Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

The calculated electronic and optical properties of ß-Ga2O3 based on the first principles.

INTRODUCTION: The electronic and optical properties of ß-Ga2O3 have been investigated by CASTEP using first principles. It is found that ß-Ga2O3 has an indirect band gap and the conduction band base is located at the Γ point. The stability of ß-Ga2O3 is demonstrated by the calculation of elastic constants, and the ductility of ß-Ga2O3 is demonstrated by the ratio of Poisson's ratio to shear modulus. The optical property analysis shows that ß-Ga2O3 has a high absorption capacity in the ultraviolet region, but a low absorption capacity in visible and infrared light. CONTEXT: The structure, optical, and electronic properties of ß-Ga2O3 are calculated and analyzed based on first-principles calculation. The optimized structures of ß-Ga2O3 are in good agreement with previously studied. In this paper, the elastic, electronic, and optical properties of ß-Ga2O3 are calculated. METHODS: The CASTEP code was employed to execute these calculations in the present work, where the exchange-correlation interactions were treated in the generalized gradient approximation (GGA) using the Perdew-Burke-Ernzerhof (PBE) functional in the geometry optimizations and electronic and elastic properties.

SERT-StructNet: Protein secondary structure prediction method based on multi-factor hybrid deep model.

Protein secondary structure prediction (PSSP) is a pivotal research endeavour that plays a crucial role in the comprehensive elucidation of protein functions and properties. Current prediction methodologies are focused on deep-learning techniques, particularly focusing on multi-factor features. Diverging from existing approaches, in this study, we placed special emphasis on the effects of amino acid properties and protein secondary structure propensity scores (SSPs) on secondary structure during the meticulous selection of multi-factor features. This differential feature-selection strategy results in a distinctive and effective amalgamation of the sequence and property features. To harness these multi-factor features optimally, we introduced a hybrid deep feature extraction model. The model initially employs mechanisms such as dilated convolution (D-Conv) and a channel attention network (SENet) for local feature extraction and targeted channel enhancement. Subsequently, a combination of recurrent neural network variants (BiGRU and BiLSTM), along with a transformer module, was employed to achieve global bidirectional information consideration and feature enhancement. This approach to multi-factor feature input and multi-level feature processing enabled a comprehensive exploration of intricate associations among amino acid residues in protein sequences, yielding a Q3 accuracy of 84.9% and an Sov score of 85.1%. The overall performance surpasses that of the comparable methods. This study introduces a novel and efficient method for determining the PSSP domain, which is poised to deepen our understanding of the practical applications of protein molecular structures.

Posttraumatic stress disorder and spousal relationships in natural disaster victims: a longitudinal study.

BACKGROUND: Posttraumatic stress disorder (PTSD) symptoms after natural disaster can have a detrimental effect on marital relationships, which may be through parenting-related factor. AIMS: The study aimed to examine the mechanism underlying the long-term effects of PTSD symptoms on marital satisfaction via coparenting, and its differences between men and women following the Super Typhoon Lekima. METHODS: Participants were 465 married victims with children. They reported their PTSD, coparenting, and marital satisfaction at three and fifteen months after the tropical cyclone. RESULTS: The results showed that for women, only higher negative cognitive and emotional alterations (NCEA) symptoms were associated with lower marital satisfaction through conflict coparenting. For men, higher intrusion, NCEA, and hyperarousal symptoms were associated with marital satisfaction through different coparenting. To be specific, for men, higher intrusion symptoms were associated with lower marital satisfaction via less reprimand coparenting; higher NCEA symptoms were associated with lower marital satisfaction via less integrity coparenting, and associated with higher marital satisfaction via less conflict coparenting; higher hyperarousal symptoms were associated with lower marital satisfaction via more conflict coparenting. CONCLUSIONS: These findings suggested that the long-term effect of PTSD symptoms on marital satisfaction via coparenting mainly showed for men.

Benign mixed mammary tumor with sebaceous differentiation in a dog.

We describe here a case of canine mammary benign mixed tumor with sebaceous metaplasia in the right fifth mammary gland of an eight-year-old, intact female Poodle dog. Grossly, the mass was firm with off-white, poorly lobulated cut surfaces. Histologically, the luminal epithelial cells and myoepithelial cells proliferated with cartilage formation and focal squamous metaplasia. Moreover, a large number of nests of various sizes, which were filled with foamy cells in the center and associated with basaloid reserve-like cells in the periphery, showed sebaceous gland-like structures. Immunohistochemically, myoepithelial cells and reserve-like cells in the metaplastic sebaceous gland-like structures were CK14, α-smooth muscle actin (α-SMA) and p63 positive, suggesting a possibility that these two components may have a common cell of origin.

[Formation Potential of Secondary Organic Aerosols and Sources of Volatile Organic Compounds During an Air Pollution Episode in Autumn, Langfang].

A typical particulate matter pollution process occurred from October 9 to 17,2018,in Langfang,and 99 types of volatile organic compounds (VOCs) were monitored by using ZF-KU-1007. The characteristics of VOCs,formation potential of secondary organic aerosol (SOA),and source of VOCs were systematically analyzed. The results showed that the maximum concentration of PM2.5 was 198 µg·m-3 during the pollution process and was 2.64 times the National Ambient Air Quality Standard (GB 3095-2012). The average concentration of VOCs was 56.8×10-9,127.8×10-9,and 72.5×10-9 in the early,middle,and late stages of the pollution process,respectively,and the concentration of VOCs increased significantly in the middle stage. The formation potential of SOA was significantly positively correlated with PM2.5,and the contribution of aromatic hydrocarbon for SOA was larger and significantly correlated with the concentration of PM2.5. In the middle pollution stage,SOA increased,and the contribution ratio of aromatic hydrocarbon increased significantly. Conversely,the contribution of alkanes and olefin decreased significantly,which showed that aromatic hydrocarbons,namely benzene series,were the dominant species of SOA generation and had a great influence on the pollution process. Benzene,toluene,m-/p-xylene,o-xylene,and ethylbenzene and nonane,n-undecane,and methylcyclohexane were the priority control species in this pollution process. Solvent use source and motor vehicle emission source (gasoline and diesel vehicles) were the main sources affecting the concentration of VOCs during the autumn pollution process of Langfang,among which the contribution of gasoline vehicle emissions increased significantly in the middle pollution contribution and was the key control source.

[Factors influencing the occurrence of small for gestational age at different degrees]. / ä¸åŒç¨‹åº¦å°äºŽèƒŽé¾„å„¿å‘ç”Ÿçš„å½±å“å› ç´ åˆ†æž.

OBJECTIVES: To investigate the factors influencing the occurrence of small for gestational age (SGA) at different degrees and provide a basis for early identification of severe SGA cases. METHODS: Neonatal and maternal prenatal information were retrospectively collected from January 2018 to December 2022 at Peking University People's Hospital. The neonates were divided into three groups: severe SGA group (birth weight below the 3rd percentile for gestational age and sex), mild SGA group (birth weight ≥3rd percentile and <10th percentile), and non-SGA group (birth weight ≥10th percentile). An ordered multinomial logistic regression model was used to analyze the factors influencing the occurrence of SGA at different degrees. RESULTS: A total of 14 821 neonates were included, including 258 cases (1.74%) in the severe SGA group, 902 cases (6.09%) in the mild SGA group, and 13 661 cases (92.17%) in the non-SGA group. The proportions of preterm births and stillbirths were higher in the severe SGA group compared to the mild SGA and non-SGA groups (P<0.0125). The proportion of neonatal asphyxia was higher in both the severe SGA and mild SGA groups compared to the non-SGA group (P<0.0125). Ordered multinomial logistic regression analysis showed that maternal pre-pregnancy underweight (OR=1.838), maternal pre-pregnancy obesity (OR=3.024), in vitro fertilization-embryo transfer (OR=2.649), preeclampsia (OR=1.743), connective tissue disease during pregnancy (OR=1.795), nuchal cord (OR=1.213), oligohydramnios (OR=1.848), and intrauterine growth restriction (OR=27.691) were all associated with a higher risk of severe SGA (P<0.05). Maternal parity as a multipara (OR=0.457) was associated with a lower likelihood of severe SGA (P<0.05). CONCLUSIONS: Maternal pre-pregnancy underweight, maternal pre-pregnancy obesity, in vitro fertilization-embryo transfer, preeclampsia, connective tissue disease during pregnancy, oligohydramnios, nuchal cord, and intrauterine growth restriction are closely related to the occurrence of more severe SGA. Maternal parity as a multipara acts as a protective factor against the occurrence of severe SGA.

UFObow: A single-wavelength excitable Brainbow for simultaneous multicolor ex-vivo and in-vivo imaging of mammalian cells.

Brainbow is a genetic cell-labeling technique that allows random colorization of multiple cells and real-time visualization of cell fate within a tissue, providing valuable insights into understanding complex biological processes. However, fluorescent proteins (FPs) in Brainbow have distinct excitation spectra with peak difference greater than 35 nm, which requires sequential imaging under multiple excitations and thus leads to long acquisition times. In addition, they are not easily used together with other fluorophores due to severe spectral bleed-through. Here, we report the development of a single-wavelength excitable Brainbow, UFObow, incorporating three newly developed blue-excitable FPs. We have demonstrated that UFObow enables not only tracking the growth dynamics of tumor cells in vivo but also mapping spatial distribution of immune cells within a sub-cubic centimeter tissue, revealing cell heterogeneity. This provides a powerful means to explore complex biology in a simultaneous imaging manner at a single-cell resolution in organs or in vivo.

The novel HLA-C*03:94:02 allele identified by next-generation sequencing in a Chinese individual.

HLA-C*03:94:02 differs from HLA-C*03:94:01 by a single nucleotide substitution in exon 2 (codon 17 GGA->GGG).

Neuroinflammation of Microglial Regulation in Alzheimer's Disease: Therapeutic Approaches.

Alzheimer's disease (AD) is a complex degenerative disease of the central nervous system that is clinically characterized by a progressive decline in memory and cognitive function. The pathogenesis of AD is intricate and not yet fully understood. Neuroinflammation, particularly microglial activation-mediated neuroinflammation, is believed to play a crucial role in increasing the risk, triggering the onset, and hastening the progression of AD. Modulating microglial activation and regulating microglial energy metabolic disorder are seen as promising strategies to intervene in AD. The application of anti-inflammatory drugs and the targeting of microglia for the prevention and treatment of AD has emerged as a new area of research interest. This article provides a comprehensive review of the role of neuroinflammation of microglial regulation in the development of AD, exploring the connection between microglial energy metabolic disorder, neuroinflammation, and AD development. Additionally, the advancements in anti-inflammatory and microglia-regulating therapies for AD are discussed.

Advantage of whole-mount histopathology in prostate cancer: current applications and future prospects.

BACKGROUND: Whole-mount histopathology (WMH) has been a powerful tool to investigate the characteristics of prostate cancer. However, the latest advancement of WMH was yet under summarization. In this review, we offer a comprehensive exposition of current research utilizing WMH in diagnosing and treating prostate cancer (PCa), and summarize the clinical advantages of WMH and outlines potential on future prospects. METHODS: An extensive PubMed search was conducted until February 26, 2023, with the search term "prostate", "whole-mount", "large format histology", which was limited to the last 4 years. Publications included were restricted to those in English. Other papers were also cited to contribute a better understanding. RESULTS: WMH exhibits an enhanced legibility for pathologists, which improved the efficacy of pathologic examination and provide educational value. It simplifies the histopathological registration with medical images, which serves as a convincing reference standard for imaging indicator investigation and medical image-based artificial intelligence (AI). Additionally, WMH provides comprehensive histopathological information for tumor volume estimation, post-treatment evaluation, and provides direct pathological data for AI readers. It also offers complete spatial context for the location estimation of both intraprostatic and extraprostatic cancerous region. CONCLUSIONS: WMH provides unique benefits in several aspects of clinical diagnosis and treatment of PCa. The utilization of WMH technique facilitates the development and refinement of various clinical technologies. We believe that WMH will play an important role in future clinical applications.

Disordered GPR43/NLRP3 expression in peripheral leukocytes of patients with atrial fibrillation is associated with intestinal short chain fatty acids levels.

BACKGROUND: Atrial fibrillation (AF) is associated with circulating inflammation. Short-chain fatty acids (SCFAs) derived from gut microbiota (GM) regulate leukocyte function and inhibit the release of inflammatory cytokines, which are partly mediated by the G-protein-coupled receptor 43 (GPR43) signaling. This study aimed to investigate the expression of GPR43/NOD-like receptors family pyrin domain containing 3 (NLRP3) in leukocytes and the interaction with intestinal SCFAs levels in AF patients. METHODS: Expressions of GPR43 and NLRP3 mRNA in peripheral blood leukocytes from 23 AF patients and 25 non-AF controls were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Expressions of leukocyte GPR43 and NLRP3 protein were evaluated by western blot analysis. The levels of plasma IL-1ß were measured by enzyme-linked immunosorbent assay (ELISA). The fecal SCFAs levels based on GC/MS metabolome of corresponding 21 controls and 14 AF patients were acquired from our published dataset. To evaluate the expression of NLRP3 and GPR43 and the release of IL-1ß, human THP-1 cells were stimulated with or without SCFAs (acetate, propionate, and butyrate), lipopolysaccharide (LPS), and nigericin in vitro, respectively. RESULTS: Compared to the controls, the mRNA expression in peripheral leukocytes was significantly reduced in AF patients (P = 0.011) coupled with the increase in downstream leukocyte NLRP3 mRNA expression (P = 0.007) and plasma IL-1ß levels (P < 0.001), consistent with changes in GPR43 and NLRP3 protein expression. Furthermore, leukocyte GPR43 mRNA levels were positively correlated with fecal GM-derived acetic acid (P = 0.046) and negatively correlated with NLRP3 mRNA expression (P = 0.024). In contrast to the negative correlation between left atrial diameter (LAD) and GPR43 (P = 0.008), LAD was positively correlated with the leukocyte NLRP3 mRNA levels (P = 0.024). Subsequent mediation analysis showed that 68.88% of the total effect of intestinal acetic acid on AF might be mediated by leukocyte GPR43/NLRP3. The constructed GPR43-NLRP3 score might have a predictive potential for AF detection (AUC = 0.81, P < 0.001). Moreover, SCFAs treatment increased GPR43 expression and remarkably reduced LPS/nigericin-induced NLRP3 expression and IL-1ß release in human THP-1 cells in vitro. CONCLUSIONS: Disrupted interactions between GPR43 and NLRP3 expression in peripheral blood leukocytes, associated with reduced intestinal GM-derived SCFAs, especially acetic acid, may be involved in AF development and left atrial enlargement by enhancing circulating inflammation.

ALLENE OXIDE SYNTHASE (AOS) induces petal senescence through a novel JA-associated regulatory pathway in Arabidopsis.

Flowers are crucial for the reproduction of flowering plants and their senescence has drastic effects on plant-animal interactions as well as pollination. Petal senescence is the final phase of flower development which is regulated by hormones and genes. Among these, jasmonic acid (JA) has emerged as a major contributor to petal senescence, but its molecular mechanisms remain elusive. Here, the role of JA in petal senescence in Arabidopsis was investigated. We showed that petal senescence in aos mutant was significantly delayed, which also affected petal cell size and proliferation. Similar significant delays in petal senescence were observed in dad1 and coi1 mutants. However, MYB21/24 and MYC2/3/4, known downstream regulators of JA in flower development, played no role in petal senescence. This indicated that JA regulates petal senescence by modulating other unknown transcription factors. Transcriptomic analysis revealed that AOS altered the expression of 3681 genes associated, and identified groups of differentially expressed transcription factors, highlighting the potential involvement of AP-2, WRKY and NAC. Furthermore, bHLH13, bHLH17 and URH2 were identified as potential new regulators of JA-mediated petal senescence. In conclusion, our findings suggest a novel genetic pathway through which JA regulates petal senescence in Arabidopsis. This pathway operates independently of stamen development and leaf senescence, suggesting the evolution of specialized mechanisms for petal senescence. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01425-w.

A Method for Predicting the Melting Temperature of Ionic Compounds.

Predicting the melting temperature of materials has always been a topic of great concern. This article proposes an alternative model for determining the melting temperature of materials based on the main idea of the Lindemann melting criterion combined with the first-principles calculations of density functional theory. To verify the accuracy of the melting model, this article selected typical ionic crystals of MgO and 10 alkali metal halides as the validation objects. The calculation results indicate that the melting temperature of the MgO crystals and I-VII compounds is in good agreement with the experimental results.

Study of the relationship between pressure and sensitivity of energetic materials based on first-principles calculation.

CONTEXT: In order to study the relationship between the sensitivity and pressure of energetic materials, six kinds of energetic materials were selected as the research object. The crystal structure, electronic, and phonon properties under hydrostatic pressure of 0 ~ 45 GPa were calculated by first principles. The calculation results show that the lattice parameters and band gap values of these six energetic materials decrease with the increase of pressure. The peak of the density of states decreases and moves to the low energy direction, and the electrons become more active. Meanwhile, the effect of pressure on the sensitivity of the energetic materials is analyzed based on the multi-phonon up-pumping theory. The number of doorway modes and integral of projected phonon density of states under high pressure is calculated. The results show that both of them increase with the increase of pressure. And the smaller the value of the band gap, the larger the number of doorway modes and integral of projected phonon density of states, and the more sensitive the energetic material is. METHODS: All calculations are performed using the Materials Studio software based on density functional theory. The Perdew-Burke-Ernzerhof (PBE) functional of the generalized gradient approximation (GGA) is used to calculate the exchange correlation function, and the Grimme dispersion correction method is used to deal with the weak intermolecular interaction. The structure of the compound was optimized by BFGS algorithm. The linear response is used to calculate the phonon properties of energetic materials. The plane wave cutoff energy was set to 830 eV. The K-point grids of TATB, FOX-7, TNX, RDX, TNT, and HMX were chosen as 2 × 2 × 2, 2 × 2 × 1, 2 × 1 × 1, 1 × 1 × 1, 1 × 2 × 1, and 2 × 1 × 2.

TRA-ACGAN: A motor bearing fault diagnosis model based on an auxiliary classifier generative adversarial network and transformer network.

Motor bearing fault diagnosis is essential to guarantee production efficiency and avoid catastrophic accidents. Deep learning-based methods have been developed and widely used for fault diagnosis, and these methods have proven to be very effective in accurately diagnosing bearing faults. In this paper, study the application of generative adversarial networks (GANs) in motor bearing fault diagnosis to address the practical issue of insufficient fault data in industrial testing. Focus on the auxiliary classifier generative adversarial network (ACGAN), and the data expansion is carried out for small datasets. This paper present a novel transformer network and auxiliary classifier generative adversarial network (TRA-ACGAN) for motor bearing fault diagnosis, where the TRA-ACGAN combines an ACGAN with a transformer network to avoid the traditional iterative and convolutional structures. The attention mechanism is fully utilized to extract more effective features, and the dual-task coupling problem encountered in classical ACGANs is avoided. Experimental results with the CWRU dataset and the PU dataset in the field of motor bearing fault diagnosis demonstrate the suitability and superiority of the TRA-ACGAN.

The long-term developmental outcomes of children born to mothers with systemic lupus erythematosus at different parities.

BACKGROUND: In recent years, China has adjusted its fertility policies to optimize the population structure by implementing the two-child and three-child policies. Some patients with systemic lupus erythematosus (SLE) are considering the possibility of having a second child. The issue is whether the offspring from the second childbirth will have favorable long-term developmental outcomes. OBJECTIVE: The research aims to investigate the long-term physical, neurological, and social-emotional development outcomes of children born to mothers with SLE at different parities. This study aims to offer valuable insights and references for SLE patients who are considering subsequent pregnancies and require information about potential developmental outcomes for their future children. METHODS: The study conducted a follow-up of children born to SLE mothers who were admitted to the obstetrics department between January 1, 2016, and September 30, 2021. The SLE patients were categorized into two groups based on their history of live delivery: the primiparity group and the multiparity group. The physical development status, including weight, height (length), and other relevant factors, was evaluated in both groups. The Ages and Stages Questionnaires, Third Edition (ASQ-3) was utilized to assess the neurological development in five domains, encompassing communication, gross motor, fine motor, problem solving and personal-social. Social-emotional development was assessed using the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE). The weight, height (length), body mass index, and ASQ-3 domain scores were standardized into Z-scores to enable comparison across various ages and genders. RESULTS: The study revealed that the weight Z-score and BMI Z-score of the children in the multiparity group were significantly higher compared to those in the primiparity group. However, there were no statistically significant differences in the proportions of overweight and obesity between the two groups. In terms of neurological developmental outcomes, the Z-scores of the communication and gross motor domains in the ASQ-3 assessment were significantly higher in the multiparity group compared to those in the primiparity group. The proportion of abnormal screening for social and emotional development in the children of the multiparity group was lower than that of the primiparity group, although this difference did not reach statistical significance. CONCLUSIONS: The long-term weight development, communication and gross motor development of children born to SLE patients in the multiparity group were better than those in the primiparity group. However, there was no significant difference in social-emotional development between the two groups.

Extraordinary Enhancement of Nonlinear Optical Interaction in NbOBr2 Microcavities.

2D materials are burgeoning as promising candidates for investigating nonlinear optical effects due to high nonlinear susceptibilities, broadband optical response, and tunable nonlinearity. However, most 2D materials suffer from poor nonlinear conversion efficiencies, resulting from reduced light-matter interactions and lack of phase matching at atomic thicknesses. Herein, a new 2D nonlinear material, niobium oxide dibromide (NbOBr2) is reported, featuring strong and anisotropic optical nonlinearities with scalable nonlinear intensity. Furthermore, Fabry-Pérot (F-P) microcavities are constructed by coupling NbOBr2 with air holes in silicon. Remarkable enhancement factors of ≈630 times in second harmonic generation (SHG) and 210 times in third harmonic generation (THG) are achieved on cavity at the resonance wavelength of 1500 nm. Notably, the cavity enhancement effect exhibits strong anisotropic feature tunable with pump wavelength, owing to the robust optical birefringence of NbOBr2. The ratio of the enhancement factor along the b- and c-axis of NbOBr2 reaches 2.43 and 5.27 for SHG and THG at 1500 nm pump, respectively, which leads to an extraordinarily high SHG anisotropic ratio of 17.82 and a 10° rotation of THG polarization. The research presents a feasible and practical strategy for developing high-efficiency and low-power-pumped on-chip nonlinear optical devices with tunable anisotropy.

Structural, elastic, mechanical, electronic, and optical properties of cubic K2Pb2O3 from first-principle study.

CONTEXT: Based on first principles, the structure, elasticity, mechanics, electronics, and optical properties of cubic K2Pb2O3 were studied. The structural parameters calculated by this method are close to the previous theoretical results. The elastic constant, bulk modulus, shear modulus, Young's modulus, Poisson's ratio, and mechanical stability are studied, and it is shown that cubic K2Pb2O3 is mechanically stable, isotropic, and brittleness. The electrical conductivity and chemical bonding of cubic K2Pb2O3 were analyzed based on the calculated band structure, density of states (DOS), and bond populations. The dispersion of optical functions, including the dielectric function, refractive index, extinction coefficient, reflectivity, absorption coefficient, and loss function, is displayed and analyzed. METHODS: All computations have been carried out based on density functional theory (DFT) as implemented in the CASTEP code. The norm conservation pseudopotential method is used to exchange correlation functionals within the generalized gradient approximation (GGA).

Structural insights into the transporting and catalyzing mechanism of DltB in LTA D-alanylation.

DltB, a model member of the Membrane-Bound O-AcylTransferase (MBOAT) superfamily, plays a crucial role in D-alanylation of the lipoteichoic acid (LTA), a significant component of the cell wall of gram-positive bacteria. This process stabilizes the cell wall structure, influences bacterial virulence, and modulates the host immune response. Despite its significance, the role of DltB is not well understood. Through biochemical analysis and cryo-EM imaging, we discover that Streptococcus thermophilus DltB forms a homo-tetramer on the cell membrane. We further visualize DltB in an apo form, in complex with DltC, and in complex with its inhibitor amsacrine (m-AMSA). Each tetramer features a central hole. The C-tunnel of each protomer faces the intratetramer interface and provides access to the periphery membrane. Each protomer binds a DltC without changing the tetrameric organization. A phosphatidylglycerol (PG) molecule in the substrate-binding site may serve as an LTA carrier. The inhibitor m-AMSA bound to the L-tunnel of each protomer blocks the active site. The tetrameric organization of DltB provides a scaffold for catalyzing D-alanyl transfer and regulating the channel opening and closing. Our findings unveil DltB's dual function in the D-alanylation pathway, and provide insight for targeting DltB as a anti-virulence antibiotic.