The binding effects and mechanisms of dissolved organic matter (DOM) on the fate of mercury in sludge anaerobic digestion combined with thermal hydrolysis.

Dissolved organic matter (DOM) plays an important role in regulating the fate of mercury (Hg), e.g., mobility, bioavailability, and toxicity. Clarifying the role of DOM in binding Hg in the treatment processes of sewage sludge is important for relieving Hg contamination risks in land applications. However, the impacts of DOM on Hg binding in sewage sludge are still unclear. In this study, we investigated the evolution of Hg and its speciation in full-scale sludge anaerobic digestion (AD) with thermal hydrolysis. The role of DOM in binding Hg(II) was further analyzed. The results showed that AD with thermal hydrolysis led to an increase in the Hg content in the sludge (from 3.72 ± 0.47 mg/kg to 10.75 ± 0.16 mg/kg) but a decrease in Hg mobility (the mercury sulfide fraction increased from 60.56 % to 79.78 %). Further adsorption experiments revealed that at equivalent DOM concentrations, DOM with a low molecular weight (MW<1 kDa) in activated sludge, DOM with a medium molecular weight (1 kDa 5 kDa) in both anaerobically digested sludge and conditioned sludge showed high binding amounts of Hg(II), with 1372.54, 535.28, 942.09 and 801.51 mg Hg/g DOM, respectively. Parallel factor analysis (PARAFAC) and fluorescence quotient (FQ) results showed that tryptophan-like and tyrosine-like substances had high binding affinities for Hg(II). Furthermore, X-ray photoelectron spectroscopy (XPS) indicated that the reduced organic sulfur contained in the DOM was potentially bound to Hg through the interactions of Hg-S and Hg-O. These results indicated that DOM may play special roles in regulating Hg speciation. The association between DOM and Hg(II), such as the significant positive correlation (p < 0.05) between the dissolution rate of Hg(II) and release of tryptophan-like substances during thermal hydrolysis, suggested the potential way for removing Hg from sludge.

In Silico Immunogenicity Assessment of Therapeutic Peptides.

The application of therapeutic peptides in clinical practice has significantly progressed in the past decades. However, immunogenicity remains an inevitable and crucial issue in the development of therapeutic peptides. The prediction of antigenic peptides presented by MHC class II is a critical approach to evaluating the immunogenicity of therapeutic peptides. With the continuous upgrade of algorithms and databases in recent years, the prediction accuracy has been significantly improved. This has made in silico evaluation an important component of immunogenicity assessment in therapeutic peptide development. In this review, we summarize the development of peptide-MHC-II binding prediction methods for antigenic peptides presented by MHC class II molecules and provide a systematic explanation of the most advanced ones, aiming to deepen our understanding of this field that requires particular attention.

Application of coffee ground-based skeleton builder with FeCl3 for conditions of pre-dewatered sludge toward further deep dewatering.

Skeleton builders are essential for achieving deep sludge dewatering. In this study, a novel spent coffee ground (SCG)-based skeleton builder was developed to attain deep sludge dewatering by combined conditioning with FeCl3, and possible mechanisms were examined. Through different surface analysis techniques, it was demonstrated that at a pyrolysis temperature of 300 °C, the spent coffee ground biochar (SCGB-300) has an intact pore structure, a rigid carbon skeleton, and large oxygen-containing functional groups, making it the best skeleton builder for sludge dewatering. When combined with FeCl3 for conditioning, the structure of SCGB-300 remained intact under high pressure and played important role. The rich porous structure facilitated water drainage. During the sludge conditioning, small amount of positive charge on the surface of SCGB-300 further increased the zeta potential of sludge through charge neutralization. At the same time, the adsorption of SCGB-300 removed viscous hydrophilic substances and further improved the dewatering performance. At an optimum dosage of 6% (dry solid, DS) FeCl3 and 30% SCGB-300 (DS), the moisture content of sludge was reduced from 85.47% to 63.35%, and the dewatering rate was increased from 46.08% to 70.03%. Therefore, SCGB is a promising skeleton builder for sludge conditioning and deep dewatering.

Deep learning in preclinical antibody drug discovery and development.

Antibody drugs have become a key part of biotherapeutics. Patients suffering from various diseases have benefited from antibody therapies. However, its development process is rather long, expensive and risky. To speed up the process, reduce cost and improve success rate, artificial intelligence, especially deep learning methods, have been widely used in all aspects of preclinical antibody drug development, from library generation to hit identification, developability screening, lead selection and optimization. In this review, we systematically summarize antibody encodings, deep learning architectures and models used in preclinical antibody drug discovery and development. We also critically discuss challenges and opportunities, problems and possible solutions, current applications and future directions of deep learning in antibody drug development.

Understanding of mercury and methylmercury transformation in sludge composting by metagenomic analysis.

Municipal sewage especially the produced sewage sludge is a significant source releasing mercury (Hg) to the environment. However, the Hg speciation especially methylmercury (MeHg) transformation in sewage sludge treatment process remains poorly understood. This study investigated the transformation of Hg speciation especially MeHg in sludge composting. The distribution of Hg transformation related gene pairs hgcAB and merAB, and their putative microbial hosts were comprehensively analyzed. Both Hg (from 3.16±0.22 mg/kg to 3.20±0.19 mg/kg) and MeHg content (from 4.77±0.64 ng/g to 4.36±0.37 ng/g) were not obviously changed before and after composting, but about 19.69% of Hg and 27.36% of MeHg were lost according to mass balance calculation. The metagenomic analysis further revealed that anaerobes (Desulfobacterota and Euryarchaeota) were the mainly putative Hg methylators especially carrying high abundance of hgcA gene in the initial periods of composting. Among the 151 reconstructed metagenome-assembled genomes (MAGs), only 4 hgcA gene carriers (Myxococcota, Firmicutes, Cyclobacteriaceae, and Methanothermobacter) and 16 merB gene carriers were identified. But almost all of the MAGs carried hgcB gene and merA gene. The merA gene was widely distributed in genomes, which indicated the widespread functionality of microbes for reducing Hg(II) to Hg(0). The hgcA carrying microbes tends to present the similar metabolic pathways including methanogenesis and sulfur metabolism. Besides, both the irregular distribution of hgcA in various species (including Actinobacteria, Archaea, Bacteroidetes, Desulfobacterota, Euryarchaeota, and Nitrospirae, etc.) and opposite evolution trends between hgcA gene abundance and its host genome abundance can be an indication of horizontal gene transfer or gene deletions of hgcA during composting. Our findings thus revealed that sludge composting is not only a hotspot for Hg speciation transformation, but also a potential hotspot for MeHg transformation.

Prospective comparison of acupuncture with sham acupuncture to determine impact on sedation and analgesia in mechanically ventilated critically ill patients (PASSION study): protocol for a randomised controlled trial.

INTRODUCTION: Sedation and analgesia are recommended to be employed in the intensive care unit (ICU) to enhance patient comfort and safety, facilitate mechanical ventilation and reduce oxygen demands. However, the increasing evidence demonstrates that excessive sedation and analgesia might prolong mechanical ventilation and increase costs and mortality. Acupuncture is known to be able to attenuate pain, anxiety and agitation symptoms while avoiding excessive sedation and analgesia caused by drugs. Therefore, we present a protocol to investigate whether acupuncture, used for sedation and analgesia, can reduce the duration of mechanical ventilation, save medical resources and reduce the mortality of critically ill patients receiving mechanical ventilation. METHODS AND ANALYSIS: Prospective, randomised controlled trial is conducted on 180 adult medical/surgical ICU patients with mechanical ventilation needing sedation at 3 ICUs between 03 November 2021 and 16 August 2023. Patients will be treated with analgesia and sedation to achieve desired target sedation levels (Richmond Agitation Sedation Score of -2 to 1). Enrolled patients will be randomly assigned in a ratio of 1:1:1 to receive deep needle insertion with combined manual and alternating-mode electrical stimulation on acupoints (AC group), superficial needle insertion without manual stimulation and electrical stimulation on non-acupoints (SAC group), or no acupuncture intervention (NAC group). The primary outcome is the duration of mechanical ventilation from randomisation until patients are free of mechanical ventilation (including non-invasive) without reinstitution for the following 48 hours. Secondary endpoints include the dose of administered sedatives and analgesic at comparable sedation levels throughout the study, ICU length of stay, hospital length of stay. Additional outcomes include the prevalence and days of delirium in ICU, mortality in ICU and within 28 days after randomisation, and the number of ventilator free days in 28 days. ETHICS AND DISSEMINATION: This trial was approved by the ethics committee at Guangdong Provincial Hospital of Chinese Medicine. We will publish the study results. TRIAL REGISTRATION NUMBER: ChiCTR2100052650.

Sclerostin aggravates cardiac remodeling after myocardial infarction by inhibition of Wnt/ß-catenin signaling pathway.

Background: The serum levels of sclerostin (SOST) are significant elevated in patients with pathological cardiac remodeling after myocardial infarction (MI). However, the mechanisms of SOST in cardiac remodeling remain largely uncharacterized. Methods: Collecting patients with MI who presented with or without left ventricular (LV) remodeling, we investigated differences in SOST expression. The influence of overexpression and silenced of SOST on the angiogenesis of cardiac microvascular endothelial cells (CMECs) was explored through in vitro experiments, and the impact of SOST on Wnt signaling marker proteins was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Finally, we observed the effects of SOST on cardiac function and morphology in mice MI model, and verified the role of the Wnt signaling marker proteins in vivo. Results: Serum SOST was significantly increased in patients with cardiac remodeling. Increased SOST expression was also observed in the infarcted hearts of C57BL/6 mice that underwent ligation of the left anterior descending branch of the coronary artery to induce MI. Furthermore, loss and gain of function experiments were conducted to investigate the role of SOST in post-infarct cardiac remodeling in vivo and in vitro. Overexpression of SOST promoted the proliferation and migration of cardiac fibroblasts (CFs), and inhibited angiogenesis of CMECs. In addition, overexpressing SOST in mice significantly deteriorated the post-infarct cardiac remodeling, as shown by the increased LV end systolic and end diastolic dimensions, decreased ejection fraction, and increased myocyte cross-section area and myocardial fibrosis. However, suppressing SOST expression showed the opposite results. The expression of Wnt signaling marker proteins was inhibited after overexpression of SOST, and enhanced after suppression of SOST in vivo and in vitro, suggesting involvement of the Wnt signaling pathway. Conclusions: The present study demonstrated that SOST aggravates post-infarct pathological myocardial remodeling by inhibiting angiogenesis of CMECs while promoting the proliferation of CFs, and this may be mediated by the Wnt signaling pathway. These results suggested that SOST might act as a biomarker to predict detrimental postinfarct cardiac remodeling, and may be a potential therapeutic target for the treatment of MI.

Oxygen vacancies generated by Sn-doped ZrO2 promoting the synthesis of dimethyl carbonate from methanol and CO2.

Oxygen vacancy sites on a catalyst surface have been extensively studied and been proved to promote the adsorption and activation of carbon dioxide. We use Sn-doped ZrO2 to prepare a Zr/Sn catalyst rich in oxygen vacancies (OVs) by co-precipitation. The yield of dimethyl carbonate is 5 times that of ZrO2. Compared with the original ZrO2, Zr/Sn exhibits a higher specific surface area, number of acid-base sites and a lower band gap, which improves the conductivity of electrons and creates more surface. The number of reaction sites greatly enhances the adsorption and activation capacity of CO2 molecules on the catalyst surface. In situ infrared spectroscopy shows that CO2 adsorbs on oxygen vacancies to form monomethyl carbonate, and participates in the reaction as an intermediate species. This work provides new clues for the preparation of ZrO2-based catalysts rich in oxygen vacancies to directly catalyze the synthesis of dimethyl carbonate from methanol and CO2.

The complete mitogenome of Lasioglossum affine (Hymenoptera: Halictidae) and phylogenetic analysis.

The complete mitogenome of Lasioglossum affine (Hymenoptera: Halictidae) was sequenced and analyzed. The whole mitogenome is 17,352 bp (AT%=84.1%) and encodes 37 typical eukaryotic mitochondrial genes, including 13 protein-coding genes (PCGs), 22 tRNAs, two rRNAs, and an AT-rich region. Further analysis found three gene rearrangements, where trn I-Q-M â†’ trn M-I-Q, trn W-C-Y â†’ trn C-W-Y, and trn K-D â†’ trn D-K were shuffled. The phylogenetic relationships of 19 species of Hymenoptera were established using maximum-likelihood method based on 13 concatenated PCGs. The result showed that Lasioglossum affine is a sister of Lasioglossum sp. SJW-2017.

Consistent Biomarkers and Related Pathogenesis Underlying Asthma Revealed by Systems Biology Approach.

Asthma is a common chronic airway disease worldwide. Due to its clinical and genetic heterogeneity, the cellular and molecular processes in asthma are highly complex and relatively unknown. To discover novel biomarkers and the molecular mechanisms underlying asthma, several studies have been conducted by focusing on gene expression patterns in epithelium through microarray analysis. However, few robust specific biomarkers were identified and some inconsistent results were observed. Therefore, it is imperative to conduct a robust analysis to solve these problems. Herein, an integrated gene expression analysis of ten independent, publicly available microarray data of bronchial epithelial cells from 348 asthmatic patients and 208 healthy controls was performed. As a result, 78 up- and 75 down-regulated genes were identified in bronchial epithelium of asthmatics. Comprehensive functional enrichment and pathway analysis revealed that response to chemical stimulus, extracellular region, pathways in cancer, and arachidonic acid metabolism were the four most significantly enriched terms. In the protein-protein interaction network, three main communities associated with cytoskeleton, response to lipid, and regulation of response to stimulus were established, and the most highly ranked 6 hub genes (up-regulated CD44, KRT6A, CEACAM5, SERPINB2, and down-regulated LTF and MUC5B) were identified and should be considered as new biomarkers. Pathway cross-talk analysis highlights that signaling pathways mediated by IL-4/13 and transcription factor HIF-1α and FOXA1 play crucial roles in the pathogenesis of asthma. Interestingly, three chemicals, polyphenol catechin, antibiotic lomefloxacin, and natural alkaloid boldine, were predicted and may be potential drugs for asthma treatment. Taken together, our findings shed new light on the common molecular pathogenesis mechanisms of asthma and provide theoretical support for further clinical therapeutic studies.