ETLD: an encoder-transformation layer-decoder architecture for protein contact and mutation effects prediction.

The latent features extracted from the multiple sequence alignments (MSAs) of homologous protein families are useful for identifying residue-residue contacts, predicting mutation effects, shaping protein evolution, etc. Over the past three decades, a growing body of supervised and unsupervised machine learning methods have been applied to this field, yielding fruitful results. Here, we propose a novel self-supervised model, called encoder-transformation layer-decoder (ETLD) architecture, capable of capturing protein sequence latent features directly from MSAs. Compared to the typical autoencoder model, ETLD introduces a transformation layer with the ability to learn inter-site couplings, which can be used to parse out the two-dimensional residue-residue contacts map after a simple mathematical derivation or an additional supervised neural network. ETLD retains the process of encoding and decoding sequences, and the predicted probabilities of amino acids at each site can be further used to construct the mutation landscapes for mutation effects prediction, outperforming advanced models such as GEMME, DeepSequence and EVmutation in general. Overall, ETLD is a highly interpretable unsupervised model with great potential for improvement and can be further combined with supervised methods for more extensive and accurate predictions.

CASK and FARP localize two classes of post-synaptic ACh receptors thereby promoting cholinergic transmission.

Changes in neurotransmitter receptor abundance at post-synaptic elements play a pivotal role in regulating synaptic strength. For this reason, there is significant interest in identifying and characterizing the scaffolds required for receptor localization at different synapses. Here we analyze the role of two C. elegans post-synaptic scaffolding proteins (LIN-2/CASK and FRM-3/FARP) at cholinergic neuromuscular junctions. Constitutive knockouts or muscle specific inactivation of lin-2 and frm-3 dramatically reduced spontaneous and evoked post-synaptic currents. These synaptic defects resulted from the decreased abundance of two classes of post-synaptic ionotropic acetylcholine receptors (ACR-16/CHRNA7 and levamisole-activated AChRs). LIN-2's AChR scaffolding function is mediated by its SH3 and PDZ domains, which interact with AChRs and FRM-3/FARP, respectively. Thus, our findings show that post-synaptic LIN-2/FRM-3 complexes promote cholinergic synaptic transmission by recruiting AChRs to post-synaptic elements.

Association Between Different Types of Physical Activity and Hepatic Steatosis and Liver Fibrosis: A Cross-Sectional Study Based on NHANES.

BACKGROUND AND AIMS: Many studies have shown a link between physical activity (PA) and nonalcoholic fatty liver disease (NAFLD). However, more research is needed to investigate the relationship between different types of PA and NAFLD. This study aimed to explore the potential link between different types of PA, hepatic steatosis, and liver fibrosis. STUDY: A cross-sectional study was conducted using the data set from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. A multiple linear regression model was used to examine the linear relationship between different types of PA, the controlled attenuation parameter (CAP), and liver stiffness measurement (LSM). In addition, smoothing curve fitting and threshold effect analysis were used to depict their nonlinear relationship. RESULTS: This study involved 5933 adults. Multiple linear regression analysis revealed a significantly negative correlation between leisure-time PA and CAP, while the relationship between occupation-related PA, transportation-related PA, and CAP was not significant. Subgroup analysis further revealed that leisure-time PA was significantly negatively correlated with CAP in women and younger age groups (under 60 y old), while the relationship was not significant in men and older age groups. In addition, there was a significant negative correlation between leisure-time PA and liver fibrosis in men. CONCLUSIONS: Leisure-time PA can prevent hepatic steatosis, and women and young people benefit more. Occupation-related PA is not associated with hepatic steatosis and cannot replace leisure-time PA. In men, increasing leisure-time PA is more effective in preventing liver fibrosis.

Research progress of inland river water quality monitoring technology based on unmanned aerial vehicle hyperspectral imaging technology.

In recent years, increasing demand for inland river water quality precision management has heightened the necessity for real-time, rapid, and continuous monitoring of water conditions. By analyzing the optical properties of water bodies remotely, unmanned aerial vehicle (UAV) hyperspectral imaging technology can assess water quality without direct contact, presenting a novel method for monitoring river conditions. However, there are currently some challenges to this technology that limit the promotion application of this technology, such as underdeveloped sensor calibration, atmospheric correction algorithms, and limitations in modeling non-water color parameters. This article evaluates the advantages and disadvantages of traditional sensor calibration methods and considers factors like sensor aging and adverse weather conditions that impact calibration accuracy. It suggests that future improvements should target hardware enhancements, refining models, and mitigating external interferences to ensure precise spectral data acquisition. Furthermore, the article summarizes the limitations of various traditional atmospheric correction methods, such as complex computational requirements and the need for multiple atmospheric parameters. It discusses the evolving trends in this technology and proposes streamlining atmospheric correction processes by simplifying input parameters and establishing adaptable correction algorithms. Simplifying these processes could significantly enhance the accuracy and feasibility of atmospheric correction. To address issues with the transferability of water quality inversion models regarding non-water color parameters and varying hydrological conditions, the article recommends exploring the physical relationships between spectral irradiance, solar zenith angle, and interactions with water constituents. By understanding these relationships, more accurate and transferable inversion models can be developed, improving the overall effectiveness of water quality assessment. By leveraging the sensitivity and versatility of hyperspectral sensors and integrating interdisciplinary approaches, a comprehensive database for water quality assessment can be established. This database enables rapid, real-time monitoring of non-water color parameters which offers valuable insights for the precision management of inland river water quality.

Inferior displacement of the lateral rectus muscle insertion in exotropia with mild V-pattern or vertical deviation.

BACKGROUND: To describe clinical features and intraoperative findings of the patients with exotropia who presented mild V-pattern or vertical deviation, and to investigate the surgical outcomes of anatomical relocation of inferiorly displaced lateral rectus (LR) muscle insertion. METHODS: Detailed ophthalmological evaluations were obtained in 42 consecutive patients, and the horizontal rectus muscle insertions were detected intraoperatively. The displaced insertion of LR muscle was corrected accompanied with classic recession-resection procedure. RESULTS: The inferiorly displaced LR muscle insertions were detected in 19 patients (Group A), while the remaining 23 patients (Group B) had normal insertions. The mean distance of displaced insertion from the normal position was 2.92 ± 1.05 mm (range: 1.0-4.0). Mild V-pattern was more common in Group A (78.9%, 15/19) than Group B (47.8%, 11/23), and the magnitude of V-pattern in Group A (6.16 ± 3.91 PD) was also greater than Group B (3.43 ± 3.92 PD). The fundus extorsions of the affected eyes (9.68 ± 4.77 °) were greater than the contralateral eyes (5.91 ± 5.82 °) in Group A. At the 2 months follow-up, mild V-pattern and mild vertical deviation were corrected by upward transposition. The significant correlations were identified between the pre-operative misalignments and the amounts of misalignments correction. CONCLUSIONS: Nearly half of the cases with mild V-pattern or vertical deviation resulted from the inferiorly displaced LR muscle insertion, so the intraoperative exploration of the LR muscle insertion is strongly suggested. Upward transposition may effectively correct both the mild V-pattern and vertical deviation.

Factors influencing the therapeutic effect of hyperopic correction on esotropia in patients with partially accommodative esotropia.

OBJECTIVES: To collate data on partially accommodative esotropia (PAET) to better understand this condition's aetiology and to evaluate and predict the therapeutic effect of a hyperopic correction on PAET. METHODS: Eighty-nine consecutive patients diagnosed with PAET with a spherical equivalent (SE) refractive error >+2.50 D were included in this retrospective review. Clinical characteristics, including gender, age, SE, angle of esodeviation, accommodative convergence/accommodation (AC/A) ratio, near-distance disparity (NDD) and anatomical features of the rectus muscles were compared among different PAET subgroups. Multiple linear regression was used to identify independent factors that influenced the therapeutic effect of a hyperopic correction on esotropia. RESULTS: No significant differences were observed for the angle of esodeviation as a function of age in individuals with PAET. The incidence of SE in PAET participants >9 years old was significantly greater than in those <5 and 6-8 years of age. The therapeutic effect of hyperopic correction on esotropia was positively associated with SE both at distance and near. In addition, the limbus insertion distance (LID) of the lateral rectus (LR) muscle was positively associated with NDD at distance, but negatively associated at near. CONCLUSION: A greater incidence of hyperopia was observed in older (>9 years old) PAET patients. A hyperopic correction had a greater effect on esotropia in individuals with a higher SE, larger LID of the LR muscle and a smaller NDD.

Office-based vergence and anti-suppression therapy for the treatment of small-to-moderate angle intermittent exotropia: A randomised clinical trial.

PURPOSE: To evaluate the short-term (1 week after completion of treatment) effect of office-based vergence and anti-suppression therapy (OBVAT) on the Office Control Score when compared to observation alone in children with small-to-moderate angle intermittent exotropia (IXT). METHODS: In this single-masked (examiner masked), two-arm, single-centre randomised clinical trial, 40 participants, 6 to <18 years of age with untreated IXT, were randomly assigned to OBVAT or observation alone. Participants assigned to therapy received 60 min of OBVAT with home reinforcement once per week for 16 weeks. Therapy included vergence, accommodation and anti-suppression techniques. The primary outcome measure was the comparison of the distance Office Control Score between the two groups at the primary outcome visit (i.e., 17-week follow-up visit). RESULTS: At the primary outcome visit, the OBVAT group (n = 20) had a significantly better distance Office Control Score (adjusted mean difference: -0.9; 95% CI: -0.2 to -1.5; p = 0.008; partial eta squared: 0.19) than the observation group (n = 16). Participants from the OBVAT group were more likely than those from the observation group to have ≥1 point of improvement at the 17-week visit (OBVAT group: 75%; Observation group: 25%; p = 0.006). CONCLUSIONS: In this randomised clinical trial of participants aged 6 to <18 years with IXT, we found that the OBVAT group had a significantly better distance Office Control Score than the observation group at the 17-week visit. This study provides the first data from a randomised clinical trial demonstrating the effectiveness of OBVAT for improving the control of IXT. Eye care practitioners should consider OBVAT as a viable, non-surgical treatment option for IXT. A full-scale randomised clinical trial investigating the long-term effectiveness of OBVAT in treating IXT is warranted.

Sensitive and reliable analysis of endometrial cancer related microRNA using ternary hybridization hairpin probe.

MicroRNA (miRNA), as a kind of small non-coding ribonucleic acid (RNA) that plays a crucial role in regulating transcriptional activities, is a potential biomarker for EC diagnosis. However, reliable detection of miRNA remains a huge challenge, especially for these methods that require multiple probes for signal amplifications, due to the detective deviation caused by variation of probe concentrations. Herein, we present a novel approach for miRNA-205 identification and quantification by employing simply a ternary hairpin probe (TH probe). The ternary hybridization of three sequences results in the construction of the TH probe, which combines high-efficient signal amplification and specific target recognition. A significant number of G-rich sequences have been produced as a result of the enzymes assisted signal amplification process. The G-rich sequences can fold into G-quadruplexes, which can then be detected in a label-free manner by a common fluorescent dye (thioflavin T). Eventually, the approach exhibits a low limit of detection of 278 aM with a wide detection range of 7 orders of magnitude. In summary, the proposed approach possesses a great potential for both clinical diagnosis of EC and fundamental biomedical researches.

Proposal to transfer Bacillus massiliigorillae to the genus Peribacillus as Peribacillus massiliigorillae comb. nov., and Bacillus sinesaloumensis to the genus Ferdinandcohnia as Ferdinandcohnia sinesaloumensis comb. nov.

The present study was carried out to clarify the taxonomic position of Bacillus massiliigorillae and Bacillus sinesaloumensis. The 16S rRNA gene sequences extracted from the Bacillus sinesaloumensis Marseille-P3516T (FTOX00000000) and Bacillus massiliigorillae G2T (CAVL000000000) genomes showed 98.5 and 99.1% similarity with the type strains of Ferdinandcohnia humi and Peribacillus endoradicis, respectively. The amino acid identity (AAI) values of Bacillus sinesaloumensis Marseille-P3516T were higher with Ferdinandcohnia members, while Bacillus massiliigorillae G2T with Peribacillus members. In phylogenomic and phylogenetic trees, Bacillus sinesaloumensis Marseille-P3516T and Bacillus massiliigorillae G2T clade with members of the genera Ferdinandcohnia and Peribacillus, respectively. Based on the above results, we propose to transfer Bacillus massiliigorillae to the genus Peribacillus as Peribacillus massiliigorillae comb. nov., and Bacillus sinesaloumensis to the genus Ferdinandcohnia as Ferdinandcohnia sinesaloumensis comb. nov.

Early detection of myocardial ischemia in resting ECG: analysis by HHT.

BACKGROUND: Exercise electrocardiography (ECG) is a noninvasive test aiming at producing ischemic changes. However, resting ECG cannot be adopted in diagnosing myocardial ischemia till ST-segment depressions. Therefore, this study aimed to detect myocardial energy defects in resting ECG using the Hilbert-Huang transformation (HHT) in patients with angina pectoris. METHODS: Electrocardiographic recordings of positive exercise ECG by performing coronary imaging test (n = 26) and negative exercise ECG (n = 47) were collected. Based on the coronary stenoses severity, patients were divided into three categories: normal, < 50%, and ≥ 50%. During the resting phase of the exercise ECG, all 10-s ECG signals are decomposed by HHT. The RT intensity index, composed of the power spectral density of the P, QRS, and T components, is used to estimate the myocardial energy defect. RESULTS: After analyzing the resting ECG using HHT, the RT intensity index was significantly higher in patients with positive exercise ECG (27.96%) than in those with negative exercise ECG (22.30%) (p < 0.001). In patients with positive exercise ECG, the RT intensity index was gradually increasing with the severity of coronary stenoses: 25.25% (normal, n = 4), 27.14% (stenoses < 50%, n = 14), and 30.75% (stenoses ≥ 50%, n = 8). The RT intensity index of different coronary stenoses was significantly higher in patients with negative exercise ECG, except for the normal coronary imaging test. CONCLUSIONS: Patients with coronary stenoses had a higher RT index at the resting stage of exercise ECG. Resting ECG analyzed using HHT could be a method for the early detection of myocardial ischemia.

Porcine antilymphocyte globulin versus rabbit antithymocyte globulin for intensive immunosuppressive therapy of acquired aplastic anemia: A meta-analysis and systematic review.

OBJECTIVE: Several studies have reported that porcine antilymphocyte globulin (pALG) has a significant effect on aplastic anemia (AA), but their conclusions are inconsistent. To objectively evaluate its efficacy and safety, a meta-analysis was conducted. MATERIALS AND METHODS: We systematically searched the relevant literature on pALG vs. rabbit antithymocyte globulin (rATG) as the first-line treatment in AA patients until August 31, 2022, in electronic databases: PubMed, Cochrane Library, Web of Science, etc. Two researchers independently extracted data and evaluated the quality of the study. Stata 14.0 was used for statistical analysis. RESULTS: 50 studies were included in the analysis. The overall responses at 3, 6, and 12 months between the pALG group and rATG group were equivalent. We analyzed early mortality, total mortality, relapse rates, and 5-year survival after the administration of pALG or rATG, and there was no significant difference between the pALG and rATG groups. In our study, the incidence of infection in the pALG group was better than that in the rATG group, OR = 0.63, 95% CI (0.44 - 0.88), p = 0.008, which showed a statistically significant difference. CONCLUSION: The efficacy of pALG in AA patients is equivalent to that of rATG. rATG was associated with a significantly higher incidence rate of infection than pALG.

The Signaling Pathway of the ADP Receptor P2Y12 in the Immune System: Recent Discoveries and New Challenges.

P2Y12 is a G-protein-coupled receptor that is activated upon ADP binding. Considering its well-established role in platelet activation, blocking P2Y12 has been used as a therapeutic strategy for antiplatelet aggregation in cardiovascular disease patients. However, receptor studies have shown that P2Y12 is functionally expressed not only in platelets and the microglia but also in other cells of the immune system, such as in monocytes, dendritic cells, and T lymphocytes. As a result, studies were carried out investigating whether therapies targeting P2Y12 could also ameliorate inflammatory conditions, such as sepsis, rheumatoid arthritis, neuroinflammation, cancer, COVID-19, atherosclerosis, and diabetes-associated inflammation in animal models and human subjects. This review reports what is known about the expression of P2Y12 in the cells of the immune system and the effect of P2Y12 activation and/or inhibition in inflammatory conditions. Lastly, we will discuss the major problems and challenges in studying this receptor and provide insights on how they can be overcome.

Solubility Determination and Comprehensive Analysis of the New Heat-Resistant Energetic Material TNBP.

To improve the crystal quality of 4,8-bis(2,4,6-trinitrophenyl)difurazolo [3,4-b:3',4'-e] pyrazine (TNBP), the solubility of TNBP in organic solvents (six pure and four mixed solvents) was determined by the laser monitoring technique from 293.15 to 353.15 K. The results showed that the solubility was positively correlated with the increase in the experimental temperature and the main solvent content, except for the co-solvent phenomenon in the DMSO + ethyl acetate solvent mixture. To explain the dissolution behavior of TNBP, the KAT-SER model was analyzed for pure solvent systems, and it was found that hydrogen bonding alkalinity and self-cohesiveness were the main influencing factors. The free energy of solvation and radial distribution function of TNBP in mixed solvents were also obtained by molecular dynamics simulation, and the effect of solute-solvent and solvent-solvent interactions on the solubility trend was analyzed. The experimental data were correlated using three empirical equations (van't Hoff equation, modified Apelblat equation, and λh equation), and the deviation analysis showed the good applicability of the modified Apelblat model. Furthermore, the dissolution of TNBP was heat-absorbing and not spontaneous, according to the thermodynamic characteristics estimated by the van't Hoff equation.

[Effect of acetylalkannin from Arnebia euchroma on proliferation, migration, and invasion of human melanoma A375 cells].

This study aimed to explore the effect and mechanism of acetylalkannin from Arnebia euchroma on the proliferation, migration, and invasion of human melanoma A375 cells. A375 cells were divided into a blank group, and low-, medium-, and high-dose acetylalkannin groups(0.5, 1.0, and 2.0 µmol·L~(-1)). The MTT assay was used to detect cell proliferation. Cell scratch and transwell migration assays were used to detect cell migration ability, and the transwell invasion assay was used to detect cell invasion ability. Western blot was used to detect the protein expression of migration and invasion-related N-cadherin, vimentin, matrix metalloproteina-se-9(MMP-9), and Wnt/ß-catenin pathway-related Wnt1, Axin2, glycogen synthase kinase-3ß(GSK-3ß), phosphorylated GSK-3ß(p-GSK-3ß), ß-catenin, cell cycle protein D_1(cyclin D_1), and p21. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) was used to detect the mRNA expression of E-cadherin, matrix metalloproteinase-2(MMP-2), N-cadherin, vimentin, ß-catenin, snail-1, and CD44. MTT results showed that the cell inhibition rates in the acetylalkannin groups significantly increased as compared with that in the blank group(P<0.01). The results of cell scratch and transwell assays showed that compared with the blank group, the acetylalkannin groups showed reduced cell migration and invasion, and migration and invasion rates(P<0.05, P<0.01) and weakened horizontal and vertical migration and invasion abilities. Western blot results showed that compared with the blank group, the high-dose acetylalkannin group showed increased expression of Axin2 protein(P<0.05), and decreased expression of N-cadherin, vimentin, MMP-9, Wnt1, p-GSK-3ß, ß-catenin, cyclin D_1, and p21 proteins(P<0.05, P<0.01). The expression of GSK-3ß protein did not change significantly. PCR results showed that the overall trend of MMP-2, N-cadherin, vimentin, ß-catenin, snail-1, and CD44 mRNA expression was down-regulated(P<0.01), and the expression of E-cadherin mRNA increased(P<0.01). Acetylalkannin can inhibit the proliferation, migration, and invasion of human melanoma A375 cells, and its mechanism of action may be related to the regulation of Wnt/ß-catenin signaling pathway.

[Mechanism of Berberis atrocarpa anthocyanin against Alzheimer's disease based on network pharmacology and experimental verification].

This study aimed to explore the potential mechanism of Berberis atrocarpa Schneid. anthocyanin against Alzheimer's disease(AD) based on network pharmacology, molecular docking technology, and in vitro experiments. Databases were used to screen out the potential targets of the active components of B. atrocarpa and the targets related to AD. STRING database and Cytoscape 3.9.0 were adopted to construct a protein-protein interaction(PPI) network and carry out topological analysis of the common targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed on the target using the DAVID 6.8 database. Molecular docking was conducted to the active components and targets related to the nuclear factor kappa B(NF-κB)/Toll-like receptor 4(TLR4) pathway. Finally, lipopolysaccharide(LPS) was used to induce BV2 cells to establish the model of AD neuroinflammation for in vitro experimental validation. In this study, 426 potential targets of active components of B. atrocarpa and 329 drug-disease common targets were obtained, and 14 key targets were screened out by PPI network. A total of 623 items and 112 items were obtained by GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking results showed that NF-κB, NF-κB inhibitor(IκB), TLR4, and myeloid differentiation primary response 88(MyD88) had good binding abilities to the active components, and malvidin-3-O-glucoside had the strongest binding ability. Compared with the model group, the concentration of nitric oxide(NO) decreased at different doses of malvidin-3-O-glucoside without affecting the cell survival rate. Meanwhile, malvidin-3-O-glucoside down-regulated the protein expressions of NF-κB, IκB, TLR4, and MyD88. This study uses network pharmacology and experimental verification to preliminarily reveal that B. atrocarpa anthocyanin can inhibit LPS-induced neuroinflammation by regulating the NF-κB/TLR4 signaling pathway, thereby achieving the effect against AD, which provides a theoretical basis for the study of its pharmacodynamic material basis and mechanism.

Design and Synthesis of Glycosylated Cholera Toxin B Subunit as a Tracer of Glycoprotein Trafficking in Organelles of Living Cells.

Glycosylation of proteins is known to be essential for changing biological activity and stability of glycoproteins on the cell surfaces and in body fluids. Delivering of homogeneous glycoproteins into the endoplasmic reticulum (ER) and the Golgi apparatus would enable us to investigate the function of asparagine-linked (N-) glycans in the organelles. In this work, we designed and synthesized an intentionally glycosylated cholera toxin B-subunit (CTB) to be transported to the organelles of mammalian cells. The heptasaccharide, the intermediate structure of various complex-type N-glycans, was introduced to the CTB. The synthesized monomeric glycosyl-CTB successfully entered mammalian cells and was transported to the Golgi and the ER, suggesting the potential use of synthetic CTB to deliver and investigate the functions of homogeneous N-glycans in specific organelles of living cells.

Chemotherapy dose per kilogram lean body mass increased dose-limiting toxicity event in male head and neck cancer with taxane and platinum-based induction therapy.

BACKGROUND: This study aimed to determine whether drug doses per kilogram of lean body mass (LBM) were associated with dose-limiting toxicity (DLT) events in head and neck cancer (HNC) patients. METHODS: This retrospective cohort study included 179 HNC patients who underwent induction chemotherapy (IC) at a medical center from May 1, 2014, to May 31, 2021. HNC patients' characteristics, tumor factors, IC regimen and dose, laboratory data, and body composition factors, including lean body mass (LBM) and skeletal muscle index (SMI), derived from CT, MRI, or PET scan images and drug dose per kilogram LBM were recorded. Dose-limiting toxicity (DLT) events were regarded as the primary outcome. Multivariate logistic regression was used to establish a novel risk score for DLT events by the abovementioned variables. The above-mentioned risk score was validated in another cohort. RESULTS: The overall DLT events during the first cycle of IC for 179 HNC patients was 24%. After stratifying by gender, docetaxel per kilogram LBM > 2.52 mg/kg (adjusted odds ratio [aOR]: 3.18; 95% confidence interval [CI], 1.25-8.09), pre-treatment glutamic pyruvic transaminase (GPT) > 40 U/L (aOR, 2.61; 95% CI, 1.03-6.64), and history of chronic liver diseases (aOR, 3.98; 95% CI, 1.03-15.46) were significant variables in male HNC patients. The DLT events risk was categorized by summation of the above-mentioned risk factors for male HNC patients. Three risk groups were stratified by overall event of 17.6%, 25.8%, and 75%. The above-mentioned risk score had an acceptable discriminatory ability in another validation cohort. CONCLUSIONS: Among male HNC patients treated with IC, docetaxel per kilogram LBM more than 2.52 mg/kg, pre-treatment GPT > 40 U/L, and history of chronic liver disease were significant risk factors for DLT events. Identifying high-risk patients could help physicians prevent severe/fatal complications among HNC patients undergoing IC, especially for the male individuals.

Proposal for transfer Bacillus alkalicola to the genus Evansella as Evansella alkalicola comb. nov.

The taxonomic position of Bacillus alkalicola was evaluated using phylogenetic and genome-based comparisons. In phylogenetic (based on 16S rRNA gene sequence) and phylogenomic (based on concatenation of protein-marker genes) trees, Bacillus alkalicola clade with the members of the genus Evansella. The amino acid identity (AAI) values suggested to reclassify Bacillus alkalicola as a member of the genus Evansella. The average nucleotide identity (ANI) value between Bacillus alkalicola and the members of the genus Evansella was lower than the threshold values for bacterial species delineation. Based on the results, we propose to transfer Bacillus alkalicola to the genus Evansella as Evansella alkalicola comb. nov. The type strain is Zby6T (=CGMCC 1.10368T=JCM 17098T=NBRC 107743T).

Proposal to transfer Bacillus lacisalsi Dong et al. 2021 to the genus Alteribacter as Alteribacter lacisalsi comb. nov.

In the present study, the taxonomic position of Bacillus lacisalsi YSP-3T was evaluated using phylogenetic and genome-based comparison. B. lacisalsi YSP-3T showed the highest 16S rRNA gene sequence similarity to Alteribacter natronophilus M30T (98.4 %), followed by Alteribacter aurantiacus K1-5T (97.5 %) and Alteribacter populi FJAT-45347T (97.2 %). In phylogenetic (based on 16S rRNA gene sequences) and phylogenomic (based on 71 bacterial single-copy genes) trees, B. lacisalsi YSP-3T clustered with the members of the genus Alteribacter. The amino acid identity (AAI) values between B. lacisalsi YSP-3T and the members of the genus Alteribacter were >65 %, which is above the cut-off level (65-95 %) for genus delineation. The average nucleotide identity (ANI) values between B. lacisalsi YSP-3T and the members of the genus Alteribacter were <95 %, which is lower than the threshold value (95-96 %) for bacterial species delineation. The AAI value suggested that B. lacisalsi YSP-3T was a member of the genus Alteribacter while the ANIb value suggested it as a novel species of the genus Alteribacter. Based on the results, we propose to transfer Bacillus lacisalsi to the genus Alteribacter as Alteribacter lacisalsi comb. nov.

p38α Kinase Auto-Activation through Its Conformational Transition Induced by Tyr323 Phosphorylation.

p38α is a key serine/threonine kinase that can enable atypical auto-activation through Zap70 phosphorylation and initiate T cell receptor signaling. The auto-activation plays an important role in autoimmune diseases. Although the classical activation mechanism of p38α has been studied in-depth, the atypical activation mechanism of Y323 phosphorylation-induced p38α auto-activation remains largely unexplained, especially the regulatory effects of phosphorylation on different sites (Y323 vs T180). From the X-ray experimental data, we identified the inactive and active states of p38α using principal component analysis. To understand the auto-activation process and the internal driving mechanism, a computational paradigm that couples the targeted molecular dynamics simulations, the String Method, and the umbrella sampling strategy were employed to generate the conformational landscape of p38α, including p38α T180-Y323, p38α T180-pY323, and p38α pT180-pY323 systems (pT180/pY323: phosphorylated T180/Y323). We explored that pY323 could change the conformational distribution and promote the conformational transition of p38α from the inactive state to the active state. Auto-activation of p38α is regulated by pY323 through destabilization of the hydrophobic core structure and aided by R173. This study will further explain the conformational transition of p38α induced by Y323 phosphorylation and provide insights into the universal molecular auto-activation mechanism of the p38 subfamily at the atomic level.