Characteristics of Neonatal Sepsis and Predictive Values of Polyfunctional Assessment of Umbilical Cord Neutrophils Based on Single Cell Proteomic Secretion.

The early diagnosis of neonatal sepsis is crucial as it remains a prevalent cause of neonatal mortality. In this study, we conducted an analysis on the clinical data and detection indicators of 22 cases with sepsis and 62 cases without sepsis among neonates. Our findings indicate that the clinical signs observed in neonates with sepsis lack specificity. In addition, the commonly used clinical inflammatory indicators (such as leukocyte count, neutrophil-to-lymphocyte ratio [NLR], C-reactive protein [CRP], procalcitonin) exhibit limited sensitivity and specificity. Furthermore, the current clinical measures lack the assessment of inflammatory factors. Therefore, in order to enhance the accuracy of early sepsis diagnosis in neonates, we have employed a novel microfluidic-based single-cell technology platform for the analysis of 32 cytokines secreted by neutrophils at the individual cell level under various toxin stimulation conditions. We have further investigated and compared the disparities in single-cell protein secretomics between umbilical cord blood neutrophils and healthy adult peripheral neutrophils within an in vitro sepsis model. Our findings indicate that in a resting state UCB neutrophils exhibited lower polyfunctionality compared with healthy adult blood neutrophils, and notable variations in cytokine secretion profiles were detected between the two groups. However, the polyfunctionality of UCB neutrophils significantly increased and surpassed that of healthy adult neutrophils when exposed to alpha-hemolysin or lipopolysaccharide. UCB neutrophils secreted a wide range of chemokines and inflammatory factors, among which GM-CSF and IL-18 were the most significant. Furthermore, we initially categorized the functional subgroups of neutrophils by considering the secretion of five primary cytokines by neutrophils (GM-CSF, IL-18, IL-8, MIP-1ß, and MIF). The current study, for the first time, examined in detail the heterogeneity of protein secretion and the functional diversity of UCB neutrophils stimulated by different antigens. Moreover, new insight into neonatal sepsis, early diagnosis, and wider clinical applications of UCB neutrophils are provided by these data.

Protecting Prostate Cancer Classification From Rectal Artifacts via Targeted Adversarial Training.

Magnetic resonance imaging (MRI)-based deep neural networks (DNN) have been widely developed to perform prostate cancer (PCa) classification. However, in real-world clinical situations, prostate MRIs can be easily impacted by rectal artifacts, which have been found to lead to incorrect PCa classification. Existing DNN-based methods typically do not consider the interference of rectal artifacts on PCa classification, and do not design specific strategy to address this problem. In this study, we proposed a novel Targeted adversarial training with Proprietary Adversarial Samples (TPAS) strategy to defend the PCa classification model against the influence of rectal artifacts. Specifically, based on clinical prior knowledge, we generated proprietary adversarial samples with rectal artifact-pattern adversarial noise, which can severely mislead PCa classification models optimized by the ordinary training strategy. We then jointly exploited the generated proprietary adversarial samples and original samples to train the models. To demonstrate the effectiveness of our strategy, we conducted analytical experiments on multiple PCa classification models. Compared with ordinary training strategy, TPAS can effectively improve the single- and multi-parametric PCa classification at patient, slice and lesion level, and bring substantial gains to recent advanced models. In conclusion, TPAS strategy can be identified as a valuable way to mitigate the influence of rectal artifacts on deep learning models for PCa classification.

The impact of renaming schizophrenia on destigmatization: The Asian experience.

The term "schizophrenia" can indeed carry stigmatizing connotations. Proposals to rename schizophrenia have emerged as a potential strategy to alleviate this stigma, but the impact of such a change is not yet fully understood. In several Asian countries that have adopted a new name for schizophrenia, there is evidence that renaming is associated with improved attitudes towards individuals with schizophrenia and an increased willingness to disclose diagnoses. However, the portrayal of schizophrenia in the media seems unaffected by these name changes. In other countries where "schizophrenia" is still the standard term, alternative names have been suggested, but research on their effectiveness in reducing stigma shows mixed results. Mental health professionals frequently support a name change, recognizing the term's negative implications. However, it is crucial to recognize that a mere semantic revision, devoid of substantial conceptual alterations, may only offer a temporary decrease in stigma. Thus, renaming schizophrenia, coupled with a re-conceptualization of the disorder, may be a constructive step toward reducing its stigmatization.

Exploring the role of anticipatory postural adjustment duration within APA2 subphase as a potential mediator between clinical disease severity and fall risk in Parkinson's disease.

Introduction: People with Parkinson's Disease (PD) often show reduced anticipatory postural adjustments (APAs) before voluntary steps, impacting their stability. The specific subphase within the APA stage contributing significantly to fall risk remains unclear. Methods: We analyzed center of pressure (CoP) trajectory parameters, including duration, length, and velocity, throughout gait initiation. This examination encompassed both the postural phase, referred to as anticipatory postural adjustment (APA) (APA1, APA2a, APA2b), and the subsequent locomotor phases (LOC). Participants were instructed to initiate a step and then stop (initiating a single step). Furthermore, we conducted assessments of clinical disease severity using the Unified Parkinson's Disease Rating Scale (UPDRS) and evaluated fall risk using Tinetti gait and balance scores during off-medication periods. Results: Freezing of gait (FOG) was observed in 18 out of 110 participants during the measurement of CoP trajectories. The Ramer-Douglas-Peucker algorithm successfully identified CoP displacement trajectories in 105 participants (95.5%), while the remaining 5 cases could not be identified due to FOG. Tinetti balance and gait score showed significant associations with levodopa equivalent daily dose, UPDRS total score, disease duration, duration (s) in APA2a (s) and LOC (s), length in APA1 (cm) and APA2b (cm), mediolateral velocity in APA1 (X) (cm/s), APA2a (X) (cm/s), APA2b (X) (cm/s) and LOC (X) (cm/s), and anterior-posterior velocity in APA2a (Z) (cm/s) and APA2b (Z) (cm/s). Multiple linear regression revealed that only duration (s) in APA2a and UPDRS total score was independently associated with Tinetti gait and balance score. Further mediation analysis showed that the duration (s) in APA2a served as a mediator between UPDRS total score and Tinetti balance and gait score (Sobel test, p = 0.047). Conclusion: APA2 subphase duration mediates the link between disease severity and fall risk in PD, suggesting that longer APA2a duration may indicate reduced control during gait initiation, thereby increasing fall risk.

Primary thyroid nuclear protein in testis carcinoma: a case report and literature review.

Background: Nuclear protein in testis (NUT) carcinoma (NC) is a rare, highly aggressive neoplasm, usually accompanying with NUTM1 (NUT midline carcinoma family member 1) gene fusions. Primary thyroid NC is clinically rare and to date there is no established treatment guideline available for NC. We report a case of histopathologically confirmed thyroid NC and provide reference for diagnosis and treatment. Case Description: We presented a 32-year-old female admitted to hospital with "painful neck swelling and progressive dysphagia". Preoperative ultrasound-guided core needle aspiration biopsy suggested a poorly differentiated tumor. Considering the tumor was totally unresected on computed tomography (CT) scan, a partial thyroidectomy was performed to obtain sufficient tissue for a clear diagnosis. Histopathological specimens showed features of sudden keratosis. Strong immunoreactivity with NUT was detected by immunohistochemistry (IHC) and thus confirmed the diagnosis of NC. CK5/6, P40 and P63 were partially positive exclusively in keratosis area. Next-generation sequencing (NGS) and RNA sequencing results revealed a NSD3-NUTM1 fusion. The patient was treated with a combined regimen of radiotherapy of 70 Gy, chemotherapy with paclitaxel (albumin-bound), immunotherapy with nivolumab, targeted therapy with anlotinib and BET inhibitor NHWD-870, but the patient died 7 months after diagnosis. Conclusions: Thyroid NC is a rare and distinct pathological subset of NUT carcinoma with a higher rate of NSD3-NUTM1 fusion. In the clinical diagnosis process, we recommended performing NUT IHC for poorly differentiated thyroid tumors. Gene rearrangement detection is also helpful for diagnosis and treatment. At present, surgery and radiation are still first choices for NC, and advances in targeted immunotherapy such as bromodomain and end motif inhibitors (BETi) may bring better treatment options to patients.

Intracapsular Enucleation of Cervical Sympathetic Chain Schwannoma: Improved Strategy of Intraoperative Hemostasis and Better Outcome.

Objective: Intracapsular enucleation (ICE) of cervical sympathetic chain schwannoma (CSCS) is associated with technical difficulties, with diffuse hemorrhage being the main challenge in our previous attempts. This article presents our new strategy for achieving better hemostasis during ICE procedures in CSCS cases. Methods: A retrospective review of CSCS cases treated at our tertiary medical institution was undertaken between April 2018 and February 2024. Only cases with successful ICE were included. Results: A total of 8 cases were included, with 4 male and 4 female patients and an age range of 23 to 77 (average and median ages were 48.5 and 49.5 years, respectively). The presenting symptom was a neck mass for all the patients, with 4 masses on the left and 4 on the right sides. Enucleation was first undertaken for the first 3 cases (before March 2022), followed by hemostasis; this strategy was quite difficult and time-consuming. For the remaining 5 cases, a new strategy was developed to preemptively manage any potential nourishing vessel between the capsule and tumor parenchyma, which significantly decreased operation time (P = .0155) and facilitated hemorrhage control. First bite syndrome (FBS) was avoided in all cases. Postoperative Horner's syndrome (HS) was avoided in 1 patient (Case 6, new strategy) but occurred in 7 patients, taking 8 days to 1 month to recover with the new strategy (4 patients), significantly shorter (P = .0364) than before (3 patients, 1-3 months). The median duration of follow-up was 20 months. No recurrence was documented. Conclusions: ICE was achieved for CSCS cases, especially with our newly developed strategy, by preemptively and securely managing potential nourishing vessels. Operation time and duration of recovery of postoperative HS could both be shortened. Moreover, FBS could be avoided.

Investigating spatiotemporal and kinematic gait parameters in individuals with Parkinson's disease with a history of freezing of gait and exploring the effects of dopaminergic therapy on freezing of gait subtypes.

Introduction: Freezing of Gait (FOG) is a prevalent and debilitating symptom in idiopathic Parkinson's disease (PD). This study evaluated spatiotemporal and kinematic gait parameters in individuals with PD with a history of FOG and explored the effects of dopaminergic therapy on FOG subtypes. Methods: One hundred and nine individuals with PD underwent clinical assessments and quantitative biomechanical measures during walking cycles before and after dopaminergic therapy. Individuals with FOG were classified into levodopa-responsive and levodopa-unresponsive groups. Results: Individuals with FOG displayed longer disease duration and higher Unified Parkinson's Disease Rating Scale (UPDRS) II, III, IV scores, and total scores and levodopa equivalent dose, than those without FOG (all p < 0.0001). Following propensity score matching of 15 pairs based on UPDRS total score and disease duration during the off-medication state, the analysis comparing the FOG and non-FOG groups revealed no significant differences in spatiotemporal and kinematic parameters. In 39 cases of FOG, dopaminergic therapy improved gait performance in individuals with PD, enhancing spatiotemporal parameters (speed, stride length, step length, step variability) and kinematic parameters (shoulder and elbow flexion/extension range of motion (ROM), pelvic rotation, and hip abduction/adduction ROM) regardless of FOG responsiveness to dopaminergic therapy. A significant difference in trunk sway ROM (p = 0.029) remained before and after dopaminergic therapy, even after adjusting for disease duration and clinical severity. Discussion: Dopaminergic therapy had varying effects on PD with FOG, improving several spatiotemporal and kinematic gait parameters but being less effective in levodopa-unresponsive cases. Quantitative biomechanical measures offer detailed insights into gait performance, aiding personalized fall risk assessment and guiding individualized rehabilitation programs.

High-Tcsuperconductivity in doped molecular superconductors ofK4B8-xMxH32(M = C, N) under high pressure.

Stabilized and metallic light elements hydrides have provided a potential route to achieve the goal of room-temperature superconductors at moderate or ambient pressures. Here, we have performed systematic DFT theoretical calculations to examine the effects of different light elements C and N atoms doped in cubic K4B8H32hydrides on the superconductivity at low pressures. As a result of various atoms substituting, we have found that metallic K4B_{8-x}MxH32(M = C, N) hydrides are dynamically stable at 50 GPa, band structures and density of states (DOS) indicate that sizeableTccorrelates with a high B-H DOS at the Fermi level. With the increasing of B atoms in K4B_{8-x}MxH32hydrides, the DOS values at Fermi level have been improved due to the delocalized electrons in B-H bonds, which result in strong electron-phonon coupling (EPC) interaction and increase theTcfrom 19.04 to 77.07 K for KC2H8and KB2H8at 50 GPa. The NH4unit in stable K4B7NH32hydrides has weakened the EPC and led to lowTcvalue of 21.47 K. Our results suggest the light elements hydrides KB2H8and K4B7CH32could estimate highTcvalues at 50 GPa, and the boron hydrides would be potential candidates to design or modulate hydrides superconductors with highTcat moderate or ambient pressures.

Epithelial Membrane Protein 2 (EMP2) Blockade Attenuates Pathological Neovascularization in Murine Oxygen-Induced Retinopathy.

Purpose: Retinopathy of prematurity (ROP) results from postnatal hyperoxia exposure in premature infants and is characterized by aberrant neovascularization of retinal blood vessels. Epithelial membrane protein-2 (EMP2) regulates hypoxia-inducible factor (HIF)-induced vascular endothelial growth factor (VEGF) production in the ARPE-19 cell line and genetic knock-out of Emp2 in a murine oxygen-induced retinopathy (OIR) model attenuates neovascularization. We hypothesize that EMP2 blockade via intravitreal injection protects against neovascularization. Methods: Ex vivo choroid sprouting assay was performed, comparing media and human IgG controls versus anti-EMP2 antibody (Ab) treatment. In vivo, eyes from wild-type (WT) mice exposed to hyperoxia from postnatal (P) days 7 to 12 were treated with P12 intravitreal injections of control IgG or anti-EMP2 Abs. Neovascularization was assessed at P17 by flat mount imaging. Local and systemic effects of anti-EMP2 Ab treatment were assessed. Results: Choroid sprouts treated with 30 µg/mL of anti-EMP2 Ab demonstrated a 48% reduction in vessel growth compared to control IgG-treated sprouts. Compared to IgG-treated controls, WT OIR mice treated with 4 µg/g of intravitreal anti-EMP2 Ab demonstrated a 42% reduction in neovascularization. They demonstrated down-regulation of retinal gene expression in pathways related to vasculature development and up-regulation in genes related to fatty acid oxidation and tricarboxylic acid cycle respiratory electron transport, compared to controls. Anti-EMP2 Ab-treated OIR mice did not exhibit gross retinal histologic abnormalities, vision transduction abnormalities, or weight loss. Conclusions: Our results suggest that EMP2 blockade could be a local and specific treatment modality for retinal neovascularization in oxygen-induced retinopathies, without systemic adverse effects.

Co-immobilization of ß-agarase and α-agarase for degradation of agarose to prepare bioactive 3,6-anhydro-L-galactose.

Agarose from biomass can be used to synthesize the rare sugar 3,6-anhydro-L-galactose (L-AHG), and the new synthesis route and functional properties of L-AHG have always been the focus of research. Here we developed a novel method to co-immobilize Aga50D and BpGH117 onto streptavidin-coated magnetic nanoparticles and achieved the conversion of agarose to bioactive L-AHG in one pot. Results showed that enzymes were successfully immobilized on the carrier. The activity of co-immobilized enzymes was 2.5-fold higher than that of single immobilized enzymes. Compared with free enzymes, co-immobilized enzymes exhibited enhanced thermal stability. The co-immobilized enzymes retained 79.45 % relative activity at 40 °C for 3 h, while the free enzymes only possessed 21.40 % residual activity. After eight cycles, the co-immobilized enzymes still retained 73.47 % of the initial activity. After silica gel chromatography, the purity of L-AHG obtained by co-immobilized enzymes hydrolysis reached 83.02 %. Furthermore, bioactivity experiments demonstrated that L-AHG displayed better antioxidant and antibacterial effects than neoagarobiose. L-AHG had broad-spectrum antibacterial activity, while neoagarobiose and D-galactose did not show an obvious antibacterial effect. This study provides a feasible method for the production of L-AHG by a co-immobilized multi-enzyme system and confirms that L-AHG plays a key role in the bioactivity of neoagarobiose.

Misdiagnosed as Fungal Keratitis: Herpes Simplex Virus-1 Keratitis Confirmed by Next-Generation Sequencing.

Objective: The purpose of this study was to report a case of herpes simplex virus-1 (HSV-1) keratitis misdiagnosed as fungal keratitis due to its clinical presentation being similar to that of fungal keratitis, ultimately diagnosed by NGS. Patients and Methods: A 59-year-old male presented with reduced vision in the right eye, combined with a history of trauma with vegetative matter. The corneal ulcer was accompanied with feathery infiltration, satellite lesion, and endothelial plaques. In vivo confocal microscopy (IVCM) showed hyper-reflective linear, thin, and branching interlocking structures. Fungal keratitis was diagnosed. Voriconazole 100 mg orally daily, topical tobramycin and 1% voriconazole were initiated empirically right away. The condition was aggravated and penetrating keratoplasty was performed. Anterior segment optical coherence tomography (AS-OCT) demonstrated the presence of plaques with a clear boundary between plaques and endothelium, resembling the AS-OCT images observed in cases of viral keratitis. Next-generation sequencing (NGS) further detected HSV-1 deoxyribonucleic acid, and no fungal component was found. Antifungal agents were discontinued and antiviral treatments were added. Results: We successfully treated a patient with HSV-1 keratitis who was misdiagnosed due to clinical features and IVCM findings similar to fungal keratitis. The patient's infection was controlled. At 2 years after surgery, the cornea recovered well. Conclusions: HSV-1 keratitis with atypical clinical presentation can be easily misdiagnosed. This case report emphasizes the importance of NGS in diagnosing the pathogens of keratitis.

CroMAM: A Cross-Magnification Attention Feature Fusion Model for Predicting Genetic Status and Survival of Gliomas using Histological Images.

Predicting the gene mutation status in whole slide images (WSI) is crucial for the clinical treatment, cancer management, and research of gliomas. With advancements in CNN and Transformer algorithms, several promising models have been proposed. However, existing studies have paid little attention on fusing multi-magnification information, and the model requires processing all patches from a whole slide image. In this paper, we propose a cross-magnification attention model called CroMAM for predicting the genetic status and survival of gliomas. The CroMAM first utilizes a systematic patch extraction module to sample a subset of representative patches for downstream analysis. Next, the CroMAM applies Swin Transformer to extract local and global features from patches at different magnifications, followed by acquiring high-level features and dependencies among single-magnification patches through the application of a Vision Transformer. Subsequently, the CroMAM exchanges the integrated feature representations of different magnifications and encourage the integrated feature representations to learn the discriminative information from other magnification. Additionally, we design a cross-magnification attention analysis method to examine the effect of cross-magnification attention quantitatively and qualitatively which increases the model's explainability. To validate the performance of the model, we compare the proposed model with other multi-magnification feature fusion models on three tasks in two datasets. Extensive experiments demonstrate that the proposed model achieves state-of-the-art performance in predicting the genetic status and survival of gliomas. The implementation of the CroMAM will be publicly available upon the acceptance of this manuscript at https://github.com/GuoJisen/CroMAM.

Integrating Single-Cell and Spatial Transcriptomics to Uncover and Elucidate GP73-Mediated Pro-Angiogenic Regulatory Networks in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) was characterized as being hypervascular. In the present study, we generated a single-cell spatial transcriptomic landscape of the vasculogenic etiology of HCC and illustrated overexpressed Golgi phosphoprotein 73 (GP73) HCC cells exerting cellular communication with vascular endothelial cells with high pro-angiogenesis potential via multiple receptor-ligand interactions in the process of tumor vascular development. Specifically, we uncovered an interactive GP73-mediated regulatory network coordinated with c-Myc, lactate, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, and endoplasmic reticulum stress (ERS) signals in HCC cells and elucidated its pro-angiogenic roles in vitro and in vivo. Mechanistically, we found that GP73, the pivotal hub gene, was activated by histone lactylation and c-Myc, which stimulated the phosphorylation of downstream STAT3 by directly binding STAT3 and simultaneously enhancing glucose-regulated protein 78 (GRP78)-induced ERS. STAT3 potentiates GP73-mediated pro-angiogenic functions. Clinically, serum GP73 levels were positively correlated with HCC response to anti-angiogenic regimens and were essential for a prognostic nomogram showing good predictive performance for determining 6-month and 1-year survival in patients with HCC treated with anti-angiogenic therapy. Taken together, the aforementioned data characterized the pro-angiogenic roles and mechanisms of a GP73-mediated network and proved that GP73 is a crucial tumor angiogenesis niche gene with favorable anti-angiogenic potential in the treatment of HCC.

Studies on the Properties and Stability Mechanism of Double Emulsion Gels Prepared by Heat-Induced Aggregates of Egg White Protein-Oligosaccharides Glycosylation Products.

Multiple emulsions can dissolve some substances with different properties, such as hydrophilicity and lipophilicity, into different phases. They play an important role in protection, controlled release and targeted release of the encapsulated substances. However, it's poor stability has always been one of the main problems restricting its application in the food industry. For this reason, a heat-induced aggregate (HIA) of Maillard graft product of isomalto-oligosaccharides (IMO), as well as egg white protein (EWP), was used as hydrophilic emulsifier to improve the stability of W1/O/W2 emulsions. Moreover, gelatin was added into the internal aqueous phase (W1) to construct W1/O/W2 emulsion-gels system. The encapsulation efficiency of HIA-stabilized W1/O/W2 emulsions remained nearly unaltered, dropping by only 0.86%, significantly outperforming the conjugates and physical mixture of IMO and EWP in terms of encapsulation stability. The emulsion-gels system was constructed by adding 5% gelatin in the W1, and had the highest EE% and good salt and heat stability after 30 days of storage. This experiment provides guidance for improving the stability of W1/O/W2 emulsions system and its application in the package delivery of functional substances in the food field.

Phyllanthus emblica fruit extract alleviates halitosis and reduces the inflammatory response to oral bacteria.

OBJECTIVE: To assess the efficacy of Phyllanthus emblica extract in alleviating halitosis and reducing the inflammatory response to halitosis-related bacteria. METHODOLOGY: This investigation, using Phyllanthus emblica fruit extract (PE), involved four aspects. First, we evaluated the effect on growth and aggregation of halitosis-related bacteria, including Fusobacterium nucleatum, Porphyromonas gingivalis, and Solobacterium moorei, using a microdilution assay and scanning electron microscopy. Second, volatile sulfur compound (VSC) levels were measured on individuals with halitosis in randomized short-term (26 participants) and double-blind randomized long-term trials (18 participants in each group) after rinsing with PE for 3, 6, and 12 h, and 28 days. Third, we analyzed pro-inflammatory cytokine expression in TR146 cells using quantitative real-time PCR and enzyme-linked immunosorbent assays. Lastly, we assessed pro-inflammatory cytokine secretion and Toll-like receptor (TLR) 2 mRNA expression via the same experimental methods in a three-dimensional oral mucosal epithelial model (3D OMEM). RESULTS: PE extract dose-dependently inhibited the growth of F. nucleatum (50% inhibition concentration [IC50]=0.079%), P. gingivalis (IC50=0.65%), and S. moorei (IC50=0.07%) and effectively prevented bacterial aggregation. Furthermore, VSC contents decreased significantly at 3, 6, and 12 h after rinsing with 5% PE compared with those in the control. Long-term use of mouthwash containing 5% PE for 28 days led to a significant decrease in VSC contents. PE attenuated the F. nucleatum- or P. gingivalis-stimulated mRNA expression and protein release of interleukin (IL)-6 and IL-8 in TR146 cells. It also suppressed IL-8 and prostaglandin E2 secretion and TLR2 mRNA expression in F. nucleatum-induced OMEMs. CONCLUSION: Our findings support the use of PE in oral care products to alleviate halitosis and it may reduce inflammation.

Exploration of the Molecular Mechanism by Which Caveolin-1 Regulates Changes in Blood-Brain Barrier Permeability Leading to Eosinophilic Meningoencephalitis.

Angiostrongylus cantonensis, a zoonotic parasite, can invade the human central nervous system (CNS) and cause acute eosinophilic meningitis or eosinophilic meningoencephalitis. Mice infected with A. cantonensis show elevated levels of pro-inflammatory cytokines, plasminogen activators, and matrix metalloproteinase-9, resulting in disruption of the blood-brain barrier (BBB) and immune cell infiltration into the CNS. Caveolin-1 (Cav-1) regulates the permeability of the BBB, which affects immune cells and cerebrospinal fluid. This intricate interaction ultimately fuels the progression of brain damage and edema. This study aims to investigate the regulatory role of Cav-1 in the pathogenesis of meningoencephalitis induced by A. cantonensis infection. We investigated pathological alterations by triphenyl-tetrazolium chloride, brain water content, BBB permeability, Western blot analysis, and gelatin zymography in BALB/c mice after A. cantonensis. The study evaluates the critical role of Cav-1 regulation through the TLR4/MyD88 signaling pathway, modulates tight junction proteins, influences BBB permeability, and contributes to brain damage in A. cantonensis-induced meningoencephalitis.

A Co-MOF encapsulated microneedle patch activates hypoxia induction factor-1 to pre-protect transplanted flaps from distal ischemic necrosis.

Avoiding ischemic necrosis after flap transplantation remains a significant clinical challenge. Developing an effective pretreatment method to promote flap survival postoperatively is crucial. Cobalt chloride (CoCl2) can increase cell tolerance to ischemia and hypoxia condition by stimulating hypoxia-inducible factor-1 (HIF-1) expression. However, the considerable toxic effects severely limit the clinical application of CoCl2. In this study, cobalt-based metal-organic frameworks (Co-MOF) encapsulated in a microneedle patch (Co-MOF@MN) was developed to facilitate the transdermal sustained release of Co2+ for rapid, minimally invasive rapid pretreatment of flap transplantation. The MN patch was composed of a fully methanol-based two-component cross-linked polymer formula, with a pyramid structure and high mechanical strength, which satisfied the purpose of penetrating the skin stratum corneum of rat back to achieve subcutaneous vascular area administration. Benefiting from the water-triggered disintegration of Co-MOF and the transdermal delivery via the MN patch, preoperative damage and side effects were effectively mitigated. Moreover, in both the oxygen-glucose deprivation/recovery (OGD/R) cell model and the rat dorsal perforator flap model, Co-MOF@MN activated the HIF-1α pathway and its associated downstream proteins, which reduced reperfusion oxidative damage, improved blood supply in choke areas, and increased flap survival rates post-transplantation. This preprotection strategy, combining MOF nanoparticles and the MN patch, meets the clinical demands for trauma minimization and uniform administration in flap transplantation. STATEMENT OF SIGNIFICANCE: Cobalt chloride (CoCl2) can stimulate the expression of hypoxia-inducible factor (HIF-1) and improve the tolerance of cells to ischemia and hypoxia conditions. However, the toxicity and narrow therapeutic window of CoCl2 severely limit its clinical application. Herein, we explored the role of Co-MOF as a biocompatible nanocage for sustained release of Co2+, showing the protective effect on vascular endothelial cells in the stress model of oxygen-glucose deprivation. To fit the clinical needs of minimal trauma in flap transplantation, a Co-MOF@MN system was developed to achieve local transdermal delivery at the choke area, significantly improving blood supply opening and flap survival rate. This strategy of two-step delivery of Co2+ realized the enhancement of biological functions while ensuring the biosafety.

Development and validation of a prognostic model for assessing long COVID risk following Omicron wave-a large population-based cohort study.

BACKGROUND: Long coronavirus disease (COVID) after COVID-19 infection is continuously threatening the health of people all over the world. Early prediction of the risk of Long COVID in hospitalized patients will help clinical management of COVID-19, but there is still no reliable and effective prediction model. METHODS: A total of 1905 hospitalized patients with COVID-19 infection were included in this study, and their Long COVID status was followed up 4-8 weeks after discharge. Univariable and multivariable logistic regression analysis were used to determine the risk factors for Long COVID. Patients were randomly divided into a training cohort (70%) and a validation cohort (30%), and factors for constructing the model were screened using Lasso regression in the training cohort. Visualize the Long COVID risk prediction model using nomogram. Evaluate the performance of the model in the training and validation cohort using the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: A total of 657 patients (34.5%) reported that they had symptoms of long COVID. The most common symptoms were fatigue or muscle weakness (16.8%), followed by sleep difficulties (11.1%) and cough (9.5%). The risk prediction nomogram of age, diabetes, chronic kidney disease, vaccination status, procalcitonin, leukocytes, lymphocytes, interleukin-6 and D-dimer were included for early identification of high-risk patients with Long COVID. AUCs of the model in the training cohort and validation cohort are 0.762 and 0.713, respectively, demonstrating relatively high discrimination of the model. The calibration curve further substantiated the proximity of the nomogram's predicted outcomes to the ideal curve, the consistency between the predicted outcomes and the actual outcomes, and the potential benefits for all patients as indicated by DCA. This observation was further validated in the validation cohort. CONCLUSIONS: We established a nomogram model to predict the long COVID risk of hospitalized patients with COVID-19, and proved its relatively good predictive performance. This model is helpful for the clinical management of long COVID.

Calycosin Enhances Heat Shock Related-Proteins in H9c2 Cells to Modulate Survival and Apoptosis against Heat Shock.

Heat shock proteins (HSPs), which function as chaperones, are activated in response to various environmental stressors. In addition to their role in diverse aspects of protein production, HSPs protect against harmful protein-related stressors. Calycosin exhibits numerous beneficial properties. This study aims to explore the protective effects of calycosin in the heart under heat shock and determine its underlying mechanism. H9c2 cells, western blot, TUNEL staining, flow cytometry, and immunofluorescence staining were used. The time-dependent effects of heat shock analyzed using western blot revealed increased HSP expression for up to 2[Formula: see text]h, followed by protein degradation after 4[Formula: see text]h. Hence, a heat shock damage duration of 4[Formula: see text]h was chosen for subsequent investigations. Calycosin administered post-heat shock demonstrated dose-dependent recovery of cell viability. Under heat shock conditions, calycosin prevented the apoptosis of H9c2 cells by upregulating HSPs, suppressing p-JNK, enhancing Bcl-2 activation, and inhibiting cleaved caspase 3. Calycosin also inhibited Fas/FasL expression and activated cell survival markers (p-PI3K, p-ERK, p-Akt), indicating their cytoprotective properties through PI3K/Akt activation and JNK inhibition. TUNEL staining and flow cytometry confirmed that calycosin reduced apoptosis. Moreover, calycosin reversed the inhibitory effects of quercetin on HSF1 and Hsp70 expression, illustrating its role in enhancing Hsp70 expression through HSF1 activation during heat shock. Immunofluorescence staining demonstrated HSF1 translocation to the nucleus following calycosin treatment, emphasizing its cytoprotective effects. In conclusion, calycosin exhibits pronounced protective effects against heat shock-induced damages by modulating HSP expression and regulating key signaling pathways to promote cell survival in H9c2 cells.

Therapeutic effects of flavonoids on pulmonary fibrosis: A preclinical meta-analysis.

BACKGROUND: The efficacy of flavonoid supplementation in animal models of pulmonary fibrosis has been demonstrated. PURPOSE: We conducted a systematic review and meta-analysis to evaluate the efficacy and underlying mechanisms of flavonoids in animal models of bleomycin-induced pulmonary fibrosis. STUDY DESIGN: Relevant studies (n = 45) were identified from English- and Chinese-language databases from the inception of the database until October 2023. METHODS: Methodological quality was evaluated using the SYRCLE risk of bias tool. Statistical analyses were conducted using RevMan 5.3 and Stata 17.0. Lung inflammation and fibrosis score were the primary outcome indicators. RESULTS: Flavonoids can alleviate pathological changes in the lungs. The beneficial effects of flavonoids on pulmonary fibrosis likely relate to their inhibition of inflammatory responses, restoration of oxidative and antioxidant homeostasis, and regulation of fibroblast proliferation, migration, and activation by transforming growth factor ß1/mothers against the decapentaplegic homologue/AMP-activated protein kinase (TGF-ß1/Smad3/AMPK), inhibitor kappa B alpha/nuclear factor-kappa B (IκBα/NF-κB), phosphatidylinositol 3-kinase (PI3K)/AKT, interleukin 6/signal transducer/activator of transcription 3 (IL6/STAT3), and nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2-Keap1) pathways. CONCLUSION: Flavonoids are potential candidate compounds for the prevention and treatment of pulmonary fibrosis. However, extensive preclinical research is necessary to confirm the antifibrotic properties of natural flavonoids.