Single-cell tumor heterogeneity landscape of hepatocellular carcinoma: unraveling the pro-metastatic subtype and its interaction loop with fibroblasts.

BACKGROUND: Tumor heterogeneity presents a formidable challenge in understanding the mechanisms driving tumor progression and metastasis. The heterogeneity of hepatocellular carcinoma (HCC) in cellular level is not clear. METHODS: Integration analysis of single-cell RNA sequencing data and spatial transcriptomics data was performed. Multiple methods were applied to investigate the subtype of HCC tumor cells. The functional characteristics, translation factors, clinical implications and microenvironment associations of different subtypes of tumor cells were analyzed. The interaction of subtype and fibroblasts were analyzed. RESULTS: We established a heterogeneity landscape of HCC malignant cells by integrated 52 single-cell RNA sequencing data and 5 spatial transcriptomics data. We identified three subtypes in tumor cells, including ARG1+ metabolism subtype (Metab-subtype), TOP2A+ proliferation phenotype (Prol-phenotype), and S100A6+ pro-metastatic subtype (EMT-subtype). Enrichment analysis found that the three subtypes harbored different features, that is metabolism, proliferating, and epithelial-mesenchymal transition. Trajectory analysis revealed that both Metab-subtype and EMT-subtype originated from the Prol-phenotype. Translation factor analysis found that EMT-subtype showed exclusive activation of SMAD3 and TGF-ß signaling pathway. HCC dominated by EMT-subtype cells harbored an unfavorable prognosis and a deserted microenvironment. We uncovered a positive loop between tumor cells and fibroblasts mediated by SPP1-CD44 and CCN2/TGF-ß-TGFBR1 interaction pairs. Inhibiting CCN2 disrupted the loop, mitigated the transformation to EMT-subtype, and suppressed metastasis. CONCLUSION: By establishing a heterogeneity landscape of malignant cells, we identified a three-subtype classification in HCC. Among them, S100A6+ tumor cells play a crucial role in metastasis. Targeting the feedback loop between tumor cells and fibroblasts is a promising anti-metastatic strategy.

A Simple and Universal Approach to Synthesizing Multi-Confined Carbon Dots with Thermally Activated Delayed Fluorescence.

Afterglow materials possess the remarkable capability to harness the energy and subsequently emit light after irradiation is turned off. Owing to their extraordinary ultralong lifetime, afterglow materials have garnered significant interest across various domains such as sensing, optoelectronics, bioimaging, and information encryption. However, these materials typically exhibit temperature sensitivity, rendering their afterglow emission susceptible to efficient quenching at room temperature. Consequently, this study presents herein a straightforward, simple, and universal approach for synthesizing metal-free carbon dots (CDs) endowed with thermally activated delayed fluorescence (TADF) characteristics at room temperature. In this study, TADF-CDs were simply synthesized by pyrolyzing boronic acid (BA) and urea at 500 ℃ for 3 h. Benefiting from the multi-confined effects facilitated by the robust structure of BA matrix, in conjunction with the co-doped heteroatoms of nitrogen and boron, the resultant TADF-CDs manifest remarkably prolonged afterglow TADF emission, characterized by a calculated lifetime of 184.64 ms; moreover, the blue afterglow emission remains perceptible to the naked eye for more than 6 s. The attributes of TADF-CDs were comprehensively elucidated through rigorous characterization, and the universality of the approach was corroborated through experimentation involving fourteen control CDs. Leveraging their distinctive TADF attributes, the prepared TADF-CDs were subsequently employed in advanced applications such as anti-counterfeiting and information encryption.

Water-land-energy efficiency and nexus within global agricultural trade during 1995-2019.

Agricultural product demand driven by population and economic growth poses challenges to water, land, and energy utilization, and this increasing local demand is largely met through trade. However, the efficiency and nexus pattern of the water, land, and energy embodied in agricultural trade are not well understood. This study uses the multi-regional input-output framework to analyze agricultural water, land, and energy utilization efficiency of resource footprints per unit economic output as well as their transfer and nexus pattern in global agricultural trade for 1995-2019. The results show that many international agricultural trade paths are inefficient in the water, land, and energy resource use because the agricultural products in these paths are exported from relatively low- to high-efficiency economies/regions. However, these inefficient transfer paths show an increasing trend over the study period. Regarding the water-land-energy nexus, conflicts are prevalent in land-energy and water-energy couplings. Most trade paths are conducted to alleviate the pressure on a specific resource, inadvertently increasing the pressure on other resources. Although agricultural trade is important for meeting global food demands, it is not consistently beneficial to the local environment when considering agricultural resources use efficiency. This study is expected to improve our understanding of agricultural trade impacts to the agricultural resources and support the sustainable development of global agriculture.

Nonintrusive and Effective Volume Reconstruction Model of Swimming Sturgeon Based on RGB-D Sensor.

The sturgeon is an important commercial aquaculture species in China. The measurement of sturgeon mass plays a remarkable role in aquaculture management. Furthermore, the measurement of sturgeon mass serves as a key phenotype, offering crucial information for enhancing growth traits through genetic improvement. Until now, the measurement of sturgeon mass is usually conducted by manual sampling, which is work intensive and time consuming for farmers and invasive and stressful for the fish. Therefore, a noninvasive volume reconstruction model for estimating the mass of swimming sturgeon based on RGB-D sensor was proposed in this paper. The volume of individual sturgeon was reconstructed by integrating the thickness of the upper surface of the sturgeon, where the difference in depth between the surface and the bottom was used as the thickness measurement. To verify feasibility, three experimental groups were conducted, achieving prediction accuracies of 0.897, 0.861, and 0.883, which indicated that the method can obtain the reliable, accurate mass of the sturgeon. The strategy requires no special hardware or intensive calculation, and it provides a key to uncovering noncontact, high-throughput, and highly sensitive mass evaluation of sturgeon while holding potential for evaluating the mass of other cultured fishes.

Application of urine proteomics in the diagnosis and treatment effectiveness monitoring of early-stage Mycosis Fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma. As the early clinical manifestations of MF are non-specific (e.g., erythema or plaques), it is often misdiagnosed as inflammatory skin conditions (e.g., atopic dermatitis, psoriasis, and pityriasis rosea), resulting in delayed treatment. As there are no effective biological markers for the early detection and management of MF, the aim of the present study was to perform a proteomic analysis of urine samples (as a non-invasive protein source) to identify reliable MF biomarkers. METHODS: Thirteen patients with early-stage MF were administered a subcutaneous injection of interferon α-2a in combination with phototherapy for 6 months. The urine proteome of patients with early-stage MF before and after treatment was compared against that of healthy controls by liquid chromatography-tandem mass spectrometry. The differentially expressed proteins were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Clusters of Orthologous Groups analyses. For validation, the levels of the selected proteins were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: We identified 41 differentially expressed proteins (11 overexpressed and 30 underexpressed) between untreated MF patients and healthy control subjects. The proteins were mainly enriched in focal adhesion, endocytosis, and the PI3K-Akt, phospholipase D, MAPK, and calcium signaling pathways. The ELISA results confirmed that the urine levels of Serpin B5, epidermal growth factor (EGF), and Ras homologous gene family member A (RhoA) of untreated MF patients were significantly lower than those of healthy controls. After 6 months of treatment, however, there was no significant difference in the urine levels of Serpin B5, EGF, and RhoA between MF patients and healthy control subjects. The area under the receiver operating characteristic curve values for Serpin B5, EGF, and RhoA were 0.817, 0.900, and 0.933, respectively. CONCLUSIONS: This study showed that urine proteomics represents a valuable tool for the study of MF, as well as identified potential new biomarkers (Serpin B5, EGF, and RhoA), which could be used in its diagnosis and management.

Steam Explosion Pretreatment of Polysaccharide from Hypsizygus marmoreus: Structure and Antioxidant Activity.

This paper investigated the effects of steam explosion (SE) pretreatment on the structural characteristics and antioxidant activity of Hypsizygus marmoreus polysaccharides (HPS). Hypsizygus marmoreus samples were pretreated at different SE temperatures (120-200 °C) and polysaccharides were extracted using the water extraction and alcohol precipitation method. The results showed that SE pretreatment improved the extraction rate of HPS. Under the conditions of SE treatment time of 60 s and temperature of 160 °C, the extraction rate of HPS was the highest (8.78 ± 0.24%). After SE pretreatment, the structural changes of HPS tended to enhance the antioxidant activity, which showed that the content of Gal and Man in the monosaccharide composition increased and the molecular weight decreased. When testing antioxidant activity in vitro, the ability of SE-pretreated HPS to scavenge DPPH radicals, hydroxyl radicals, and superoxide anion radicals was better than that of HPS without SE pretreatment. Our findings shed light on SE pretreatment as an efficient method for extracting active polysaccharides, providing a new way to improve their extraction rate and biological activity.

Empagliflozin rescues pro-arrhythmic and Ca2+ homeostatic effects of transverse aortic constriction in intact murine hearts.

We explored physiological effects of the sodium-glucose co-transporter-2 inhibitor empagliflozin on intact experimentally hypertrophic murine hearts following transverse aortic constriction (TAC). Postoperative drug (2-6 weeks) challenge resulted in reduced late Na+ currents, and increased phosphorylated (p-)CaMK-II and Nav1.5 but not total (t)-CaMK-II, and Na+/Ca2+ exchanger expression, confirming previous cardiomyocyte-level reports. It rescued TAC-induced reductions in echocardiographic ejection fraction and fractional shortening, and diastolic anterior and posterior wall thickening. Dual voltage- and Ca2+-optical mapping of Langendorff-perfused hearts demonstrated that empagliflozin rescued TAC-induced increases in action potential durations at 80% recovery (APD80), Ca2+ transient peak signals and durations at 80% recovery (CaTD80), times to peak Ca2+ (TTP100) and Ca2+ decay constants (Decay30-90) during regular 10-Hz stimulation, and Ca2+ transient alternans with shortening cycle length. Isoproterenol shortened APD80 in sham-operated and TAC-only hearts, shortening CaTD80 and Decay30-90 but sparing TTP100 and Ca2+ transient alternans in all groups. All groups showed similar APD80, and TAC-only hearts showed greater CaTD80, heterogeneities following isoproterenol challenge. Empagliflozin abolished or reduced ventricular tachycardia and premature ventricular contractions and associated re-entrant conduction patterns, in isoproterenol-challenged TAC-operated hearts following successive burst pacing episodes. Empagliflozin thus rescues TAC-induced ventricular hypertrophy and systolic functional, Ca2+ homeostatic, and pro-arrhythmogenic changes in intact hearts.

Application of a novel nested ensemble algorithm in predicting motor function recovery in patients with traumatic cervical spinal cord injury.

Traumatic cervical spinal cord injury (TCSCI) often causes varying degrees of motor dysfunction, common assessed by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), in association with the American Spinal Injury Association (ASIA) Impairment Scale. Accurate prediction of motor function recovery is extremely important for formulating effective diagnosis, therapeutic and rehabilitation programs. The aim of this study is to investigate the validity of a novel nested ensemble algorithm that uses the very early ASIA motor score (AMS) of ISNCSCI examination to predict motor function recovery 6 months after injury in TCSCI patients. This retrospective study included complete data of 315 TCSCI patients. The dataset consisting of the first AMS at ≤ 24 h post-injury and follow-up AMS at 6 months post-injury was divided into a training set (80%) and a test set (20%). The nested ensemble algorithm was established in a two-stage manner. Support Vector Classification (SVC), Adaboost, Weak-learner and Dummy were used in the first stage, and Adaboost was selected as second-stage model. The prediction results of the first stage models were uploaded into second-stage model to obtain the final prediction results. The model performance was evaluated using precision, recall, accuracy, F1 score, and confusion matrix. The nested ensemble algorithm was applied to predict motor function recovery of TCSCI, achieving an accuracy of 80.6%, a F1 score of 80.6%, and balancing sensitivity and specificity. The confusion matrix showed few false-negative rate, which has crucial practical implications for prognostic prediction of TCSCI. This novel nested ensemble algorithm, simply based on very early AMS, provides a useful tool for predicting motor function recovery 6 months after TCSCI, which is graded in gradients that progressively improve the accuracy and reliability of the prediction, demonstrating a strong potential of ensemble learning to personalize and optimize the rehabilitation and care of TCSCI patients.

Poor therapeutic outcomes in KRAS-mutant non-small cell lung cancer due to chemoresistance conferred by SLC7A11.

PURPOSE: This study aimed to confirm whether Kirsten rat sarcoma viral oncogene (KRAS) mutations affect the therapeutic efficacy of non-small cell lung cancer (NSCLC) and, if so, to explore what the possible mechanisms might be. METHODS: We retrospectively analyzed the efficacy of immunochemotherapy in KRAS-mutant NSCLC patients compared to driver-negative patients. Online data platforms were used to find immunotherapy cases, and survival analysis compared treatments' efficacy. Cytotoxicity assays measured chemosensitivity in KRAS-mutant versus wild-type NSCLC to drugs like paclitaxel, carboplatin, and pemetrexed. Bioinformatics confirmed the KRAS-SLC7A11 link and cell experiments tested SLC7A11's role in chemoresistance. Animal studies verified the antitumor effects of SLC7A11 inhibitors with chemotherapy. RESULTS: Patients with KRAS-mutated NSCLC have a shorter therapeutic effectiveness duration with immunochemotherapy than patients with driver gene-negative status. The efficacy of immunotherapy alone is similar between the two groups. The KRAS mutation can enhance chemoresistance by upregulating SLC7A11, and inhibiting SLC7A11 can increase the sensitivity of KRAS-mutated NSCLC to chemotherapy. CONCLUSION: This study suggests that KRAS-mutant NSCLC can enhance its acquired chemoresistance by overexpressing SLC7A11, leading to poorer therapeutic outcomes. Targeting the KRAS-SLC7A11 axis could increase sensitivity to chemotherapeutic drugs, providing theoretical support for future treatment directions.

Hollow Nanoreactors Unlock New Possibilities for Persulfate-Based Advanced Oxidation Processes.

As a novel type of catalytic material, hollow nanoreactors are expected to bring new development opportunities in the field of persulfate-based advanced oxidation processes due to their peculiar void-confinement, spatial compartmentation, and size-sieving effects. For such materials, however, further clarification on basic concepts and construction strategies, as well as a discussion of the inherent correlation between structure and catalytic activity are still required. In this context, this review aims to provide a state-of-the-art overview of hollow nanoreactors for activating persulfate. Initially, hollow nanoreactors are classified according to the constituent components of the shell structure and their dimensionality. Subsequently, the different construction strategies of hollow nanoreactors are described in detail, while common synthesis methods for these construction strategies are outlined. Furthermore, the most representative advantages of hollow nanoreactors are summarized, and their intrinsic connections to the nanoreactor structure are elucidated. Finally, the challenges and future prospects of hollow nanoreactors are presented.

Comprehensive pan­cancer analysis of MTDH for human tumor prognosis and as an immunological biomarker including breast and kidney cancer.

Metadherin (MTDH), initially discovered in primary astrocytes of the human fetus through rapid subtraction hybridization and labeled as astrocyte elevated gene-1, represents a widely recognized oncogene present in multiple types of cancers. However, the role of MTDH in different types of cancer remains unclear. To address this, a comprehensive analysis of MTDH across various types of cancers was conducted by utilizing multiple databases such as The Cancer Genome Atlas. The present analysis discovered that MTDH exhibits differential expression in different types of cancer and is associated with important factors including tumor mutational burden and microsatellite instability. These findings highlighted the significance of MTDH in the tumor microenvironment and its involvement in the development of immune cells in specific cancers. Furthermore, the results of the present study indicated that the expression of MTDH is strongly correlated with clinical prognosis, mutations and immune cell infiltration. MTDH could serve as a potential indicator of patient prognosis and potentially play a role in modulating the immune system. Given its potential as a novel immunological checkpoint, MTDH may be a viable target for tumor immunotherapy.

Using individualized structural covariance networks to analyze the heterogeneity of cerebral small vessel disease with cognitive impairment.

BACKGROUND: Cerebral small vessel disease (CSVD) includes vascular disorders characterized by heterogeneous pathomechanisms and different neuropathological clinical manifestations. Cognitive dysfunction in CSVD is associated with reductions in structural covariance networks (SCNs). A majority of research conducted on SCNs focused on group-level analysis. However, it is crucial to investigate the individualized variations in order to gain a better understanding of heterogeneous disorders such as CSVD. Therefore, this study aimed to utilize individualized differential structural covariance network (IDSCN) analysis to detect individualized structural covariance aberration. METHODS: A total of 35 healthy controls and 33 CSVD patients with cognitive impairment participated in this investigation. Using the regional gray matter volume in their T1 images, the IDSCN was constructed for each participant. Finally, the differential structural covariance edges between the two groups were determined by comparing their IDSCN using paired-sample t-tests. On the basis of these differential edges, the two subtypes of cognitively impaired CSVD patients were identified. RESULTS: The findings revealed that the differential structural covariance edges in CSVD patients with cognitive impairment showed a highly heterogeneous idistribution, with the edges primarily cross-distributed between the occipital lobe (specifically inferior occipital gyrus and cuneus), temporal lobe (specifically superior temporal gyrus), and the cerebellum. To varying degrees, the inferior frontal gyrus and the superior parietal gyrus were also distributed. Subsequently, a correlation analysis was performed between the resulting differential edges and the cognitive scale scores. A significant negative association was observed between the cognitive scores and the differential edges distributed in the inferior frontal gyrus and inferior occipital gyrus, the superior temporal gyrus and inferior occipital gyrus, and within the temporal lobe. Particularly in the cognitive domain of attention, the two subtypes separated by differential edges exhibited differences in cognitive scale scores [Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)]. The differential edges of the subtype 1, characterized by lower cognitive level, were mainly cross-distributed in the limbic lobe (specifically the cingulate gyrus and hippocampus), the parietal lobe (including the superior parietal gyrus and precuneus), and the cerebellum. In contrast, the differential edges of the subtype 2 with a relatively high level of cognition were distributed between the cuneus and the cerebellum. CONCLUSIONS: The differential structural covariance was investigated between the healthy controls and the CSVD patients with cognitive impairment, showing that differential structural covariance existed between the two groups. The edge distributions in certain parts of the brain, such as cerebellum and occipital and temporal lobes, verified this. Significant associations were seen between cognitive scale scores and some of those differential edges .The two subtypes that differed in both differential edges and cognitive levels were also identified. The differential edges of subtype 1 with relatively lower cognitive levels were more distributed in the cingulate gyrus, hippocampus, superior parietal gyrus, and precuneus. This could potentially offer significant benefits in terms of accurate diagnosis and targeted treatment of heterogeneous disorders such as CSVD.

Incorporating Adaptive Survey Design in a Two-Stage National Web or Mail Mixed-Mode Survey: An Experiment in the American Family Health Study.

This article presents the results of an adaptive design experiment in the recruitment of households and individuals for a two-stage national probability web or mail mixed-mode survey, the American Family Health Study (AFHS). In the screening stage, we based the adaptive design's subgroup differentiation on Esri Tapestry segmentation. We used tailored invitation materials for a subsample where a high proportion of the population was Hispanic and added a paper questionnaire to the initial mailing for a subsample with rural and older families. In the main-survey stage, the adaptive design targeted the households where a member other than the screening respondent was selected for the survey. The adaptations included emailing and/or texting, an additional prepaid incentive, and seeking screening respondents' help to remind the selected individuals. The main research questions are (i) whether the adaptive design improved survey production outcomes and (ii) whether combining adaptive design and postsurvey weighting adjustments improved survey estimates compared to performing postsurvey adjustments alone. Unfortunately, the adaptive designs did not improve the survey production outcomes. We found that the weighted AFHS estimates closely resemble those of a benchmark national face-to-face survey, the National Survey of Family Growth, although the adaptive design did not additionally change survey estimates beyond the weighting adjustments. Nonetheless, our experiment yields useful insights about the implementation of adaptive design in a self-administered mail-recruit web or mail survey. We were able to identify subgroups with potentially lower response rates and distinctive characteristics, but it was challenging to develop effective protocol adaptations for these subgroups under the constraints of the two primary survey modes and the operational budget of the AFHS. In addition, for self-administered within-household selection, it was difficult to obtain contact information from, reach, and recruit selected household members that did not respond to the screening interview.

Effects of ambient temperature on pediatric incident seizure: A case-crossover analysis using distributed lag non-linear models.

OBJECTIVE: Emerging evidence supports that brain dysfunction may be attributable to environmental factors. This study aims to examine associations of ambient temperature and temperature variability (TV) with seizure incidence in children, which has not been explored. MATERIAL AND METHODS: Data on 2718 outpatient visits due to seizure were collected in Shanghai, China, from 2018 to 2023. Exposure to ambient temperature was estimated at children's residential addresses using spatial-temporal models. A time-stratified case-crossover design with a distributed lag non-linear model (DLNM) was conducted to assess the association between seizure incidence and daily average of ambient temperature over a period of 21 days prior to a case date of disease onset. For a given case date, we selected all dates falling on the same day of the week within the same month as control dates. We calculated a composite index of intra-day and inter-day TV, which was the standard deviation of the daily minimum and maximum temperatures, respectively, over 7 days preceding a case date. We then assessed the association between TV and seizure incidence. Stratified analyses were conducted by age (73.51% < 5 years old and 26.49 % ≥ 5 years old), sex (41.83% female), presence of fever (69.72%), and diagnosis of epilepsy (27.63%). RESULTS: We observed inversed J-shaped temperature-response curves. Lower temperatures had a significant and prolonged effect than higher temperatures. Using 20 °C (with the minimum effect) as the reference, the cumulative odds ratios (ORs) for over 0-21 days preceding the onset at the 5th percentile of the temperature (3 °C) and at the 95th percentile (29 °C) were 3.17 (95% CI: 1.77, 5.68) and 1.54 (95% CI: 0.97, 2.44), respectively. In addition, per 1 °C increases in TV0-7 was associated with OR of 1.08 (95% CI: 1.01, 1.15). Older children and those experiencing seizure with fever exhibited a higher risk of seizure onset at both lower and higher ambient temperatures. CONCLUSION: Both low and high temperatures can contribute to the morbidity related to pediatric seizure. Lower temperatures, however, exerted a longer period of effect prior to seizure onset than higher temperatures. An increased risk for incident seizure was significantly associated with temperature variability during preceding 7 days.

Alternative splicing of the conserved drug-resistant orthologue FpNcb2 is associated with its nuclear accumulation of products and full virulence of Fusarium pseudograminearum.

BACKGROUND: Negative cofactor 2 NC2ß (Ncb2 or Dr1) is the beta subunit of a conserved heterodimeric regulator of transcription negative cofactor 2 (NC2) complex that has been identified as key regulator of drug resistance in model fungi. However, its role in plant pathogens is still unclear. RESULTS: We identified an NC2ß orthologue, FpNcb2, in Fusarium pseudograminearum, which is not only a significant regulatory function in drug resistance, but also essential for growth, conidiation and penetration. Moreover, FpNcb2 undergoes alternative splicing which creates two mRNA isoforms. As a putative CCAAT binding protein, FpNcb2 concentrates in the nuclei, contributing to the expression of two spliced mRNA of FpNcb2 in hypha, conidiophores and conidia, with exception of FpNcb2ISOA in germlings. Expression of each spliced mRNA of FpNcb2 in Δfpncb2 mutant could full complement the defects on growth, conidiation and fungicides sensitivity to that of wild type. However, FpNcb2ISOA and FpNcb2ISOB have different effects on virulence. FpNcb2 acts as a regulator for the transcription of some genes encoding drug efflux and hydrolases. CONCLUSION: Our analysis showed the existence of alternative mRNA splicing in the NC2ß orthologue, which is associated with protein subcellular localization and fungal virulence. The further elucidation of the target genes of NC2ß will provide insights into the potential regulation mechanisms in the antifungal resistance and pathogenesis of F. pseudograminearum. © 2024 Society of Chemical Industry.

Mitigation of ammonia and hydrogen sulfide emissions during aerobic composting of laying hen waste through NaOH-modified biochar.

The impact of NaOH-modified biochar on the release of NH3 and H2S from laying hens' manure was examined for 44 days, using a small-scale simulated aerobic composting system. The findings revealed that the NaOH-modified biochar reduced NH3 and H2S emissions by 40.63% and 77.78%, respectively, compared to the control group. Moreover, the emissions of H2S were significantly lower than those of the unmodified biochar group (p < 0.05). The increased specific surface area and microporous structure of the biochar, as well as the higher content of alkaline and oxygenated functional groups, were found to facilitate the adsorption of NH3 and H2S. This enhanced adsorption capability was the primary reason for the significant reduction in NH3 emissions. Furthermore, during the high-temperature phase of composting, there was a notable alteration in the microbial community. The abundance of Limnochordaceae, Savagea, and IMCC26207 increased significantly which aided in the conversion of H2S to stable sulfate. These microorganisms also influenced the abundance of functional genes involved in sulfur metabolism, thereby inhibiting cysteine synthesis, along with the decomposition and conversion of sulfate to sulfite. This led to a significant decrease in H2S emissions. This study provides valuable data for the selection of deodorizers in the composting process of egg-laying hens. The results have significant implications for the application of NaOH-modified biochar for odor reduction in aerobic composting processes.

Evaluation of parietal pleural adhesion and invasion in subpleural lung cancer: value of B-mode ultrasound and contrast-enhanced ultrasound.

Background: The parietal pleural adhesion/invasion of lung cancer can contribute substantially to poor prognosis and difficulty in surgery. The value of ultrasound in evaluating the parietal pleural adhesion or invasion (pleural adhesion/invasion) of lung cancer remains uncertain. This study investigated the value of B-mode ultrasound and contrast-enhanced ultrasound (CEUS) in diagnosing parietal pleural adhesion/invasion of subpleural lung cancer. Methods: The study animals included 40 male New Zealand white rabbits. A rabbit subpleural lung cancer model was constructed by injecting VX2 tumor tissue under ultrasound guidance. In the 1-3 weeks after subpleural lesion formation, parietal pleural adhesion/invasion of the largest subpleural lesion was evaluated with B-mode ultrasound and CEUS by two sonographers. The parietal pleural adhesion/invasion was also determined using the gold standard method of findings from anatomical and pathological examination. Results: Ultimately, 34 rabbits were subjected to complete ultrasonic evaluation. There were 20 and 14 cases with and without parietal pleural adhesion/invasion, respectively, as confirmed by anatomical and pathological evaluations. The diagnostic sensitivity, specificity, and accuracy of sonographer 1 using B-mode ultrasound were 50.0% [95% confidence interval (CI): 26.0-74.0%], 100%, and 70.6% (95% CI: 54.5-86.7%), respectively; for CEUS, they were 90.0% (95% CI: 75.6-100.0%), 100.0%, and 94.1% (95% CI: 85.8-100.0%), respectively. The diagnostic sensitivity, specificity, and accuracy of sonographer 2 using B-mode ultrasound were 45.0% (95% CI: 21.1-68.9%), 92.9% (95% CI: 77.5-100.0%), and 64.7% (95% CI: 47.8-81.6%), respectively; for CEUS, they were 85.0% (95% CI: 67.9-100.0%), 100.0%, and 91.2% (95% CI: 81.1-100.0%), respectively. The diagnostic accuracy of sonographer 1 was higher with CEUS than with B-mode ultrasound, but not significantly so (94.1% vs. 70.6%; P=0.08). The diagnostic accuracy of sonographer 2 was significantly higher with CEUS than with B-mode ultrasound (91.2% vs. 64.7%; P=0.03). The interrater reliability was higher for CEUS than for B-mode ultrasound (κ=0.941 vs. κ =0.717). Conclusions: Based on an animal model, B-mode ultrasound and CEUS both exhibited good diagnostic efficacy and interrater reliability in evaluating parietal pleural adhesion/invasion of subpleural lung cancer although CEUS outperformed B-mode ultrasound for both measures.

PA28γ induces dendritic cell maturation and activates T-cell immune responses in oral lichen planus.

Oral lichen planus (OLP) is a common chronic inflammatory disease of the oral mucosa, the mechanism of its inflammatory progression has not yet been fully elucidated. PA28γ plays a significant role in a variety of immune-related diseases. However, the exact role of PA28γ in the pathogenesis of OLP remains unclear. Here, we demonstrated that PA28γ is overexpressed in epithelial cells and inflammatory cells of OLP tissues but has no significant relationship with OLP subtypes. Functionally, keratinocytes with high PA28γ expression could induce dendritic cell (DC) maturation and promote the T-cell differentiation into Th1 cells in response to the immune response. In addition, we found that a high level of PA28γ expression is associated with high numbers of infiltrating mature DCs and activated T-cells in OLP tissues. Mechanistically, keratinocytes with high PA28γ expression could promote the secretion of C-C motif chemokine (CCL)5, blocking CCL5 or/and its receptor CD44 could inhibit the induction of T-cell differentiation by keratinocytes with high PA28γ expression. In conclusion, we reveal that keratinocytes with high expression of PA28γ in OLP can induce DC maturation and promote T-cell differentiation through the CCL5-CD44 pathway, providing previously unidentified mechanistic insights into the mechanism of inflammatory progression in OLP.

Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study.

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. METHODS: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001). CONCLUSIONS: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.

Rapid and sustained improvements in itch and quality of life with upadacitinib plus topical corticosteroids in adults and adolescents with atopic dermatitis: 52-week outcomes from the phase 3 AD Up study.

Purpose: Atopic dermatitis (AD) adversely impacts quality of life (QoL). We evaluated the effect of upadacitinib, an oral selective Janus kinase inhibitor approved for moderate-to-severe AD, plus topical corticosteroids (+TCS) on patient-reported outcomes (PROs) over 52 weeks.Materials and methods: In the phase 3 AD Up study (NCT03568318), adults and adolescents with moderate-to-severe AD were randomized 1:1:1 to once-daily upadacitinib 15 mg, 30 mg, or placebo + TCS. Itch, skin pain/symptoms, sleep, QoL, daily activities, emotional state, mental health, and patient impressions of disease severity/improvement/treatment satisfaction were assessed.Results: This analysis included 901 patients. Within 1-2 weeks, PRO improvements were greater with both upadacitinib doses than with placebo (p <.05). Improvements increased through weeks 4-8; rates were generally maintained through week 52. At week 52, the proportion of patients with clinically meaningful improvements in itch (Worst Pruritus Numerical Rating Scale improvement ≥4), skin pain (AD Symptom Scale Skin Pain improvement ≥4), sleep (AD Impact Scale [ADerm-IS] Sleep improvement ≥12), daily activities (ADerm-IS Daily Activities improvement ≥14), and emotional state (ADerm-IS Emotional State improvement ≥11) ranged from 62.1%-77.7% with upadacitinib 15 mg + TCS and 71.3%-83.6% with upadacitinib 30 mg + TCS.Conclusions: Upadacitinib + TCS results in rapid, sustained improvements in burdensome AD symptoms and QoL.