Identification of a novel de novo PUF60 variant causing Verheij syndrome in a fetus.

Verheij syndrome (VRJS) is a craniofacial spliceosomopathy with a wide phenotypic spectrum. Haploinsufficiency of the poly-uridine binding splicing factor 60 gene (PUF60) and its loss-of-function (LOF) variants are involved in VRJS. We evaluated a human fetus with congenital heart defects and preaxial polydactyly. Clinical data were obtained from the medical record. Whole-exome sequencing (WES) was used to explore the potential genetic etiology, and the detected variant verified using Sanger sequencing. Functional studies were performed to validate the pathogenic effects of the variant. Using trio-WES, we identified a novel PUF60 variant (NM_078480.2; c.1678 T > A, p.*560Argext*204) in the pedigree. Bioinformatic analyses revealed that the variant is potentially pathogenic, and functional studies indicated that it leads to degradation of the elongated protein and subsequently PUF60 LOF, producing some VRJS phenotypes. These findings confirmed the pathogenicity of the variant. This study implicates PUF60 LOF in the etiopathogenesis of VRJS. It not only expands the PUF60 variant spectrum, and also provides a basis for genetic counseling and the diagnosis of VRJS. Although trio-WES is a well-established approach for identifying the genetic etiology of rare multisystemic conditions, functional studies could aid in verifying the pathogenicity of novel variants.

Interactions of Indoleamine 2,3-dioxygenase-expressing LAMP3+ dendritic cells with CD4+ regulatory T cells and CD8+ exhausted T cells: synergistically remodeling of the immunosuppressive microenvironment in cervical cancer and therapeutic implications.

BACKGROUND: Cervical cancer (CC) is the fourth most common cancer in women worldwide. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of CC immune remodeling and exploration of novel treatment targets. This study aimed to investigate the mechanism of CC immune remodeling and explore potential therapeutic targets. METHODS: We conducted single-cell RNA sequencing on a total of 17 clinical specimens, including normal cervical tissues, high-grade squamous intraepithelial lesions, and CC tissues. To validate our findings, we conducted multicolor immunohistochemical staining of CC tissues and constructed a subcutaneous tumorigenesis model in C57BL/6 mice using murine CC cell lines (TC1) to evaluate the effectiveness of combination therapy involving indoleamine 2,3-dioxygenase 1 (IDO1) inhibition and immune checkpoint blockade (ICB). We used the unpaired two-tailed Student's t-test, Mann-Whitney test, or Kruskal-Wallis test to compare continuous data between two groups and one-way ANOVA with Tukey's post hoc test to compare data between multiple groups. RESULTS: Malignant cervical epithelial cells did not manifest noticeable signs of tumor escape, whereas lysosomal-associated membrane protein 3-positive (LAMP3+ ) dendritic cells (DCs) in a mature state with immunoregulatory roles were found to express IDO1 and affect tryptophan metabolism. These cells interacted with both tumor-reactive exhausted CD8+ T cells and CD4+ regulatory T cells, synergistically forming a vicious immunosuppressive cycle and mediating CC immune escape. Further validation through multicolor immunohistochemical staining showed co-localization of neoantigen-reactive T cells (CD3+ , CD4+ /CD8+ , and PD-1+ ) and LAMP3+ DCs (CD80+ and PD-L1+ ). Additionally, a combination of the IDO1 inhibitor with an ICB agent significantly reduced tumor volume in the mouse model of CC compared with an ICB agent alone. CONCLUSIONS: Our study suggested that a combination treatment consisting of targeting IDO1 and ICB agent could improve the therapeutic efficacy of current CC immunotherapies. Additionally, our results provided crucial insights for designing drugs and conducting future clinical trials for CC.

Hand Motions Reveal Attentional Status and Subliminal Semantic Processing: A Mouse-Tracking Technique.

Theories of embodied cognition suggest that hand motions and cognition are closely interconnected. An emerging technique of tracking how participants move a computer mouse (i.e., the mouse-tracking technique) has shown advantages over the traditional response time measurement to detect implicit cognitive conflicts. Previous research suggests that attention is essential for subliminal processing to take place at a semantic level. However, this assumption is challenged by evidence showing the presence of subliminal semantic processing in the near-absence of attention. The inconsistency of evidence could stem from the insufficient sensitivity in the response time measurement. Therefore, we examined the role of attention in subliminal semantic processing by analyzing participants' hand motions using the mouse-tracking technique. The results suggest that subliminal semantic processing is not only enhanced by attention but also occurs when attention is disrupted, challenging the necessity of facilitated top-down attention for subliminal semantic processing, as claimed by a number of studies. In addition, by manipulating the color of attentional cues, our experiment shows that the cue color per se could influence participants' response patterns. Overall, the current study suggests that attentional status and subliminal semantic processing can be reliably revealed by temporal-spatial features extracted from cursor motion trajectories.

Reaction-induced iodine adsorption on Cu surfaces facilitates electrocatalytic CO2 reduction.

The electrolyte effect has been key to the electrochemical CO2 reduction reaction (CO2RR) and has received extensive attention in recent years. Here we combined atomic force microscopy, quasi-in situ X-ray photoelectron spectroscopy, and in situ attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS) to study the effect of iodine anions on Cu-catalyzed CO2RR in the absence or presence of KI in the KHCO3 solution. Our results suggested that iodine adsorption caused coarsening of the Cu surface and altered its intrinsic activity for CO2RR. As the potential of the Cu catalyst became more negative, there was an increase in surface iodine anion concentration ([I-]), which could be connected to the reaction-enhanced adsorption of I- ions accompanying the increase in CO2RR activity. A linear relationship was observed between [I-] and current density. SEIRAS results further suggested that the presence of KI in the electrolyte strengthened the Cu-CO bond and facilitated the hydrogenation process, enhancing the production of CH4. Our results have thus provided insight into the role of halogen anions and aided in the design of an efficient CO2RR process.

Spatiotemporally deciphering the mysterious mechanism of persistent HPV-induced malignant transition and immune remodelling from HPV-infected normal cervix, precancer to cervical cancer: Integrating single-cell RNA-sequencing and spatial transcriptome.

BACKGROUND: The mechanism underlying cervical carcinogenesis that is mediated by persistent human papillomavirus (HPV) infection remains elusive. AIMS: Here, for the first time, we deciphered both the temporal transition and spatial distribution of cellular subsets during disease progression from normal cervix tissues to precursor lesions to cervical cancer. MATERIALS & METHODS: We generated scRNA-seq profiles and spatial transcriptomics data from nine patient samples, including two HPV-negative normal, two HPV-positive normal, two HPV-positive HSIL and three HPV-positive cancer samples. RESULTS: We not only identified three 'HPV-related epithelial clusters' that are unique to normal, high-grade squamous intraepithelial lesions (HSIL) and cervical cancer tissues but also discovered node genes that potentially regulate disease progression. Moreover, we observed the gradual transition of multiple immune cells that exhibited positive immune responses, followed by dysregulation and exhaustion, and ultimately established an immune-suppressive microenvironment during the malignant program. In addition, analysis of cellular interactions further verified that a 'homeostasis-balance-malignancy' change occurred within the cervical microenvironment during disease progression. DISCUSSION: We for the first time presented a spatiotemporal atlas that systematically described the cellular heterogeneity and spatial map along the four developmental steps of HPV-related cervical oncogenesis, including normal, HPV-positive normal, HSIL and cancer. We identified three unique HPV-related clusters, discovered critical node genes that determined the cell fate and uncovered the immune remodeling during disease escalation. CONCLUSION: Together, these findings provided novel possibilities for accurate diagnosis, precise treatment and prognosis evaluation of patients with precancer and cervical cancer.

Single-Cell Landscape Highlights Heterogenous Microenvironment, Novel Immune Reaction Patterns, Potential Biomarkers and Unique Therapeutic Strategies of Cervical Squamous Carcinoma, Human Papillomavirus-Associated (HPVA) and Non-HPVA Adenocarcinoma.

Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)-associated (HPVA) and non-HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation into their differences. Herein a transcriptomic atlas of SCC, HPVA, and NHPVA-ADC using single-cell RNA (scRNA) and T-cell receptor sequencing (TCR-seq) is presented. Regarding structural cells, the malignancy origin of epithelial cells, angiogenic tip cells and two subtypes of fibroblasts is revealed. The promalignant properties of the structural cells using organoids are further confirmed. Regarding immune cells, myeloid cells with multiple functions other than antigen presentation and exhausted T lymphocytes contribute to immunosuppression. From the perspective of HPV infection, not only is HPV-dependent and independent cervical cancer oncogenesis proposed but also three immune reaction patterns mediated by T cells (coordinated/inactive/imbalanced) are identified. Strikingly, diagnostic biomarkers to distinguish ADC from SCC are discovered and prognostic biomarkers with marker genes for malignant epithelial cells, tip cells, and SPP1/C1QC macrophages are generated. Importantly, the efficacy of anti-CD96 and anti-TIGIT, not inferior to anti-PD1, in animal experiments is confirmed and targeted therapies specifically for HPV-positive SCC, HPVA and NHPVA-ADC, providing essential clues for further clinical trials, are proposed.

A novel Silva pattern-based model for precisely predicting recurrence in intermediate-risk cervical adenocarcinoma patients.

BACKGROUND: Considering the unique biological behavior of cervical adenocarcinoma (AC) compared to squamous cell carcinoma, we now lack a distinct method to assess prognosis for AC patients, especially for intermediate-risk patients. Thus, we sought to establish a Silva-based model to predict recurrence specific for the intermediate-risk AC patients and guide adjuvant therapy. METHODS: 345 AC patients were classified according to Silva pattern, their clinicopathological data and survival outcomes were assessed. Among them, 254 patients with only intermediate-risk factors were identified. The significant cutoff values of four factors (tumor size, lymphovascular space invasion (LVSI), depth of stromal invasion (DSI) and Silva pattern) were determined by univariate and multivariate Cox analyses. Subsequently, a series of four-, three- and two-factor Silva-based models were developed via various combinations of the above factors. RESULTS: (1) We confirmed the prognostic value of Silva pattern using a cohort of 345 AC patients. (2) We established Silva-based models with potential recurrence prediction value in 254 intermediate-risk AC patients, including 12 four-factor models, 30 three-factor models and 16 two-factor models. (3) Notably, the four-factor model, which includes any three of four intermediate-risk factors (Silva C, ≥ 3 cm, DSI > 2/3, and > mild LVSI), exhibited the best recurrence prediction performance and surpassed the Sedlis criteria. CONCLUSIONS: Our study established a Silva-based four-factor model specific for intermediate-risk AC patients, which has superior recurrence prediction performance than Sedlis criteria and may better guide postoperative adjuvant therapy.

Accumulation of dysfunctional tumor-infiltrating PD-1+ DCs links PD-1/PD-L1 blockade immunotherapeutic response in cervical cancer.

Various predictive biomarkers are needed to select candidates for optimal and individualized treatments. Tumor-infiltrating immune cells have gained increasing interest in cancer research for the prediction of therapeutic response and survival. However, the role of dendritic cells (DCs) in PD-1 blockade immunotherapy remains unclear. In this study, we identified a population of PD-1+ DCs in the tumor microenvironment (TME) of cervical cancer (CC). The accumulation of PD-1+ DCs in cervical tumors was correlated with advanced stages, elevated preoperative squamous cell carcinoma antigen levels and lymph-vascular space invasion. PD-1 expression was induced on activated tumor-associated DCs (TADCs) in vitro compared with their resting counterparts. This PD-1+ DC population was characterized by reduced secretion of cytokines (IL-12, TNF-α, and IL-1ß) and dysfunctional induction of T cell proliferation and cytotoxic reaction. PD-1 blockade significantly reinvigorated PD-1+ DCs to release IL-12, TNF-α, and IL-1ß compared with PD-1- DCs. TILs from samples with higher PD-1+ DC infiltration could be induced to achieve a greater killing effect of PD-1 blockade treatment. Our findings suggested a role for PD-1+ DCs in immune surveillance dysfunction and CC progression. PD-1+ DC density in the TME may serve as a diagnostic factor for predicting the optimal beneficiaries of PD-1/PD-L1 blockade immunotherapy in CC.

Identification of clinical trait-related small RNA biomarkers with weighted gene co-expression network analysis for personalized medicine in endocervical adenocarcinoma.

Endocervical adenocarcinoma (EAC) is an aggressive type of endocervical cancer. At present, molecular research on EAC mainly focuses on the genome and mRNA transcriptome, the investigation of small RNAs in EAC has not been fully described. Here, we systematically explored small RNAs in 14 EAC patients with different subtypes using small RNA sequencing. MiRNAs and tRNA-derived RNAs (tDRs) accounted for the majority of mapped reads and the total number of miRNAs and tDRs maintained a relative balance. To explore the correlations between small RNAs expression and EAC with different clinical characteristics, we performed the weighted gene co-expression network analysis (WGCNA) and screened for hub small RNAs. From the key modules, we identified 9 small RNAs that were significantly related to clinical characteristics in EAC patients. Gene ontology and pathway analyses revealed that these molecules were involved in the pathogenesis of EAC. Our work provided new insights into EAC pathogenesis and successfully identified several small RNAs as candidate biomarkers for diagnosis and prognosis of EAC.

Identification of a novel six-gene signature with potential prognostic and therapeutic value in cervical cancer.

INTRODUCTION: Cervical cancer has high mortality, high recurrence and poor prognosis. Although prognostic biomarkers such as clinicopathological features have been proposed, their accuracy and precision are far from satisfactory. Therefore, novel biomarkers are urgently needed for disease surveillance, prognosis prediction and treatment selection. MATERIALS: Differentially expressed genes (DEGs) between cervical cancer and normal tissues from three microarray datasets extracted from the Gene Expression Omnibus platform were identified and screened. Based on these DEGs, a six-gene prognostic signature was constructed using cervical squamous cell carcinoma and endocervical adenocarcinoma data from The Cancer Genome Atlas. Next, the molecular functions and related pathways of the six genes were investigated through gene set enrichment analysis and co-expression analysis. Additionally, immunophenoscore analysis and the QuartataWeb Server were employed to explore the therapeutic value of the six-gene signature. RESULTS: We discovered 178 overlapping DEGs in three microarray datasets and established a six-gene (APOC1, GLTP, ISG20, SPP1, SLC24A3 and UPP1) prognostic signature with stable and excellent performance in predicting overall survival in different subgroups. Intriguingly, the six-gene signature was closely associated with the immune response and tumour immune microenvironment. The six-gene signature might be used for predicting response to immune checkpoint inhibitors (ICIs) and the six genes may serve as new drug targets for cervical cancer. CONCLUSION: Our study established a novel six-gene (APOC1, GLTP, ISG20, SPP1, SLC24A3 and UPP1) signature that was closely associated with the immune response and tumour immune microenvironment. The six-gene signature was indicative of aggressive features of cervical cancer and therefore might serve as a promising biomarker for predicting not only overall survival but also ICI treatment effectiveness. Moreover, three genes (UPP1, ISG20 and GLTP) within the six-gene signature have the potential to become novel drug targets.

Characteristics, complications, and outcomes of early-stage cervical stump carcinoma: laparoscopy versus laparotomy.

OBJECTIVE: To compare the characteristics, surgical complications, and overall survival between patients undergoing laparoscopy versus laparotomy for treatment of early-stage cervical stump carcinoma. METHODS: Patients with International Federation of Gynecology and Obstetrics (FIGO, 2009) stage IA2 to IIA2 cervical stump carcinoma who underwent laparoscopy or laparotomy in the Obstetrics and Gynecology Hospital of Fudan University from January 2000 to June 2018 were retrospectively reviewed. All patients' clinical characteristics, pathological features, complications, and follow-up data were retrieved. RESULTS: Seventy-two patients were included in the analysis; 58 underwent laparoscopy and 14 underwent laparotomy. With respect to surgical complications, laparoscopy was associated with a significantly lower complication rate, less blood loss, a shorter operative time, and a higher hospitalization fee than laparotomy. Survival was not significantly different between the laparoscopy and laparotomy groups. CONCLUSIONS: Although survival was not significantly different between the two surgical approaches, the rate of surgical complications was much lower in the laparoscopy than laparotomy group.

Novel artificial intelligence machine learning approaches to precisely predict survival and site-specific recurrence in cervical cancer: A multi-institutional study.

BACKGROUND: Machine learning (ML) has been gradually integrated into oncologic research but seldom applied to predict cervical cancer (CC), and no model has been reported to predict survival and site-specific recurrence simultaneously. Thus, we aimed to develop ML models to predict survival and site-specific recurrence in CC and to guide individual surveillance. METHODS: We retrospectively collected data on CC patients from 2006 to 2017 in four hospitals. The survival or recurrence predictive value of the variables was analyzed using multivariate Cox, principal component, and K-means clustering analyses. The predictive performances of eight ML models were compared with logistic or Cox models. A novel web-based predictive calculator was developed based on the ML algorithms. RESULTS: This study included 5112 women for analysis (268 deaths, 343 recurrences): (1) For site-specific recurrence, larger tumor size was associated with local recurrence, while positive lymph nodes were associated with distant recurrence. (2) The ML models exhibited better prognostic predictive performance than traditional models. (3) The ML models were superior to traditional models when multiple variables were used. (4) A novel predictive web-based calculator was developed and externally validated to predict survival and site-specific recurrence. CONCLUSION: ML models might be a better analytic approach in CC prognostic prediction than traditional models as they can predict survival and site-specific recurrence simultaneously, especially when using multiple variables. Moreover, our novel web-based calculator may provide clinicians with useful information and help them make individual postoperative follow-up plans and further treatment strategies.

A novel prognostic nomogram utilizing the 2018 FIGO staging system for cervical cancer: A large multicenter study.

OBJECTIVE: To evaluate the prognostic performance of the revised 2018 FIGO staging system for cervical cancer. METHODS: This retrospective multicenter study enrolled cervical cancer patients with 2009 FIGO Stage IA1-IIA2 who underwent surgeries between January 2006 and December 2017 in four tertiary hospitals. Patients were restaged according to the 2018 FIGO staging system by reviewing their medical data. RESULTS: Of 3238 cervical cancer patients included, 1841 (56.9%) patients were restaged: 641 (34.9%) due to tumor size, 544 (29.5%) due to lymph node metastasis, 614 (33.4%) due to the inconsistency between pre- and postoperative assessments, and 42 due to the cancellation of invasion width in Stage IA. After restaging, a clear tendency of decreased recurrence-free survival (RFS) and overall survival (OS) with increasing stage was observed. Multivariate Cox analysis showed that 2018 FIGO stage, parametrial involvement, and histology were independent prognostic factors for both OS and RFS (P < 0.05). Based on these factors, we established predictive nomograms with c-indexes of 0.735 and 0.721, showing good predictive ability for cervical cancer. CONCLUSION: The revised 2018 FIGO staging system can better reflect the survival of cervical cancer patients. Based on it, we established a nomogram that can predict the prognosis of cervical cancer patients more precisely.

Effect of the surgical approach on survival outcomes in patients undergoing radical hysterectomy for cervical cancer: A real-world multicenter study of a large Chinese cohort from 2006 to 2017.

OBJECTIVE: To compare survival outcomes of minimally invasive surgery (MIS) and laparotomy in early-stage cervical cancer (CC) patients. METHODS: A multicenter retrospective cohort study was conducted with International Federation of Gynecology and Obstetrics (FIGO, 2009) stage IA1 (lymphovascular invasion)-IIA1 CC patients undergoing MIS or laparotomy at four tertiary hospitals from 2006 to 2017. Propensity score matching and weighting and multivariate Cox regression analyses were performed. Survival was compared in various matched cohorts and subgroups. RESULTS: Three thousand two hundred and fifty-two patients (2439 MIS and 813 laparotomy) were included after matching. (1) The 2- and 5-year recurrence-free survival (RFS) (2-year, hazard ratio [HR], 1.81;95% confidence interval [CI], 1.09-3.0; 5-year, HR, 2.17; 95% CI, 1.21-3.89) or overall survival (OS) (2-year, HR, 1.87; 95% CI, 1.03-3.40; 5-year, HR, 2.57; 95% CI, 1.29-5.10) were significantly worse for MIS in patients with stage I B1, but not the cohort overall (2-year RFS, HR, 1.04; 95% CI, 0.76-1.42; 2-year OS, HR, 0.99; 95% CI, 0.70-1.41; 5-year RFS, HR, 1.12; 95% CI, 0.76-1.65; 5-year OS, HR, 1.20; 95% CI, 0.79-1.83) or other stages (2) In a subgroup analysis, MIS exhibited poorer survival in many population subsets, even in patients with less risk factors, such as patients with squamous cell carcinoma, negative for parametrial involvement, with negative surgical margins, negative for lymph node metastasis, and deep stromal invasion < 2/3. (3) In the cohort treated with (2172, 54%) or without adjuvant treatment (1814, 46%), MIS showed worse RFS than laparotomy in patients treated without adjuvant treatment, whereas no differences in RFS and OS were observed in adjuvant-treatment cohort. (4) Inadequate surgeon proficiency strongly correlated with poor RFS and OS in patients receiving MIS compared with laparotomy. CONCLUSIONS: MIS exhibited poorer survival outcomes than laparotomy group in many population subsets, even in low-risk subgroups. Therefore, laparotomy should be the recommended approach for CC patients.

Serum Circular FoxO3a Serves as a Novel Prognostic Biomarker in Squamous Cervical Cancer.

PURPOSE: Circular RNAs (circRNAs) are novel type of noncoding RNAs that play important roles and serve as noninvasive biomarkers in various cancers. In the present study, we focused on circFoxO3a and aimed to investigate its prognostic value as a novel serum biomarker for squamous cervical cancer (SCC). PATIENTS AND METHODS: Our study included 103 SCC patients from Obstetrics and Gynecology Hospital of Fudan University. Expression levels of circFoxO3a in the serum of patients with SCC were examined by reverse transcription­quantitative PCR (RT­qPCR). The correlation between serum circFoxO3a expression and clinicopathologic factors was analyzed. The Kaplan-Meier method and multivariate Cox regression analysis were applied to evaluate the independent prognostic factors for SCC. A prognostic predictive nomogram was constructed using R software. RESULTS: Levels of serum circFoxO3a were decreased in SCC patients compared with controls. Low expression of circFoxO3a was correlated with deeper stromal invasion and positive lymph node metastasis. Moreover, SCC patients with lower expression of serum circFoxO3a showed poorer prognosis, including both overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox analysis indicated low serum circFoxO3a levels to be an unfavorable prognostic factor for both OS and RFS, independent of positive lymph node metastasis. Notably, the predictive nomogram we established further confirmed that serum circFoxO3a is a useful tool for predicting survival in SCC. CONCLUSION: Altogether, our findings demonstrated that serum circFoxO3a could serve as a potential novel noninvasive predictive prognostic biomarker and therapeutic target for SCC.

Nano MnO2 Radially Grown on Lignin-Based Carbon Fiber by One-Step Solution Reaction for Supercapacitors with High Performance.

MnO2-deposited lignin-based carbon fiber (MnO2-LCF) mats are fabricated for supercapacitor applications. LCF mats are produced from alkali lignin via electrospinning followed by stabilization and carbonization. The carbonization process is carried out at 800, 900, and 1000 °C, and the corresponding mats are denoted as MnO2-LCF-800, MnO2-LCF-900, and MnO2-LCF-1000, respectively. The LCF mats are immersed in a KMnO4 solution at room temperature for 72 h to obtain MnO2-LCF mats. The scanning electron microscopy and X-ray diffraction analysis confirm the deposition of MnO2 on the LCFs. The Brunauer-Emmett-Teller analysis, X-ray spectroscopy, and Raman spectroscopy reveal that MnO2-LCF-800 mat possesses a large number of mesopores and Mn vacancies as compared to MnO2-LCF-900 mat and MnO2-LCF-1000 mat. Consequently, MnO2-LCF-800 mat possesses the best electrochemical properties with a specific capacitance of 131.28 F∙g-1, an energy density of 14.77 Wh∙kg-1, and a power density of 135.01 W∙kg-1 at a specific current of 0.3 A∙g-1. Hence, MnO2-LCF-800 mat shows high potential to be used as a high-performance supercapacitor.

Comparing impacts of physicochemical properties and hydrolytic inhibitors on enzymatic hydrolysis of sugarcane bagasse.

An autohydrolysis pretreatment with different conditions was applied to sugarcane bagasse to compare the impacts of the physicochemical properties and hydrolytic inhibitors on its enzymatic hydrolysis. The results indicate that the autohydrolysis conditions significantly affected the physicochemical properties and inhibitors, which further affected the enzymatic hydrolysis. The inhibitor amount, pore size, and crystallinity degree increased with increasing autohydrolysis severity. Furthermore, the enzymatic hydrolysis was enhanced with increasing severity owing to the removal of hemicellulose and lignin. The physicochemical obstruction impeded the enzymatic hydrolysis more than the inhibitors. The multivariate correlated component regression analysis enabled an evaluation of the correlations between the physicochemical properties (and inhibitors) and enzymatic hydrolysis for the first time. According to the results, an autohydrolysis with a severity of 4.01 is an ideal pretreatment for sugarcane bagasse for sugar production.

How Pseudo-lignin Is Generated during Dilute Sulfuric Acid Pretreatment.

Pseudo-lignin is generated from lignocellulose biomass during pretreatment with dilute sulfuric acid and has a significant inhibitory effect on cellulase. However, the mechanism of pseudo-lignin generation remains unclear. The following main points have been addressed to help elucidate the pseudo-lignin generation pathway. Cellulose and xylan were pretreated with sulfuric acid at different concentrations; aliquots were periodically collected; and the changes in the byproducts of the prehydrolysate were quantified. Milled wood lignin (MWL) mixed with cellulose and xylan was pretreated to evaluate the impact of lignin on pseudo-lignin generation. Furfural, 5-hydroxymethylfurfural, and MWL were pretreated as model compounds to investigate pseudo-lignin generation. The result indicated that the increasing acid concentration significantly promoted the generation of pseudo-lignin. When the acid concentration was increased from 0 to 1.00 wt %, pseudo-lignin was increased from 1.36 to 4.05 g. In addition, lignin promoted the pseudo-lignin generation through the condensation between lignin and the generated intermediates.

Fe3O4Nanoparticles Loaded on Lignin Nanoparticles Applied as a Peroxidase Mimic for the Sensitively Colorimetric Detection of H2O2.

Lignin is the second largest naturally renewable resource and is primarily a by-product of the pulp and paper industry; however, its inefficient use presents a challenge. In this work, Fe3O4 nanoparticles loaded on lignin nanoparticles (Fe3O4@LNPs) were prepared by the self-assembly method and it possessed an enhanced peroxidase-like activity. Fe3O4@LNPs catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2 to generate a blue color, was observable by the naked eye. Under the optimal conditions, Fe3O4@LNPs showed the ability of sensitive colorimetric detection of H2O2within a range of 5⁻100 µM and the limit of detection was 2 µM. The high catalytic activity of Fe3O4@LNPs allows its prospective use in a wide variety of applications, including clinical diagnosis, food safety, and environmental monitoring.

Study on enhancing sludge methanogenesis by adding acetylene black and effect on the characteristics & microbial community of anaerobic granular sludge.

The effect of acetylene black (ACET) as additives on methane production, extracellular polymeric substances (EPS), microbial community structure and methanogenesis pathway during sludge anaerobic digestion (AD) was investigated in this study. The results indicated that the addition of 2 g L-1 ACET resulted in a 44.36% increase in methane accumulation. ACET, which resulted in the increase of EPS and VSS/TSS by 4.71-50.64%, effectively improved the physicochemical properties of anaerobic granular sludge (AnGS). During anaerobic digestion, the high throughput sequencing presented direct evidence that the ACET increased microbial diversity and enriched functional microorganisms such as norank_f__Synergistaceae, norank_f__Anaerolineaceae, and unclassified_f__Clostridiaceae_3, which can improve the hydrolysis acidification process and the acetotrophic pathway. These results were reaffirmed by applying metagenome inference and gene content inference (16S function prediction). Microscopically, significant enhancement in the AD efficiency can be due to the methanogenesis promoted by the ACET that can construct direct interspecies electron transfer (DIET) between the unclassified_f__Clostridiaceae_3, norank_f__Anaerolineaceae, and Methanosaeta. These results were expected to provide primary research data for improving the performance of anaerobic reactors and the development of microbial fuel cells.