Multi-organ involvement caused by Scedosporium apiospermum infection after near drowning: a case report and literature review.

BACKGROUND: Scedosporium apiospermum (S. apiospermum) is a rare fungal pathogen that causes disseminated infections. It rarely affects immunocompetent individuals and has a poor prognosis. CASE PRESENTATION: A 37-year-old woman presented with multiple lesions in the lungs, brain, and eyes, shortly after near drowning in a car accident. The primary symptoms were chest tightness, limb weakness, headache, and poor vision in the left eye. S. apiospermum infection was confirmed by metagenomic next-generation sequencing (mNGS) of intracranial abscess drainage fluid, although intracranial metastases were initially considered. After systemic treatment with voriconazole, her symptoms improved significantly; however, she lost vision in her left eye due to delayed diagnosis. CONCLUSION: While S. apiospermum infection is rare, it should be considered even in immunocompetent patients. Prompt diagnosis and treatment are essential. Voriconazole may be an effective treatment option.

Effect of moxibustion on the SIRT1/FOXO3a signaling pathway in ApoE-/- mice with atherosclerosis. / 艾灸对ApoE-/-åŠ¨è„‰ç²¥æ ·ç¡¬åŒ–å°é¼ SIRT1/FOXO3a信号通路的影响.

OBJECTIVES: To observe the effects of moxibustion on blood lipid metabolism, pathological morphology of thoracic aorta, and the expression of silent information regulator 1 (SIRT1) and forkhead box transcription factor O3a (FOXO3a) in ApoE-/- atherosclerosis (AS) mice, so as to explore the potential mechanism of moxibustion in preventing and treating AS. METHODS: Ten C57BL/6J mice were fed a normal diet as the control group, and 30 ApoE-/- mice were fed a high-fat diet to establish the AS model, which were randomly divided into the model group, simvastatin group, and moxibustion group, with 10 mice in each group. From the first day of modeling, mice in the moxibustion group received mild moxibustion treatment at "Shenque"(CV8), "Yinlingquan"(SP9), bilateral "Neiguan"(PC6) and "Xuehai"(SP10) for 30 min per time；the mice in the simvastatin group were given simvastatin orally (2.5 mg·kg-1·d-1), with both treatments given once daily, 5 times a week, with a total intervention period of 12 weeks. The body weight and general condition of the mice were observed and recorded during the intervention period. After the intervention, the contents of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automated biochemistry analyzer. Hematoxylin eosin (HE) staining was used to observe the pathological morphology of the thoracic aorta. ELISA was used to measure the contents of serum oxidized low-density lipoprotein (ox-LDL) and superoxide dismutase (SOD) activity. Western blot and real-time fluorescent quantitative PCR analysis were used to detect the expression levels of SIRT1 and FOXO3a protein and mRNA in the thoracic aorta. RESULTS: Compared with the control group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of the model group mice were significantly increased(P<0.05, P<0.01), while the HDL-C contents, SOD activity, and the expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly decreased(P<0.05, P<0.01). HE staining showed thickening of the aortic intima, endothelial cell degeneration, swelling, and shedding. Compared with the model group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of mice in the simvastatin group and moxibustion group were significantly decreased(P<0.01), while the serum SOD activity, expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly increased(P<0.01). The HDL-C contents were significantly increased in the simvastatin group(P<0.05). The thoracic aortic structure was more intact in both groups, with a more regular lumen and orderly arrangement of the elastic membrane in the media, and a slight amount of endothelial cell degeneration and swelling in the intima. There was no significant difference in the evaluated indexes between the moxibustion group and the simvastatin group and the pathological changes in the thoracic aorta were similar between the two groups. CONCLUSIONS: Moxibustion can reduce the body weight of AS model mice, regulate lipid levels, repair vascular intima, and alleviate endothelial damage. Its mechanism of action may be related to the regulation of the SIRT1/FOXO3a signaling pathway to improve oxidative damage.

SIVA-1 enhances acquired chemotherapeutic drug resistance of gastric cancer in vivo by regulating the ARF/MDM2/p53 pathway.

SIVA-1 has been shown to affect apoptotic processes in various different cell lines, and SIVA-1 significantly contributes to the decreased responsiveness of cancer cells to some chemotherapy agents. However, whether SIVA-1 has potential application in gastric cancer remains unknown. Therefore, the objective of this investigation was to clarify the distinct function of SIVA-1 in chemotherapeutic drug resistance within a living murine model with gastric malignancy, and initially elucidate the underlying mechanisms. In an established multidrug-resistant gastric cancer xenograft mouse model, lentivirus, named Lv-SIVA-1, was injected into xenograft tumors, and increased the mRNA and protein expression of endogenous SIVA-1 in tumors. Immunohistochemical assays of xenograft tumor showed that SIVA-1 was significantly upregulated, and the protein expression levels of SIVA-1 were highly increased, as detected by Western blotting. In addition, we detected the role of SIVA-1 in cell proliferation and cell apoptosis in gastric cancer cells by TUNEL and found that SIVA-1 decreased tumor cell apoptosis and promoted tumor growth in vivo. Using a TMT assay between tumor tissues of experimental and control groups, differentially expressed proteins were examined and three potential biomarkers of multidrug resistance (ARF, MDM2, and p53) were screened. We further investigated the molecular mechanism by which SIVA-1 played an efficient role against chemotherapies and found that overexpressed SIVA-1 leads to increased ARF and MDM2 expression and suppressed expression of p53 in tumor tissue. In conclusion, SIVA-1 plays a significant role in the multidrug resistance of gastric tumors. In addition, overexpressed SIVA-1 positively regulates cell proliferation, adjusts cycle progression, and reduces the response to drug treatment for gastric cancer in an ARF/MDM2/p53-dependent manner. This novel research provides a basis for chemical management of gastric cancer through regulation of SIVA-1 expression.

Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aß pathology in Alzheimer's disease models.

Autophagy impairment is a key factor in Alzheimer's disease (AD) pathogenesis. TFEB (transcription factor EB) and TFE3 (transcription factor binding to IGHM enhancer 3) are nuclear transcription factors that regulate autophagy and lysosomal biogenesis. We previously showed that corynoxine (Cory), a Chinese medicine compound, protects neurons from Parkinson's disease (PD) by activating autophagy. In this study, we investigated the effect of Cory on AD models in vivo and in vitro. We found that Cory improved learning and memory function, increased neuronal autophagy and lysosomal biogenesis, and reduced pathogenic APP-CTFs levels in 5xFAD mice model. Cory activated TFEB/TFE3 by inhibiting AKT/mTOR signaling and stimulating lysosomal calcium release via transient receptor potential mucolipin 1 (TRPML1). Moreover, we demonstrated that TFEB/TFE3 knockdown abolished Cory-induced APP-CTFs degradation in N2aSwedAPP cells. Our findings suggest that Cory promotes TFEB/TFE3-mediated autophagy and alleviates Aß pathology in AD models.

Advances in Immunomodulatory MOFs for Biomedical Applications.

Given the crucial role of immune system in the occurrence and progression of various diseases such as cancer, wound healing, bone defect, and inflammation-related diseases, immunomodulation is recognized as a potential solution for treatment of these diseases. Immunomodulation includes both immunosuppression in hyperactive immune conditions and immune activation in hypoactive conditions. For these purposes, metal-organic frameworks (MOFs) are investigated to modulate immune responses either by their own bioactivities or by delivering immunomodulatory agents due to their excellent biodegradability and high delivery capacity. This review starts with an overview of the synthesis strategies of immunomodulatory MOFs, followed by a summarization on the latest applications of immunomodulatory MOFs in cancer immunomodulatory, wound healing, inflammatory disease, and bone tissue engineering. A variety of design considerations, in order to optimize immunomodulatory properties and efficacy of MOFs, is also involved. Last, the challenges and perspectives of future research, which are expected to provide researchers with new insight into the design and application of immunomodulatory MOFs, are discussed.

Moisture chamber goggles for the treatment of postoperative dry eye in patients receiving SMILE and FS-LASIK surgery.

BACKGROUND: The incidence of refractive surgery-related dry eye disease (DED) is rising due to the increasing popularity of corneal refractive surgery. The moisture chamber goggles (MCGs) have been shown to tear evaporation by increasing local humidity and minimizing airflow. The current study aims to evaluate the efficacy of moisture chamber goggles for refractive surgery-related DED. METHODS: In this nonrandomized open-label controlled study, 78 participants (156 eyes) receiving refractive surgery were enrolled between July 2021 and April 2022, and sequentially allocated to MGC and control groups. 39 participants were allocated to the MGC groups, of which 53.8% received small-incision lenticule extraction (SMILE) and 46.2% received femtosecond laser-assisted in situ keratomileusis (FS-LASIK), and were instructed to wear MCGs for the duration of 1 month postoperatively, in addition to the standard postoperative treatment received by the control groups (56.4% SMILE, 43.6% FS-LASIK). Participants underwent full ophthalmic examinations, including visual acuity, manifest refraction, DED evaluations, and higher-order aberrations (HOAs), both preoperatively and at routine follow-ups 1 day, 1 week, and 1 month after surgery. DED parameters included non-invasive tear film break-up time (NIBUT), tear meniscus height (TMH), conjunctival congestion, lipid layer thickness (LLT), and ocular surface disease index (OSDI) questionnaires. Student's t-test was used for comparisons between control and MCG groups, and between preoperative and postoperative parameters within groups. RESULTS: Postoperative NIBUT decreased in both SMILE and FS-LASIK control groups 1 day after the surgery (SMILE, P = 0.001; FS-LASIK, P = 0.008), but not in the corresponding MCG groups (SMILE, P = 0.097; FS-LASIK, P = 0.331). TMH in the MCG group was significantly higher at 1 week (P = 0.039) and 1 month (P = 0.015) in SMILE, and 1 day (P = 0.003) in FS-LASIK groups. In FS-LASIK participants, significantly lower HOAs and coma levels in the MCG group were observed 1 day (total HOAs, P = 0.023; coma, P = 0.004) and 1 week (total HOAs, P = 0.010, coma, P = 0.004) after surgery. No consistent statistically significant intergroup difference was observed between MCG and control groups in conjunctival congestion, LLT, and OSDI. CONCLUSIONS: MCGs effectively slowed tear evaporation, increased tear film stability, and improved HOAs in patients receiving SMILE and FS-LASIK surgeries. MCG is an effective adjuvant therapy in the comprehensive management of refractive surgery-related DED.

Effect of acupuncture on the expression of neuropeptides and related inflammatory factors in rats with diarrhea-predominant irritable bowel syndrome. / é’ˆåˆºå¯¹è ¹æ³»åž‹è‚ æ˜“æ¿€ç»¼åˆå¾å¤§é¼ è„‘è‚ è‚½åŠç›¸å ³ç‚Žæ€§å› å­è¡¨è¾¾çš„å½±å“.

OBJECTIVES: To observe the effect of acupuncture on the expressions of neuropeptides and related inflammatory factors in rats with diarrhea-predominant irritable bowel syndrome(IBS-D), so as to explore the mechanism of acupuncture in the treatment of IBS-D. METHODS: Male Wistar rats were randomly divided into blank group, model group, medication group, and acupuncture group, with 6 rats in each group. Except for the blank group, the other groups were subjected to 14-day "acetic acid enema + restraint stress" to establish the IBS-D rat model. After successful modeling, the medication group received gavage of pinaverium bromide(15 mg/kg) once a day, and the acupuncture group received acupuncture at "Baihui"(GV20) and bilateral "Tianshu"(ST25), "Shangjuxu"(ST37), "Zusanli"(ST36), and "Taichong"(LR3) for 20 min every day, both groups were treated continuously for 14 days. The general state of the rats in each group was observed, and the body weight of the rats was measured. The open-field experiment was conducted to measure the horizontal and vertical movements, and the number of fecal pellets of rats. The histopathological morphology of hypothalamus and colon of rats was observed by HE staining. Toluidine blue staining was used to observe and count the mast cells(MCs) in the colon tissue of rats. ELISA was used to detect the serum contents of tumor necrosis factor-α(TNF-α) and interleukin(IL)-10. Real-time fluorescence quantitative PCR was performed to detect the mRNA expressions of calcitonin gene-related peptide(CGRP) in the hypothalamus and colon tissue. Western blot was used to detect the expressions of corticotropin-releasing factor(CRF) in the hypothalamus and colon tissue. RESULTS: HE staining showed that there was inflammatory cell infiltration in the lamina propria of colon in the model group, and it was reduced in the other groups. Compared with the blank group, the model group showed significantly decreased body weight, decreased walking distance and upright times in open field experiment, decreased serum IL-10 contents(P<0.05, P<0.01), increased fecal pellet number (P<0.01), increased MC number in the colon tissue, serum TNF-α contents, and CGRP mRNA expressions and CRF expressions in the hypothalamus and colon tissue(P<0.01). Compared with the model group, both medication and acupuncture groups showed significantly increased body weight, walking distance and upright times in the open-field experiment, and serum IL-10 contents(P<0.01, P<0.05), significantly decreased fecal pellet number (P<0.05), significantly decreased MC number in the colon tissue, serum TNF-α contents, and CGRP mRNA expressions in the hypothalamus and colon tissue(P<0.01)；at the same time, the acupuncture group showed significantly decreased CRF expressions in the hypothalamus and colon tissue(P<0.01, P<0.05). There was no significant difference in the above indicators between the medication group and the acupuncture group. CONCLUSIONS: Acupuncture can improve the general and emotional state, inflammatory response, and neuropeptide expression in rats with IBS-D, and alleviate the symptoms of IBS-D, which may be related to the regulation of neuropeptides and inflammatory factors levels.

Successful Treatment of Concurrent Follicular Lymphoma and Triple-Negative Breast Cancer Using Rituximab Plus Nab-Paclitaxel and Cisplatin: A Case Report and Literature Review.

Background: Co-occurrence of breast cancer and non-Hodgkin's lymphoma is a rare condition with diagnostic and therapeutic challenges. The coexistence of follicular lymphoma (FL) and triple-negative breast cancer (TNBC) has not been described previously. Case Presentation: A 46-year-old woman, already suffering a history of untreated, advanced-stage, high tumor burden FL, was admitted for a rapidly progressing right breast mass. Ultrasonography showed an 8.3 × 3.6 × 4.1 cm fungating mass in the right breast with enlarged lymph nodes (LNs) in bilateral axillae. PET-CT demonstrated increased 18F- FDG activity in right breast mass, LNs on both sides of the diaphragm, enlarged spleen, and bone marrow. Biopsy of the right breast mass revealed TNBC. The patient underwent neoadjuvant therapy with R-CHOP and achieved partial response of breast tumor. However, TNBC progressed after three cycles of R-CHOP. According to the next-generation sequencing (NGS) assay on breast mass showing a homologous recombination repair (HRR) deficiency (HRD) score of 72, the neoadjuvant regimen was changed to rituximab plus nab-paclitaxel and cisplatin (R-TP) and resulted in significant tumor regression. The patient then underwent right mastectomy with an axillary LN dissection. After the surgery, she was regularly monitored and given adjuvant therapy with R-TP and radiotherapy. Conclusion: The coexistence of FL and HRD-positive TNBC poses diagnostic and treatment challenges. Well-founded neoadjuvant strategy based on multidisciplinary team (MDT) discussion and NGS warranted a good outcome in this case.

Efficacy and safety of gemcitabine plus S-1 vs. gemcitabine plus nab-paclitaxel in treatment-naïve advanced pancreatic ductal adenocarcinoma.

OBJECTIVE: Gemcitabine plus nab-paclitaxel (GnP) is the standard first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC). S-1, an oral fluoropyrimidine derivative, as compared with gemcitabine, is non-inferior in terms of overall survival (OS) and is associated with lower hematologic toxicity. Accordingly, S-1 is a convenient oral alternative treatment for advanced PDAC. This study was aimed at comparing the efficacy and safety of gemcitabine plus S-1 (GS) vs. GnP as first-line chemotherapy for advanced PDAC. METHODS: Patients with advanced PDAC who received first-line GS or GnP at the Peking Union Medical College Hospital between March 2011 and November 2022 were evaluated. RESULTS: A total of 300 patients were assessed, of whom 84 received GS and 216 received GnP. The chemotherapy completion rate was higher with GS than GnP (50.0% vs. 30.3%, P = 0.0028). The objective response rate (ORR) was slightly higher (14.3% vs. 9.7%, P = 0.35), and the median OS was significantly longer (17.9 months vs. 13.3 months, P = 0.0078), in the GS group than the GnP group. However, the median progression-free survival (PFS) did not significantly differ between groups. Leukopenia risk was significantly lower in the GS group than the GnP group (14.9% vs. 28.1%, P = 0.049). CONCLUSIONS: As first-line chemotherapy for advanced PDAC, the GS regimen led to a significantly longer OS than the GnP regimen. The PFS, ORR, and incidence of severe adverse events were comparable between the GS and GnP groups.

DpCoA tagSeq: Barcoding dpCoA-Capped RNA for Direct Nanopore Sequencing via Maleimide-Thiol Reaction.

Recent discoveries of noncanonical RNA caps, such as nicotinamide adenine dinucleotide (NAD+) and 3'-dephospho-coenzyme A (dpCoA), have expanded our knowledge of RNA caps. Although dpCoA has been known to cap RNAs in various species, the identities of its capped RNAs (dpCoA-RNAs) remained unknown. To fill this gap, we developed a method called dpCoA tagSeq, which utilized a thiol-reactive maleimide group to label dpCoA cap with a tag RNA serving as the 5' barcode. The barcoded RNAs were isolated using a complementary DNA strand of the tag RNA prior to direct sequencing by nanopore technology. Our validation experiments with model RNAs showed that dpCoA-RNA was efficiently tagged and captured using this protocol. To confirm that the tagged RNAs are capped by dpCoA and no other thiol-containing molecules, we used a pyrophosphatase NudC to degrade the dpCoA cap to adenosine monophosphate (AMP) moiety before performing the tagSeq protocol. We identified 44 genes that transcribe dpCoA-RNAs in mouse liver, demonstrating the method's effectiveness in identifying and characterizing the capped RNAs. This strategy provides a viable approach to identifying dpCoA-RNAs that allows for further functional investigations of the cap.

The prognostic role of WeChat-based instant doctor-patient communication in patients with advanced pancreatic cancer.

BACKGROUND: Patients with advanced pancreatic ductal adenocarcinoma (PDAC) need timely medical assistance since the emergence of complications due to the disease and antitumor treatment. Studies have confirmed that instant messaging can improve the quality of life and compliance of cancer patients. However, the prognostic role of instant doctor-patient communication based on instant messaging applications in PDAC has not been studied. METHODS: Patients with PDAC who received first-line chemotherapy at Peking Union Medical College Hospital between January 2015 and October 2022 were reviewed. We categorized patients into two groups according to whether they received WeChat-based instant doctor-patient communication, and the prognosis and toxicity data between the two groups were compared. RESULTS: A total of 431 PDAC patients were enrolled, of whom 163 had long-term instant communication with their doctors based on WeChat, and 268 did not receive WeChat-based instant communication. There was no significant correlation between WeChat-based communication and first-line chemotherapy overall response rate (14.1% vs. 8.6%, p = 0.074), incidence of grade ≥ 3 adverse events (66.9% vs. 65.7%, p = 0.814) or overall survival (14.7 vs. 13.9 months, p = 0.170) in all enrolled patients. However, patients who received WeChat-based instant communication had a higher completion rate of first-line chemotherapy (42.0% vs. 30.7%, p = 0.023). Consistently, in the patients who developed grade ≥ 3 adverse events (n = 231), those who received WeChat-based instant communication had significantly longer overall survival (17.3 vs. 15.3 months, p = 0.018), even after adjustment for biases. CONCLUSIONS: WeChat-based instant doctor-patient communication demonstrated no superiority in improving the efficacy of chemotherapy or preventing chemotherapy toxicity in PDAC patients, but it may contribute to improving the completion rate of chemotherapy and the prognosis in patients who experienced severe adverse events. IMPLICATIONS FOR CANCER SURVIVORS: Instant doctor‒patient communication may help to timely and appropriately deal with adverse events and prolong the survival time of patients with PDAC, supporting the promotion of mobile technology in clinical practice.

Blue-ringed octopus-inspired microneedle patch for robust tissue surface adhesion and active injection drug delivery.

Intratissue topical medication is important for the treatment of cutaneous, mucosal or splanchnic diseases. However, penetrating surface barriers to providing adequate and controllable drug delivery while guaranteeing adhesion in bodily fluids remains challenging. Here, the predatory behavior of the blue-ringed octopus inspired us with a strategy to improve topical medication. For effective intratissue drug delivery, the active injection microneedles were prepared in a manner inspired by the teeth and venom secretion of blue-ringed octopus. With on demand release function guided by temperature-sensitive hydrophobic and shrinkage variations, these microneedles can supply adequate drug delivery at an early stage and then achieve the long-term release stage. Meanwhile, the bionic suction cups were developed to facilitate microneedles to stay firmly in place (>10 kilopascal) when wet. With wet bonding ability and multiple delivery mode, this microneedle patch achieved satisfactory efficacy, such as accelerating the ulcers' healing speed or halting early tumor progression.

Pancreatic tumors exhibit myeloid-driven amino acid stress and upregulate arginine biosynthesis.

Nutrient stress in the tumor microenvironment requires cancer cells to adopt adaptive metabolic programs for survival and proliferation. Therefore, knowledge of microenvironmental nutrient levels and how cancer cells cope with such nutrition is critical to understand the metabolism underpinning cancer cell biology. Previously, we performed quantitative metabolomics of the interstitial fluid (the local perfusate) of murine pancreatic ductal adenocarcinoma (PDAC) tumors to comprehensively characterize nutrient availability in the microenvironment of these tumors. Here, we develop Tumor Interstitial Fluid Medium (TIFM), a cell culture medium that contains nutrient levels representative of the PDAC microenvironment, enabling us to study PDAC metabolism ex vivo under physiological nutrient conditions. We show that PDAC cells cultured in TIFM adopt a cellular state closer to that of PDAC cells present in tumors compared to standard culture models. Further, using the TIFM model, we found arginine biosynthesis is active in PDAC and allows PDAC cells to maintain levels of this amino acid despite microenvironmental arginine depletion. We also show that myeloid derived arginase activity is largely responsible for the low levels of arginine in PDAC tumors. Altogether, these data indicate that nutrient availability in tumors is an important determinant of cancer cell metabolism and behavior, and cell culture models that incorporate physiological nutrient availability have improved fidelity to in vivo systems and enable the discovery of novel cancer metabolic phenotypes.

Nomogram including indirect bilirubin for the prediction of post-stroke depression at 3 months after mild acute ischemic stroke onset.

Background: Post-stroke depression (PSD) has been proven to be associated with stroke severity. Thus, we hypothesized that the prevalence of PSD would be lower in patients with mild stroke. We aim to explore predictors of depression at 3 months after mild acute ischemic stroke (MAIS) onset and to develop a practical and convenient prediction model for the early identification of patients at high risk. Methods: A total of 519 patients with MAIS were consecutively recruited from three hospitals in Wuhan city, Hubei province. MAIS was defined as a National Institute of Health Stroke Scale (NIHSS) score of ≤5 at admission. Meeting the DSM-V diagnostic criteria and a 17-item Hamilton Rating Scale for Depression (HAMD-17) score of >7 at their 3-month follow-up were considered the primary outcomes. A multivariable logistic regression model was used to determine the factors adjusted for potential confounders, and all independent predictors were brought into the construction of a nomogram to predict PSD. Results: The prevalence of PSD is up to 32% at 3 months after MAIS onset. After adjusting for potential confounders, indirect bilirubin (p = 0.029), physical activity (p = 0.001), smoking (p = 0.025), hospitalization days (p = 0.014), neuroticism (p < 0.001), and MMSE (p < 0.001) remained independently and significantly related with PSD. The concordance index (C-index) of the nomogram jointly constructed by the aforementioned six factors was 0.723 (95% CI: 0.678-0.768). Conclusion: The prevalence of PSD seems equally high even if the ischemic stroke is mild, which calls for great concern from clinicians. In addition, our study found that a higher level of indirect bilirubin can lower the risk of PSD. This finding may provide a potential new approach to PSD treatment. Furthermore, the nomogram including bilirubin is convenient and practical to predict PSD after MAIS onset.

Comprehensive landscape of the IPAF inflammasomes in pan-cancer: A bulk omics research and single-cell sequencing validation.

BACKGROUND: IPAF (ICE-protease Activating Factor) is a nucleotide-binding/leucine-rich repeat (NLR) protein known as the cysteine-associated recruitment domain 12 (CARD12). Previous studies only discuss the role of IPAF inflammasomes in specific tumors. The role of IPAF inflammasomes in pan-cancer is still unclear. Therefore, we performed a comprehensive analysis of IPAF inflammasome in 33 tumors. METHODS: We used databases like The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) from the UCSC XENA (http://xena.ucsc.edu/) to retrieve and analyze gene expression. The influence of IPAF inflammasome on the prognosis of tumor patients was analyzed using univariate Cox regression analysis and Kaplan-Meier survival analysis. Furthermore, we conducted the following analysis: Single-sample gene set enrichment analysis, single-cell level functional state analysis, single-cell sequencing, immune cell infiltration analysis, and tumor immune dysfunction and exclusion (TIDE) score. RESULTS: First, the differential expression of IPAF inflammasome-related genes (IPAF-RGs) in 33 tumors were analyzed. The results revealed that IPAF-RGs were significantly and differentially expressed in eight tumors. The prognostic significance of IPAF inflammasome scores was different in different tumors. A positive correlation was observed between IPAF inflammasomes scores and CD8+ T cells in most tumors. Further analysis revealed that IPAF inflammasome might affect tumor immunity mainly by mediating effector T cell recruitment via the expression of chemokines such as CXCL9, CXCL10, and CCL5. The analysis of TIDE and IPAF inflammasome scores revealed a significant negative correlation between IPAF inflammasome and TIDE scores in 11 tumors. CONCLUSION: A pan-cancer analysis of IPAF inflammasome in various tumors was performed. The results highlight the potential value of IPAF inflammasome in response to immunotherapy in patients and provide a new direction for future immunotherapy.

Gold nanoparticles: promising biomaterials for osteogenic/adipogenic regulation in bone repair.

Bone defects are a common bone disease, which are usually caused by accidents, trauma and tumors. However, the treatment of bone defects is still a great clinical challenge. In recent years, research on bone repair materials has continued with great success, but there are few reports on the repair of bone defects at a high lipid level. Hyperlipidemia is a risk factor in the process of bone defect repair, which has a negative impact on the process of osteogenesis, increasing the difficulty of bone defect repair. Therefore, it is necessary to find materials that can promote bone defect repair under the condition of hyperlipidemia. Gold nanoparticles (AuNPs) have been applied in the fields of biology and clinical medicine for many years and developed to modulate osteogenic differentiation and adipogenic differentiation. In vitro and vivo studies displayed that they promoted bone formation and inhibited fat accumulation. Further, the metabolism and mechanisms of AuNPs acting on osteogenesis/adipogenesis were partially revealed by researchers. This review further clarifies the role of AuNPs in osteogenic/adipogenic regulation during the process of osteogenesis and bone regeneration by summarizing the related in vitro and in vivo research, discussing the advantages and challenges of AuNPs and highlighting several possible directions for future research, with the aim to provide a new strategy for dealing with bone defects in hyperlipidemic patients.

Janus-Inspired Core-Shell Structure Hydrogel Programmatically Releases Melatonin for Reconstruction of Postoperative Bone Tumor.

At present, surgery is one of the main treatments for bone tumor. However, the risk of recurrence and the large area of bone defects after surgery pose a great challenge. Therefore, a Janus-inspired core-shell structure bone scaffold was designed to achieve the self-programmed release of melatonin at different concentrations, clearing the residual tumor cells at early stage after resection and promoting bone repair later. The layered differential load designs inspired by Janus laid the foundation for the differential release of melatonin, where sufficient melatonin inhibited tumor growth as low dose promoted osteogenesis. Then, the automatically programmed delivery of melatonin is achieved by the gradient degradation of the core-shell structure. In the material characterization, scanning electron microscopy revealed the core-shell structure. The drug release experiment and in vivo degradation experiment reflected the programmed differential release of melatonin. In the biological experiment part, in vivo and in vitro experiments not only confirmed the significant inhibitory effect of the core-shell hydrogel scaffold on tumor but also confirmed its positive effect on osteogenesis. Our Janus-inspired core-shell hydrogel scaffold provides a safe and efficient means to inhibit tumor recurrence and bone repair after bone tumor, and it also develops a new and efficient tool for differential and programmed release of other drugs.

Wogonin attenuates neutrophilic inflammation and airway smooth muscle proliferation through inducing caspase-dependent apoptosis and inhibiting MAPK/Akt signaling in allergic airways.

BACKGROUND: Severe neutrophilic asthma is often characterized by persistent airway inflammation and irreversible airway remodeling, which are overstimulated by the high-mobility group box protein 1 (HMGB1). Although wogonin, an O-methylated flavone, has been widely used to treat inflammatory and allergic diseases, its therapeutic effects and potential mechanisms on severe neutrophilic asthma remain elusive. OBJECTIVE: To evaluate whether wogonin alleviates airway neutrophilia through inducing neutrophil apoptosis and attenuates airway smooth muscle cells (ASMCs) proliferation and migration. METHODS: The effect of wogonin on reducing neutrophilic airway inflammation, including neutrophil infiltration and inflammatory mediators, was examined in a mouse model of severe neutrophilic asthma sensitized with ovalbumin and lipopolysaccharide. Also, the effect of wogonin on inducing human neutrophil apoptosis was manifested using cellular morphology, flow cytometry, and caspase inhibition assays. Furthermore, the effect of wogonin on inhibiting HMGB1-mediated ASMCs proliferation and migration was determined. RESULTS: Wogonin reduced the frequency of neutrophils and inhibited the production of multiple inflammatory mediators, including ovalbumin-specific IgE, tumor necrosis factor-α, interleukin-6, and HMGB1, in bronchoalveolar lavage fluid and lung tissues of the neutrophilic asthmatic mouse model. These data strongly support a significantly suppressed neutrophilic airway inflammation, functionally consistent to the relieved airway hyperresponsiveness by wogonin in vivo. Wogonin induced human neutrophil apoptosis in a dose-dependent manner by activating caspase-8 and caspase-3 in vitro. Wogonin pretreatment abolished HMGB1-induced ASMCs proliferation and migration, which can be explained by the inhibition of phosphorylation in the mitogen-activated protein kinase (MAPK) /Akt singling pathways. CONCLUSION: Our findings demonstrate that wogonin augments caspase-dependent apoptosis in neutrophils to alleviate neutrophilic inflammatory responses and regulates intracellular signaling to inhibit HMGB1-mediated ASMCs activation, providing a promising therapeutic agent for severe neutrophilic asthma.

Genetic variations in the bitter taste receptor gene TAS2R38 are related to cigarette smoking behavior in Han Chinese smokers.

BACKGROUND: Smoking behavior is influenced by multiple genes, including the bitter taste gene TAS2R38. It has been reported that the correlation between TAS2R38 and smoking behavior has ethnicity-based differences. However, the TAS2R38 status in Chinese smokers is still unclear. OBJECTIVE: This study aims to investigate the possible relationship between genetic variations in TAS2R38 (A49P, V262A and I296V) and smoking behaviors in the Han Chinese population. METHODS: The haplotype analyses were performed and smoking behavior questionnaire was completed by 1271 individuals. Genetic association analyses for smoking behavior were analyzed using chi-square test. Further, for investigating the molecular mechanism of TAS2R38 variants effect on smoking behavior, we conducted TAS2R38-PAV and TAS2R38-AVI expression plasmids and tested the cellular calcium assay by cigarette smoke compounds stimulus in HEK293. RESULTS: Significant associations of genetic variants within TAS2R38 were identified with smoking behavior. We found a higher PAV/PAV frequency than AVI/AVI in moderate and high nicotine dependence (FTND ≥ 4; X2 = 4.611, 1 df, p = 0.032) and strong cigarette smoke flavor intensity preference (X2 = 4.5383, 1 df, p = 0.033) in participants. Furthermore, in the in vitro cellular calcium assay, total particle matter (TPM), N-formylnornicotine and cotinine, existing in cigarette smoke, activated TAS2R38-PAV but not TAS2R38-AVI-transfected cells. CONCLUSION: Our data highlights that genetic variations in TAS2R38 are related to smoking behavior, especially nicotine dependence and cigarette smoke flavor intensity preference. Our findings may encourage further consideration of the taste process to identify individuals susceptible to nicotine dependence, particularly Han Chinese smokers.

Evaluation of the knowledge, awareness, and attitudes toward epilepsy among nurses.

BACKGROUND: The standard of care provided to patients with chronic epilepsy might be affected by clinical nurses' understanding, awareness, and attitudes toward the condition. The objective of this study was to assess the knowledge, awareness, and attitudes toward chronic epilepsy among clinical nurses in the Second Affiliated Hospital of Zhejiang University School of Medicine, China. METHODS: Two hundred and thirty-eight nurses from the neurosurgery, neurology, epilepsy center, other internal medicine and other surgery department working at our hospital participated in this descriptive and cross-sectional study in 2022. The data were collected through an electronic questionnaire, which comprised four domains including demographic and clinical epilepsy-related questions, awareness of epilepsy section, 18 items for knowledge and a 15-item scale for attitudes. Mann-Whitney U tests, Kruskal-Wallis H tests, post hoc analysis, Pearson correlation analysis, and descriptive statistics were used to analyze the non-normal distribution of the dataset. RESULTS: The clinical nurses' average score on the awareness of epilepsy section was 14.93 ± 2.69 (maximum score: 20), the knowledge of epilepsy section scored 15.41 ± 2.30 (maximum score: 18), and the epilepsy attitude section scored 30.65 ± 7.40. The knowledge and awareness accuracy of the responses to the epilepsy-related questions were positively and significantly correlated (r = 0.251, p < 0.001). The multiple linear regression model found that the department (p < 0.001) and rank (p = 0.015) of nurses were independently associated with awareness toward epilepsy. Meanwhile, there was a statistically significant difference between the departments of nurses and accuracy on the Epilepsy Knowledge Scale (H = 18.340, p < 0.001). In addition, 92.77% of nurses agreed that people with chronic epilepsy have the same rights as all people. Unfortunately, over 30% of nurses maintained an uncertain attitude toward the employment, marriage, and emotion related to epilepsy. CONCLUSION: Our findings revealed that nurses had a general awareness and understanding of epilepsy, attitudes toward epilepsy. Specifically, nurses working in the Neurology Department and the Epilepsy Center were predisposed to have a considerably better level of awareness and knowledge of epilepsy. Additionally, as their understanding of epilepsy grew, so did their sensitivity to those who suffer from the condition. The study also recommends that epilepsy experts deliver additional lectures and training sessions to enhance nurses' knowledge of first-aid for seizures.