Neutrophil extracellular traps promote invasion and metastasis via NLRP3-mediated oral squamous cell carcinoma pyroptosis inhibition.

Neutrophil extracellular traps (NETs) are reticular structures composed of neutrophil elastase (NE), cathepsin G (CG) and DNA-histone enzyme complexes. Accumulating evidence has revealed that NETs play important roles in tumor progression, metastasis, and thrombosis. However, our understanding of its clinical value and mechanism of action in oral squamous cell carcinoma (OSCC) is limited and has not yet been systematically described. Here, we aimed to investigate the clinical significance of NETs in OSCC and the mechanisms by which they affect its invasive and metastatic capacity. Our results demonstrated that high enrichment of NETs is associated with poor prognosis in OSCC, and mechanistic studies have shown that NE in NETs promotes invasion and metastasis via NLRP3-mediated inhibition of pyroptosis in OSCC. These findings may provide a new therapeutic approach for OSCC.

Minor hepatectomy combined with cholangioplasty and cholangiojejunostomy for Bismuth II hilar cholangiocarcinoma: A propensity score matching analysis.

BACKGROUND: The optimal surgical approach for Bismuth II hilar cholangiocarcinoma (HCCA) remains controversial. This study compared perioperative and oncological outcomes between minor and major hepatectomy. MATERIALS AND METHODS: One hundred and seventeen patients with Bismuth II HCCA who underwent hepatectomy and cholangiojejunostomy between January 2018 and December 2022 were retrospectively investigated. Propensity score matching created a cohort of 62 patients who underwent minor (n = 31) or major (n = 31) hepatectomy. Perioperative outcomes, complications, quality of life, and survival outcomes were compared between the groups. Continuous data are expressed as the mean ± standard deviation, categorical variables are presented as n (%). RESULTS: Minor hepatectomy had a significantly shorter operation time (245.42 ± 54.31 vs. 282.16 ± 66.65 min; P = 0.023), less intraoperative blood loss (194.19 ± 149.17 vs. 315.81 ± 256.80 mL; P = 0.022), a lower transfusion rate (4 vs. 11 patients; P = 0.038), more rapid bowel recovery (17.77 ± 10.00 vs. 24.94 ± 9.82 h; P = 0.005), and a lower incidence of liver failure (1 vs. 6 patients; P = 0.045). There were no significant between-group differences in wound infection, bile leak, bleeding, pulmonary infection, intra-abdominal fluid collection, and complication rates. Postoperative laboratory values, length of hospital stay, quality of life scores, 3-year overall survival (25.8 % vs. 22.6 %; P = 0.648), and 3-year disease-free survival (12.9 % vs. 16.1 %; P = 0.989) were comparable between the groups. CONCLUSION: In this propensity score-matched analysis, overall survival and disease-free survival were comparable between minor and major hepatectomy in selected patients with Bismuth II HCCA. Minor hepatectomy was associated with a shorter operation time, less intraoperative blood loss, less need for transfusion, more rapid bowel recovery, and a lower incidence of liver failure. Besides, this findings need confirmation in a large-scale, multicenter, prospective randomized controlled trial with longer-term follow-up.

Characterization of Extended-Spectrum ß-Lactamase-Producing Escherichia coli in Animal Farms in Hunan Province, China.

Multi-drug resistance of bacteria producing extended-spectrum ß-lactamase (ESBL) is a public health challenge. Thus, this study aimed to investigate the antimicrobial susceptibility of ESBL-producing Escherichia coli (ESBL-EC) in Hunan Province, China. A total of 1366 fecal samples were collected from pig, chicken, and cattle farms over a six-year period, which were assessed using strain isolation, 16S rRNA identification, polymerase chain reaction, drug sensitivity testing, whole-genome sequencing, and bioinformatics analysis. The results showed an overall prevalence of 6.66% for ESBL-EC strains, with ESBL positivity extents for pigs, chickens, and cattle isolates at 6.77%, 6.54%, and 12.5%, respectively. Most ESBL-EC isolates were resistant to cefotaxime, tetracycline, and trimethoprim-sulfamethoxazole; however, all the isolates were susceptible to meropenem, with relatively low resistance to amikacin and tigecycline. Various multi-locus sequence types with different origins and similar affinities were identified, with ST155 (n = 16) being the most common subtype. Several types of resistance genes were identified among the 91 positive strains, with beta-lactamase blaCTX-M-55 being the most common ESBL genotype. IncFIB was the predominant plasmid type. Widespread use of antibiotics in animal farming may increase antibiotic resistance, posing a serious threat to the health of farmed animals and, thus, to human food security and health.

Simultaneous SERS Sensing of Cysteine and Homocysteine in Blood Based on the CBT-Cys Click Reaction: Toward Precisive Diagnosis of Schizophrenia.

At present, there is a lack of sufficiently specific laboratory diagnostic indicators for schizophrenia. Serum homocysteine (Hcy) levels have been found to be related to schizophrenia. Cysteine (Cys) is a demethylation product in the metabolism of Hcy, and they always coexist with highly similar structures in vivo. There are few reports on the use of Cys as a diagnostic biomarker for schizophrenia in collaboration with Hcy, mainly because the rapid, economical, accurate, and high-throughput simultaneous detection of Cys and Hcy in serum is highly challenging. Herein, a click reaction-based surface-enhanced Raman spectroscopy (SERS) sensor was developed for simultaneous and selective detection of Cys and Hcy. Through the efficient and specific CBT-Cys click reaction between the probe containing cyan benzothiazole and Cys/Hcy, the tiny methylene difference between the molecular structures of Cys and Hcy was converted into the difference between the ring skeletons of the corresponding products that could be identified by plasmonic silver nanoparticle enhanced molecular fingerprint spectroscopy to realize discriminative detection. Furthermore, the SERS sensor was successfully applied to the detection in related patient serum samples, and it was found that the combined analysis of Cys and Hcy can improve the diagnostic accuracy of schizophrenia compared to a single indicator.

Tracheobronchial mucosal keratosis: A literature review of this rare disorder.

Background: Tracheobronchial mucosal keratosis (TBMK) is a rare airway disease that may cause refractory cough and airway stenosis. The characteristics of this disease remain unknown. In the present study, we describe this disorder based on a review of the current literature, emphasizing its diagnostic and therapeutic aspects. Methods: A comprehensive search of TBMK was performed in Medline, Google Scholar, Web of Science, Cochrane Library (UK), Embase, China National Knowledge Infrastructure (CNKI) (China), and Wan Fang Med Online (China). The following data were collected: patient characteristics, chest imaging findings, bronchoscopy, histopathologic findings, pathogen testing, treatment, and prognosis. Results: As of 2023, eighteen cases of TBMK have been reported. The main clinical manifestations were cough and expectoration. Chest imaging findings were non-specific. The main bronchoscopy findings were nodular protrusion of airway lumen and yellow-white purulent moss above the nodular lesion. The lesions were mainly located in the trachea and mainstem bronchus. The main pathological manifestations include keratinocytes or keratinocyte beads, squamous metaplasia, and mucosal inflammatory changes. The treatments that were administered include antibiotics, symptomatic treatment, and glucocorticoids. All methods were ineffective except for bronchoscopy-guided high-frequency electric knife and recombinant human epidermal growth factor treatment. Conclusions: TBMK is a rare respiratory disease with atypical clinical manifestations and chest computed tomography findings. Bronchoscopy revealed that nodular hyperplasia of the airway and purulent fur-covered lesions are typical manifestations. The final diagnosis needs to be confirmed by histopathological examination. There is a lack of effective treatment for this disease, and bronchoscopy-guided intervention therapy may be a candidate treatment.

Multi-region calcium imaging in freely behaving mice with ultra-compact head-mounted fluorescence microscopes.

To investigate the circuit-level neural mechanisms of behavior, simultaneous imaging of neuronal activity in multiple cortical and subcortical regions is highly desired. Miniature head-mounted microscopes offer the capability of calcium imaging in freely behaving animals. However, implanting multiple microscopes on a mouse brain remains challenging due to space constraints and the cumbersome weight of the equipment. Here, we present TINIscope, a Tightly Integrated Neuronal Imaging microscope optimized for electronic and opto-mechanical design. With its compact and lightweight design of 0.43 g, TINIscope enables unprecedented simultaneous imaging of behavior-relevant activity in up to four brain regions in mice. Proof-of-concept experiments with TINIscope recorded over 1000 neurons in four hippocampal subregions and revealed concurrent activity patterns spanning across these regions. Moreover, we explored potential multi-modal experimental designs by integrating additional modules for optogenetics, electrical stimulation or local field potential recordings. Overall, TINIscope represents a timely and indispensable tool for studying the brain-wide interregional coordination that underlies unrestrained behaviors.

Research progress on the mechanism of astragaloside IV in the treatment of asthma.

Asthma is a common chronic respiratory disease, and its treatment is a core problem and challenge in clinical practice. Glucocorticoids (GCs) are the first-line therapy for the treatment of asthma. Local and systemic adverse reactions caused by GCs create obstacles to the treatment of asthma. Therefore, the research target is to find a new, safe, and effective therapeutic medicine at present. Natural products are an important source for treating asthma with low cost and low toxicity. Astragaloside IV (AS-IV) is an active ingredient of traditional Chinese medicine Astragalus mongholicus Bunge. Previous studies have indicated that AS-IV plays a therapeutic role in the treatment of asthma by inhibiting airway inflammation and remodeling the airway, and by regulating immunity and neuroendocrine function (Fig. 1) . It has a variety of biological characteristics such as multi-target intervention, high safety, and good curative effect. This article reviews the specific mechanism of AS-IV for the treatment of asthma to provide references for subsequent research.

C5a/C5aR1 axis as a key driver promotes epithelial-to-mesenchymal transition in airway epithelial cells in silica nanoparticles-induced pulmonary fibrosis.

Previous studies have shown that silica nanoparticles (SiNPs) exposure can affect the respiratory, cardiovascular, reproductive and other systems, with the lung being the primary target organ for the direct effect, causing damage with a central feature of pulmonary inflammation and fibrosis. However, the underlying mechanisms of pulmonary fibrosis due to SiNPs are not fully understood. The aim of the study was to investigate the role of complement anaphylatoxin C5a in SiNPs-induced pulmonary fibrosis. A mouse model of SiNPs-induced pulmonary fibrosis was established, and pulmonary fibrosis-related indicators, epithelial-to-mesenchymal transition (EMT), C5a/C5aR1 and high mobility group protein B1 (HMGB1) proteins were measured. An in vitro study using the human lung epithelial cell line BEAS-2B investigated whether C5a leads to epithelial-to-mesenchymal trans-differentiation. In vivo studies revealed that SiNPs-induced pulmonary fibrosis mainly manifested as EMT trans-differentiation in airway epithelial cells, which subsequently led to excessive deposition of extracellular matrix (ECM). Furthermore, we found that C5a and C5aR1 proteins were also increased in SiNPs-induced pulmonary fibrosis tissue. In vitro studies also showed that C5a directly activated HMGB1/RAGE signaling and induced EMT in BEAS-2B cells. Finally, treatment of SiNPs-exposed mice with the C5aR1 inhibitor PMX205 effectively reduced C5aR1 levels and inhibited the activation of HMGB1/RAGE signaling and the expression of EMT-related proteins, culminating in a significant alleviation of pulmonary fibrosis. Taken together, our results suggest that C5a/C5aR1 is the main signaling pathway for SiNPs-induced pulmonary fibrosis, which induces EMT in airway epithelial cells via the HMGB1/RAGE axis.

OGT/HIF-2α axis promotes the progression of clear cell renal cell carcinoma and regulates its sensitivity to ferroptosis.

O-GlcNAc transferase (OGT) acts in the development of various cancers, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we found that OGT was upregulated in ccRCC and this upregulation was associated with a worse survival. Moreover, OGT promoted the proliferation, clone formation, and invasion of VHL-mutated ccRCC cells. Mechanistically, OGT increased the protein level of hypoxia-inducible factor-2α (HIF-2α) (the main driver of the clear cell phenotype) by repressing ubiquitin‒proteasome system-mediated degradation. Interestingly, the OGT/HIF-2α axis conferred ccRCC a high sensitivity to ferroptosis. In conclusion, OGT promotes the progression of VHL-mutated ccRCC by inhibiting the degradation of HIF-2α, and agents that can modulate the OGT/HIF-2α axis may exert therapeutic effects on mutated VHL ccRCC.

maskNMF: A denoise-sparsen-detect approach for extracting neural signals from dense imaging data.

A number of calcium imaging methods have been developed to monitor the activity of large populations of neurons. One particularly promising approach, Bessel imaging, captures neural activity from a volume by projecting within the imaged volume onto a single imaging plane, therefore effectively mixing signals and increasing the number of neurons imaged per pixel. These signals must then be computationally demixed to recover the desired neural activity. Unfortunately, currently-available demixing methods can perform poorly in the regime of high imaging density (i.e., many neurons per pixel). In this work we introduce a new pipeline (maskNMF) for demixing dense calcium imaging data. The main idea is to first denoise and temporally sparsen the observed video; this enhances signal strength and reduces spatial overlap significantly. Next we detect neurons in the sparsened video using a neural network trained on a library of neural shapes. These shapes are derived from segmented electron microscopy images input into a Bessel imaging model; therefore no manual selection of "good" neural shapes from the functional data is required here. After cells are detected, we use a constrained non-negative matrix factorization approach to demix the activity, using the detected cells' shapes to initialize the factorization. We test the resulting pipeline on both simulated and real datasets and find that it is able to achieve accurate demixing on denser data than was previously feasible, therefore enabling faithful imaging of larger neural populations. The method also provides good results on more "standard" two-photon imaging data. Finally, because much of the pipeline operates on a significantly compressed version of the raw data and is highly parallelizable, the algorithm is fast, processing large datasets faster than real time.

Identification of the H3K36me3 reader LEDGF/p75 in the pancancer landscape and functional exploration in clear cell renal cell carcinoma.

Lens epithelium-derived growth factor (LEDGF/p75) is a reader of epigenetic marks and a potential target for therapeutic intervention. Its involvement in human immunodeficiency virus (HIV) integration and the development of leukemia driven by MLL (also known as KMT2A) gene fusion make it an attractive candidate for drug development. However, exploration of LEDGF/p75 as an epigenetic reader of H3K36me3 in tumors is limited. Here, for the first time, we analyze the role of LEDGF/p75 in multiple cancers via multiple online databases and in vitro experiments. We used pancancer bulk sequencing data and online tools to analyze correlations of LEDGF/p75 with prognosis, genomic instability, DNA damage repair, prognostic alternative splicing, protein interactions, and tumor immunity. In summary, the present study identified that LEDGF/p75 may serve as a prognostic predictor for tumors such as adrenocortical carcinoma, kidney chromophobe, liver hepatocellular carcinoma, pancreatic adenocarcinoma, skin cutaneous melanoma, and clear cell renal cell carcinoma (ccRCC). In addition, in vitro experiments and gene microarray sequencing were performed to explore the function of LEDGF/p75 in ccRCC, providing new insights into the pathogenesis of the nonmutated SETD2 ccRCC subtype.

Soft Bioelectronics for Therapeutics.

Soft bioelectronics play an increasingly crucial role in high-precision therapeutics due to their softness, biocompatibility, clinical accuracy, long-term stability, and patient-friendliness. In this review, we provide a comprehensive overview of the latest representative therapeutic applications of advanced soft bioelectronics, ranging from wearable therapeutics for skin wounds, diabetes, ophthalmic diseases, muscle disorders, and other diseases to implantable therapeutics against complex diseases, such as cardiac arrhythmias, cancer, neurological diseases, and others. We also highlight key challenges and opportunities for future clinical translation and commercialization of soft therapeutic bioelectronics toward personalized medicine.

Transcription Factor GLI1 Induces IL-6-Mediated Inflammatory Response and Facilitates the Progression of Adamantinomatous Craniopharyngioma.

Adamantinomatous craniopharyngioma (ACP) is a neuroendocrine tumor whose pathogenesis remains unclear. This study investigated the role of glioma-associated oncogene family zinc finger 1 (GLI1), a transcription factor in the sonic hedgehog (SHH) signaling pathway, in ACP. We discovered that GLI1 regulates the expression of IL-6, thereby triggering inflammatory responses in ACP and influencing the tumor's progression. Analyzing the Gene Expression Omnibus (GEO) database chip GSE68015, we found that GLI1 is overexpressed in ACP, correlating positively with the spite of ACP and inflammation markers. Knockdown of GLI1 significantly inhibited the levels of tumor necrosis factor α, interleukin-6 (IL-6), and IL-1ß in ACP cells, as well as cell proliferation and migration. We further identified a binding site between GLI1 and the promoter region of IL-6, demonstrating that GLI1 can enhance the expression of IL-6. These findings were verified in vivo, where activation of the SHH pathway significantly promoted GLI1 and IL-6 expressions in nude mice, inducing inflammation and tumor growth. Conversely, GLI1 knockdown markedly suppressed these processes. Our study uncovers a potential molecular mechanism for the occurrence of inflammatory responses and tumor progression in ACP.

Neutralizing activity of a third dose of CoronaVac against Omicron subvariants within a 20-month follow-up study.

The durability of antibody responses induced by the three-dose of CoronaVac vaccination, especially against SARS-CoV-2 Omicron subvariants, remains unclear. Here in our study, 160 plasma samples from 32 healthy individuals who received three doses of CoronaVac were longitudinally tracked for a period of 20 months. The results showed that a third homologous dose of CoronaVac efficiently increased the SARS-CoV-2 IgG and neutralizing antibody titers and enhanced neutralization activity against Omicron subvariants. The levels of IgG and neutralizing antibody declined from peak levels but remained detectable in most subjects over the course of the next 10-12 months. However, most of the individuals kept neutralizing titers against ancestral Wuhan-Hu-1, while they lost their neutralizing activities against Omicron B.1.1.529, BA.2, BA.4/BA.5, and BA.2.75.2 subvariants at 10-12 months post the third vaccination. Our results suggest that a fourth dose of vaccine may be necessary for uninfected individuals to confer higher neutralization against emerging Omicron subvariants.

Transcriptional regulation of Glis2 in hepatic fibrosis.

The role of Gli-similar 2 (Glis2) in hepatic fibrosis (HF) is controversial. In this study, we focused on the functional and molecular mechanisms involved in the Glis2-mediated activation of hepatic stellate cells (HSCs)-a milestone event leading to HF. The expression levels of Glis2 mRNA and protein were significantly decreased in the liver tissues of patients with severe HF and in mouse fibrotic liver tissues as well as HSCs activated by TGFß1. Functional studies indicated that upregulated Glis2 significantly inhibited HSC activation and alleviated BDL-induced HF in mice. Downregulation of Glis2 was found to correlate significantly with DNA methylation of the Glis2 promoter mediated by methyltransferase 1 (DNMT1), which restricted the binding of hepatic nuclear factor 1-α (HNF1-α), a liver-specific transcription factor, to Glis2 promoters. In addition, the enrichment of DNMT1 in the Glis2 promoter region was mediated by metastasis-associated lung adenocarcinoma transcriptor-1 (MALAT1) lncRNA, leading to transcriptional silencing of Glis2 and activation of HSCs. In conclusion, our findings reveal that the upregulation of Glis2 can maintain the resting state of HSCs. The decreased expression of Glis2 under pathological conditions may lead to the occurrence and development of HF with the expression silencing of DNA methylation mediated by MALAT1 and DNMT1.

Longitudinal analysis of memory Tfh cells and antibody response following CoronaVac vaccination.

The inactivated vaccine CoronaVac is one of the most widely used COVID-19 vaccines globally. However, the longitudinal evolution of the immune response induced by CoronaVac remains elusive compared with other vaccine platforms. Here, we recruited 88 healthy individuals who received 3 doses of CoronaVac vaccine. We longitudinally evaluated their polyclonal and antigen-specific CD4+ T cells and neutralizing antibody response after receiving each dose of vaccine for over 300 days. Both the second and third doses of vaccine induced robust spike-specific neutralizing antibodies, with a third vaccine further increasing the overall magnitude of antibody response and neutralization against Omicron sublineages B.1.1.529, BA.2, BA.4/BA.5, and BA.2.75.2. Spike-specific CD4+ T cells and circulating T follicular helper (cTfh) cells were markedly increased by the second and third dose of CoronaVac vaccine, accompanied by altered composition of functional cTfh cell subsets with distinct effector and memory potential. Additionally, cTfh cells were positively correlated with neutralizing antibody titers. Our results suggest that CoronaVac vaccine-induced spike-specific T cells are capable of supporting humoral immunity for long-term immune protection.

Effects of Different Pre-Cooling Methods on the Shelf Life and Quality of Sweet Corn (Zea mays L.).

The strong wind pre-cooling (SWPC), ice water pre-cooling (IWPC), vacuum pre-cooling (VPC), natural convection pre-cooling (NCPC), and slurry ice pre-cooling (SIPC) techniques were used to pre-cool the fresh sweet corn (Zea mays L.), and then the pre-cooling treated sweet corn samples were stored at 4 °C for 28 days. During refrigeration, quality indicators, such as hardness, water loss, color, soluble solids content, and soluble sugar, were determined. In addition, oxidation indicators, such as peroxidase, catalase, ascorbic acid-peroxidase activity, and carotene content, were also measured. The results showed that the main problems of sweet corn during cold storage were water loss and respiration. The pre-cooling speed of SWPC is the fastest, and the latent heat of sweet corn can be removed in only 31 min. SWPC and IWPC could reduce the loss of fruit quality, maintain good color and hardness, inhibit the decrease of water, soluble solids, soluble sugars, and carotenoid contents, maintain balance between POD, APX, and CAT, and extend the shelf life of sweet corn. The shelf life of SWPC and IWPC corn reached 28 days, 14 days longer than SIPC and VPC treated samples, and 7 days longer than NCPC treated samples. Therefore, SWPC and IWPC are the appropriate methods to pre-cool the sweet corn before cold storage.

Downregulated liver-elevated long intergenic noncoding RNA (LINC02428) is a tumor suppressor that blocks KDM5B/IGF2BP1 positive feedback loop in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and poor prognoses worldwide. Many studies have reported that long noncoding RNAs (lncRNAs) are related to the progression and prognosis of HCC. However, the functions of downregulated liver-elevated (LE) lncRNAs in HCC remain elusive. Here we report the roles and mechanisms of downregulated LE LINC02428 in HCC. Downregulated LE lncRNAs played significant roles in HCC genesis and development. LINC02428 was upregulated in liver tissues compared with other normal tissues and showed low expression in HCC. The low expression of LINC02428 was attributed to poor HCC prognosis. Overexpressed LINC02428 suppressed the proliferation and metastasis of HCC in vitro and in vivo. LINC02428 was predominantly located in the cytoplasm and bound to insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) to prevent it from binding to lysine demethylase 5B (KDM5B) mRNA, which decreased the stability of KDM5B mRNA. KDM5B was found to preferentially bind to the promoter region of IGF2BP1 to upregulate its transcription. Therefore, LINC02428 interrupts the KDM5B/IGF2BP1 positive feedback loops to inhibit HCC progression. The KDM5B/IGF2BP1 positive feedback loop is involved in tumorigenesis and progression of HCC.