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Abstract 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: β = 23.65 95%CI:20.90–26.40; TPF: β = 25.91 95%CI:23.02–28.80; APF: β = 25.21 95%CI:22.49–27.93; GPF: β = 19.65 95%CI:16.96–22.34; VPF: β = 12.49 95%CI:9.08–15.90; SPF: β = 5.69, 95%CI:2.89–8.49; AGR: β = 21.14 95%CI:18.16–24.12; VSR: β = 9.35 95%CI:6.11–12.59, all P

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.

The purpose of this study was to assess the influence and the clinical effectiveness of the short stature homeobox 2 (SHOX2) and ras association domain family 1A (RASSF1A) genes by tissue sampling through ultrasound endoscopy-guided fine-needle aspiration (EUS-FNA) as auxiliary diagnostic tools for pancreatic cancer (PC). Methylation markers were detected in 96 patients using real-time fluorescence quantitative PCR (qPCR), and the performance of this diagnostic assay was compared with CA19-9, CEA, and puncture fluid-based exfoliative cytology using receiver operating characteristic curve (ROC) analysis. The PC group exhibited higher methylation rates for SHOX2, RASSF1A, and the combined assay of both genes compared to the control group (95.7 % vs. 54.0 %, 78.3 % vs. 36.0 %, and 73.9 % vs. 16.0 %, P

Abstract Background and aims Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) predicts a poor prognosis. The aim of the present study was to evaluate the efficacy and safety of using lenvatinib and camrelizumab combined with transarterial chemoembolization (TACE) to treat HCC with PVTT. Methods This was a single‐arm, open‐label, multicenter, and prospective study. Eligible patients with advanced HCC accompanied by PVTT were enrolled to receive TACE combined with lenvatinib and camrelizumab. The primary endpoint was progression‐free survival (PFS), while the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results Between April 2020 and April 2022, 69 patients were successfully enrolled. With a median follow‐up time of 17.3 months, the median age of the patient cohort was 57 years (range: 49–64 years). According to modified Response Evaluation Criteria in Solid Tumors, the ORR was 26.1% (18 partial responses [PRs]) and the DCR was 78.3% (18 PRs, 36 stable diseases [SDs]). The median PFS (mPFS) and median OS (mOS) were 9.3 and 18.2 months, respectively. And tumor number >3 was identified as an adverse risk factor for both PFS and OS. The most common adverse events across all grades included fatigue (50.7%), hypertension (46.4%), and diarrhea (43.5%). Twenty‐four patients (34.8%) experienced Grade 3 toxicity that was relieved by dose adjustment and symptomatic treatment. No treatment‐related deaths occurred. Conclusions TACE combined with lenvatinib and camrelizumab is a well‐tolerated modality treatment with promising efficacy for advanced HCC with PVTT.

Diabetic foot ulcers (DFU) and cutaneous lupus erythematosus (CLE) are both diseases that can seriously affect a patient’s quality of life and generate economic pressure in society. Symptomatically, both DLU and CLE exhibit delayed healing and excessive inflammation; however, there is little evidence to support a molecular and cellular connection between these two diseases. In this study, we investigated potential common characteristics between DFU and CLE at the molecular level to provide new insights into skin diseases and regeneration, and identify potential targets for the development of new therapies. The gene expression profiles of DFU and CLE were obtained from the Gene Expression Omnibus (GEO) database and used for analysis. A total of 41 common differentially expressed genes (DEGs), 16 upregulated genes and 25 downregulated genes, were identified between DFU and CLE. GO and KEGG analysis showed that abnormalities in epidermal cells and the activation of inflammatory factors were both involved in the occurrence and development of DFU and CLE. Protein-protein interaction network (PPI) and sub-module analysis identified enrichment in seven common key genes which is KRT16, S100A7, KRT77, OASL, S100A9, EPGN and SAMD9. Based on these seven key genes, we further identified five miRNAs(has-mir-532-5p, has-mir-324-3p,has-mir-106a-5p,has-mir-20a-5p,has-mir-93-5p) and7 transcription factors including CEBPA, CEBPB, GLI1, EP30D, JUN,SP1, NFE2L2 as potential upstream molecules. Functional immune infiltration assays showed that these genes were related to immune cells. The CIBERSORT algorithm and Pearson method were used to determine the correlations between key genes and immune cells, and reverse key gene-immune cell correlations were found between DFU and CLE. Finally, the DGIbd database demonstrated that Paquinimod and Tasquinimod could be used to target S100A9 and Ribavirin could be used to target OASL. Our findings highlight common gene expression characteristics and signaling pathways between DFU and CLE, indicating a close association between these two diseases. This provides guidance for the development of targeted therapies and mutual interactions.

Inadequate information sharing and difficult information diffusion are the main factors that cause upstream and downstream enterprises to default on supply chain finance. Blockchain technology, which exploits distributed storage and a consensus mechanism, can provide effective solutions to overcome these problems such as information sharing. When blockchain technology is adopted by the enterprises that comprise the supply chain finance business, this technology shows a diffusion trend. As a result, the decision pertaining to the application of novel technologies is affected. Therefore, to investigate the diffusion mechanism pertaining to the blockchain technology that is applied in supply chain finance, the study exploited the idea of a class of SEIR infectious disease models, and built a blockchain model that considers the supply chain financial system. Besides, the study verifies the stability of the model by constructing a Lyapunov function. The results indicate that the basic reproduction number determines the proliferation of the blockchain technology. When the basic reproduction number is less than 1, the proliferation of the blockchain technology that is applied in supply chain finance system would terminate. By contrast, when the basic reproduction number is greater than 1, during the average infection period, the number of non-adopting enterprises that accept the blockchain technology becomes greater than 1, which can maintain a continuous impact on supply chain finance system. Over time, the number of enterprises that accept blockchain technology tends to be stable. Through numerical simulations that consider the influencing parameters pertaining to the basic regeneration number, which has important effect on blockchain technology diffusion, we enlarge the diffusion efficiency and increase the transfer rate of potential on-chain enterprises or decrease the default exit rate. As a result, we facilitate the diffusion of blockchain technology in the system.

Endogenous hydrogen (H2) is produced through rhizobium-legume associations in terrestrial ecosystems worldwide through dinitrogen fixation. In turn, this gas may alter rhizosphere microbial community structure and modulate biogeochemical cycles. However, very little is understood about the role that this H2 leaking to the rhizosphere plays in shaping the persistent organic pollutants degrading microbes in contaminated soils. Here, we combined DNA-stable isotope probing (DNA-SIP) with metagenomics to explore how endogenous H2 from the symbiotic rhizobium-alfalfa association drives the microbial biodegradation of tetrachlorobiphenyl PCB 77 in a contaminated soil. The results showed that PCB77 biodegradation efficiency increased significantly in soils treated with endogenous H2. Based on metagenomes of 13C-enriched DNA fractions, endogenous H2 selected bacteria harboring PCB degradation genes. Functional gene annotation allowed the reconstruction of several complete pathways for PCB catabolism, with different taxa conducting successive metabolic steps of PCB metabolism. The enrichment through endogenous H2 of hydrogenotrophic Pseudomonas and Magnetospirillum encoding biphenyl oxidation genes drove PCB biodegradation. This study proves that endogenous H2 is a significant energy source for active PCB-degrading communities and suggests that elevated H2 can influence the microbial ecology and biogeochemistry of the legume rhizosphere.

The application of blockchain has become a trend in the development of supply chain finance. Aiming to bridge the gap in the existing literature, this paper investigates a supply chain finance system based on blockchain technology which contains a manufacturer, a retailer and a financial institution and incorporates blockchain costs into the model. Firstly, this paper establishes a supply chain finance model based on blockchain technology and it presents a comparison with the process employed under the traditional model. Secondly, this paper establishes the revenue mathematical model of supply chain finance based on blockchain technology. Thirdly, the optimal decisions of each participant under centralized and decentralized decision-making are proved and obtained, respectively, and the influencing factors of the optimal decisions are analyzed. Finally, the conclusions are verified via simulations. This study finds that, when blockchain is used, the benefits of each participant in the chain are increased. In addition, centralized decision-making, which is more optimal in the traditional model, is also enhanced under blockchain. This paper demonstrates the superiority of blockchain-enabled supply chain finance in terms of model and revenue. This provides some suggestions for companies in the supply chain with regard to solving the problem of financing difficulties.

Over the years, natural gas hydrates (NGHs) have attracted significant attention as an emerging energy resource. Microfluidics is a novel technology used to observe the behaviour of NGHs in microchannels directly and has been applied to hydrates. Gas hydrate distributions and phase transitions are key parameters for exploitation and application. In this paper, advances in related research with microfluidics-based technology are reviewed, including the hydrate phase transition process and its mechanism of influence. Hydrate formation and decomposition directly influence the efficiency and sustainability of exploitation. In addition, studies of the hydrate phase transition provide basic data for future commercial exploitation. Moreover, extended applications, further developments and potential improvements in microfluidic techniques are also discussed. We believe that with an improved understanding of the hydrate phase transition mechanism, commercial exploitation of hydrates can be expected soon.

Abstract Natural gas hydrate is regarded as a potential clean energy source. However, hydrate phase transition during gas production leads to significant hydrate‐bearing sedimentary layer deformation, which is one of the main obstacles for safe hydrate exploitation. In this study, distributed optical fiber sensors were used to examine the porous medium deformation induced by phase change and verify its feasibility for application in hydrate research. Experiments on ice formation in a porous medium were conducted to mimic the hydrate formation in sediments. Optical fiber sensors were used to record and analyze the strain characteristics caused by the deformation of porous medium during the phase change process. The frequency shift during the cooling process shows that the fiber segment sensitivity is influenced by its initial length and tightness. In experiments with porous medium, the strain caused by the phase change exhibited a linear trend. In a comparative experiment using pure water, the strain caused by the phase change showed a nonlinear trend. The results indicate that the porous medium deformation induced by phase change can be accurately evaluated using strain data from distributed optical fiber sensors. The strain results also reflect the rate of the phase change. This study proves that the distributed optical fiber sensor has the potential to clarify the deformation characteristics of porous medium caused by hydrate phase change.

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.

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

BackgroundPatients with advanced intrahepatic cholangiocarcinoma (iCCA) have a poor prognosis and a substantial unmet clinical need. The study was aimed to investigate the efficacy and safety of sintilimab combined with lenvatinib for advanced iCCA in second-line setting.MethodsThe patients at multiple centers, who progressed after the first-line chemotherapy or could not tolerate chemotherapy, were treated with the combination of sintilimab plus lenvatinib. The primary endpoint was time to progression (TTP), and the secondary endpoints included tumor objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Prognostic factors were analyzed using Cox regression analysis.ResultsA total of 41 patients with advanced iCCA were enrolled for this multi-center observational study. Under a median follow-up of 12.1 months, the median age was 59 years (range, 33–75 years). Sixteen patients died of disease progression, with a median TTP of 6.6 months (95% CI, 4.9–8.3). ORR and DCR were 46.3% and 70.3%, respectively. The patients with PD-L1 TPS ≥10% reported a significantly higher ORR compared to those with PD-L1 TPS

ABSTRACT Soil microbiota plays fundamental roles in maintaining ecosystem functions and services, including biogeochemical processes and plant productivity. Despite the ubiquity of soil microorganisms from the topsoil to deeper layers, their vertical distribution and contribution to element cycling in subsoils remain poorly understood. Here, nine soil profiles (0 to 135 cm) were collected at the local scale (within 300 km) from two canonical paddy soil types (Fe-accumuli and Hapli stagnic anthrosols), representing redoximorphic and oxidative soil types, respectively. Variations with depth in edaphic characteristics and soil bacterial and diazotrophic community assemblies and their associations with element cycling were explored. The results revealed that nitrogen and iron status were the most distinguishing edaphic characteristics of the two soil types throughout the soil profile. The acidic Fe-accumuli stagnic anthrosols were characterized by lower concentrations of free iron oxides and total iron in topsoil and ammonia in deeper layers compared with the Hapli stagnic anthrosols. The bacterial and diazotrophic community assemblies were mainly shaped by soil depth, followed by soil type. Random forest analysis revealed that nitrogen and iron cycling were strongly correlated in Fe-accumuli stagnic anthrosol, whereas in Hapli soil, available sulfur was the most important variable predicting both nitrogen and iron cycling. The distinctive biogeochemical processes could be explained by the differences in enrichment of microbial taxa between the two soil types. The main discriminant clades were the iron-oxidizing denitrifier Rhodanobacter, Actinobacteria, and diazotrophic taxa (iron-reducing Geobacter, Nitrospirillum, and Burkholderia) in Fe-accumuli stagnic anthrosol and the sulfur-reducing diazotroph Desulfobacca in Hapli stagnic anthrosol. IMPORTANCE Rice paddy ecosystems support nearly half of the global population and harbor remarkably diverse microbiomes and functions in a variety of soil types. Diazotrophs provide significant bioavailable nitrogen in paddy soil, priming nitrogen transformation and other biogeochemical processes. This study provides a novel perspective on the vertical distribution of bacterial and diazotrophic communities in two hydragric anthrosols. Microbiome analysis revealed divergent biogeochemical processes in the two paddy soil types, with a dominance of nitrogen-iron cycling processes in Fe-accumuli stagnic anthrosol and sulfur-nitrogen-iron coupling in Hapli stagnic anthrosol. This study advances our understanding of the multiple significant roles played by soil microorganisms, especially diazotrophs, in biogeochemical element cycles, which have important ecological and biogeochemical ramifications.

Objective : We assessed the efficacy and safety of transarterial chemoembolization (TACE) in combination with lenvatinib plus programmed death receptor-1 (PD-1) signaling inhibitors (camrelizumab or sintilimab) in unresectable hepatocellular carcinoma (uHCC). Methods : In this retrospective study, patients with uHCC were pretreated with lenvatinib for 1 to 2 weeks before TACE. Camrelizumab or sintilimab were initially administered intravenously in 1 week after TACE of a 21-day cycle. Primary objectives were objective response rate (ORR) and disease control rate (DCR) by modified Response Evaluation Criteria in Solid Tumors (mRECIST). The secondary endpoints included the progression-free survival (PFS), overall survival (OS), and toxicity. Results : Between March 5, 2019 and February 30, 2021, 53 patients were screened for eligibility. At data cutoff, 35.8% of patients remained on treatment. Median follow-up was 15.4 months. Confirmed ORR in the 51 evaluable patients was 54.9% (95% CI 41.4%-67.7%). DCR was 84.3% (95% CI 72.0%-91.8%). Median PFS was 8.5 months (95% CI 6.4 to 10.6 months). The median OS was not estimable. Grade ≥3 treatment-related adverse events occurred in 32.1% of patients. No new safety signals were identified. Conclusion : TACE in combination with lenvatinib plus anti-PD-1 inhibitors may have promising antitumor activity in uHCC. Toxicities were manageable, with no unexpected safety signals.

The damaged dockless shared-bikes are increasingly common in large cities of China, which not only reduce users' satisfactions but also harm the public environment. It is a merging issue for dockless bike-sharing systems to timely recall unusable bikes and replenish new/usable bikes. This paper addresses a maintenance network for a dockless bike-sharing system within a specific region in which the random demands and returns of shared-bikes are considered and the returned bikes have a certain probability to be unusable. The problem is to jointly determine the numbers of unusable and usable bikes to be recalled and replenished, respectively, and the corresponding routes of maintenance vehicles via the maintenance network. The problem is formulated as a stochastic mixed-integer programming model with the objective to maximize the expected revenue of the maintenance network within a operational period. To resolve the such complicated integration-optimization problem efficiently, the formulated model is decomposed into a multi-location newsvendor subproblem and a multiple vehicle routing subproblem with simultaneous delivery and pick-up. An efficient two-stage heuristics is then proposed, which resolves the two subproblems in the two stages of the algorithm, respectively. The computational results based on an real numerical case and a large number of numerical instances validate the performance of the proposed model and algorithm.

This paper deals with the multi-objective job shop scheduling problem in a robotic cell (MOJRCSP). All the jobs are processed according to their operations order on workstations. Different from classical job shop scheduling problem, the studied problem considers that jobs' transportation is handled by a robot. Also, the jobs are expected to be finished in a time window, instead of a constant due date. A mixed Integer Programming (MIP) model is proposed to formulate this problem. Due to the special characteristics of the studied problem and its NP-hard computational complexity, a metaheuristic based on Teaching Learning Based Optimization (TLBO) algorithm has been proposed. The proposed algorithm determines simultaneously the operations' assignments on workstations, the robot assignments for transportation operations, and the robot moving sequence. The objective is to minimize the makespan and the total earliness and tardiness. Computational results further validated the effectiveness and robustness of our proposed algorithm.

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.

We examine how interlocking directorates influence innovation performance differentials between firms. Our study offers a new perspective of the effect of interlocking directorate ties upon innovation performance, focusing on network effects on interfirm performance. Using a sample of China’s listed companies for the period 2012–2016, we empirically examined the relationship between board interlocks and interfirm innovation performance differentials. The results demonstrate that the presence of board interlocks reduces interfirm innovation performance differentials and leads to a convergence of innovation performance between the connected companies. Furthermore, cross-level analysis found that the relationship between board interlocks and interfirm innovation performance differentials is moderated by the interfirm industry attributes and demographic characteristics of the board. This study expands the existing research in explaining the driving mechanism of enterprise innovation performance as affected by interlocking directorate ties.

Background: Cancer stem cells (CSCs) are considered the main cause of cancer recurrence and metastasis, and DNA methylation is involved in the maintenance of CSCs. However, the methylation profile of esophageal CSCs remains unknown. Methods: Side population (SP) cells were isolated from esophageal squamous cell carcinoma (ESCC) cell lines KYSE150 and EC109. Sphere-forming cells were collected from human primary esophageal cancer cells. SP cells and sphere-forming cells were used as substitutes for cancer stem-like cells. We investigated the genome-wide DNA methylation profile in esophageal cancer stem-like cells using reduced representation bisulfite sequencing (RRBS). Results: Methylated cytosine (mC) was found mostly in CpG dinucleotides, located mostly in the intronic, intergenic, and exonic regions. Forty intersected differentially methylated regions (DMRs) were identified in these 3 groups of samples. Thirteen differentially methylated genes with the same alteration trend were detected; these included OTX1, SPACA1, CD163L1, ST8SIA2, TECR, CADM3, GRM1, LRRK1, CHSY1, PROKR2, LINC00658, LOC100506688 , and NKD2 . DMRs covering ST8SIA2 and GRM1 were located in exons. These differentially methylated genes were involved in 10 categories of biological processes and 3 cell signaling pathways. Conclusions: When compared to non-CSCs, cancer stem-like cells have a differential methylation status, which provides an important biological base for understanding esophageal CSCs and developing therapeutic targets for esophageal cancer.

BackgroundHepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) portends a worse prognosis. The objective of this study was to compare the efficacy of percutaneous radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) plus sorafenib to that of the most commonly utilized regimen of TACE plus sorafenib in large HCCs with type I/II PVTT.MethodsAn open-label, single-center, prospective, randomized trial of participants with tumors ≥5 cm and type I/II PVTT was performed. Participants with previously untreated HCCs were divided into two groups: RFA + cTACE + sorafenib (study group, n = 40) and cTACE + sorafenib (control group, n = 40). The primary endpoint was the objective response rate (ORR), the secondary endpoints included the overall survival (OS); time to progression (TTP); and toxicity. Prognostic factors were analyzed using cox-regression analysis.Results80 patients were enrolled into this study with integrated clinical data. Under a median follow-up of 506 days, the median age was 57.5 years (range: 28–80 years). The ORR of study group was higher than control group (70% vs 22.5%, p0.99), but no treatment-related deaths were recorded. Tumor encapsulation and attaining treatment response predict favorable OS in a multivariate Cox model. The rates of adverse events in both groups were 100% (p>0.99). There were no treatment-related deaths.ConclusionsRFA combined with TACE plus sorafenib is a safe, well-tolerated three-modality treatment for large HCCs with types I/II PVTT, and it demonstrated better efficacy than TACE plus sorafenib alone.

Hydrogen (H2) metabolism has attracted considerable interest because the activities of H2-producing and consuming microbes shape the global H2 cycle and may have vital relationships with the global cycling of other elements. There are many pathways of microbial H2 emission and consumption which may affect the structure and function of microbial communities. A wide range of microbial groups employ H2 as an electron donor to catalyze the reduction of pollutants such as organohalides, azo compounds, and trace metals. Syntrophy coupled mutualistic interaction between H2-producing and H2-consuming microorganisms can transfer H2 and be accompanied by the removal of toxic compounds. Moreover, hydrogenases have been gradually recognized to have a key role in the progress of pollutant degradation. This paper reviews recent advances in elucidating role of H2 metabolism involved in syntrophy and hydrogenases in environmental bioremediation. Further investigations should focus on the application of bioenergy in bioremediation to make microbiological H2 metabolism a promising remediation strategy.

CO2 convective dissolution has been regarded as one of the fundamental mechanisms to accelerate the mass transfer of CO2 into brine. We present a new spectrophotometric method to characterize the convective instability and measure the dissolved CO2 mass, which enables the real-time quantitative visualization of CO2/brine transport mechanisms. Successive images were captured to identify the finger development regimes, and the convection morphologies were analyzed by the fingers length and affected area. CO2 solubility was experimentally studied, and the results are in agreement with the theoretical calculations. CO2 mass transfer flux was investigated as the Sherwood number changed. The increase in salinity and temperature has a negative effect on CO2 dissolution; here, numerical simulation and experimental phenomena are qualitatively consistent. In general, these findings confirm the feasibility of the method and improve the understanding of the physical process of CO2 convective dissolution, which can help assess the CO2 solubility trapping mass.

Fertilization is one of the most common agricultural practices to achieve high yield. Although microbes play a critical role in nutrient cycling and organic matter decomposition, knowledge of the long-term responses of the soil bacterial community to organic and inorganic fertilizers is still limited. This study was conducted to evaluate the effects of century-long organic (manure), inorganic (NPK), and no fertilization (control) treatments on soil bacterial community structure under continuous winter wheat (Triticum aestivum L.) cultivation. Fertilization treatments altered the richness, diversity and composition of the soil bacterial community. Compared with the control, manure significantly increased the operational taxonomic units (OTUs), Chao 1 and Shannon indices, and taxonomic groups, while NPK significantly decreased these parameters. Fertilization treatments did not alter the types of dominant phyla but did significantly affect their relative abundances. Acidobacteria and Proteobacteria were the most dominant phyla in all treatments. Manure led to enrichment of most phyla, with a diazotrophic group, Cyanobacteria, being an exception; NPK reduced most phyla, but enriched Chloroflexi; control led to promotion of Cyanobacteria. Soil pH and NO3− were two dominant parameters influencing the bacterial community structure. Soil pH positively correlated with the relative abundances of Proteobacteria and Gemmatimonadetes but negatively correlated with those of Acidobacteria and Chloroflexi; NO3− negatively correlated with the relative abundance of Cyanobacteria, which was 14–52 times higher in control than the fertilized soils. Cyanobacteria, especially M. paludosus and L. appalachiana, could be the key players in maintaining wheat productivity in the century-long unfertilized control.

The CO2-brine dissolution homogenizes the distribution of residual CO2 and reduces the leakage risk in the saline aquifer. As a key parameter to immobilize the free CO2, the dissolution rate of CO2-brine could be accelerated through mechanisms like diffusion and dispersion, which are affected by the subsurface condition, pore structure, and background hydrological flow. This study contributed the calculated dissolution rates of both gaseous and supercritical CO2 during brine imbibition at a pore-scale. The flow development and distribution in porous media during dynamic dissolution were imaged in two-dimensional visualization using X-ray microtomography. The fingerings branching and expansion resulted in greater dissolution rates of supercritical CO2 with high contact between phases, while the brine bypassed the clusters of gaseous CO2 with a slower dissolution and longer duration due to the isolated bubbles. The dissolution rate of supercritical CO2 was about two or three orders of magnitude greater than that of gaseous CO2, while the value distributions both spanned about four orders of magnitude. The dissolution rates of gaseous CO2 increased with porosity, but the relationship was the opposite for supercritical CO2. CO2 saturation and the Reynolds number were analyzed to characterize the different impacts on gaseous and supercritical CO2 at different dissolution periods.

Purpose: Teratozoospermia is the main pathogenic factor of male infertility. However, the genetic etiology of teratozoospermia is largely unknown. This study aims to clarify the relationship between novel variations in TENT5D and teratozoospermia in infertile patients. Materials and methods: Two infertile patients were enrolled. Routine semen analysis of patients and normal controls was conducted with the WHO guidelines. Whole‐exome sequencing (WES) was conducted to identify pathogenic variants in the two patients. Morphology and ultrastructure analysis of spermatozoa in the two patients was determined by Papanicolaou staining, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The functional effect of the identified variants was analyzed by immunofluorescence staining and western blotting. The expression of TENT5D in different germ cells was detected by immunofluorescence staining. Results: Two new hemizygous variations, c.101C > T (p.P34L) and c.125A > T (p.D42V), in TENT5D were detected in two patients with male infertility. Morphology analysis showed abnormalities in spermatozoa morphology in the two patients, including multiple heads, headless, multiple tails, coiled, and/or bent flagella. Ultrastructure analysis showed that most of the spermatozoa exhibited missing or irregularly arranged '9+2' structures. Further functional experiments confirmed the abrogated TENT5D protein expression in patients. In addition, both p.P34L and p.D42V substitutions resulted in a conformational change of the TENT5D protein. We precisely analyzed the subcellular localization of TENT5D in germ cells in humans and mice. And we found that TENT5D was predominantly detected in the head and flagellum of elongating spermatids and epididymal spermatozoa. Conclusions: Our results showed further evidence of a relationship between TENT5D mutation and human male infertility, providing new genetic insight for use in the diagnosis and treatment of male infertility. [ABSTRACT FROM AUTHOR]

This study sought to assess leaf extracts of matoa (Pometia pinnata) and pulasan (Nephelium ramboutan-ake) for antibacterial, antifungal, antioxidant, and cytotoxic activities, beside phytochemical content. Four extracts (hexane, ethyl acetate, ethanol, and water) were obtained from each plant via sequential extraction. The antimicrobial activities were evaluated using colorimetric broth microdilution methods. The antioxidant activities were studied using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric-reducing antioxidant power (FRAP) assays. Cytotoxicity was examined using mouse fibroblasts NIH/3T3, while the phytochemical content was detected using various chemical tests. Among the extracts, only the water extract of matoa and ethyl acetate extract of pulasan exerted bactericidal effects on Bacillus cereus (minimum bactericidal concentration (MBC): 0.63 mg/mL) and Staphylococcus aureus (MBC: 1.25 mg/mL), respectively. In contrast, all extracts, except hexane extract, of both plants exhibited fungicidal effects with minimum fungicidal concentrations of 0.31-1.25 mg/mL. All extracts of matoa leaves displayed higher DPPH radical scavenging activity and FRAP than the extracts of pulasan leaves. Notably, the water extract of matoa showed the lowest half-maximal inhibitory concentration (IC50) value of 9.88 ± 1.70 µg/mL and the highest FRAP value of 6.11 ± 0.51 mmol Fe2+ equivalent/g extract (n=3). These antioxidant activities were significantly correlated (P < 0.01) with the amounts of phenolic compounds in the extracts. All extracts of both plants, except the water extracts, showed significant toxicities (P < 0.05) towards NIH/3T3 cells. Alkaloids, terpenoids, saponins, and glycosides were detected in the leaves of both plants. The matoa and pulasan leaves contained bioactive compounds with antibacterial, antifungal, and antioxidant activities. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers (DFU) and cutaneous lupus erythematosus (CLE) are both diseases that can seriously affect a patient's quality of life and generate economic pressure in society. Symptomatically, both DLU and CLE exhibit delayed healing and excessive inflammation; however, there is little evidence to support a molecular and cellular connection between these two diseases. In this study, we investigated potential common characteristics between DFU and CLE at the molecular level to provide new insights into skin diseases and regeneration, and identify potential targets for the development of new therapies. The gene expression profiles of DFU and CLE were obtained from the Gene Expression Omnibus (GEO) database and used for analysis. A total of 41 common differentially expressed genes (DEGs), 16 upregulated genes and 25 downregulated genes, were identified between DFU and CLE. GO and KEGG analysis showed that abnormalities in epidermal cells and the activation of inflammatory factors were both involved in the occurrence and development of DFU and CLE. Protein-protein interaction network (PPI) and sub-module analysis identified enrichment in seven common key genes which is KRT16, S100A7, KRT77, OASL, S100A9, EPGN and SAMD9. Based on these seven key genes, we further identified five miRNAs(has-mir-532-5p, has-mir-324-3p,has- mir-106a-5p,has-mir-20a-5p,has-mir-93-5p) and7 transcription factors including CEBPA, CEBPB, GLI1, EP30D, JUN,SP1, NFE2L2 as potential upstream molecules. Functional immune infiltration assays showed that these genes were related to immune cells. The CIBERSORT algorithm and Pearson method were used to determine the correlations between key genes and immune cells, and reverse key gene-immune cell correlations were found between DFU and CLE. Finally, the DGIbd database demonstrated that Paquinimod and Tasquinimod could be used to target S100A9 and Ribavirin could be used to target OASL. Our findings highlight common gene expression characteristics and signaling pathways between DFU and CLE, indicating a close association between these two diseases. This provides guidance for the development of targeted therapies and mutual interactions. [ABSTRACT FROM AUTHOR]