase 39 (USP39), a component of the RNA splicing machinery, maintained RNA-splicing-mediated CTLA-4 expression to control Treg cell function. Mechanistically, lactate promoted USP39-mediated RNA splicing to facilitate CTLA-4 expression in a Foxp3-dependent manner. Moreover, the efficiency of CTLA-4 RNA splicing was increased in tumor-infiltrating Treg cells from patients with colorectal cancer. These findings highlight the immunological relevance of RNA splicing in Treg cells and provide important insights into the environmental mechanism governing CTLA-4 expression in Treg cells.

SENP3 senses oxidative stress to facilitate STING-dependent dendritic cell antitumor function.

STING-dependent cytosolic DNA sensing in dendritic cells (DCs) initiates antitumor immune responses, but how STING signaling is metabolically regulated in the tumor microenvironment remains unknown. Here, we show that oxidative stress is required for STING-induced DC antitumor function through a process that directs SUMO-specific protease 3 (SENP3) activity. DC-specific deletion of Senp3 drives tumor progression by blunting STING-dependent type-I interferon (IFN) signaling in DCs and dampening antitumor immune responses. DC-derived reactive oxygen species (ROS) trigger SENP3 accumulation and the SENP3-IFI204 interaction, thereby catalyzing IFI204 deSUMOylation and boosting STING signaling activation in mice. Consistently, SENP3 senses ROS to facilitate STING-dependent DC activity in tissue samples from colorectal cancer patients. Our results reveal that oxidative stress as a metabolic regulator promotes STING-mediated DC antitumor immune responses and highlights SENP3 as an overflow valve for STING signaling induction in the metabolically abnormal tumor microenvironment.

Optical spatial differentiation enabled layer sensing of two-dimensional atomic crystals.

Zero-thickness model and slab model are two important models in the description of optical behaviors in two-dimensional atomic crystals. The predicted difference in optical behaviors between the two models is very small, which is difficult to distinguish by established measurement methods. Here, we present an optical spatial differentiation method to examine the difference in edge images of different graphene layers. The theoretical results show that the edge imaging is significantly different between the two different models. When the beam reflection is at the Brewster angle, different graphene layers are used to adjust the spatial differentiation. It is shown that the slab model is more sensitive to the number of graphene layers. The zero-thickness model is more suitable for one-dimensional optical differential operation. Moreover, the spatial differentiation plays the role of a band-pass filter. The high-frequency edge information components will pass through the filter, thus realizing layer-sensitive edge-enhanced imaging. In addition, we do not focus on the verification of the exact model, but only provide an alternative method to characterize the number of graphene layers based on two models, and also provide possibilities for achieving imaging edge detection by graphene differential operators. This study may provide a possible method for the optical characterization of two-dimensional atomic crystals.

Isolation and identification of NEAU-CP5: A seed-endophytic strain of B. velezensis that controls tomato bacterial wilt.

Bacterial wilt of tomato caused by Ralstonia solanacearum is a critical soilborne disease that drastically reduces yield. In the current study, an endophytic strain NEAU-CP5 with strong antagonistic activity against R. solanacearum was isolated from tomato seeds and characterized. The strain was identified as Bacillus velezensis based on 16S rRNA gene and whole genome sequence analysis. NEAU-CP5 can secrete amylase, protease, and cellulase, and also produce known antibacterial metabolites, including cyclo (leucylprolyl), cyclo (phenylalanyl-prolyl), cyclo (Pro-Gly), 3-benzyl-2,5-piperazinedione, pentadecanoic acid, eicosane, 2-methyoic acid, isovaleric acid, dibuty phthalate, and esters of fatty acids (HFDU), which may be responsible for its strong antibacterial activity. Fourteen gene clusters associated with antibacterial properties were also identified in the whole genome sequence of NEAU-CP5. Pot experiment demonstrated that the application of 108 CFU/mL NEAU-CP5 on tomato plants significantly reduced the incidence of tomato bacterial wilt by 68.36 ± 1.67 %. NEAU-CP5 also increased the activity of defense-related enzymes (CAT, POD, PPO, SOD, and PAL) in tomato plants. This is the first report of an effective control of bacterial wilt on tomato plants by B. velezensis and highlights the potential of NEAU-CP5 as a potential biocontrol agent for the management of tomato bacterial wilt.

Correlation of Neuroendocrine Differentiation with a Distinctively Suppressive Immune Microenvironment in Gastric Cancer.

INTRODUCTION: Neuroendocrine neoplasms (NENs) harbored significantly suppressive tumor immune microenvironments (TIMEs). However, the immunological effects of neuroendocrine differentiation (NED) on non-NENs, such as gastric cancer (GC), were unknown. METHODS: Between pure gastric cancer (PGC) and GC-NED, TIME features were scored based on expression data and validated on serial whole-tissue sections of surgical samples, with tertiary lymphoid structures (TLSs) and the extra-TLS zone evaluated independently using multi-marker immunohistochemical staining. Risk analyses of TIME features on tumor behaviors were performed in GC-NED. The universal immunological effects of NED were explored preliminarily in adenocarcinomas arising in other organs. RESULTS: Based on over 11,500 annotated TLSs and 2,700 extra-TLS zones, compared with PGC, GC-NED harbored a distinctively more suppressive TIME characterized by increased but immature TLSs, with higher naïve B-cell and follicular regulatory T-cell densities and downregulated TLS maturation-related cell ratios inside TLSs; increased naïve B-cell and regulatory T-cell densities; and a high proportion of exhausted T cells in the extra-TLS zone. The upregulated tumor PD-L1 expression and its close correlations with TLS formation and maturation were remarkable exclusively in GC-NED. TIME features, especially those regarding TLSs, were significantly correlated with tumor growth and invasion. The desynchrony between TLS formation and maturation and increased naïve or regulatory immune cell infiltration was observed in adenocarcinomas of the colorectum, pancreas, lung, and prostate. CONCLUSION: NED highlighted a distinct GC entity with more suppressive TIME features correlated with tumor behaviors, indicating a cohort that would benefit more from immunotherapies.

Methylobacterium amylolyticum sp. nov. and Methylobacterium ligniniphilum sp. nov., isolated from soil.

Two pink-pigmented bacteria, designated strains NEAU-140T and NEAU-KT, were isolated from field soil collected from Linyi, Shandong Province, PR China. Both isolates were aerobic, Gram-stain-negative, rod-shaped, and facultatively methylotrophic. 16S rRNA gene sequences analysis showed that these two strains belong to the genus Methylobacterium. Strain NEAU-140T exhibited high 16S rRNA gene sequence similarities to Methylobacterium radiotolerans NBRC 15690T (97.43 %) and Methylobacterium phyllostachyos NBRC 105206T (97.36 %). Strain NEAU-KT exhibited high 16S rRNA gene sequence similarities to M. phyllostachyos NBRC 105206T (99.00 %) and Methylobacterium longum DSM 23933T (98.72 %). A phylogenetic tree based on 16S rRNA gene sequences showed that strain NEAU-140T formed a clade with Methylobacterium aerolatum (95.94 %), Methylobacterium persicinum (95.66 %) and Methylobacterium komagatae (96.87 %), and strain NEAU-KT formed a cluster with M. phyllostachyos and M. longum. The predominant fatty acid in both strains was C18 : 1 ω7c. Both strains contained ubiquinone Q-10 as the only respiratory quinone. The polar lipid profiles of both strains contained diphosphatidylglycerol, phosphatidylethanolamine, and phosphatidylcholine. Whole-genome phylogeny showed that strains NEAU-140T and NEAU-KT formed a phyletic line with M. aerolatum, M. persicinum, Methylobacterium radiotolerans, Methylobacterium fujisawaense, Methylobacterium oryzae, Methylobacterium tardum, M. longum and M. phyllostachyos. The orthologous average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain NEAU-140T and its closely related strains were lower than 82.62 and 25.90  %, respectively. The ANI and dDDH values between strain NEAU-KT and its closely related strains were lower than 86.29 and 31.7 %, respectively. The genomic DNA G+C contents were 71.63 mol% for strain NEAU-140T and 69.08 mol% for strain NEAU-KT. On the basis of their phenotypic and phylogenetic distinctiveness and the results of dDDH and ANI hybridization, these two isolates represent two novel species within the genus Methylobacterium, for which the names Methylobacterium amylolyticum sp. nov. (type strain NEAU-140T=MCCC 1K08801T=DSM 110568T) and Methylobacterium ligniniphilum sp. nov. (type strain NEAU-KT=MCCC 1K08800T=DSM 110567T) are proposed.

Desflurane improves electrical activity of neurons and alleviates oxygen-glucose deprivation-induced neuronal injury by activating the Kcna1-dependent Kv1.1 channel.

Several volatile anesthetics have presented neuroprotective functions in ischemic injury. This study investigates the effect of desflurane (Des) on neurons following oxygen-glucose deprivation (OGD) challenge and explores the underpinning mechanism. Mouse neurons HT22 were subjected to OGD, which significantly reduced cell viability, increased lactate dehydrogenase release, and promoted cell apoptosis. In addition, the OGD condition increased oxidative stress in HT22 cells, as manifested by increased ROS and MDA contents, decreased SOD activity and GSH/GSSG ratio, and reduced nuclear protein level of Nrf2. Notably, the oxidative stress and neuronal apoptosis were substantially blocked by Des treatment. Bioinformatics suggested potassium voltage-gated channel subfamily A member 1 (Kcna1) as a target of Des. Indeed, the Kcna1 expression in HT22 cells was decreased by OGD but restored by Des treatment. Artificial knockdown of Kcna1 negated the neuroprotective effects of Des. By upregulating Kcna1, Des activated the Kv1.1 channel, therefore enhancing K+ currents and inducing neuronal repolarization. Pharmacological inhibition of the Kv1.1 channel reversed the protective effects of Des against OGD-induced injury. Collectively, this study demonstrates that Des improves electrical activity of neurons and alleviates OGD-induced neuronal injury by activating the Kcna1-dependent Kv1.1 channel.

Psychological pathway to emotional exhaustion among nurses and midwives who provide perinatal bereavement care in China: a path analysis.

BACKGROUND: A lack of confidence in perinatal bereavement care (PBC) and the psychological trauma experienced by nurses and midwives during bereavement care leads to their strong need for sufficient organisational support. The current study intended to test a hypothesised model of the specific impact paths among organisational support, confidence in PBC, secondary traumatic stress, and emotional exhaustion among nurses and midwives. METHODS: A descriptive, cross-sectional survey was conducted in sixteen maternity hospitals in Zhejiang Province, China, from August to October 2021. The sample (n = 779) consisted of obstetric nurses and midwives. A path analysis was used to test the relationships among study variables and assess model fit. RESULTS: Organisational support directly and positively predicted confidence in PBC and demonstrated a direct, negative, and significant association with secondary traumatic stress and emotional exhaustion. Confidence in PBC had a positive direct effect on secondary traumatic stress and a positive indirect effect on emotional exhaustion via secondary traumatic stress. Secondary traumatic stress exhibited a significant, direct effect on emotional exhaustion. CONCLUSIONS: This study shows that nurses' and midwives' confidence in PBC and mental health were leadingly influenced by organisational support in perinatal bereavement practice. It is worth noting that higher confidence in PBC may lead to more serious psychological trauma symptoms in nurses and midwives. Secondary traumatic stress plays an essential role in contributing to emotional exhaustion. The findings suggest that support from organisations and self-care interventions were required to improve confidence in PBC and reduce negative psychological outcomes among those providing PBC. The development of objective measures for assessing competence in PBC and organizational support are essential.

Pharmacologic Analgesia for Cesarean Section: An Update in 2024.

PURPOSE OF THE REVIEW: With the increasing prevalence of cesarean section globally, the importance of perioperative analgesia for cesarean section is becoming increasingly evident. This article provides an overview and update on the current status of cesarean section worldwide and associated analgesic regimens. RECENT FINDINGS: Some recent studies unveiled potential association of neuraxial analgesia might be associated with children's autism, pharmacologic analgesia in obstetric will potentially gain some more attention. Various commonly used techniques and medications for analgesia in cesarean section are highlighted. While neuraxial administration of opioid remains the most classic method, the use of multimodal analgesia, particularly integration of nonsteroidal anti-inflammatory drugs, acetaminophen, peripheral nerve blocks has provided additional and better options for patients who are not suitable for intrathecal and neuraxial techniques and those experiencing severe pain postoperatively. Optimal pain management is crucial for achieving better clinical outcomes and optimal recovery, and with the continuous development of medications, more and better pharmacologic regimen will be available in the future.

Identification and evaluation of an endophytic antagonistic yeast for the control of gray mold (Botrytis cinerea) in apple and mechanisms of action.

Gray mold, caused by Botrytis cinerea, is a prevalent postharvest disease of apple that limits their shelf life, resulting in significant economic losses. The use of antagonistic microorganisms has been shown to be an effective approach for managing postharvest diseases of fruit. In the present study, an endophytic yeast strain PGY-2 was isolated from apples and evaluated for its biocontrol efficacy against gray mold and its mechanisms of action. Results indicated that strain PGY-2, identified as Bullera alba, reduced the occurrence of gray mold on apples and significantly inhibited lesion development in pathogen-inoculated wounds. Gray mold control increased with the use of increasing concentrations of PGY-2, with the best disease control observed at 108 cells/mL. Notably, Bullera alba PGY-2 did not inhibit the growth of Botrytis cinerea in vitro indicating that the yeast antagonist did not produce antimicrobial compounds. The rapid colonization and stable population of PGY-2 in apple wounds at 4 °C and 25 °C confirmed its ability to compete with pathogens for nutrients and space. PGY-2 also had a strong ability to form a biofilm and enhanced the activity of multiple defense-related enzymes (POD, PPO, APX, SOD, PAL) in host tissues. Our study is the first time to report the use of Bullera alba PGY-2 as a biocontrol agent for postharvest diseases of apple and provide evidence that Bullera alba PGY-2 represents an endophytic antagonistic yeast with promising biocontrol potential and alternative to the use of synthetic, chemical fungicides for the control of postharvest gray mold in apples.

Exploring Potential Targets and Pathways of Toxicity Attenuation Through Serum Pharmacochemistry and Network Pharmacology in the Processing of Aconiti Lateralis Radix Praeparata.

Aconiti Lateralis Radix Praeparata (Fuzi, FZ) is a frequently utilized traditional Chinese medicine (TCM) in clinical settings. However, its toxic and side effects, particularly cardiac injury, are apparent, necessitating processing before use. To investigate the mechanism of toxicity induced by absorbed components and the mitigating effect of processed FZ, we established a comprehensive method combining serum pharmacochemistry and a network pharmacology approach. In total, 31 chemical components were identified in the plasma, with a general decrease in response intensity observed for these components in processed FZ. Subsequently, four components were selected for network pharmacology analysis. This analysis revealed 150 drug action targets and identified 1162 cardiac toxicity targets. Through intersection analysis, 41 key targets related to cardiac toxicity were identified, along with 9 significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The most critical targets identified were AKT1, MTOR, and PARP1. The key biological pathways implicated were adrenergic signaling in cardiomyocytes, proteoglycans in cancer, and the calcium signaling pathway. Significant differences were observed in histological staining and biochemical indicators in the cardiac tissue of rats treated with FZ, indicating that processing could indeed reduce its cardiotoxicity. Indeed, this article presents a valuable strategy for elucidating the toxification mechanism of toxic TCM.

Quantitative evaluation of the impact of indoor relative humidity on deposition of aerosols generated during tooth grinding in a real-world clinical setting.

OBJECTIVES: Exposure to aerosol particles generated from tooth grinding has a negative impact on the health of dental personnel. The aim of this study was to quantitatively analyze the impact of indoor relative humidity (IRH) on the deposition of these suspended particles in a well-controlled dental environment. MATERIALS AND METHODS: In this study, a humidity control system was employed to effectively regulate and maintain indoor relative humidity (IRH). A novel computer-assisted numerical control system was developed to pre-treat the molar specimens, and accurately simulate clinical tooth grinding procedures. Each procedure was performed in triplicate, with an online real-time particle counter (ORPC; TR-8301, TongrenCo.) measuring aerosol production. All testing devices were controlled remotely. The data obtained were statistically analyzed using descriptive statistics and non-parametric tests (Kruskal-Wallis/ Dunn's post hoc test with Bonferroni correction, p < 0.05). RESULTS: The findings showed that with increasing IRH, the maximum peak concentration of aerosol particles decreased by 397% from 6.51 × 107 particles/m3 at 30% to 1.64 × 107 particles/m3 at 80%. The Kruskal-Wallis test results indicated a statistically significant effect of IRH on the aerosol increment (p < 0.05). CONCLUSIONS: Increasing the IRH level can effectively promote the deposition of aerosol particles, with a return to baseline within 15 min after reaching 60% or above. CLINICAL RELEVANCE: Our study suggested that maintaining IRH above 70% during the cleaning process, allowing natural recovery to ambient humidity levels within 15 min after cleaning, and taking basic precautions, may lead to an adequate reduction in the possible health risks of aerosol contamination.

Fracture resistance of CAD/CAM endocrowns made from different materials in maxillary premolar interproximal defects.

OBJECTIVES: This in vitro study aims to compare the fracture resistance of three CAD/CAM materials used in endocrown restoration of interproximal defects in maxillary premolars. MATERIALS AND METHODS: 45 maxillary premolars extracted as part of orthodontic treatment were included. Following standardized root canal treatment, all teeth were prepared into Mesial-Occlusal (MO) cavity types. The samples were then randomly divided into three groups: LD [repaired with lithium disilicate glass ceramics (IPS e.max CAD)], VE [treated with polymer-infiltrated ceramics (Vita Enamic)], and LU [repaired with resin-based nanoceramics (Lava Ultimate)]. Axial static loading was applied using a universal testing machine at 1 mm/min until fracture, and fracture resistance and failure modes were recorded. RESULTS: Regarding Fracture Resistance Values (FRVs), the LD group exhibited significantly higher values than the other two groups, VE (P = 0.028) and LU (P = 0.005), which showed no significant difference (P = 0.778). On the other hand, regarding failure modes, the LD group had a higher prevalence of irreparable fractures compared to the other two groups, VE (P < 0.001) and LU (P < 0.001), which showed no significant difference. CONCLUSIONS: Although lithium disilicate glass ceramics exhibited higher FRVs, they had a lower repair probability. In contrast, polymer-infiltrated ceramics and resin-based nanoceramics contributed to tooth structure preservation. CLINICAL RELEVANCE: For maxillary premolars with interproximal defects following root canal treatment, resin ceramic composites are recommended for restoration to enhance abutment teeth protection.

Study of aerosol dispersion and control in dental practice.

OBJECTIVES: In this study, we investigated the dispersion patterns of aerosols and droplets in dental clinics and developed a suction device to evaluate its effectiveness in reducing aerosols during dental procedures. MATERIALS AND METHODS: Firstly, the continuous images of oral aerosols and droplets were photographed with a high-speed camera, and the trajectories of these particles were recognized and processed by Image J to determine key parameters affecting particle dispersion: diffusion velocity, distance, and angle. Secondly, based on the parameter data, the flow field of aerosol particles around the oral cavity was simulated using computational fluid dynamics (CFD), and the flow field under adsorption conditions was simulated to demonstrate the aerodynamic characteristics and capture efficiencies of the single-channel and three-channel adsorption ports at different pressures. Finally, according to the simulated data, a three-channel suction device was developed, and the capture efficiency of the device was tested by the fluorescein tracer method. RESULTS: The dispersion experimental data showed that aerosol particles' maximum diffusion velocity, distance, and angle were 6.2 m/s, 0.55 m, and 130°, respectively. The simulated aerosol flow-field distribution was consistent with the aerosol dispersion patterns. The adsorption simulation results showed that the outlet flow rate of single-channel adsorption was 184.5 L/s at - 350 Pa, and the aerosol capture efficiency could reach 79.4%. At - 350 Pa and - 150 Pa, the outlet flow rate of three-channel adsorption was 228.9 L/s, and the capture efficiency was 99.23%. The adsorption experimental data showed that the capture efficiency of three-channel suction device was 97.71%. CONCLUSIONS: A three-channel suction device was designed by simulations and experiments, which can capture most aerosols in the dental clinic and prevent them from spreading. CLINICAL RELEVANCE: Using three-channel suction devices during oral treatment effectively reduces the spread of oral aerosols, which is essential to prevent the spread of epidemics and ensure the health and safety of patients and dental staff.

Enhancing thermal comfort prediction in high-speed trains through machine learning and physiological signals integration.

Heating, Ventilation, and Air Conditioning (HVAC) systems in high-speed trains (HST) are responsible for consuming approximately 70% of non-operational energy sources, yet they frequently fail to ensure provide adequate thermal comfort for the majority of passengers. Recent advancements in portable wearable sensors have opened up new possibilities for real-time detection of occupant thermal comfort status and timely feedback to the HVAC system. However, since occupant thermal comfort is subjective and cannot be directly measured, it is generally inferred from thermal environment parameters or physiological signals of occupants within the HST compartment. This paper presents a field test conducted to assess the thermal comfort of occupants within HST compartments. Leveraging physiological signals, including skin temperature, galvanic skin reaction, heart rate, and ambient temperature, we propose a Predicted Thermal Comfort (PTC) model for HST cabin occupants and establish an intelligent regulation model for the HVAC system. Nine input factors, comprising physiological signals, individual physiological characteristics, compartment seating, and ambient temperature, were formulated for the PTS model. In order to obtain an efficient and accurate PTC prediction model for HST cabin occupants, we compared the accuracy of different subsets of features trained by Machine Learning (ML) models of Random Forest, Decision Tree, Vector Machine and K-neighbourhood. We divided all the predicted feature values into four subsets, and did hyperparameter optimisation for each ML model. The HST compartment occupant PTC prediction model trained by Random Forest model obtained 90.4% Accuracy (F1 macro = 0.889). Subsequent sensitivity analyses of the best predictive models were then performed using SHapley Additive explanation (SHAP) and data-based sensitivity analysis (DSA) methods. The development of a more accurate and operationally efficient thermal comfort prediction model for HST occupants allows for precise and detailed feedback to the HVAC system. Consequently, the HVAC system can make the most appropriate and effective air supply adjustments, leading to improved satisfaction rates for HST occupant thermal comfort and the avoidance of energy wastage caused by inaccurate and untimely predictive feedback.

Exploring factors that affect nurse staffing: a descriptive qualitative study from nurse managers' perspective.

BACKGROUND: The appropriate nurse staffing reflects the situation of nursing management of human resources. Nurse managers have a pivotal role in determining a competent and sufficient number of nurses. It is important to understand the factors influencing nurse staffing to promote appropriate staffing levels. The study aimed to explore the factors affecting nurse staffing from the perspective of nursing managers. METHODS: Purposive sampling was adopted to recruit 14 nurse managers from secondary and tertiary hospitals located in the central region of China, and semi-structured interviews via telephone were conducted from April to May 2022. Interview transcripts were analyzed and collated using thematic analysis. RESULTS: This research identified four themes and ten subthemes influencing nurse staffing. Extracted themes include: government level (inadequacy of mandatory policies, budgetary constraints), hospital level (hospital characteristics, the control of nurse labor costs, inadequate support on nursing), patient level (patient characteristics, increasing care needs), and nurse level (nurse shortage, skill-mix, individual high-level needs). CONCLUSION: The findings indicate that it is crucial for decision-makers or policymakers to legislate for safe nurse staffing and establish effective supervision and funding incentives. Tailored interventions are also needed to improve the organizational context, address the nurse workforce and balance the structure of nurse staff.

Knowledge, attitude, practice, needs, and implementation status of intensive care unit staff toward continuous renal replacement therapy: a survey of 66 hospitals in central and South China.

BACKGROUND: Continuous renal replacement therapy (CRRT) is a commonly utilized form of renal replacement therapy (RRT) in the intensive care unit (ICU). A specialized CRRT team (SCT, composed of physicians and nurses) engage playing pivotal roles in administering CRRT, but there is paucity of evidence-based research on joint training and management strategies. This study armed to evaluate the knowledge, attitude, and practice (KAP) of ICU staff toward CRRT, and to identify education pathways, needs, and the current status of CRRT implementation. METHODS: This study was performed from February 6 to March 20, 2023. A self-made structured questionnaire was used for data collection. Descriptive statistics, T-tests, Analysis of variance (ANOVA), multiple linear regression, and Pearson correlation coefficient tests (α = 0.05) were employed. RESULTS: A total of 405 ICU staff from 66 hospitals in Central and South China participated in this study, yielding 395 valid questionnaires. The mean knowledge score was 51.46 ± 5.96 (61.8% scored highly). The mean attitude score was 58.71 ± 2.19 (73.9% scored highly). The mean practice score was 18.15 ± 0.98 (85.1% scored highly). Multiple linear regression analysis indicated that gender, age, years of CRRT practice, ICU category, and CRRT specialist panel membership independently affected the knowledge score; Educational level, years of CRRT practice, and CRRT specialist panel membership independently affected the attitude score; Education level and teaching hospital employment independently affected the practice score. The most effective method for ICU staff to undergo training and daily work experience is within the department. CONCLUSION: ICU staff exhibit good knowledge, a positive attitude and appropriately practiced CRRT. Extended CRRT practice time in CRRT, further training in a general ICU or teaching hospital, joining a CRRT specialist panel, and upgraded education can improve CRRT professional level. Considering the convenience of training programs will enhance ICU staff participation. Training should focus on basic CRRT principles, liquid management, and alarm handling.

DEPDC1B-mediated USP5 deubiquitination of ß-catenin promotes breast cancer metastasis by activating the wnt/ß-catenin pathway.

Breast cancer has become the malignant disease with the highest morbidity and mortality among female cancer patients. The prognosis of metastatic breast cancer is very poor, and the therapeutic effects still need to be improved. The molecular mechanism of breast cancer has not been fully clarified. Bioinformatics analysis was used to find the differentially expressed gene that affects the occurrence and development of breast cancer. Furthermore, scratch assays, Transwell assays, immunofluorescence, and Western blotting were used to determine the biological behavior of breast cancer cells affected by DEP domain-containing protein 1B (DEPDC1B). The molecular mechanism was investigated by mass spectrometry analysis, coimmunoprecipitation, and ubiquitin assays. Here, we found that DEPDC1B was highly expressed in breast cancer cells and tissues and was associated with lower overall survival (OS) in patients. We found that DEPDC1B interference significantly inhibited tumor invasion and migration in vitro and tumor metastasis in vivo. Mechanistically, DEPDC1B was first shown to activate the wnt/ß-catenin signaling pathway as an oncogene in breast cancer cells. In addition, we also confirmed the interaction between DEPDC1B, ubiquitin-specific protease 5 (USP5), and ß-catenin. Then, we found that DEPDC1B mediates the deubiquitination of ß-catenin via USP5, which promotes cell invasion and migration. Our findings provide new insights into the carcinogenic mechanism of DEPDC1B, suggesting that DEPDC1B can be considered a potential therapeutic target for breast cancer.NEW & NOTEWORTHY By using bioinformatics analysis and the experimental techniques of cell biology and molecular biology, we found that DEP domain-containing protein 1B (DEPDC1B) can promote the invasion and migration of breast cancer cells and that DEPDC1B mediates the deubiquitination of ß-catenin by ubiquitin-specific protease 5 (USP5), thus activating the wnt/ß-catenin pathway. Our findings provide new insights into the carcinogenic mechanism of DEPDC1B, suggesting that DEPDC1B can be used as a potential therapeutic target for breast cancer.

Temporal-specific roles of fragile X mental retardation protein in the development of the hindbrain auditory circuit.

Fragile X mental retardation protein (FMRP) is an RNA-binding protein abundant in the nervous system. Functional loss of FMRP leads to sensory dysfunction and severe intellectual disabilities. In the auditory system, FMRP deficiency alters neuronal function and synaptic connectivity and results in perturbed processing of sound information. Nevertheless, roles of FMRP in embryonic development of the auditory hindbrain have not been identified. Here, we developed high-specificity approaches to genetically track and manipulate throughout development of the Atoh1+ neuronal cell type, which is highly conserved in vertebrates, in the cochlear nucleus of chicken embryos. We identified distinct FMRP-containing granules in the growing axons of Atoh1+ neurons and post-migrating NM cells. FMRP downregulation induced by CRISPR/Cas9 and shRNA techniques resulted in perturbed axonal pathfinding, delay in midline crossing, excess branching of neurites, and axonal targeting errors during the period of circuit development. Together, these results provide the first in vivo identification of FMRP localization and actions in developing axons of auditory neurons, and demonstrate the importance of investigating early embryonic alterations toward understanding the pathogenesis of neurodevelopmental disorders.

All-optical image edge detection based on the two-dimensional photonic spin Hall effect in anisotropic metamaterial.

Optical image processing based on the photonic spin Hall effect (SHE) has been gaining significant attention as a convenient and an accurate way for image edge detection. However, the recent edge imaging techniques depending on optical differentiation is mainly achieved by modulation of one-dimensional photonic SHE. Here, we theoretically predict the two-dimensional photonic SHE in the anisotropic metamaterial, and find that its longitudinal and transverse displacements exhibit spin-dependent property at filling factors with increasing incidence angle. As the transverse and in-plane displacements induced by the photonic SHE can be controlled by the filling factor of the crystal structure, the optical axis angle, and the incident angle, this intrinsical effect can be used to realize a tunable edge imaging. Interestingly, by changing the optical axis of the anisotropic metamaterial, the in-plane displacements are equal to the transverse displacements for a certain filling factor and the corresponding incident angle. Therefore, we propose a two-dimensional image edge detection method based on the photonic SHE in anisotropic metamaterial. Further numerical results validate the theoretical proposal.