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Alyssa M Volmrich,1 Lauren M Cuénant,1 Irman Forghani,2 Sharon L Hsieh,3 Lauren T Shapiro1 1Department of Physical Medicine & Rehabilitation, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA; 3MD/MPH Program, University of Miami Miller School of Medicine, Miami, FL, USACorrespondence: Lauren T Shapiro, Department of Physical Medicine & Rehabilitation; University of Miami Miller School of Medicine, P.O. Box 016960 (C-206), Miami, FL, 33101, USA, Tel +1 305 243-6605, Fax +1 305 243-4650, Email lxs973@med.miami.eduAbstract: Pathogenic variants in the ABCD1 gene on the X chromosome may result in widely heterogenous phenotypes, including adrenomyeloneuropathy (AMN). Affected males typically present in their third or fourth decade of life with progressive lower limb weakness and spasticity, and may develop signs and symptoms of adrenal insufficiency and/or cerebral demyelination. Heterozygous females may be asymptomatic, but may develop a later-onset and more slowly progressive spastic paraparesis. In this review, we describe the clinical presentation of AMN, as well as its diagnosis and management. The role of rehabilitative therapies and options for management of spasticity are highlighted.Keywords: adrenoleukodystrophy, spastic paraparesis, adrenal insufficiency

RATIONALE: Acute respiratory distress syndrome (ARDS), a serious inflammatory reaction to acute lung injury, is associated with high mortality rates. Decoy receptor (DcR) 3 is a soluble protein with immunomodulatory effects. Biomarkers that reliably predict outcomes in ARDS are not currently available. OBJECTIVES: Comparing DcR3 with the Acute Physiology and Chronic Health Evaluation (APACHE) II scores and three other plasma markers to explore the association of DcR3 and the clinical outcome in ARDS. METHODS: Eighty-eight patients with ARDS were studied. Baseline APACHE II scores and clinical data were recorded. Plasma levels of DcR3, soluble triggering receptor expressed on myeloid cells (sTREM)-1, tumor necrosis factor (TNF)-alpha, and IL-6 were measured on Day 1 and later time points, and correlated with the survival status on Day 28 after the onset of ARDS. For validation, 59 patients with ARDS from another medical center were studied. MEASUREMENTS AND MAIN RESULTS: Among the biomarkers evaluated, only DcR3 discriminated the survivors and nonsurvivors at all time points in the first week of ARDS. DcR3 independently associated with and best predicted the 28-day mortality of patients with ARDS. Plasma DcR3 levels most correlated to multiple-organ dysfunction and ventilator dependence. Compared with survivors, the nonsurvivors had higher DcR3 levels regardless of the APACHE II scores. Kaplan-Meier survival analysis showed higher mortality in patients with ARDS with higher DcR3 levels. The outcome prediction of patients with ARDS by plasma DcR3 levels was recapitulated by the validation cohort. CONCLUSIONS: High plasma DcR3 levels correlate with development of multiple-organ dysfunction and independently predict the 28-day mortality in patients with ARDS. [ABSTRACT FROM AUTHOR]

Background and Aims: Immune system activation, along with lipotoxicity due to excessive lipid droplet (LD) accumulation in the liver, are key drivers of NASH. Extracellular vesicles (EVs) released by cells that carry biological signals contribute to intercellular communication. However, the roles of immune cell-derived EVs in the pathogenesis of NASH are unclear., Approach and Results: Platelets are abundant in blood. We explored the role of platelet-derived EVs (pEVs) in LD accumulation from 30 patients with nonalcoholic fatty liver disease of different severity as well as 20 healthy subjects, a rat model, and an in vitro cell-based assay. There was increased platelet activation, accompanied by pEVs release, in NASH patients/rat model, and palmitate-treated cells. The mitochondria in the platelets and pEVs from NASH patients/rats were increased but dysfunctional, including a reduction in fatty acid β-oxidation, inactivated acetyl-CoA carboxylase 2, and suppressed oxidative phosphorylation system complex II/III/IV activity. These damaged mitochondria could be transferred to hepatocytes through pEVs to increase the number of lipid droplet-bound mitochondria. An increase in dysfunctional lipid droplet-bound mitochondria in hepatocytes affects lipid metabolism, resulting in excessive LD accumulation, elevated mitochondrial reactive oxygen species production, and apoptosis., Conclusions: We offer a novel molecular mechanism that connects platelets, pEVs, and excessive LD accumulation to the development of NASH. Our results suggest that NASH progression may be alleviated by specifically inhibiting the production and release of pEVs, or by targeting pEV components and inhibiting their uptake. Additional experiments are required to confirm this potentiality., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Diverticulitis, an inflammation of diverticula in the colon, can lead to severe complications such as perforation and abscess formation. A 42-year-old female with polycystic kidney disease and chronic kidney disease stage III presented with severe abdominal pain, fever, and inability to tolerate oral intake. The patient was a previous smoker who smoked 0.5 packs per day for 25 years. Initial evaluation revealed leukocytosis and elevated creatinine. A CT scan identified pneumoperitoneum and mild sigmoid diverticulitis, suggesting a perforated viscus. She underwent urgent exploratory laparotomy, which confirmed the CT findings and resulted in an appendectomy, sigmoid colon resection, and ostomy creation. Postoperatively, the patient faced complications, including recurrent pneumoperitoneum and subcutaneous emphysema, detected through follow-up CT scans, leading to further surgical interventions. CT imaging was pivotal in diagnosing, monitoring, and guiding treatment, with noncontrast CT being beneficial given her renal impairment. Early diagnosis and CT imaging are crucial in managing complicated diverticulitis. Postoperative monitoring with CT scans is essential for detecting complications. Follow-up care should include regular colonoscopies to assess diverticular disease and dietary modifications to prevent recurrence. Combining clinical, surgical, and radiologic data ensures effective management and improves patient outcomes., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: Alzheimer's disease (AD) is a neurodegenerative disease that causes cognitive dysfunction in older adults. One of the AD pathological factors, β-Amyloid (Aβ), triggers inflammatory responses and phagocytosis of microglia. C-type lectin domain family 5 member A (CLEC5A) induces over-reactive inflammatory responses in several virus infections. Yet, the role of CLEC5A in AD progression remains unknown. This study aimed to elucidate the contribution of CLEC5A to Aβ-induced microglial activation and behavioral deficits., Methods: The AD mouse model was crossed with Clec5a knockout mice for subsequent behavioral and pathological tests. The memory deficit was revealed by the Morris water maze, while the nociception abnormalities were examined by the von Frey filament and hotplate test. The Aβ deposition and microglia recruitment were identified by ELISA and immunohistochemistry. The inflammatory signals were identified by ELISA and western blotting. In the Clec5a knockdown microglial cell model and Clec5a knockout primary microglia, the microglial phagocytosis was revealed using the fluorescent-labeled Aβ., Results: The AD mice with Clec5a knockout improved Aβ-induced memory deficit and abnormal nociception. These mice have reduced Aβ deposition and increased microglia coverage surrounding the amyloid plaque, suggesting the involvement of CLEC5A in AD progression and Aβ clearance. Moreover, the phagocytosis was also increased in the Aβ-stressed Clec5a knockdown microglial cell lines and Clec5a knockout primary microglia., Conclusion: The Clec5a knockout ameliorates AD-like deficits by modulating microglial Aβ clearance. This study implies that targeting microglial Clec5a could offer a promising approach to mitigate AD progression., (© 2024. The Author(s).)

The usage of peptides in the colorectal cancer (CRC) treatment promises to be a new anti-cancer therapy with improved treatment efficacy. Carnosine, a natural dipeptide molecule, has been demonstrated to be a potential anti-cancer drug. Nonetheless, it shows an exhibition of high-water solubility and is quickly degraded by carnosinase. Meanwhile, agar and magnetic iron oxide are the most used materials for drug delivery due to some of their advantages such as the low cost and the larger biocompatibility feature. The purpose of this study was to investigate the anti-cancer ability of agar-encapsulated carnosine nanoparticles (AgCa-NPs) and agar-encapsulated carnosine nanoparticles-coated magnetic iron oxide nanoparticles (AgCaN-MNPs) in human CRC cells, HCT-116. We evaluated the effects of AgCa-NPs and AgCaN-MNPs with a variety of concentrations (0, 5, 10, 15, 30, 40, or 50 mM) on HCT-116 cells after 72 h and 96 h by using MTT assay and observation cell morphology. We then analyzed the cell cycle progression and assessed the expression changes of genes related to apoptosis, autophagy, necroptosis, and angiogenesis after treatment for 96 h. The results showed that AgCa-NPs and AgCaN-MNPs in vitro study decreased HCT-116 cells viability. This effect was attributed to arrest of cell cycle, induction of programmed cell death, and suppression of angiogenesis by AgCa-NPs and AgCaN-MNPs. These findings revealed the antitumor efficacy of AgCa-NPs or AgCaN-MNPs for CRC treatment., 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.)

This study examines the combined effects of polyethylene microplastics (PE-MP) and copper (Cu 2+ ) on the immune and oxidative response of Litopenaeus vannamei. PE-MP adsorbed with Cu 2+ at 2.3, 6.8, and 16.8 ng (g shrimp) -1 ) were injected into L. vannamei. Over 14 days, survival rates were monitored, and immune and oxidative stress parameters were assessed. The results showed that combined exposure to PE-MP and Cu 2+ significantly reduced the survival rate and decreased total haemocyte count. Immune-related parameters (phagocytic rate, phenoloxidase and superoxide dismutase (SOD)) and antioxidant-related parameters (SOD, catalase and glutathione peroxidase mRNA and enzyme) also decreased, while respiratory burst activity significantly increased, indicating immune and antioxidant system disruption. Additionally, there was a significant increase in oxidative stress, as measured by malondialdehyde levels. Histopathological analysis revealed severe muscle, hepatopancreas, and gill damage. These results suggest that simultaneous exposure to PE-MP and Cu 2+ poses greater health risks to white shrimp., Competing Interests: Declaration of competing interest The authors state that they have no known financial conflicts of interest or personal relationships that could have influenced the work presented in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The C-type lectin family 18 (CLEC18) with lipid and glycan binding capabilities is important to metabolic regulation and innate immune responses against viral infection. However, human CLEC18 comprises three paralogous genes with highly similar sequences, making it challenging to distinguish genetic variations, expression patterns, and biological functions of individual CLEC18 paralogs. Additionally, the evolutionary relationship between human CLEC18 and its counterparts in other species remains unclear., Methods: To identify the sequence variation and evolutionary divergence of human CLEC18 paralogs, we conducted a comprehensive analysis using various resources, including human and non-human primate reference genome assemblies, human pangenome assemblies, and long-read-based whole-genome and -transcriptome sequencing datasets., Results: We uncovered paralogous sequence variants (PSVs) and polymorphic variants (PVs) of human CLEC18 proteins, and identified distinct signatures specific to each CLEC18 paralog. Furthermore, we unveiled a novel segmental duplication for human CLEC18A gene. By comparing CLEC18 across human and non-human primates, our research showed that the CLEC18 paralogy probably occurred in the common ancestor of human and closely related non-human primates, and the lipid-binding CAP/SCP/TAPS domain of CLEC18 is more diverse than its glycan-binding CTLD. Moreover, we found that certain amino acids alterations at variant positions are exclusive to human CLEC18 paralogs., Conclusions: Our findings offer a comprehensive profiling of the intricate variations and evolutionary characteristics of human CLEC18., (© 2024. The Author(s).)

Osteoarthritis (OA) is a low-grade inflammatory joint illness in which monocytes migrate and infiltrate synovial tissue, differentiating into the pro-inflammatory M1 macrophage phenotype. IL-17 is a proinflammatory mediator principally generated by Th17 cells, which is elevated in OA patients; nevertheless, investigators have yet to elucidate the function of IL-17 in M1 polarization during OA development. Our analysis of clinical tissues and results from the open online dataset discovered that the level of M1 macrophage markers is elevated in human OA tissue samples than in normal tissue. High-throughput screening demonstrated that MCP-1 is a potential candidate factor after IL-17 treatment in OA synovial fibroblasts (OASFs). Immunohistochemistry data revealed that the level of MCP-1 is higher in humans and mice with OA than in normal tissues. IL-17 stimulation facilitates MCP-1-dependent macrophage polarization to the M1 phenotype. It also appears that IL-17 enhances MCP-1 synthesis in human OASFs, enhancing monocyte migration via the JAK and STAT3 signaling cascades. Our findings indicate the IL-17/MCP-1 axis as a novel strategy for the remedy of OA., 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.)

Chondrosarcoma is a malignant bone tumor that arises from abnormalities in cartilaginous tissue and is associated with lung metastases. Lymphangiogenesis plays an essential role in cancer metastasis. Visfatin is an adipokine reported to enhance tumor metastasis, but its relationship with VEGF-D generation and lymphangiogenesis in chondrosarcoma remains undetermined. Our results from clinical samples reveal that VEGF-D levels are markedly higher in chondrosarcoma patients than in normal individuals. Visfatin stimulation promotes VEGF-D-dependent lymphatic endothelial cell lymphangiogenesis. We also found that visfatin induces VEGF-D production by activating HIF-1α and reducing miR-2277-3p generation through the Raf/MEK/ERK signaling cascade. Importantly, visfatin controls chondrosarcoma-related lymphangiogenesis in vivo. Therefore, visfatin is a promising target in the treatment of chondrosarcoma lymphangiogenesis.

Exposure to hypoxia results in the development of pulmonary arterial hypertension (PAH). An increase in the intracellular Ca 2+ concentration ([Ca 2+ ] i ) in pulmonary artery smooth muscle cells (PASMCs) is a major trigger for pulmonary vasoconstriction and proliferation. This study investigated the mechanism by which KMUP-1, a xanthine derivative with phosphodiesterase inhibitory activity, inhibits hypoxia-induced canonical transient receptor potential channel 1 (TRPC1) protein overexpression and regulates [Ca 2+ ] i through store-operated calcium channels (SOCs). Ex vivo PASMCs were cultured from Sprague-Dawley rats in a modular incubator chamber under 1% O 2 /5% CO 2 for 24 h to elucidate TRPC1 overexpression and observe the Ca 2+ release and entry. KMUP-1 (1 μM) inhibited hypoxia-induced TRPC family protein encoded for SOC overexpression, particularly TRPC1. KMUP-1 inhibition of TRPC1 protein was restored by the protein kinase G (PKG) inhibitor KT5823 (1 μM) and the protein kinase A (PKA) inhibitor KT5720 (1 μM). KMUP-1 attenuated protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 1 μM)-upregulated TRPC1. We suggest that the effects of KMUP-1 on TRPC1 might involve activating the cyclic guanosine monophosphate (cGMP)/PKG and cyclic adenosine monophosphate (cAMP)/PKA pathways and inhibiting the PKC pathway. We also used Fura 2-acetoxymethyl ester (Fura 2-AM, 5 μM) to measure the stored calcium release from the sarcoplasmic reticulum (SR) and calcium entry through SOCs in hypoxic PASMCs under treatment with thapsigargin (1 μM) and nifedipine (5 μM). In hypoxic conditions, store-operated calcium entry (SOCE) activity was enhanced in PASMCs, and KMUP-1 diminished this activity. In conclusion, KMUP-1 inhibited the expression of TRPC1 protein and the activity of SOC-mediated Ca 2+ entry upon SR Ca 2+ depletion in hypoxic PASMCs.

As microplastics (MP) become ubiquitous, their interactions with heavy metals threatens the coral ecosystem. This study aimed to assess the combined toxicity of MP and copper (Cu) in the environment of coral. Goniopora columna was exposed to polyethylene microplastics (PE-MP) combined with Cu 2+ at 10, 20, 50, 100, and 300 μg/L for 7 days. Polyp length and adaptability were recorded daily, and coral samples were collected at 1, 3, 5, and 7 days to analyse zooxanthellae density and antioxidant activity. Tissue observations and the analysis of MP and Cu 2+ accumulation were conducted on the 7th day. After 1 day of exposure, PE-MP combined with different concentrations of Cu 2+ significantly decreased polyp length and adaptability compared with PE-MP alone. Simultaneously, a significant increase in malondialdehyde (MDA) content, lead to coral oxidative stress, which was a combined effect with PE-MP. After 3 days of exposure, PE-MP combined with Cu 2+ at >50 μg/L significantly reduced zooxanthellae density, damaging the coral's symbiotic relationship. In antioxidant enzyme activity, superoxide dismutase (SOD) activity decreased significantly after 1 day of exposure. After 3 days of exposure, glutathione peroxidase (GPx) activity significantly increased with Cu 2+ at >20 μg/L. After 5 days of exposure, PE-MP combined with different concentrations of Cu 2+ significantly reduced catalase (CAT), glutathione (GSH), and glutathione transferase (GST) activity, disrupting the antioxidant enzyme system, and acting antagonistically to PE-MP alone. Tissue observations revealed that the PE-MP combined with Cu 2+ at >50 μg/L caused severe mesenteric atrophy, vacuolar, and Cu 2+ accumulation in the coral mesenteric compared with PE-MP alone. The results suggest that combined exposure of PE-MP and copper leads to more severe oxidative stress, disruption antioxidant enzyme system, tissue damage, and Cu 2+ accumulation, resulting in a significant maladaptation of corals to the environment., 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.)

IL-23-activation of IL-17 producing T cells is involved in many rheumatic diseases. Herein, we investigate the role of IL-23 in the activation of myeloid cell subsets that contribute to skin inflammation in mice and man. IL-23 gene transfer in WT, IL-23R GFP reporter mice and subsequent analysis with spectral cytometry show that IL-23 regulates early innate immune events by inducing the expansion of a myeloid MDL1 + CD11b + Ly6G + population that dictates epidermal hyperplasia, acanthosis, and parakeratosis; hallmark pathologic features of psoriasis. Genetic ablation of MDL-1, a major PU.1 transcriptional target during myeloid differentiation exclusively expressed in myeloid cells, completely prevents IL-23-pathology. Moreover, we show that IL-23-induced myeloid subsets are also capable of producing IL-17A and IL-23R + MDL1 + cells are present in the involved skin of psoriasis patients and gene expression correlations between IL-23 and MDL-1 have been validated in multiple patient cohorts. Collectively, our data demonstrate a novel role of IL-23 in MDL-1-myelopoiesis that is responsible for skin inflammation and related pathologies. Our data open a new avenue of investigations regarding the role of IL-23 in the activation of myeloid immunoreceptors and their role in autoimmunity., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Nondisplaced femoral neck fractures are sometimes misdiagnosed by radiographs, which may deteriorate into displaced fractures. However, few efficient artificial intelligent methods have been reported. We developed an automatic detection method using deep learning networks to pinpoint femoral neck fractures on radiographs to assist physicians in making an accurate diagnosis in the first place. Our proposed accurate automatic detection method, called the direction-aware fracture-detection network (DAFDNet), consists of two steps, namely region-of-interest (ROI) segmentation and fracture detection. The first step removes the noise region and pinpoints the femoral neck region. The fracture-detection step uses a direction-aware deep learning algorithm to mark the exact femoral neck fracture location in the region detected in the first step. A total of 3840 femoral neck parts in anterior-posterior (AP) pelvis radiographs collected from the China Medical University Hospital database were used to test our method. The simulation results showed that DAFDNet outperformed the U-Net and DenseNet methods in terms of the IOU value, Dice value, and Jaccard value. Our proposed DAFDNet demonstrated over 94.8% accuracy in differentiating non-displaced Garden type I and type II femoral neck fracture cases. Our DAFDNet method outperformed the diagnostic accuracy of general practitioners and orthopedic surgeons in accurately locating Garden type I and type II fracture locations. This study can determine the feasibility of applying artificial intelligence in a clinical setting and how the use of deep learning networks assists physicians in improving correct diagnoses compared to the current traditional orthopedic manual assessments.

In this study, we develop an innovative method that assists computer-aided diagnosis in the determination process of the exact location of the femoral neck junction in plain radiographs. Our algorithm consists of two phases, i.e., coarse prediction and fine matching, which are implemented by supervised deep learning method and unsupervised clustering, respectively. In coarse prediction, standard masks are first produced by a specialist and trained in our proposed feature propagation network (FPU-Net) with supervised learning on the femoral neck dataset. In fine matching, the standard masks are first classified into different categories using our proposed three parameters with unsupervised learning. The predicted mask from FPU-Net is matched with each category of standard masks by calculating the values of intersection of union (IOU), and finally the predicted mask is substituted by the standard mask with the largest IOU value. A total of 4320 femoral neck parts in anterior-posterior (AP) pelvis radiographs collected from China Medical University Hospital database were used to test our method. Simulation results show that, on the one hand, compared with other segmentation methods, the method proposed in this paper has a larger IOU value and better suppression of noise outside the region of interest; on the other hand, the introduction of unsupervised learning for fine matching can help in the accurate localization segmentation of femoral neck images. Accurate femoral neck segmentation can assist surgeons to diagnose and reduce the misdiagnosis rate and burden.

Objective: To investigate the role of interleukin-23 (IL-23) in pathologic bone remodeling in inflammatory arthritis., Methods: In this study we investigated the role of IL-23 in osteoclast differentiation and activation using in vivo gene transfer techniques in wild-type and myeloid DNAX-activation protein 12-associating lectin-1 (MDL-1)-deficient mice, and by performing in vitro and in vivo osteoclastogenesis assays using spectral flow cytometry, micro-computed tomography analysis, Western blotting, and immunoprecipitation., Results: Herein, we show that IL-23 induces the expansion of a myeloid osteoclast precursor population and supports osteoclastogenesis and bone resorption in inflammatory arthritis. Genetic ablation of C-type lectin domain family member 5A, also known as MDL-1, prevents the induction of osteoclast precursors by IL-23 that is associated with bone destruction, as commonly observed in inflammatory arthritis. Moreover, osteoclasts derived from the bone marrow of MDL-1-deficient mice showed impaired osteoclastogenesis, and MDL-1 -/- mice had increased bone mineral density., Conclusion: Our data show that IL-23 signaling regulates the availability of osteoclast precursors in inflammatory arthritis that could be effectively targeted for the treatment of inflammatory bone loss in inflammatory arthritis., (© 2023 American College of Rheumatology.)

Fish bone fermented using Monascus purpureus (FBF) has total phenols and functional amino acids that contribute to its anti-oxidant and anti-inflammatory properties. Colorectal cancer, one of the most prevalent cancers and the third largest cause of death worldwide, has become a serious threat to global health. This study investigates the anti-cancer effects of FBF (1, 2.5 or 5 mg/mL) on the cell growth and molecular mechanism of HCT-116 cells. The HCT-116 cell treatment with 2.5 or 5 mg/mL of FBF for 24 h significantly decreased cell viability ( p < 0.05). The S and G2/M phases significantly increased by 88-105% and 25-43%, respectively ( p < 0.05). Additionally, FBF increased the mRNA expression of caspase 8 (38-77%), protein expression of caspase 3 (34-94%), poly (ADP-ribose) polymerase (PARP) (31-34%) and induced apoptosis (236-773%) of HCT-116 cells ( p < 0.05). FBF also increased microtubule-associated protein 1B light chain 3 (LC3) (38-48%) and phosphoinositide 3 kinase class III (PI3K III) (32-53%) protein expression, thereby inducing autophagy (26-52%) of HCT-116 cells ( p < 0.05). These results showed that FBF could inhibit HCT-116 cell growth by inducing S and G2/M phase arrest of the cell cycle, apoptosis and autophagy. Thus, FBF has the potential to treat colorectal cancer.

Thromboinflammation is the major cause of morbidity and mortality in COVID-19 patients, and post-mortem examination demonstrates the presence of platelet-rich thrombi and microangiopathy in visceral organs. Moreover, persistent microclots were detected in both acute COVID-19 and long COVID plasma samples. However, the molecular mechanism of SARS-CoV-2-induced thromboinflammation is still unclear. We found that the spleen tyrosine kinase (Syk)-coupled C-type lectin member 2 (CLEC2), which was highly expressed in platelets and alveolar macrophages, interacted with the receptor-binding domain (RBD) of SARS-CoV-2 spike protein (SARS-CoV-2 RBD) directly. Unlike the thread-like NETs, SARS-CoV-2-induced aggregated NET formation in the presence of wild-type (WT), but not CLEC2-deficient platelets. Furthermore, SARS-CoV-2 spike pseudotyped lentivirus was able to induce NET formation via CLEC2, indicating SARS-CoV-2 RBD engaged CLEC2 to activate platelets to enhance NET formation. Administration of CLEC2.Fc inhibited SARS-CoV-2-induced NET formation and thromboinflammation in AAV-ACE2-infected mice. Thus, CLEC2 is a novel pattern recognition receptor for SARS-CoV-2, and CLEC2.Fc and may become a promising therapeutic agent to inhibit SARS-CoV-2-induced thromboinflammation and reduced the risk of post-acute sequelae of COVID-19 (PASC) in the future., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Climate change is contributing to increasingly hazardous tropical cyclones that endanger persons living in susceptible coastal and island communities. People living with chronic illness, including multiple sclerosis (MS), face unique challenges and vulnerabilities when exposed to hurricane hazards. Disaster and emergency preparedness requires a customized approach that considers the necessary adaptations to accommodate the mobility, self-care, sensory, cognitive, and communication impairments of persons living with MS. Related considerations include the potential for worsening neurologic signs and symptoms during and after a catastrophic storm. The impact of emotional and financial stresses, as well as disruptions in health care delivery, on this population are also key concerns. This paper addresses the challenges faced by individuals with MS in advance of, during, and in the aftermath of extreme storms. We propose new guidelines on how health care professionals can assist persons with MS when creating tailored disaster readiness and response plans., Competing Interests: FINANCIAL DISCLOSURES: The authors declare no conflicts of interest., (© 2023 The Consortium of Multiple Sclerosis Centers.)

Mixed cryoglobulinemia (MC) is a hepatitis C virus (HCV)-related extrahepatic manifestation that is characterized by the abnormal presence of immune complexes (ICs). This may be due to the reduced uptake and clearance of ICs. The C-type lectin member 18A (CLEC18A) is a secretory protein that is expressed abundantly in hepatocytes. We previously observed that CLEC18A increased significantly in the phagocytes and sera of patients with HCV, particularly those with MC. Herein, we explored the biological functions of CLEC18A in the MC syndrome development of patients with HCV by using an in vitro cell-based assay with quantitative reverse transcription-PCR, immunoblotting, immunofluorescence, flow cytometry, and enzyme-linked immunosorbent assays. HCV infection or Toll-like receptor 3/7/8 activation could induce CLEC18A expression in Huh7.5 cells. Upregulated CLEC18A interacts with Rab5 and Rab7 and enhances type I/III interferon production to inhibit HCV replication in hepatocytes. However, overexpressed CLEC18A suppressed phagocytic activity in phagocytes. Significantly decreased levels of the Fc gamma receptor (FcγR) IIA were found in the neutrophils of HCV patients, particularly in those with MC ( P  < 0.005). We demonstrated that CLEC18A could inhibit FcγRIIA expression in a dose-dependent manner through the production of NOX-2-dependent reactive oxygen species to impair the uptake of ICs. Additionally, CLEC18A suppresses the Rab7 expression that is induced by starvation. Overexpressed CLEC18A does not affect autophagosome formation but does reduce the recruitment of Rab7 to autophagosomes, thereby retarding the maturation of autophagosomes and affecting autophagosome-lysosome fusion. We offer a novel molecular machinery with which to understand the association of HCV infection with autoimmunity and propose that CLEC18A may act as a candidate biomarker for HCV-associated MC. IMPORTANCE During infection, the host immune system produces cellular factors to protect against pathogen invasion. However, when the immune response overreacts and there is dysregulated cytokine homeostasis, autoimmunity occurs following an infection. We identified a cellular factor that is involved in HCV-related extrahepatic manifestation, namely, CLEC18A, which is expressed abundantly in hepatocytes and phagocytes. It inhibits HCV replication in hepatocytes by interacting with Rab5/7 and enhancing type I/III IFN expression. However, overexpressed CLEC18A inhibited FcγRIIA expression in phagocytes to impair phagocytosis. Furthermore, the interaction between CLEC18A and Rab5/7 may reduce the recruitment of Rab7 to autophagosomes and thereby retard autophagosome maturation and cause immune complex accumulation. A decreasing trend in CLEC18A levels that was accompanied by reduced HCV RNA titers and diminished cryoglobulin was observed in the sera of HCV-MC patients after direct-acting antiviral therapy. CLEC18A may be used for the evaluation of anti-HCV therapeutic drug effects and could be a potential predisposing factor for the development of MC syndrome., Competing Interests: The authors declare no conflict of interest.

Cystic echinococcosis is caused by the larval stages (hydatids) of cestode parasites belonging to the species cluster Echinococcus granulosus sensu lato , with E. granulosus sensu stricto being the main infecting species. Hydatids are bladderlike structures that attain large sizes within various internal organs of livestock ungulates and humans. Hydatids are protected by the massive acellular laminated layer (LL), composed mainly of mucins. Parasite growth requires LL turnover, and abundant LL-derived particles are found at infection sites in infected humans, raising the question of how LL materials are dealt with by the hosts. In this article, we show that E. granulosus sensu stricto LL mucins injected into mice are taken up by Kupffer cells, the liver macrophages exposed to the vascular space. This uptake is largely dependent on the intact mucin glycans and on Clec4F, a C-type lectin receptor which, in rodents, is selectively expressed in Kupffer cells. This uptake mechanism operates on mucins injected both in soluble form intravenously (i.v.) and in particulate form intraperitoneally (i.p.). In mice harboring intraperitoneal infections by the same species, LL mucins were found essentially only at the infection site and in the liver, where they were taken up by Kupffer cells via Clec4F. Therefore, shed LL materials circulate in the host, and Kupffer cells can act as a sink for these materials, even when the parasite grows in sites other than the liver., Competing Interests: The authors declare no conflict of interest.

Sargassum are brown algae belonging to the class Phaeophyceae . Brown algae are rich in nutrients and widely used in food. Most previous experiments have focused on the functional evaluation of organic solvent extracts of Sargassum . Considering food safety, this study investigated the antioxidant and antiobesity activities of Sargassum hemiphyllum water extract (SE). The antioxidant activity of SE (500-4000 mg/mL) was determined in vitro. The results indicated that SE has good DPPH radical scavenging activity (14-74%), reducing power (20-78%), ABTS + radical scavenging activity (8-91%), and Fe 2+ chelating ability (5-25%). Furthermore, the antiobesity activity of SE (50-300 mg/mL) was analysed in a 3T3-L1 adipocyte model. SE effectively inhibited lipid accumulation (determined by methods including measuring the absorbance of Oil red O after staining and the triglyceride content, which were decreased by 10% and 20%, respectively) by reducing peroxisome proliferator-activated receptor gamma (PPARγ) protein expression in 3T3-L1 adipocytes. This study suggested that SE has good antioxidant and antiobesity properties., Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05707-1., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (© Association of Food Scientists & Technologists (India) 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Pelvic-acetabular fractures lead to high mortality in elders and their association between different groups is not known. Our results indicate that older age with pelvic-acetabular fracture was significantly associated with mortality. This finding may help planning and allocating healthcare resources, risk stratification, and optimizing the treatment of pelvic fractures., Purpose: Pelvic or acetabular fractures are among main outcomes of low-energy trauma such as falls, especially in older adults. They represent approximately 3-8% of all fractures and are associated with a high mortality rate ranging from 4 to 28%. This study is aimed at comparing the incidence and trends of hip fractures and pelvic-acetabular fractures in the Taiwanese general population, gender differences in adults aged over 65 years, and mortality risk between pelvic or acetabular fractures and hip fractures and surgery trends in patients with these fractures., Methods: A retrospective study was conducted extracting data from the National Health Insurance Research Database of patients diagnosed with hip fracture and pelvic acetabular fracture between 2000 and 2018., Results: Older age with pelvic-acetabular fracture was significantly associated with increased mortality. No significant differences were found in comorbidities between the two fracture groups. Results provide clear epidemiological evidence for trends in pelvic-acetabular fractures in Taiwan and demonstrate the need for better strategies to manage these fractures and comorbidities, particularly in older adults., Conclusion: Findings of this study may aid in planning and allocating healthcare resources, risk stratification, and optimizing the treatment of pelvic fractures among older adults in Taiwan., (© 2023. The Author(s).)

The small molecule characteristics and nutritional value of egg white hydrolysates have been widely used. In the present study, in vitro and in vivo models were used to investigate the hepatoprotective effect of egg protein hydrolysate (EWH) by regulating the expression of antioxidant enzymes. The in vitro experiment results showed that 0.1, 0.5, and 1 mg/mL of EWH enhanced antioxidant activity in HepG2 cells by increased glutathione peroxidase (GPx) activity and reduced glutathione (GSH) levels. The in vivo experiment results showed that EWH (L) (38.5 mg/kg BW) and EWH (H) (385 mg/kg BW) alleviated carbon tetrachloride (CCl 4 )-induced hepatotoxicity in SD rats through reduced levels of serum aspartate aminotransferase (AST) alanine aminotransferase (ALT), and lipid peroxidation products malondialdehyde (MDA). In addition, EWH also ameliorates CCl 4 -induced hepatotoxicity in SD rats by increasing the antioxidant activity of GSH levels with a decrease in oxidized glutathione (GSSG) levels. Besides, EWH ameliorates liver tissue injuries by CCl4-induction. EWH has the highest glutamic acid in free amino acid composition, the second highest was aspartic acid, and the third was cystine, 204, 141, and 125 mg/100 g, respectively. These results suggest EWH has hepatoprotective potential through reduced lipid peroxidation products and enhanced antioxidant activity., Competing Interests: Conflict of interestsThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (© Association of Food Scientists & Technologists (India) 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: The shock index (SI) predicts short-term mortality in trauma patients. Other shock indices have been developed to improve discriminant accuracy. The authors examined the discriminant ability of the SI, modified SI (MSI), and reverse SI multiplied by the Glasgow Coma Scale (rSIG) on short-term mortality and functional outcomes., Methods: The authors evaluated a cohort of adult trauma patients transported to emergency departments. The first vital signs were used to calculate the SI, MSI, and rSIG. The areas under the receiver operating characteristic curves and test results were used to compare the discriminant performance of the indices on short-term mortality and poor functional outcomes. A subgroup analysis of geriatric patients with traumatic brain injury, penetrating injury, and nonpenetrating injury was performed., Results: A total of 105 641 patients (49±20 years, 62% male) met the inclusion criteria. The rSIG had the highest areas under the receiver operating characteristic curve for short-term mortality (0.800, CI: 0.791-0.809) and poor functional outcome (0.596, CI: 0.590-0.602). The cutoff for rSIG was 18 for short-term mortality and poor functional outcomes with sensitivities of 0.668 and 0.371 and specificities of 0.805 and 0.813, respectively. The positive predictive values were 9.57% and 22.31%, and the negative predictive values were 98.74% and 89.97%. rSIG also had better discriminant ability in geriatrics, traumatic brain injury, and nonpenetrating injury., Conclusion: The rSIG with a cutoff of 18 was accurate for short-term mortality in Asian adult trauma patients. Moreover, rSIG discriminates poor functional outcomes better than the commonly used SI and MSI., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

This study aimed to investigate the potential of egg white protein hydrolysate (EWH) as a functional food by identifying the optimum production conditions for EWH with response surface methodology (the results of the sensory evaluation were considered as an essential quality indicator). At the same time, its physicochemical and biological activity was also evaluated. The optimal economic production conditions were selected: substrate concentration of 12.5%, enzyme content of 7.5%, and hydrolysis time at 100 min. The degree of hydrolysis (DH %) was 13.51%. In addition, to the better acceptance of the evaluation, it also helps to reduce the production cost of the protein hydrolysate, which is beneficial to future processing and applications. The antioxidant capacity experiments showed that EWH has good antioxidant activity, which presents a dose-dependent relationship. Hence, this study provides a theoretical basis for future research and application of EWH for processing applications, including dietary supplementation., Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05708-0., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (© Association of Food Scientists & Technologists (India) 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Panax notoginseng (Burk) F. H. Chen is a traditional Chinese herbal medicine commonly used in clinical applications. This study examined the effects of the Panax notoginseng water extract (PNWE) on the immune responses and digestive enzyme activity of Litopenaeus vannamei ( L. vannamei ). The PNWE (50, 100, and 200 μg (g shrimp) -1 ) was injected into L. vannamei to analyze the immune response parameters, including the total haemocyte count (THC), granular haemocytes (GC), semi-granular haemocytes (SGC), hialin haemocyte (HC), the respiratory burst (RB), the phagocytic ratio (PR), the phagocytic index (PI), and phenoloxidase (PO). We evaluated the activity of the intestinal digestive enzymes (trypsin, chymotrypsin, amylase, and lipase), the histopathology, and the intestine Vibrio numbers. The results showed that different concentrations of the PNWE significantly increased THC, GC, SGC, PO and RB activity, the PR, and the PI of L. vannamei while reducing the HC. In addition, the PNWE also significantly increased the chymotrypsin, trypsin, and amylase activity of L. vannamei. Furthermore, 50 µg (g shrimp) -1 of PNWE regulated the lipase activity. Additionally, different concentrations of the PNWE significantly reduced the Vibrio numbers in the intestine without damaging the hepatopancreas and intestine tissues. These results indicate that the PNWE improves the immune responses of L. vannamei by increasing the haemocyte count and regulating intestinal digestive enzymes.

Previous literature has suggested physical exercise may improve cognitive impairments and mitigate depressive symptoms. However, few studies examined the impact of resistance exercise intervention on cognition and depression in older Chinese Americans. The purpose of this pilot study was to assess the effects of resistance exercise training on cognitive performance and depressive symptoms among community-dwelling older Chinese Americans. The study was a two-arm randomized controlled trial with pre-test/post-test design. Thirty older adults were randomly assigned into the resistance exercise intervention group or the wait-list control group. Participants' cognitive performance and depressive symptoms were evaluated at baseline (pre-test) and at 12 weeks (post-test). The results showed that there were significant differences between the intervention and control groups on changes in symptoms of depression, global cognitive function, visuospatial/executive functions, attention, language, and orientation. However, there were no significant differences between both groups on changes in naming, abstraction, and delayed recall domains. The findings of this study suggest that resistance exercise training has a positive impact on improving cognitive performance and depressive symptoms in older adults.

Inverse restricted kinematic alignment (irKA) was modified from restricted kinematic alignment for total knee arthroplasty (TKA). This prospective single-center study aimed to evaluate the outcomes of irKA-TKA on all knee subtypes classified by Asia specific (Huang's) phenotypes. A total of 96 knees that underwent irKA-TKA at one hospital between January 2018 and June 2020 were included, with 15 knees classified in Type 1, nine in Type 2, 15 in Type 3, 47 in Type 4, and 10 in Type 5 by Huang's phenotypes. Outcomes were knee alignment measures and patient-reported satisfaction evaluated by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and traditional Chinese version of the Forgotten Joint Score-12 (FJS-12). Follow-up was one year. Type 4 knee was most significantly corrected in all angles by irKA-TKA, followed by Type 2 and 3 knees. Type 5 and 1 knee were only significantly corrected in some angles. The correlation between FJS-12 and WOMAC was good at 6 months (Pearson correlation coefficient (r) = 0.74) and moderate at 6 weeks, 3 months, and 12 months during follow-up (r = 0.37~0.47). FJS-12 and WOMAC displayed comparable hip-knee-ankle angle cut-off value (4.71° vs. 6.20°), sensitivity (70.49% vs. 67.19%), specificity (84.00% vs. 85.71%), and Youden index (54.49% vs. 52.90%) in prediction of good prognosis. In conclusion, irKA-TKA corrects knee alignment in all knee types with increasing satisfaction for one-year follow-up. Knees with presurgical varus deformity are most recommended for irKA-TKA. Both presurgical scores of the traditional Chinese version of FJS-12 and WOMAC predict the prognosis of irKA-TKA.

Fish bones are the by-products of aquatic and fishery processing, which are often discarded. However, it has been considered having health-promoting by containing many essential nutrients. This study investigates the anti-inflammatory effect of fish bone fermented by Monascus purpureus (FBF) and the NF-κB pathway regulation mechanism in lipopolysaccharides (LPS)-induced RAW 264.7 cells. FBF has inhibited the production of PGE 2 (prostaglandin E 2 ), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in LPS-induced RAW264.7 cells. The FBF has significantly inhibited mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, FBF has suppressed activation of NF-κB (nuclear factor kappa-B) by increasing IκB mRNA expression and reduced of p65, p50 mRNA expression, as well as nuclear NF-κB DNA binding activity in LPS-induced RAW 246.7 cells. These findings demonstrate that FBF has inhibited LPS-induced inflammation by subsiding the activation of NF-κB in RAW 246.7 cells, implying that FBF could be employed as a promising natural product., Competing Interests: Conflict of interestThe authors declare that there are no conflicts of interest., (© Association of Food Scientists & Technologists (India) 2022.)

Background: Cirrhosis-related acute-on-chronic liver failure (ACLF) is associated with high morbidity and mortality rates. Prognostic models of ACLF have been developed; however, few studies have focused on the occurrence of ACLF. This study aimed to identify the factors that predict the development of ACLF, hepatic encephalopathy (HE), and infection in patients with cirrhosis., Methods: Patients with cirrhosis were enrolled, and the serum levels of calcitriol, Cluster of Differentiation 26 (CD206), and macrophage-inducible lectin receptor (Mincle) were measured, and lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio were calculated; all the patients were tracked for 6 months. A generalized estimating equation (GEE) was used to assess the factors associated with ACLF development, HE, and infection. The aforementioned model was derived based on immunological markers, and receiver operating characteristic analysis with area under the curve (AUC) was adopted to evaluate accuracy., Results: After screening 325 patients with cirrhosis, 65 patients were eligible. In the GEE model, low levels of calcitriol (odds ratio [OR] = 3.259; 95% confidence interval [CI] = 1.118-8.929) and CD206 (OR = 2.666; 95% CI = 1.082-6.567) were associated with the development of ACLF, and the LMR was a protective factor (OR = 0.356; 95% CI = 0.147-0.861). Low calcitriol levels were a risk factor for HE (OR = 3.827) and infection (OR = 2.489). LMR was found to be a protective factor against HE (OR = 0.388). An immunological model for the discrimination of ACLF development within 6 months was proposed, with an AUC of 0.734 (95% CI = 0.598-0.869)., Conclusion: Single and combined immunological markers, including low LMR and low levels of calcitriol and CD206, were promising for early prediction of the development of ACLF, HE, and infection in patients with cirrhosis., Competing Interests: Conflicts of interest: Dr. Ming-Chih Hou, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Resveratrol butyrate esters (RBEs), which are novel resveratrol-synthesized derivatives, exhibit increased biological activity. This study elucidated the effect of RBEs on fat metabolism and their anti-obesity characteristics. Their molecular mechanism was investigated in the 3T3-L1 murine preadipocyte cells and adipocytes. RBE doses of < 2 μM did not induce a significant change in the viability of 3T3-L1 adipocytes. After RBEs treatment, intracellular lipid droplet accumulation in 3T3-L1 adipocytes was stimulated by methylisobutylxanthine, dexamethasone, and insulin-containing medium. However, a significant dose-dependent reduction in intracellular lipid levels was observed. The mRNA levels of two adipogenic transcription factors (peroxisome proliferator-activated receptor [PPAR] and CCAAT/enhancer-binding proteins [C/EBP]) and lipogenic proteins (fatty acid-binding protein 4 [FABP4] and fatty acid synthase [FAS]) were significantly attenuated by RBE treatment in both MDI-stimulated and differentiated 3T3-L1 adipocytes. Moreover, the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) also dramatically increased in the MDI + RBE-treated group compared to that in the MDI + vehicle-treated group. Collectively, our study provides strong evidence that RBEs inhibit adipogenesis by regulating adipogenic protein expression and increasing the p-AMPK/AMPK ratio. Future studies will be conducted on animal models to validate the application of RBEs as a functional food ingredient in improving human health., Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05436-x., Competing Interests: Conflicts of interestThe authors declare no conflict of interest., (© Association of Food Scientists & Technologists (India) 2022.)

Citrus limon (lemon) possesses immunoregulatory, antioxidant, and lipid-lowering effects. Our previous study showed that lemon fermented products (LFP) which were lemon fermented with Lactobacillus OPC1 had the ability to avert obesity. However, the LFP effects on the pathway of lipid metabolism by gut microbiota were still unclear. This study was aimed to investigate the LFP effects on liver lipid metabolism and gut microbiota in a rat model of obesity caused by a high-calorie diet. LFP effectively reduced the total triglyceride (49.7%) and total cholesterol (53.3%) contents of the liver. Additionally, the mRNA levels of genes related to triglyceride metabolism (SREBP-1c, PPARγ, and ACC), cholesterol metabolism (HMG-CoA reductase, ACAT, and LCAT), and lipid β-oxidation (PPARα, and CPT-1) were regulated by LFP. Furthermore, LFP reduced the ratio of Firmicutes / Bacteroidetes and enhanced the ratio of Firmicutes Clostridia . Overall, these findings suggested that LFP might use as a potential dietary supplement for preventing obesity by modulating the lipid metabolism and improving the gut microbiota., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© Association of Food Scientists & Technologists (India) 2022.)

Background: Zika virus (ZIKV) infection is clinically known to induce testicular swelling, termed orchitis, and potentially impact male sterility, but the underlying mechanisms remain unclear. Previous reports suggested that C-type lectins play important roles in mediating virus-induced inflammatory reactions and pathogenesis. We thus investigated whether C-type lectins modulate ZIKV-induced testicular damage., Methods: C-type lectin domain family 5 member A (CLEC5A) knockout mice were generated in a STAT1-deficient immunocompromised background (denoted clec5a -/- stat1 -/- ) to enable testing of the role played by CLEC5A after ZIKV infection in a mosquito-to-mouse disease model. Following ZIKV infection, mice were subjected to an array of analyses to evaluate testicular damage, including ZIKV infectivity and neutrophil infiltration estimation via quantitative RT-PCR or histology and immunohistochemistry, inflammatory cytokine and testosterone detection, and spermatozoon counting. Furthermore, DNAX-activating proteins for 12 kDa (DAP12) knockout mice (dap12 -/- stat1 -/- ) were generated and used to evaluate ZIKV infectivity, inflammation, and spermatozoa function in order to investigate the potential mechanisms engaged by CLEC5A., Results: Compared to experiments conducted in ZIKV-infected stat1 -/- mice, infected clec5a -/- stat1 -/- mice showed reductions in testicular ZIKV titer, local inflammation and apoptosis in testis and epididymis, neutrophil invasion, and sperm count and motility. CLEC5A, a myeloid pattern recognition receptor, therefore appears involved in the pathogenesis of ZIKV-induced orchitis and oligospermia. Furthermore, DAP12 expression was found to be decreased in the testis and epididymis tissues of clec5a -/- stat1 -/- mice. As for CLEC5A deficient mice, ZIKV-infected DAP12-deficient mice also showed reductions in testicular ZIKV titer and local inflammation, as well as improved spermatozoa function, as compared to controls. CLEC5A-associated DAP12 signaling appears to in part regulate ZIKV-induced testicular damage., Conclusions: Our analyses reveal a critical role for CLEC5A in ZIKV-induced proinflammatory responses, as CLEC5A enables leukocytes to infiltrate past the blood-testis barrier and induce testicular and epididymal tissue damage. CLEC5A is thus a potential therapeutic target for the prevention of injuries to male reproductive organs in ZIKV patients., (© 2023. The Author(s).)

D-limonene (LIM) is a common monoterpene compound, principally found in citrus essential oils. This study investigated the anti-obesity effect of LIM on the 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway in 3T3-L1 adipocytes and high-calorie diet-induced obese rats and confirmed the optimally effective dose of LIM. The 3T3-L1 adipocytes were treated with 0.05−0.4 mg/mL LIM for 10 days and oil red O and triglyceride (TG) content were used to determine the levels of lipid accumulation. The results showed that more than 0.05 mg/mL LIM inhibited lipid accumulation by reducing oil red O in 3T3-L1 adipocytes. Masses of 0.2 and 0.4 mg/mL LIM also decreased the TG contents in 3T3-L1 adipocytes. On the other hand, Wistar rats were given high-calorie diets, combined with LLIM (154 mg/kg) and HLIM (1000 mg/kg) treatments, for 16 weeks. The result shows that LLIM and HLIM decreased body weight, total fat tissue weight, and serum low-density lipoprotein-cholesterol (LDLc) levels. HLIM reduced serum TG and increased serum lipase and high-density lipoprotein-cholesterol (HDLc) levels. Moreover, the anti-obesity metabolic pathway showed that LIM (>0.05 mg/mL) in 3T3-L1 adipocytes and LIM (>154 mg/kg) in high-calorie diet-induced obese rats could activate the AMPK signaling pathway. The activated AMPK regulated the mRNA expression related to adipogenesis (PPARγ, C/EBPα, FABP4), lipogenesis (SREBP-1c, ACC, FAS), and lipolysis (ATGL, HSL) to inhibit obesity. This finding demonstrates that LIM has anti-obesity properties. Namely, it is seen that LIM acts by regulating the AMPK signaling pathway in 3T3-L1 adipocytes and high-calorie diet-induced obese rats. In terms of dose−response, LIM (154 mg/kg) would be an optimal effective dose for anti-obesity induced by a high-calorie diet.

The presence of di-(2-ethylhexyl) phthalate (DEHP) in the aquatic systems, specifically marine sediments has attracted considerable attention worldwide, as it enters the food chain and adversely affects the aquatic environment and subsequently human health. This study reports an efficient carbocatalytic activation of calcium peroxide (CP) using water hyacinth biochar (WHBC) toward the efficient remediation of DEHP-contaminated sediments and offer insights into biochar-mediated cellular cytotoxicity, using a combination of chemical and bioanalytical methods. The pyrolysis temperature (300-900 °C) for WHBC preparation significantly controlled catalytic capacity. Under the experimental conditions studied, the carbocatalyst exhibited 94% of DEHP removal. Singlet oxygen ( 1 O 2 ), the major active species in the WHBC/CP system and electron-rich carbonyl functional groups of carbocatalyst, played crucial roles in the non-radical activation of CP. Furthermore, cellular toxicity evaluation indicated lower cytotoxicity in hepatocarcinoma cells (HepG2) after exposure to WHBC (25-1000 μg mL -1 ) for 24 h and that WHBC induced cell cycle arrest at the G2/M phase. Findings clearly indicated the feasibility of the WHBC/CP process for the restoration of contaminated sediment and contributing to understanding the mechanisms of cytotoxic effects and apoptotic of carbocatalyst on HepG2., 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 © 2022 Elsevier Inc. All rights reserved.)

Formaldehyde has an extremely reactive carbonyl group, commonly used as an antibacterial agent to sterilize and prevent food to spoil. This article describes an efficient and rapid detection method of formaldehyde from an aqueous solution by synthesizing 3-Aminopropyltriethoxysilane (APTES) quantum dots (Nano A) which react with formaldehyde to generate a Schiff base reaction. The photoinduced electron transfer produced by the quantum dots themselves results in fluorescence quenching to detect formaldehyde. The detection limit can reach 10 -9 M, and it can further be used to detect formaldehyde content in foods, such as baby vegetables, mushrooms, and vermicelli among other daily foods., 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 © 2022. Published by Elsevier B.V.)

Autophagy facilitates the degradation of organelles and cytoplasmic proteins in a lysosome-dependent manner. It also plays a crucial role in cell damage. Whether loganin affects autophagy in chronic constriction injury (CCI)-induced neuropathic pain remains unclear. We investigated the neuroprotective effect of loganin on the autophagic-lysosomal pathway in the rat CCI model. Sprague-Dawley rats were divided into sham, CCI, sham + loganin, and CCI + loganin. Loganin (5 mg/kg/day) was intraperitoneally injected once daily, and rats were sacrificed on day 7 after CCI. This study focused on the mechanism by which loganin modulates autophagic flux after CCI. CCI enhanced the autophagic marker LC3B-II in the ipsilateral spinal cord. The ubiquitin-binding protein p62 binds to LC3B-II and integrates into autophagosomes, which are degraded by autophagy. CCI caused the accumulation of p62, indicating the interruption of autophagosome turnover. Loganin significantly attenuated the expression of Beclin-1, LC3B-II, and p62. Double immunofluorescence staining was used to confirm that LC3B-II and p62 were reduced by loganin in the spinal microglia and astrocytes. Loganin also lessened the CCI-increased colocalization of both proteins. Enhanced lysosome-associated membrane protein 2 (LAMP2) and pro-cathepsin D (pro-CTSD) in CCI rats were also attenuated by loganin, suggesting that loganin improves impaired lysosomal function and autophagic flux. Loganin also attenuated the CCI-increased apoptosis protein Bax and cleaved caspase-3. Loganin prevents CCI-induced neuropathic pain, which could be attributed to the regulation of neuroinflammation, neuronal autophagy, and associated cell death. These data suggest autophagy could be a potential target for preventing neuropathic pain.

Panax notoginseng (PN) exerts cardiovascular-disease-protective effects, but the effect of PN on reducing vascular calcification (VC) is unknown. Under the VC process, however, endothelial bone morphogenetic protein-2 (BMP-2) signals connect endothelial and smooth muscle cells. To investigate the effects of PN water extract (PNWE) on BMP-2 expression, human EA.hy926 endothelial cells were pretreated with PNWE for 48 h, and BMP-2 expression was then induced using warfarin/β-glycerophosphate (W/BGP) for another 24 h. The expression of BMP-2, the degrees of oxidative stress and inflammation, and the activation of noncanonical NF-κB and Wnt/β-catenin signaling were analyzed. The results showed that the BMP-2 levels in EA.hy926 cells were reduced in the groups treated with 10, 50, or 100 μg/mL PNWE combined with W/BGP. PNWE combined with W/BGP significantly reduced thiobarbituric-acid-reactive substrate and reactive oxygen species levels as well as prostaglandin E2, IL-1β, IL-6, and TNF-α. PNWE (10, 50, and 100 μg/mL) reduced the p52 levels and p52/p100 protein ratio. Wnt and β-catenin protein expression was decreased in the groups treated with PNWE combined with W/BGP. These results showed that PNWE reduced BMP-2 expression in EA.hy926 cells by inhibiting the noncanonical NF-κB and Wnt/β-catenin signaling pathways.

In fish processing, reducing the waste rate and increasing the economic value of products is an important issue for global environmental protection and resource sustainability. It has been discovered that cuttlefish bones can be an excellent resource for producing attractive amounts of chitin and chitosan. Therefore, this study optimized chitosan extraction conditions using response surface methodology (RSM) to establish application conditions suitable for industrial production and reducing environmental impact. In addition, Fourier-transform infrared spectroscopy (FTIR), 1 H NMR and scanning electron microscope (SEM) characteristics of extracted chitosan were evaluated. The optimum extraction conditions for chitosan from cuttlebone chitin were 12.5M NaOH, 6 h and 80 °C, and the highest average yield was 56.47%. FTIR spectroscopy, 1 H NMR, and SEM identification proved that the chitosan prepared from cuttlefish bone has a unique molecular structure, and the degree of deacetylation of chitosan was about 81.3%. In addition, it was also confirmed that chitosan has significant anti-oxidation and oil-absorbing abilities. This research has successfully transformed the by-products of cuttlefish processing into value-added products. The process not only achieved the recycling and utilization of by-products but also enhanced industrial competitiveness and resource sustainability.

Caspase-8 activity controls the switch from cell death to pyroptosis when apoptosis and necroptosis are blocked, yet how caspase-8 inactivation induces inflammasome assembly remains unclear. We show that caspase-8 inhibition via IETD treatment in Toll-like receptor (TLR)-primed Fadd -/- Ripk3 -/- myeloid cells promoted interleukin-1β (IL-1β) and IL-18 production through inflammasome activation. Caspase-8, caspase-1/11, and functional GSDMD, but not NLRP3 or RIPK1 activity, proved essential for IETD-triggered inflammasome activation. Autophagy became prominent in IETD-treated Fadd -/- Ripk3 -/- macrophages, and inhibiting it attenuated IETD-induced cell death and IL-1β/IL-18 production. In contrast, inhibiting GSDMD or autophagy did not prevent IETD-induced septic shock in Fadd -/- Ripk3 -/- mice, implying distinct death processes in other cell types. Cathepsin-B contributes to IETD-mediated inflammasome activation, as its inhibition or down-regulation limited IETD-elicited IL-1β production. Therefore, the autophagy and cathepsin-B axis represents one of the pathways leading to atypical inflammasome activation when apoptosis and necroptosis are suppressed and capase-8 is inhibited in myeloid cells.

Lower ambient temperatures impair neuromuscular function and balance. However, whether lower ambient temperatures could alter joint angles and symmetry of lower limbs during crossing obstacles in males still remains unknown. Therefore, we investigated whether there is reduction of ambient temperature (20°C; 15°C; 10°C) on lower limbs joint angles and symmetry when crossing obstacles in males. On three different occasions, eighteen male participants underwent 30 min exposure to three different environmental temperatures (10°C, 15°C, and 20°C), which was followed by the obstacle crossing test at 10%, 20%, and 30% of the participant leg length. In each trial, we assessed joint angles and symmetry of lower limbs when crossing obstacles at 10%, 20%, and 30% of the participants' leg length. The results showed that leading limb maximum joint angles were greater in 10°C than in 15°C and 20°C when leading limb crossed obstacle heights of 20% and 30% leg length ( p < 0.05). Trailing limb maximum joint angles were not different ( p > 0.05). Lower limb asymmetry increased when participants crossed obstacle heights of 20% and 30% leg length at 10°C ( p < 0.05). This study concluded that in male participants, cold exposure can increase lower limb asymmetry to increase falling risk when crossing obstacles. Also, the increased leading limb joint angles and constant trailing limb joint angles increase safety during crossing obstacles., Competing Interests: All authors declare that they have no conflict of interest regarding the contents of this article., (Copyright © 2022 Shun Yao et al.)

The adsorption of Pb ions, on high-density polyethylene (PE) microplastics (MPs) with the diameter of 48-500 μm, was examined in this study. According to the Langmuir isotherm, MP of the smallest size, 48 μm, had the greatest adsorption capacity of 0.38 μmol g -1 . The mechanism of Pb ions adsorption onto PE MPs was chemical adsorption, in particular, hydrogen bonding and surface complexation. Pb adsorption onto PE particles was proceeded at a rapid rate, as predicted by the pseudo-second-order rate model (R 2  > 0.99). The PE 48 μm had the maximum adsorption capacity of 0.44 μmol g-1 (or 0.2 mol m -2 ) at pH 5. While humic acid can operate as a bridging agent, boosting heavy metal adsorption on the surface of PE MPs, fulvic acid has the reverse effect. The findings indicated that PE particles may serve as a carrier of heavy metals in the aquatic environment, posing perceived risks to the environment and public health., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

D-limonene (4-isopropenyl-1-methylcyclohexene) is an important compound in several citrus essential oils (such as orange, lemon, tangerine, lime, and grapefruit). It has been used as a flavoring agent and as a food preservative agent, with generally recognized as safe (GRAS) status. D-limonene has been well-studied for its anti-inflammatory, antioxidant, anti-cancer, and antibacterial properties. The antibacterial activity of D-limonene against food-borne pathogens was investigated in this study by preparing a D-limonene nanoemulsion. The D-limonene solution and nanoemulsion have been prepared in six concentrations, 0.04%, 0.08%, 0.1%, 0.2%, 0.4%, and 0.8% ( v / v ), respectively, and the antibacterial activity was tested against four food-borne pathogens ( Staphylococcus aureus , Listeria monocytogenes , Salmonella enterica , and Escherichia coli ). The results showed that the D-limonene nanoemulsion had good nanoscale and overall particle size uniformity, and its particle size was about 3~5 nm. It has been found that the D-limonene solution and nanoemulsion have a minimal inhibitory concentration of 0.336 mg/mL, and that they could inhibit the growth of microorganisms efficiently. The data indicate that the D-limonene nanoemulsion has more antibacterial ability against microorganisms than the D-limonene essential oil. After bananas are treated with 1.0% and 1.5% D-limonene nanoemulsion coatings, the water loss of the bananas during storage and the percentage of weight loss are reduced, which can inhibit the activity of pectinase. The application of a biocoating provides a good degree of antibacterial activity and air and moisture barrier properties, which help with extending the shelf life of bananas.

Pseudomonas aeruginosa is one of the most common nosocomial infections worldwide, and it frequently causes ventilator-associated acute pneumonia in immunocompromised patients. Abundant neutrophil extracellular traps (NETs) contribute to acute lung injury, thereby aggravating ventilator-induced lung damage. While pattern recognition receptors (PRRs) TLR4 and TLR5 are required for host defense against P. aeruginosa invasion, the PRR responsible for P. aeruginosa-induced NET formation, proinflammatory cytokine release, and acute lung injury remains unclear. We found that myeloid C-type lectin domain family 5 member A (CLEC5A) interacts with LPS of P. aeruginosa and is responsible for P. aeruginosa-induced NET formation and lung inflammation. P. aeruginosa activates CLEC5A to induce caspase-1-dependent NET formation, but it neither causes gasdermin D (GSDMD) cleavage nor contributes to P. aeruginosa-induced neutrophil death. Blockade of CLEC5A attenuates P. aeruginosa-induced NETosis and lung injury, and simultaneous administration of anti-CLEC5A mAb with ciprofloxacin increases survival rate and decreases collagen deposition in the lungs of mice challenged with a lethal dose of P. aeruginosa. Thus, CLEC5A is a promising therapeutic target to reduce ventilator-associated lung injury and fibrosis in P. aeruginosa-induced pneumonia.

Abnormal lipolysis is correlated with metabolic syndrome. Caffeic acid phenethyl ester (CAPE), a natural product from honeybee hives, has been reported to improve metabolic syndrome. However, the effects of CAPE on lipolysis and perilipin-1 (the major lipid droplet-associated protein) in mature adipocytes were not clarified. In this study, mature adipocytes were isolated from the epididymal fat pads of male rats and incubated with CAPE to estimate lipolysis by measuring glycerol release. It was found that the basal lipolysis was inhibited by CAPE in a dose- and time-dependent manner. The lipid droplet-associated perilipin-1 and phosphorylated peroxisome proliferator-activated receptor (PPAR) gamma levels increased following CAPE treatment by Western blot analysis. Moreover, a specific PPAR-gamma inhibitor (T0070907) could partly reverse the effect of CAPE on basal lipolysis. Furthermore, treatment of adipocytes with dibutyryl-cAMP (db-cAMP) or isoproterenol (ISO) increased lipolysis, but the drug-induced lipolysis was abrogated by combination treatment with CAPE. The lipid droplet-associated perilipin-1 level was also decreased in the drug-induced groups but increased when combined treatment with CAPE. In conclusion, our results revealed that a decrease in basal lipolysis and an increase in lipid droplet-associated perilipin-1 levels induced by CAPE may be involved in the regulation of lipid metabolism through activation of PPAR-gamma in mature adipocytes., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Nguyen Thi Thu Trang et al.)

Chronic otitis media (COM) has been considered as a localized disease, and its systemic impact is poorly understood. Whether COM-induced inflammation could be associated with systemic bone loss and hip fracture is unknown at present. Our study tried to determine the risk of hip fracture among COM patients. We selected the comparison individuals without the COM coding and paired the controls with COM patients by gender, age, and comorbidities (including osteoporosis) by about a one-to-two ratio. Our study showed that the incidence of hip fracture was 4.48 and 3.92 per 1000 person-years for comparison and COM cohorts respectively. The cumulative incidence of hip fracture is higher in the COM cohort (p < 0.001). After adjustment for gender, age, and comorbidities, the COM patients had a 1.11-fold (aHR = 1.11; 95% CI = 1.05−1.17) risk of hip fracture than the control subjects. Among COM patients, a history of hearing loss is associated with higher (aHR = 1.21; 95% CI = 1.20−1.42) fracture risk. Our study showed that COM patients, especially those with hearing loss, are susceptible to a higher risk for hip fracture.

The relationships and interactions between extracellular polymeric substances (EPS) and microplastics (MPs) in coral reef ecosystems were symmetrically investigated. The current study aims to investigate the responses of scleractinian coral (Goniopora columna) to exposure of model MPs, exemplified by polyethylene (PE), in the size range of 40-48 μm as affected by MPs concentration of MP in the range between 0 and 300 mg L -1 for 14 days. The structure of EPS-associated microbial community was studied using a series of techniques including high-throughput sequencing of 16 S rRNA, transmission electron microscopy (TEM), hydrodynamic diameter, surface charge (via zeta potential), X-ray diffraction (XRD), attenuated total reflectance‒Fourier transform infrared (ATR‒FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and fluorescence excitation-emission matrix (FEEM) spectroscopy. Microbial interactions between PE-MPs and coral caused aggregation and formation of EPS matrix, which resulted in increase and decrease in the relative abundance of Donghicola (Proteobacteria phylum) and Marivita (Proteobacteria phylum) in PE-MP-associated EPS, respectively. Particle size, electrostatic interactions, and complexation with the functional groups of the EPS-based matrix affected the humification index. FEEM spectroscopy analyses suggested the presence of humic- and fulvic-like fluorophores in EPS and dissolved organic matter (DOM) in PE-MP-derived DOM. The findings provided insights into the potential environmental implications of coral-based EPS and co-existing microbial assemblages due to EPS-PE-MP-microbiome interactions throughout the dynamic PE-MP exposure process., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: This study examined the association between lapsed time and trauma patients, suggesting that a shorter time to definitive care leads to a better outcome., Methods: We used the Pan-Asian Trauma Outcome Study registry to analyze a retrospective cohort of 963 trauma patients who received surgical intervention or transarterial embolization within 2 h of injury in Asian countries between January 2016 and December 2020. Exposure measurement was recorded every 30 min from injury to definitive care. The 30 day mortality rate and functional outcome were studied using the Modified Rankin Scale ratings of 0-3 vs 4-6 for favorable vs poor functional outcomes, respectively. Subgroup analyses of different injury severities and patterns were performed., Results: The mean time from injury to definitive care was 1.28 ± 0.69 h, with cases categorized into the following subgroups: < 30, 30-60, 60-90, and 90-120 min. For all patients, a longer interval was positively associated with the 30 day mortality rate (p = 0.053) and poor functional outcome (p < 0.05). Subgroup analyses showed the same association in the major trauma (n = 321, p < 0.05) and torso injury groups (n = 388, p < 0.01) with the 30 day mortality rate and in the major trauma (p < 0.01), traumatic brain injury (n = 741, p < 0.05), and torso injury (p < 0.05) groups with the poor functional outcome., Conclusion: Even within 2 h, a shorter time to definitive care is positively associated with patient survival and functional outcome, especially in the subgroups of major trauma and torso injury., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)