Cerium doping of 45S5 bioactive glass improves redox potential and cellular bioactivity.

45S5 Bioglass (BG) is composed of a glass network with silicate based on the component and can be doped with various therapeutic ions for the enhancement of hard tissue therapy. Nanoceria (CeO2) has been shown to indicate redox reaction and enhance the biological response. However, few studies focus on the proportion of CeO2-doped and its effect on the cellular bioactivity of CeO2-doped BG (CBG). In this study, we synthesized the CBG series with increasing amounts of doping CeO2 ranging (1 to 12) wt.%. The synthesized CBG series examined the characterization, mineralization capacity, and cellular activity against BG. Our results showed that the CBG series exhibited a glass structure and indicated the redox states between Ce3+ and Ce4+, thus they showed the antioxidant activity by characterization of Ce. The CBG series had a stable glass network structure similar to BG, which showed the preservation of bioactivity by exhibiting mineralization on the surface. In terms of biological response, although the CBG series showed the proliferative activity of pre-osteoblastic cells similar to BG, the CBG series augmented not only the alkaline phosphatase activity but also the osteogenic marker in the mRNA level. As stimulated the osteogenic activity, the CBG series improved the biomineralization. In conclusion, the CBG series might have a potential application for hard tissue therapeutic purposes.

Volatile metabolomics and transcriptomics analyses provide insights into the mechanism of volatile changes during fruit development of 'Ehime 38' (Citrus reticulata) and its bud mutant.

Volatile compounds are important determinants affecting fruit flavor. Previous study has identified a bud mutant of 'Ehime 38' (Citrus reticulata) with different volatile profile. However, the volatile changes between WT and MT during fruit development and underlying mechanism remain elusive. In this study, a total of 35 volatile compounds were identified in the pulps of WT and MT at five developmental stages. Both varieties accumulated similar and the highest levels of volatiles at stage S1, and showed a downward trend as the fruit develops. However, the total volatile contents in the pulps of MT were 1.4-2.5 folds higher than those in WT at stages S2-S5, which was mainly due to the increase in the content of d-limonene. Transcriptomic and RT-qPCR analysis revealed that most genes in MEP pathway were positively correlated with the volatile contents, of which DXS1 might mainly contribute to the elevated volatiles accumulation in MT by increasing the flux into the MEP pathway. Moreover, temporal expression analysis indicated that these MEP pathway genes functioned at different developmental stages. This study provided comprehensive volatile metabolomics and transcriptomics characterizations of a citrus mutant during fruit development, which is valuable for fruit flavor improvement in citrus.

Sodium bicarbonate treatment and clinical outcomes in chronic kidney disease with metabolic acidosis: a meta-analysis.

BACKGROUND: In patients with chronic kidney disease (CKD), impaired kidney acid excretion leads to the onset of metabolic acidosis (MA). However, the evidence is not yet conclusive regarding the effects of sodium bicarbonate in treating CKD with MA. METHODS: Databases with PubMed, Embase, and the Cochrane Library were used to search for randomized controlled trials from the inception until November 11, 2023 to identify randomized controlled trials investigating the effect of sodium bicarbonate in participants with CKD and MA. The primary outcome was the change in estimated glomerular filtration rate (eGFR). Secondary outcomes included hospitalization rates, change in systolic blood pressure (SBP), all-cause mortality, and mid-arm muscle circumference (MAMC). A random-effects model was applied for analysis, and subgroup, sensitivity analyses were also performed. RESULTS: Fourteen RCTs comprising 2,037 patients demonstrated that sodium bicarbonate supplementation significantly improved eGFR (standardized mean difference [SMD]: 0.33, 95% CI: 0.03 to 0.63, P = 0.03). The group receiving sodium bicarbonate had a lower hospitalization rate (odds ratio: 0.37, 95% CI: 0.25 to 0.55, P < 0.001). Higher MAMC was observed with sodium bicarbonate treatment compared with those without (SMD:0.23, 95% CI: 0.08 to 0.38, P = 0.003, I2 < 0.001). However, higher risk of elevated SBP was found with sodium bicarbonate treatment (SMD:0.10, 95% CI: 0.01 to 0.20, P = 0.03). No significant difference in all-cause mortality was noted. CONCLUSION: In patients with CKD and MA, sodium bicarbonate supplementation may provide potential benefits in preventing the deterioration of kidney function and increasing muscle mass. However, treatment may be associated with higher blood pressure. Due to the risk of bias stemming from the absence of double-blinded designs and inconsistencies in control group definitions across the studies, further research is crucial to verify these findings.

Morphological characteristics and phylogenetic analyses revealed four new wood inhabiting fungi (Agaricomycetes, Basidiomycota) in Xizang Autonomous Region, China.

Four new fungi from Xizang in southwest China, Caloceraramaria, Ceraceomycesrhizomorphus, Leptosporomyceslinzhiensis, and Ramariaxizangensis are described and illustrated based on the morphological and molecular evidence. Caloceraramaria is characterized by the ramal and bright orange basidiomata, a monomitic hyphal system with simple septa generative hyphae, usually 4-septate basidiospores; Ceraceomycesrhizomorphus is characterized by the cream to yellowish basidiomata with rhizomorphs, cylindrical basidiospores; Leptosporomyceslinzhiensis is characterized by white with pink basidiomata, cylindrical to oblong ellipsoid basidiospores; Ramariaxizangensis is characterized by flesh pink basidiomata, branched dichotomously in 4-5 ranks, a monomitic hyphal system with clamped generative hyphae, ellipsoid to cylindrical and densely warted basidiospores.

Cranial-first approach for laparoscopic extended right hemicolectomy.

Complete mesocolic excision and central vascular ligation with D3 lymphadenectomy are important surgical principles for improving oncological outcomes in colon cancer. The cranial-first approach is a colonic mobilization-first approach to radical right hemicolectomy, which has several advantages, including early feasibility assessment, safe dissection from surrounding organs, preestablished inferior margin of lymph node dissection, and revelation of the tangible anatomy of the tributaries of the gastrocolic trunk. This video demonstrates the cranial-first approach to radical right hemicolectomy in a 66-year-old man with locally advanced cecal cancer.

Eosinophilic gastroenteritis in an elderly men associated with antibiotic use post maxillofacial space infection: a case report.

A 79-year-old man underwent operative drainage and 2-week cephalosporin treatment due to a maxillofacial space infection (bilateral submaxillaris, submentum, and left face). However, he experienced anorexia, nausea, vomiting, and emaciation in the following 2 months. It was initially considered that a malignancy might be present, thus a series of examinations were performed. Laboratory investigations showed increases in inflammatory markers and a significant eosinophilia, which seemed to be a hematological system disease. Combined with the gastrointestinal endoscopes and histology examination, the patient was diagnosed with eosinophilic gastroenteritis (EGE). After cessation of antibiotic treatment and administration of corticosteroid, our patient experienced a rapid progress in his clinical condition. Despite the low incidence, EGE should be considered in patients with unknown cause of gastrointestinal disorder, elevated eosinophilia, and so on.

Histone deacetylase complexes: Structure, regulation and function.

Histone deacetylases (HDACs) are key epigenetic regulators, and transcriptional complexes with deacetylase function are among the epigenetic corepressor complexes in the nucleus that target the epigenome. HDAC-bearing corepressor complexes such as the Sin3 complex, NuRD complex, CoREST complex, and SMRT/NCoR complex are common in biological systems. These complexes activate the otherwise inactive HDACs in a solitary state. HDAC complexes play vital roles in the regulation of key biological processes such as transcription, replication, and DNA repair. Moreover, deregulated HDAC complex function is implicated in human diseases including cancer. Therapeutic strategies targeting HDAC complexes are being sought actively. Thus, illustration of the nature and composition of HDAC complexes is vital to understanding the molecular basis of their functions under physiologic and pathologic conditions, and for designing targeted therapies. This review presents key aspects of large multiprotein HDAC-bearing complexes including their structure, function, regulatory mechanisms, implication in disease development, and role in therapeutics.

Improved Biocompatibility and Osseointegration of Nanostructured Calcium-Incorporated Titanium Implant Surface Treatment (XPEED®).

Surface treatment of implants facilitates osseointegration, with nanostructured surfaces exhibiting accelerated peri-implant bone regeneration. This study compared bone-to-implant contact (BIC) in implants with hydroxyapatite (HA), sand-blasted and acid-etched (SLA), and SLA with calcium (Ca)-coated (XPEED®) surfaces. Seventy-five disk-shaped grade 4 Ti specimens divided into three groups were prepared, with 16 implants per group tested in New Zealand white rabbits. Surface characterization was performed using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), digital microscopy, and a contact angle analyzer. Cell viability, proliferation, and adhesion were assessed using MC3T3-E1 cells. Apatite formation was evaluated using modified simulated body fluid (m-SBF) incubation. After 4 weeks of healing, the outcomes reviewed were BIC, bone area (BA), removal torque tests, and histomorphometric evaluation. A microstructure analysis revealed irregular pores across all groups, with the XPEED group exhibiting a nanostructured Ca-coated surface. Surface characterization showed a crystalline CaTiO3 layer on XPEED surfaces, with evenly distributed Ca penetrating the implants. All surfaces provided excellent environments for cell growth. The XPEED and SLA groups showed significantly higher cell density and viability with superior osseointegration than HA (p < 0.05); XPEED exhibited the highest absorbance values. Thus, XPEED surface treatment improved implant performance, biocompatibility, stability, and osseointegration.

Multi-Branch Network for Color Image Denoising Using Dilated Convolution and Attention Mechanisms.

Image denoising is regarded as an ill-posed problem in computer vision tasks that removes additive noise from imaging sensors. Recently, several convolution neural network-based image-denoising methods have achieved remarkable advances. However, it is difficult for a simple denoising network to recover aesthetically pleasing images owing to the complexity of image content. Therefore, this study proposes a multi-branch network to improve the performance of the denoising method. First, the proposed network is designed based on a conventional autoencoder to learn multi-level contextual features from input images. Subsequently, we integrate two modules into the network, including the Pyramid Context Module (PCM) and the Residual Bottleneck Attention Module (RBAM), to extract salient information for the training process. More specifically, PCM is applied at the beginning of the network to enlarge the receptive field and successfully address the loss of global information using dilated convolution. Meanwhile, RBAM is inserted into the middle of the encoder and decoder to eliminate degraded features and reduce undesired artifacts. Finally, extensive experimental results prove the superiority of the proposed method over state-of-the-art deep-learning methods in terms of objective and subjective performances.

Fabrication of antimicrobial packaging based on polyaminopropyl biguanide incorporated pectin/polyvinyl alcohol films for fruit preservation.

Pectin (PEC)/polyvinyl alcohol (PVA), plasticizers, and polyaminopropyl biguanide (Pb) (0.125%-1%) were used to prepare the film solution. The results demonstrated significantly enhanced tensile strength and elongation at break of PEC/PVA/Pb 0.25% film than PEC/PVA film. Scanning electron microscopy was carried out to investigate the continuous and dense structure of the PEC/PVA/ Pb0.25% film. FTIR, XPS, and XRD revealed that Pb addition to the PEC/PVA film matrix changed its physicochemical properties by forming new hydrogen and CN bonds. Moreover, the composite films exhibited strong antimicrobial activity against food-borne microorganisms (E. coli and S. aureus), and post-harvest pathogens (P. italicum and F. proliferatum) in vitro. The composite film effectively inhibited P. italicum growth during citrus experiments, while maintaining nutritional components (vitamin C, total flavonoid, and total polyphenol content). Overall, the antimicrobial composite film presented promising applicability in food packaging.

Effect of prophylactic abdominal drainage on postoperative pain in laparoscopic hemicolectomy for colon cancer: a single-center observational study in Korea.

Purpose: This study aimed to evaluate the effect of prophylactic abdominal drainage (AD) in laparoscopic hemicolectomy, focusing on assessing postoperative pain outcomes. Methods: Patients were categorized into two groups: those with and without AD (AD group vs. no-AD group). A numerical rating scale (NRS) was used to assess postoperative pain on each postoperative day (POD). Further, the inverse probability of treatment weighting (IPTW) method was used to reduce intergroup bias. Results: In total, 204 patients who underwent laparoscopic hemicolectomies by a single surgeon between June 2013 and September 2022 at a single institution were retrospectively reviewed. After adjusting for IPTW, NRS scores on POD 2 were significantly lower in the no-AD group (3.2 ± 0.8 vs. 3.4 ± 0.8, p = 0.043). Further examination of postoperative outcomes showed no statistically significant differences in complications between the AD (17.3%) and no-AD (12.4%) groups (p = 0.170). The postoperative length of hospital stay was 7.3 ± 2.8 days in the AD group and 6.9 ± 3.0 days in the no-AD group, with no significant difference (p = 0.298). Time to first flatus was 3.0 ± 0.9 days in the AD group and 2.7 ± 0.9 days in the no-AD group, with no significant difference (p = 0.078). Regarding readmission within 1 month, there were four cases each in the AD (2.3%) and no-AD (1.7%) groups, with no significant difference (p = 0.733). Conclusion: Laparoscopic hemicolectomy without AD resulted in no significant differences in postoperative clinical outcomes, except for postoperative pain. This finding suggests that prophylactic AD may exacerbate postoperative pain.

Comparison of partial and total cystectomy for colorectal cancer with histologically confirmed bladder invasion.

BACKGROUND: Although organs are preserved and quality of life is improved, insufficient evidence is available for the oncologic safety of partial cystectomy in patients with colorectal cancer with suspected bladder invasion. Therefore, we aimed to compare partial and total cystectomy outcomes in patients with pathologically confirmed or clinically suspected bladder invasion. METHODS: Patients with colorectal cancer with suspected bladder invasion who underwent R0 resection from 2000 to 2020 were evaluated. Long-term outcomes were determined in patients with histologically confirmed bladder invasion. RESULTS: Of the 151 consecutive patients, 96 (64.6%) had histologically confirmed bladder involvement, and 105 (69.5%) underwent partial cystectomy. Operative time, estimated blood loss, and reoperation rate in ≤30 days were significantly worse in the total cystectomy group than in the partial cystectomy group. The overall recurrence rate was significantly higher in the total cystectomy group than in the partial cystectomy group (39.1% vs 21.9%; P = .046). Five-year overall survival (75.8% vs 53.2%; P = .006) rates were higher in the partial cystectomy group than in the total cystectomy group; however, disease-free survival (60.8% vs 41.6%; P = .088) rates were similar in patients with suspected bladder invasion. In patients with histologically confirmed bladder invasion, 5-year overall survival rates (78.1% vs 52.1%; P = .017) were higher in the partial cystectomy group than in the total cystectomy group; however, disease-free survival rates (53.4% vs 41.2%; P = .220) did not differ significantly. CONCLUSION: R0 resection is associated with favorable long-term outcomes in patients with locally advanced colorectal cancer. If R0 resection is possible, partial cystectomy is considered safe.

Saiga antelope horn suppresses febrile seizures in rats by regulating neurotransmitters and the arachidonic acid pathway.

BACKGROUND: Saiga antelope horn (SAH) is a traditional Chinese medicine for treating febrile seizure (FS) with precise efficacy, but its mechanism of action and functional substances are still unclear. Given the need for further research on SAH, our group conducted studies to elucidate its mechanisms and active substances. METHODS: An FS rat pup model was constructed through intraperitoneal injection of LPS and hyperthermia induction. Behavioural indicators of seizures, hippocampal histopathological alterations, serum levels of inflammatory cytokines and hippocampal levels of neurotransmitters were observed and measured to investigate the effects of SAH on FS model rats. Hippocampal metabolomics and network pharmacology analyses were conducted to reveal the differential metabolites, key peptides and pathways involved in the suppression of FS by SAH. RESULTS: SAH suppressed FS, decreased the inflammatory response and regulated the Glu-GABA balance. Metabolomic analysis revealed 13 biomarkers of FS, of which SAH improved the levels of 8 differential metabolites. Combined with network pharmacology, a "biomarker-core target-key peptide" network was constructed. The peptides of SAH, such as YGQL and LTGGF, could exert therapeutic effects via the arachidonic acid pathway. Molecular docking and ELISA results indicated that functional peptides of SAH could bind to PTGS2 target, inhibiting the generation of AA and its metabolites in hippocampal samples. CONCLUSION: In summary, the functional peptides contained in SAH are the main material basis for the treatment of FS, potentially acting through neurotransmitter regulation and the arachidonic acid pathway.

Aptamer-Based DNA Allosteric Switch for Regulation of Protein Activity.

Allostery is a fundamental way to regulate the function of biomolecules playing crucial roles in cell metabolism and proliferation and is deemed the second secret of life. Given the limited understanding of the structure of natural allosteric molecules, the development of artificial allosteric molecules brings a huge opportunity to transform the allosteric mechanism into practical applications. In this study, the concept of bionics is introduced into the design of artificial allosteric molecules and an allosteric DNA switch with an activity site and an allosteric site based on two aptamers for selective inhibition of thrombin activity. Compared with the single aptamer, the allosteric switch possesses a significantly enhanced inhibition ability, which can be precisely regulated by converting the switch states. Moreover, the dynamic allosteric switch is further subjected to the control of the DNA threshold circuit for realizing automatic concentration determination and activity inhibition of thrombin. These compelling results confirm that this allosteric switch equipped with self-sensing and information-processing modules puts a new slant on the research of allosteric mechanisms and further application of allosteric tactics in chemical and biomedical fields.

Single-cell analysis reveals cellular and molecular factors counteracting HPV-positive oropharyngeal cancer immunotherapy outcomes.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) induced by human papillomavirus (HPV-positive) is associated with better clinical outcomes than HPV-negative OPSCC. However, the clinical benefits of immunotherapy in patients with HPV-positive OPSCC remain unclear. METHODS: To identify the cellular and molecular factors that limited the benefits associated with HPV in OPSCC immunotherapy, we performed single-cell RNA (n=20) and T-cell receptor sequencing (n=10) analyses of tonsil or base of tongue tumor biopsies prior to immunotherapy. Primary findings from our single-cell analysis were confirmed through immunofluorescence experiments, and secondary validation analysis were performed via publicly available transcriptomics data sets. RESULTS: We found significantly higher transcriptional diversity of malignant cells among non-responders to immunotherapy, regardless of HPV infection status. We also observed a significantly larger proportion of CD4+ follicular helper T cells (Tfh) in HPV-positive tumors, potentially due to enhanced Tfh differentiation. Most importantly, CD8+ resident memory T cells (Trm) with elevated KLRB1 (encoding CD161) expression showed an association with dampened antitumor activity in patients with HPV-positive OPSCC, which may explain their heterogeneous clinical outcomes. Notably, all HPV-positive patients, whose Trm presented elevated KLRB1 levels, showed low expression of CLEC2D (encoding the CD161 ligand) in B cells, which may reduce tertiary lymphoid structure activity. Immunofluorescence of HPV-positive tumors treated with immune checkpoint blockade showed an inverse correlation between the density of CD161+ Trm and changes in tumor size. CONCLUSIONS: We found that CD161+ Trm counteracts clinical benefits associated with HPV in OPSCC immunotherapy. This suggests that targeted inhibition of CD161 in Trm could enhance the efficacy of immunotherapy in HPV-positive oropharyngeal cancers. TRIAL REGISTRATION NUMBER: NCT03737968.

A phase 2 study of spartalizumab (PDR001) among patients with recurrent or metastatic esophageal squamous cell carcinoma (KCSG HN18-17, K-MASTER project 12).

Spartalizumab (PDR001) is a humanized IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1). We conducted a single-arm, phase 2 trial to investigate the efficacy and safety of spartalizumab in patients with refractory esophageal squamous cell carcinoma (ESCC). Patients with histologically confirmed ESCC who experienced disease progression after platinum-based chemotherapy received 300 mg of intravenous spartalizumab every three weeks until disease progression or occurrence of unacceptable toxicity. The primary endpoint was centrally assessed objective response according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Adverse events were closely monitored throughout the study. From March 2020 through April 2021, 44 patients with ESCC were enrolled. Of the 44 patients, the objective response rate was 20.5% (95% confidence interval: 8.5-32.4). With a median follow-up of 10.9 months, median progression-free survival and overall survival were 3.2 months and 11.2 months, respectively. In addition, the median duration of response was 24.7 months. The most common grade 3 or 4 adverse event was grade 3 dysphagia (eight [18%] patients). Biomarker analyses explored programmed cell death ligand 1 and CD20 as potential predictive markers for PD-1 blockade. Spartalizumab showed promising activity with a manageable safety profile, indicating its potential as a new treatment option for patients with refractory ESCC. Trial registration: The trial was registered at ClinicalTrials.gov under the identifier NCT03785496.

Exploration of immune-modulatory effects of amivantamab in combination with pembrolizumab in lung and head and neck squamous cell carcinoma.

Immune checkpoint inhibitors are effective first-line therapy for solid cancers. However, low response rate and acquired resistance over time has led to the need for additional therapeutic options. Here, we evaluated synergistic anti-tumor efficacy of EGFR x MET targeting bispecific antibody, amivantamab with PD-L1 immunotherapy, pembrolizumab in head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma (LUSC) tumor bearing humanized PDX models. We demonstrated that pembrolizumab or amivantamab alone was ineffective and that combination treatment induced a significant reduction of tumor growth in both models (p<0.0001 and p<0.01, respectively). It appeared that combination of amivantamab and pembrolizumab significantly enhanced infiltration of granzyme B-producing CD8 T cells was in the TME of HNSCC PDX (p<0.01), and enhanced neoantigen-associated central memory CD8 T cells in circulating immune cells. Analysis of single cell RNA transcriptomics suggested that the tumor cells dramatically upregulated EGFR and MET in response to PD-L1 immunotherapy, potentially creating a metabolic state fit for tumor persistence in the tumor microenvironment (TME) and rendered pembrolizumab ineffective. We demonstrated that EGFRHIGHMETHIGH subcluster displayed an increased expression of genes implicated in production of lactate (SLC16A3 and LDHA) compared to the EGFRLOWMETLOW cluster. Accumulation of lactate in the TME has been associated with immunosuppression by hindering the infiltration of tumor killing CD8 T and NK cells. This study proved that amivantamab reduced glycolytic markers in the EGFRHIGHMETHIGH subcluster including SLC16A3 and LDHA and highlighted remodeling of the TME by combination treatment, providing rationale for additional therapy of amivantamab with PD-1 immunotherapy.

Performance Comparison of Convolutional Neural Network-Based Hearing Loss Classification Model Using Auditory Brainstem Response Data.

This study evaluates the efficacy of several Convolutional Neural Network (CNN) models for the classification of hearing loss in patients using preprocessed auditory brainstem response (ABR) image data. Specifically, we employed six CNN architectures-VGG16, VGG19, DenseNet121, DenseNet-201, AlexNet, and InceptionV3-to differentiate between patients with hearing loss and those with normal hearing. A dataset comprising 7990 preprocessed ABR images was utilized to assess the performance and accuracy of these models. Each model was systematically tested to determine its capability to accurately classify hearing loss. A comparative analysis of the models focused on metrics of accuracy and computational efficiency. The results indicated that the AlexNet model exhibited superior performance, achieving an accuracy of 95.93%. The findings from this research suggest that deep learning models, particularly AlexNet in this instance, hold significant potential for automating the diagnosis of hearing loss using ABR graph data. Future work will aim to refine these models to enhance their diagnostic accuracy and efficiency, fostering their practical application in clinical settings.

Portable sensing methods based on carbon dots for food analysis.

Food analysis is significantly important in monitoring food quality and safety for human health. Traditional methods for food detection mainly rely on benchtop instruments and require a certain amount of analysis time, which promotes the development of portable sensors. Portable sensing methods own many advantages over traditional techniques such as flexibility and accessibility in diverse environments, real-time monitoring, cost-effectiveness, and rapid deployment. This review focuses on the portable approaches based on carbon dots (CDs) for food analysis. CDs are zero-dimensional carbon-based material with a size of less than 10 nm. In the manner of sensing, CDs exhibit rich functional groups, low biotoxicity, good biocompatibility, and excellent optical properties. Furthermore, there are many methods for the synthesis of CDs using various precursor materials. The incorporation of CDs into food science and engineering for enhancing food safety control and risk assessment shows promising prospects.