P4HA2 promotes tumor progression and is transcriptionally regulated by SP1 in colorectal cancer.

P4HA2 has been implicated in various malignant tumors; however, its expression and functional role in colorectal cancer (CRC) remain poorly elucidated. This study aims to investigate the involvement of P4HA2 in CRC metastasis and progression, uncovering the underlying mechanisms. In colorectal cancer (CRC), P4HA2 exhibited overexpression, and elevated levels of P4HA2 expression were associated with an unfavorable prognosis. Functional assays demonstrated P4HA2's regulation of cell proliferation, and epithelial-mesenchymal transition (EMT) both in vitro and in vivo. Additionally, the AGO1 expression was correlated with P4HA2, and depletion of AGO1 reversed the proliferation and EMT function induced by P4HA2. Chromatin immunoprecipitation (ChIP) and luciferase assays suggested that the transcription factor SP1 binds to the promoter sequence of P4HA2, activating its expression in CRC. This study unveiled SP1 as a transcriptional regulator of P4HA2 in CRC and AGO1 is a probable target of P4HA2. In conclusion, P4HA2 emerges as a potential prognostic biomarker and promising therapeutic target in colorectal cancer.

Comprehensive Proteogenomic Profiling Reveals the Molecular Characteristics of Colorectal Cancer at Distinct Stages of Progression.

Colorectal cancer (CRC) is the second most common malignant tumor world-wide. Analysis of the changes that occur during CRC progression could provide insights into the molecular mechanisms driving CRC development and identify improved treatment strategies. Here, we performed an integrated multi-omics analysis of 435 trace-tumor-samples from 148 colorectal cancer (CRC) patients, covering non-tumor (NT), intraepithelial neoplasia (IEN), infiltration (IFT), and advanced-stage CRC (A-CRC) phases. Proteogenomics analyses demonstrated that KRAS and BRAF mutations were mutually exclusive and elevated oxidation phosphorylation in the IEN phase. Chr17q loss and chr20q gain were also mutually exclusive, occurred predominantly in the IEN and IFT phases, respectively, and impacted the cell cycle. Mutation of TP53 was frequent in the A-CRC phase and associated with tumor microenvironment, including increased extracellular matrix rigidity and stromal infiltration. Analysis of the profiles of CRC based on CMS and CRIS classifications revealed the progression paths of each subtype and indicated that microsatellite instability was associated with specific subtype classifications. Additional comparison of molecular characteristics of CRC based on location showed that ANKRD22 amplification by chr10q23.31 gain enhanced glycolysis in the right-sided CRC. The AOM/DSS-induced CRC carcinogenesis mouse model in mice indicated that DDX5 deletion due to chr17q loss promoted CRC development, consistent with the findings from the patient samples. Collectively, this study provides an informative resource for understanding the driving events of different stages of CRC and identifying the potential therapeutic targets.

Aspirin-Mediated Acetylation of SIRT1 Maintains Intestinal Immune Homeostasis.

Aspirin, also named acetylsalicylate, can directly acetylate the side-chain of lysine in protein, which leads to the possibility of unexplained drug effects. Here, the study used isotopic-labeling aspirin-d3 with mass spectrometry analysis to discover that aspirin directly acetylates 10 HDACs proteins, including SIRT1, the most studied NAD+-dependent deacetylase. SIRT1 is also acetylated by aspirin in vitro. It is also identified that aspirin directly acetylates lysine 408 of SIRT1, which abolishes SIRT1 deacetylation activity by impairing the substrates binding affinity. Interestingly, the lysine 408 of SIRT1 can be acetylated by CBP acetyltransferase in cells without aspirin supplement. Aspirin can inhibit SIRT1 to increase the levels of acetylated p53 and promote p53-dependent apoptosis. Moreover, the knock-in mice of the acetylation-mimic mutant of SIRT1 show the decreased production of pro-inflammatory cytokines and maintain intestinal immune homeostasis. The study indicates the importance of the acetylated internal functional site of SIRT1 in maintaining intestinal immune homeostasis.

Unveiling NRlncRNAs as prognostic biomarkers and therapeutic targets for head-and-neck squamous cell carcinoma through machine learning.

Head-and-neck squamous cell carcinoma (HNSCC) patients often exhibit insensitivity to immunotherapy, leading to treatment failure. Identifying potential biomarkers that can predict prognosis and improve the efficacy of treatment is crucial. In this study, we aimed to identify necroptosis-related long noncoding RNAs (NRlncRNAs) as potential therapeutic targets to improve the prognosis of HNSCC patients. By exploring the Genotype-Tissue Expression Project (GTEx) and the Cancer Genome Atlas (TCGA) databases, we identified NRlncRNAs and developed a risk model comprising 17 NRlncRNAs to predict the prognosis of HNSCC patients and to classify patients into two clusters based on their expression levels. We conducted various analyses, such as the Kaplan-Meier analysis, GSEA and IC50 prediction, to evaluate the differences in sensitivity to immunotherapy between the two clusters. Our findings suggest that NRlncRNAs have potential as therapeutic targets for improving the prognosis of HNSCC patients, and that individualized treatment approaches based on NRlncRNA expression levels can improve the sensitivity of immunotherapy and overall treatment outcomes. This study highlights new perspectives within clinical cancer informatics and provides insight into potential therapeutic strategies for HNSCC patients.

Unravelling chilling-stress resistance mechanisms in endangered Mangrove plant Lumnitzera littorea (Jack) Voigt.

Lumnitzera littorea (Jack) Voigt is one of the most endangered mangrove species in China. Previous studies have showed the impact of chilling stress on L. littorea and the repsonses at physiological and biochemical levels, but few attentions have been paid at molecular level. In this study, we conducted genome-wide investigation of transcriptional and post-transcriptional dynamics in L. littorea in response to chilling stress (8 °C day/5 °C night). In the seedlings of L. littorea, chilling sensing and signal transducing, photosystem II regeneration and peroxidase-mediated reactive oxygen species (ROS) scavenging were substantially enhanced to combat the adverse impact induced by chilling exposure. We further revealed that alternative polyadenylation (APA) events participated in chilling stress-responsive processes, including energy metabolism and steroid biosynthesis. Furthermore, APA-mediated miRNA regulations downregulated the expression of the genes involved in fatty acid biosynthesis and elongation, and protein phosphorylation, reflecting the important role of post-transcriptional regulation in modulating chilling tolerance in L. littorea. Our findings present a molecular view to the adaptive characteristics of L. littorea and shed light on the conservation genomic approaches of endangered mangrove species.

CERCAM is a prognostic biomarker associated with immune infiltration of macrophage M2 polarization in head and neck squamous carcinoma.

PURPOSE: This study aimed to investigate the relevance of cerebral endothelial cell adhesion molecule (CERCAM) expression to head and neck squamous cell carcinoma (HNSCC) prognosis and immune infiltration by macrophage M2 polarization. METHODS: Timer, UALCAN and HPA databases was used to analyze the differences in mRNA and protein levels of CERCAM expression in HNSCC. The Timer database was also applied to analyze the correlation between CERCAM in HNSCC and immune infiltration. TCGA-HNSCC database was applied to analyze the correlation between CERCAM expression levels and clinicopathological features, and its diagnostic and prognostic value in HNSCC was also assessed. The cBioPortal and MethSurv databases were then applied to analyze the genetic variation and methylation status of CERCAM. In vitro cellular assays were performed to provide evidence that CERCAM promotes malignant biological behavior of tumors and promotes macrophage M2 polarization in tumors. Finally, underlying pathophysiological mechanisms of CERCAM involvement in the development of HNSCC were predicted using a bioinformatics approach. RESULTS: CERCAM is significantly overexpressed in HNSCC and correlates with poor prognostic levels and has good performance in predicting survival status in HNSCC patients. Cox regression analysis indicates that CERCAM expression levels are independent risk factors for predicting OS, DSS, and PFI. CERCAM promotes tumor malignant biological behavior and promotes macrophage M2 polarization immune infiltration in HNSCC. In addition, CERCAM promotes tumor cell adhesion in head and neck squamous carcinoma and promotes tumor progression through several oncogenic signaling pathways. CONCLUSION: CERCAM may serve as a new diagnostic and prognostic biomarker in HNSCC and is a promising therapeutic target for HNSCC.

Arsenic speciation in freshwater fish: challenges and research needs.

Food and water are the main sources of human exposure to arsenic. It is important to determine arsenic species in food because the toxicities of arsenic vary greatly with its chemical speciation. Extensive research has focused on high concentrations of arsenic species in marine organisms. The concentrations of arsenic species in freshwater fish are much lower, and their determination presents analytical challenges. In this review, we summarize the current state of knowledge on arsenic speciation in freshwater fish and discuss challenges and research needs. Fish samples are typically homogenized, and arsenic species are extracted using water/methanol with the assistance of sonication and enzyme treatment. Arsenic species in the extracts are commonly separated using high-performance liquid chromatography (HPLC) and detected using inductively coupled plasma mass spectrometry (ICPMS). Electrospray ionization tandem mass spectrometry, used in combination with HPLC and ICPMS, provides complementary information for the identification and characterization of arsenic species. The methods and perspectives discussed in this review, covering sample preparation, chromatography separation, and mass spectrometry detection, are directed to arsenic speciation in freshwater fish and applicable to studies of other food items. Despite progress made in arsenic speciation analysis, a large fraction of the total arsenic in freshwater fish remains unidentified. It is challenging to identify and quantify arsenic species present in complex sample matrices at very low concentrations. Further research is needed to improve the extraction efficiency, chromatographic resolution, detection sensitivity, and characterization capability.

Amorphous Transparent Cu(S,I) Thin Films with Very High Hole Conductivity.

Amorphous transparent conductors (a-TCs) are key materials for flexible and transparent electronics but still suffer from poor p-type conductivity. By developing an amorphous Cu(S,I) material system, record high hole conductivities of 103-104 S cm-1 have been achieved in p-type a-TCs. These high conductivities are comparable with commercial n-type TCs made of indium tin oxide and are 100 times greater than any previously reported p-type a-TCs. Responsible for the high hole conduction is the overlap of large p-orbitals of I- and S2- anions, which provide a hole transport pathway insensitive to structural disorder. In addition, the bandgap of amorphous Cu(S,I) can be modulated from 2.6 to 2.9 eV by increasing the iodine content. These unique properties demonstrate that the Cu(S,I) system holds great potential as a promising p-type amorphous transparent electrode material for optoelectronics.

Quantifying the spatial spillover effects of non-pharmaceutical interventions on pandemic risk.

BACKGROUND: Non-pharmaceutical interventions (NPIs) implemented in one place can affect neighboring regions by influencing people's behavior. However, existing epidemic models for NPIs evaluation rarely consider such spatial spillover effects, which may lead to a biased assessment of policy effects. METHODS: Using the US state-level mobility and policy data from January 6 to August 2, 2020, we develop a quantitative framework that includes both a panel spatial econometric model and an S-SEIR (Spillover-Susceptible-Exposed-Infected-Recovered) model to quantify the spatial spillover effects of NPIs on human mobility and COVID-19 transmission. RESULTS: The spatial spillover effects of NPIs explain [Formula: see text] [[Formula: see text] credible interval: 52.8-[Formula: see text]] of national cumulative confirmed cases, suggesting that the presence of the spillover effect significantly enhances the NPI influence. Simulations based on the S-SEIR model further show that increasing interventions in only a few states with larger intrastate human mobility intensity significantly reduce the cases nationwide. These region-based interventions also can carry over to interstate lockdowns. CONCLUSIONS: Our study provides a framework for evaluating and comparing the effectiveness of different intervention strategies conditional on NPI spillovers, and calls for collaboration from different regions.

Dramatic decline of observed atmospheric CO2 and CH4 during the COVID-19 lockdown over the Yangtze River Delta of China.

The temporal variation of greenhouse gas concentrations in China during the COVID-19 lockdown in China is analyzed in this work using high resolution measurements of near surface △CO2, △CH4 and △CO concentrations above the background conditions at Lin'an station (LAN), a regional background station in the Yangtze River Delta region. During the pre-lockdown observational period (IOP-1), both △CO2 and △CH4 exhibited a significant increasing trend relative to the 2011-2019 climatological mean. The reduction of △CO2, △CH4 and △CO during the lockdown observational period (IOP-2) (which also coincided with the Chinese New Year Holiday) reached up to 15.0 ppm, 14.2 ppb and 146.8 ppb, respectively, and a reduction of △CO2/△CO probably due to a dramatic reduction from industrial emissions. △CO2, △CH4 and △CO were observed to keep declining during the post-lockdown easing phase (IOP-3), which is the synthetic result of lower than normal CO2 emissions from rural regions around LAN coupled with strong uptake of the terrestrial ecosystem. Interestingly, the trend reversed to gradual increase for all species during the later easing phase (IOP-4), with △CO2/△CO constantly increasing from IOP-2 to IOP-3 and finally IOP-4, consistent with recovery in industrial emissions associated with the staged resumption of economic activity. On average, △CO2 declined sharply throughout the days during IOP-2 but increased gradually throughout the days during IOP-4. The findings showcase the significant role of emission reduction in accounting for the dramatic changes in measured atmospheric △CO2 and △CH4 associated with the COVID-19 lockdown and recovery.

Expedient delivery of quinolinone drugs via a traceless N-nitroso enabled oxidative Heck/amidation cascade.

The exploration of green C-H oxidation for the rapid construction of functional molecules, remains a permanent goal in synthetic chemistry. Herein, a traceless N-nitroso enabled oxidative Heck and amidation cascade was realized, leading to quinolinones that feature green oxidation and great functional group tolerance. The expedient construction of quinolinone containing pharmaceuticals including Flucarbril, Clostamide and Aripiprazole was achieved in a concise and environmentally friendly manner.

Preparation and mechanism of lightweight wood fiber/poly(lactic acid) composites.

The high density and poor thermal insulation of traditional wood-plastic composites limited the application in the field of building materials. In this paper, wood fiber (WF) and PLA were used as raw materials and azodicarbonamide was used as the foaming agent. Lightweight WF/PLA composites were prepared by the hot-pressing foaming method, aiming to obtain renewable, low-density material with high strength-to-weight ratio and thermal insulation performance. The results showed that after adding 20 % WF into PLA, the cell morphology was excellent and the cell size was uniform. The magnification reached the minimum value of 0.36 g/cm3 and the foaming magnification was 3.42 times. The impact strength and compressive strength were 3.16 kJ/m3 and 4.12 MPa, its comprehensive mechanical properties were outstanding. The thermal conductivity of foamed materials was 0.110-0.148 (W/m·K), which was significantly lower than that of unfoamed materials and common wood. Its excellent mechanical properties and thermal insulation can be suitable for application in the construction field to replace traditional wood.

Solar-assisted self-heating Ti3C2Tx-decorated wood aerogel for adsorption and recovery of highly viscous crude oil.

Frequent oil-spill accidents have posed serious threats to ecosystem balance and the efficiency of resources use. Hydrophobic adsorbents that can adsorb and recover oil without causing secondary pollution are ideal candidates for the remediation of oil contamination in water. However, these composites are inefficient for crude oil-spills cleanup because crude oil has low liquidity of at room temperature. Increasing the temperature can effectively enhance the flowability of crude oil. To achieve efficient crude-oil heating and removal in situ, wood aerogels were immersed in Ti3C2Tx suspensions and then coated with polydimethylsiloxane (PDMS) to obtain a solar-heated adsorbent (PT-WA). The prepared PT-WA exhibits super-hydrophobicity (water contact angle: 154° ± 2°), mechanical robustness (withstanding 20 loading-unloading cycles under 50% strain without structural damage), strong solar absorption, and favorable photothermal-conversion capability (rising to ~85 °C within 90 s under 1.5 sun). Owing to these advantages, PT-WA is an effective adsorbent for crude oil cleanup. In addition, a 'self-heating crude oil collector' was assembled for the fast adsorption and restoration of crude oil from the water surface. This solar-assisted self-heating sorbent offers a competitive platform for the cleanup and recycling of viscous crude oil spills.

Comparison of Properties of Poly(Lactic Acid) Composites Prepared from Different Components of Corn Straw Fiber.

In recent years, under the pressure of resource shortage and white pollution, the development and utilization of biodegradable wood-plastic composites (WPC) has become one of the hot spots for scholars' research. Here, corn straw fiber (CSF) was chosen to reinforce a poly(lactic acid) (PLA) matrix with a mass ratio of 3:7, and the CSF/PLA composites were obtained by melt mixing. The results showed that the mechanical properties of the corn straw fiber core (CSFC) and corn straw fiber skin (CSFS) loaded PLA composites were stronger than those of the CSFS/PLA composites when the particle size of CSF was low. The tensile strength and bending strength of CSFS/CSFC/PLA are 54.08 MPa and 87.24 MPa, respectively, and the elongation at break is 4.60%. After soaking for 8 hours, the water absorption of CSF/PLA composite reached saturation. When the particle size of CSF is above 80 mesh, the saturated water absorption of the material is kept below 7%, and CSF/PLA composite has good hydrophobicity, which is mainly related to the interfacial compatibility between PLA and CSF. By observing the microstructure of the cross section of the CSF/PLA composite, the research found that the smaller the particle size of CSF, the smoother the cross section of the composite and the more unified the dispersion of CSF in PLA. Therefore, exploring the composites formed by different components of CSF and PLA can not only expand the application range of PLA, but also enhance the application value of CSF in the field of composites.

Different human papillomavirus types share early natural history transitions in immunocompetent women.

Necessary stages of cervical carcinogenesis include acquisition of a carcinogenic human papillomavirus (HPV) type, persistence associated with the development of precancerous lesions, and invasion. Using prospective data from immunocompetent women in the Guanacaste HPV Natural History Study (NHS), the ASCUS-LSIL Triage Study (ALTS) and the Costa Rica HPV Vaccine Trial (CVT), we compared the early natural history of HPV types to inform transition probabilities for health decision models. We excluded women with evidence of high-grade cervical abnormalities at any point during follow-up and restricted the analysis to incident infections in all women and prevalent infections in young women (aged <30 years). We used survival approaches accounting for interval-censoring to estimate the time to clearance distribution for 20 529 HPV infections (64% were incident and 51% were carcinogenic). Time to clearance was similar across HPV types and risk classes (HPV16, HPV18/45, HPV31/33/35/52/58, HPV 39/51/56/59 and noncarcinogenic HPV types); and by age group (18-29, 30-44 and 45-54 years), among carcinogenic and noncarcinogenic infections. Similar time to clearance across HPV types suggests that relative prevalence can predict relative incidence. We confirmed that there was a uniform linear association between incident and prevalent infections for all HPV types within each study cohort. In the absence of progression to precancer, we observed similar time to clearance for incident infections across HPV types and risk classes. A singular clearance function for incident HPV infections has important implications for the refinement of microsimulation models used to evaluate the cost-effectiveness of novel prevention technologies.

Contribution of Etiologic Cofactors to CIN3+ Risk Among Women With Human Papillomavirus-Positive Screening Test Results.

OBJECTIVE: The US screening and management guidelines for cervical cancer are based on the absolute risk of precancer estimated from large clinical cohorts and trials. Given the widespread transition toward screening with human papillomavirus (HPV) testing, it is important to assess which additional factors to include in clinical risk assessment to optimize management of HPV-infected women. MATERIALS AND METHODS: We analyzed data from HPV-infected women, ages 30-65 years, in the National Cancer Institute-Kaiser Permanente Northern California Persistence and Progression study. We estimated the influence of HPV risk group, cytology result, and selected cofactors on immediate risk of cervical intraepithelial neoplasia grade 3 or higher (CIN 3+) among 16,094 HPV-positive women. Cofactors considered included, age, race/ethnicity, income, smoking, and hormonal contraceptive use. RESULTS: Human papillomavirus risk group and cytology test result were strongly correlated with CIN 3+ risk. After considering cytology and HPV risk group, other cofactors (age, race/ethnicity, income, smoking, and hormonal contraceptive use) had minimal impact on CIN 3+ risk and did not change recommended management based on accepted risk thresholds. We had insufficient data to assess the impact of long-duration heavy smoking, parity, history of sexually transmitted infection, or immunosuppression. CONCLUSIONS: In our study at the Kaiser Permanente Northern California, the risk of CIN 3+ was determined mainly by HPV risk group and cytology results, with other cofactors having limited impact in adjusted analyses. This supports the use of HPV and cytology results in risk-based management guidelines.

Preparation of glycidyl methacrylate grafted starch adhesive to apply in high-performance and environment-friendly plywood.

In this paper, cassava starch was used as the main raw material to prepare high performance and environment-friendly starch-based adhesive. Starch was grafted with glycidyl methacrylate (GMA), and then cross-linked with sodium trimetaphosphate (STMP). Before preparation of plywood, polyaryl polymethylene isocyanate (PAPI) was mixed as chain extension agent. Prepared starch adhesives are used in wood-based panel applications. From the Fourier transform infrared (FTIR) analysis, it was found that GMA was successfully grafted to the starch adhesives which improved the hydrophobicity and shear strength of the adhesive. The plywood using modified starch adhesive at pH 4.50-5.50 showed the highest wet shear strength, 1.00 MPa, which was 163% higher than that using unmodified starch adhesive. The Scanning electron microscopy (SEM) results showed that the original morphology of starch particles were destroyed and became smaller during GMA grafting, which made the modified starch-based adhesive easier to penetrate into the bonding interface of plywood. The characterization results of the adhesive film also showed that the mechanical properties of the adhesive were better when the grafting reaction pH was 4.50-5.50. Graft copolymerization modification of starch improves the hydrophobic properties of starch binders.

Human adipose tissue-derived MSCs improve psoriasis-like skin inflammation in mice by negatively regulating ROS.

BACKGROUND: Psoriasis is chronic incurable skin inflammation. The anti-inflammatory properties of mesenchymal stem cells (MSCs) have been put forward to be involved in several inflammatory diseases. However, little was known about the role of human adipose tissue-derived stem cells (hAD-MSCs) in psoriasis. OBJECTIVE: We sought to explore the feasibility of using hAD-MSCs infusion as a therapeutic approach in psoriatic mice. METHODS: We constructed the psoriasis-like model by IMQ implication, treated with hAD-MSCs by subcutaneous injection. To evaluate the efficacy, we examined the histology, CD45 and ROS positive cells by HE and flow cytometry respectively. We also tested the key cytokines with PCR. Moreover, to achieve a better therapeutic effect, we treated the model by combing with vitamin E application. RESULTS: We found that the classic histological symptoms of psoriasis were relieved after treatment with hAD-MSCs, also, the splenic index, the infiltration of immune cells and several pro-inflammatory cytokines were decreased. Interestingly, we also found that hAD-MSCs could inhibit ROS generation. Moreover, the combination therapy of hAD-MSCs and vitamin E could promote the curative effect with greater ROS inhibition. CONCLUSION: These results suggested that hAD-MSCs could be useful for treating psoriasis by negatively regulating ROS.

Effective Doses of Nalbuphine Combined With Propofol for Painless Gastroscopy in Adults: A Randomized Controlled Trial.

Objective: This prospective study evaluated the 50% effective dose (ED50) and 95% effective dose (ED95) of nalbuphine combined with propofol during painless gastroscopy. Methods: Seventy-five patients who underwent painless gastroscopy were randomly divided into five groups (group N0, N0.05, N0.1, N0.15, and N0.2), with doses of 0, 0.05, 0.1, 0.15, or 0.2 mg/kg nalbuphine in each group. Propofol was given to all groups as the sedative. The bispectral index (BIS) value, propofol dose, examination time, and awakening time were recorded. The number of patients with intolerance indexes (coughing, retching, swallowing, or limb movement) was recorded in each group. The ED50/ED95 of nalbuphine combined with propofol for gastroscopy were calculated. Results: Compared with those of groups N0, N0.05, or N0.1, the propofol dose and awakening time were significantly reduced in group N0.15 or N0.2 (p < 0.05). The successful rate of painless gastroscopy in group N0.15 or N0.2 significantly increased compared to that of group N0 or N0.05 (p < 0.05). When combined with propofol, nalbuphine had an ED50 and ED95 for painless gastroscopy of 0.078 mg/kg (95% CI, 0.056-0.098 mg/kg) and 0.162 mg/kg (95% CI, 0.134-0.217 mg/kg), respectively. Conclusion: The ED50/ED95 of nalbuphine combined with propofol are 0.078 and 0.162 mg/kg, respectively, for painless gastroscopy. Nalbuphine at 0.162 mg/kg combined with propofol is effective and safe for painless gastroscopy in adults.