EiG-Search: Generating Edge-Induced Subgraphs for GNN Explanation in Linear Time.

Understanding and explaining the predictions of Graph Neural Networks (GNNs), is crucial for enhancing their safety and trustworthiness. Subgraph-level explanations are gaining attention for their intuitive appeal. However, most existing subgraph-level explainers face efficiency challenges in explaining GNNs due to complex search processes. The key challenge is to find a balance between intuitiveness and efficiency while ensuring transparency. Additionally, these explainers usually induce subgraphs by nodes, which may introduce less-intuitive disconnected nodes in the subgraph-level explanations or omit many important subgraph structures. In this paper, we reveal that inducing subgraph explanations by edges is more comprehensive than other subgraph inducing techniques. We also emphasize the need of determining the subgraph explanation size for each data instance, as different data instances may involve different important substructures. Building upon these considerations, we introduce a training-free approach, named EiG-Search. We employ an efficient linear-time search algorithm over the edge-induced subgraphs, where the edges are ranked by an enhanced gradient-based importance. We conduct extensive experiments on a total of seven datasets, demonstrating its superior performance and efficiency both quantitatively and qualitatively over the leading baselines. Our code is available at: https://github.com/sluxsr/EiG-Search.

TBC1D15-regulated mitochondria-lysosome membrane contact exerts neuroprotective effects by alleviating mitochondrial calcium overload in seizure.

Mitochondrial calcium overload plays an important role in the neurological insults in seizure. The Rab7 GTPase-activating protein, Tre-2/Bub2/Cdc16 domain family member 15 (TBC1D15), is involved in the regulation of mitochondrial calcium dynamics by mediating mitochondria-lysosome membrane contact. However, whether TBC1D15-regulated mitochondria-lysosome membrane contact and mitochondrial calcium participate in neuronal injury in seizure is unclear. We aimed to investigate the effect of TBC1D15-regulated mitochondria-lysosome membrane contact on epileptiform discharge-induced neuronal damage and further explore the underlying mechanism. Lentiviral vectors (Lv) infection and stereotaxic adeno-associated virus (AAV) injection were used to regulate TBC1D15 expression before establishing in vitro epileptiform discharge and in vivo status epilepticus (SE) models. TBC1D15's effect on inter-organellar interactions, mitochondrial calcium levels and neuronal injury in seizure was evaluated. The results showed that abnormalities in mitochondria-lysosome membrane contact, mitochondrial calcium overload, mitochondrial dysfunction, increased levels of reactive oxygen species, and prominent neuronal damage were partly relieved by TBC1D15 overexpression, whereas TBC1D15 knockdown markedly deteriorated these phenomena. Further examination revealed that epileptiform discharge-induced mitochondrial calcium overload in primary hippocampal neurons was closely associated with abnormal mitochondria-lysosome membrane contact. This study highlights the crucial role played by TBC1D15-regulated mitochondria-lysosome membrane contact in epileptiform discharge-induced neuronal injury by alleviating mitochondrial calcium overload.

[Treatment of New Daily Persistent Headache With Esketamine: Report of One Case].

New daily persistent headache (NDPH) is a kind of persistent headache that patients can identify the exact date of the sudden onset.It is one of the rare primary headaches difficult to be cured and may lead to disability,seriously affecting the daily life and work.The exact pathogenesis of NDPH remains unclear,which makes the treatment difficult.Here we report a case of refractory NDPH treated by intravenous injection of esketamine at a sub-anesthetic dose.

Low concentrations of tetrabromobisphenol A promote the biofilm formation of methicillin-resistant Staphylococcus aureus.

The effect and underlying mechanism of tetrabromobisphenol A (TBBPA), a plastic additive, on biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA USA300) remain unknown. This study first investigated the impact of different concentrations of TBBPA on the growth and biofilm formation of USA300. The results indicated that a low concentration (0.5 mg/L) of TBBPA promoted the growth and biofilm formation of USA300, whereas high concentrations (5 mg/L and 10 mg/L) of TBBPA had inhibitory effects. Further exploration revealed that the low concentration of TBBPA enhance biofilm formation by promoting the synthesis of extracellular proteins, release of extracellular DNA (eDNA), and production of staphyloxanthin. RTqPCR analysis demonstrated that the low concentration of TBBPA upregulated genes associated with extracellular protein synthesis (sarA, fnbA, fnbB, aur) and eDNA formation (atlA) and increased the expression of genes involved in staphyloxanthin biosynthesis (crtM), suggesting a potential mechanism for enhanced resistance of USA300 to adverse conditions. These findings shed light on how low concentrations of TBBPA facilitate biofilm formation in USA300 and highlight the indirect impact of plastic additives on pathogenic bacteria in terms of human health. In the future, in-depth studies about effects of plastic additives on pathogenicity of pathogenic bacteria should be conducted. CAPSULE: The protein and eDNA contents in biofilms of methicillin-resistant Staphylococcus aureus are increased by low concentrations of TBBPA.

Abdominal perfusion pressure is critical for survival analysis in patients with intra-abdominal hypertension: mortality prediction using incomplete data.

BACKGROUND: Abdominal perfusion pressure (APP) is a salient feature in the design of a prognostic model for patients with intra-abdominal hypertension (IAH). However, incomplete data significantly limits the size of the beneficiary patient population in clinical practice. Using advanced artificial intelligence methods, we developed a robust mortality prediction model with APP from incomplete data. METHODS: We retrospectively evaluated the patients with IAH from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Incomplete data were filled in using generative adversarial imputation nets (GAIN). Lastly, demographic, clinical, and laboratory findings were combined to build a 7-day mortality prediction model. RESULTS: We included 1354 patients in this study, of which 63 features were extracted. Data imputation with GAIN achieved the best performance. Patients with an APP< 60 mmHg had significantly higher all-cause mortality within 7 to 90 days. The difference remained significant in long-term survival even after propensity score matching (PSM) eliminated other mortality risks between groups. Lastly, the built machine learning model for 7-day modality prediction achieved the best results with an AUC of 0.80 in patients with confirmed IAH outperforming the other four traditional clinical scoring systems. CONCLUSIONS: APP reduction is an important survival predictor affecting the survival prognosis of patients with IAH. We constructed a robust model to predict the 7-day mortality probability of patients with IAH, which is superior to the commonly used clinical scoring systems.

[Research on the classification model of chronic sinusitis based on VGG].

Objective:To build a VGG-based computer-aided diagnostic model for chronic sinusitis and evaluate its efficacy. Methods:①A total of 5 000 frames of diagnosed sinus CT images were collected. The normal group consisted of 1 000 frames（250 frames each of maxillary sinus, frontal sinus, septal sinus, and pterygoid sinus）, while the abnormal group consisted of 4 000 frames（1 000 frames each of maxillary sinusitis, frontal sinusitis, septal sinusitis, and pterygoid sinusitis）. ②The models were trained and simulated to obtain five classification models for the normal group, the pteroid sinusitis group, the frontal sinusitis group, the septal sinusitis group and the maxillary sinusitis group, respectively. The classification efficacy of the models was evaluated objectively in six dimensions: accuracy, precision, sensitivity, specificity, interpretation time and area under the ROC curve（AUC）. ③Two hundred randomly selected images were read by the model with three groups of physicians（low, middle and high seniority） to constitute a comparative experiment. The efficacy of the model was objectively evaluated using the aforementioned evaluation indexes in conjunction with clinical analysis. Results:①Simulation experiment: The overall recognition accuracy of the model is 83.94%, with a precision of 89.52%, sensitivity of 83.94%, specificity of 95.99%, and the average interpretation time of each frame is 0.2 s. The AUC for sphenoid sinusitis was 0.865（95%CI 0.849-0.881）, for frontal sinusitis was 0.924（0.991-0.936）, for ethmoidoid sinusitis was 0.895（0.880-0.909）, and for maxillary sinusitis was 0.974（0.967-0.982）. ②Comparison experiment: In terms of recognition accuracy, the model was 84.52%, while the low-seniority physicians group was 78.50%, the middle-seniority physicians group was 80.50%, and the seniority physicians group was 83.50%; In terms of recognition accuracy, the model was 85.67%, the low seniority physicians group was 79.72%, the middle seniority physicians group was 82.67%, and the high seniority physicians group was 83.66%. In terms of recognition sensitivity, the model was 84.52%, the low seniority group was 78.50%, the middle seniority group was 80.50%, and the high seniority group was 83.50%. In terms of recognition specificity, the model was 96.58%, the low-seniority physicians group was 94.63%, the middle-seniority physicians group was 95.13%, and the seniority physicians group was 95.88%. In terms of time consumption, the average image per frame of the model is 0.20 s, the average image per frame of the low-seniority physicians group is 2.35 s, the average image per frame of the middle-seniority physicians group is 1.98 s, and the average image per frame of the senior physicians group is 2.19 s. Conclusion:This study demonstrates the potential of a deep learning-based artificial intelligence diagnostic model for chronic sinusitis to classify and diagnose chronic sinusitis; the deep learning-based artificial intelligence diagnosis model for chronic sinusitis has good classification performance and high diagnostic efficacy.

Understanding the structures and interactions in gaseous mixtures of water-alcohol by high-resolution infrared spectroscopy.

Interactions of water and chemical or bio-compound have a universal concern and have been extensively studied. For spectroscopic analysis, the complexity and the low resolution of the spectra make it difficult to obtain the spectral features showing the interactions. In this work, the structures and interactions in gaseous water and water-alcohol mixtures were studied using high-resolution infrared (HR-IR) spectroscopy. The spectral features of water clusters of different sizes, including dimer, trimer, tetramer and pentamer, were observed from the measured spectra of the samples in different volume concentrations, and the interactions of water and methanol/ethanol in the mixtures were obtained. In the analysis, a method based on principal component analysis was used to separate the overlapping spectra. In water-alcohol mixtures, when water is less, water molecules tend to interact with the OH groups on the exterior of the alcohol aggregate, and with the increase of water, a water cage forms around the aggregates. Furthermore, the ratio of the molecule number of methanol in the aggregate to that of water in the cage is around 1:2.3, and the ratio for ethanol is about 1:3.2.

[Effects of Polyethylene Microplastics on Soil Nutrients and Enzyme Activities].

The threat of microplastic pollution in soil ecosystems has caused widespread concern. In order to clarify the effect of polyethylene microplastics on soil properties, a 4-month soil incubation experiment was conducted in this study to investigate the effect of different mass fraction (1 %, 2.5 %, and 5 %) and particle sizes (30 mesh and 100 mesh) of polyethylene microplastics on soil chemical properties, nutrient contents, and enzyme activities. The results showed that:① When the particle size was 100 mesh, microplastics at the mass concentrations of the 2.5 % and 5 % treatments significantly reduced soil pH, and the exposure of polyethylene microplastics had no significant effect on soil conductivity. ② Compared to that in CK, the addition of microplastics reduced soil available potassium, available phosphorus, and nitrate nitrogen to varying degrees. The addition of 100 mesh microplastics significantly increased soil organic matter and ammonium nitrogen. ③ When the particle size was 100 mesh, compared to that in CK, treatments of all concentrations significantly increased soil catalase activity and alkaline phosphatase, showing an increasing but not significant trend, and the 5 % concentration treatment significantly decreased soil sucrase activity. ④ Changes in soil properties were influenced by the addition of microplastics of different concentrations and sizes, with higher concentrations and smaller particle sizes having more significant effects. In conclusion, the effects of microplastics on soil properties were not as pronounced as expected, and future research should focus on the mechanisms involved in the different effects.

Integrative and conjugative elements of Pasteurella multocida: Prevalence and signatures in population evolution.

Pasteurella multocida (P. multocida) is a bacterial pathogen responsible for a range of infections in humans and various animal hosts, causing significant economic losses in farming. Integrative and conjugative elements (ICEs) are important horizontal gene transfer elements, potentially enabling host bacteria to enhance adaptability by acquiring multiple functional genes. However, the understanding of ICEs in P. multocida and their impact on the transmission of this pathogen remains limited. In this study, 42 poultry-sourced P. multocida genomes obtained by high-throughput sequencing together with 393 publicly available P. multocida genomes were used to analyse the horizontal transfer of ICEs. Eighty-two ICEs were identified in P. multocida, including SXT/R391 and Tn916 subtypes, as well as three subtypes of ICEHin1056 family, with the latter being widely prevalent in P. multocida and carrying multiple resistance genes. The correlations between insertion sequences and resistant genes in ICEs were also identified, and some ICEs introduced the carbapenem gene blaOXA-2 and the bleomycin gene bleO to P. multocida. Phylogenetic and collinearity analyses of these bioinformatics found that ICEs in P. multocida were transmitted vertically and horizontally and have evolved with host specialization. These findings provide insight into the transmission and evolution mode of ICEs in P. multocida and highlight the importance of understanding these elements for controlling the spread of antibiotic resistance.

Facile synthesis of Bi3O(OH)(AsO4)2 and simultaneous photocatalytic oxidation and adsorption of Sb(III) from wastewater.

Antimony (Sb) decontamination in water is necessary owing to the worsening pollution which seriously threatens human life safety. Designing bismuth-based photocatalysts with hydroxyls have attracted growing interest because of the broad bandgap and enhanced separation efficiency of photogenerated electron/hole pairs. Until now, the available photocatalysis information regarding bismuth-based photocatalysts with hydroxyls has remained scarce and the contemporary report has been largely limited to Bi3O(OH)(PO4)2 (BOHP). Herein, Bi3O(OH)(AsO4)2 (BOHAs), a novel ultraviolet photocatalyst, was fabricated via the co-precipitation method for the first time, and developed to simultaneous photocatalytic oxidation and adsorption of Sb(III). The rate constant of Sb(III) removal by the BOHAs was 32.4, 3.0, and 4.3 times higher than those of BiAsO4, BOHP, and TiO2, respectively, indicating that the introduction of hydroxyls could increase the removal of Sb(III). Additionally, the crucial operational parameters affecting the adsorption performance (catalyst dosage, concentration, pH, and common anions) were investigated. The BOHAs maintained 85% antimony decontamination of the initial yield after five successive cycles of photocatalysis. The Sb(III) removal involved photocatalytic oxidation of adsorbed Sb(III) and subsequent adsorption of the yielded Sb(V). With the acquired knowledge, we successfully applied the photocatalyst for antimony removal from industrial wastewater. In addition, BOHAs could also be powerful photocatalysts in the photodegradation of organic pollutants studies of which are ongoing. It reveals an effective strategy for synthesizing bismuth-based photocatalysts with hydroxyls and enhancing pollutants' decontamination.

Association of 25-hydroxyvitamin D, lipoprotein-associated phospholipase A2 and asymptomatic coronary artery disease in patients with type 2 diabetes mellitus.

AIM: To evaluate the relationship of 25-hydroxyvitamin D (25(OH)D), lipoprotein-associated phospholipase A2 (Lp-PLA2), and coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) patients with no history or symptoms of cardiovascular disease. METHODS: The study identified 66 pairs of T2DM patients with and without CAD using propensity score matching. All subjects performed coronary computed tomography angiography (CCTA). Data on 25(OH)D, Lp-PLA2, and metabolic indexes were collected and analyzed. RESULTS: Compared to the patients without CAD, the patients with CAD had lower 25(OH)D levels and the rate of vitamin D sufficiency, but higher Lp-PLA2 levels. Meanwhile, subjects in the vitamin D sufficiency group had a lower prevalence of CAD and Lp-PLA2 levels. Furthermore, 25(OH)D was inversely correlated with Lp-PLA2, Gensini score, Leiden score, segment involvement score, and segment stenosis score (P < 0.05). After adjusting for age, gender, blood lipids and blood pressure, 25(OH)D was associated with a decreased risk of CAD (aOR 0.933, 95 %CI 0.887-0.983, P = 0.009), while Lp-PLA2 was associated with an increased risk of CAD (aOR 1.014, 95 %CI 1.005-1.022, P = 0.002). CONCLUSIONS: Decreased 25(OH)D and increased Lp-PLA2 could identify patients with a high risk of CAD and are associated with the severity of coronary artery stenosis in T2DM.

Mo-doping and construction of the heterostructure between NiFe LDH and NiSx co-trigger the activity enhancement for overall water splitting.

To reduce the preparation cost of high-purity hydrogen, it is necessary to search suitable non-precious metal catalysts with high activity and robust stability. Herein, two means (heteroatom-doping and the heterostructure construction) were adopted together to improve the dual-function activity of NiFe LDH which was widely used in water electrolysis. Mo doped NiFe LDH nanoflowers were firstly generated by hydrothermal reaction, and then NiSx was modified on the petals via electrodeposition. Finally, the obtained NF/Mo-NiFe LDH/NiSx with large electrochemical active area exhibits the expected electrochemical performance with the overpotential at 100 mA cm-2 of 169 and 249 mV for hydrogen evolution (HER) and oxygen evolution reaction (OER) respectively. Assembling NF/Mo-NiFe LDH/NiSx into a two-electrode device for the integral water electrolysis, it just requires a cell voltage of 1.69 V to drive a current density of 100 mA cm-2, and keeps stable after 50-hour continuous operation in 1.0 M KOH. Mo-doping not only regulates the electronic structure of the transition metals and reduces the energy barrier of HER intermediates, but also facilitates the generation of reactive sites for OER. Meanwhile, the construction of heterointerface ensures the synergism between NiSx and Mo-NiFe LDH and accelerates the electron transfer across interfaces, thus enhancing the bifunctional performance.

Mucoadhesive liposomal delivery system synergizing anti-inflammation and anti-oxidation for enhanced treatment against dry eye disease.

Dry eye disease (DED) is a common and frequent ocular surface disease worldwide, which can cause severe ocular surface discomfort and blurred vision. Inflammation and reactive oxygen species (ROS) play decisive roles in the development of DED. However, existing treatments usually focus on anti-inflammation while ignore the role of ROS in DED. Ever worse, the clinical preparations are easily cleared by nasolacrimal ducts, resulting in poor therapeutic effect. To circumvent these obstacles, here we designed a phenylboronic acid (PBA) modified liposome co-loading immunosuppressant cyclosporin A (CsA) and antioxidant crocin (Cro). The CsA/Cro PBA Lip achieved mucoadhesion through the formation of covalent bonds between PBA and the sialic acid residues on mucin, and consequently improved the retention of drugs on the ocular surface. By inhibiting ROS production and blocking NF-κB inflammatory pathway, CsA/Cro PBA Lip successfully promoted the healing of damaged corneal epithelium, eventually achieving the goal of relieving DED. CsA/Cro PBA Lip is proven a simple yet effective dual-drug delivery system, exhibiting superior antioxidant and anti-inflammatory effects both in vitro and in vivo. This approach holds great potential in the clinical treatment of DED and other related mucosal inflammations.

Inflammation-Driven Nanohitchhiker Enhances Postoperative Immunotherapy by Alleviating Prostaglandin E2-Mediated Immunosuppression.

Inflammation contributes to the immunosuppressive microenvironment and leads to the recurrence of surgically resected tumors. The COX-2/PGE2 axis is considered a key player in shaping the immunosuppression microenvironment. However, targeted modulation of the postoperative tumor microenvironment is challenging. To specifically curb the inflammation and alleviate immunosuppression, here, we developed a PGE2 inhibitor celecoxib (CXB)-loaded bionic nanoparticle (CP@CM) coated with activated murine vascular endothelial cell (C166 cells) membrane to target postoperative melanoma and inhibit its recurrence. CP@CM adhered to inflammatory white blood cells (WBCs) through the adhesion molecules, including ICAM-1, VCAM-1, E-selectin, and P-selection, expressed on the surface of C166 cells. Leveraging the natural tropism of the WBC to the inflammatory postoperative tumor site, CP@CM efficiently targeted postoperative tumors. In melanoma postoperative recurrence models, CXB significantly reduced PGE2 secretion and the recruitment of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Treg) by inhibiting the activity of COX-2. This was followed by an increase in the infiltration of CD8+ T cells and CD4+ T cells in tumor tissues. Additionally, the immune responses were further enhanced by combining a PD-L1 monoclonal antibody. Ultimately, this immunotherapeutic strategy reversed the tumor immunosuppressive microenvironment and inhibited tumor recurrence, demonstrating a promising potential for postoperative immunotherapy for melanoma.

Morphological and phylogenetic analyses reveal three new species of Fusarium (Hypocreales, Nectriaceae) associated with leaf blight on Cunninghamialanceolata in China.

Chinese fir (Cunninghamialanceolata) is a special fast-growing commercial tree species in China with high economic value. In recent years, leaf blight disease on C.lanceolata has been observed frequently. The diversity of Fusarium species associated with leaf blight on C.lanceolata in China (Fujian, Guangxi, Guizhou, and Hunan provinces) was evaluated using morphological study and molecular multi-locus analyses based on RNA polymerase second largest subunit (RPB2), translation elongation factor 1-alpha (TEF-1α), and RNA polymerase largest subunit (RPB1) genes/region as well as the pairwise homoplasy index tests. A total of five Fusarium species belonging to four Fusarium species complexes were recognized in this study. Two known species including Fusariumconcentricum and F.fujikuroi belonged to the F.fujikuroi species complex, and three new Fusarium species were described, i.e., F.fujianense belonged to the F.lateritium species complex, F.guizhouense belonged to the F.sambucinum species complex, and F.hunanense belonged to the F.solani species complex. To prove Koch's postulates, pathogenicity tests on C.lanceolata revealed a wide variation in pathogenicity and aggressiveness among the species, of which F.hunanense HN33-8-2 caused the most severe symptoms and F.fujianense LC14 led to the least severe symptoms. To our knowledge, this study also represented the first report of F.concentricum, F.fujianense, F.fujikuroi, F.guizhouense, and F.hunanense causing leaf blight on C.lanceolata in China.

Facile synthesis of δ-MnO2 biotemplated by waste tobacco stem-silks for enhanced removal of Sb(III).

The elimination of antimony pollution has attracted increasing concerns because of its high toxicity to human health and the natural environment. In this work, biomimetic δ-MnO2 was synthesized by using waste tobacco stem-silks as biotemplate (Bio-δ-MnO2) and used in the capture of Sb(III)from aqueous solution. The tobacco stem-silks not only provided unique wrinkled morphologies but also contained carbon element self-doped into the resulting samples. The maximum Sb(III) adsorption capacity reached 763.4 mg∙g -1, which is 2.06 times higher than δ-MnO2 without template (370.0 mg∙g -1), 4.53 times than tobacco stem-silks carbon (168.5 mg∙g -1), and 10.39 times than commercial MnO2 (73.5 mg∙g -1), respectively. The isotherm and kinetic studies indicated that the adsorption behavior was consistent with the Langmuir isotherm model and the pseudo-second-order kinetic equation. As far as we are aware, the adsorption capacity of Bio-δ-MnO2 is much higher than that of most Sb(III) adsorbents. FT-IR, XPS, SEM, XRD, and Zeta potential analyses showed that the main mechanism for the adsorption of Sb(III) by Bio-δ-MnO2 includes electrostatic attraction, surface complexation, and redox. Overall, this study provides a new sustainable way to convert agricultural wastes to more valuable products such as biomimetic adsorbent for Sb(III) removal in addition to conventional activated carbon and biochar.

Synthesis of organic-solvent-soluble cellulose and preparation of fluorescent polyurethanes for the detection and removal of Hg+ ions.

Modifying cellulose to obtain materials with favorable processing properties and functions is highly significant, especially, for the detection and removal of heavy metal ions. In this study, fluorescent cellulose-based polyurethane (PU) films containing naphthalimide fluorophore were synthesized and could use for the convenient detection and removal of Hg+ ions. Firstly, the microcrystalline cellulose was treated with SOCl2 to convert some -OH groups into -Cl. Simultaneously, a naphthalimide derivative (NAN) with -NH- groups was synthesized. Subsequently, a fluorescent cellulose-based probe (Cel-NAN) was prepared by utilizing the substitution reaction between -Cl on cellulose and -NH- on NAN. Finally, two cellulose-based fluorescent PU films (Cel-NAN-PU1 and Cel-NAN-PU2) were successfully synthesized by reacting the unreacted -OH groups on Cel-NAN with PEG-1000 and HDI/IPDI. These as-prepared PU films could serve as portable fluorescence test papers to Hg+ ions in aqueous solutions. Upon contact with Hg+ ions, the fluorescence was quenched, acting as a "turn-off" probe. Simultaneously, these films could serve as adsorbents for the removal of Hg+ ions from aqueous systems. Cel-NAN-PU1 film exhibited a removal efficiency over 80 % and an adsorption capacity of 8.4 mg·cm-2 for Hg+. These cellulose-based fluorescent PU films possess promising potential in the field of mercury pollution control.

Seven new species of Alternaria (Pleosporales, Pleosporaceae) associated with Chinese fir, based on morphological and molecular evidence.

Chinese fir (Cunninghamialanceolata) is a special fast-growing commercial tree species in China and has significant ecological and economic value. However, it experienced damage from leaf blight caused by pathogenic fungi of the genus Alternaria. To determine the diversity of Alternaria species associated with leaf blight of Chinese fir in China, infected leaves were collected from five major cultivation provinces (Fujian, Henan, Hunan, Jiangsu and Shandong provinces). A total of 48 fungal strains of Alternaria were obtained. Comparison of morphology and phylogenetic analyses, based on nine loci (ITS, SSU, LSU, GAPDH, RPB2, TEF1, Alt a1, endoPG and OPA10-2) of the representative isolates as well as the pairwise homoplasy index tests, revealed that the fungal strains belonged to seven undescribed taxa of Alternaria, which are described here and named as Alternariacunninghamiicolasp. nov., A.dongshanqiaoensissp. nov., A.hunanensissp. nov., A.kunyuensissp. nov., А. longqiaoensissp. nov., A.shandongensissp. nov. and A.xinyangensissp. nov. In order to prove Koch's postulates, pathogenicity tests on detached Chinese fir leaves revealed significant pathogenicity amongst these species, of which A.hunanensis is the most pathogenic to Chinese fir. This study represents the first report of A.cunninghamiicola, A.dongshanqiaoensis, A.hunanensis, A.kunyuensis, A.longqiaoensis, A.shandongensis and A.xinyangensis causing leaf blight on Chinese fir. Knowledge obtained in this study enhanced our understanding of Alternaria species causing leaf blight on Chinese fir and was crucial for the disease management and the further studies in the future.

Constructed competitive endogenous RNA network and patterns of immune infiltration revealing the prognostic signature for cervical cancer.

Aim: To investigate the relationship between potential abnormal epigenetic modification and immune cell infiltration in patients with cervical carcinoma. Materials & methods: RNA expression profiles from The Cancer Genome Atlas database were used to explore the relationship between key biomarkers and tumor-infiltrating immune cells and for clinical specimen validation. Results: Two nomogram models were developed, one with specific ceRNA and the other based on biological markers of related tumor-infiltrating immune cells. Moreover, a key biomarker (RIPOR2), which was significantly relevant to CD8 T cells. Conclusion: RIPOR2 and CD8 T cells play a crucial role in the development and progression of cervical carcinoma, suggesting their potential as markers for guiding future therapeutic strategies.

Genomics and tumor microenvironment of breast mucoepidermoid carcinoma based on whole-exome and RNA sequencing.

Mammary mucoepidermoid carcinoma (MEC) is a rare entity. The molecular characteristics of breast MEC have not been fully investigated due to its rarity. We performed a retrospective study among 1000 patients with breast carcinomas and identified four cases of breast MEC. Clinical and demographic data were collected. Immunohistochemistry panels which were used to diagnose salivary gland MEC and breast carcinomas were also performed. MAML2 rearrangements were detected by FISH and fusion partners were identified by RNA sequencing. Whole-exome sequencing (WES) was used to reveal the genomes of these four breast MEC. Then, the biological functions and features of breast MEC were further compared with those of invasive breast carcinomas and salivary gland MEC.According to Ellis and Auclair's methods, these four breast MEC could be classified as low-grade breast MEC. All the patients were alive, and disease-free survival (PFS) ranged from 20 months to 67 months. Among these four breast MEC, two cases were triple-negative, and the other two cases were found to be ER positive, with one also showing HER2 equivocal by immunohistochemical staining, but no amplification in FISH. FISH analysis confirmed the presence of the MAML2 translocation in three of four tumors, and CRTC1-MAML2 fusion was confirmed in two of them by RNA-sequencing. The average coverage size of WES for the tumor mutation burden estimation was 32 Mb. MUC4, RP1L1 and QRICH2 mutations were identified in at least three tumors, and these mutation also existed in breast invasive carcinoma databases (TCGA, Cell 2015; TCGA, Nature 2012). The results showed that there were many genes in breast MEC overlapping with the breast invasive carcinoma databases mentioned above, range from 5 to 63 genes (median:21 genes). Next, we assessed immune cell infiltration levels in these tumors. In all these tumors, M2 macrophages and plasma cell were in the high infiltration group. Our breast MEC showed different results from the salivary gland MEC, whose plasma cells were in the low infiltration group. Overall, we first analyzed the genomics and tumor microenvironment of breast mucoepidermoid carcinoma and proposed our hypothesis that although MECs arising in the breast resemble their salivary gland counterparts phenotypically, our findings indicate that breast MECs probably resemble invasive breast carcinomas at the genetic level and immune cell infiltration levels. More cases and in deep research need to be done to further understand this rare carcinoma.