Targeting the oncogenic m6A demethylase FTO suppresses tumourigenesis and potentiates immune response in hepatocellular carcinoma.

OBJECTIVE: Fat mass and obesity-associated protein (FTO), an eraser of N 6-methyadenosine (m6A), plays oncogenic roles in various cancers. However, its role in hepatocellular carcinoma (HCC) is unclear. Furthermore, small extracellular vesicles (sEVs, or exosomes) are critical mediators of tumourigenesis and metastasis, but the relationship between FTO-mediated m6A modification and sEVs in HCC is unknown. DESIGN: The functions and mechanisms of FTO and glycoprotein non-metastatic melanoma protein B (GPNMB) in HCC progression were investigated in vitro and in vivo. Neutralising antibody of syndecan-4 (SDC4) was used to assess the significance of sEV-GPNMB. FTO inhibitor CS2 was used to examine the effects on anti-PD-1 and sorafenib treatment. RESULTS: FTO expression was upregulated in patient HCC tumours. Functionally, FTO promoted HCC cell proliferation, migration and invasion in vitro, and tumour growth and metastasis in vivo. FTO knockdown enhanced the activation and recruitment of tumour-infiltrating CD8+ T cells. Furthermore, we identified GPNMB to be a downstream target of FTO, which reduced the m6A abundance of GPNMB, hence, stabilising it from degradation by YTH N 6-methyladenosine RNA binding protein F2. Of note, GPNMB was packaged into sEVs derived from HCC cells and bound to the surface receptor SDC4 of CD8+ T cells, resulting in the inhibition of CD8+ T cell activation. A potential FTO inhibitor, CS2, suppresses the oncogenic functions of HCC cells and enhances the sensitivity of anti-PD-1 and sorafenib treatment. CONCLUSION: Targeting the FTO/m6A/GPNMB axis could significantly suppress tumour growth and metastasis, and enhance immune activation, highlighting the potential of targeting FTO signalling with effective inhibitors for HCC therapy.

A polyfunctionalized carbon framework composite for efficient decontamination of Cr(VI) and polycyclic aromatic nitrides from acidic wastewater.

Developing multifunctional engineered adsorbents is an effective strategy for decontaminating the environment from various pollutants. In this study, a polyfunctionalized carbon-framework composite, MSC-CFM, was synthesized. The composite comprises an aromatic carbon framework enriched with various functional groups, including magnetic nanoparticles, hydroxyl, and amino groups. MSC-CFM was used to decontaminate Cr(VI) and polycyclic aromatic nitrides (p-dimethylaminoazobenzene sulfonate (DAS) and diphenyl-4, 4 '-di [sodium (azo-2 -) -1-amino-naphthalene-4-sulfonate] (DANS)) from acidic wastewater. The adsorption capacities of MSC-CFM for Cr(VI), DAS and DANS, quantified using the Langmuir isotherm model, were 161.28, 310.83, and 1566.09 mg/g, respectively. Cr(VI) and PAHs (DAS and DANS) were monolayer adsorbed controlled by chemisorption. MSC-CFM could maintain good adsorption efficiency after up to 6 adsorption and desorption cycles. The presence of polycyclic aromatic nitrides promoted the adsorption of Cr(VI) in the Cr(VI)-DAS/DANS binary systems. Removal of pollutants by MSC-CFM involved a variety of unreported reaction mechanisms, such as electrostatic attraction, redox reaction, anion exchange, intermolecular hydrogen bonding, complexation reaction, π-π interaction, and anion-π interaction. MSC-CFM, enriched with a variety of functional groups, is a promising new material for environmental protection. It has good potential for practical application in treating polluted wastewater.

Utilizing synchronous care to improve cardiovascular and renal health among patients with type 2 diabetes: Proof-of-concept results from the DECIDE-CV clinical programme.

AIM: The management of patients with type 2 diabetes is asynchronous, i.e. not coordinated in time, resulting in delayed access to care and low use of guideline-directed medical therapy (GDMT). METHODS: We retrospectively analysed consecutive patients assessed in the 'synchronized' DECIDE-CV clinic. In this outpatient clinic, patients with type 2 diabetes and cardiovascular or chronic kidney disease are simultaneously assessed by an endocrinologist, cardiologist and nephrologist in the same visit. The primary outcome was use of GDMT before and after the assessment in the clinic, including sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, renin-angiotensin system blockers and mineralocorticoid receptor antagonists. Secondary outcomes included the baseline-to-last-visit change in surrogate laboratory biomarkers. RESULTS: The first 232 patients evaluated in the clinic were included. The mean age was 67 ± 12 years, 69% were men and 92% had diabetes. In total, 73% of patients had atherosclerotic cardiovascular disease, 65% heart failure, 56% chronic kidney disease and 59% had a urinary albumin-to-creatinine ratio ≥30 mg/g. There was a significant increase in the use of GDMT:sodium-glucose cotransporter 2 inhibitors (from 44% to 87% of patients), glucagon-like peptide 1 receptor agonists (from 8% to 45%), renin-angiotensin system blockers (from 77% to 91%) and mineralocorticoid receptor antagonists (from 25% to 45%) (p < .01 for all). Among patients with paired laboratory data, glycated haemoglobin, urinary albumin-to-creatinine ratio and N-terminal proB-type natriuretic peptide levels significantly dropped from baseline (p < .05 for all). CONCLUSIONS: Joint assessment of patients with diabetes in a synchronized cardiometabolic clinic holds promise for enhancing GDMT use and has led to significant reductions in surrogate cardiovascular and renal laboratory biomarkers.

Sorted-Cell Sequencing on HCC Specimens Reveals EPS8L3 as a Key Player in CD24/CD13/EpCAM-Triple Positive, Stemness-Related HCC Cells.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a heterogeneous cancer with varying levels of liver tumor initiating or cancer stem cells in the tumors. We aimed to investigate the expression of different liver cancer stem cell (LCSC) markers in human HCCs and identify their regulatory mechanisms in stemness-related cells. METHODS: We used an unbiased, single-marker sorting approach by flow cytometry, fluorescence-activated cell sorting, and transcriptomic analyses on HCC patients' resected specimens. Knockdown approach was used, and relevant functional assays were conducted on the identified targets of interest. RESULTS: Flow cytometry on a total of 60 HCC resected specimens showed significant heterogeneity in the expression of LCSC markers, with CD24, CD13, and EpCAM mainly contributing to this heterogeneity. Concomitant expression of CD24, CD13, and EpCAM was detected in 32 HCC samples, and this was associated with advanced tumor stages. Transcriptomic sequencing on the HCC cells sorted for these individual markers identified epidermal growth factor receptor kinase substrate 8-like protein 3 (EPS8L3) as a common gene associated with the 3 markers and was functionally validated in HCC cells. Knocking down EPS8L3 suppressed the expression of all 3 markers. To search for the upstream regulation of EPS8L3, we found SP1 bound to EPS8L3 promoter to drive EPS8L3 expression. Furthermore, using Akt inhibitor MK2206, we showed that Akt signaling-driven SP1 drove the expression of the 3 LCSC markers. CONCLUSIONS: Our findings suggest that Akt signaling-driven SP1 promotes EPS8L3 expression, which is critical in maintaining the downstream expression of CD24, CD13, and EpCAM. The findings provide insight into potential LCSC-targeting therapeutic strategies.

Integrating water quality data with a Bayesian network model to improve spatial and temporal phosphorus attribution: Application to the Maumee River Basin.

Surface water nutrient pollution, the primary cause of eutrophication, remains a major environmental concern in Western Lake Erie despite intergovernmental efforts to regulate nutrient sources. The Maumee River Basin has been the largest nutrient contributor. The two primary nutrient sources are inorganic fertilizer and livestock manure applied to croplands, which are later carried to the streams via runoff and soil erosion. Prior studies of nutrient source attribution have focused on large watersheds or counties at annual time scales. Source attribution at finer spatiotemporal scales, which enables more effective nutrient management, remains a substantial challenge. This study aims to address this challenge by developing a generalizable Bayesian network model for phosphorus source attribution at the subwatershed scale (12-digit Hydrologic Unit Code). Since phosphorus release is uncertain, we combine excess phosphorus derived from manure and fertilizer application and crop uptake data, flow information simulated by the SWAT model, and in-stream water quality measurements using Approximate Bayesian Computation to derive a posterior that attributes phosphorus contributions to subwatersheds. Our results show significant variability in subwatershed-scale phosphorus release that is lost in coarse-scale attribution. Phosphorus contributions attributed to the subwatersheds are on average lower than the excess phosphorus estimated by the nutrient balance approach currently adopted by environmental agencies. Fertilizer contributes more soluble reactive phosphorus than manure, while manure contributes most of the unreactive phosphorus. While developed for the specific context of Maumee River Basin, our lightweight and generalizable model framework could be adapted to other regions and pollutants and could help inform targeted environmental regulation and enforcement.

Spontaneous coronary artery dissection: a difficult journey from emergency coronary artery bypass grafting to left ventricular assist device.

Background: Excluding spontaneous coronary artery dissection (SCAD) as an aetiology of acute coronary syndrome in young adults is imperative. Case summary: A previously healthy 39-year-old woman experienced sudden severe chest pain, ST-segment elevation on electrocardiogram, necessitating high-dose aspirin and urgent transfer to a revascularization centre. Suffering ventricular tachycardia (VT) and ventricular fibrillation (VF), she underwent two rounds of advanced life support and venoarterial extracorporeal membrane oxygenation. Diagnosed with left main coronary artery (LMCA) SCAD, she was initially started on conservative therapy for declining left ventricular ejection fraction. However, she continued to experience an escalating anginal symptoms, worsening biomarkers, and LMCA SCAD progression, which urged the need for surgical intervention with coronary artery bypass graft surgery (CABG). Following her CABG, she experienced a worsening of her functional mitral regurgitating, which she underwent transcatheter edge-to-edge repair of her severe mitral regurgitation. Despite being listed for orthotopic heart transplantation (OHTx), her low body mass index and elevated antibodies necessitated the HeartMate III left ventricular assist device (LVAD) for bridge to transplant. After treating frequent VT episodes with medications, she eventually received a LVAD as a bridge to cardiac transplantation. Within 1 year of her receiving LVAD, she underwent a successful OHTx. Discussion: The pathogenesis of SCAD involves intramural haematoma formation through intimal tears or vasa vasorum haemorrhage. Adverse outcomes that could occur in SCAD patients include cardiac arrest, cardiogenic shock, reduced left ventricle systolic function, and occasionally serious cardiac arrhythmia-such as VF-which can lead to sudden cardiac death. Although most SCAD cases heal spontaneously, revascularization can be considered in case of worsening SCAD progression. Advanced therapeutic intervention including mechanical circulatory support and OHTx should be considered in refractory cases.

Reliability and Validity of Maximal Respiratory Pressures.

BACKGROUND: Maximal respiratory pressure is used to assess the inspiratory and expiratory muscles strength by using maximal inspiratory pressure (PImax ) and maximal expiratory pressure (PEmax). This study aimed to summarize and evaluate the reliability and validity of maximal respiratory pressure measurements. METHODS: This systematic review followed the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) recommendations and was reported by using the PRISMA checklist. Studies published before March 2023 were searched in PubMed and EMBASE databases. RESULTS: A total of 642 studies were identified by using the online search strategy and manual search (602 and 40, respectively). Twenty-three studies were included. The level of evidence for test-retest reliability was moderate for PImax and PEmax (intraclass correlation coefficient > 0.70 for both), inter-rater reliability was low for PImax and very low for PEmax (intraclass correlation coefficient > 0.70 for both), and the measurement error was very low for PImax and PEmax. In addition, concurrent validity presented a high level of evidence for PImax and PEmax (r > 0.80). CONCLUSIONS: Only concurrent validity of maximal respiratory pressure measured with the manometers evaluated in this review presented a high level of evidence. The quality of clinical studies by using maximal respiratory pressure would be improved if more high-quality studies on measurement properties, by following well established guidelines and the COSMIN initiative, were available.

Navigating drug use, cessation, and recovery: a retrospective case notes review among sexual minority men at a community-based service in Singapore.

BACKGROUND: In Singapore, where drug use is a highly stigmatized and criminalized issue, there is limited understanding of the challenges faced by individuals, particularly sexual minority men, in their journey towards recovery from substance dependence or addiction. This qualitative study aimed to investigate the driving forces behind drug use, the factors contributing to drug cessation, and the elements influencing the recovery process. METHODS: Data were extracted from clinical records provided by  The Greenhouse Community Services Limited between January 2020 to May 2022. These records encompassed information from four distinct forms: the intake assessment, progress notes, case closing summary, and the care plan review. Thematic analysis was employed to identify and categorize recurring themes within the data. RESULTS: Data from beneficiaries (n = 125) were analyzed and yielded a series of themes related to facilitators of drug use, motivations to cease drug use, and managing one's ongoing recovery. Within the facilitators of drug use, two sub-themes were identified: (a) addressing trauma and triggers and (b) managing emotions. Additionally, managing one's recovery was marked by four significant sub-themes: (a) uncovering personal identities, (b) losing motivation and drive, (c) overcoming obstacles, and (d) preparing for aftercare. CONCLUSIONS: The study contributes valuable insights into the dynamics of ongoing recovery management, offering potential avenues for interventions that could enhance support for individuals in their journey to overcome substance dependence. Enhancing psychoeducation and fostering peer support have the potential to facilitate the recovery process. Clearly, a holistic approach is needed to address these complex issues that cuts across our societies.

Enhancing the Small-Scale Screenable Biological Space beyond Known Chemogenomics Libraries with Gray Chemical Matter─Compounds with Novel Mechanisms from High-Throughput Screening Profiles.

Phenotypic assays have become an established approach to drug discovery. Greater disease relevance is often achieved through cellular models with increased complexity and more detailed readouts, such as gene expression or advanced imaging. However, the intricate nature and cost of these assays impose limitations on their screening capacity, often restricting screens to well-characterized small compound sets such as chemogenomics libraries. Here, we outline a cheminformatics approach to identify a small set of compounds with likely novel mechanisms of action (MoAs), expanding the MoA search space for throughput limited phenotypic assays. Our approach is based on mining existing large-scale, phenotypic high-throughput screening (HTS) data. It enables the identification of chemotypes that exhibit selectivity across multiple cell-based assays, which are characterized by persistent and broad structure activity relationships (SAR). We validate the effectiveness of our approach in broad cellular profiling assays (Cell Painting, DRUG-seq, and Promotor Signature Profiling) and chemical proteomics experiments. These experiments revealed that the compounds behave similarly to known chemogenetic libraries, but with a notable bias toward novel protein targets. To foster collaboration and advance research in this area, we have curated a public set of such compounds based on the PubChem BioAssay dataset and made it available for use by the scientific community.

The use of carbon fiber/polyetheretherketone (CF/PEEK) in pedicle screw fixation for spinal neoplasms-potential advantages in postoperative imaging and radiotherapy planning.

Background: Titanium pedicle screw fixation complicates postoperative care in patients with spinal neoplasms due to postoperative imaging artefacts and dose perturbation. This study aims to measure the benefits of using carbon fiber/polyetheretherketone (CF/PEEK) pedicle fixation compared to titanium in postoperative imaging, radiotherapy planning and delivery for spinal neoplasms treated with conventional external beam radiotherapy with a commercial treatment planning system. Methods: The properties of CF/PEEK pedicle fixation systems were compared to titanium in radiotherapy dose planning accuracy and postoperative computed tomography (CT) image quality. Dose profiles through the screw, tulip and longitudinal axis of the screw were acquired with radiochromic films and compared to a collapsed cone algorithm simulation, to measure dose agreement. The image quality of postoperative CTs were compared by defining four regions of interest around the vertebrae and screws in water phantom models and previous planning CTs, and comparing calculated artefact indexes (AIs). Results: CF/PEEK screws have non-inferior dosimetric prediction accuracy up to 50 mm beneath the screw for collapsed-cone algorithm planning systems. There is a statistically significant reduction in the absolute difference between calculated and measured dose at a depth of 2 mm beneath the screw. There is minimal attenuation with CF/PEEK relative to the surrounding dose, extending to 50 mm beneath the screw. There is a statistically significant improvement in CT imaging quality with reduced AIs in CF/PEEK fixation compared to titanium in both model and patient CT plans. Conclusions: CF/PEEK pedicle fixation can provide benefits in postoperative imaging and photon radiotherapy planning and delivery to patients with spinal neoplasms.

Insight into the humification and carbon balance of biogas residual biochar amended co-composting of hog slurry and wheat straw.

The impact of biogas residual biochar (BRB) on the humification and carbon balance process of co-composting of hog slurry (HGS) and wheat straw (WTS) was examined. The 50-day humification process was significantly enhanced by the addition of BRB, particular of 5% BRB, as indicated by the relatively higher humic acid content (67.28 g/kg) and humification ratio (2.31) than other treatments. The carbon balance calculation indicated that although BRB addition increased 22.16-46.77% of C lost in form of CO2-C, but the 5% BRB treatment showed relatively higher C fixation and lower C loss than other treatments. In addition, the BRB addition reshaped the bacterial community structure during composting, resulting in increased abundances of Proteobacteria (25.50%) during the thermophilic phase and Bacteroidetes (33.55%) during the maturation phase. Combined these results with biological mechanism analysis, 5% of BRB was likely an optimal addition for promoting compost humification and carbon fixation in practice.

Safety of fluconazole in kidney transplant recipients for prevention of coccidioidomycosis.

Coccidioides is an endemic fungus that causes infections ranging from mild respiratory illness to life-threatening disease, and immunocompromised hosts such as solid organ transplant recipients are at higher risk for disseminated infection and mortality. Our center administers fluconazole prophylaxis to kidney transplant recipients residing in geographic areas with higher incidences of coccidioidomycosis. However, because drug-drug interactions occur between triazoles and immunosuppressants used in transplant medicine, we undertook a study to ascertain whether fluconazole prophylaxis was associated with any important safety outcomes in kidney transplant recipients. This retrospective study evaluated patients who had undergone kidney transplantation between 2016 and 2019. Data on patient demographics, transplant-related clinical information, use of fluconazole prophylaxis (200 mg daily for 6-12 months post-transplant), and patient outcomes were obtained. The primary outcome was mean estimated glomerular filtration rate (eGFR) at 12 months, comparing those who received fluconazole prophylaxis to those who did not. Secondary outcomes included mean eGFR at 3 months, 6 months, and 9 months post-transplant, patient survival, biopsy-proven graft rejection, graft loss, or a new requirement for post-transplant dialysis, all within 12 months post-transplant. The mean eGFR at 12 months was similar between both groups, with 66.4 ml/min/1.73 m² in the fluconazole prophylaxis group vs. 64.3 ml/min/1.73 m² in the non-fluconazole prophylaxis group (P = 0.55). Secondary outcomes were similar across both groups. Multivariable linear regression found no significant association between fluconazole use and graft function. Fluconazole prophylaxis for prevention of coccidioidomycosis was not associated with adverse graft outcomes in kidney transplant recipients.

Solid organ transplant recipients can be highly immune suppressed, and infection with Coccidioides (valley fever) after transplant can lead to severe infections in these patients. Our study showed that fluconazole was safe and effective for preventing Coccidioides in kidney transplant recipients.

Multimodal Integrative Genomics and Pathology Analyses in Neoadjuvant Nivolumab Treatment for Intermediate and Locally Advanced Hepatocellular Carcinoma.

Introduction: Immunotherapy has resulted in pathologic responses in hepatocellular carcinoma (HCC), but the benefits and molecular mechanisms of neoadjuvant immune checkpoint blockade are largely unknown. Methods: In this study, we evaluated the efficacy and safety of preoperative nivolumab (anti-PD-1) in patients with intermediate and locally advanced HCC and determined the molecular markers for predicting treatment response. Results: Between July 2020 and November 2021, 20 treatment-naive HCC patients with intermediate and locally advanced tumors received preoperative nivolumab at 3 mg/kg for 3 cycles prior to surgical resection. Nineteen patients underwent surgical resection on trial. Seven (36.8%) of the 19 patients had major pathologic tumor necrosis (≥60%) in the post-nivolumab resection specimens, with 3 having almost complete (>90%) tumor necrosis. The tumor necrosis was hemorrhagic and often accompanied by increased or dense immune cell infiltrate at the border of the tumors. None of the patients developed major adverse reactions contradicting hepatectomy. RNA-sequencing analysis on both pre-nivolumab tumor biopsies and post-nivolumab resected specimens showed that, in cases with major pathologic necrosis, the proportion of CD8 T cells in the HCC tissues predominantly increased after treatment. Moreover, to investigate noninvasive biomarker for nivolumab response, we evaluated the copy number variation (CNV) using target-panel sequencing on plasma cell-free DNA of the patients and derived a CNV-based anti-PD-1 score. The score correlated with the extent of tumor necrosis and was validated in a Korean patient cohort with anti-PD-1 treatment. Conclusion: Neoadjuvant nivolumab demonstrated promising clinical activity in intermediate and locally advanced HCC patients. We also identified useful noninvasive biomarker predicting responsiveness.

Horizontal gene transfer after faecal microbiota transplantation in adolescents with obesity.

BACKGROUND: Horizontal gene transfer (HGT) describes the transmission of DNA outside of direct ancestral lineages. The process is best characterised within the bacterial kingdom and can enable the acquisition of genetic traits that support bacterial adaptation to novel niches. The adaptation of bacteria to novel niches has particular relevance for faecal microbiota transplantation (FMT), a therapeutic procedure which aims to resolve gut-related health conditions of individuals, through transplanted gut microbiota from healthy donors. RESULTS: Three hundred eighty-one stool metagenomic samples from a placebo-controlled FMT trial for obese adolescents (the Gut Bugs Trial) were analysed for HGT, using two complementary methodologies. First, all putative HGT events, including historical HGT signatures, were quantified using the bioinformatics application WAAFLE. Second, metagenomic assembly and gene clustering were used to assess and quantify donor-specific genes transferred to recipients following the intervention. Both methodologies found no difference between the level of putative HGT events in the gut microbiomes of FMT and placebo recipients, post-intervention. HGT events facilitated by engrafted donor species in the FMT recipient gut at 6 weeks post-intervention were identified and characterised. Bacterial strains contributing to this subset of HGT events predominantly belonged to the phylum Bacteroidetes. Engraftment-dependent horizontally transferred genes were retained within recipient microbiomes at 12 and 26 weeks post-intervention. CONCLUSION: Our study suggests that novel microorganisms introduced into the recipient gut following FMT have no impact on the basal rate of HGT within the human gut microbiome. Analyses of further FMT studies are required to assess the generalisability of this conclusion across different FMT study designs and for the treatment of different gut-related conditions. Video Abstract.

Limitations of Reporting Requirements under California's Livestock Antimicrobial Restriction Law.

BACKGROUND: Antimicrobial use in livestock production is considered a key contributor to growing antimicrobial resistance in bacteria. In 2015, California became the first state to enact restrictions on routine antimicrobial use in livestock production via Senate Bill 27 (SB27). SB27 further required the California Department of Food and Agriculture (CDFA) to collect and disseminate data on antimicrobial use in livestock production. OBJECTIVE: The goal of this report is to assess whether CDFA's data release allows us to evaluate how antimicrobial use changed after the implementation of SB27. METHODS: We combine the CDFA data with feed drug concentration ranges from the Code of Federal Regulation to evaluate the spread of plausible antimicrobial use trends. We also estimate antimicrobial consumption rates using data from the National Agricultural Statistical Service (NASS) and compare these to changes in medicated feed production reported by the CDFA. DISCUSSION: We show that CDFA's reported data are insufficient to reliably estimate whether antimicrobial usage has increased or decreased, most notably because no information is provided about the mass of antimicrobials approved for use or medicated feed drug concentrations. After incorporating additional external data on feed drug concentrations, one can at best provide uninformative bounds on the effect of SB27. We find some evidence that antimicrobial use has decreased by incorporating data on national sales of antimicrobials for food-producing animals, but the weakness of this inference underlines the need for improved data collection and dissemination, especially as other states seek to implement similar policies. We provide recommendations on how to improve reporting and data collection under SB27. https://doi.org/10.1289/EHP13702.

Potential and benefits of biochar production: crop straw management and carbon emission mitigation in Shaanxi Province, China.

Shaanxi Province is an important agricultural province in western China. Its profit-oriented management of crop residues remains a concern in the agriculture sector. Aiming to accelerate the valorization of agricultural straw and offer potential solutions for profit-oriented use of crop residues in Shaanxi, this study estimated the quantity of resources and collectable amount of crop straw by using the grain-to-straw ratio, analyzed the carbon emission reduction potential considering biochar energy and soil uses with the help of a life cycle assessment (LCA) model, and calculated the economic benefits of biochar production using waste and abandoned straw in Weinan (a city of Shaanxi). The theoretical resources and collectible amount of crop straw in Shaanxi showed an overall growth trend from 1949 to 2021, reaching 1.47 × 107 and 1.26 × 107 t in 2021 respectively. In 2021, straw from corn, wheat, and other grains accounted for 94.32% of the total straw. Among the 11 cities in Shaanxi, Weinan had the largest straw resources of 2.82 × 106 t, Yulin had the largest per capita straw resources of 0.72 t/person, and Yangling had the highest resource density of 7.60 t/hm2. The total carbon emission reduction was 3.11 × 104 t under scenario A with crop straw used for power generation. The emission reduction ranged from 1.25 × 107 to 1.27 × 107 CO2e t under scenario B with biochar production for energy and soil use. By using waste and abandoned straw in Weinan for biochar production, carbon emissions could be reduced by up to 2.07 × 105 t CO2e. In terms of the economic benefit from straw pyrolysis, the actual income was estimated to range from 0.67 × 108 to 1.33 × 108 ¥/a with different carbon prices. This study sheds light on the economic and environmental benefits of agricultural straw valorization through pyrolysis in Shaanxi, and provided an important basis for promoting the agricultural straw utilization in view of its potential for carbon emission reduction.

Reciprocal interactions between malignant cells and macrophages enhance cancer stemness and M2 polarization in HBV-associated hepatocellular carcinoma.

Background: The tumor microenvironment of cancers has emerged as a crucial component in regulating cancer stemness and plays a pivotal role in cell-cell communication. However, the specific mechanisms underlying these phenomena remain poorly understood. Methods: We performed the single-cell RNA sequencing (scRNA-seq) on nine HBV-associated hepatocellular carcinoma (HCC) patients. The heterogeneity of the malignant cells in pathway functions, transcription factors (TFs) regulation, overall survival, stemness, as well as ligand-receptor-based intercellular communication with macrophages were characterized. The aggressive and stemness feature for the target tumor subclone was validated by the conduction of in vitro assays including sphere formation, proliferation, Annexin V apoptosis, flow cytometry, siRNA library screening assays, and multiple in vivo preclinical mouse models including mouse hepatoma cell and human HCC cell xenograft models with subcutaneous or orthotopic injection. Results: Our analysis yielded a comprehensive atlas of 31,664 cells, revealing a diverse array of malignant cell subpopulations. Notably, we identified a stemness-related subclone of HCC cells with concurrent upregulation of CD24, CD47, and ICAM1 expression that correlated with poorer overall survival. Functional characterization both in vitro and in vivo validated S100A11 as one of the top downstream mediators for tumor initiation and stemness maintenance of this subclone. Further investigation of cell-cell communication within the tumor microenvironment revealed a propensity for bi-directional crosstalk between this stemness-related subclone and tumor-associated macrophages (TAMs). Co-culture study showed that this interaction resulted in the maintenance of the expression of cancer stem cell markers and driving M2-like TAM polarization towards a pro-tumorigenic niche. We also consolidated an inverse relationship between the proportions of TAMs and tumor-infiltrating T cells. Conclusions: Our study highlighted the critical role of stemness-related cancer cell populations in driving an immunosuppressive tumor microenvironment and identified the S100A11 gene as a key mediator for stemness maintenance in HCC. Moreover, our study provides support that the maintenance of cancer stemness is more attributed to M2 polarization than the recruitment of the TAMs.

Simultaneous decontamination of phosphorus and bisphenol A from livestock wastewater with boehmite-modified carbon composite.

In this work, a novel boehmite-modified carbon adsorbent (BMCC) derived from moldy corn was used for simultaneous removal of P and bisphenol A (BPA) from livestock wastewater. The results showed that BMCC had a high specific surface area (308.82 m2/g) with boehmite nanoparticles anchored on its surface. BMCC showed high P and BPA decontamination capabilities (40.98 mg/g for P and 54.65 mg/g for BPA by Langmuir model). The adsorbed amount of P declined as pH increased from 4 to 10, while the adsorbed amount of BPA remained steady until pH increased to 10. After 6 cycles of BMCC use, the P and BPA adsorption efficiencies reduced by 21.75 % and 19.41 %, respectively. The adsorption of P was dominated by electrostatic attraction and complexation, while the adsorption of BPA was controlled by hydrogen bonding, electrostatic interaction, and π-π association. In conclusion, BMCC is an effective treatment for decontaminating P- and BPA-contaminated livestock wastewater.

LANCL1, a cell surface protein, promotes liver tumor initiation through FAM49B-Rac1 axis to suppress oxidative stress.

BACKGROUND AND AIMS: HCC is an aggressive cancer with a poor clinical outcome. Understanding the mechanisms that drive tumor initiation is important for improving treatment strategy. This study aimed to identify functional cell membrane proteins that promote HCC tumor initiation. APPROACH AND RESULTS: Tailor-made siRNA library screening was performed for all membrane protein-encoding genes that are upregulated in human HCC (n = 134), with sphere formation as a surrogate readout for tumor initiation. Upon confirmation of membranous localization by immunofluorescence and tumor initiation ability by limiting dilution assay in vivo, LanC-like protein-1 (LANCL1) was selected for further characterization. LANCL1 suppressed intracellular reactive oxygen species (ROS) and promoted tumorigenicity both in vitro and in vivo. Mechanistically, with mass spectrometry, FAM49B was identified as a downstream binding partner of LANCL1. LANCL1 stabilized FAM49B by blocking the interaction of FAM49B with the specific E3 ubiquitin ligase TRIM21, thus protecting FAM49B from ubiquitin-proteasome degradation. The LANCL1-FAM49B axis suppressed the Rac1-NADPH oxidase-driven ROS production, but this suppression of ROS was independent of the glutathione transferase function of LANCL1. Clinically, HCCs with high co-expression of LANCL1 and FAM49B were associated with more advanced tumor stage, poorer overall survival, and disease-free survival. In addition, anti-LANCL1 antibodies targeting the extracellular N-terminal domain were able to suppress the self-renewal ability, as demonstrated by the sphere formation ability of HCC cells. CONCLUSIONS: Our data showed that LANCL1 is a cell surface protein and a key contributor to HCC initiation. Targeting the LANCL1-FAM49B-Rac1-NADPH oxidase-ROS signaling axis may be a promising therapeutic strategy for HCC.

Distributed Energy-Based Estimation Over Harvesting-Constrained Sensor Networks.

This article investigates the distributed joint state and fault estimation issue for a class of nonlinear time-varying systems over sensor networks constrained by energy harvesting. It is assumed that data transmission between sensors requires energy consumption, and each sensor can harvest energy from the external environment. A Poisson process models the energy harvested by each sensor, and the sensor's transmission decision depends on its current energy level. One can obtain the sensor transmission probability through a recursive calculation of the probability distribution of the energy level. Under such energy harvesting constraints, the proposed estimator only uses local and neighbor data to simultaneously estimate the system state and the fault, thereby establishing a distributed estimation framework. Moreover, the estimation error covariance is determined to possess an upper bound, which is minimized by devising energy-based filtering parameters. The convergence performance of the proposed estimator is analyzed. Finally, a practical example is presented to verify the usefulness of the main results.