Large-scale soil application of hydrochar: Reducing its polycyclic aromatic hydrocarbon content and toxicity by heating.

The beneficial roles of hydrochar in carbon sequestration and soil improvement are widely accepted. Despite few available reports regarding polycyclic aromatic hydrocarbons (PAHs) generated during preparation, their potential negative impacts on ecosystems remain a concern. A heating treatment method was employed in this study for rapidly removing PAHs and reducing the toxicity of corn stover-based hydrochar (CHC). The result showed total PAHs content (∑PAH) decreased and then sharply increased within the temperature range from 150 °C to 400 °C. The ∑PAH and related toxicity in CHC decreased by more than 80% under 200 °C heating temperature, compared with those in the untreated sample, representing the lowest microbial toxicity. Benzo(a)pyrene produced a significant influence on the ecological toxicity of the hydrochar among the 16 types of PAHs. The impact of thermal treatment on the composition, content, and toxicity of PAHs was significantly influenced by the adsorption, migration, and desorption of PAHs within hydrochar pores, as well as the disintegration and aggregation of large molecular polymers. The combination of hydrochar with carbonized waste heat and exhaust gas collection could be a promising method to efficiently and affordably reduce hydrochar ecological toxicity.

The safety and feasibility Assessment of Overlap Esophagojejunostomy with Self-pulling and Latter Transection Technique in Totally Laparoscopic Total Gastrectomy.

BACKGROUND: This study presents an innovative technique in totally laparoscopic total gastrectomy (TLTG) for Overlap esophagojejunostomy, termed self-pulling and latter transection (Overlap SPLT). It evaluates the effectiveness and short-term outcomes of this novel method through a comparative analysis with the established functional end-to-end esophagojejunostomy incorporating self-pulling and latter transection (FETE SPLT). METHODS: From September 2018 to September 2023, this study enrolled 68 gastric cancer patients who underwent totally laparoscopic total gastrectomy (TLTG) with Overlap SPLT anastomosis and 120 patients who underwent TLTG with FETE SPLT anastomosis. Clinicopathological characteristics, surgical and postoperative outcomes data for Overlap SPLT cases were gathered and retrospectively compared with those from FETE SPLT TLTG to evaluate the effectiveness and clinical safety. RESULTS: The duration of anastomosis for Overlap SPLT was 25.3 ± 7.4minutes, significantly longer than that for the FETE SPLT (18.1 ± 4.0minutes, P = 0.031). Perioperatively, one anastomosis-related complication occurred in each group, but this did not constitute a statistically significant difference (P = 0.682). No statistically significant differences were found between the two groups in terms of operative time, postoperative hospital stay, operative cost, surgical margins, or number of lymph nodes removed. Postoperative morbidity rates were similar between the groups (4.4% vs. 5.8%, P = 0.676). CONCLUSION: The Overlap SPLT technique is regarded as a safe and feasible method for anastomosis. There were no apparent differences in complications between Overlap SPLT and FETE SPLT, but Overlap SPLT costed one additional stapler cartridge and required a longer duration.

A BIOCOMPATIBLE GLASS-ENCAPSULATED TRIAXIAL FORCE SENSOR FOR IMPLANTABLE TACTILE SENSING APPLICATIONS.

This paper reports a microfabricated triaxial capacitive force sensor. The sensor is fully encapsulated with inert and biocompatible glass (fused silica) material. The sensor comprises two glass plates, on which four capacitors are located. The sensor is intended for subdermal implantation in fingertips and palms and providing tactile sensing capabilities for patients with paralyzed hands. Additional electronic components, such as passives and IC chips, can also be integrated with the sensor in a hermetic glass package to achieve an implantable tactile sensing system. Through attachment to a human palm, the sensor has been shown to respond appropriately to typical hand actions, such as squeezing or picking up a bottle.

Identification of osteoporosis ferroptosis-related markers and potential therapeutic compounds based on bioinformatics methods and molecular docking technology.

RESEARCH BACKGROUND AND PURPOSE: Osteoporosis (OP) is one of the most common bone diseases worldwide, characterized by low bone mineral density and susceptibility to pathological fractures, especially in postmenopausal women and elderly men. Ferroptosis is one of the newly discovered forms of cell death regulated by genes in recent years. Many studies have shown that ferroptosis is closely related to many diseases. However, there are few studies on ferroptosis in osteoporosis, and the mechanism of ferroptosis in osteoporosis is still unclear. This study aims to identify biomarkers related to osteoporosis ferroptosis from the GEO (Gene Expression Omnibus) database through bioinformatics technology, and to mine potential therapeutic small molecule compounds through molecular docking technology, trying to provide a basis for the diagnosis and treatment of osteoporosis in the future. MATERIALS AND METHODS: We downloaded the ferroptosis-related gene set from the FerrDb database ( http://www.zhounan.org/ferrdb/index.html ), downloaded the data sets GSE56815 and GSE7429 from the GEO database, and used the R software "limma" package to screen differentially expressed genes (DEGs) from GSE56815, and intersected with the ferroptosis gene set to obtain ferroptosis-related DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by the R software "clusterProfiler" package. The random forest model was further screened to obtain essential ferroptosis genes. R software "corrplot" package was used for correlation analysis of essential ferroptosis genes, and the Wilcox test was used for significance analysis. The lncRNA-miRNA-mRNA-TF regulatory network was constructed using Cytoscape software. The least absolute shrinkage and selection operator (LASSO) was used to construct a disease diagnosis model, and a Receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic performance, and then GSE7429 was used to verify the reliability of the diagnosis model. Molecular docking technology was used to screen potential small molecule compounds from the Drugbank database. Finally, a rat osteoporosis model was constructed, and peripheral blood mononuclear cells were extracted for qRT-PCR detection to verify the mRNA expression levels of crucial ferroptosis genes. RESULT: Six DEGs related to ferroptosis were initially screened out. GO function and KEGG pathway enrichment analysis showed that ferroptosis-related DEGs were mainly enriched in signaling pathways such as maintenance of iron ion homeostasis, copper ion binding function, and ferroptosis. The random forest model identified five key ferroptosis genes, including CP, FLT3, HAMP, HMOX1, and SLC2A3. Gene correlation analysis found a relatively low correlation between these five key ferroptosis genes. The lncRNA-miRNA-mRNA-TF regulatory network shows that BAZ1B and STAT3 may also be potential molecules. The ROC curve of the disease diagnosis model shows that the model has a good diagnostic performance. Molecular docking technology screened out three small molecule compounds, including NADH, Midostaurin, and Nintedanib small molecule compounds. qRT-PCR detection confirmed the differential expression of CP, FLT3, HAMP, HMOX1 and SLC2A3 between OP and normal control group. CONCLUSION: This study identified five key ferroptosis genes (CP, FLT3, HAMP, HMOX1, and SLC2A3), they were most likely related to OP ferroptosis. In addition, we found that the small molecule compounds of NADH, Midostaurin, and Nintedanib had good docking scores with these five key ferroptosis genes. These findings may provide new clues for the early diagnosis and treatment of osteoporosis in the future.

Possible mechanisms of auricular acupoint stimulation in the treatment of migraine by activating auricular vagus nerve. / 从耳迷走神经探讨耳穴治疗偏头痛的可能机制.

Under the guidance of traditional Chinese medicine theory, the clinical research of auricular acupoint stimulation in the treatment of migraine has gained a lot, and the curative efficacy is definite, but its mechanism remains unclear. In the present paper, we discussed the efficacy of auricular acupoint stimulation including "transcutaneous auricular vagus nerve stimulation" (taVNS) in the treatment of migraine in recent years. Through bibliometric analysis, we screened out top 10 auricular acupoints (Shenmenï¼»TF4ï¼½, Pizhixiaï¼»AT4ï¼½, Jiaoganï¼»AH6aï¼½, Ganï¼»CO12ï¼½, Yidanï¼»CO11ï¼½, Neifenmiï¼»CO18ï¼½, Shenï¼»CO10ï¼½, Nieï¼»AT2ï¼½, Zhenï¼»AT3ï¼½ and Eï¼»AT1ï¼½) which were the most frequently used for migraine. Majority of these auricular acupoints just distributed in the region innervated by auricular vagus nerve. Thus, we thought that the analgesic effect of needling these auricular acupoints for migraine was produced by triggering the auricular vagus nerve, and concluded that the central mechanism underlying induction of analgesic effect by activating auricular vagus nerve may be achieved by activating the descending pain regulation pathway of the locus coeruleus nucleus and dorsal raphe nucleus. In addition, taVNS-induced 1) regulation of the activities of brain's default network and pain matrix, 2) activation of the cortical descending pain regulation pathway, and 3) inhibition of the neuroinflammatory response may also contribute to its ameliorating effect of migraine. This paper may provide ideas for the future research on the mechanism of auricular acupoint treatment of migraine.

Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): five-year outcomes of a randomised trial.

Background: Concerns remain over the long-term safety of vascular endothelial growth factor (VEGF) inhibitors to treat retinopathy of prematurity (ROP). RAINBOW is an open label randomised trial comparing intravitreal ranibizumab (in 0.2 mg and 0.1 mg doses) with laser therapy in very low birthweight infants (<1500 g) with ROP. Methods: Of 201 infants completing RAINBOW, 180 were enrolled in the RAINBOW Extension Study. At 5 years, children underwent ophthalmic, development and health assessments. The primary outcome was visual acuity in the better-seeing eye. The study is registered with ClinicalTrial.gov, NCT02640664. Findings: Between 16-6-2016 and 21-4-2022, 156 children (87%) were evaluated at 5 years. Of 32 children with no acuity test result, 25 had a preferential looking test, for 4 children investigators reported low vision for each eye, and in 3 further children no vision measurement was obtained. 124 children completed the acuity assessment, the least square mean (95% CI) letter score in the better seeing eye was similar in the three trial arms-66.8 (62.9-70.7) following ranibizumab 0.2 mg, 64.6 (60.6-68.5) following ranibizumab 0.1 mg and 62.1 (57.8-66.4) following laser therapy; differences in means: ranibizumab 0.2 mg v laser: 4.7 (95% CI: -1.1, 10.5); 0.1 mg v laser: 2.5 (-3.4, 8.3); 0.2 mg v 0.1 mg: 2.2 (-3.3, 7.8). High myopia (worse than -5 dioptres) in at least one eye occurred in 4/52 (8%) children following ranibizumab 0.2 mg, 8/55 (15%) following ranibizumab 0.1 mg and 11/45 (24%) following laser therapy (0.2 mg versus laser: odds ratio: 3.99 (1.16-13.72)). Ocular and systemic secondary outcomes and adverse events were distributed similarly in each trial arm. Interpretation: 5-year outcomes confirm the findings of the original RAINBOW trial and a planned interim analysis at 2 years, including a reduced frequency of high myopia following ranibizumab treatment. No effects of treatment on non-ocular outcomes were detected. Funding: Novartis Pharma AG.

TMC7 functions as a suppressor of Piezo2 in primary sensory neurons blunting peripheral mechanotransduction.

The transmembrane channel-like (TMC) protein family comprises eight members, with TMC1 and TMC2 being extensively studied. This study demonstrates substantial co-expression of TMC7 with the mechanosensitive channel Piezo2 in somatosensory neurons. Genetic deletion of TMC7 in primary sensory ganglia neurons in vivo enhances sensitivity in both physiological and pathological mechanosensory transduction. This deletion leads to an increase in proportion of rapidly adapting (RA) currents conducted by Piezo2 in dorsal root ganglion (DRG) neurons and accelerates RA deactivation kinetics. In HEK293 cells expressing both proteins, TMC7 significantly suppresses the current amplitudes of co-expressed Piezo2. Our findings reveal that TMC7 and Piezo2 exhibit physical interactions, and both proteins also physically interact with cytoskeletal ß-actin. We hypothesize that TMC7 functions as an inhibitory modulator of Piezo2 in DRG neurons, either through direct inhibition or by disrupting the transmission of mechanical forces from the cytoskeleton to the channel.

The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channels.

Introduction: The transmembrane channel-like (TMC) protein family contains eight members, TMC1-TMC8. Among these members, only TMC1 and TMC2 have been intensively studied. They are expressed in cochlear hair cells and are crucial for auditory sensations. TMC6 and TMC8 contribute to epidermodysplasia verruciformis, and predispose individuals to human papilloma virus. However, the impact of TMC on peripheral sensation pain has not been previously investigated. Methods: RNAscope was employed to detect the distribution of TMC6 mRNA in DRG neurons. Electrophysiological recordings were conducted to investigate the effects of TMC6 on neuronal characteristics and M channel activity. Zn2+ indicators were utilized to detect the zinc concentration in DRG tissues and dissociated neurons. A series of behavioural tests were performed to assess thermal and mechanical sensation in mice under both physiological and pathological conditions. Results and Discussion: We demonstrated that TMC6 is mainly expressed in small and medium dorsal root ganglion (DRG) neurons and is involved in peripheral heat nociception. Deletion of TMC6 in DRG neurons hyperpolarizes the resting membrane potential and inhibits neuronal excitability. Additionally, the function of the M channel is enhanced in TMC6 deletion DRG neurons owing to the increased quantity of free zinc in neurons. Indeed, heat and mechanical hyperalgesia in chronic pain are alleviated in TMC6 knockout mice, particularly in the case of heat hyperalgesia. This suggests that TMC6 in the small and medium DRG neurons may be a potential target for chronic pain treatment.

Reply to comments by Dr. Ali Shayanfar.

Several clarifications are made pertaining to the study on the cocrystallization of 5-fluorouracil (5-FU) and gallic acid (GA). Dr. Shayanfar's perspective in the solubility and biological activity of cocrystals is recognized, and his insightful guidance on solubility determination methodologies is greatly appreciated. A misconception concerning the cytotoxicity assay methodology in the Shayanfar's comments is addressed. Furthermore, the stability of the 5-FU-GA cocrystal during solubility measurement is highlighted, as evidenced by XRD analysis of residual solids. Lastly, the independence of the elevated cytotoxicity of the cocrystal from 5-FU solubility is deliberated, aligning with preceding research outcomes.

Constraints-related microscopic fatigue crack propagation behaviour of polycrystalline alloys.

Based on the microscopic polycrystalline fatigue crack propagation (MPFCP) model, the MPFCP behaviours of GH4169 alloy under different micro-notch depths and lengths (constraints) were studied from aspects of MPFCP path, MPFCP rate and stress distribution. The influences of the initial crack angle on MPFCP behaviour were further explored. It was observed that the grain boundary, the grain size and the stress state were different during crack propagation under different constraints, resulting in different MPFCP paths. The MPFCP path was straighter under high constraints, and the MPFCP rate was related to the micro-notch size and the loading direction. The crack tip needed more stress accumulation at low constraints than under high constraints to ensure smooth MPFCP behaviour. The influence of the initial crack angle on the MPFCP path was mainly reflected in the grain interior where the initial crack was located. The initial crack angle had a greater influence on the MPFCP rate than on the MPFCP path.

Monolithic optical PAM-4 transmitter with autonomous carrier tracking.

We present two single channel optical PAM-4 transmitters, one based on a novel 3-section PN-capacitive micro-ring modulator with on-chip low-power driver and a near-zero power capacitive wavelength locking system and another one based on a 2-section thermally tuned PN micro-ring modulator of the similar size with the same modulator driver. The maximum error-free data-rate of 16 Gb/s and 22 Gb/s at the energy efficiency of 200 fJ/b and 430 fJ/b for the former and the latter transmitters are measured, respectively, and the design trade-offs are discussed. The chips are fabricated in the GlobalFoundries 90 nm CMOS SOI process.

An item response theory approach to the measurement of working memory capacity.

Complex span tasks are perhaps the most widely used paradigm to measure working memory capacity (WMC). Researchers assume that all types of complex span tasks assess domain-general WM. However, most research supporting this claim comes from factor analysis approaches that do not examine task performance at the item level, thus not allowing comparison of the characteristics of verbal and spatial complex span tasks. Item response theory (IRT) can help determine the extent to which different complex span tasks assess domain-general WM. In the current study, spatial and verbal complex span tasks were examined using IRT. The results revealed differences between verbal and spatial tasks in terms of item difficulty and block difficulty, and showed that most subjects with below-average ability were able to answer most items correctly across all tasks. In line with previous research, the findings suggest that examining domain-general WM by using only one task might elicit skewed scores based on task domain. Further, visuospatial complex span tasks should be prioritized as a measure of WMC if resources are limited.

KLHDC7B as a novel diagnostic biomarker in urine exosomal mRNA promotes bladder urothelial carcinoma cell proliferation and migration, inhibits apoptosis.

Bladder cancer is a common kind of urinary system cancer, in which bladder urothelial carcinoma (BLCA) comprises approximately 90% of all bladder cancer types. In our previous study, we discovered KLHDC7B in urine exosomal messenger RNA (mRNA) as a prospective molecular marker for bladder cancer detection. To systematically study the role and mechanism of KLHDC7B in BLCA, we focused on the most common type of BLCA in this study. First, we used RNA sequencing to discover that KLHDC7B was considerably increased in BLCA patients' urine exosomes compared to healthy controls. Then, we validated this result in an independent cohort and identified it as an effective tool for diagnosing and distinguishing high-grade and low-grade BLCA. Finally, we studied the role and mechanism of KLHDC7B in BLCA at the cellular level, providing a functional basis for its expression as a novel laboratory diagnostic biomarker for BLCA exosomal mRNA, which has important theoretical and clinical significance.

The induced and intrinsic resistance of Escherichia coli to sanguinarine is mediated by AcrB efflux pump.

IMPORTANCE: The use of plant extracts is increasing as an alternative to synthetic compounds, especially antibiotics. However, there is no sufficient knowledge on the mechanisms and potential risks of antibiotic resistance induced by these phytochemicals. In the present study, we found that stable drug resistant mutants of E. coli emerged after repetitive exposure to sanguinarine and demonstrated that the AcrB efflux pump contributed to the emerging of induced and intrinsic resistance of E. coli to this phytochemical. Our results offered some insights into comprehending and preventing the onset of drug-resistant strains when utilizing products containing sanguinarine.

AI-Driven Design System for Fabrication of Inhalable Nanocatchers for Virus Capture and Neutralization.

The global pandemic presents a critical threat to humanity, with no effective rapid-response solutions for early-stage virus dissemination. This study aims to create an AI-driven entry-blocker design system (AIEB) to fabricate inhalable virus-like nanocatchers (VLNCs) fused with entry-blocking peptides (EBPs) to counter pandemic viruses and explore therapeutic applications. This work focuses on developing angiotensin-converting enzyme 2 (ACE2)-mimic domain-fused VLNCs (ACE2@VLNCs) using AIEB and analyzing their interaction with the SARS-CoV-2 receptor binding domain (RBD), demonstrating their potential to hinder SARS-CoV-2 infection. Aerosol-based tests show ACE2@VLNCs persist over 70 min in the air and neutralize pseudoviruses within 30 min, indicating their utility in reducing airborne virus transmission. In vivo results reveal ACE2@VLNCs mitigate over 67% of SARS-CoV-2 infections. Biosafety studies confirm their safety, causing no damage to eyes, skin, lungs, or trachea, and not eliciting significant immune responses. These findings offer crucial insights into pandemic virus prevention and treatment, highlighting the potential of the ACE2@VLNCs system as a promising strategy against future pandemics.

Peripheral gating of pain by glial endozepine.

We report that diazepam binding inhibitor (DBI) is a glial messenger mediating satellite glia-sensory neuron crosstalk in the dorsal root ganglion (DRG). DBI is highly and specifically expressed in satellite glia cells (SGCs) of mice, rat and human, but not in sensory neurons or other DRG-resident cells. Knockdown of DBI results in a robust mechanical hypersensitivity without significant effects on other sensory modalities. In vivo overexpression of DBI in SGCs reduces sensitivity to mechanical stimulation and alleviates mechanical allodynia in neuropathic and inflammatory pain models. We further show that DBI acts as a partial agonist and positive allosteric modulator at the neuronal GABAA receptors, particularly strongly effecting those with a high-affinity benzodiazepine binding site. Such receptors are selectively expressed by a subpopulation of mechanosensitive DRG neurons and these are also more enwrapped with DBI-expressing glia, as compared to other DRG neurons, suggesting a mechanism for specific effect of DBI on mechanosensation. These findings identified a new, peripheral neuron-glia communication mechanism modulating pain signalling, which can be targeted therapeutically.

Prediction of Tumor Microenvironment Characteristics and Treatment Response in Lung Squamous Cell Carcinoma by Pseudogene OR7E47P-related Immune Genes.

OBJECTIVE: Pseudogenes are initially regarded as nonfunctional genomic sequences, but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities. Olfactory receptor family 7 subfamily E member 47 pseudogene (OR7E47P) is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment (TME) of lung adenocarcinoma (LUAD). This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma (LUSC). METHODS: Clinical and molecular information from The Cancer Genome Atlas (TCGA) LUSC cohort was used to identify OR7E47P-related immune genes (ORIGs) by weighted gene correlation network analysis (WGCNA). Based on the ORIGs, 2 OR7E47P clusters were identified using non-negative matrix factorization (NMF) clustering, and the stability of the clustering was tested by an extreme gradient boosting classifier (XGBoost). LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model (ORPScore) for immunotherapy. The Botling cohorts and 8 immunotherapy cohorts (the Samstein, Braun, Jung, Gide, IMvigor210, Lauss, Van Allen, and Cho cohorts) were included as independent validation cohorts. RESULTS: OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC. A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters (Cluster 1 and Cluster 2) with distinct immune, mutation, and stromal programs. Compared to Cluster 1, Cluster 2 had more infiltration by immune and stromal cells, lower mutation rates of driver genes, and higher expression of immune-related proteins. The clustering performed well in the internal and 5 external validation cohorts. Based on the 7 ORIGs (HOPX, STX2, WFS, DUSP22, SLFN13, GGCT, and CCSER2), the ORPScore was constructed to predict the prognosis and the treatment response. In addition, the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients. The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts. CONCLUSION: Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC. ORIGs can be applied to molecularly stratify patients, and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.

Inhibition of UFM1 expression suppresses cancer progression and is linked to the dismal prognosis and immune infiltration in oral squamous cell carcinoma.

BACKGROUND: Ubiquitin fold modifier 1 (UFM1) overexpression is associated with cancer cell proliferation, migration and invasion. However, the roles and pathways of UFM1 in oral squamous cell carcinoma (OSCC) has remained undefined. METHODS: The expression of UFM1 and the relationship between UFM1 expression and prognosis were investigated using data of OSCC patients from The Cancer Genome Atlas (TCGA) database. The UFM1 co-expressed genes, and the association between the UFM1 expression and immune cells and ubiquitination were explored. The effects of UFM1 expression on the growth and migration of OSCC cells were investigated by siRNA interference, Cell Counting Kit-8 (CCK-8), Transwell, Western blotting, and wound healing experiments. RESULTS: UFM1 was highly expressed in OSCC. UFM1 overexpression was associated with short overall survival, disease-specific survival, and progression-free interval, and was an adverse factor for prognosis in OSCC. UFM1-related nomograms were significantly associated with poor prognosis in OSCC patients. Decreased UFM1 expression could inhibit the proliferation, migration, and invasion of OSCC cells. UFM1 was associated with the immune cells (such as the Th17 cells, T helper cells, and cytotoxic cells) and ubiquitination. CONCLUSION: Elevated UFM1 expression was associated with poor prognosis, ubiquitination and immune infiltration in OSCC, and inhibition of UFM1 expression delayed OSCC progression, showing that UFM1 could be a biomarker for prognosis and treating OSCC patients.