Efficient removal of tetracycline hydrochloride by high entropy oxides in visible photo-Fenton catalytic process.

A novel type of oxide material, high entropy oxide (Mn0.2Fe0.2Co0.2Ni0.2Cu0.2)3O4 (MFO) composites with spinel structure were successfully synthesized by a simple solution combustion in this paper, and it was first applied to the degradation of antibiotic organic pollutants in water by photo-Fenton. SEM and BET characterization showed that the composite was porous and had a large specific surface area. XPS results showed that Fe, Mn, Cu, Co and Ni all participated in the redox reaction of the catalytic process. The redox pairs of Mn2+/Mn3+, Cu+/Cu2+, Co2+/Co3+, Ni2+/Ni3+ can accelerate the Fe2+/Fe3+ redox cycling in MFO to activate H2O2 and produce more reactive oxygen species. The catalytic performance of MFO composite was investigated using tetracycline hydrochloride (TC-HCl) as a model pollutant. The results displayed that the degradation rate of TC-HCl by MFO was 92.9% when the initial pH was 4, the dose of H2O2 was 50 mM, and the irradiation time was 60 min. The high entropy oxide MFO composites could build up an internal electric field, which restrains electron-hole recombination, improves the transfer of photogenerated charge carriers and maximize photocatalytic property. In addition, the free radical capture experiment determined that the main active species of the degradation reaction were e-, •O2- and •OH. The synergistic effect of the five components in the high entropy oxide strengthens lattice distortion and defects, increases oxygen vacancies, and thus has enhanced catalytic effect for TC-HCl degradation. This work shows that high entropy oxides have excellent catalytic performance for tetracycline organic pollutants, and it is speculated that high entropy oxides have good application prospects in the field of advanced oxidation technology for the degradation of organic pollutants.

Establishment of Ferroptosis-Associated Molecular Subtypes and Hub Genes Related to the Immune Microenvironment of Heart Failure.

BACKGROUND: Ferroptosis is a form of iron-dependent regulated cell death, and prior work has highlighted the potential utility of ferroptosis-inducing agents as tools to treat heart failure (HF). To date, however, no detailed examinations of the prognostic utility of ferroptosis-related genes (FRGs) in HF have been conducted. METHODS: We used established genomic identification of FRGs for total samples in the gene expression omnibus (GEO) database, screened for differentially expressed FRGs, performed protein-protein interaction analysis and functional analysis of HF immune microenvironment subtypes. Subsequently, we applied tools to calculate immune cell infiltration, compare immune cell, immune response genomic and HLA gene differences between subtypes, and perform candidate drug identification. Finally, preliminary in vivo validation of the screened central genes was performed in animal models. RESULTS: FRGs were compared between samples from HF and healthy control donors, revealing 62 of these genes to be differentially expressed as a function of HF status. HF patient-derived tissues exhibited significant changes in the expression of HLA genes, increase immune cell infiltration, and higher levels of other immune-related genes within the associated immune microenvironment. These FRGs were then leveraged to establish two different immune-related subtypes of HF based on clustering analysis results, after which these subtypes were characterized in further detail. Functional enrichment analyses revealed the identified differentially expressed genes to be enriched in key immune-related pathways including the primary immunodeficiency, natural killer cell-mediated cytotoxicity, FcϵRI signaling, and antigen processing and presentation pathways. The impact of the immune microenvironment was also explored through functional analyses, core gene analyses, and efforts to identify potential drug candidates for HF patients. Moreover, four key hub genes were identified as promising targets for therapeutic intervention in HF, including HDAC1, LNPEP, PSMA1, and PSMA6. Subsequent preclinical work in a mouse model system supported a potential role for HDAC1 as an important biomarker associated with the incidence of HF. CONCLUSIONS: To sum up, these results emphasize the importance of ferroptosis as a regulator of the HF-related immune microenvironment, highlighting viable avenues for the further study of molecular targets amenable to pharmacological intervention with the aim of treating this debilitating disease.

The cerebellopontine angle cistern volumetric differences in trigeminal neuralgia patients with and without vertebrobasilar compression: a case-matched study.

Previous studies have indicated that the small cerebellopontine angle (CPA) cistern plays a role in the pathogenesis of trigeminal neuralgia (TN), but they are likely not involved in TN associated with vertebrobasilar artery (VBA) compression because of its rarity. Forty-four patients with VBA-associated TN and 44 age-, sex-, and hypertension-matched TN patients without VBA compression (non-VBA-associated) were included. All patients underwent high-resolution MRI. The CPA cistern volumes were measured bilaterally. The presence of vertebrobasilar dolichoectasia (VBD) and laterality of the vertebrobasilar junction (VBJ) were observed. The CPA cistern volume on the affected side was smaller than the unaffected side (714.4 ± 372.8 vs 890.2 ± 462.2 mm3, p < 0.001) in non-VBA-associated TN patients, while VBA-associated TN patients show a larger CPA cistern on the affected side than the unffected side (1107.0 ± 500.5 vs 845.3 ± 314.8 mm3, p < 0.001). The prevalence of VBD was higher in patients with VBA-associated TN than in matched non-VBA-associated TN patients (90.9% vs 4.5%, p < 0.001). A positive correlation between the laterality of VBJ and the affected side was found in the VBA-associated TN group (p < 0.0001). Large CPA cistern may be a neuroradiological feature of VBA-associated TN, and most of the VBA-associated TN is accompanied by VBD. The presence of VBD and the lateral shift of VBJ may expand the CPA cistern by squeezing the surrounding tissue on the affected side and also increase the chance of VBA compression on the trigeminal nerve, resulting in the genesis of VBA-associated TN.

Unraveling the molecular crosstalk and immune landscape between COVID-19 infections and ischemic heart failure comorbidity: New insights into diagnostic biomarkers and therapeutic approaches.

BACKGROUND: Coronavirus disease 2019 (COVID-19), resulting from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), remains a persistent global health concern. Evidence has highlighted a significant association between COVID-19 and ischemic heart failure (IHF), contributing to disease progression and increased mortality. This study identified diagnostic biomarkers for these comorbidities and elucidated disease progression's molecular mechanisms. METHODS: We retrieved differentially expressed gene (DEG) data for COVID-19 and IHF from publicly available microarray and RNA-Seq datasets to investigate the underlying mechanisms and potential pathways associated with the co-occurrence of COVID-19 and IHF. By intersecting the results from the two diseases, we obtained diagnostic biomarkers using SVM-RFE and LASSO algorithms. Animal experiments and immunological analyses were conducted to help understand the association between SARS-CoV-2 and IHF in patients, enabling early diagnosis of disease progression. Finally, we analyzed the regulatory network of critical genes and identified potential drug compounds that could target the genetic links identified in our study. RESULTS: 1974 common DEGs were identified between COVID-19 and IHF, contributing to disease progression and potential cancer risk by participating in immune and cancer-related pathways. In addition, we identified six hub genes (VDAC3, EIF2AK2, CHMP5, FTL, VPS4A, and CHMP4B) associated with the co-morbidity, and their diagnostic potential was confirmed through validation using relevant datasets and a mouse model. Functional enrichment analysis and examination of immune cell infiltration revealed immune dysregulation after disease progression. The comorbid hub genes exhibited outstanding immunomodulatory capacities. We also constructed regulatory networks tightly linked to both disorders, including transcription factors (TFs), miRNAs, and genes at both transcriptional and post-transcriptional levels. Finally, we identified 92 potential drug candidates to enhance the precision of anti-comorbidity treatment strategies. CONCLUSION: Our study reveals a shared pathogenesis between COVID-19 and IHF, demonstrating that their coexistence exacerbates disease severity. By identifying and consolidating hub genes as pivotal diagnostic biomarkers for COVID-19 and IHF comorbidity, we have made significant advancements in understanding the underlying mechanisms of these conditions. Moreover, our study highlights dysregulated immunity and increased cancer risk in the advanced stages of disease progression. These findings offer novel perspectives for diagnosing and treating IHF progression during SARS-CoV-2 infection.

Early lateral spread response loss during microvascular decompression for hemifacial spasm: its preoperative predictive factors and impact on surgical outcomes.

When early lateral spread response (LSR) loss before decompression in HFS surgery happens, the value of intraoperative monitoring of LSR for locating neurovascular conflicts and confirming adequate decompression was considered to be reduced. This study aimed to identify preoperative parameters predicting early LSR loss and figure out the impact of early LSR loss on prognosis. Hemifacial spasm (HFS) patients who received microvascular decompression (MVD) under intraoperative electrophysiological monitoring during the period of March 2013-January 2021 were reviewed retrospectively. The patients were divided into two groups according to the disappearance of their LSR before or after decompression. Preoperative clinical and radiological predictors for early LSR loss were evaluated using logistic regression. The relationship between early LSR loss and surgical outcomes was statistically analyzed. A total of 523 patients were included in the study, and the disappearance of their LSR before decompression occurred in 129 patients. In the multivariate analysis, three independent factors predicting early LSR loss were identified: (1) smaller vessel compression; (2) milder nerve deviation; (3) lower posterior fossa crowdedness index (PFCI, calculated as hindbrain volume (HBV)/the posterior fossa volume (PFV) using 3D Slicer software). The median follow-up time was about five years, and no significant differences in the spasm relief and complication rates were found between the 2 groups. Smaller responsible vessels, milder nerve deviation, and more spacious posterior cranial fossa are associated with early LSR loss. However, early LSR loss seems to have no significant adverse effect on MVD outcomes in skilled hands.

Direct Synthesis of Esters from Alkylarenes and Carboxylic Acids: The C-H Bond Dehydroesterification.

Herein, a reaction in which the benzyl C-H bonds of alkylarenes are directly esterified by carboxylic acids to produce benzyl esters in high yields is reported. This reaction is catalyzed by Pd nanoparticles (NPs) on N-doped carbon (CN) composites based on a carbonizing Al-MIL-101(NH2) material, and no oxidants or hydrogen acceptors are required. Use of o-alkylbenzoic acids as substrates leads to phthalides, whereas with carboxylic acids and alkylarenes as the feedstock, the reaction produces the benzyl esters. These reactions that use readily available alkylarenes instead of benzyl halides or benzyl alcohols as raw materials for one-step synthesis of benzyl esters without oxidants are inherently atom- and step-efficient. The CN composites and the CN-supported Pd NP catalysts were prepared and are well characterized. The proposed mechanism involves dehydrogenation of both the carboxylic groups and the benzylic groups and the transformation of benzylic C-H bond into the C-O bond via hydrogen abstraction from the benzylic group through an organopalladium intermediate. The kinetic isotope effect (kH/kD = 2.77) indicated that C(sp3)-H bond cleavage of the alkane aromatics is the rate-determining step.

Novel prognostic features and personalized treatment strategies for mitochondria-related genes in glioma patients.

Background: Gliomas are the most common intracranial nervous system tumours that are highly malignant and aggressive, and mitochondria are an important marker of metabolic reprogramming of tumour cells, the prognosis of which cannot be accurately predicted by current histopathology. Therefore, Identify a mitochondrial gene with immune-related features that could be used to predict the prognosis of glioma patients. Methods: Gliomas data were downloaded from the TCGA database and mitochondrial-associated genes were obtained from the MITOCARTA 3.0 dataset. The CGGA, kamoun and gravendeel databases were used as external datasets. LASSO(Least absolute shrinkage and selection operator) regression was applied to identify prognostic features, and area and nomograms under the ROC(Receiver Operating Characteristic) curve were used to assess the robustness of the model. Single sample genomic enrichment analysis (ssGSEA) was employed to explore the relationship between model genes and immune infiltration, and drug sensitivity was used to identify targeting drugs. Cellular studies were then performed to demonstrate drug killing against tumours. Results: COX assembly mitochondrial protein homolog (CMC1), Cytochrome c oxidase protein 20 homolog (COX20) and Cytochrome b-c1 complex subunit 7 (UQCRB) were identified as prognostic key genes in glioma, with UQCRB, CMC1 progressively increasing and COX20 progressively decreasing with decreasing risk scores. ROC curve analysis of the TCGA training set model yielded AUC (Area Under The Curve) values >0.8 for 1-, 2- and 3-year survival, and the model was associated with both CD8+ T cells and immune checkpoints. Finally, using cellMiner database and molecular docking, it was confirmed that UQCRB binds covalently to Amonafide via lysine at position 78 and threonine at position 82, while cellular assays showed that Amonafide inhibits glioma migration and invasion. Conclusion: Our three mitochondrial genomic composition-related features accurately predict Survival in glioma patients, and we also provide glioma chemotherapeutic agents that may be mitochondria-related targets.

Machine learning screening for Parkinson's disease-related cuproptosis-related typing development and validation and exploration of personalized drugs for cuproptosis genes.

Background: Parkinson's disease (PD) is a common, degenerative disease of the nervous system that is characterized by the death of dopaminergic neurons in the substantia nigra densa (SNpc). There is growing evidence that copper (Cu) is involved in myelin formation and is involved in cell death through modulation of synaptic activity as well as neurotrophic factor-induced excitotoxicity. Methods: This study aimed to explore potential cuproptosis-related genes (CRGs) and immune infiltration patterns in PD and the development of Cu chelators relevant for PD treatment. The PD datasets GSE7621, GSE20141, and GSE49036 were downloaded from the Gene Expression Omnibus (GEO) database. The consensus clustering method was used to classify the specimens of PD. Using weighted gene co-expression network analysis (WGCNA) and random forest (RF) tree model, support vector machine (SVM) learning model, extreme gradient boosting (XGBoost) model, and general linear model (GLM) algorithms to screen disease progression-related models, the column charts were created to verify the accuracy of these CRGs in predicting PD progression. Single sample genomic enrichment analysis (ssGSEA) was used to estimate the correlation between genes associated with copper poisoning and genes associated with immune cells and immune function. Molecular docking was used to verify interactions with copper chelating agents associated with cuproptosis for PD treatment. Results: Through ssGSEA, we identified three copper poisoning related genes ATP7A, NFE2L2 and MTF1, which are related to immune cells in PD. We also verified that LAGASCATRIOL can bind to NFE2L2 through molecular docking. Consistent cluster analysis identified two subtypes, among which C2 subtype was just enriched in PD. And to more accurately diagnose PD progression, patients can benefit from a feature map based on these genes. Conclusions: CRGs such as NFE2L2, MTF1, and ATP7B were identified to be associated with the pathogenesis of PD and provide a possible new direction for the treatment of PD, which needs further in-depth study.

Kaempferol suppresses glioma progression and synergistically enhances the antitumor activity of gefitinib by inhibiting the EGFR/SRC/STAT3 signaling pathway.

Kaempferol (Kae) is a natural flavonoid that has multiple biological activities, such as anti-inflammatory and antitumor activities. However, few studies have been reported on antiglioma effects of Kae. This study aimed to explore the effects and potential mechanisms of Kae and synergistic antitumor activities with gefitinib (Gef) on glioma. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to detect cytotoxicity and cell proliferation. Cell apoptosis and the cell cycle were detected by flow cytometry. Transwell assays were used to detect the migratory and invasive abilities of glioma cells. Network pharmacology and molecular docking analysis were used to screen for core targets of Kae in glioma therapy. Xenograft tumor nude mice were established with U251 cells to verify the antiglioma effects of Kae in vivo. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to detect apoptosis in tumor tissues. The expression of proteins was detected by immunohistochemistry and western blot analysis. Kae inhibited cell proliferation, promoted apoptosis, and induced cell cycle arrest in the G2/M phase of glioma cells in a concentration-dependent manner. Kae inhibited the migration and invasion of glioma cells at low concentrations. Network pharmacology analyses showed that epidermal growth factor receptor (EGFR) and SRC proto-oncogene (SRC) might be direct molecular-binding targets of Kae. Our results showed that Kae inhibited the levels of phosphorylated EGFR, phosphorylated SRC (p-SRC), and phosphorylated signal transducer and activator of transcription 3 (STAT3). In addition, the combination of Kae with Gef significantly inhibited the proliferation of glioma cells. Kae further inhibited EGFR phosphorylation after treatment with Gef. Similarly, Kae further enhanced the inhibition of p-SRC caused by SU6656. Finally, we demonstrated that Kae exerted great antitumor activities and enhanced the antitumor effect of Gef by inhibiting EGFR/SRC/STAT3 signaling pathway in vivo. Kae played a potential role and synergistic antiglioma effects with Gef by inhibiting the phosphorylation of EGFR/SRC dual targets. Kae is expected to be a candidate drug or chemosensitizer in glioma therapy.

Bimetallic Mn-Ce loaded on different zeolite carriers applied in the toluene abatement in air by non-thermal plasma DDBD reactor.

A sequence of zeolite carriers (Carrier = ZSM-5, Small crystal ZSM-5, MCM-41, SBA-15) were used to support active metals Mn-Ce, which have presented an enormous potential for plasma oxidation of toluene in air. The prepared samples were detected by means of N2 adsorption-desorption, SEM, XPS, H2-TPR, etc. Through the activity evaluation in the Non-thermal Plasma Reactor, we found that the catalysts with different carriers showed distinct degradation activities. The performance of mesoporous supported catalysts was better than that of microporous catalysts, of which MCM-41 performed best. 96.3% of toluene can be decomposed, and 97.3% of degraded toluene converted into final products CO2 completely at the initial concentration of 1000 ppm and SIE of 9 kJ/L. From the results, we can see that the appropriate carrier is conducive to maximizing the efficiency of the active metal, and Mn-Ce/MCM-41 got the best performance in the plasma catalysis for toluene abatement.

Pyrroloquinoline quinone modulates YAP-related anti-ferroptotic activity to protect against myocardial hypertrophy.

Background: Pyrroloquinoline quinone (PQQ) has been reported to exhibit cardioprotective and antioxidant activities. Accordingly, this study was developed to explore the effects of PQQ treatment on myocardial hypertrophy and the underlying mechanism of action governing any observed beneficial effects. Methods: A transverse aortic constriction (TAC) model of myocardial hypertrophy was established in vivo using C57BL/6 mice, while neonatal murine cardiomyocytes were stimulated with phenylephrine (PE) as an in vitro validation model system. Results: Treatment of TAC model mice with PQQ significantly suppressed myocardial hypertrophy and fibrosis, in addition to inhibiting the ferroptotic death of hypertrophic myocardial cells in vivo. Subsequent in vitro analyses revealed that treatment with PQQ was sufficient to significantly alleviate PE-induced hypertrophic activity and to prevent ferroptotic induction in these primary murine cardiomyocytes. At the mechanistic level, PQQ was found to promote the upregulation of Yes-associated Protein (YAP), to suppress YAP phosphorylation, and to drive the nuclear translocation of YAP within hypertrophic cardiomyocytes. The use of a specific siRNA construct to knock down YAP expression in vitro further confirmed the ability of PQQ to protect against myocardial hypertrophy at least in part through anti-ferroptotic mechanisms. Conclusion: PQQ can regulate the pathogenesis of myocardial hypertrophy through the induction of YAP-related anti-ferroptotic activity, highlighting the potential value of PQQ as a novel therapeutic agent capable of slowing or preventing the progression of myocardial hypertrophy and thus delaying the onset of heart failure.

MiR-34b/c play a role in early sex differentiation of Amur sturgeon, Acipenser schrenckii.

BACKGROUND: Sex differentiation can be viewed as a controlled regulatory balance between sex differentiation-related mRNAs and post-transcriptional mechanisms mediated by non-coding RNAs. In mammals, increasing evidence has been reported regarding the importance of gonad-specific microRNAs (miRNAs) in sex differentiation. Although many fishes express a large number of gonadal miRNAs, the effects of these sex-biased miRNAs on sex differentiation in teleost fish remain unknown. Previous studies have shown the exclusive and sexually dimorphic expression of miR-34b/c in the gonads of the Amur sturgeon (Acipenser schrenckii), suggesting its potential role in the sex differentiation process. RESULTS: Using quantitative real-time PCR (qPCR), we observed that miR-34b/c showed consistent spatiotemporal expression patterns; the expression levels significantly increased during early sex differentiation. Using in situ hybridization, miR-34c was found to be located in the germ cells. In primary germ cells in vitro, the group subjected to overexpression and inhibition of miR-34c showed significantly higher proliferation ability and lower apoptosis, respectively, compared to the corresponding control group. Luciferase reporter assays using the ar-3'UTR-psiCHECK-2 luciferase vector suggested a targeted regulatory interaction between miR-34b/c and the 3'UTR of the androgen receptor (ar) mRNA. Furthermore, miR-34b/c and ar showed negative expression patterns during early sex differentiation. Additionally, a negative feedback regulation pattern was observed between foxl2 expression in the ovaries and amh and sox9 expression in the testes during early sex differentiation. CONCLUSIONS: This study sheds new light on the roles of miR-34b/c in gonad development of Amur sturgeon, and provides the first comprehensive evidence that the gonad-predominant microRNAs may have a major role in sex differentiation in teleost fish.

Detection of a novel Pestivirus strain in Java ticks (Amblyomma javanense) and the hosts Malayan pangolin (Manis javanica) and Chinese pangolin (Manis pentadactyla).

Pangolins are endangered animals and are listed in the CITES Appendix I of the Convention International Trade Endangered Species of Wild Fauna and Flora as well as being the national first-level protected wild animal in China. Based on a few reports on pangolins infected with pestiviruses of the Flaviviridae family, Pestivirus infections in pangolins have attracted increasing attention. Pangolin pestivirus is a pathogen that may cause diseases such as acute diarrhea and acute hemorrhagic syndrome. To better understand the epidemiology and genomic characterization of pestiviruses carried by pangolins, we detected pestiviruses in dead Malayan pangolin using metavirome sequencing technology and obtained a Pestivirus sequence of 12,333 nucleotides (named Guangdong pangolin Pestivirus, GDPV). Phylogenetic tree analysis based on the entire coding sequence, NS3 gene or RdRp gene sequences, showed that GDPV was closely related to previously reported pangolin-derived Pestivirus and clustered into a separate branch. Molecular epidemiological investigation revealed that 15 Pestivirus-positive tissues from two pangolins individuals with a positivity rate of 5.56%, and six Amblyomma javanense carried pestiviruses with a positivity rate of 19.35%. Moreover, the RdRp gene of the Pestivirus carried by A. javanense showed a high similarity to that carried by pangolins (93-100%), indicating A. javanense is likely to represent the vector of Pestivirus transmission. This study expands the diversity of viruses carried by pangolins and provides an important reference value for interrupting the transmission route of the virus and protecting the health of pangolins.

Full-length gonad transcriptome analysis of Amur sturgeon Dmrt family genes: identification, characterization, and expression patterns during gonadal differentiation.

The regulatory mechanisms that govern sex differentiation in sturgeon are still poorly understood. The doublesex and Mab-3-related transcription factor (Dmrt) gene family is known for its extensive roles in sex determination and differentiation across vertebrates. This study aimed to identify new members of sturgeon Dmrt family genes and core actors in the gonadal differentiation of Amur sturgeon. A full-length gonad transcriptome database was exploited to identify Dmrt gene orthologs. Analyses of phylogenetic relationships and selection pressure were performed, and tissue expression profiles and spatiotemporal expression patterns in gonads were then analyzed using real-time PCR. In total, five Dmrt family genes were identified from the full-length gonad transcriptome, including Dmrt2, DmrtA1, DmrtA2, DmrtB1a, and DmrtB1b. Phylogenetic analysis showed that these genes were clustered into clades corresponding to the doublesex/Mav-3 (DM) genes of vertebrates. Furthermore, the analysis of evolutionary selective pressure indicated that DmrtB1a and DmrtB1b were subject to positive selection, suggesting the existence of adaptive evolution in sturgeon. The extensive tissue expression profiling of each Dmrt family gene revealed typical characteristics. Remarkably, according to a spatiotemporal expression pattern analysis, in later stages, DmrtB1b expression increased in testes and was significantly higher in testes than in ovaries at 24 months after hatching (M) and 36 M. This study provides a genetic resource of full-length Dmrt family genes and increases the understanding of Dmrt functions in sex differentiation in sturgeon.

The assembled and annotated genome of the masked palm civet (Paguma larvata).

BACKGROUND: The masked palm civet (Paguma larvata) acts as an intermediate host of severe acute respiratory syndrome coronavirus (SARS-CoV), which caused SARS, and transfered this virus from bats to humans. Additionally, P. larvata has the potential to carry a variety of zoonotic viruses that may threaten human health. However, genome resources for P. larvata have not been reported to date. FINDINGS: A chromosome-level genome assembly of P. larvata was generated using PacBio sequencing, Illumina sequencing, and Hi-C technology. The genome assembly was 2.44 Gb in size, of which 95.32% could be grouped into 22 pseudochromosomes, with contig N50 and scaffold N50 values of 12.97 Mb and 111.81 Mb, respectively. A total of 21,582 protein-coding genes were predicted, and 95.20% of the predicted genes were functionally annotated. Phylogenetic analysis of 19 animal species confirmed the close genetic relationship between P. larvata and species belonging to the Felidae family. Gene family clustering revealed 119 unique, 243 significantly expanded, and 58 significantly contracted genes in the P. larvata genome. We identified 971 positively selected genes in P. larvata, and one known human viral receptor gene PDGFRA is positively selected in P. larvata, which is required for human cytomegalovirus infection. CONCLUSIONS: This high-quality genome assembly provides a valuable genomic resource for exploring virus-host interactions. It will also provide a reliable reference for studying the genetic bases of the morphologic characteristics, adaptive evolution, and evolutionary history of this species.

The Pan-Cancer Landscape of Crosstalk Between TRP Family and Tumour Microenvironment Relevant to Prognosis and Immunotherapy Response.

Background: Transient Receptor Potential (TRP) channel is a kind of channel protein widely distributed in peripheral and central nervous system. They can be regulated by natural aromatic substances and serve as a therapeutic target for many diseases. However, the role and function of the TRP family genes in tumours remain unclear. Methods: Gene alterations (mutation, copy number, methylation), expression, clinical features, and prognostic value of the TRP family genes were evaluated in pan-cancer using data from The Cancer Genome Atlas and Genotype-Tissue Expression databases. TRP score was calculated by the ssGSEA function of the R package "GSVA". The association of TRP score and the tumour microenvironment (TME), especially the tumour immune microenvironment (TIME), along with immunotherapy response were explored in-depth. Results: TRP family genes were involved in tumour progression and highly associated with poor prognosis in a variety of cancers. TRP score was positively associated with malignant pathways in pan-cancer, such as IL6-JAK-STAT3 signalling, interferon-gamma response, and inflammatory response. All pathways were closely associated with TIME. Elevated TRP score also correlated with multiple immune-related characteristics of the TIME in pan-cancer. Moreover, the TRP score was a predictive biomarker for immune checkpoint inhibitor (ICI) treatments in patients with tumours. Conclusions: TRP family genes play a key role in pan-cancer and are closely associated with TME. Patients with high TRP scores have excellent immune-activated TIME and immunotherapy sensitivity. Therefore, the TRP score could be a potential biomarker for patients with tumours treated with ICI.

Epidemiology and Genomic Characterization of Two Novel SARS-Related Coronaviruses in Horseshoe Bats from Guangdong, China.

Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and SARS-CoV-2, the causative agents of SARS, which broke out in 2003, and coronavirus disease 2019 (COVID-2019), which broke out in 2019, probably originated in Rhinolophus sinicus and R. affinis, respectively. Rhinolophus bats are important hosts for coronaviruses. Many SARS-related coronaviruses (SARSr-CoVs) have been detected in bats from different areas of China; however, the diversity of bat SARSr-CoVs is increasing, and their transmission mechanisms have attracted much attention. Here, we report the findings of SARSr-CoVs in R. sinicus and R. affinis from South China from 2008 to 2021. The full-length genome sequences of the two novel SARSr-CoVs obtained from Guangdong shared 83 to 88% and 71 to 72% nucleotide identities with human SARS-CoV and SARS-CoV-2, respectively, while sharing high similarity with human SARS-CoV in hypervariable open reading frame 8 (ORF8). Significant recombination occurred between the two novel SARSr-CoVs. Phylogenetic analysis showed that the two novel bat SARSr-CoVs from Guangdong were more distant than the bat SARSr-CoVs from Yunnan to human SARS-CoV. We found that transmission in bats contributes more to virus diversity than time. Although our results of the sequence analysis of the receptor-binding motif (RBM) and the expression pattern of angiotensin-converting enzyme 2 (ACE2) inferred that these viruses could not directly infect humans, risks still exist after some unpredictable mutations. Thus, this study increased our understanding of the genetic diversity and transmission of SARSr-CoVs carried by bats in the field. IMPORTANCE Severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 probably originated from the SARS-related coronaviruses (SARSr-CoVs) carried by Rhinolophus bats from Yunnan, China. Systematic investigations of the reservoir hosts carrying SARSr-CoVs in Guangdong and the reservoir distribution and transmission are urgently needed to prevent future outbreaks. Here, we detected SARSr-CoV in Rhinolophus bat samples from Guangdong in 2009 and 2021 and found that the transmission of SARSr-CoV from different host populations contributes more to increased virus diversity than time. Bat SARSr-CoVs in Guangdong had genetic diversity, and Guangdong was also the hot spot for SARSr-CoVs. We once again prove that R. sinicus plays an important role in the maintenance of the SARS-CoVs. Besides, the SARSr-CoVs are mainly transmitted through the intestines in bats, and these SARSr-CoVs found in Guangdong could not use human ACE2 (hACE2), but whether they can pass through intermediate hosts or directly infect humans requires further research. Our findings demonstrate the ability of SARSr-CoVs to spread across species.

Skin Microbiota Was Altered in Crocodile Lizards (Shinisaurus crocodilurus) With Skin Ulcer.

Skin diseases commonly affect reptiles, but their relationships to the closely related skin microbiome are not well-understood. In recent years, both the wild and captive populations of the crocodile lizard, a Class I protected endangered animal in China, have suffered serious skin diseases that hamper the rescue and release projects for their conservation. This study conducted a detailed prevalence investigation of a major dermatosis characterized by foot skin ulcer in crocodile lizards. It should be noticed that skin ulcer has been prevalent in both captive and wild populations. There was positive correlation between skin ulcer and temperature, while no significant relationship between skin ulcer and humidity, sex, and age. We further studied the relationship between skin ulcer and the skin microbiota using meta-taxonomics. Results showed that the skin microbiota of crocodile lizards was significantly different from those of the environmental microbial communities, and that skin microbiota had a significant relationship with skin ulcer despite the impact of environment. Both bacterial and fungal communities on the ulcerated skin were significantly changed, which was characterized by lower community diversity and different dominant microbes. Our findings provide an insight into the relationship between skin microbiota and skin disease in reptile, serving as a reference for dermatological etiology in wildlife conservation.

Enhanced catalytic performance of Cu-doped MnFe2O4 magnetic ferrites: Tetracycline hydrochloride attacked by superoxide radicals efficiently in a strong alkaline environment.

It is important to develop a catalyst that can maintain good activity in alkaline environment for Fenton or Fenton-like reactions. In order to achieve stable Fenton catalytic degradation in a wide pH range, this study reports Cu-doped MnFe2O4 heterogeneous catalysts still has excellent effect when the pH is extended to 11 for removing organic pollutants, such as tetracycline hydrochloride (TC-HCl). The synergistic effect among Fe, Mn and Cu ions has been proved to enhanced the catalytic activity in this work. When the molar ratio of Cu/Mn = 4:1, the porous Cu0·8Mn0·2Fe2O4 materials had the highest photo-Fenton catalytic activity compared with pure MnFe2O4, CuFe2O4 and other CuxMn1-xFe2O4. The XPS showed that Cu0·8Mn0·2Fe2O4 formed oxygen vacancies, which exposed more active sites to attract more H2O2 for TC-HCl degradation. Results indicated 94.3% of TC-HCl was efficiently degraded by 0.1 g/L Cu0·8Mn0·2Fe2O4 with 50 mM H2O2 at pH = 11 under 30 min visible light irradiation, and the corresponding apparent rate constant was 0.08286 min-1. With free radicals quenching experiment, O2- was responsible for the high catalytic degradation and OH was participated in the photo-Fenton reaction. To sum up, Cu0·8Mn0·2Fe2O4 exhibited high activity, great stability and easily recyclable, which eliminated the pH limitation of the Fenton reaction and provided practical application performance for water purification.

Emodin Attenuates LPS-Induced Acute Lung Injury by Inhibiting NLRP3 Inflammasome-Dependent Pyroptosis Signaling Pathway In vitro and In vivo.

Emodin, the effective component of the traditional Chinese medicine Dahuang, has anti-inflammatory effects. However, the protective effects and potential mechanisms of emodin are not clear. This study investigated the protective effects and potential mechanisms of emodin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in vitro and in vivo. In vivo, we designed an LPS-induced ALI rat model. In vitro, we chose the J774A.1 cell line to establish an inflammatory cellular model, and knocked down NOD-like receptor family pyrin domain containing 3 (NLRP3) using small interfering RNA. The mRNA and protein expression of NLRP3, a C-terminal caspase recruitment domain (ASC), caspase 1 (CASP1), and gasdermin D (GSDMD) in cells and lung tissues were detected by western blot and real-time quantitative polymerase chain reaction (PCR). The expression levels of interleukin 1 beta (IL-1ß) and IL-18 in the serum and supernatant were determined by the enzyme-linked immunosorbent assay. The degree of pathological injury in lung tissue was evaluated by hematoxylin and eosin (H&E) staining. In vitro, we demonstrated that emodin could inhibit NLRP3 and then inhibit the expression of ASC, CASP1, GSDMD, IL-1ß, and IL-18. In vivo, we confirmed that emodin had protective effects on LPS-induced ALI and inhibitory effects on NLRP3 inflammasome -dependent pyroptosis. Emodin showed excellent protective effects against LPS-induced ALI by regulating the NLRP3 inflammasome-dependent pyroptosis signaling pathway.