Aerodynamic Simulation of Small Airway Resistance: A New Imaging Biomarker for Chronic Obstructive Pulmonary Disease.

Purpose: To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD. Patients and Methods: 24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (RSA) and RSA as a percentage of total airway resistance (RSA%) were calculated by CFD combined with airway resistance and FEV1 measured by pulmonary function test. A correlation analysis was conducted between RSA and pulmonary function parameters, including FEV1/FVC, FEV1% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted. Results: The RSA and RSA% were significantly different among the three groups (p<0.05) and related to FEV1/FVC (r = -0.70, p < 0.001; r = -0.67, p < 0.001), FEV1% predicted (r = -0.60, p = 0.002; r = -0.57, p = 0.004), MEF50% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001), MEF75% predicted (r = -0.71, p < 0.001; r = -0.60, p = 0.002) and MMEF 75/25% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001). Conclusion: Airway CFD is a valuable method for estimating the small airway resistance, where the derived RSA will aid in the early diagnosis of COPD.

Dietary Flavonoid and Subclass Intakes are not Associated with Markers of Bone Health in U.S. Adults Age 50+ Years.

BACKGROUND: Dietary flavonoid intakes have been associated with improved markers of bone health in Chinese and Scottish cohorts, but little data exist in middle aged to older adults in the United States. OBJECTIVES: The objective of our research was to assess if dietary flavonoid intakes are associated with bone mineral density (BMD), bone mineral content (BMC), and bone area of the lumbar spine and femoral neck in a nationally representative population of middle aged to older U.S. adults. We further sought to investigate if relationships of the main flavonoid subgroups (i.e., anthocyanins, flavan-3-ols, flavanones, flavones, flavonols, and isoflavones) exist, as a secondary objective. METHODS: Cross-sectional data from individuals aged 50+ years enrolled in the 2017-2018 National Health and Nutrition Examination Survey (NHANES) were used in our analyses (N = 2590). Weighted multivariate logistic regression models were used to investigate the relationship between quartiles of flavonoid intake and BMD, BMC, and bone area of the lumbar spine and femoral neck of participants. RESULTS: Mean age of participants was 63.4 ± 0.52 years and 64.1 ± 0.52 years for men and women, respectively. Average total flavonoid intake was 217 ± 19.4 mg/day and 306 ± 26.9 mg/day for men and women, respectively. Total flavonoid intakes were not significantly associated with BMD, BMC, or bone area of the femoral neck or lumbar spine in male or female participants. Flavonoid subclass intakes were also not consistently associated with improved markers of bone health. CONCLUSION: Although several limitations exist, this cross-sectional analysis of U.S. adults aged 50+ years provides contradictory evidence to the hypothesis that higher flavonoid and flavonoid subclass intakes beneficially impacts markers of bone health. Large prospective cohort investigations that better capture long-term dietary flavonoid intake and ascertain fractures the primary outcome, as well as randomized controlled trials, are needed to fully elucidate the effects flavonoids on bone health.

In Situ Fabrication of Electrospun Magnetic Film Under Laparoscopic Guidance for Preventing Postoperative Recurrence of Hepatocellular Carcinoma.

Despite laparoscopic-guided minimally invasive hepatectomy emerging as the primary approach for resecting hepatocellular carcinoma (HCC), there's still a significant gap in suitable biomaterials that seamlessly integrate with these techniques to achieve effective hemostasis and suppress residual tumors at the surgical margin. Electrospun films are increasingly used for wound closure, yet the employment of prefabricated electrospun films for hemostasis during minimally invasive HCC resection is hindered by prolonged operation times, complexity in implementation, limited visibility during surgery, and inadequate postoperative prevention of HCC recurrence. In this study, we integrated montmorillonite-iron oxide sheets into the PVP polymer framework, enhancing the resulting electrospun polyvinylpyrrolidone (PVP) /montmorillonite-iron oxide (MI) film (abbreviated as PMI) with robustness, hemostatic capability, and magnetocaloric properties. In contrast to the in vitro prefabricated electrospun films, the electrospun PMI film is designed to be formed in situ on liver wounds under laparoscopic guidance during hepatectomy. This design affords superior wound adaptability, facilitating meticulous wound closure and expeditious hemostasis, thereby simplifying the operative process and ultimately alleviating the workload of healthcare professionals. Moreover, when exposed to an alternating magnetic field, the film can efficiently ablate residual tumors, significantly augmenting the treatment efficacy of HCC. This article is protected by copyright. All rights reserved.

Discovery of orally bioavailable phenyltetrazolium derivatives for the acute treatment and the secondary prevention of ischemic stroke.

The potential for secondary stroke prevention, which can significantly reduce the risk of recurrent strokes by almost 90%, underscores its critical importance. N-butylphthalide (NBP) has emerged as a promising treatment for acute cerebral ischemia, yet its efficacy for secondary stroke prevention is hindered by inadequate pharmacokinetic properties. This study, driven by a comprehensive structural analysis, the iterative process of structure optimization culminated in the identification of compound B4, which demonstrated exceptional neuroprotective efficacy and remarkable oral exposure and oral bioavailability. Notably, in an in vivo transient middle cerebral artery occlusion (tMCAO) model, B4 substantially attenuated infarct volumes, surpassing the effectiveness of NBP. While oral treatment with B4 exhibited stronger prevention potency than NBP in photothrombotic (PT) model. In summary, compound B4, with its impressive oral bioavailability and potent neuroprotective effects, offers promise for both acute ischemic stroke treatment and secondary stroke prevention.

Preparation and efficacy of antibacterial methacrylate monomer-based polymethyl methacrylate bone cement containing N-halamine compounds.

Introduction: Our objective in this study was to prepare a novel type of polymethyl methacrylate (PMMA) bone cement, analyze its material properties, and evaluate its safety and antibacterial efficacy. Methods: A halamine compound methacrylate antibacterial PMMA bone cement containing an N-Cl bond structure was formulated, and its material characterization was determined with Fourier transform infrared spectroscopy (FT-IR) and 1H-NMR. The antibacterial properties of the material were studied using contact bacteriostasis and releasing-type bacteriostasis experiments. Finally, in vitro and in vivo biocompatibility experiments were performed to analyze the toxic effects of the material on mice and embryonic osteoblast precursor cells (MC3T3-E1). Results: Incorporation of the antibacterial methacrylate monomer with the N-halamine compound in the new antibacterial PMMA bone cement significantly increased its contact and releasing-type bacteriostatic performance against Staphylococcus aureus. Notably, at 20% and 25% additions of N-halamine compound, the contact and releasing-type bacteriostasis rates of bone cement samples reached 100% (p < 0.001). Furthermore, the new antibacterial bone cement containing 5%, 10%, and 15% N-halamine compounds showed good biocompatibility in vitro and in vivo. Conclusion: In this study, we found that the novel antibacterial PMMA bone cement with N-halamine compound methacrylate demonstrated good contact and releasing-type bacteriostatic properties against S. aureus. In particular, bone cement containing a 15% N-halamine monomer exhibited strong antibacterial properties and good in vitro and in vivo biocompatibility.

The relationship between rehabilitation motivation and upper limb motor function in stroke patients.

Objective: Insufficient motivation among post-stroke survivors may be an important factor affecting their motor function recovery. This study seeks to investigate the relationship between motivation and functional recovery in stroke patients undergoing rehabilitation training. Materials and methods: 103 stroke patients with upper limb impairments were studied during their hospital stays. Assessments were done before and after rehabilitation training to measure motivation, emotional state, motor function, and independence in daily activities. Data analysis was conducted to examine the distribution of these factors among the participants. Pearson and Spearman correlation analyses were used to study the relationships between motivation, emotional state, and motor function. Patients were divided into high and low motivation groups based on the Rehabilitation Motivation Scale (RMS), and chi-square and rank-sum tests were used to compare functional differences before and after treatment among patients with varying levels of motivation. Results: 66 participants were found to have low motivation in the initial assessment of the RMS (64.08%). Consistency in motivation levels was observed among patients with high motivation (r = 0.648, P<0.001). Apathy was identified as the main factor affecting motivation in patients with low motivation (p = 0.027), while depression and anxiety were not significantly correlated. Motivation was strongly linked to improvements in upper limb motor function, daily living activities, and self-exercise duration (p < 0.001) for stroke patients undergoing rehabilitation. Post-training, there was a notable increase in motivation, motor function, and independence in daily activities (p < 0.001). Increased rehabilitation motivation was linked to better upper limb motor function and daily independence in patients, particularly those with low motivation. This correlation was significant for both the FMA-UE and FIM scores. Discussion: Old patients with poor upper limb motor function often have low motivation, which hinders their recovery. Using strategies to boost motivation in stroke patients with impaired upper limb function could greatly improve their rehabilitation and motor skills. It is crucial to prioritize these intervention strategies. Conclusion: Enhancing rehabilitation motivation in stroke patients with low motivation and upper limb motor impairments can foster the restoration of their functional capabilities.

Total Synthesis of Brevitaxin.

Brevitaxin was prepared in nine steps from commercially available carnosic acid. The construction of the 1,4-benzodioxin moiety involved an unique stepwise ortho-quinone-engaged [4+2] cycloaddition. Two strategic stages were employed to prepare the highly unsaturated cycloaddition precursor 3: (1) synthesizing the diene moiety (C1-C2 and C10-C20 double bonds) by regioselective ortho-quinone tautomerization, and (2) installing four sp2-hybridized carbon atoms (C3, C5, C6 and C7) in one step using a SeO2-promoted chemo- and regioselective oxidation reaction.

Association of C-reactive protein with all-cause and cause-specific mortality in people with gout.

AIMS: To test the association of C-reactive protein (CRP) with all-cause and cause-specific mortality in people with gout. METHODS: This cohort study included 502 participants with gout from the National Health and Nutrition Examination Survey. Multivariate Cox regression analysis, subgroup analysis, and restricted cubic spline (RCS) analyses were utilized to examine the association of CRP levels with all-cause, cardiovascular, and cancer mortality. RESULTS: After adjusting for multiple variables, Cox regression analysis showed that compared with individuals in the lowest tertile of CRP levels, those in the middle and highest tertiles experienced increases in all-cause mortality risk of 74.2% and 149.7%, respectively. Similarly, the cancer mortality risk for individuals in the highest tertile of CRP levels increased by 283.9%. In addition, for each standard deviation increase in CRP, the risks of all-cause and cancer mortality increased by 25.9% and 35.4%, respectively (P < 0.05). Subgroup analyses demonstrated that the association between CRP levels and all-cause mortality remained significant across subgroups of age (≤ 60 and > 60 years), gender (male), presence or absence of hypertension, non-diabetes, cardiovascular disease, non-cardiovascular disease and non-cancer. Furthermore, the association with cancer mortality was significant in subgroups including males, those without hypertension and cancer, and those with or without diabetes. However, the association with cardiovascular mortality was only significant in the non-hypertension subgroup (P < 0.05). Nonlinear association of CRP with all-cause mortality and linear association with cancer mortality were also confirmed (P for nonlinearity = 0.008 and 0.135, respectively). CONCLUSIONS: CRP levels were associated with increased all-cause and cancer mortality among individuals with gout.

Examining the Social Networks Types and Their Effects on Caregiving Experience of Family Caregivers for Individuals With Dementia: A Mixed-Methods Study.

Background and Objectives: Social networks are crucial to personal health, particularly among caregivers of individuals with dementia; however, different types of social networks among caregivers of those with dementia and how these differences are associated with caregiver burden and positive appraisal, remain underexamined. This study aims to depict dementia caregivers' social network types, related factors, and impact on caregiving experiences. Research Design and Methods: A questionnaire-based survey was conducted with a total of 237 family caregivers of individuals with dementia nested additional semistructured interviews conducted with 14 caregivers in Chongqing, China. A quantitative study was designed to collect data on personal and situational information, social networks, caregiver burden, and positive aspects of caregiving. Qualitative data were collected via semistructured interviews. Latent class analysis and multivariate regression analyses were applied to quantitative data, and inductive content analysis to qualitative data. Results: The 3 social network types-family-limited (n = 39, 16.46%), family-dominant (n = 99, 41.77%), and diverse network (n = 99, 41.77%)-differed in age and sex of caregivers and individuals with dementia, stage of dementia, and caregiving intensity. Caregivers in family-dominant networks had a lower caregiver burden (ß= -0.299, p = .003) and greater positive aspects of caregiving (ß= 0.228, p = .021) than those in family-limited networks. Three themes-accessibility, reciprocity, and reliance-emerged as facilitators and barriers when asking for support. Caregivers frequently cited the perception of economic, practical, and emotional support, yet reported a lack of adequate formal support from healthcare providers. Discussion and Implication: Family caregivers of individuals with dementia have different social network types that vary considerably among sociocultural contexts and perceive various types of support from social networks. Solid family networks and diverse social networks are contributors to long-term dementia care.

Nanometabolomics Elucidated Biological Prospective of Mo4/3B2-x Nanosheets: Toward Metabolic Reprogramming of Amino Acid Metabolism.

Mo4/3B2-x nanosheets are newly developed, and 2D transition metal borides (MBene) were reported in 2021, but there is no report on their further applications and modification; hence, this article sheds light on the significance of potential biological prospects for future biomedical applications. Therefore, elucidation of the biocompatibility, biotoxicology, and bioactivity of Mo4/3B2-x nanosheets has been an urgent need to be fulfilled. Nanometabolomics (also referred as nanomaterials-based metabolomics) was first proposed and utilized in our previous work, which specialized in interpreting nanomaterials-induced metabolic reprogramming through aqueous metabolomics and lipidomics approach. Hence, nanometabolomics could be considered as a novel concept combining nanoscience and metabolomics to provide bioinformation on nanomaterials' biomedical applications. In this work, the safe range of concentration (<50 mg/L) with good biosafety toward human umbilical vein endothelial cells (HUVECs) was discovered. The low concentration (5 mg/L) and high concentration (50 mg/L) of Mo4/3B2-x nanosheets were utilized for the in vitro Mo4/3B2-x-cell interaction. Nanometabolomics has elucidated the biological prospective of Mo4/3B2-x nanosheets via monitoring its biocompatibility and metabolic shift of HUVECs. The results revealed that 50 mg/L Mo4/3B2-x nanosheets could lead to a stronger alteration of amino acid metabolism with disturbance of the corresponding amino acid-related pathways (including amino acid metabolism, amino acid degradation, fatty acid biosynthesis, and lipid biosynthesis and metabolism). These interesting results were closely involved with the oxidative stress and production of excess ROS. This work could be regarded as a pathbreaking study on Mo4/3B2-x nanosheets at a biological level, which also designates their further biochemical, medical, and industrial application and development based on nanometabolomics bioinformation.

Versatile separators toward advanced lithium-sulfur batteries: status, recent progress, challenges and perspective.

Lithium-sulfur batteries (LSBs) have recently gained extensive attention due to their high energy density, low cost, and environmental friendliness. However, serious shuttle effect and uncontrolled growth of lithium dendrites restrict them from further commercial applications. As "the third electrode", functional separators are of equal significance as both anodes and cathodes in LSBs. The challenges mentioned above are effectively addressed with rational design and optimization in separators, thereby enhancing their reversible capacities and cycle stability. The review discusses the status/operation mechanism of functional separators, then primarily focuses on recent research progress in versatile separators with purposeful modifications for LSBs, and summarizes the methods and characteristics of separator modification, including heterojunction engineering, single atoms, quantum dots, and defect engineering. From the perspective of the anodes, distinct methods to inhibit the growth of lithium dendrites by modifying the separator are discussed. Modifying the separators with flame retardant materials or choosing a solid electrolyte is expected to improve the safety of LSBs. Besides, in-situ techniques and theoretical simulation calculations are proposed to advance LSBs. Finally, future challenges and prospects of separator modifications for next-generation LSBs are highlighted. We believe that the review will be enormously essential to the practical development of advanced LSBs.

Three-dimensional evaluation of dental characteristics in patients with Cleidocranial dysplasia.

BACKGROUND: Cleidocranial dysplasia (CCD) is an autosomal dominant hereditary disorder. Besides skeletal abnormalities, CCD is often associated with dental complications, such as multiple supernumerary teeth and permanent teeth impaction or delayed eruption. METHODS: Supernumerary teeth of axial, sagittal and coronal CBCT view was characterized in detail and 3D image reconstruction was performed. Number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth, direction of supernumerary teeth in CCD patients were analyzed. RESULTS: The mean age of the 3 CCD patients in this study was 16.7 years. Among 36 supernumerary teeth, the majority of them were identified as apical side located and lingual side located. Normal orientation was the most common type in this study, followed by sagittal orientation, and horizontal orientation. Horizontal orientation teeth were all distributed in the mandible. Supernumerary teeth exhibited significantly shorter crown and dental-root lengths, as well as smaller crown mesiodistal and buccolingual diameters (P < 0.01). There was no difference in the number of supernumerary teeth between the maxilla and mandible, and the premolars region had the largest number of supernumerary teeth and the incisor region had the smallest number. CONCLUSIONS: This study compares number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth and direction of supernumerary teeth, this study also provides a reference for the comprehensive evaluation of CCD patients before surgery.

Quercetin-loaded Human Umbilical cord Mesenchymal Stem Cell-derived sEVs for Spinal Cord Injury Recovery.

Following spinal cord injury, the inflammatory environment at the injury site causes local microglia and astrocytes to activate, which worsens the nerve damage in the affected area. Quercetin, an anti-inflammatory agent, has been limited in spinal cord injury due to its poor water solubility and easy degradation. Stem cell-derived extracellular vesicles can go through the blood-brain barrier and are an ideal drug delivery system. In this study, umbilical cord mesenchymal stem cell-derived extracellular vesicles were used to load quercetin to prevent its degradation and allow it to accumulate at the site of spinal cord injury. Our results showed that quercetin-loaded extracellular vesicles could inhibit the activation of microglia to M1 phenotype through the TLR4/NF-κB pathway, and the activation of astrocytes to A1 phenotype through the JAK2/STAT3 pathway. This reduced the production of inflammatory factors, mitigated neuronal damage, and inhibited the growth of astroglial scar, but promoted the recovery of motor function in rats with spinal cord injury.

Fabrication of an Antifouling Surface Plasmon Resonance Sensor with Stratified Zwitterionic Peptides for Highly Efficient Detection of Peanut Allergens in Biscuits.

Peanut allergen monitoring is currently an effective strategy to avoid allergic diseases, while food matrix interference is a critical challenge during detection. Here, we developed an antifouling surface plasmon resonance sensor (SPR) with stratified zwitterionic peptides, which provides both excellent antifouling and sensing properties. The antifouling performance was measured by the SPR, which showed that stratified peptide coatings showed much better protein resistance, reaching ultralow adsorption levels (<5 ng/cm2). Atomic force microscopy was used to further analyze the antifouling mechanism from a mechanical perspective, which demonstrated lower adsorption forces on hybrid peptide coatings, confirming the better antifouling performance of stratified surfaces. Moreover, the recognition of peanut allergens in biscuits was performed using an SPR with high efficiency and appropriate recovery results (98.2-112%), which verified the feasibility of this assay. Therefore, the fabrication of antifouling sensors with stratified zwitterionic peptides provides an efficient strategy for food safety inspection.

Human amniotic epithelial stem cell is a cell therapy candidate for preventing acute graft-versus-host disease.

Graft-versus-host disease (GVHD), an immunological disorder that arises from donor T cell activation through recognition of host alloantigens, is the major limitation in the application of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Traditional immunosuppressive agents can relieve GVHD, but they induce serious side effects. It is highly required to explore alternative therapeutic strategy. Human amniotic epithelial stem cells (hAESCs) were recently considered as an ideal source for cell therapy with special immune regulatory property. In this study, we evaluated the therapeutic role of hAESCs in the treatment of GVHD, based on our previous developed cGMP-grade hAESCs product. Humanized mouse model of acute GVHD (aGVHD) was established by injection of huPBMCs via the tail vein. For prevention or treatment of aGVHD, hAESCs were injected to the mice on day -1 or on day 7 post-PBMC infusion, respectively. We showed that hAESCs infusion significantly alleviated the disease phenotype, increased the survival rate of aGVHD mice, and ameliorated pathological injuries in aGVHD target organs. We demonstrated that hAESCs directly induced CD4+ T cell polarization, in which Th1 and Th17 subsets were downregulated, and Treg subset was elevated. Correspondingly, the levels of a series of pro-inflammatory cytokines were reduced while the levels of the anti-inflammatory cytokines were upregulated in the presence of hAESCs. We found that hAESCs regulated CD4+ subset polarization in a paracrine mode, in which TGFß and PGE2 were selectively secreted to mediate Treg elevation and Th1/Th17 inhibition, respectively. In addition, transplanted hAESCs preserved the graft-versus-leukemia (GVL) effect by inhibiting leukemia cell growth. More intriguingly, hAESCs infusion in HSCT patients displayed potential anti-GVHD effect with no safety concerns and confirmed the immunoregulatory mechanisms in the preclinical study. We conclude that hAESCs infusion is a promising therapeutic strategy for post-HSCT GVHD without compromising the GVL effect. The clinical trial was registered at www.clinicaltrials.gov as #NCT03764228.

New Cocrystals of Ligustrazine: Enhancing Hygroscopicity and Stability.

Ligustrazine (TMP) is the main active ingredient extracted from Rhizoma Chuanxiong, which is used in the treatment of cardiovascular and cerebrovascular diseases, with the drawback of being unstable and readily sublimated. Cocrystal technology is an effective method to improve the stability of TMP. Three benzoic acid compounds including P-aminobenzoic acid (PABA), 3-Aminobenzoic acid (MABA), and 3,5-Dinitrobenzoic acid (DNBA) were chosen for co-crystallization with TMP. Three novel cocrystals were obtained, including TMP-PABA (1:2), TMP-MABA (1.5:1), and TMP-DNBA (0.5:1). Hygroscopicity was characterized by the dynamic vapor sorption (DVS) method. Three cocrystals significantly improved the hygroscopicity stability, and the mass change in TMP decreased from 25% to 1.64% (TMP-PABA), 0.12% (TMP-MABA), and 0.03% (TMP-DNBA) at 90% relative humidity. The melting points of the three cocrystals were all higher than TMP, among which the TMP-DNBA cocrystal had the highest melting point and showed the best stability in reducing hygroscopicity. Crystal structure analysis shows that the mesh-like structure formed by the O-H⋯N hydrogen bond in the TMP-DNBA cocrystal was the reason for improving the stability of TMP.

Research on Bearing Surface Scratch Detection Based on Improved YOLOV5.

Bearings are crucial components of machinery and equipment, and it is essential to inspect them thoroughly to ensure a high pass rate. Currently, bearing scratch detection is primarily carried out manually, which cannot meet industrial demands. This study presents research on the detection of bearing surface scratches. An improved YOLOV5 network, named YOLOV5-CDG, is proposed for detecting bearing surface defects using scratch images as targets. The YOLOV5-CDG model is based on the YOLOV5 network model with the addition of a Coordinate Attention (CA) mechanism module, fusion of Deformable Convolutional Networks (DCNs), and a combination with the GhostNet lightweight network. To achieve bearing surface scratch detection, a machine vision-based bearing surface scratch sensor system is established, and a self-made bearing surface scratch dataset is produced as the basis. The scratch detection final Average Precision (AP) value is 97%, which is 3.4% higher than that of YOLOV5. Additionally, the model has an accuracy of 99.46% for detecting defective and qualified products. The average detection time per image is 263.4 ms on the CPU device and 12.2 ms on the GPU device, demonstrating excellent performance in terms of both speed and accuracy. Furthermore, this study analyzes and compares the detection results of various models, demonstrating that the proposed method satisfies the requirements for detecting scratches on bearing surfaces in industrial settings.

Specificity of DNA ADP-Ribosylation Reversal by NADARs.

Recent discoveries establish DNA and RNA as bona fide substrates for ADP-ribosylation. NADAR ("NAD- and ADP-ribose"-associated) enzymes reverse guanine ADP-ribosylation and serve as antitoxins in the DarT-NADAR operon. Although NADARs are widespread across prokaryotes, eukaryotes, and viruses, their specificity and broader physiological roles remain poorly understood. Using phylogenetic and biochemical analyses, we further explore de-ADP-ribosylation activity and antitoxin functions of NADAR domains. We demonstrate that different subfamilies of NADAR proteins from representative E. coli strains and an E. coli-infecting phage retain biochemical activity while displaying specificity in providing protection from toxic guanine ADP-ribosylation in cells. Furthermore, we identify a myxobacterial enzyme within the YbiA subfamily that functions as an antitoxin for its associated DarT-unrelated ART toxin, which we termed YarT, thus presenting a hitherto uncharacterised ART-YbiA toxin-antitoxin pair. Our studies contribute to the burgeoning field of DNA ADP-ribosylation, supporting its physiological relevance within and beyond bacterial toxin-antitoxin systems. Notably, the specificity and confinement of NADARs to non-mammals infer their potential as highly specific targets for antimicrobial drugs with minimal off-target effects.

An inorganic-blended p-type semiconductor with robust electrical and mechanical properties.

Inorganic semiconductors typically have limited p-type behavior due to the scarcity of holes and the localized valence band maximum, hindering the progress of complementary devices and circuits. In this work, we propose an inorganic blending strategy to activate the hole-transporting character in an inorganic semiconductor compound, namely tellurium-selenium-oxygen (TeSeO). By rationally combining intrinsic p-type semimetal, semiconductor, and wide-bandgap semiconductor into a single compound, the TeSeO system displays tunable bandgaps ranging from 0.7 to 2.2 eV. Wafer-scale ultrathin TeSeO films, which can be deposited at room temperature, display high hole field-effect mobility of 48.5 cm2/(Vs) and robust hole transport properties, facilitated by Te-Te (Se) portions and O-Te-O portions, respectively. The nanosphere lithography process is employed to create nanopatterned honeycomb TeSeO broadband photodetectors, demonstrating a high responsibility of 603 A/W, an ultrafast response of 5 µs, and superior mechanical flexibility. The p-type TeSeO system is highly adaptable, scalable, and reliable, which can address emerging technological needs that current semiconductor solutions may not fulfill.