Genetic diversity and prevalence of emerging Rickettsiales in Yunnan Province: a large-scale study.

BACKGROUND: Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province. METHODS: Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters. RESULTS: A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified. CONCLUSIONS: This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China.

Identification and Validation of a Novel Tertiary Lymphoid Structures-Related Prognostic Gene Signature in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors originating from the digestive system. Tertiary lymphoid structures (TLS), non-lymphoid tissues outside of the lymphoid organs, are closely connected to chronic inflammation and tumorigenesis. However, the detailed relationship between TLS and HCC prognosis remained unclear. In this study, we aimed to construct a TLS-related gene signature for predicting the prognosis of HCC patients. Methods: The Cancer Genome Atlas (TCGA) clinical data from 369 HCC tissues and 50 normal liver tissues were utilized to examine the differential expression of TLS-related genes. Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Furthermore, Cox regression analysis was applied to identify whether the TLS score could be employed as an independent prognosis factor. A nomogram was developed to predict the survival probability of HCC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for TLS-related genes. Genetic mutation analysis, the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA) were used to assess the tumor mutation landscape and immune infiltration. Finally, the role of the TLS score in HCC therapy was investigated. Results: Six genes were included in the construction of our prognostic model (CETP, DNASE1L3, PLAC8, SKAP1, C7, and VNN2), and we validated its accuracy. Survival analysis showed that patients in the high-TLS score group had a significantly better overall survival than those in the low-TLS score group. Univariate, multivariate Cox regression analysis and the establishment of a nomogram indicated that the TLS score could independently function as a potential prognostic marker. A significant association between TLS score and immunity was revealed by an analysis of gene alterations and immune cell infiltration. In addition, two subtypes of the TLS score could accurately predict the effectiveness of sorafenib, transcatheter arterial chemoembolization (TACE), and immunotherapy in HCC patients. Conclusion: In this research, we conducted and validated a prognostic model associated with TLS that may be helpful for predicting clinical outcomes and treatment responsiveness for HCC patients.

Advanced topology of triply periodic minimal surface structure for osteogenic improvement within orthopedic metallic screw.

Metallic screws are one of the most common implants in orthopedics. However, the solid design of the screw has often resulted in stress shielding and postoperative loosening, substantially impacting its long-term fixation effect after surgery. Four additive manufacturing porous structures (Fischer-Koch S, Octet, Diamond, and Double Gyroid) are now introduced into the screw to fix those issues. Upon applying the four porous structures, elastic modulus in the screw decreased about 2∼15 times to reduce the occurrence of stress shielding, and bone regeneration effect on the screw surface increased about 1∼50 times to improve bone tissue regrowing. With more bone tissue regrowing on the inner surface of porous screw, a stiffer integration between screw and bone tissue will be achieved, which improves the long-term fixation of the screw tremendously. The biofunctions of the four topologies on osteogenesis have been fully explored, which provides an advanced topology optimization scheme for the screw utilized in orthopedic fixation.

Systematic investigation of the Borrelia miyamotoi spirochetes in ticks, wildlife and domestic animal hosts in Yunnan province, Southwest China.

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

Epidemiology and survival of patients with spinal meningiomas: a large retrospective cohort study.

INTRODUCTION: Spinal meningiomas (SMs) are relatively rare central nervous system tumors that usually trigger neurological symptoms. The prevalence of SMs is increasing with the aging of the global population. This study aimed to perform a systematic epidemiologic and survival prognostic analysis of SMs to evaluate their public health impact and to develop a novel method to estimate the overall survival at 3-year, 5-year, and 10-year in patients with SMs. METHODS: Five thousand one hundred fifty eight patients with SMs were recruited from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019. Firstly, descriptive analysis was performed on the epidemiology of SMs. Secondly, these individuals were randomly allocated to the training and validation sets in a ratio of 7:3. Kaplan-Meier method and Cox regression analysis were utilized in the training set to identify independent prognostic factors and to construct a nomogram for survival prognosis. Subsequently, the discriminative power, predictive performance, and clinical utility of the nomogram were evaluated by receiver operating characteristic curve and decision curve analysis. Finally, a mortality risk stratification system and a web-based dynamic nomogram were constructed to quantify the risk of mortality in patients with SMs. RESULTS: The annual age-adjusted incidence rates of SMs increased steadily since 2004, reaching a rate of 0.40 cases per 100 000 population in 2019, with a female-to-male ratio of ~4:1. The age groups of 50-59, 60-69, and 70-79 years old were the most prevalent ages for SMs, accounting for 19.08, 24.93, and 23.32%, respectively. In addition, seven independent prognostic factors were identified to establish a prognostic nomogram for patients with SMs. The decision curve analysis and receiver operating characteristic curve indicated that the nomogram had high clinical utility and favorable accuracy. Moreover, the mortality risk stratification system effectively divided patients into low-risk, middle-risk, and high-risk subgroups. CONCLUSIONS: SMs are relatively rare benign spinal tumors prevalent in the white elderly female population. Clinicians could use the nomogram to personalize the prediction of the overall survival probability of patients with SMs, categorize these patients into different mortality risk subgroups, and develop personalized decision-making plans. Moreover, the web-based dynamic nomogram could help to further promote clinical application and assist clinicians in providing personalized counseling, timely monitoring, and clinical assessment for patients.

CG -SLENP: A chemical genetics strategy to selectively label existing proteins and newly synthesized proteins.

Protein synthesis and subsequent delivery to the target locations in cells are essential for their proper functions. Methods to label and distinguish newly synthesized proteins from existing ones are critical to assess their differential properties, but such methods are lacking. We describe the first chemical genetics-based approach for selective labeling of existing and newly synthesized proteins that we termed as CG -SLENP. Using HaloTag in-frame fusion with lamin A (LA), we demonstrate that the two pools of proteins can be selectively labeled using CG -SLENP in living cells. We further employ our recently developed selective small molecule ligand LBL1 for LA to probe the potential differences between newly synthesized and existing LA. Our results show that LBL1 can differentially modulate these two pools of LA. These results indicate that the assembly states of newly synthesized LA are distinct from existing LA in living cells. The CG -SLENP method is potentially generalizable to study any cellular proteins.

Application of advanced biomaterials in photothermal therapy for malignant bone tumors.

Malignant bone tumors are characterized by severe disability rate, mortality rate, and heavy recurrence rate owing to the complex pathogenesis and insidious disease progression, which seriously affect the terminal quality of patients' lives. Photothermal therapy (PTT) has emerged as an attractive adjunctive treatment offering prominent hyperthermal therapeutic effects to enhance the effectiveness of surgical treatment and avoid recurrence. Simultaneously, various advanced biomaterials with photothermal capacity are currently created to address malignant bone tumors, performing distinctive biological functions, including nanomaterials, bioceramics (BC), polymers, and hydrogels et al. Furthermore, PTT-related combination therapeutic strategies can provide more significant curative benefits by reducing drug toxicity, improving tumor-killing efficiency, stimulating anti-cancer immunity, and improving immune sensitivity relative to monotherapy, even in complex tumor microenvironments (TME). This review summarizes the current advanced biomaterials applicable in PTT and relevant combination therapies on malignant bone tumors for the first time. The multiple choices of advanced biomaterials, treatment methods, and new prospects for future research in treating malignant bone tumors with PTT are generalized to provide guidance. Malignant bone tumors seriously affect the terminal quality of patients' lives. Photothermal therapy (PTT) has emerged as an attractive adjunctive treatment enhancing the effectiveness of surgical treatment and avoiding recurrence. In this review, advanced biomaterials applicable in the PTT of malignant bone tumors and their distinctive biological functions are comprehensively summarized for the first time. Simultaneously, multiple PTT-related combination therapeutic strategies are classified to optimize practical clinical issues, contributing to the selection of biomaterials, therapeutic alternatives, and research perspectives for the adjuvant treatment of malignant bone tumors with PTT in the future.

NTRK1 knockdown induces mouse cognitive impairment and hippocampal neuronal damage through mitophagy suppression via inactivating the AMPK/ULK1/FUNDC1 pathway.

Hippocampal neuronal damage may induce cognitive impairment. Neurotrophic tyrosine kinase receptor 1 (NTRK1) reportedly regulates neuronal damage, although the underlying mechanism remains unclear. The present study aimed to investigate the role of NTRK1 in mouse hippocampal neuronal damage and the specific mechanism. A mouse NTRK1-knockdown model was established and subjected to pre-treatment with BAY-3827, followed by a behavioral test, Nissl staining, and NeuN immunofluorescence (IF) staining to evaluate the cognitive impairment and hippocampal neuronal damage. Next, an in vitro analysis was conducted using the CCK-8 assay, TUNEL assay, NeuN IF staining, DCFH-DA staining, JC-1 staining, ATP content test, mRFP-eGFP-LC3 assay, and LC3-II IF staining to elucidate the effect of NTRK1 on mouse hippocampal neuronal activity, apoptosis, damage, mitochondrial function, and autophagy. Subsequently, rescue experiments were performed by subjecting the NTRK1-knockdown neurons to pre-treatment with O304 and Rapamycin. The AMPK/ULK1/FUNDC1 pathway activity and mitophagy were detected using western blotting (WB) analysis. Resultantly, in vivo analysis revealed that NTRK1 knockdown induced mouse cognitive impairment and hippocampal tissue damage, in addition to inactivating the AMPK/ULK1/FUNDC1 pathway activity and mitophagy in the hippocampal tissues of mice. The treatment with BAY-3827 exacerbated the mouse depressive-like behavior induced by NTRK1 knockdown. The results of in vitro analysis indicated that NTRK1 knockdown attenuated viability, NeuN expression, ATP production, mitochondrial membrane potential, and mitophagy, while enhancing apoptosis and ROS production in mouse hippocampal neurons. Conversely, pre-treatment with O304 and rapamycin abrogated the suppression of mitophagy and the promotion of neuronal damage induced upon NTRK1 silencing. Conclusively, NTRK1 knockdown induces mouse hippocampal neuronal damage through the suppression of mitophagy via inactivating the AMPK/ULK1/FUNDC1 pathway. This finding would provide insight leading to the development of novel strategies for the treatment of cognitive impairment induced due to hippocampal neuronal damage.

Advances in materials used for minimally invasive treatment of vertebral compression fractures.

Vertebral compression fractures are becoming increasingly common with aging of the population; minimally invasive materials play an essential role in treating these fractures. However, the unacceptable processing-performance relationships of materials and their poor osteoinductive performance have limited their clinical application. In this review, we describe the advances in materials used for minimally invasive treatment of vertebral compression fractures and enumerate the types of bone cement commonly used in current practice. We also discuss the limitations of the materials themselves, and summarize the approaches for improving the characteristics of bone cement. Finally, we review the types and clinical efficacy of new vertebral implants. This review may provide valuable insights into newer strategies and methods for future research; it may also improve understanding on the application of minimally invasive materials for the treatment of vertebral compression fractures.

Comprehensive evaluation and advanced modification of polymethylmethacrylate cement in bone tumor treatment.

Bone tumors are invasive diseases with a tendency toward recurrence, disability, and high mortality rates due to their grievous complications. As a commercial polymeric biomaterial, polymethylmethacrylate (PMMA) cement possesses remarkable mechanical properties, injectability, and plasticity and is, therefore, frequently applied in bone tissue engineering. Numerous positive effects in bone tumor treatment have been demonstrated, including biomechanical stabilization, analgesic effects, and tumor recurrence prevention. However, to our knowledge, a comprehensive evaluation of the application of the PMMA cement in bone tumor treatment has not yet been reported. This review comprehensively evaluates the efficiency and complications of the PMMA cement in bone tumor treatment, for the first time, and introduces advanced modification strategies, providing an objective and reliable reference for the application of the PMMA cement in treating bone tumors. We have also summarized the current research on modifications to enhance the anti-tumor efficacy of the PMMA cement, such as drug carriers and magnetic hyperthermia.

First-Principles Study of χ3-Borophene as a Candidate for Gas Sensing and the Removal of Harmful Gases.

The potential application of borophene as a sensing material for gas-sensing devices is investigated in this work. We utilize density functional theory (DFT) to systematically study the adsorption mechanism and sensing performance of χ3-borophene to search for high-sensitivity sensors for minor pollutant gases. We compare the results to those for two Pmmn borophenes. The first-principles calculations are used to analyze the sensing performance of the three different borophenes (2 Pmmn borophene, 8 Pmmn borophene, and χ3-borophene) on five leading harmful gases (CO, NH3, SO2, H2S, and NO2). The adsorption configuration, adsorption energy, and electronic properties of χ3-borophene are investigated. Our results indicate that the mechanism of adsorption on χ3-borophene is chemisorption for NO2 and physisorption for SO2 and H2S. The mode of adsorption of CO and NH3 on χ3-borophene can be both physisorption and chemisorption, depending on the initially selected sites. Analyses of the charge transfer and density of states show that χ3-borophene is selective toward the adsorption of harmful gases and that N and O atoms form covalent bonds when chemisorbed on the surface of χ3-borophene. An interesting phenomenon is that when 8 Pmmn borophene adsorbs SO2, the gas molecules are dismembered and strongly adsorb on the surface of 8 Pmmn borophene, which provides a way of generating O2 while adsorbing harmful substances. Overall, the results of this work demonstrate the potential applications of borophene as a sensing material for harmful gas sensing or removal.

Case Report: Complete pathologic response to neoadjuvant selpercatinib in a patient with resectable early-stage RET fusion-positive non-small cell lung cancer.

The LIBRETTO-001 trial demonstrated the activity of the selective rearrangement during transfection (RET) inhibitor selpercatinib in advanced RET fusion-positive non-small cell lung cancer (NSCLC) and resulted in the drug's approval for this indication. A cohort that included neoadjuvant and adjuvant selpercatinib was opened on LIBRETTO-001 for early-stage RET fusion-positive NSCLC with the primary endpoint of major pathologic response. A patient with a stage IB (cT2aN0M0) KIF5B-RET fusion-positive NSCLC received 8 weeks of neoadjuvant selpercatinib at 160 mg twice daily followed by surgery. While moderate regression in the primary tumor (stable disease, Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1) was observed radiologically, assessment via an Independent Pathologic Review Committee revealed a pathologic complete response (0% viable tumor). This consensus assessment by three independent pathologists was aided by RET fluorescence in situ hybridization testing of a reactive pneumocyte proliferation showing no rearrangement. Neoadjuvant selpercatinib was well-tolerated with only low-grade treatment-emergent adverse events. The activity of prospective preoperative selpercatinib in this case establishes proof of concept of the potential utility of RET inhibitor therapy in early-stage RET fusion-positive NSCLC.

Arsenene as a promising sensor for the detection of H2S: a first-principles study.

To explore the feasibility of arsenene in detecting H2S gas, we employ the density-functional theory to investigate the geometry, electronic structure and magnetic properties of defected and doped arsenene. Point defects do not appreciably improve the sensing performance of arsenene due to small adsorption energies and charge transfer. The doping of transition metals (Ti, V, Cr, Mn, Co and Ni) introduces magnetic moments and narrows the band gap of arsenene. Transition metal (TM) dopants can enhance the interaction between H2S and a modified arsenene substrate. Adsorption energies and charge transfers increase significantly, and the adsorption converts to chemisorption. After adsorption, the Ti and Cr-doped system's band gap change is twice that of the pristine and defective arsenene. The adsorption of H2S changes the system properties of two TM-doped arsenenes: Ti-doped arsenene transforms from semiconductor to half-metal, and Ni-doped arsenene transforms from half-metal to conductor. Electrical signals can be observed in this process to detect H2S molecules. Our calculations show that doping improves the detecting performance of arsenene to H2S molecules more efficiently than defects. Our results indicate that arsenene has a promising future in developing H2S gas sensors.

LIBRETTO-432, a phase III study of adjuvant selpercatinib or placebo in stage IB-IIIA RET fusion-positive non-small-cell lung cancer.

Selpercatinib, a first-in-class, highly selective and potent central nervous system-active RET kinase inhibitor demonstrated clinically meaningful activity with manageable toxicity in pretreated and treatment-naive advanced/metastatic RET fusion-positive non-small-cell lung cancer (NSCLC). LIBRETTO-432 is a global, randomized, double-blind, phase III trial evaluating selpercatinib versus placebo in stage IB-IIIA, RET fusion-positive NSCLC, previously treated with definitive surgery or radiation; participants must have undergone available anti-cancer therapy (including chemotherapy or durvalumab) or not be suitable for it, per investigator's discretion. The primary end point is investigator-assessed event-free survival (EFS) in the primary analysis population (stage II-IIIA RET fusion-positive NSCLC). Key secondary end points include EFS in the overall population, overall survival, and time to distant disease recurrence in the central nervous system.

Selpercatinib is approved in multiple countries for the treatment of advanced or metastatic RET-altered lung cancers. Selpercatinib has shown promising efficacy and safety results in patients with advanced/metastatic RET fusion-positive NSCLC. This is a summary of the LIBRETTO-432 study which compares selpercatinib with placebo in patients with earlier stages (stage IB-IIIA) of RET fusion-positive NSCLC, who have already undergone surgery or radiotherapy and applicable adjuvant chemotherapy. This study is active and currently recruiting new participants. This trial will evaluate how long people live without evidence of cancer recurrence, both during and after treatment. Side effects will also be evaluated in this study. Clinical Trial Registration: NCT04819100 (ClinicalTrials.gov).

Biomaterials for Interbody Fusion in Bone Tissue Engineering.

In recent years, interbody fusion cages have played an important role in interbody fusion surgery for treating diseases like disc protrusion and spondylolisthesis. However, traditional cages cannot achieve satisfactory results due to their unreasonable design, poor material biocompatibility, and induced osteogenesis ability, limiting their application. There are currently 3 ways to improve the fusion effect, as follows. First, the interbody fusion cage is designed to facilitate bone ingrowth through the preliminary design. Second, choose interbody fusion cages made of different materials to meet the variable needs of interbody fusion. Finally, complete post-processing steps, such as coating the designed cage, to achieve a suitable osseointegration microstructure, and add other bioactive materials to achieve the most suitable biological microenvironment of bone tissue and improve the fusion effect. The focus of this review is on the design methods of interbody fusion cages, a comparison of the advantages and disadvantages of various materials, the influence of post-processing techniques and additional materials on interbody fusion, and the prospects for the future development of interbody fusion cages.

Construction and Research on Chinese Semantic Mapping Based on Linguistic Features and Sparse Self-Learning Neural Networks.

In this paper, we adopt the algorithms of linguistic feature Rong and sparse self-learning neural network to conduct an in-depth study and analysis of Chinese semantic mapping, which complements the emotion semantic representation ability of traditional word embedding and fully explores the emotion semantic information contained in the text in the task preprocessing stage. We incorporate various semantic features such as lexical information and location information to make the model have richer emotion semantic expression, and the model also uses an attention mechanism to allow various features to interact and abstract deeper contextual internal semantic associations to improve the model's sentiment classification performance. Finally, experiments are conducted on two publicly available English sentiment classification corpora, and the results prove that the model outperforms other comparison models and effectively improves the sentiment classification performance. The model uses deep memory networks and capsule networks to construct a transfer learning framework and effectively leverages the transfer learning properties of capsule networks to transfer knowledge embedded in large-scale labeled data from similar domains to the target domain, improving the classification performance on small data sets. The use of multidimensional combined features compensates for the lack of a one-dimensional feature attention mechanism, while multiple domain category-based attention computation layers are superimposed to obtain deeper domain-specific sentiment feature information. Based on the segmented convolutional neural network, the model first introduces the dependent subtree of relational attributes to obtain the position weights of each word in the sentence, then introduces domain ontology knowledge in the output layer to constrain the extraction results, and conducts experimental comparison through the data set to verify the validity of the model, which ensures the accuracy of the network term entity and relational attribute recognition extraction and makes the knowledge map constructed in this paper. It ensures the accuracy of the extraction rate of the web term entities and relationship attributes and makes the knowledge map constructed in this paper more factual.

Effect of starch-derived organic acids on the removal of polycyclic aromatic hydrocarbons in an aquaculture-sediment microbial fuel cell.

This study constructed sediment microbial fuel cells (SMFCs) for polycyclic aromatic hydrocarbons (PAHs) removal in contaminated aquaculture sediment. Starch, a waste deposited in aquaculture sediment, was employed as the co-substrate for electricity generation and PAHs removal, and the effect of starch-derived organic acids on SMFC performance was assessed. The results indicated that sufficient starch promoted PAHs removal (69.9% for naphthalene, 55.6% for acenaphthene, and 46.8% for pyrene) in dual-chamber SMFC, whereas excessive starch attenuated SMFC performance because the organic acids accumulation reduced anode pH, decreased species diversity, and changed the microbial communities. The electricity generation and PAHs removal were positively correlated (R > 0.96), and both of them were related to Macellibacteroides belonging to Bacteroidetes. However, a larger single-chamber SMFC device did not obtain enhanced PAHs removal owing to the restricted "effective range" of the anode. Hence, more challenges need to be addressed to realize the practical application of SMFC.

Effects of carbon source on electricity generation and PAH removal in aquaculture sediment microbial fuel cells.

Sediment microbial fuel cells (SMFCs) have been used for treating pollutants in sediment or overlying water. This study investigated the feasibility of constructing SMFCs under aquaculture conditions by employing indigenous carbohydrates as substrates to enhance the removal efficiency of polycyclic aromatic hydrocarbons (PAHs) in sediment, as well as the correlation between PAHs removal and electricity generation in SMFCs. The results showed that adding glucose could allow SMFCs to generate more electrical power and increase the removal efficiency of PAHs (by 57.2% for naphthalene, 41.3% for acenaphthene, and 36.5% for pyrene). In addition, starch enhanced PAHs removal by 49.9%, 35.8%, and 31.2%, respectively, whereas cellulose enhanced removal by 44.3%, 29.3%, and 26.9%, respectively. Pearson correlation coefficients between the level of electrical power generated and the removal masses of the three PAHs were 0.485, 0.830**, and 0.851**. Thus, the use of SMFCs could be an effective approach for PAH treatment in aquaculture, and the electrical power generated could be used as an in-situ indicator for the biodegradation rate of SMFCs.

Predicting the prognosis of glioma by pyroptosis-related signature.

Glioma is the most common malignant primary brain tumour. It is of great significance for the prognosis and personalized treatment of glioma patients to accurate identification of glioma based on biomarkers. Pyroptosis, a kind of programmed cell death, is closely related to tumour progression and tumour immune microenvironment. However, the role of pyroptosis in glioma remained unclear. Herein, we used glioma clinical and expression data from TCGA and CGGA to explore the relationship between pyroptosis and glioma. We first summarized the incidence of copy number variations and somatic mutations of 33 pyroptosis-related genes and explored prognostic correlation of these genes. Based on pyroptosis-related genes, three molecular subgroups of glioma related to prognosis were identified. We also found that each subgroup has unique immune and biological behaviours characteristics. Finally, based on 7 pyroptosis-related genes (CASP3, CASP4, CASP6, CASP8, CASP9, PRKACA and ELANE), we constructed a prognosis model by Lasso and Cox regression, which had a strong predictive power for the overall survival in CGGA test cohort (p < 0.05). In summary, we explored the role of pyroptosis-related genes in gliomas and the association of these genes with tumour immunity. We found the biomarkers valuable to diagnosis and prognosis, hence, provide reference to the development and treatment of tumorigenesis in glioma.

Phosphorylation of Lamin A/C at serine 22 modulates Nav 1.5 function.

Variants in the LMNA gene, which encodes for Lamin A/C, are associated with cardiac conduction disease (CCD). We previously reported that Lamin A/C variants p.R545H and p.A287Lfs*193, which were identified in CCD patients, decreased peak INa in HEK-293 cells expressing Nav 1.5. Decreased peak INa in the cardiac conduction system could account for patients' atrioventricular block. We found that serine 22 (Ser 22) phosphorylation of Lamin A/C was decreased in the p.R545H variant and hypothesized that lamin phosphorylation modulated Nav 1.5 activity. To test this hypothesis, we assessed Nav 1.5 function in HEK-293 cells co-transfected with LMNA variants or treated with the small molecule LBL1 (lamin-binding ligand 1). LBL1 decreased Ser 22 phosphorylation by 65% but did not affect Nav 1.5 function. To test the complete loss of phosphorylation, we generated a version of LMNA with serine 22 converted to alanine 22 (S22A-LMNA); and a version of mutant R545H-LMNA that mimics phosphorylation via serine 22 to aspartic acid 22 substitution (S22D-R545H-LMNA). We found that S22A-LMNA inhibited Lamin-mediated activation of peak INa by 63% and shifted voltage-dependency of steady-state inactivation of Nav 1.5. Conversely, S22D-R545H-LMNA abolished the effects of mutant R545H-LMNA on voltage-dependency but not peak INa . We conclude that Lamin A/C Ser 22 phosphorylation can modulate Nav 1.5 function and contributes to the mechanism by which R545H-LMNA alters Nav 1.5 function. The differential impact of complete versus partial loss of Ser 22 phosphorylation suggests a threshold of phosphorylation that is required for full Nav 1.5 modulation. This is the first study to link Lamin A/C phosphorylation to Nav 1.5 function.