An Immunoreceptor-Targeting Strategy with Minimalistic C3b Peptide Fusion Enhances SARS-CoV-2 RBD mRNA Vaccine Immunogenicity.

Introduction: The clinical success of mRNA vaccine during the COVID-19 pandemic has inspired emerging approaches to elevate mRNA vaccine immunogenicity. Among them, antigen fusion protein designs for improved immune cell targeting have been shown to augment humoral immunity against small antigen targets. Methods: This research demonstrates that SARS-CoV-2 receptor binding domain (RBD) fusion with a minimalistic peptide segment of complement component 3b (C3b, residues 727-767) ligand can improve mRNA vaccine immunogenicity through antigen targeting to complement receptor 1 (CR1). We affirm vaccines' antigenicity and targeting ability towards specific receptors through Western blot and immunofluorescence assay. Furthermore, mice immunization studies help the investigation of the antibody responses. Results: Using SARS-CoV-2 Omicron RBD antigen, we compare mRNA vaccine formulations expressing RBD fusion protein with mouse C3b peptide (RBD-mC3), RBD fusion protein with mouse Fc (RBD-Fc), and wild-type RBD. Our results confirm the proper antigenicity and normal functionality of RBD-mC3. Upon validating comparable antigen expression by the different vaccine formulations, receptor-targeting capability of the fusion antigens is further confirmed. In mouse immunization studies, we show that while both RBD-mC3 and RBD-Fc elevate vaccine immunogenicity, RBD-mC3 leads to more sustained RBD-specific titers over the RBD-Fc design, presumably due to reduced antigenic diversion by the minimalistic targeting ligand. Conclusion: The study demonstrates a novel C3b-based antigen design strategy for immune cell targeting and mRNA vaccine enhancement.

Incidence and co-infection with COVID-19 of dengue during the COVID-19 pandemic.

The co-infection of dengue and COVID-19 has been regarded as a public health issue for dengue-endemic countries during the COVID-19 pandemic. Travel restrictions might decrease the chance of mosquitoes biting and, thus, reduce the risk of dengue transmission. However, the spread of dengue was reported to increase with the policies of lockdowns and social distancing in specific areas due to delayed interventions in dengue transmission. Of cases experiencing dengue and COVID-19 co-infection, most recovered after receiving supportive care and/or steroid therapy. However, some episodes of severe or fatal diseases in specific individuals, such as pregnant women, have been reported, and the clinical course of this co-infection is unrecognized or unpredictable. Accordingly, it is crucial to promptly identify predictors of developing severe viral diseases among co-infection patients.

Sex differences in clinical characteristics and long-term clinical outcomes in Asian hospitalized heart failure patients.

AIMS: Sex differences in long-term post-discharge clinical outcomes in Asian patients hospitalized for acute decompensated heart failure (HF) persist despite the world-wide implementation of guideline-directed medical therapy for decades. The present study aims to elucidate the puzzling dilemma and to depict the directions of solution. METHODS AND RESULTS: Between 2011 and 2020, a total of 12 428 patients (6518 men and 5910 women, mean age 73.50 ± 14.85) hospitalized for acute decompensated HF were retrospectively enrolled from a university HF cohort. Compared with men, women hospitalized for acute decompensated HF were older in age (76.40 ± 13.43 vs. 71.20 ± 15.67 years old, P < 0.0001) with more coexisting hypertension, diabetes, hyperlipidaemia and moderate to severe chronic kidney disease, but less with ischaemic heart disease, cerebrovascular disease and chronic obstructive pulmonary disease (P < 0.0001). In echocardiography measurement parameters, women had smaller left ventricular and left atrial dimensions, higher left ventricular mass index, higher left ventricular ejection fraction (LVEF) and more in HF with preserved ejection fraction (EF) category (LVEF > 50%) than men (P < 0.0001). In HF therapy, women compared with men received more guideline-directed medical HF therapies including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors, but similar beta-blockers and mineralocorticoid receptor antagonists (P < 0.0001). Post-discharge long-term clinical outcomes after multivariate-adjusted analysis revealed that women compared with men had lower all-cause mortality [adjusted hazard ratio (aHR): 0.89, 95% confidence interval (CI): 0.84-0.93], lower cardiovascular mortality (aHR: 0.89, 95% CI: 0.80-0.99) and lower 1 year mortality (aHR: 0.91, 95% CI: 0.84-0.99) but similar HF rehospitalization rate (aHR: 1.02, 95% CI: 0.95-1.09) over 8 years of follow-up. The superiority of women over men in all-cause mortality was shown in HF with preserved EF (>50%) and HF with mildly reduced EF (40%-50%), but not in HF with reduced EF (<40%) category. Subgroup forest plot analysis showed body mass index, coexisting hypertension and chronic obstructive pulmonary disease as significant interacting factors. CONCLUSIONS: With more coronary risk factors and medical comorbidities, less cardiac remodelling and better adherence to guideline-directed HF therapy, women hospitalized for acute decompensated HF demonstrated superiority over men in long-term post-discharge clinical outcomes, including all-cause mortality, cardiovascular mortality and 1 year mortality, and mainly in HF with preserved and mid-range EF categories, in the Asian HF cohort.

Discovery of Dual MER/AXL Kinase Inhibitors as Bifunctional Small Molecules for Inhibiting Tumor Growth and Enhancing Tumor Immune Microenvironment.

A series of bifunctional compounds have been discovered for their dual functionality as MER/AXL inhibitors and immune modulators. The furanopyrimidine scaffold, renowned for its suitability in kinase inhibitor discovery, offers at least three distinct pharmacophore access points. Insights from molecular modeling studies guided hit-to-lead optimization, which revealed that the 1,3-diketone side chain hybridized with furanopyrimidine scaffold that respectively combined amino-type substituent and 1H-pyrazol-4-yl substituent on the top and bottom of the aryl regions to produce 22 and 33, exhibiting potent antitumor activities in various syngeneic and xenograft models. More importantly, 33 demonstrated remarkable immune-modulating activity by upregulating the expression of total T-cells, cytotoxic CD8+ T-cells, and helper CD4+ T-cells in the spleen. These findings underscored the bifunctional capabilities of 33 (BPR5K230) with excellent oral bioavailability (F = 54.6%), inhibiting both MER and AXL while modulating the tumor microenvironment and highlighting its diverse applicability for further studies to advance its therapeutic potential.

Interfacial Reactions between Sn-Based Solders and n-Type Bi2(Te,Se)3 Thermoelectric Material.

This study investigated the interfacial reactions between n-type Bi2(Te,Se)3 thermoelectric material, characterized by a highly-oriented (110) plane, and pure Sn and Sn-3.0Ag-0.5Cu (wt.%) solders, respectively. At 250 °C, the liquid-state Sn/Bi2(Te,Se)3 reactions resulted in the formation of both SnTe and BiTe phases, with Bi-rich particles dispersed within the SnTe phase. The growth of the SnTe phase exhibited diffusion-controlled parabolic behavior over time. In contrast, the growth rate was considerably slower compared to that observed with p-type (Bi,Sb)2Te3. Solid-state Sn/Bi2(Te,Se)3 reactions conducted between 160 °C and 200 °C exhibited similar interfacial microstructures. The SnTe phase remained the primary reaction product, embedded with tiny Bi-rich particles, revealing a diffusion-controlled growth. However, the BiTe layer had no significant growth. Further investigation into growth kinetics of intermetallic compounds and microstructural evolution was conducted to elucidate the reaction mechanism. The slower growth rates in Bi2(Te,Se)3, compared to the reactions with (Bi,Sb)2Te3, could be attributed to the strong suppression effect of Se on SnTe growth. Additionally, the interfacial reactions of Bi2(Te,Se)3 with Sn-3.0Ag-0.5Cu were also examined, showing similar growth behavior to those observed with Sn solder. Notably, compared with Ag, Cu tends to diffuse towards the interfacial reaction phases, resulting in a high Cu solubility within the SnTe phase.

Diastolic/systolic blood pressure ratio for predicting febrile children with sepsis and progress to septic shock in the emergency department.

OBJECTIVE: Given the scarcity of studies analyzing the clinical predictors of pediatric septic cases that would progress to septic shock, this study aimed to determine strong predictors for pediatric emergency department (PED) patients with sepsis at risk for septic shock and mortality. METHODS: We conducted chart reviews of patients with ≥ 2 age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) criteria to recognize patients with an infectious disease in two tertiary PEDs between January 1, 2021, and April 30, 2022. The age range of included patients was 1 month to 18 years. The primary outcome was development of septic shock within 48 h of PED attendance. The secondary outcome was sepsis-related 28-day mortality. Initial important variables in the PED and hemodynamics with the highest and lowest values during the first 24 h of admission were also analyzed. RESULTS: Overall, 417 patients were admitted because of sepsis and met the eligibility criteria for the study. Forty-nine cases progressed to septic shock within 48 h after admission and 368 were discharged without progression. General demographics, laboratory data, and hemodynamics were analyzed by multivariate analysis. Only the minimum diastolic blood pressure/systolic blood pressure ratio (D/S ratio) during the first 24 h after admission remained as an independent predictor of progression to septic shock and 28-day mortality. The best cutoff values of the D/S ratio for predicting septic shock and 28-day mortality were 0.52 and 0.47, respectively. CONCLUSIONS: The D/S ratio is a practical bedside scoring system in the PED and had good discriminative ability in predicting the progression of septic shock and in-hospital mortality in PED patients. Further validation is essential in other settings.

Monitoring coronavirus disease progression and clinical impact through quantitative viral load testing.

BACKGROUND: The viral load (VL) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals is critical for improving clinical treatment strategies, care, and decisions. Several studies have reported that the initial SARS-CoV-2 VL is associated with disease severity and mortality. Cycle threshold (Ct) values and/or copies/mL are often used to quantify VL. However, a multitude of platforms, primer/probe sets of different SARS-CoV-2 target genes, and reference material manufacturers may cause inconsistent interlaboratory interpretations. The first International Standard for SARS-CoV-2 RNA quantitative assays has allowed diagnostic laboratories to transition SARS-CoV-2 VL results into international units per milliliter (IU/mL). The Cobas SARS-CoV-2 Duo quantitative assay provides VL results expressed in IU/mL. MATERIALS AND METHODS: We enrolled 145 and 50 SARS-CoV-2-positive, hospitalized and 50-negative individuals at the Tri-Service General Hospital, Taiwan from January to May 2022. Each participant's electronic medical record was reviewed to determine asymptomatic, mild, moderate, and severe cases. Nasopharyngeal swabs were collected using universal transport medium. We investigated the association of SARS-CoV-2 VL with disease severity using the Cobas SARS-CoV-2 Duo quantitative assay and its functionality in clinical assessment and decision making to further improve clinical treatment strategies. Limit of detection (LOD) was assessed. RESULTS: All 50 SARS-CoV-2-negative samples confirmed negative for SARS-CoV-2, demonstrating 100 % specificity of the Cobas SARS-CoV-2 Duo assay. Patients with severe symptoms had longer hospital stays, and the length of hospital stay (30.56 days on average) positively correlated with the VL (8.22 ± 1.21 log10 IU/mL). Asymptomatic patients had the lowest VL (5.54 ± 2.06 log10 IU/mL) at admission and the shortest hospital stay (14.1 days on average). CONCLUSIONS: VL is associated with disease severity and duration of hospitalization; therefore, its quantification should be considered when making clinical care decisions and treatment strategies. The Cobas SARS-CoV-2 Duo assay provides a commutable unitage IU/mL for interlaboratory interpretations.

A PTER-dependent pathway of taurine metabolism linked to energy balance.

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in biosynthesis of taurine from cysteine as well as the downstream derivatization of taurine into secondary taurine metabolites4,5. One such taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by diverse physiologic perturbations that alter taurine and/or acetate flux, including endurance exercise7, nutritional taurine supplementation8, and alcohol consumption6,9. While taurine N-acetyltransferase activity has been previously detected in mammalian cells6,7, the molecular identity of this enzyme, and the physiologic relevance of N-acetyltaurine, have remained unknown. Here we show that the orphan body mass index-associated enzyme PTER (phosphotriesterase-related)10 is the principal mammalian taurine N-acetyltransferase/hydrolase. In vitro, recombinant PTER catalyzes bidirectional taurine N-acetylation with free acetate as well as the reverse N-acetyltaurine hydrolysis reaction. Genetic ablation of PTER in mice results in complete loss of tissue taurine N-acetyltransferase/hydrolysis activities and systemic elevation of N-acetyltaurine levels. Upon stimuli that increase taurine levels, PTER-KO mice exhibit lower body weight, reduced adiposity, and improved glucose homeostasis. These phenotypes are recapitulated by administration of N-acetyltaurine to wild-type mice. Lastly, the anorexigenic and anti-obesity effects of N-acetyltaurine require functional GFRAL receptors. Together, these data uncover enzymatic control of a previously enigmatic pathway of secondary taurine metabolism linked to energy balance.

AZGP1 deficiency promotes angiogenesis in prostate cancer.

BACKGROUND: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive. METHOD: AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1± mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples. RESULT: Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1-/- mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues. CONCLUSION: AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.

Quantitative identification and sensor sensitivity analysis in detection of odor volatile compounds emitted by scaly grain mites, Suidasia pontifica Oudemans.

BACKGROUND: In Thailand, the scaly grain mite, Suidasia pontifica Oudemans, impacts the feed industry by emitting a lemongrass-like odor in contaminated feed, reducing its palatability. This study focused on identifying volatile organic compounds (VOCs) associated with this odor in contaminated chicken feeds and ground maize, as well as individual mites using gas chromatography-mass spectrometry (GC-MS). We explored the relationship between VOC concentration and mite population size in chicken feed cultures, aiming to detect minimal mite presence through regression models. Additionally, we tested the sensitivity of nine electronic odor sensors in detecting these VOCs. RESULTS: Our results showed Z-citral and E-citral present in mite-contaminated ground maize, chicken feeds, but absent in uncontaminated samples. Mite populations in chicken feed followed a normal distribution, increasing rapidly, peaking, and then declining, a pattern mirrored in the concentrations of Z-citral and E-citral. Simple linear regression models confirmed a positive correlation between mite density and citral concentrations. Polynomial regression models indicated Z-citral is detectable at mite densities over 67 individuals per gram and E-citral over 3.89 individuals per gram. Odor sensors showed varying readings across different citral concentrations, uncontaminated, and mite-infested chicken feeds. CONCLUSIONS: Our study confirms that S. pontifica are responsible for the lemongrass-like odor in infested samples, due to Z-citral and E-citral. The citral concentrations increase with mite population growth and are detectable at low mite densities, suggesting their effectiveness as biomarkers for early mite infestation detection. Additionally, MQ series odor sensors detected these VOCs, indicating their potential for monitoring mite infestations in storage environments. © 2024 Society of Chemical Industry.

Decreased risk of renal cell carcinoma in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors.

Patients with type 2 diabetes (T2D) are at a higher risk of developing renal cell carcinoma (RCC) than the general population. In vitro and in vivo investigations of the effects of sodium glucose cotransporter-2 inhibitors (SGLT2I) have shown a significantly reduced risk of RCC. However, the impact of these drugs on the incidence of RCC in the human population is unclear. This study aimed to examine the association between SGLT2I use and RCC risk in patients with T2D. We undertook a nationwide retrospective cohort study using the Health and Welfare Data Science Center database (2016-2020). The primary outcome was the risk of incident RCC by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression modeling was applied to analyze the association between SGLT2I use and RCC risk in patients with T2D. In a cohort of 241,772 patients with T2D who were using SGLT2Is and 483,544 participants who were not, 220 and 609 RCC cases, respectively, were recorded. The mean follow-up period of the study subjects was 2 years. There was a decreased risk of RCC for SGLT2I users after adjusting for the index year, sex, age, comorbidities, and concurrent medication (adjusted HR 0.68; 95% CI, 0.58-0.81). The sensitivity test for the propensity score 1:1-matched analyses showed similar results (adjusted HR 0.67; 95% CI, 0.55-0.81). The subgroup analysis revealed consistent results for sex, age (<70 years), and comorbidity with chronic kidney disease. The present study indicates that SGLT2I therapy significantly decreases RCC risk in patients with T2D. This finding was also consistent among the sensitivity test and subgroup analysis for those with or without chronic kidney disease/hypertension.

Biodiversity and Spatiotemporal Variations of Mecoptera in Thailand: Influences of Elevation and Climatic Factors.

Ecological analyses of the small and lesser-known insect order Mecoptera in Thailand are presented. Specimens were collected monthly over a period of 12 consecutive months, using both Malaise and pan traps, from 29 sampling sites located in 18 national parks throughout Thailand. A total of 21 species in four genera were identified from 797 specimens, including Panorpa (1 species), Neopanorpa (18 species), Bittacus (1 species), and Terrobittacus (1 species), with the latter genus representing a new genus record to Thailand. Neopanorpa harmandi, N. siamensis, N. byersi, and N. malaisei were the most abundant species, representing 27.4%, 11.3%, 10.3% and 8.8% of the total specimens, respectively. The species with the highest frequency, as indicated by the high percentage of species occurrence (%SO), was N. siamensis (51%), followed by N. byersi (34%), N. harmandi (34%), N. spatulata (27%), and N. inchoata (27%). Eleven species (52%) exhibited specific regional occurrences. N. tuberosa and N. siamensis had the widest distribution, being found in almost all regions except for western and southern regions for the first and second species, respectively. The seasonal species richness of Mecoptera was high during the rainy season in the northern, northeastern, central, eastern, and western regions, with the highest richness observed in July (15 species), followed by the hot (10 species) and cold seasons (7 species), while there was no significant difference in species richness between seasons in the southern region. Multiple regression models revealed a negative association between species richness and abundance of Mecoptera with both elevation and temperature, and a positive association between rainfall and species evenness. It is predicted that climatic changes will have a detrimental effect on the mecopteran community. The results of this study enhance the understanding of the ecological aspects of Mecoptera, offering crucial insights into its biodiversity and distribution, which are vital for conservation and forest management.

Impact of oseltamivir on the risk of cancer.

Purpose: Mounting evidence has revealed the anti-cancer activity of various anti-viral drugs. Oseltamivir phosphate (OP), namely Tamiflu®, is routinely used to combat influenza infections. Although evidence has indicated the anti-cancer effects of OP in vitro and in vivo, little information is known about the effect of OP use on cancers in humans. Methods: A nationwide population-based cohort study involving 13,977,101 cases with 284,733 receiving OP was performed to examine the association between OP use and cancers using the National Health Insurance Research Database in Taiwan between 2009 and 2018. Results: The cohort study found that OP users showed a significantly lower incidence of lung cancer, colon cancer, liver, and intrahepatic bile duct cancer, oral cancer, pancreas cancer, esophagus cancer, stomach cancer, and prostate cancer. Additionally, OP users exhibited a lower risk of cancer-related mortality (adjusted HR=0.779; 95% confidence interval [CI] 0.743-0.817; p<0.001) and a reduced risk of developing liver cancer (adjusted HR=0.895; 95% CI 0.824-0.972; p=0.008), esophagus cancer (adjusted HR=0.646; 95% CI 0.522-0.799; p<0.001) and oral cancer (adjusted HR=0.587; 95% CI 0.346-0.995; p=0.048). Notably, OP users had a significant reduction in liver cancer occurrence over a 10-year period follow-up and a lower cancer stage at liver cancer diagnosis. Conclusion: These findings first suggest the beneficial effects and therapeutic potential of OP use for certain cancers, especially liver cancer.

Novel sterol binding domains in bacteria.

Sterol lipids are widely present in eukaryotes and play essential roles in signaling and modulating membrane fluidity. Although rare, some bacteria also produce sterols, but their function in bacteria is not known. Moreover, many more species, including pathogens and commensal microbes, acquire or modify sterols from eukaryotic hosts through poorly understood molecular mechanisms. The aerobic methanotroph Methylococcus capsulatus was the first bacterium shown to synthesize sterols, producing a mixture of C-4 methylated sterols that are distinct from those observed in eukaryotes. C-4 methylated sterols are synthesized in the cytosol and localized to the outer membrane, suggesting that a bacterial sterol transport machinery exists. Until now, the identity of such machinery remained a mystery. In this study, we identified three novel proteins that may be the first examples of transporters for bacterial sterol lipids. The proteins, which all belong to well-studied families of bacterial metabolite transporters, are predicted to reside in the inner membrane, periplasm, and outer membrane of M. capsulatus, and may work as a conduit to move modified sterols to the outer membrane. Quantitative analysis of ligand binding revealed their remarkable specificity for 4-methylsterols, and crystallographic structures coupled with docking and molecular dynamics simulations revealed the structural bases for substrate binding by two of the putative transporters. Their striking structural divergence from eukaryotic sterol transporters signals that they form a distinct sterol transport system within the bacterial domain. Finally, bioinformatics revealed the widespread presence of similar transporters in bacterial genomes, including in some pathogens that use host sterol lipids to construct their cell envelopes. The unique folds of these bacterial sterol binding proteins should now guide the discovery of other proteins that handle this essential metabolite.

Ptychographic Nanoscale Imaging of the Magnetoelectric Coupling in Freestanding BiFeO3.

Understanding the magnetic and ferroelectric ordering of magnetoelectric multiferroic materials at the nanoscale necessitates a versatile imaging method with high spatial resolution. Here, soft X-ray ptychography is employed to simultaneously image the ferroelectric and antiferromagnetic domains in an 80 nm thin freestanding film of the room-temperature multiferroic BiFeO3 (BFO). The antiferromagnetic spin cycloid of period 64 nm is resolved by reconstructing the corresponding resonant elastic X-ray scattering in real space and visualized together with mosaic-like ferroelectric domains in a linear dichroic contrast image at the Fe L3 edge. The measurements reveal a near perfect coupling between the antiferromagnetic and ferroelectric ordering by which the propagation direction of the spin cycloid is locked orthogonally to the ferroelectric polarization. In addition, the study evinces both a preference for in-plane propagation of the spin cycloid and changes of the ferroelectric polarization by 71° between multiferroic domains in the epitaxial strain-free, freestanding BFO film. The results provide a direct visualization of the strong magnetoelectric coupling in BFO and of its fine multiferroic domain structure, emphasizing the potential of ptychographic imaging for the study of multiferroics and non-collinear magnetic materials with soft X-rays.

Rapid proteome-wide prediction of lipid-interacting proteins through ligand-guided structural genomics.

Lipids are primary metabolites that play essential roles in multiple cellular pathways. Alterations in lipid metabolism and transport are associated with infectious diseases and cancers. As such, proteins involved in lipid synthesis, trafficking, and modification, are targets for therapeutic intervention. The ability to rapidly detect these proteins can accelerate their biochemical and structural characterization. However, it remains challenging to identify lipid binding motifs in proteins due to a lack of conservation at the amino acids level. Therefore, new bioinformatic tools that can detect conserved features in lipid binding sites are necessary. Here, we present Structure-based Lipid-interacting Pocket Predictor (SLiPP), a structural bioinformatics algorithm that uses machine learning to detect protein cavities capable of binding to lipids in experimental and AlphaFold-predicted protein structures. SLiPP, which can be used at proteome-wide scales, predicts lipid binding pockets with an accuracy of 96.8% and a F1 score of 86.9%. Our analyses revealed that the algorithm relies on hydrophobicity-related features to distinguish lipid binding pockets from those that bind to other ligands. Use of the algorithm to detect lipid binding proteins in the proteomes of various bacteria, yeast, and human have produced hits annotated or verified as lipid binding proteins, and many other uncharacterized proteins whose functions are not discernable from sequence alone. Because of its ability to identify novel lipid binding proteins, SLiPP can spur the discovery of new lipid metabolic and trafficking pathways that can be targeted for therapeutic development.

A meta-analysis on the efficacy of low-intensity cognitive behavioural therapy for generalised anxiety disorder.

BACKGROUND: Low-intensity cognitive behavioural therapy (LICBT) has been recommended as a primary intervention in the tiered care for mild to moderate generalised anxiety disorder. However, LICBT for generalised anxiety disorder are markedly diverse and efficacy data on various outcomes have not been systematically reviewed. This meta-analysis aimed to synthesise effect sizes of three NICE-recommended LICBT for generalised anxiety disorder: non-facilitated self-help, guided self-help, and psychoeducational groups. METHODS: A systematic literature review of randomised controlled trials (RCTs) examining LICBT for generalised anxiety disorder in the last 23 years (2000-2023) was conducted. Efficacy data for anxiety, depression, and worry outcomes were separately meta-analysed. The study was reported following the PRISMA guidelines. RESULTS: The systematic review identified 12 RCTs out of 1205 papers. The three meta-analyses consisted of 12 (anxiety), 11 (depression), and 9 (worry) effect sizes respectively, including total sample sizes of 1201 (anxiety), 1164 (depression), and 908 (worry). The adjusted effect sizes for reductions in anxiety (g = -0.63), depression (g = -0.48), and worry (g = -0.64) were all in the medium range, favouring LICBT over control conditions. Between-study heterogeneity was significant on anxiety and worry, with no specific moderators identified by meta-regression. CONCLUSIONS: LICBT has shown promise as an effective and efficient treatment modality for individuals with generalised anxiety disorder. Future research comparing various LICBT subtypes and treatment components will further inform clinical practice. TRIAL REGISTRATION: This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO; record ID CRD42021285590).

Fitness consequences of intraguild predation between Spodoptera frugiperda (Lepidoptera: Noctuidae) and Ostrinia furnacalis (Lepidoptera: Crambidae).

The introduction of the fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), into Thailand has significantly altered the dynamics of maize pests. It has overshadowed Ostrinia furnacalis (Guenée) (Asian corn borer) (Lepidoptera: Crambidae), previously the most severe maize insect in Thailand. This transition is postulated to stem from the superior intraguild predation (IGP) capabilities of S. frugiperda. To validate this supposition, we assessed the co-distribution patterns and damage locales of both pests within maize fields and analyzed the IGP's repercussions on their larval growth, survival, and fecundity. Our findings demonstrate that: (i) incidence of O. furnacalis in maize fields is markedly reduced following the introduction of S. frugiperda; (ii) abundance of S. frugiperda and O. furnacalis is negatively correlated in field; (iii) interspecific interactions affect the spatial distributions of S. frugiperda and O. furnacalis on shared plants; (iv) S. frugiperda has lower generation time and higher fecundity; and (v) IGP amplifies the growth rate of S. frugiperda and elevates mortality in O. furnacalis. Moreover, in response to the competitive pressure exerted by S. frugiperda, O. furnacalis exhibited expedited molting and growth without a commensurate increase in size. Our data suggest IGP proficiency underpins S. frugiperda's dominance in Thai maize fields. We propose a niche differentiation on spatiotemporal distribution facilitating the coexistence of S. frugiperda and O. furnacalis. The impact of S. frugiperda on pest management strategies is discussed.

Tunable Nano-Bending Structures of Loosened/Tightened Lassos with Bi-Stable Vibration-Induced Emissions for Multi-Manipulations of White-Light Emissions and Sensor Applications.

The first tunable nano-bending structures of [1]rotaxane containing a single-fluorophoric N,N'-diphenyl-dihydrodibenzo[a,c]phenazine (DPAC) moiety (i.e., [1]RA) are developed as a loosened lasso structure to feature the bright white-light emission [CIE (0.27, 0.33), Φ = 21.2%] in THF solution, where bi-stable states of bending and twisted structures of DPAC unit in [1]RA produce cyan and orange emissions at 480 and 600 nm, respectively. With acid/base controls, tunable loosened/tightened nano-loops of corresponding [1]rotaxanes (i.e., [1]RA/[1]RB) can be achieved via the shuttling of macrocycles reversibly, and thus to adjust their respective white-light/cyan emissions, where the cyan emission of [1]RB is obtained due to the largest conformational constraint of DPAC moiety in its bending form of [1]RB with a tightened lasso structure. Additionally, the non-interlocked analog M-Boc only shows the orange emission, revealing the twisted form of DPAC fluorophore in M-Boc without any conformational constraint. Moreover, the utilization of solvents (with different viscosities and polarities), temperatures, and water fractions could serve as effective tools to adjust the bi-stable vibration-induced emission (VIE) colors of [1]rotaxanes. Finally, tuning ratiometric emission colors of adaptive conformations of DPAC moieties by altering nano-bending structures in [1]rotaxanes and external stimuli can be further developed as intelligent temperature and viscosity sensor materials.