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Dawei Ren,1 Yan Zhang,1 Bo Du,1 Lina Wang,2 Meiheng Gong,1 Wei Zhu1 1Department of Otorhinolaryngology, the First Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Pediatric Respiration, the First Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Wei Zhu, Email zhuwei@jlu.edu.cnBackground: Electrical stimulation (ES) can effectively promote skin wound healing; however, single-electrode-based ES strategies are difficult to cover the entire wound area, and the effectiveness of ES is often limited by the inconsistent mechanical properties of the electrode and wound tissue. The above factors may lead to ES treatment is not ideal.Methods: A multifunctional conductive hydrogel dressing containing methacrylated gelatin (GelMA), Ti3C2 and collagen binding antimicrobial peptides (V-Os) was developed to improve wound management. Ti3C2 was selected as the electrode component due to its excellent electrical conductivity, the modified antimicrobial peptide V-Os could replace traditional antibiotics to suppress bacterial infections, and GelMA hydrogel was used due to its clinical applicability in wound healing.Results: The results showed that this new hydrogel dressing (GelMA@Ti3C2/V-Os) not only has excellent electrical conductivity and biocompatibility but also has a durable and efficient bactericidal effect. The modified antimicrobial peptides V-Os used were able to bind more closely to GelMA hydrogel to exert long-lasting antibacterial effects. The results of cell experiment showed that the GelMA@Ti3C2/V-Os hydrogel dressing could enhance the effect of current stimulation and significantly improve the migration, proliferation and tissue repair related genes expression of fibroblasts. In vitro experiments results showed that under ES, GelMA@Ti3C2/V-Os hydrogel dressing could promote re-epithelialization, enhance angiogenesis, mediate immune response and prevent wound infection.Conclusion: This multifunctional nanocomposite hydrogel could provide new strategies for promoting infectious wound healing. Keywords: MXene, GelMA, electrical stimulation, antimicrobial peptides, wound healing

Qingzhu Zhang,1,2 Yinhui Yao,3 Yufeng Chen,1 Dong Ren,1 Pengcheng Wang1 1Orthopedic Trauma Service Center, Third Hospital of Hebei Medical University, Major Laboratory of Orthopedic Biomechanics in Hebei Province, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Orthopedics, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, People’s Republic of China; 3Department of Pharmacy, the Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, People’s Republic of ChinaCorrespondence: Pengcheng Wang, Orthopedic Trauma Service Center, Third Hospital of Hebei Medical University, Major Laboratory of Orthopedic Biomechanics in Hebei Province, Shijiazhuang, Hebei Province, People’s Republic of China, Email zhengzainingmeng@163.comAim: A high percentage of the elderly suffer from knee osteoarthritis (KOA), which imposes a certain economic burden on them and on society as a whole. The purpose of this study is to examine the risk of KOA and to develop a KOA nomogram model that can timely intervene in this disease to decrease patient psychological burdens.Methods: Data was collected from patients with KOA and without KOA at our hospital from February 2021 to February 2023. Initially, a comparison was conducted between the variables, identifying statistical differences between the two groups. Subsequently, the risk of KOA was evaluated using the Least Absolute Shrinkage and Selection Operator method and multivariate logistic regression to determine the most effective predictive index and develop a prediction model. The examination of the disease risk prediction model in KOA includes the corresponding nomogram, which encompasses various potential predictors. The assessment of disease risk entails the application of various metrics, including the consistency index (C index), the area under the curve (AUC) of the receiver operating characteristic curve, the calibration chart, the GiViTi calibration band, and the model for predicting KOA. Furthermore, the potential clinical significance of the model is explored through decision curve analysis (DCA) and clinical influence curve analysis.Results: The study included a total of 582 patients, consisting of 392 patients with KOA and 190 patients without KOA. The nomogram utilized age, haematocrit, platelet count, apolipoprotein a1, potassium, magnesium, hydroxybutyrate dehydrogenase, creatine kinase, and estimated glomerular filtration rate as predictors. The C index, AUC, calibration plot, Giviti calibration band, DCA and clinical influence KOA indicated the ability of nomogram model to differentiate KOA.Conclusion: Using nomogram based on disease risk, high-risk KOA can be identified directly without imaging.Keywords: decision support, knee osteoarthritis, nomogram, predictors, risk factors

Keyang Li,1,* Debao Li,2,* Hongliang Dong,1 Dongmei Ren,2 Dandan Gong,1 Shubo Wang,1 Yang Li,1 Yuanyuan Wu,1 Jikang Yang,3 Wenjuan Yan,4 Yi Li4 1Department of Clinical Pharmacy, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 2Department of Clinical Laboratory, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 3Infectious Diseases Department, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 4Department of Clinical Laboratory, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenjuan Yan; Yi Li, Department of Clinical Laboratory, Henan Provincial People’s Hospital, Weiwu Road 7#, Jinshui District, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86 15225061830 ; +86 15939039006, Email yanwenjuan2008@126.com; liyilabmed@henu.edu.cnPurpose: Since the introduction of ceftazidime–avibactam (CZA) in the Chinese market, accumulating clinical evidence has substantiated its efficacy in the treatment of infections caused by carbapenem-resistant gram-negative bacteria (CR-GNB). Nevertheless, an ongoing debate persists concerning the choice between monotherapy and combination therapy when devising clinical anti-infection protocols.Patients and Methods: This retrospective, single-center observational study enrolled patients with CR-GNB infections who received CZA treatment between December 2019 and August 2023. The primary outcome assessed was 30-day mortality, and the secondary outcome measured was 14-day bacterial clearance. A multivariate Cox regression model was used to identify variables that were independently associated with 30-day mortality rate.Results: Eighty-three patients were enrolled in the study; of which, 45 received CZA monotherapy, whereas 38 received combination therapy. The overall 30-day mortality rate was 31.3%, and no significant difference was observed in the 30-day mortality rates between the CZA combination therapy and monotherapy groups (31.6% vs 31.1%, p=0.963). After adjustment by propensity score matching, the 30-day mortality rate was not significantly different between the two groups (28.6% vs 31.4%, p=0.794). Multivariate COX analysis revealed that age and SOFA score were independent predictors of 30-day mortality.Conclusion: Combination therapy with CZA and other antimicrobials was not found to have an advantage over monotherapy in reducing the 30-day mortality rate.Keywords: ceftazidime-avibactam, carbapenem-resistant gram-negative bacteria, combination therapy K. pneumoniae carbapenemase

Zheng Yang, Zhanli Shi, Kun Fang, Danhong Ren Department of Intensive Care Unit, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, 310003, People’s Republic of ChinaCorrespondence: Danhong Ren, Department of Intensive Care Unit, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, 310003, People’s Republic of China, Email rendanhong330@zcmu.edu.cnBackground: Rickettsia japonica infection is a rare disease, it is rare to report critical and severe case caused by this disease in Zhejiang Province, China.Patient Concerns: We report a patient who initially sought medical attention due to fever and developed coma and convulsions during treatment. The patient did not develop typical eschar and rash. Eventually, the patient needed to be treated in the intensive care unit due to acute respiratory failure.Diagnoses: The patient was diagnosed with Rickettsia japonica bloodstream infection by metagenomic next-generation sequencing (mNGS).Outcomes: Due to the critical illness, the patient was transferred to the intensive care unit, received doxycycline and other treatments, and rapidly recovered and discharged.Conclusion: The patient developed a critical illness after being infected with Rickettsia, when the medical history is unclear and clinical symptoms and signs are atypical, it is necessary to use mNGS examination for diagnosis.Keywords: rickettsia japonica, rickettsiosis, infection, metagenomic next-generation sequencing, critical illness

Solar wind heating is an outstanding issue that has been discussed for decades. Research on the connection between solar wind particle temperatures and turbulence may provide insight into this issue. Based on Parker Solar Probe observations, this paper investigates the properties of solar wind proton and electron temperatures in relation to turbulent magnetic energy, via the calculation of correlation coefficients (CCs) between particle temperatures and magnetic energy. The calculations are regulated by the spatial scale, plasma beta (β), and the angle between the solar wind velocity and background magnetic field, where the plasma beta is the ratio of plasma thermal to magnetic pressure. Results show that the correlation between proton temperature and magnetic energy is positive and can be strong with a CC exceeding 0.8. The strong correlation preferentially occurs at ion scales, with the wind velocity and background magnetic field quasi-perpendicular and over a wide beta range (β < 3.0). On the other hand, the correlation between electron temperature and magnetic energy is commonly negative, often with an intermediate or negligible CC, accordingly. The CC with an amplitude up to 0.8 can arise at larger scales with the wind velocity and background magnetic field quasi-(anti)parallel and in the low-beta case (β < 0.6). The implication of these findings on the physics of turbulent heating in the solar wind is discussed. [ABSTRACT FROM AUTHOR]

In recent decades, global aquaculture has expanded rapidly, raising concerns about coastal environmental degradation due to unregulated or poorly regulated discharge of aquaculture tailwater. Despite the crucial role of dissolved organic matter (DOM) in biogeochemical processes and aquatic biodiversity, the influence of aquaculture type on the molecular characteristics of DOM remains largely unexplored. Herein, this study investigated the variations in chemical and spectroscopic properties as well as molecular characteristics and composition of DOM across different aquaculture types including crustacean, fish and shellfish. Our findings revealed notable differences in DOM quantities among different aquaculture types, with crustacean and fish aquaculture water containing higher DOM amount compared to shellfish aquaculture water. This disparity can be attributed to the more frequent formulated feeds of crustacean and fish in contrast to shellfish aquaculture. Furthermore, distinct differences were also observed in the characteristics and composition of DOM among the different aquaculture waters. Specifically, DOM in shellfish aquaculture water exhibited a higher abundance of unsaturated and reduced molecules as well as increased aromaticity compared to the other two aquaculture waters. Conversely, DOM from fish aquaculture water showed a greater contribution from terrestrial origin characterized by elevated levels of plant-based components such as lignin-like and tannin-like compounds. Interestingly, DOM from shellfish aquaculture water contained lower levels of microbial-derived components such as lipid-like and protein-like compounds, likely due to reduced microorganism populations resulting from lower nutrients availability and higher salinity. Overall, these significant variations in characteristics and composition of DOM underscore the potential impacts of aquaculture type on the DOM biogeochemical cycle and the environmental quality in aquatic ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Group 2 innate lymphoid cells (ILC2s) play a crucial role in allergic diseases by coordinating a complex network of various effector cell lineages involved in type 2 inflammation. However, their function in regulating airway neutrophil infiltration, a deleterious symptom of severe asthma, remains unknown. Here, we observed ILC2-dependent neutrophil accumulation in the bronchoalveolar lavage fluid (BALF) of allergic mouse models. Chromatography followed by proteomics analysis identified the alarmin high mobility group box-1 (HMGB1) in the supernatant of lung ILC2s initiated neutrophil chemotaxis. Genetic perturbation of Hmgb1 in ILC2s reduced BALF neutrophil numbers and alleviated airway inflammation. HMGB1 was loaded onto the membrane of lipid droplets (LDs) released from activated lung ILC2s. Genetic inhibition of LD accumulation in ILC2s significantly decreased extracellular HMGB1 abundance and BALF neutrophil infiltration. These findings unveil a previously uncharacterized extracellular LD-mediated immune signaling delivery pathway by which ILC2s regulate airway neutrophil infiltration during allergic inflammation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Streptococcus gallolyticus subspecies pasteurianus (SGSP) is a rare pathogen responsible for infant sepsis and meningitis and is potentially overlooked because it is not included in routine group B streptococcal screenings. Hence, we present a case of SGSP-induced infant meningitis and sepsis, accompanied by bronchopneumonia induced by multidrug-resistant Staphylococcus aureus (MRSA), providing insights into the identification, management, and prognosis of this bacterial infection., Case Summary: A 45-day-old female infant presented with two episodes of high fever (maximum temperature: 39.5 °C) and two generalized grand mal seizure episodes that lasted over ten seconds and self-resolved without concomitant symptoms. Postadmission, the patient's C-reactive protein level was 40.73 mg/L, white blood cell count was 13.42 × 10 9 /L, neutrophil ratio was 78.4%, procalcitonin level was 7.89 μg/L, cerebrospinal fluid (CSF) white cell count was 36 × 10 6 /L, multinucleated cell ratio was 95.2%, and protein concentration was 0.41 g/L. Blood and CSF culture revealed that the pathogen was SGSP. The bacterium was sensitive to ampicillin, furazolidone, penicillin, lincomycin, moxifloxacin, rifampicin, vancomycin, and levofloxacin but resistant to clindamycin and tetracycline. Sputum culture revealed the presence of MRSA, which was sensitive to vancomycin. The patient was diagnosed with meningitis and sepsis caused by SGSP, accompanied by bronchopneumonia induced by MRSA. Ceftriaxone (100 mg/kg/d) combined with vancomycin (10 mg/kg/dose, q6h) was given as an anti-infective treatment postadmission. After 12 days of treatment, the infant was discharged from the hospital with normal CSF, blood culture, and routine blood test results, and no complications, such as subdural effusion, were observed on cranial computed tomography. No growth retardation or neurological sequelae occurred during follow-up., Conclusion: SGPSP-induced infant bacterial meningitis and sepsis should be treated with prompt blood and CSF cultures, and a sensitive antibiotic therapy to ensure a favorable prognosis., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Two-dimensional ferroelectric materials have emerged as a promising candidate for the development of next-generation photodetectors owing to their inherent photogalvanic effect (PGE) and strong light-matter interactions. Recently, the first-ever elemental-based ferroelectric material, black-phosphorus-like Bi (BP-Bi), has been successfully synthesized. In this work, we investigate the PGE of the monolayer (ML) BP-Bi by using ab initio quantum transport simulation. We find that the photocurrent of the ML BP-Bi in the ferroelectric direction (armchair) is significantly larger than that in the vertical ferroelectric direction [zigzag (ZZ)]. For example, despite the comparable optical absorption rates of BP-Bi in the armchair (ARM) and ZZ directions, the maximum photocurrent (133 mA/W) in the ARM direction is 2 orders of magnitude greater than that (4.70 mA/W) in the ZZ direction. The asymmetry is attributed to the breaking and existence of the mirror inversion symmetries along the ARM and ZZ directions, respectively. Our work paves the way for the research of the low-dimensional ferroelectric photodetector.

Dysfunction of zinc finger protein 652 (ZNF652) is associated with various malignant tumors. However, the role of ZNF652 in lung cancer (LC) is poorly understood. Here, we identified that ZNF652 was downregulated in human LC tissues and cell lines. Low ZNF652 expression was associated with poor survival in LC patients. Overexpression of ZNF652 inhibited cell viability, proliferation, migration, and invasion of LC cells, whereas ZNF652 knockdown promoted these malignant phenotypes. Using RNA-seq analysis revealed that ZNF652 overexpression resulted in obvious alterations of various biological processes, especially cell cycle and cellular senescence. Subsequently, we confirmed that ZNF652 overexpression arrested the cell cycle at the G1 phase, increased ROS-mediated DNA damage, induced LC cell senescence, and enhanced cisplatin-induced apoptosis in LC cells. Mechanistically, ZNF652 directly bound to the promoter of cyclin D3 (CCND3), inhibited its transcription, thereby arresting the cell cycle at the G1 phase. Ectopic expression of cyclin D3 rescued the decreased cell viability and cell cycle arrest induced by ZNF652. In vivo studies further showed that ZNF652 overexpression suppressed the tumorigenic potential of LC. Collectively, our findings reveal that ZNF652 exerts a tumor suppressor role in lung cancer by inducing cell cycle arrest and cellular senescence via transcriptionally downregulating cyclin D3. Thus, ZNF652 may be a prognostic predictive factor for LC patients., (© 2024. The Author(s).)

Objective: To characterize labor progress among nulliparous women by applying group-based trajectory analysis and examining predictors of group membership., Design: Retrospective observational., Setting: An existing biobank and database from a birth hospital in Western Pennsylvania., Participants: Nulliparous women with low-risk pregnancies at term gestation with singleton fetuses in vertex presentation (N = 401)., Methods: We characterized labor progress by applying group-based trajectory analysis. We conducted a multinomial logistic regression analysis to examine the relationships among labor trajectory groups and various demographic and clinical variables., Results: We identified three trajectories of labor in the group-based trajectory analyses: precipitously progressing (n = 76, 20.1%), average (n = 245, 59.1%), and slow progress (n = 80, 20.7%). Only gestational age at birth significantly predicted trajectory group membership, and an increased gestational age was associated with greater odds of belonging to the slower progress group (OR = 1.43, 95% CI [1.06, 1.92])., Conclusion: We identified multiple trajectories of labor progress in a sample of nulliparous women with low-risk pregnancies at term gestation. Gestational age may help predict the trajectory of labor., Competing Interests: Conflict of Interest The authors report no conflicts of interest or relevant financial relationships., (Copyright © 2024 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

An integrated system for in vivo multi-spectral imaging (MSI) and Raman spectroscopy was developed to understand the external morphology and internal molecular information of biological tissues. The achieved MSI images were reconstructed by eighteen separated images from 400 nm to 760 nm, whose illumination bands were selected with six tri-channel band filters. Based on the spectral analysis algorithms, the spatial distribution patterns of blood volume, blood oxygen content and tissue scatterer volume fraction were visualized. In vivo Raman spectral measurements were executed by inserting specially designed optical probe into instrumental channel of endoscope. By this way, the molecular composition at selected sampling points could be identified with its fingerprint spectral information under the guidance of molecular imaging modality. Therefore, both structural and compositional features of intestinal membrane could be addressed without labeling and continuously. The achieved results testified that our presented methodology reveals insights not easily extracted from either MSI or Raman spectroscopy individually, which brings the enrichment of biological and chemical meanings for future in vivo studies., Competing Interests: Declaration of competing interest The authors have claimed that they have no known competing financial interests or personal relationships that could influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Laminaria digitata is a high-quality seaweed resource that is widely cultured and has good application prospects. In this study, Laminaria digitata fucoidan (LF) was extracted from Laminaria digitata, and purified using DEAE-Sepharose Fast Flow gel column to obtain four different grades. Among those, LF4 (Mw:165 kDa), mainly composed of fucose(56.80 %), had the highest total sugar (66.91 %) and sulfate (17.07 %) content. FT-RT and NMR results showed that LF4 was mainly composed of galactosylated galactofucose, and has a sulfate group attached to fucose C4. With the animal experimentation, it was revealed that hyperlipidaemic mice had significantly higher levels of TC (5.52 mmol/L), TG (2.28 mmol/L) and LDL-C (5.12 mmol/L) and significantly lower levels of HDL-C (2 mmol/L). However, LF had the efficacy in modulating the lipid metabolism disturbances induced by hyperlipidemia, as well as the ability to regulate cholesterol transport in serum. Moreover, it regulated AMPK/ACC, PPAR-α/LAXRa, Nrf2/Nqo1, TLR4/NF-κB signaling pathway genes and proteins expression in the liver. In addition, it promoted the production of beneficial short-chain fatty acids (SCFAs) while improving the composition and structure of gut microbiota, including balancing the abundance of Bacteroidota, Firmicutes, Muribaculaceae, Alloprevotella, Escherichia-Shigella, Prevotella and NK4A136. The results clearly indicated that LF4 could significantly ameliorate hyperlipidemia, suggesting its prospective application as a functional food., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Nicotinamide (NAM) is easily degraded in the rumen, but the rumen-protected NAM (RPN) supplementation might enable the use of NAM in ruminants. This study aimed to elucidate the effects of RPN supplementation on growth performance, rumen fermentation, antioxidant status and amino acid (AA) metabolism in growing lambs., Methods: A total of 128 healthy and similar lambs (21.3±0.28 kg, 70±6.3 days of age) were allotted to 1 of 4 groups. The treatments were 0, 0.5, 1, and 2 g/d RPN supplementation. The RPN products (50% bioavailability) were fed at 0700 h every day for 12 weeks. All lambs were fed the same pelleted total mixed rations to allow ad libitum consumption and had free access to water., Results: The RPN tended to increase the average daily gain and feed efficiency. The tendencies of RPN×day interaction were found for dry matter intake during the entire study (p = 0.078 and 0.073, respectively). The proportions of acetic acid, isobutyric acid and isovaleric acid were decreased, whereas the proportions of propionic acid and valeric acid were increased (p<0.05). The ratio of acetic acid to propionic acid was decreased (p<0.05). Moreover, the antioxidative status was enhanced and the glucose concentration was increased by RPN (p<0.05). In addition, 17 AAs were detected in plasma, of which 11 AAs were increased by RPN (p<0.05). Plasma metabolomics analysis identified 1,395 compounds belonging to 15 classes, among which 7 peptides were significantly changed after RPN supplementation., Conclusion: Overall, the results suggested that RPN supplementation favoured the rumen fermentation pattern to propionic acid-type with benefited glucose metabolism, enhanced antioxidant capacity, and changed the AA and small peptide metabolism. This study provides a new perspective for studying the relationship between vitamin and AA metabolism.

Spinal cord injury (SCI) is a debilitating neurological and pathological condition that results in significant impairments in motor, sensory, and autonomic functions. By integrating multispectral imaging (MSI) with Raman spectroscopy, a label-free optical methodology was developed for achieving a non-invasive in vivo understanding on the pathological features of SCI evolution. Under the guidance of captured the spectral imaging data cube with a rigid endoscope based MSI system, a special designed fiber probe passed through the instrumental channel for acquiring the finger-print spectral information from compression rat SCI models. After identifying the main visual features of injured spinal cord tissue in all Sham, 0-, 3- and 7-days post injury (0 DPI, 3 DPI, and 7 DPI) groups, the blood volume and oxygen content were visualized to describe hemorrhage, hypoxia and inflammatory state after acute injury. The averaged reflectance spectra, which were deduced from MSI data cubes, were utilized for describing oxygen saturation and hemoglobin concentration in living tissue. The results of Raman spectroscopy addressed complex compositional and conformational phenomena during SCI progression, correlated with the well-known event like neuronal apoptosis, hemorrhage, demyelination, and even the upregulation of chondroitin sulfate proteoglycans (CSPGs). A principal component analysis and linear discriminate algorithm (PCA-LDA) based discriminate model was introduced for categorizing spectral features in different injury stages, which was applicable for intraoperative interpretations on the complex pathological courses of SCI and therapeutic outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Despite some existing studies on the safety of high static magnetic fields (SMFs), the effects of ultra-high SMFs above 20.0 T for embryonic development in early pregnancy are absent. The objective of this study is to evaluate the influence of 16.8-22.0 T SMF on the development of zebrafish embryos, which will provide important information for the future application of ultra-high field magnetic resonance imaging (MRI)., Methods: Two-hour exposure to homogenous (0 T/m) 22.0 T SMF, or 16.8 T SMFs with 123.25 T/m spatial gradient of opposite magnetic force directions was examined in the embryonic development of 200 zebrafish. Their body length, heart rate, spontaneous tail-wagging movement, hatching and survival rate, photomotor response, and visual motor response (VMR) were analyzed., Results: Our results show that these ultra-high SMFs did not significantly affect the general development of zebrafish embryos, such as the body length or spontaneous tail-wagging movement. However, the hatching rate was reduced by the gradient SMFs (p < 0.05), but not the homogenous 22.0 T SMF. Moreover, although the zebrafish larva activities were differentially affected by these ultra-high SMFs (p < 0.05), the expression of several visual and neurodevelopmental genes (p < 0.05) was generally downregulated in the eyeball., Conclusions: Our findings suggest that exposure to ultra-high SMFs, especially the gradient SMFs, may have adverse effects on embryonic development, which should cause some attention to the future application of ultra-high field MRIs., Clinical Relevance Statement: As technology advances, it is conceivable that very strong magnetic fields may be adapted for use in medical imaging. Possible dangers associated with these higher Tesla fields need to be considered and evaluated prior to human use., Key Points: Ultra-High static magnetic field may affect early embryonic development. High strength gradient static magnetic field exposure impacted zebrafish embryonic development. The application of very strong magnetic fields for MR technologies needs to be carefully evaluated., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Aims/Background Neonatal morbidity, including various diseases such as sepsis, cholestasis, and bronchopulmonary dysplasia (BPD), is a significant concern, especially in preterm infants. Selecting the appropriate lipid emulsion in parenteral nutrition (PN) is essential to improve clinical outcomes. This analysis aimed to assess the impact of a novel composite lipid emulsion, SMOFlipid, on neonates receiving PN. Methods A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted. We compared SMOFlipid to various other lipid emulsions in PN received by infants. Research findings that addressed outcomes such as mortality, sepsis, cholestasis, necrotizing enterocolitis (NEC), BPD, patent ductus arteriosus (PDA), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), and length of hospital stay were included. Subgroup analyses were conducted based on gestational age (GA). Twenty RCTs involving 1904 neonates were included. Results Compared to other lipid emulsions, SMOFlipid significantly reduced the cholestasis risk (risk ratio (RR): 0.65, 95% confidence interval (CI): 0.48-0.87, p = 0.004, I 2 = 0%). However, the incidence related to IVH, BPD, ROP, NEC, and PDA (excluding an infant subgroup with GA <28 weeks), mortality, sepsis, and duration of hospital stay did not exhibit any substantial variations. The subgroup analysis indicated a decline in PDA incidence (RR: 0.88, 95% CI: 0.79-0.99, p = 0.04, I 2 = 0%) among extremely premature infants receiving SMOFlipid. Conclusion SMOFlipid offers a promising option for neonatal PN, particularly for reducing cholestasis in preterm infants and PDA in extremely premature infants. Further investigations into its comprehensive benefits and long-term effects are warranted.

A previous study showed that kiwifruit polysaccharide (KFP) has benefits in relieving intestinal inflammation, while the underlying mechanism remains unresolved. The objective of this study was to investigate the regulatory effect of KFP on the gut microbiota metabolism and intestinal barrier of ulcerative colitis (UC) mice induced by dextran sulfate sodium (DSS). KFP significantly improved the UC symptoms including weight loss, shortened colon length, splenomegaly, diarrhea, hematochezia, and colon inflammation of mice. In addition, KFP could alleviate DSS-caused gut microbiota dysbiosis and increase the levels of short-chain fatty acids in the cecal contents of mice. Furthermore, the results of nontargeted and targeted metabolomics analysis combined with antibiotic treatment revealed that KFP could regulate gut microbiota-dependent tryptophan metabolism, activate the aryl hydrocarbon receptor (AhR) in colon cells, and enhance interleukin-22 production and tight junction proteins' (ZO-1, occludin, and claudin3) expression to repair the intestinal barrier in UC mice. Immunofluorescence results showed that KFP significantly upregulated the conjunction of lectin WGA and UEA1 in the UC mouse colon, implying that KFP promoted fucosylation in the colon. These results suggest that KFP alleviates UC primarily via targeting the gut microbiota involved in the AhR pathway and upregulating colon fucosylation.

Fructose 1,6-bisphosphate aldolase (FBA) is a class of aldolase that functions as enzyme participating in carbohydrate metabolism of the Calvin-Benson cycle, gluconeogenesis, and glycolysis, and also as non-enzymatic protein involving in protein binding, gene transcription, signal transduction. FBAs have been identified in a few plant species, however, limited information is known regarding FBA family genes, their biological functions and posttranslational regulations in maize (Zea mays). In this study, nine class I FBAs (ZmFBA1 to ZmFBA9) and one class II FBA (ZmFBA10) in maize were identified. Phosphoproteomic analysis further revealed that multiple ZmFBAs were phosphorylated. We showed that phosphorylation at Ser32 in ZmFBA8 inhibited its FBP binding and enzyme activity. Loss of ZmFBA8 function reduced the growth of maize seedlings. Our results suggest that the phosphorylation is an important regulatory mechanism of ZmFBA8 function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Two mitogen-activated protein kinase (MAPK) cascades with MPK4 and MPK3/MPK6 as the bottommost kinases are key to plant growth/development and immune signaling. Disruption of the MPK4 cascade leads to severe dwarfism and autoimmunity, complicating the study of MPK4 in plant growth/development and immunity. In this study, we successfully rescued the Arabidopsis (Arabidopsis thaliana) mpk4 mutant using a chemical-sensitized MPK4 variant, MPK4YG, creating a conditional activity-null mpk4 mutant named MPK4SR (genotype: PMPK4:MPK4YG mpk4) that could be used to examine the functions of MPK4 in plant growth/development and immunity. We discovered that the duration of the loss of MPK4 activity is important to plant immune responses. Short-term loss of MPK4 activity did not impact flg22-induced ROS burst or resistance against Pseudomonas syringae (Pst). Enhanced Pst resistance was only observed in the MPK4SR plants with stunted growth following prolonged inhibition of MPK4 activity. Transcriptome analyses in plants with short-term loss of MPK4 activity revealed a vital role of MPK4 in regulating several housekeeping processes, including mitosis, transcription initiation, and cell wall macromolecule catabolism. Furthermore, the constitutive weak activation of MPK4GA in the MPK4CA plants (genotype: PMPK4:MPK4GA mpk4) led to early flowering and premature senescence, which was associated with its compromised resistance against Pst. These findings suggest that MPK4 plays important roles in plant growth and development and in maintaining the delicate balance between growth/development and immune adaptation in plants., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Altering the physical structure and chemical property of copper, i.e., particle size, surface morphology, composition or crystal facet, has been demonstrated to be effective in steering the selectivity of products in electrochemical reduction of carbon dioxide. However, these modifications generally result in the change of active surface area, leading to differences in the geometric current density and local pH, which are also demonstrated to be the key factors for observed selectivity change. In this work, we deconvolute the effect of mass transport and local pH from the effect of crystal facet by investigating five copper-based catalysts with identical roughness factors for electrochemical reduction of carbon dioxide in an H-cell. Interestingly, CuO-derived catalyst stands out as the best catalyst for C-C coupling. At -1.07 V vs. RHE, the faradaic efficiency of C2+ product reaches 44.3%, with a partial current density of -10.8 mA cm-2. Electrochemical adsorption of *OH reveals that the C2+ product selectivity of derived-copper catalysts correlates positively with the ratio of Cu(100)/Cu(110) of five catalysts. Additionally, in situ Raman spectroscopy reveals that the percentage of low-frequency band linear CO (LFB-CO), which is attributed to the adsorbed *CO on Cu(100) facet, increases with the C-C coupling efficiency., (© 2024 Wiley‐VCH GmbH.)

Introduction: Hyperlipidemic acute pancreatitis (HLAP) is a form of pancreatitis induced by hyperlipidemia, posing significant diagnostic challenges due to its complex lipid metabolism disturbances., Methods: This study compared the serum lipid profiles of HLAP patients with those of a healthy cohort using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Orthogonal partial least squares discriminant analysis (OPLS-DA) was applied to identify distinct lipid metabolites. Logistic regression and LASSO regression were used to develop a diagnostic model based on the lipid molecules identified., Results: A total of 393 distinct lipid metabolites were detected, impacting critical pathways such as fatty acid, sphingolipid, and glycerophospholipid metabolism. Five specific lipid molecules were selected to construct a diagnostic model, which achieved an area under the curve (AUC) of 1 in the receiver operating characteristic (ROC) analysis, indicating outstanding diagnostic accuracy., Discussion: These findings highlight the importance of lipid metabolism disturbances in HLAP. The identified lipid molecules could serve as valuable biomarkers for HLAP diagnosis, offering potential for more accurate and early detection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ren, Li, Zhang, Li and Liu.)

Coccidioidomycosis is a fungal infection commonly found in the tropical regions of southwestern United States, such as Arizona, the Central Valley of California, parts of New Mexico, and western Texas. The endemic regions also extend into northern Mexico and include focal endemic areas in sections of Central America and Argentina. Coccidioides species have also been reported in central and southern Utah, Nevada, and the central part of Washington State., the pathogenic bacteria commonly colonize the lungs. China, which is outside the traditionally established endemic area, is witnessing a rise in reported cases of pulmonary coccidioidomycosis. Meanwhile, the comorbidities of the disease began to become complicated. We reported two Chinese patients with pulmonary coccidioidomycosis complicated by organizing pneumonia and reviewed 42 cases of Chinese patients in the literature from 1958 to 2024. Out of the 44 patients from 13 different provinces (Including Hong Kong Special Administrative Region and Taiwan), the average age was (43.08 ± 3.03) years. Among them, 34 (76.7 %) were male, while 10 (23.3 %) were female, cough/sputum (81.8 %) are the most common symptoms, the cases are concentrated in coastal areas. 27(61.4 %) were Imported and 17(38.6 %) were domestic primary cases, showing a higher proportion of imported cases compared to domestic primary cases. Misdiagnosis and mistreatment have a significant impact on patients, the combination of new technologies and traditional pathology diagnosis have substantially promoted precise diagnosis for clinician in non-endemic areas. Interestingly, the histopathological findings of the two patients we report showed evident organizing pneumonia and an increased eosinophil count, the application of corticosteroid drugs notably improved the patients' conditions. Overall, at least 84.1 % of patients had a favorable prognosis. Considering the changing epidemiology of pulmonary coccidioidomycosis, Chinese healthcare providers should be cautious about their patients' travel history, particularly among male individuals., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Purpose: The novel coronavirus pneumonia (COVID-19) has continually spread and mutated, requiring a patient risk stratification system to optimize medical resources and improve pandemic response. We aimed to develop a conformal prediction-based tri-light warning system for stratifying COVID-19 patients, applicable to both original and emerging variants., Methods: We retrospectively collected data from 3646 patients across multiple centers in China. The dataset was divided into a training set (n = 1451), a validation set (n = 662), an external test set from Huoshenshan Field Hospital (n = 1263), and a specific test set for Delta and Omicron variants (n = 544). The tri-light warning system extracts radiomic features from CT (computed tomography) and integrates clinical records to classify patients into high-risk (red), uncertain-risk (yellow), and low-risk (green) categories. Models were built to predict ICU (intensive care unit) admissions (adverse cases in training/validation/Huoshenshan/variant test sets: n = 39/21/262/11) and were evaluated using AUROC ((area under the receiver operating characteristic curve)) and AUPRC ((area under the precision-recall curve)) metrics., Results: The dataset included 1830 men (50.2 %) and 1816 women (50.8 %), with a median age of 53.7 years (IQR [interquartile range]: 42-65 years). The system demonstrated strong performance under data distribution shifts, with AUROC of 0.89 and AUPRC of 0.42 for original strains, and AUROC of 0.77-0.85 and AUPRC of 0.51-0.60 for variants., Conclusion: The tri-light warning system can enhance pandemic responses by effectively stratifying COVID-19 patients under varying conditions and data shifts., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiao Li reports financial support was provided by National Natural Science Foundation of China. NA reports a relationship with NA that includes:. NA has patent NA pending to NA. NA If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Abstract: We present the 18F-FDG PET/CT findings of a 64-year-old man with isolated renal metastasis. He had a history of radical surgery for squamous cell lung cancer 14 months ago, followed by chemotherapy and immunotherapy. The renal metastasis presented as a small focus of increased FDG uptake in the restaging 18F-FDG PET/CT scan, which was regarded as renal cortical tracer retention. The renal metastasis was more prominent on the second PET/CT performed 5 months later. The patient subsequently underwent radical nephrectomy, and histopathological examination confirmed the diagnosis of renal squamous cell carcinoma metastasis., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The study's objective was to assess the effect of the screw insertion depth into fractured vertebrae in treating thoracolumbar fractures., Materials and Methods: This was a retrospective analysis of 92 patients with thoracolumbar fractures from December 2018 to February 2020. Patients had AO type A2, A3 thoracolumbar fractures. The patients were divided into two groups according to the screw insertion depth. The vertebral wedge angle (VWA), Cobb angle (CA), anterior vertebral body height (AVBH), middle vertebral body height (MVBH), visual analog scale (VAS) score, and Oswestry Disability Index (ODI) were compared preoperatively and at one week and 12 months postoperatively. The correlation between Vertebral height loss and potential risk factors, such as sex, age, BMD and BMI was evaluated., Results: Compared with the preoperative data, the postoperative clinical and radiographic findings were significantly different in both groups, But no significant difference between the two groups at 1 week. At 1 year postoperatively, there was a significant difference in the CA (p < 0.0001), VWA (p = 0.047), AVBH (p < 0.0001), MVBH (p < 0.0001), VAS score (p < 0.0001), and ODI (p < 0.0001) between the two groups, Except for age, bone density and other influencing factors the long screw group had better treatment results than the short screw group., Conclusion: A longer screw provides greater grip on the fractured vertebral body and stronger support to the vertebral plate. The optimal screw placement depth exceeds 60% of the vertebral body length on the lateral view., (© 2024. The Author(s).)

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel Lindau (VHL) gene loss of function mutation, which leads to the accumulation of hypoxia-inducible factor 2α (HIF2α). HIF2α has been well-established as one of the major oncogenic drivers of ccRCC, however, its therapeutic targeting remains a challenge. Through an analysis of proteomic data from ccRCCs and adjacent non-tumor tissues, we herein revealed that Ubiquitin-Specific Peptidase 7 (USP7) was upregulated in tumor tissues, and its depletion by inhibitors or shRNAs caused significant suppression of tumor progression in vitro and in vivo. Mechanistically, USP7 expression is activated by the transcription factors FUBP1 and FUBP3, and it promotes tumor progression mainly by deubiquitinating and stabilizing HIF2α. Moreover, the combination of USP7 inhibitors and afatinib (an ERBB family inhibitor) coordinately induce cell death and tumor suppression. In mechanism, afatinib indirectly inhibits USP7 transcription and accelerates the degradation of HIF2α protein, and the combination of them caused a more profound suppression of HIF2α abundance. These findings reveal a FUBPs-USP7-HIF2α regulatory axis that underlies the progression of ccRCC and provides a rationale for therapeutic targeting of oncogenic HIF2α via combinational treatment of USP7 inhibitor and afatinib., (© 2024. The Author(s).)

Prostaglandin E2 (PGE2), an eicosane, regulates the physiological activity of inflammatory cells and represents a potential therapeutic target for facilitating tissue repair in vivo. In our work, an electrochemical immunosensor employing Ketjen black-Au nanoparticles (KB-Au) and poly tannic acid nanospheres conjugated with anti-PGE2 polyclonal antibody (PTAN-Ab) was designed to ultra-sensitively analyze PGE2 levels secreted by living cells and tissues. Antibody assembly strategies were explored to achieve signal amplification. Moreover, we studied the therapy effects of docosahexaenoic acid (DHA), arachidonic acid (AA), hyaluronic acid (HA), and small molecule 15-hydroxyprostaglandin dehydrogenase inhibitor (SW033291) on inflammation and evaluated the protective functions of HA and SW033291 in a murine model subjected to colitis induced by dextran sulfate sodium (DSS) using the developed sensor. The sensor exhibited a linear range of 10 -5 -10 6  fg/mL and a detection limit (LOD) of 10 -5  fg/mL. Fetal bovine serum (FBS) samples were used to achieve high recovery of target analytes. This study not only presents an effective strategy for ultra-sensitively monitoring PGE2 but also provides valuable insights into assessing the degree of inflammation and the therapeutic effect of related drugs. Research on human health monitoring and regenerative medicine could greatly benefit from the findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The proliferation of edge devices driven by advancements in Internet of Things (IoT) technology has intensified the challenge of achieving high-precision small target detection, as it demands extensive computational resources. This amplifies the conflict between the need for precise detection and the requirement for cost-efficiency across numerous edge devices. To solve this problem, this paper introduces an enhanced target detection algorithm, MSGD-YOLO, built upon YOLOv8. The Faster Implementation of CSP Bottleneck with 2 convolutions (C2f) module is enhanced through the integration of the Ghost module and dynamic convolution, resulting in a more lightweight architecture while enhancing feature generation. Additionally, Spatial Pyramid Pooling with Enhanced Local Attention Network (SPPELAN) replaces Spatial Pyramid Pooling Fast (SPPF) to expand the receptive field, optimizing multi-level feature aggregation for improved performance. Furthermore, a novel Multi-Scale Ghost Convolution (MSGConv) and Multi-Scale Generalized Feature Pyramid Network (MSGPFN) are introduced to enhance feature fusion and integrate multi-scale information. Finally, four optimized dynamic convolutional detection heads are employed to capture target features more accurately and improve small target detection precision. Evaluation on the VisDrone2019 dataset shows that compared with YOLOv8-n, MSGD-YOLO improves mAP@50 and mAP@50-95 by 14.1% and 11.2%, respectively. In addition, the model not only achieves a 16.1% reduction in parameters but also attains a processing speed of 24.6 Frames Per Second (FPS) on embedded devices, thereby fulfilling real-time detection requirements., (© 2024. The Author(s).)

Accurate analysis of multiple microRNA (miRNA) levels is significantly valuable for early diagnosis of colorectal cancer noninvasively considering the miRNA expression is highly relevant to the occurrence and progression of cancer. However, the low abundance and high sequence homology of miRNAs make their precise determination extremely challenging. Here, we developed a universal and programmable diagnostic strategy allowing for analyzing multiple colorectal cancer-associated miRNAs. The system combined sequentially programmable rolling circle transcription (RCT) and the CRISPR/Cas12a system with high trans-cleavage activity to achieve highly sensitive and specific detection of four target miRNAs. Owing to the remarkable performance of universal RCT-Cas12a strategy, this biosensor could detect miR-21, miR-17, miR-31 and miR-92a with a LOD of 2.1, 1.6, 3.7 and 1.0 pM, respectively. This strategy had a unique advantage in distinguishing human normal colon epithelial cells lines (NCM460) from human colon cancer cells (HT29). In particular, the designed system exhibited superior analytical capability in distinguishing paracancerous and colorectal cancer tissues from patients undergoing colorectal cancer surgery. This arbitrarily programmable, scalable, fast and specific strategy potentially offered an attractive alternative to handle varied challenges encountered with CRISPR-based systems, and held immense promise in scientific research and clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Multi-site functionalization of molecules provides a potent approach to accessing intricate compounds. However, simultaneous functionalization of the reactive site and the inert remote C(sp 3 )-H poses a formidable challenge, as chemical reactions conventionally occur at the most active site. In addition, achieving precise control over site selectivity for remote C(sp 3 )-H activation presents an additional hurdle. Here we report an alternative modular method for alkene difunctionalization, encompassing radical-triggered translocation of functional groups and remote C(sp 3 )-H desaturation via photo/cobalt dual catalysis. By systematically combining radical addition, functional group migration and cobalt-promoted hydrogen atom transfer, we successfully effectuate the translocation of the carbon-carbon double bond and another functional group with precise site selectivity and remarkable E/Z selectivity. This redox-neutral approach shows good compatibility with diverse fluoroalkyl and sulfonyl radical precursors, enabling the migration of benzoyloxy, acetoxy, formyl, cyano and heteroaryl groups. This protocol offers a resolution for the simultaneous transformation of manifold sites., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In this research, accelerated aroma release experiments and malvidin-3-O-glucoside copigmentation experiments in model red wine solutions were designed to investigate the abilities and molecular mechanisms of mannoproteins in modulating olfactory/chromatic properties of red wines. Results indicate that under orthonasal condition, mannoprotein MP2 was promising aroma modulator due to its predictable behaviors in expelling and retaining the aroma compounds during different periods. Low field nuclear magnetic resonance and molecular dynamic simulation proved that the modulation ability of MP2 should be explained by its transitionary interacting preferences with water/aroma compound molecules. Retronasal results show that the release of aroma compounds and olfactory perceptions were irregular and difficult to predict, probably due to the complexity of the retronasal condition. All mannoproteins protected malvidin-3-O-glucoside and quercetin via the formation of binary/ternary complexes, and quercetin was found prior to be protected than malvidin-3-O-glucoside. Principal mannoprotein A0A6C1DV26 might be the critical malvidin-3-O-glucoside protector. With the presence of quercetin, principal mannoproteins B3LQU1/B5VL26 in mannoprotein MP1 might exhibit intramolecular and/or intermolecular mechanisms that strengthened the hyperchromic effect, thus enhanced the copigmentation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Many medical devices implanted in patients to mitigate diseases and medical conditions have different types of topographic features. While appropriate textures can promote the integration of host cells and reduce scar tissue formation, some textured implants with inappropriate topographies have been associated with inflammation, bacterial colonization, or even malignant complications. To better understand how surface topography affects host immune response to colonizing bacteria, a protocol was developed to investigate phagocytosis of bacterial cells attached on polydimethylsiloxane (PDMS) surfaces with different square-shaped recessive patterns. The interaction between activated RAW 264.7 macrophages and Escherichia coli in recessive wells was visualized in 3D using multiple fluorescent markers. The results revealed that there is a threshold dimension of topography, below which phagocytosis of attached bacterial cells is significantly impeded. Specifically, under our experimental condition, up to 100-fold reduction in phagocytosis was observed in square-shaped patterns with 5 µm side length and 10 µm depth compared to the flat control and patterns with 10 µm or longer side length. The spacing between wells also showed significant effects; e.g., phagocytosis in the wells further decreased when spacing increased to 50 µm. These results are helpful for understanding how undesired topographies may contribute to bacterial colonization and thus infection and other associated complications. STATEMENT OF SIGNIFICANCE: Surface topography plays an important role in bacteria-material infections and thus the safety of implantable medical devices. Undesired topographic features can cause biofilm formation and related complications. However, how surface topography affects the capability of host immune cells to clear colonizing bacteria is not well understood. In this study, the interaction between macrophage RAW264.7 and colonizing E. coli cells on polydimethylsiloxane (PDMS) with recessive features is investigated. It was discovered that the size of recessive features and the spacing between these features have significant effects on phagocytosis of bacteria by macrophages. These new results are helpful for understanding the complex interaction among host cells, bacteria, and implanted biomaterials, which will help guide the rational design of safer medical devices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. All rights reserved.)

Objectives: During the COVID-19 pandemic, there was a marked shift toward telesimulation in medical education. Limited studies exist comparing the effectiveness of online and offline simulation education. The goals of this study are to evaluate active learners' perceived effectiveness of telesimulation versus in situ simulation and to identify potential shortcomings of existing online teaching platforms., Methods: Through participant evaluations after a simulation, we compared telesimulation using the Virtual Resus Room (VRR) to in situ simulation in the domains of (1) self-efficacy, (2) fidelity, (3) educational value, and (4) teaching quality. Study subjects included medical and pharmacy residents and medical students completing their pediatric emergency medicine rotation at two children's hospitals as well as nurses, nurse practitioners, and physician assistants who were recently hired and orienting to their new roles in the emergency department. Learners used a modified Michigan Standard Simulation Experience Scale to evaluate either a telesimulation or in situ simulation case. Survey responses were compared using Wilcoxon rank sum tests with Bonferroni correction for multiple comparisons., Results: In overall assessment, in situ simulation was rated higher than telesimulation. There were significant differences noted related to perceived realism, utility in training device-related skills, and utility in training team-building skills. All P values were less than 0.0036. There were no significant differences between simulation types in perception of physical examination fidelity, instructor adequacy, or self-efficacy., Conclusions: Telesimulation using the VRR is comparable to in situ simulation in learners' perception of improvement in self-efficacy and of teaching quality for pediatric emergency medicine topics. However, participants felt less able to practice tactile and communication skills virtually. Further innovation is needed to improve learners' experience with fidelity and educational value., Competing Interests: Disclosure: This project was supported by the 2021 Center for Leadership & Innovation in Medical Education (CLIME) Education Scholars' Pilot Grant. The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to investigate whether changes in presepsin, procalcitonin, high-sensitivity C-reactive protein, and interleukin 6 levels predict mortality in septic patients in the intensive care unit. This study enrolled septic patients between November 2020 and December 2021. Levels of presepsin, procalcitonin, high-sensitivity C-reactive protein, and interleukin 6 were measured on the first (PSEP&#95;0, PCT&#95;0, hsCRP&#95;0, IL-6&#95;0) and third days (PSEP&#95;3, PCT&#95;3, hsCRP&#95;3, IL-6&#95;3). Follow-up was performed on days 3, 7, 14, 21, and 28 after enrollment. The outcome was all-cause death. The study included 119 participants, and the mortality was 18.5%. In univariable Cox proportional hazards regression analysis, ΔPSEP (= PSEP&#95;3 - PSEP&#95;0) > 211.49 pg/mL (hazard ratio, 2.70; 95% confidence interval, 1.17-6.22), ΔPCT (= PCT&#95;3 - PCT&#95;0) > -0.13 ng/mL (hazard ratio, 7.31; 95% confidence interval, 2.68-19.80), ΔhsCRP (= hsCRP&#95;3 - hsCRP&#95;0) > -19.29 mg/L (hazard ratio, 6.89; 95% confidence interval, 1.61-29.40), and ΔIL-6 (= IL-6&#95;3 - IL-6&#95;0) > 1.00 pg/mL (hazard ratio, 3.13; 95% confidence interval, 1.35-7.24) indicated an increased risk of mortality. The composite concordance index for alterations in all 4 distinct biomarkers was highest (concordance index, 0.83; 95% confidence interval, 0.76-0.91), suggesting the optimal performance of this panel in mortality prediction. In decision curve analysis, compared with the Acute Physiology and Chronic Health Evaluation II and Sequential (sepsis-related) Organ Failure Assessment scores, the combination of the 4 biomarkers had a larger net benefit. Interestingly, interleukin 6 was predominantly produced by monocytes upon lipopolysaccharide stimulation in peripheral blood mononuclear cells. ΔPSEP, ΔPCT, ΔhsCRP, and ΔIL-6 are reliable biomarkers for predicting mortality in septic patients in the intensive care unit, and their combination has the best performance., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Insects have evolved complex sensory systems that are important for feeding, defence and reproduction. Parasitoid wasps often spend much time and effort in searching for concealed hosts with the help of specialized sensilla. However, the early evolution of such behaviour and sensilla is poorly known. We describe two fossil female wasps, †Tichostephanus kachinensis sp. nov. and †Tichostephanus longus sp. nov., from mid-Cretaceous Kachin amber. Phylogenetic analyses based on morphological data retrieved †Tichostephanus as deeply nested within Evanioidea and closely related to extant Gasteruptiidae and Evaniidae. Both of these Cretaceous wasps possess features, e.g. coronal tubercles and flexible ovipositor sheaths, that indicate that they might have laid eggs in wood where their larvae possibly parasitized insect larvae. They have a peculiar and unique 'bottle brush' of sensilla close to the apex of their ovipositor sheaths, which has not been observed in any extant parasitoid wasps. These sensilla comprise many regularly arranged plate-shaped setae, attached in relatively large sockets and with rows of longitudinal ridges. Such specialized sensilla perhaps served to enhance the ability to detect hosts inside wood., (© 2024 Willi Hennig Society.)

Context.—: Eosinophilic solid and cystic renal cell carcinoma is now defined in the 5th edition of the 2022 World Health Organization classification of urogenital tumors., Objective.—: To perform morphologic, immunohistochemical, and preliminary genetic studies about this new entity in China for the purpose of understanding it better., Design.—: The study includes 18 patients from a regional tertiary oncology center in northern China (Tianjin, China). We investigated the clinical and immunohistochemical features of these cases., Results.—: The mean age of patients was 49.6 years, and the male to female ratio was 11:7. Macroscopically, 1 case had the classic cystic and solid appearance, whereas the others appeared purely solid. Microscopically, all 18 tumors shared a similar solid and focal macrocystic or microcystic growth pattern, and the cells were characterized by voluminous and eosinophilic cytoplasm, along with coarse amphophilic stippling. Immunohistochemically, most of the tumors had a predominant cytokeratin (CK) 20-positive feature, ranging from focal cytoplasmic staining to diffuse membranous accentuation. Initially, we separated these cases into different immunohistochemical phenotypes. Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. Group 2 (4 of 18; 23%) was negative for NF2, probably implying a germline mutation of NF2. Group 3 (7 of 18; 38.5%) consisted of the remaining cases. One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression., Conclusions.—: Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Until the advent of phylogenomics, the atypical morphology of extant representatives of the insect orders Grylloblattodea (ice-crawlers) and Mantophasmatodea (gladiators) had confounding effects on efforts to resolve their placement within Polyneoptera. This recent research has unequivocally shown that these species-poor groups are closely related and form the clade Xenonomia. Nonetheless, divergence dates of these groups remain poorly constrained, and their evolutionary history debated, as the few well-identified fossils, characterized by a suite of morphological features similar to that of extant forms, are comparatively young. Notably, the extant forms of both groups are wingless, whereas most of the pre-Cretaceous insect fossil record is composed of winged insects, which represents a major shortcoming of the taxonomy. Here, we present new specimens embedded in mid-Cretaceous amber from Myanmar and belonging to the recently described species Aristovia daniili. The abundant material and pristine preservation allowed a detailed documentation of the morphology of the species, including critical head features. Combined with a morphological data set encompassing all Polyneoptera, these new data unequivocally demonstrate that A. daniili is a winged stem Grylloblattodea. This discovery demonstrates that winglessness was acquired independently in Grylloblattodea and Mantophasmatodea. Concurrently, wing apomorphic traits shared by the new fossil and earlier fossils demonstrate that a large subset of the former "Protorthoptera" assemblage, representing a third of all known insect species in some Permian localities, are genuine representatives of Xenonomia. Data from the fossil record depict a distinctive evolutionary trajectory, with the group being both highly diverse and abundant during the Permian but experiencing a severe decline from the Triassic onwards., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

Aims: Endoplasmic reticulum protein 29 (ERP29) is crucial for endoplasmic reticulum stress (ERS). M6A plays an important role in the progression of endometrial cancer (EC). The study investigated the role of ERS-related gene (ERP29) and m6A in EC., Materials and Methods: We screened ERS-related genes based on the GEO dataset, GSEA dataset and TCGA-UCEC database using WGCNA and two machine learning algorithms. The m6A-related GEO dataset was employed to identify the ERS-related hub genes with m6A. Expression of hub genes in different cell types were visualize through scRNA-seq data analyzing. Using qPCR, Western blot, and Immunohistochemical assays to detect the expression of ERP29, the effect of ERP29 on cancer cell proliferation was investigated through CCK8, EdU and clone formation experiments. M6A modifications were studied using m6A Dot blot and MeRIP-qPCR. Finally, we conducted rescue experiments., Key Findings: Ten ERS-related hub genes with m6A were identified. ERP29 is highly expressed in EC. ERP29 knockdown inhibits EC cell proliferation. METTL3 overexpression increases the ERP29 mRNA m6A and decreases the expression of ERP29. Cycloleucine (Cyc), a nucleic acid methylation inhibitor, treatment reduces ERP29 mRNA m6A and increases the expression of ERP29. Cyc rescue the low expression of ERP29 caused by overexpression of METTL3 through m6A. ERP29 knockdown rescued the increased proliferation of EC cells caused by low m6A., Significance: ERP29 is highly expressed in EC. m6A regulates ERP29 expression and affects the proliferation of endometrial cancer cells. This represents the premise for applying ERP29 and m6A modifications in diagnosing and treating EC., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A new genus and two new species, Tholimantispa zuoae gen. et sp. nov. and Mantispidipterella curvis sp. nov. are described from the Upper Cretaceous of northern Myanmar amber collected in 2015. Tholimantispa zuoae gen. et sp. nov. is characterized by its distinct pterostigma, broad costal space, bifurcate humeral veinlets, and so forth, and Mantispidipterella curvis sp. nov. is different from Mantispidipterella longissima Liu, Lu et Zhang, 2017 in its ScP (subcosta posterior) distinctly curved at fusing point with RA (radius anterior), RP (radius posterior) abruptly and angularly curved at ra-rp (crossvein between RA and RP), AA3 (third branches of the anterior anal vein) present. The new fossil species enrich the diversity of Dipteromantispidae in the Cretaceous., (© 2024 American Association for Anatomy.)

Valid inference of cause-and-effect relations in observational studies necessitates adjusting for common causes of the focal predictor (i.e., treatment) and the outcome. When such common causes, henceforth termed confounders, remain unadjusted for, they generate spurious correlations that lead to biased causal effect estimates. But routine adjustment for all available covariates, when only a subset are truly confounders, is known to yield potentially inefficient and unstable estimators. In this article, we introduce a data-driven confounder selection strategy that focuses on stable estimation of the treatment effect. The approach exploits the causal knowledge that after adjusting for confounders to eliminate all confounding biases, adding any remaining non-confounding covariates associated with only treatment or outcome, but not both, should not systematically change the effect estimator. The strategy proceeds in two steps. First, we prioritize covariates for adjustment by probing how strongly each covariate is associated with treatment and outcome. Next, we gauge the stability of the effect estimator by evaluating its trajectory adjusting for different covariate subsets. The smallest subset that yields a stable effect estimate is then selected. Thus, the strategy offers direct insight into the (in)sensitivity of the effect estimator to the chosen covariates for adjustment. The ability to correctly select confounders and yield valid causal inferences following data-driven covariate selection is evaluated empirically using extensive simulation studies. Furthermore, we compare the introduced method empirically with routine variable selection methods. Finally, we demonstrate the procedure using two publicly available real-world datasets. A step-by-step practical guide with user-friendly R functions is included. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Recently, it has been discovered surprisingly that tRNA can be cleaved into specific small fragments under certain conditions. Most importantly, these tRNA-derived fragments (tRFs) participate in the regulation of gene expression, playing pivotal roles in various physiological and pathological processes and thus attracting widespread attention. Detecting tRF expression in tissues and cells often involves using tRF-specific stem-loop primers for reverse transcription. However, the high specificity offered by this method limits it to transcribing only one specific tRF sequence per reaction, necessitating separate reverse transcription and qPCR steps for multiple tRFs, leading to substantially increased time and resource consumption. This becomes especially challenging in precious samples with limited RNA availability. To address these issues, there is an urgent need for a universal and cost-effective tRF identification method. This study introduces a versatile tRF detection approach based on the uniform polyadenylation of all tRFs, allowing reverse transcription with a universal oligo(dT) primer. This method enables simultaneous reverse transcription of all target tRFs in one reaction, greatly facilitating subsequent qPCR analysis. Furthermore, it demonstrates exceptional sensitivity and specificity, offering significant value in tRF-related research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rheumatoid arthritis (RA) is a chronic condition characterized by inflammation and an abnormal immune response. N6-methyladenosine (m6A) methylation has altered nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing (NLRP) 3. This change is implicated in the regulation of cell pyroptosis and inflammation. WTAP has a crucial role in regulating NLRP3 m6A. In this work, we used a rat model of collagen-induced arthritis (CIA) to investigate the involvement of WTAP in the evolution of inflammation in RA. The purpose of silencing or overexpressing WTAP in RA-fibroblast-like synoviocytes (RA-FLSs) treated with TNF-α was to identify its impact on pyroptosis, NLRP3 inflammasome-related proteins, the secretion of pro-inflammatory cytokines and migration. Bioinformatics techniques were used to pinpoint the exact target controlled by WTAP. To assess WTAP and NLRP3's role in RA-FLSs, we used methylated RNA immunoprecipitation, LDH test, flow cytometry, RT-qPCR, Western blotting, and Transwell. Our results show that WTAP expression is upregulated in both RA rats and cell models. Cell pyroptosis, NLRP3-related pro-inflammatory cytokines, and migration were reduced in TNF-α-treated RA-FLSs when WTAP was knocked down, whereas overexpression of WTAP displayed the opposite effect in RA-FLSs. WTAP mediated m6A modification in the NLRP3 mRNA and enhanced its mRNA stability. These results suggested that WTAP promoted FLSs pyroptosis and related inflammatory response via NLRP3 and identified WTAP as a potential target for treating RA., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Genome editing by CRISPR-Cas holds promise for the treatment of retinal dystrophies. For therapeutic gene editing, transient delivery of CRISPR-Cas9 is preferable to viral delivery which leads to long-term expression with potential adverse consequences. Cas9 protein and its guide RNA, delivered as ribonucleoprotein (RNP) complexes, have been successfully delivered into the retinal pigment epithelium in vivo . However, the delivery into photoreceptors, the primary focus in retinal dystrophies, has not been achieved. Here, we investigate the feasibility of direct RNP delivery into photoreceptors and retinal pigment epithelium cells. We demonstrate that Cas9 or adenine-base editors complexed with guide RNA, can enter retinal cells without the addition of any carrier compounds. Once in the retinal cells, editing rates vary based on the efficacy of the guide RNA and the specific location edited within the genes. Cas9 RNP delivery at high concentrations, however, leads to outer retinal toxicity. This underscores the importance of improving delivery efficiency for potential therapeutic applications in the future., Competing Interests: D.D. is a co-inventor on patent #9193956 (Adeno-associated virus virions with variant capsid and methods of use thereof), with royalties paid to Adverum Biotechnologies and on pending patent applications on noninvasive methods to target cone photoreceptors (EP17306429.6 and EP17306430.4) licensed to Gamut Tx now SparingVision. D.D. also has personal financial interests in Tenpoint Tx. and SparingVision, outside the scope of the submitted work., (© 2024 The Author(s).)

In this study, a quantitative method based on fluorescein isothiocyanate (FITC)-labelled Hizikia fusiforme polyphenol-polysaccharide complex (HPC) and its purified fractions (PC1, PC4) was used, and its pharmacokinetics and tissue distribution were investigated in mice. The results showed that the FITC-labelled method had good linearity (R 2 > 0.99), intra-day and inter-day precision (RSD, %) consistently lower than 15%, recovery (93.19-106.54%), and stability (RSD < 15%), which met the basic criteria for pharmacokinetic studies. The pharmacokinetic and tissue distribution results in mice after administration showed that all three sample groups could enter the blood circulation. and HPC-FITC had a longer half-life (T 1/2 : 26.92 ± 0.76 h) and mean retention time (MRT 0-∞ : 36.48 h) due to its larger molecular weight. The three groups of samples could be absorbed by the organism in a short time (0.5 h) mainly in the stomach and intestine; the samples could be detected in the urine after 2 h of administration indicating strong renal uptake, and faecal excretion reached its maximum at 12 h. The samples were also detected in the urine after 2 h of administration. This study provides some theoretical basis for the tissue distribution pattern of polyphenol-polysaccharide complex., Competing Interests: The authors declare that they have no competing financial interests.

Gaudichaudione H (GH) is a natural small molecular compound isolated from Garcinia oligantha Merr. (Clusiaceae). Being an uncommon rare caged polyprenylated xanthone, the potential pharmacological functions of GH remain to be fully elucidated currently. In this study, we primarily focused on identifying potential bioavailable targets and elucidating related therapeutic actions. Herein, the network pharmacology analysis, metabolomics analysis and genome-wide mRNA transcription assay were performed firstly to predict the major pharmacological action and potential targets of GH. To confirm the hypothesis, gene knockout model was created using CRISPR/Cas9 method. The pharmacological action of GH was evaluated in vitro and in vivo. Firstly, our results of network pharmacology analysis and omics assay indicated that GH significantly activated NRF2 signaling pathway, and the function could be associated with liver disease treatment. Then, the pharmacological action of GH was evaluated in vitro and in vivo. The treatment with GH significantly increased the protein levels of NRF2 and promoted the transcription of NRF2 downstream genes. Further analysis suggested that GH regulated NRF2 through an autophagy-mediated non-canonical mechanism. Additionally, the administration of GH effectively protected the liver from carbon tetrachloride (CCl 4 )-induced liver fibrosis and inflammation, which depended on the activation of NRF2 in hepatic stellate cells and inflammatory cells respectively. Collectively, our findings underscore the potential therapeutic effect of GH on alleviating hepatic fibrosis and inflammation through the augmentation of NRF2 signaling pathway, providing a promising avenue for the treatment of liver fibrosis and inflammation in clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)