Atmospheric Trace Gas Oxidizers Contribute to Soil Carbon Fixation Driven by Key Soil Conditions in Terrestrial Ecosystems.

Microbial oxidizers of trace gases such as hydrogen (H2) and carbon monoxide (CO) are widely distributed in soil microbial communities and play a vital role in modulating biogeochemical cycles. However, the contribution of trace gas oxidizers to soil carbon fixation and the driving environmental factors remain unclear, especially on large scales. Here, we utilized biogeochemical and genome-resolved metagenomic profiling, assisted by machine learning analysis, to estimate the contributions of trace gas oxidizers to soil carbon fixation and to predict the key environmental factors driving this process in soils from five distinct ecosystems. The results showed that phylogenetically and physiologically diverse H2 and CO oxidizers and chemosynthetic carbon-fixing microbes are present in the soil in different terrestrial ecosystems. The large-scale variations in soil carbon fixation were highly positively correlated with both the abundance and the activity of H2 and CO oxidizers (p < 0.05-0.001). Furthermore, soil pH and moisture-induced shifts in the abundance of H2 and CO oxidizers partially explained the variation in soil carbon fixation (55%). The contributions of trace gas oxidizers to soil carbon fixation in the different terrestrial ecosystems were estimated to range from 1.1% to 35.0%. The estimated rate of trace gas carbon fixation varied from 0.04 to 1.56 mg kg-1 d-1. These findings reveal that atmospheric trace gas oxidizers may contribute to soil carbon fixation driven by key soil environmental factors, highlighting the non-negligible contribution of these microbes to terrestrial carbon cycling.

The roles of organic amendments and plant treatments in soil polychlorinated biphenyl dissipation under oxic and sequential anoxic-oxic conditions.

Understanding polychlorinated biphenyl (PCB) degradation in sequential anaerobic-aerobic remediation is crucial for effective remediation strategies. In this study, microcosm and greenhouse experiments were conducted to dissect the effects of organic amendments (carbon-based) and plant treatments (ryegrass) on soil PCB dissipation under oxic and sequential anoxic-oxic conditions. We analyzed the soil bacterial community in greenhouse experiments using high-throughput sequencing to explore plant-pollutant-microbe interactions. Microcosm results showed that organic amendments alone did not facilitate aerobic PCB removal, but significantly accelerated PCB dechlorination under anoxic conditions altering the profiles of PCB congeners. In standard greenhouses, plant treatments substantially increased PCB dissipation to 50.8 ± 3.9%, while organic amendments aided phytoremediation by promoting plant growth, increasing PCB removal to 65.9 ± 3.2%. In sequential anaerobic-aerobic greenhouses, plant growth was inhibited by flooding treatment while flooding stress was markedly alleviated by organic amendments. Plant treatments alone during sequential treatments did not lead to PCB dissipation; however, dissipation was significantly promoted following organic amendments, achieving a removal of 41.2 ± 5.7%. This PCB removal was primarily due to anaerobic dechlorination during flooding (27.8 ± 0.5% removal), rather than from plant growth stimulation in subsequent planting phase. Co-occurrence network and functional prediction analyses revealed that organic amendments recruited specific bacterial clusters with distinct functions under different conditions, especially stimulating plant-microbe interactions and xenobiotics biodegradation pathways in planted systems. The findings provide valuable guidance for the design of practical remediation strategies under various remedy scenarios, such as in arable or paddy fields.

The association between fat distribution and α1-acid glycoprotein levels among adult females in the United States.

BACKGROUND: Visceral fat accumulation and obesity-induced chronic inflammation have been proposed as early markers for multiple disease states, especially in women. Nevertheless, the potential impact of fat distribution on α1-acid glycoprotein(AGP), a marker of inflammation, remains unclear. This research was conducted to investigate the relationships among obesity, fat distribution, and AGP levels. METHODS: A cross-sectional observational study was performed using blood samples from adult females recruited through the National Health and Nutrition Examination Survey from 2015 to 2018. Serum levels of AGP were measured using the Tina-quant α-1-Acid Glycoprotein Gen.2 assay. Based on the fat distribution data obtained from dual-energy X-ray absorptiometry assessments, body mass index (BMI), total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android fat/gynoid fat ratio (AGR), visceral percent fat (VPF), subcutaneous percent fat (SPF), visceral fat/subcutaneous fat ratio (VSR) were used as dependent variables. To investigate the link between fat distribution and AGP, multivariate linear regression analysis was utilized. Furthermore, a sensitivity analysis was also performed. RESULTS: The present study included 2,295 participants. After adjusting for covariates, BMI, TPF, APF, GPF, VPF, and SPF were found to be positively correlated with AGP levels (BMI: ß = 23.65 95%CI:20.90-26.40; TPF: ß = 25.91 95%CI:23.02-28.80; APF: ß = 25.21 95%CI:22.49-27.93; GPF: ß = 19.65 95%CI:16.96-22.34; VPF: ß = 12.49 95%CI:9.08-15.90; SPF: ß = 5.69, 95%CI:2.89-8.49; AGR: ß = 21.14 95%CI:18.16-24.12; VSR: ß = 9.35 95%CI:6.11-12.59, all P < 0.0001). All the above indicators exhibited a positive dose-response relationship with AGP. In terms of fat distribution, both AGR and VSR showed positive associations with AGP (P for trend < 0.0001). In particular, when compared to individuals in tertile 1 of AGR, participants in tertiles 2 and 3 had 13.42 mg/dL (95% CI 10.66-16.18) and 21.14 mg/dL (95% CI 18.16-24.12) higher AGP levels, respectively. Participants in the highest tertile of VSR were more likely to exhibit a 9.35 mg/dL increase in AGP compared to those in the lowest tertile (95% CI 6.11-12.59). CONCLUSIONS: Overall, this study revealed a positive dose-dependent relationship between fat proportion/distribution and AGP levels in women. These findings suggest that physicians can associate abnormal serum AGP and obesity with allow timely interventions.

Long-term herbicide residues affect soil multifunctionality and the soil microbial community.

Residues of herbicides with the extensive applications may impact the soil ecosystem and ultimately threaten agricultural sustainability. However, the effects of long-term herbicide residues on soil multifunctionality and the soil microbial community remain poorly understood. Here, we evaluated relationships between soil multifunctionality and soil microbial communities with residual herbicide concentrations by surveying and analyzing 62 black soil samples collected from an agricultural area in northeastern China. Total residual herbicide concentrations varied from 35 to 568 µg/kg in the soil samples. The response of soil multifunctionality to increasing residual herbicide concentrations exhibited an inverted U-shaped relationship with a peak at approximately 310 µg/kg, with net mineralized organic nitrogen (Nm) and total nitrogen (TN) exhibiting the same trend. Microbial community richness was significantly lower in soil samples with high residual herbicide concentrations (> 310 µg/kg, HG) compared to low residual herbicide concentrations (< 310 µg/kg, LG). In addition, the relative abundances of specific keystone microbial genera differed significantly between LG and HG: norank_f_Acetobacteraceae, norank_f_Caldilineaceae, Candidatus_Alysiosphaera, and Gonytrichum. The relative abundances of these genera were also significantly correlated with soil multifunctionality. Structural equation models (SEMs) further showed that herbicide residues influenced soil multifunctionality by affecting these specific keystone genera. Our study demonstrates that long-term herbicide residues significantly impact the multifunctionality of agricultural black soil, where low concentrations stimulate while high concentrations inhibit, underscoring the need for reasonable application of herbicides to maintain soil ecosystem health.

Exploring bacterial community assembly in vadose and saturated zone soil for tailored bioremediation of a long-term hydrocarbon-contaminated site.

Indigenous soil microbial communities play a pivotal role in the in situ bioremediation of contaminated sites. However, research on the distribution characteristics of microbial communities at various soil depths remains limited. In particular, there is little information on the assembly of microbial communities, especially those with degradation potential, in the vadose and saturated zones of hydrocarbon-contaminated sites. In this study, 18 soil samples were collected from the vadose zone and saturated zone at a long-term hydrocarbon-contaminated site. The diversity, composition, and driving factors of assembly of the soil bacterial community were determined by high-throughput sequencing analysis. Species richness and diversity were significantly higher in the vadose zone soils than in the saturated zone soils. Significant differences in abundance at both the phylum and genus levels were observed between the two zones. Soil bacterial community assembly was driven by the combination of pollution stress and nutrients in the vadose zone but by nutrient limitations in the saturated zone. The abundance of dechlorinating bacteria was greater in the saturated zone soils than in the vadose zone soils. Compared with contaminant concentrations, nutrient levels had a more pronounced impact on the abundance of dechlorinating bacteria. In addition, the interactions among dechlorinating bacterial populations were stronger in the saturated zone soils than in the vadose zone soils. These findings underscore the importance of comprehensively understanding indigenous microbial communities, especially those with degradation potential, across different soil layers to devise specific, effective in situ bioremediation strategies for contaminated sites.

Identification of IGF2 promotes skin wound healing by co-expression analysis.

Oral mucosa is an ideal model for studying scarless wound healing. Researchers have shown that the key factors which promote scarless wound healing already exist in basal state of oral mucosa. Thus, to identify the other potential factors in basal state of oral mucosa will benefit to skin wound healing. In this study, we identified eight gene modules enriched in wound healing stages of human skin and oral mucosa through co-expression analysis, among which the module M8 was only module enriched in basal state of oral mucosa, indicating that the genes in module M8 may have key factors mediating scarless wound healing. Through bioinformatic analysis of genes in module M8, we found IGF2 may be the key factor mediating scarless wound healing of oral mucosa. Then, we purified IGF2 protein by prokaryotic expression, and we found that IGF2 could promote the proliferation and migration of HaCaT cells. Moreover, IGF2 promoted wound re-epithelialization and accelerated wound healing in a full-thickness skin wound model. Our findings identified IGF2 as a factor to promote skin wound healing which provide a potential target for wound healing therapy in clinic.

Legacy of herbicides in water from Hailun City, Northeast China: Occurrence, source, and ecological risk assessment.

Herbicides (HBCs) are extensively used in modern agriculture. However, their potential negative impacts on environmental media have emerged as a significant environmental concern. In this study, we employed positive matrix factorization (PMF) to identify the potential sources of HBCs. Furthermore, we utilized a multi-matrix ecological risk model to assess the risks associated with HBCs in both surface water and groundwater in the black soil region of Northeast China. The findings revealed that the levels of ∑15HBCs in surface water and groundwater ranged from 585.84 to 6466.96 ng/L and 4.80 to 11,774.64 ng/L, respectively. The PMF results indicated that surface runoff and erosion accounted for 50% of the total HBCs in water, serving as the primary sources. All tested HBCs exhibited acute risk values within acceptable levels. The risk index for the ∑15HBCs was categorized as "moderate risk" in 31% of the surface waters and 13% of the groundwaters. However, 4% of the groundwater sampling sites reached the "high risk" level. The chronic risk quotient of ∑15HBCs in surface water and groundwater was 92% and 62% at the "high risk" level, respectively. Interestingly, non-carcinogenic HBCs contributed more significantly to the ecotoxicology of the aquatic system than carcinogenic HBCs. This study provides comprehensive information on the legacy of HBCs in water bodies and emphasizes the potential risks posed by HBCs to aquatic systems. The results obtained from this study could help relevant management authorities in developing and implementing effective regulations to mitigate the ecological and environmental risks associated with HBCs.

Impact of climate factors and climate-gene interaction on systemic lupus erythematosus patients' response to glucocorticoids therapy.

BACKGROUND: Glucocorticoids (GCs) were the essential drugs for systemic lupus erythematosus (SLE). However, different patients differ substantially in their response to GCs treatment. Our current study aims at investigating whether climate variability and climate-gene interaction influence SLE patients' response to the therapy of GCs. METHODS: In total, 778 SLE patients received therapy of GCs for a study of 12-week follow-up. The efficacy of GCs treatment was evaluated using the Systemic Lupus Erythematosus Disease Activity Index. The climatic data were provided by China Meteorological Data Service Center. Additive and multiplicative interactions were examined. RESULTS: Compared with patients with autumn onset, the efficacy of GCs in patients with winter onset is relatively poor (ORadj = 1.805, 95%CIadj : 1.181-3.014, padj = 0.020). High mean relative humidity during treatment decreased the efficacy of GCs (ORadj = 1.033, 95%CIadj : 1.008-1.058, padj = 0.011), especially in female (ORadj = 1.039, 95%CIadj : 1.012-1.067, padj = 0.004). There was a significant interaction between sunshine during treatment and TRAP1 gene rs12597773 on GCs efficacy (Recessive model: AP = 0.770). No evidence of significant interaction was found between climate factors and the GR gene polymorphism on the improved GCs efficacy in the additive model. Multiplicative interaction was found between humidity in the month prior to treatment and GR gene rs4912905 on GCs efficacy (Dominant model: OR = 0.470, 95%CI: 0.244-0.905, p = 0.024). CONCLUSIONS: Our findings suggest that climate variability influences SLE patients' response to the therapy of GCs. Interactions between climate and TRAP1/GR gene polymorphisms were related to GCs efficacy. The results guide the individualized treatment of SLE patients.

Novel prospects for scarless wound healing: The roles of myofibroblasts and adipocytes.

Disturbances or defects in the process of wound repair can disrupt the delicate balance of cells and molecules necessary for complete wound healing, thus leading to chronic wounds or fibrotic scars. Myofibroblasts are one of the most important cells involved in fibrotic scars, and reprogramming provides a potential avenue to increase myofibroblast clearance. Although myofibroblasts have long been recognized as terminally differentiated cells, recent studies have shown that myofibroblasts have the capacity to be reprogrammed into adipocytes. This review intends to summarize the potential of reprogramming myofibroblasts into adipocytes. We will discuss myofibroblast lineage tracing, as well as the known mechanisms underlying adipocyte regeneration from myofibroblasts. In addition, we investigated different changes in myofibroblast gene expression, transcriptional regulators, signalling pathways and epigenetic regulators during skin wound healing. In the future, myofibroblast reprogramming in wound healing will be better understood and appreciated, which may provide new ideas for the treatment of scarless wound healing.

Insight into the role of dermal white adipose tissue loss in dermal fibrosis.

The loss of dermal white adipose tissue (dWAT) is vital to the formation of dermal fibrosis (DF), but the specific mechanism is not well understood. A few studies are reviewed to explore the role of dWAT in the formation of DF. Recent findings indicated that the adipocytes-to-myofibroblasts transition in dWAT reflects the direct contribution to the DF formation. While adipose-derived stem cells (ADSCs) contained in dWAT express antifibrotic cytokines, the loss of ADSCs leads to skin protection decreased, which indirectly exacerbates DF and tissue damage. Therefore, blocking or reversing the adipocytes-to-myofibroblasts transition or improving the survival of ADSCs in dWAT and the expression of antifibrotic cytokines may be an effective strategy for the treatment of DF.

Mitochondrial DNA genetic variants are associated with systemic lupus erythematosus susceptibility, glucocorticoids efficacy and prognosis.

OBJECTIVE: To investigate the associations of mitochondrial DNA (mtDNA) genetic variants with SLE susceptibility, glucocorticoid (GC) efficacy and prognosis. METHODS: Our study was done in two stages. First, we performed whole mitochondrial genome sequencing in 100 patients and 100 controls to initially screen potential mtDNA variants associated with disease and GC efficacy. Then, we validated the results in an independent set of samples. In total, 605 SLE patients and 604 normal controls were included in our two-stage study. A two-stage efficacy study was conducted in 512 patients treated with GCs for 12 weeks. We also explored the association between mtDNA variants and SLE prognosis. RESULTS: In the combined sample, four mtDNA variants (A4833G, T5108C, G14569A, CA514-515-) were associated with SLE susceptibility (all PBH < 0.05). We confirmed that T16362C was related to efficacy of GCs (PBH = 0.014). Significant associations were detected between T16362C and T16519C and the efficacy of GCs in females with SLE (PBH < 0.05). In the prognosis study, variants A4833G (PBH = 0.003) and G14569A (PBH = 9.744 × 10-4) substantially increased SLE relapse risk. Female patients harbouring variants T5108C and T16362C were more prone to relapse (PBH < 0.05). Haplotype analysis showed that haplogroup G was linked with SLE susceptibility (PBH = 0.001) and prognosis (PBH = 0.013). Moreover, mtDNA variant-environment interactions were observed. CONCLUSION: We identified novel mtDNA genetic variants that were associated with SLE susceptibility, GC efficacy, and prognosis. Interactions between mtDNA variants and environmental factors were related to SLE risk and GC efficacy. Our findings provide important information for future understanding of the occurrence and development of SLE.

Associations of RPEL1 and miR-1307 gene polymorphisms with disease susceptibility, glucocorticoid efficacy, anxiety, depression, and health-related quality of life in Chinese systemic lupus erythematosus patients.

OBJECTIVE: Our present study intended to examine the associations of RPEL1 and miR-1307 gene polymorphisms (rs4917385 and rs7911488) with susceptibility, glucocorticoids (GCs) efficacy, anxiety, depression, and health-related quality of life (HRQoL) in Chinese systemic lupus erythematosus (SLE) patients. METHODS: Initially, 1000 participants (500 SLE cases and 500 controls) were recruited for the case-control study. Then, 429 cases who received GCs were followed through 12 weeks to explore GCs efficacy, depression, anxiety, and HRQoL. We selected the iMLDR technique for genotyping: RPEL1: rs4917385 (G/T) and miR-1307: rs7911488 (A/G). RESULTS: The minor G allele of rs7911488 reduced the risk of SLE (p = .024). Four haplotypes consisting of rs4917385 and rs7911488 were associated with SLE susceptibility (p < .025). Both rs4917385 and rs7911488 were associated with anxiety symptoms and physical function (PF) in SLE patients (p < .025). The rs4917385 was associated with depression and its improvement. No statistical significance was found between RPEL1 and miR-1307 gene polymorphisms with GCs efficacy. Meanwhile, additive interaction analysis showed a significant association between RPEL1 and miR-1307 gene polymorphisms with tea consumption in anxiety. CONCLUSION: RPEL1 and miR-1307 gene polymorphisms (rs4917385 and rs7911488) might be related to SLE susceptibility in Chinese population. Additionally, the two polymorphisms were possibly associated with depression, anxiety, and HRQoL in Chinese SLE population.

Dominant roles of torrential floods and atmospheric deposition revealed by quantitative source apportionment of potentially toxic elements in agricultural soils around a historical mercury mine, Southwest China.

Hg pollution in soils surrounding the Wanshan mercury mine (WMM), once the largest Hg-producing center in China, has been confirmed, neglecting other potential toxic elements (PTEs). Better understanding of the sources and transport pathways of soil PTEs remains insufficient. To response these limitations, eight soil PTEs (As, Cd, Cr, Cu, Hg, Ni, Pb and Zn) at two typical agricultural sites, namely AZ and WW that are located near and far from the WMM, respectively, were systemically investigated. The results showed that AZ exhibited significantly higher concentrations of all the PTEs in the surface soil than WW (p < 0.01). Hg and Cd were recognized as the priority control PTEs, with their average concentrations of 21.54 and 1.21 mg kg-1 at AZ, and 15.79 and 0.48 mg kg-1 at WW. Those affected PTEs tended to enrich in near-river areas. Atmospheric deposition contributed more to soil Hg than did regular irrigation, but these two sources could not explain the considerable soil Hg accumulation. Three sources, including natural sources, hydraulic transport (torrential floods and regular irrigation) and atmospheric deposition, were identified and quantified based on the positive matrix factorization model, statistical methods and various auxiliary information. Hydraulic transport (mainly torrential floods) dominated the soil Hg input, which could explain 83.8% and 69.8% of the soil Hg input at AZ and WW, respectively. Atmospheric deposition dominated the soil Cd input, explaining 44.3% and 59.9% of the soil Cd input at AZ and WW, respectively. More attention should be given to the safe utilization of agricultural land and long-term monitoring of atmospheric deposition of Hg and Cd. This study could provide insights to prevent PTE diffusion along the above dominant transportation pathways while developing similar mine regions.

Ecological and human health risk assessment of heavy metals based on their source apportionment in cropland soils around an e-waste dismantling site, Southeast China.

An accurate understanding of soil heavy metal (HM) pollution characteristics and source apportionment, and a recognition of the major factors influencing ecological and human health risks (HHRs) are essential for soil HM pollution control and remediation. In this study, 212 surface soils (0-20 cm) and 15 profile soils (0-100 cm) were collected from cropland soils around an e-waste dismantling site in Taizhou city, Zhejiang Province, China. Spatial analysis was used to evaluate the pollution characteristics of HMs (Cd, Cu, Pb, Zn, Cr and Ni). Principal component analysis (PCA) and positive matrix factorization (PMF) were also conducted to quantify their source contributions. A modified source-oriented HHR assessment integrated source-oriented ecological risk and source-oriented HHR assessment was developed to describe the major factors that influenced HHR. Results showed that 94.81 %, 88.21 %, 36.79 % and 47.17 % of Cd, Cu, Pb and Zn, respectively, in surface soils exceeded their screening values in the soil environmental quality standard for agricultural soils (GB 15618-2018). Spatial analysis indicated that high values of Cd, Cu, Pb and Zn were distributed near the e-waste dismantling site. The results of PCA and PMF showed that the primary sources of HMs in the study area are e-waste dismantling activities, natural sources and atmospheric deposition, which contribute 27 %, 46 % and 27 % of HM pollutants, respectively. The results of source-oriented ecological risk and HHR assessment indicated that e-waste dismantling activities and natural sources were primary sources for ecological risk and HHR. However, source-oriented HHR assessment may underestimate the contribution of e-waste dismantling activities by ignoring HM pollution levels. The modified source-oriented HHR assessment highlights that e-waste dismantling activities were major factor that affect noncarcinogenic risk. This study could provide important data support for subsequent environmental remediation of soil HM pollution in cropland soils around e-waste dismantling sites.

Emerging Effects of Resveratrol on Wound Healing: A Comprehensive Review.

Resveratrol (RSV) is a natural extract that has been extensively studied for its significant anti-inflammatory and antioxidant effects, which are closely associated with a variety of injurious diseases and even cosmetic medicine. In this review, we have researched and summarized the role of resveratrol and its different forms of action in wound healing, exploring its role and mechanisms in promoting wound healing through different modes of action such as hydrogels, fibrous scaffolds and parallel ratio medical devices with their anti-inflammatory, antioxidant, antibacterial and anti-ageing properties and functions in various cells that may play a role in wound healing. This will provide a direction for further understanding of the mechanism of action of resveratrol in wound healing for future research.

Polycystic ovary syndrome and the risk of endometrial, ovarian and breast cancer: An updated meta-analysis.

BACKGROUND AND AIMS: This updated meta-analysis aimed to further quantify the risk of endometrial, ovarian, and breast cancer in patients with polycystic ovary syndrome (PCOS), thus providing updated and more reliable estimates. METHODS AND RESULTS: We identified relevant articles by searching electronic databases of PubMed, Embase, Web of Science, and Chinese Biological Medical Literature (CBM) published up to March 20, 2021. The pooled effect estimates and their 95% confidence intervals (CIs) were calculated using the random-effect model or the fixed-effect model. A total of 26 eligible studies were included. We found that PCOS was significantly associated with endometrial cancer (odds ratios [OR]: 3.66, 95%CI: 2.05-6.54, P < 0.001), but not with ovarian or breast cancer (OR: 1.23, 95%CI: 0.99-1.53, P = 0.059; OR: 0.94, 95%CI: 0.78-1.14, P = 0.551, respectively). However, in subgroups of high-quality studies, cohort studies, younger women (54 years or less or premenopausal), and studies with unadjusted body mass index (BMI), PCOS patients had a significantly higher risk of ovarian cancer. CONCLUSION: These results indicated that PCOS is a significant risk factor for endometrial cancer independent of BMI, but not for breast cancer. PCOS may increase the risk of ovarian cancer in younger women.

Insights into the role of adipose-derived stem cells: Wound healing and clinical regenerative potential.

The incidence of acute and chronic wound diseases is rising due to various reasons. With complicated pathogenesis, long course, difficult treatment and high disability, wound diseases have become a major burden for patients, their families, and society. Therefore, the focus of research is to identify new ideas and methods for treatment. Fat grafting has gained increased attention because of its effectiveness in wound treatment, and further analysis has uncovered that the stem cells derived from fat may be the main factor affecting wound healing. We summarize the function of adipose stem cells and analyze their possible mechanisms in tissue repair, helping to provide new ideas for the treatment of wound healing.

Transarterial chemoembolization plus lenvatinib versus transarterial chemoembolization plus sorafenib as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A prospective randomized study.

BACKGROUND: The efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) have not been evaluated. METHODS: In this open-label, single-center, randomized trial (ClinicalTrials.gov identifier: NCT04127396), participants with previously untreated HCC and type I-IV PVTT were randomized 1:1 to receive TACE plus lenvatinib (arm L; orally once daily, 12 mg for body weight ≥60 kg or 8 mg for body weight <60 kg) or TACE plus sorafenib (arm S; 400 mg orally twice daily in 28-day cycles). The primary end point was time-to-progression (TTP; time from randomization to disease progression) and secondary end points included objective response rate and toxicity. Prognostic factors were evaluated using a multivariable Cox proportional hazards model. RESULTS: Between December 30, 2018 and May 31, 2020, 64 patients were randomized (arm L, n = 32; arm S, n = 32); most patients had type I/II PVTT (71.9%), and the median target tumor diameter was 9.8 cm (range, 3.8-21.8). After a median follow-up of 16.1 months, patients in arm L had a higher median TTP (4.7 vs 3.1 months; hazard ratio [HR], 0.55; 95% CI, 0.32-0.95; P = .029) and objective response rate (53.1% vs 25.0%, P = .039) versus arm S. Multivariable analysis showed that TACE plus lenvatinib was significantly associated with higher TTP versus TACE plus sorafenib (HR, 0.50; 95% CI, 0.28-0.90; P = .021). Comparable safety profiles were observed in arms L and S. CONCLUSIONS: TACE plus lenvatinib was safe, well tolerated, and had favorable efficacy versus TACE plus sorafenib in patients with advanced HCC with PVTT and large tumor burden. LAY SUMMARY: Hepatocellular carcinoma with portal vein tumor thrombus has a poor prognosis. In addition, most phase 3 trials of drugs for hepatocellular carcinoma exclude patients with major portal vein invasion, and treatment options for these patients are limited. Transarterial chemoembolization has shown promising efficacy in these patients, especially in combination with systemic treatment or radiotherapy. However, transarterial chemoembolization plus lenvatinib has not been investigated in this setting. This open-label, single-center, randomized trial showed that transarterial chemoembolization plus lenvatinib is safe, well tolerated, and has favorable efficacy versus transarterial chemoembolization plus sorafenib for the treatment of hepatocellular carcinoma with portal vein tumor thrombus.

Peripheral Blood-Based DNA Methylation of Long Non-Coding RNA H19 and Metastasis-Associated Lung Adenocarcinoma Transcript 1 Promoters are Potential Non-Invasive Biomarkers for Gastric Cancer Detection.

INTRODUCTION: The early diagnosis and detection could greatly improve the clinical outcome of gastric cancer (GC) patients. However, the non-invasive biomarkers for GC detection remain to be identified. METHOD: We used online databases (GEPIA, UALCAN, Kaplan-Meier plotter, TIMER, and MEXPRESS) to explore the association between H19 or metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in tissues and the occurrence, development, prognosis, the levels of immune cell infiltration, and methylation of GC; the correlation between mRNA expression and DNA methylation levels of genes were also examined. Methylation levels of H19 or MALAT1 in peripheral blood were compared between 150 GC patients and 100 healthy controls (HCs). Predictive nomograms were constructed among female and male groups for GC diagnosis. The calibration curves, Hosmer-Lemeshow test, and decision curve analysis were also used to examine the nomograms' predictive ability and clinical values. RESULTS: Using multiple online databases, we found that the mRNA expressions of H19 and MALAT1 in tissues were related to the occurrence of GC, and such expressions were associated with immune cell infiltration of GC and negatively correlated with DNA methylation levels of H19 and MALAT1. H19 gene, H19C island, and MALAT1B island, as well as 20 CpG sites were hypermethylated in peripheral blood of GC patients compared with HCs; similar results were also found in female and male groups (P < .05 for all). The combination of H19c3, H19c4, MALAT1b12, and age, as well as the combination of H19b7, H19c1, H19c5, and age in the nomograms could distinguish GC patients from HCs in the female group and male group, respectively. CONCLUSION: We found statistically significant hypermethylation of H19 and MALAT1 promoters in GC patients, and meaningful sensitivity and specificity of MALAT1 and H19 methylation in discriminating GC and HCs were observed in both female and male groups, which indicates that the peripheral blood-based DNA methylation of H19 and MALAT1 could act as potential non-invasive biomarkers for the diagnosis of GC.

Interleukin-33 promotes proliferation and inhibits apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis.

OBJECTIVES: The aim of our study was to determine the effect of interleukin (IL)-33 on the proliferation, apoptosis, and secretion of inflammatory cytokines by fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) and to investigate the underlying mechanisms. METHODS: Cultured RA FLSs and osteoarthritis (OA) FLSs were cocultured with different concentrations of IL-33. TUNEL assay and flow cytometry were used to detect apoptosis. Western blotting and Real-time (RT)-PCR were used to detect the expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), while the Cell Counting Kit-8 was used to determine cell proliferation in each cocultured group. Enzyme-linked immunosorbent assay was used to detect the expression levels of tumour necrosis factor (TNF)-α and IL-6 in the supernatant from each cell culture. Western blot analysis was used to determine the phosphorylated expression levels of the nuclear factor-kappa light chain enhancer of the activated B cells (NF-κB) pathway in each group. RESULTS: IL-33 inhibited RA FLS apoptosis, promoted FLS proliferation, increased Bcl-2 protein expression levels, and decreased Bax protein expression levels. It also increased the expression levels of inflammatory cytokines TNF-α and IL-6 and increased the expression levels of P-NF-κ B in FLSs. CONCLUSIONS: IL-33 inhibited apoptosis and promoted proliferation of FLSs; in addition, IL-33 increased the serum levels of inflammatory cytokines. The effect of IL-33 on RA FLSs was likely mediated via the NF-κB pathway.