Screening of genes related to programmed cell death in esophageal squamous cell carcinoma and construction of prognostic model based on transcriptome analysis.

OBJECTIVES: To screen programmed cell death (PCD)-related genes in esophageal squamous cell carcinoma (ESCC) based on transcriptomic data and to explore its clinical value. METHODS: Differentially expressed PCD genes (DEPCDGs) were screened from ESCC transcriptome and clinical data in TCGA database. Univariate COX and LASSO COX were performed on prognostically DEPCDGs in ESCC to develop prognostic model. Differences in immune cell infiltration in different RiskScore groups were determined by ssGSEA and CIBERSORT. The role of RiskScore in immunotherapy response was explored using Tumor Immune Dysfunction and Exclusion (TIDE) and IMvigor210 cohorts. RESULTS: Fourteen DEPCDGs associated with prognosis were tapped in ESCC. These DEPCDGs form a RiskScore with good predictive performance for prognosis. RiskScore demonstrated excellent prediction accuracy in three data sets. The abundance of M2 macrophages and Tregs was higher in the high RiskScore group, and the abundance of M1 macrophages was higher in the low RiskScore group. The RiskScore also showed good immunotherapy sensitivity. RT-qPCR analysis showed that AUP1, BCAP31, DYRK2, TAF9 and UBQLN2 were higher expression in KYSE-150 cells. Knockdown BCAP31 inhibited migration and invasion. CONCLUSION: A prognostic risk model can predict prognosis of ESCC and may be a useful biomarker for risk stratification and immunotherapy assessment.

Molecular insights into programmed cell death in esophageal squamous cell carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is a deadly type of esophageal cancer. Programmed cell death (PCD) is an important pathway of cellular self-extermination and is closely involved in cancer progression. A detailed study of its mechanism may contribute to ESCC treatment. Methods: We obtained expression profiling data of ESCC patients from public databases and genes related to 12 types of PCD from previous studies. Hub genes in ESCC were screened from PCD-related genes applying differential expression analysis, machine learning analysis, linear support vector machine (SVM), random forest and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. In addition, based on the HTFtarget and TargetScan databases, transcription factors (TFs) and miRNAs interacting with the hub genes were selected. The relationship between hub genes and immune cells were analyzed using the CIBERSORT algorithm. Finally, to verify the potential impact of the screened hub genes on ESCC occurrence and development, a series of in vitro cell experiments were conducted. Results: We screened 149 PCD-related DEGs, of which five DEGs (INHBA, LRRK2, HSP90AA1, HSPB8, and EIF2AK2) were identified as the hub genes of ESCC. The area under the curve (AUC) of receiver operating characteristic (ROC) curve of the integrated model developed using the hub genes reached 0.997, showing a noticeably high diagnostic accuracy. The number of TFs and miRNAs regulating hub genes was 105 and 22, respectively. INHBA, HSP90AA1 and EIF2AK2 were overexpressed in cancer tissues and cells of ESCC. Notably, INHBA knockdown suppressed ECSS cell migration and invasion and altered the expression of important apoptotic and survival proteins. Conclusion: This study identified significant molecules with promising accuracy for the diagnosis of ESCC, which may provide a new perspective and experimental basis for ESCC research.

Deciphering the impact of organic loading rate and digestate recirculation on the occurrence patterns of antibiotics and antibiotic resistance genes in dry anaerobic digestion of kitchen waste.

Organic loading rate (OLR) is crucial for determining the stability of dry anaerobic digestion (AD). Digestate recirculation contributes to reactor stability and enhances methane production. Nevertheless, the understanding of how OLR and digestate recirculation affect the abundance and diversity of antibiotics and antibiotic resistance genes (ARGs), as well as the mechanisms involved in the dissemination of ARGs, remains limited. This study thoroughly investigated this critical issue through a long-term pilot-scale experiment. The metabolome analyses revealed the enrichment of various antibiotics, such as aminoglycoside, tetracycline, and macrolide, under low OLR conditions (OLR ≤ 4.0 g·VS/L·d) and the reactor instability. Antibiotics abundance decreased by approximately 19.66-31.69 % during high OLR operation (OLR ≥ 6.0 g·VS/L·d) with digestate recirculation. The metagenome analyses demonstrated that although low OLR promoted reactor stability, it facilitated the proliferation of antibiotic-resistant bacteria, such as Pseudomonas, and triggered functional profiles related to ATP generation, oxidative stress response, EPS secretion, and cell membrane permeability, thereby facilitating horizontal gene transfer (HGT) of ARGs. However, under stable operation at an OLR of 6.0 g·VS/L·d, there was a decrease in ARGs abundance but a notable increase in human pathogenic bacteria (HPB) and mobile genetic elements (MGEs). Subsequently, during reactor instability, the abundance of ARGs and HPB increased. Notably, during digestate recirculation at OLR levels of 6.0 and 7.0 g·VS/L·d, the process attenuated the risk of ARGs spread by reducing the diversity of ARGs hosts, minimizing interactions among ARGs hosts, ARGs, and MGEs, and weakening functional profiles associated with HGT of ARGs. Overall, digestate recirculation aids in reducing the abundance of antibiotics and ARGs under high OLR conditions. These findings provide advanced insights into how OLR and digestate recirculation affect the occurrence patterns of antibiotics and ARGs in dry AD.

The responses and tolerance of photosynthetic system in Chlorella vulgaris to the pharmaceutical pollutant carbamazepine.

Screening for sensitive toxicological indicators and understanding algal tolerance to pharmaceutical contaminants (PhCs) are essential for assessing PhCs risk and their removal by microalgae. Carbamazepine (CBZ) showed adverse effects on microalgae, but the specific toxicity mechanisms on the most sensitive algal photosynthetic system (PS) remain limited. This study delved into the impact of CBZ exposure on the growth, cell viability, pigment content, and PS of Chlorella vulgaris. The findings revealed a notable inhibition of C. vulgaris growth by CBZ, with an IC50 value of 27.2 mg/L at 96 hours. CBZ exposure induced algal membrane damage and cell viability. Intriguingly, CBZ drastically diminished intracellular pigment levels, notably showing "low promotion and high inhibition" of chlorophyll b (Chl b) by 72 hours. Moreover, the study identified a decreased number of active reaction centers (RCs) within algal PSII alongside inhibited electron transport from QA to QB on the PSII receptor side, leading to PSII disruption. As an adaptive response to CBZ stress, C. vulgaris stimulated its Chl b synthesis, increased non-photochemical quenching (NPQ), and adapted its tolerance to bright light. Additionally, the alga attempted to compensate for the CBZ-induced reduction in electron transfer efficiency at the PSII receptor side and light energy utilization by increasing its electron transfer from downstream. Principal component analysis (PCA) further verified that the parameters on non-photochemical dissipation, electron transport, and integrative performance were the most sensitive algal toxicological indicators for CBZ exposure, and algal PS has energy protection capability through negative feedback regulation. However, prolonged exposure to high doses of CBZ will eventually result in permanent damage to the algal PS. Hence, attention should be paid to the concentration of CBZ in the effluent and the exposure time, while methods to mitigate algal photodamage should be appropriately sought for algal treatment of dense effluents.

Identification of Molecular Subtypes Associated with PCD in Esophageal Squamous Cell Carcinoma and Analysis of Immune Microenvironment.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly fatal malignancy with increasing incidence, and programmed cell death (PCD) plays an important role in homeostasis. AIMS: This study aimed to explore the ESCC of heterogeneity based on the PCD signatures for the diagnosis and treatment of patients. METHODS: The clinical information and RNA-seq data of patients with ESCC and the PCD-related genes set were used to identify PCD signatures.The "limma" package was used to identify the differentially expressed genes (DEGs). "Clusterprofiler" package was used for function enrichment analysis, and the "ConsensusClusterPlus" package was performed for consensus clustering. Finally, the "GSVA" package and the Cibersort algorithm were used for the immune infiltration analysis. RESULTS: We performed differential expression analysis between ESCC and normal samples and identified 1659 DEGs, of which 124 DEGs were PCD genes. Then, the patients were divided into cluster1 and cluster2 based on the expression of 124 PCD genes. There was a significant difference in immune infiltration between the two clusters. The patients in cluster 1 had a higher immune score and more CD56dim natural killer cells, monocytes, activated CD4 T cells, eosinophil, and activated B cells infiltration, while cluster2 had a higher stromal score, more immune regulation, and immune checkpoint genes expression. CONCLUSION: We identified two clusters based on PCD gene expression and characterized their tumor microenvironment and immune checkpoint difference. Our findings may provide some new insight into the treatment of ESCC.

Numerical Simulation of Reversed Austenite Evolution during Intercritical Tempering of Low-Carbon Martensitic Stainless Steel.

Since the formation of reversed austenite during critical tempering treatment is an important factor affecting the mechanical properties of 13Cr4Ni martensitic stainless steel, a detailed study of the content and morphology of reversed austenite in heat treatment is needed. In this study, the variation curves of a reversed austenite volume fraction with holding time at different tempering temperatures were measured by in situ X-ray diffraction (XRD), and the reversed austenite and carbides of each process were evaluated by transmission electron microscopy (TEM). The austenite content shows a parabolic change with the increase in the tempering temperature; the maximum can reach a peak of about 6.8% at 610 °C, and drops to 0% at 660 °C. It also shows a parabolic change with the extension of the holding time, reaching a maximum of about 9.2% at 5 h of holding time, and a decreasing trend at 10 h of holding time, about 6.8%. The results show that the precipitation of carbides in the microstructure causes elemental segregation at grain boundaries and inside, which is one of the main factors affecting the thermal stability of reversed austenite formation. The kinetic process of reversed austenite during the tempering process was simulated using the JMAK model and the KM model, which can describe the trend of reversed austenite content during the tempering process. Combining the two models, a mathematical model for the room-temperature reversed austenite content under different processes was obtained, and this can predict the room-temperature austenite content.

The Application of Biomaterials for the Vaccine, Treatment, and Detection of SARS-CoV-2.

The coronavirus disease-19 (COVID-19) pandemic has had a significant impact on human life worldwide since 2019. Specific vaccines and antiviral agents are the most effective means of preventing and treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Additionally, antiviral protective equipment and early diagnosis also contribute to controlling the spread of COVID-19. The utilization of biomaterials in medicine and pharmaceuticals is crucial to ensure the positive impact of vaccines, antiviral agents, and protective equipment. In this review, we discuss the application of various types of biomaterials, including polymers, lipid nanoparticles, inorganic biomaterials, protein- or peptide-associated biomaterials, self-assembled biomaterials, and other biomaterials, for the vaccine, treatment, and prevention of COVID-19. Finally, we provide a perspective on future opportunities and challenges for developing biomaterials to combat other viral outbreaks and diseases.

Degradation of Structurally Modified Polylactide under the Controlled Composting of Food Waste.

The degradation of polylactide (PLA) films of different structures under conditions of controlled composting has been studied. We have demonstrated that PLA underwent degradation within one month in a substrate that simulated standard industrial composting. Regardless of the initial structure of the samples, the number-average molecular weight (Mn) decreased to 4 kDa while the degree of crystallinity increased to about 70% after 21 days of composting. Addition of an inoculant to the standard substrate resulted in the accelerated degradation of the PLA samples for one week due to an abiotic hydrolysis. These findings have confirmed that industrial composting could solve the problem of plastic disposal at least for PLA.

Honeycomb Column Thin-Walled Structure Design and Mechanical Properties of Ti Alloy Fabricated through Selective Laser Melting.

A honeycomb column thin-walled structure (HCTS) was designed and the relative density was calculated for numerical simulation. The HCTS samples were fabricated via selective laser melting (SLM). The numerical simulation and a three-point bending test were conducted to evaluate the mechanical properties of the HCTS made of Ti6Al4V. The findings of the numerical simulation demonstrated that the HCTS had a stronger resistance to deformation and a maximum loading force 30% higher than the equivalent solid thin-walled structure (ESTS). The mechanical performance of the HCTS as determined by the three-point bending test was mostly comparable with the numerical simulation. The maximum loading force of the experimental HCTS050-E thin-walled structure was 1200 N higher than that of HCTS050-S. The numerical simulation can provide theoretical guidance for the SLM processing of HCTSs.

Effects of switching redox conditions on sediment phosphorus immobilization by calcium/aluminum composite capping: Performance, ecological safety and mechanisms.

There many materials were used in lake restoration to immobilize phosphorus (P) and reduce the effect of eutrophication. Among them, calcium/aluminum composite (CAC) showed a good capacity of P adsorption. However, a comprehensive of its performance, ecological safety, and the mechanism of P passivation in the aluminum-bound P (Al -P) dominated sediments under varying redox conditions remains incomplete. In the current study, both unwashed CAC (UCAC) and washed CAC (WCAC) showed good P adsorption properties, and the greatest maximum capacity for P adsorption (Qmax) reached 206.8 mg/g at pH 8.5 for UCAC. The SRP and TP in the overlying water of the uncapped sediments showed a decrease-increase-decrease trend in a sequence of transition from aerobic to anaerobic to re-aerobic stages. In contrast, the SRP and TP of the two CACs-capped sediments were maintained low. Phosphorus forms in the uncapped sediment also underwent significant changes during continuous variation of dissolved oxygen (DO) levels. In particular, the decrease in iron-bound P (Fe-P) and Al-P was significantly promoted in the anaerobic phase, and the released P was reabsorbed to form mainly Fe-P in the re-aerobic phase. The CACs-capping promoted the transformation of Fe-P to residual P (Res-P), forming a thick static layer in the surface sediment, thus significantly inhibiting sediment P release. Moreover, the CACs-capping did not induce the Al3+ leaching and significant changes of the microbial community in sediments, and their performances of P immobilization could keep stable to resist the redox variation, which promised to be a good choice for P passivation in eutrophic lake sediments dominated by Al/Fe-P. These findings also confirmed that the risk of P release from Al/Fe-P (mainly Al-P)-dominated sediments was strongly influenced by continuously changing redox conditions, and was probably enhanced by the formation of Fe-P from the resorption of the released P.

Multi-omics analysis unravels effects of salt and oil on substance transformation, microbial community, and transcriptional activity in food waste anaerobic digestion.

In this study, through quantitative detection of key substances and enzyme activities, an integrated analysis of 16S rRNA sequencing and metatranscriptomics revealed the mechanisms by which salt and oil influence the biotransformation process during anaerobic digestion (AD). The results demonstrated that a salt concentration of 6 g/L promoted lipid metabolism and hydrogenotrophic methanogenesis, while inhibiting the acetoclastic pathway. An oil concentration of 5 g/L facilitated the expression of key enzyme-encoding genes involved in ß-oxidation of long-chain fatty acids, transcription, and acetoclastic methanogenesis. It also promoted the enrichment of syntrophic propionate/butyrate oxidation bacteria (Syntrophomonas and DMER64). Salt/oil co-addition enhanced the expression of genes related to glucose metabolism, amino acid metabolism, organic acid synthesis, and quorum sensing. Furthermore, salt/oil co-addition inhibited the secretion of key enzymes related to methanogens by impeding the transcription process. Collectively, these findings provide systematic insights into how salt and oil affect the biochemical metabolic mechanisms of AD.

H/D Exchange Coupled with 2H-labeled Stable Isotope-Assisted Metabolomics Discover Transformation Products of Contaminants of Emerging Concern.

Stable isotope-assisted metabolomics (SIAM) is a powerful tool for discovering transformation products (TPs) of contaminants. Nevertheless, the high cost or lack of isotope-labeled analytes limits its application. In-house H/D (hydrogen/deuterium) exchange reactions enable direct 2H labeling to target analytes with favorable reaction conditions, providing intuitive and easy-to-handle approaches for environmentally relevant laboratories to obtain cost-effective 2H-labeled contaminants of emerging concern (CECs). We first combined the use of in-house H/D exchange and 2H-SIAM to discover potential TPs of 6PPD (N-1,3-dimethylbutyl-N'-phenyl-p-phenylenediamine), providing a new strategy for finding TPs of CECs. 6PPD-d9 was obtained by in-house H/D exchange with favorable reaction conditions, and the impurities were carefully studied. Incomplete deuteride, for instance, 6PPD-d8 in this study, constitutes a major part of the impurities. Nevertheless, it has few adverse effects on the 2H-SIAM pipeline in discovering TPs of 6PPD. The 2H-SIAM pipeline annotated 9 TPs of 6PPD, and commercial standards further confirmed the annotated 6PPDQ (2-anilino-5-(4-methylpentan-2-ylamino)cyclohexa-2,5-diene-1,4-dione) and PPPD (N-phenyl-p-phenylenediamine). Additionally, a possible new formation mechanism for 6PPDQ was proposed, highlighting the performance of the strategy. In summary, this study highlighted a new strategy for discovering the TPs of CECs and broadening the application of SIAM in environmental studies.

LncRNA-Encoded Micropeptide ACLY-BP Drives Lipid Deposition and Cell Proliferation in Clear Cell Renal Cell Carcinoma via Maintenance of ACLY Acetylation.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of lethal kidney cancer. Reprogramming of fatty acid and glucose metabolism resulting in the accumulation of lipids and glycogen in the cytoplasm is a hallmark of ccRCC. Here, we identified a micropeptide ACLY-BP encoded by the GATA3-suppressed LINC00887, which regulated lipid metabolism and promoted cell proliferation and tumor growth in ccRCC. Mechanistically, the ACLY-BP stabilizes the ATP citrate lyase (ACLY) by maintaining ACLY acetylation and preventing ACLY from ubiquitylation and degradation, thereby leading to lipid deposition in ccRCC and promoting cell proliferation. Our results may offer a new clue for the therapeutic approaches and the diagnostic assessment for ccRCC. IMPLICATIONS: This study identifies ACLY-BP encoded by LINC00887 as a lipid-related micropeptide that stabilizes ACLY to generate acetyl-CoA, driving lipid deposition and promoting cell proliferation in ccRCC.

Characteristics of denitrification activity, functional genes, and denitrifying community composition in the composting process of kitchen and garden waste.

N2O can be easily produced during the co-composting of kitchen waste (KW) and garden waste (GW). This study investigated the effects of the co-composting of KW and GW at different ratios (1:2, 1:1.5, 1:1, and 1.5:1) on the denitrifying activities, functional genes, and community composition of denitrifiers. The results showed that the denitrification activity of KW and GW at a 1:2 ratio was the lowest. The gene abundances of nirS, nirK, nosZI, and nosZII were high on days 12 and 28 under the four different ratios. Network analysis demonstrated that nosZ-type denitrifiers could construct a complex and reciprocal bacterial network to promote the reduction of N2O to N2. Mantel test results revealed that nirS-, nirK-, nosZI-, and nosZII-type denitrifiers were significantly positively correlated with pH, C/N, and moisture content. These findings demonstrated that composting with appropriate proportions of KW and GW could reduce N2O emissions caused by denitrification.

Effects of dam building on N2O-producing and N2O-reducing community structures in river sediments and the associated N2O emission potential.

Dam construction is regarded as the greatest anthropogenic disturbance in aquatic ecosystems, and it promotes denitrification, through which large N2O emissions occur. However, the effect of dams on N2O producers and other N2O-reducing microorganisms (especially for nosZ II), and the associated denitrification rates remain poorly understood. This study systematically investigated the spatial variation of potential denitrification rates in dammed river sediments in winter and summer and the microbial processes driving N2O production and reduction. Sediments in the transition zone of dammed rivers were found to be critical for N2O emission potential, with lower potential denitrification rate and N2O production rate in winter than in summer. In dammed river sediments, the dominant N2O-producing microorganisms and N2O-reducers were nirS-harboring bacteria and nosZ I-harboring bacteria, respectively. Diversity analysis showed that diversity of N2O-producing did not differ significantly between upstream and downstream sediments, whereas the population size and diversity of N2O-reducing microbial communities in upstream sediments significantly decreased, leading to biological homogenization. Further ecological network analysis revealed that the ecological network of nosZ II microbes was more complex than that of nosZ I microbes, and both exhibited more cooperation in the downstream sediments than in the upstream sediments. Mantel analysis showed that the potential N2O production rate was mainly influenced by electrical conductivity (EC), NH4+, and TC content, and that higher nosZ II/nosZ I ratios contributed to improved N2O sinks in dammed river sediments. Moreover, the Haliscomenobacter genus from the nosZ II-type community in the downstream sediments contributed significantly to N2O reduction. Collectively, this study elucidates the diversity and community distribution of nosZ-type denitrifying microorganisms influenced by dams, and also highlights the non-negligible role played by nosZ II-containing microbial groups in mitigating N2O emissions from dammed river sediments.

Data rate measurement method with selectable range in linear optical sampling.

Linear optical sampling (LOS) is one of the most powerful techniques for high-speed signal monitoring. To measure the data-rate of signal under test (SUT) in optical sampling, multi-frequency sampling (MFS) was proposed. However, the measurable data-rate range of the existing method based on MFS is limited, which makes it very difficult to measure the data-rate of high-speed signals. To solve the above problem, a range selectable data-rate measurement method based on MFS in LOS is proposed in this paper. Through this method, the measurable data-rate range can be selected to match the data-rate range of SUT and the data-rate of SUT can be measured precisely, independently of the modulation format. What's more, the sampling order can be judged using the discriminant in the proposed method, which is key for plotting eye diagrams with correct time information. We experimentally measure the baud-rates of PDM-QPSK signal from 800 MBaud to 40.8 GBaud in different ranges and judge the sampling orders. The relative error of measured baud-rate is less than 0.17% while the error vector magnitude (EVM) is less than 0.38. Compared with the existing method, under the same sampling cost, our proposed method realizes the selectivity of the measurable data-rate range and the judgment of sampling order, greatly extends the measurable data-rate range of SUT. Hence, the data-rate measurement method with selectable range has great potential for high-speed signal data-rate monitoring.

A Self-Propagating c-Met-SOX2 Axis Drives Cancer-Derived IgG Signaling That Promotes Lung Cancer Cell Stemness.

SIGNIFICANCE: Sialylated cancer IgG activates c-Met-SOX2 signaling to promote stemness properties in cancer cells and can be targeted to suppress tumor growth.

Bacteriostasis and cleaning effect of trace ozone replacing personal care products.

Ozone is widely used to inactivate bacteria, fungi, and viruses. In recent years, the treatment of itchy skin diseases (eczema and atopic dermatitis) using trace ozone has also received attention. However, the feasibility of using trace ozone to replace personal care products (PCPs) has rarely been analyzed. In this study, the applicability of trace ozone was evaluated in terms of its efficiency for microbial inactivation in three types of skin microbiomes, cleaning performance on simulated human hair and epidermis, safety for simulated human hair, and contribution to emission reduction. The results revealed that at a 10:1 ratio of ozonated water to bacterial suspension, the inactivation ratios of Malassezia, C. albicans, and S. epidermidis reached 99.63%, 83.47%, and 100%, respectively. In addition, the cleaning performance of an ozone solution (0.4 mg/L) for simulated human skin contaminated with carbon black and sebum could reach 95.89% and 95.63%, respectively, with 5 min of washing. The average scores were 0.40 and 0.37 after 5 min and 10 min of ozone treatments, respectively, indicating that trace ozone does not significantly damage simulated human hair. Results also revealed that the total emissions of COD, TP, and TN would be reduced by 1.29×106, 3.55×103, and 3.63×103 mg/ (household · year), respectively, if PCPs are replaced by trace ozone. In short, our findings indicate that trace ozone is a potential alternative to PCPs. By replacing PCPs with trace ozone, the use of synthetic chemical products can be reduced and carbon emissions from oil extraction can be countered.