A dual-function mixed-culture biofilm for sulfadiazine removal and electricity production using bio-electrochemical system.

Sulfadiazine (SDZ) is frequently detected in environmental samples, arousing much concern due to its toxicity and hard degradation. This study investigated the electricity generation capabilities, SDZ removal and microbial communities of a highly efficient mixed-culture system using repeated transfer enrichments in a bio-electrochemical system. The mixed-culture biofilm (S160-T2) produced a remarkable current density of 954.12 ± 15.08 µA cm-2 with 160 mg/L SDZ, which was 32.9 and 1.8 times higher than that of Geobacter sulfurreducens PCA with 40 mg/L SDZ and without additional SDZ, respectively. Especially, the impressive SDZ removal rate of 98.76 ± 0.79% was achieved within 96 h using the further acclimatized mixed-culture. The removal efficiency of this mixed-culture for SDZ through the bio-electrochemical system was 1.1 times higher than that using simple anaerobic biodegradation. Furthermore, the current density and removal efficiency in this system gradually decreased with increasing SDZ concentrations from 0 to 800 mg/L. In addition, community diversity data demonstrated that the dominant genera, Geobacter and Escherichia-Shigella, were enriched in mixed-culture biofilm, which might be responsible for the current production and SDZ removal. This work confirmed the important roles of acclimatized microbial consortia and co-substrates in the simultaneous removal of SDZ and electricity generation in an electrochemical system.

Spatially Varying Costs of GHG Abatement with Alternative Cellulosic Feedstocks for Sustainable Aviation Fuels.

Cellulosic biomass-based sustainable aviation fuels (SAFs) can be produced from various feedstocks. The breakeven price and carbon intensity of these feedstock-to-SAF pathways are likely to differ across feedstocks and across spatial locations due to differences in feedstock attributes, productivity, opportunity costs of land for feedstock production, soil carbon effects, and feedstock composition. We integrate feedstock to fuel supply chain economics and life-cycle carbon accounting using the same system boundary to quantify and compare the spatially varying greenhouse gas (GHG) intensities and costs of GHG abatement with SAFs derived from four feedstocks (switchgrass, miscanthus, energy sorghum, and corn stover) at 4 km resolution across the U.S. rainfed region. We show that the optimal feedstock for each location differs depending on whether the incentive is to lower breakeven price, carbon intensity, or cost of carbon abatement with biomass or to have high biomass production per unit land. The cost of abating GHG emissions with SAF ranges from $181 Mg-1 CO2e to more than $444 Mg-1 CO2e and is lowest with miscanthus in the Midwest, switchgrass in the south, and energy sorghum in a relatively small region in the Great Plains. While corn stover-based SAF has the lowest breakeven price per gallon, it has the highest cost of abatement due to its relatively high GHG intensity. Our findings imply that different types of policies, such as volumetric targets, tax credits, and low carbon fuel standards, will differ in the mix of feedstocks they incentivize and locations where they are produced in the U.S. rainfed region.

Protection effect of Dioscoreae Rhizoma against ethanol-induced gastric injury in vitro and in vivo: A phytochemical and pharmacological study.

ETHNOPHARMACOLOGICAL RELEVANCE: Dioscoreae Rhizoma, a kind of Chinese yam, is a medicinal and edible plant used in China for strengthening the spleen and stomach. However, there is a lack of modern pharmacology studies regarding its anti-gastric injury activity. AIM OF THE STUDY: This study aimed to investigate the phytochemical composition of Chinese yam aqueous extract (CYW) and evaluate its gastroprotective effects against ethanol-induced gastric injury in vitro and in vivo. MATERIALS AND METHODS: The active components of CYW were identified using HPLC-QTOF-MS/MS in combination with the GNPS molecular networking and network pharmacology. In vitro studies were performed in the RAW264.7/GES-1 cell coculture system. In vivo study, mice were treated with CYW (0.31, 0.63, and 3.14 g/kg BW, orally) for 14 days, followed by a single oral dose of ethanol (10 mL/kg BW) to induce gastric injury. The biochemical, inflammation and oxidative stress markers were analyzed using commercial kits. Histopathology was used to assess the degree of gastric injury. Gene and protein expressions were studied using RT-qPCR and western blotting, respectively. RESULTS: CYW significantly restored the levels of SOD, GPx and CAT, and reduced the MDA content. Further analyses showed that CYW significantly alleviated the gastric oxidative stress by inhibiting the inflammation via decreasing p-NF-κB and p-IκB-α expression levels and inhibiting the generation of IL-6, TNF-α, and IL-1ß. At the same time, the fraction remarkably upregulated Bcl-2, downregulated Bax and increased growth factor secretion, thereby prevented gastric mucous cell. Besides, The combination of HPLC-QTOF-MS/MS, GNPS molecular networking analysis, and network pharmacology demonstrated that linoleic acid, 3-acetyl-11-keto-beta-boswellic acid, adenosine, aminocaproic acid, tyramine, DL-tryptophan, cycloleucine, lactulose, melibiose, alpha-beta-trehalose, and sucrose would be the main active compounds of CYW against ethanol-induced gastric injury. CONCLUSION: This study showed that CYW is potentially rich source of anti-oxidant and anti-inflammatory bioactive compounds. It showed efficacy against ethanol-induced gastric injury by inhibiting inflammation, oxidative stress, and apoptosis in the stomach. The results of the current work indicate that Dioscoreae Rhizoma could be utilized as a type of natural resource for production of new medicine and functional foods to prevent and/or ameliorate ethanol-induced gastric injury.

Adar Regulates Drosophila melanogaster Spermatogenesis via Modulation of BMP Signaling.

The dynamic process of Drosophila spermatogenesis involves asymmetric division, mitosis, and meiosis, which ultimately results in the production of mature spermatozoa. Disorders of spermatogenesis can lead to infertility in males. ADAR (adenosine deaminase acting on RNA) mutations in Drosophila cause male infertility, yet the causative factors remain unclear. In this study, immunofluorescence staining was employed to visualize endogenous ADAR proteins and assess protein levels via fluorescence-intensity analysis. In addition, the early differentiation disorders and homeostatic alterations during early spermatogenesis in the testes were examined through quantification of transit-amplifying region length, counting the number of GSCs (germline stem cells), and fertility experiments. Our findings suggest that deletion of ADAR causes testicular tip transit-amplifying cells to accumulate and become infertile in older male Drosophila. By overexpressing ADAR in early germline cells, male infertility can be partially rescued. Transcriptome analysis showed that ADAR maintained early spermatogenesis homeostasis through the bone-morphogenetic-protein (BMP) signaling pathway. Taken together, these findings have the potential to help explore the role of ADAR in early spermatogenesis.

Molecular engineering of PETase for efficient PET biodegradation.

The widespread utilization of polyethylene terephthalate (PET) has caused a variety of environmental and health problems. Compared with traditional thermomechanical or chemical PET cycling, the biodegradation of PET may offer a more feasible solution. Though the PETase from Ideonalla sakaiensis (IsPETase) displays interesting PET degrading performance under mild conditions; the relatively low thermal stability of IsPETase limits its practical application. In this study, enzyme-catalysed PET degradation was investigated with the promising IsPETase mutant HotPETase (HP). On this basis, a carbohydrate-binding module from Bacillus anthracis (BaCBM) was fused to the C-terminus of HP to construct the PETase mutant (HLCB) for increased PET degradation. Furthermore, to effectively improve PET accessibility and PET-degrading activity, the truncated outer membrane hybrid protein (FadL) was used to expose PETase and BaCBM on the surface of E. coli (BL21with) to develop regenerable whole-cell biocatalysts (D-HLCB). Results showed that, among the tested small-molecular weight ester compounds (p-nitrophenyl phosphate (pNPP), p-Nitrophenyl acetate (pNPA), 4-Nitrophenyl butyrate (pNPB)), PETase displayed the highest hydrolysing activity against pNPP. HP displayed the highest catalytic activity (1.94 µM(p-NP)/min) at 50 °C and increased longevity at 40 °C. The fused BaCBM could clearly improve the catalytic performance of PETase by increasing the optimal reaction temperature and improving the thermostability. When HLCB was used for PET degradation, the yield of monomeric products (255.7 µM) was ∼25.5 % greater than that obtained after 50 h of HP-catalysed PET degradation. Moreover, the highest yield of monomeric products from the D-HLCB-mediated system reached 1.03 mM. The whole-cell catalyst D-HLCB displayed good reusability and stability and could maintain more than 54.6 % of its initial activity for nine cycles. Finally, molecular docking simulations were utilized to investigate the binding mechanism and the reaction mechanism of HLCB, which may provide theoretical evidence to further increase the PET-degrading activities of PETases through rational design. The proposed strategy and developed variants show potential for achieving complete biodegradation of PET under mild conditions.

Manipulating the Spin State of Spinel Octahedral Sites via a π-π Type Orbital Coupling to Boost Water Oxidation.

Spin state is often regarded as the crucial valve to release the reactivity of energy-related catalysts, yet it is also challenging to precisely manipulate, especially for the active center ions occupied at the specific geometric sites. Herein, a π-π type orbital coupling of 3d (Co)-2p (O)-4f (Ce) was employed to regulate the spin state of octahedral cobalt sites (CoOh) in the composite of Co3O4/CeO2. More specifically, the equivalent high-spin ratio of CoOh can reach to 54.7% via tuning the CeO2 content, thereby triggering the average eg filling (1.094) close to the theoretical optimum value. The corresponding catalyst exhibits a superior water oxidation performance with an overpotential of 251 mV at 10 mA cm-2, rivaling most cobalt-based oxides state-of-the-art. The π-π type coupling corroborated by the matched energy levels between Ce t1u/t2u-O and CoOh t2g-O π type bond in the calculated crystal orbital Hamilton population and partial density of states profiles, stimulates a π-donation between O 2p and π-symmetric Ce 4fyz2 orbital, consequently facilitating the electrons hopping from t2g to eg orbital of CoOh. This work offers an in-depth insight into understanding the 4f and 3d orbital coupling for spin state optimization in composite oxides.

Regional structural abnormalities in thalamus in idiopathic cervical dystonia.

BACKGROUND: The thalamus has a central role in the pathophysiology of idiopathic cervical dystonia (iCD); however, the nature of alterations occurring within this structure remain largely elusive. Using a structural magnetic resonance imaging (MRI) approach, we examined whether abnormalities differ across thalamic subregions/nuclei in patients with iCD. METHODS: Structural MRI data were collected from 37 patients with iCD and 37 healthy controls (HCs). Automatic parcellation of 25 thalamic nuclei in each hemisphere was performed based on the FreeSurfer program. Differences in thalamic nuclei volumes between groups and their relationships with clinical information were analysed in patients with iCD. RESULTS: Compared to HCs, a significant reduction in thalamic nuclei volume primarily in central medial, centromedian, lateral geniculate, medial geniculate, medial ventral, paracentral, parafascicular, paratenial, and ventromedial nuclei was found in patients with iCD (P < 0.05, false discovery rate corrected). However, no statistically significant correlations were observed between altered thalamic nuclei volumes and clinical characteristics in iCD group. CONCLUSION: This study highlights the neurobiological mechanisms of iCD related to thalamic volume changes.

Latent class analysis of psychological resilience and influencing factors in patients with rheumatoid arthritis: a cross-sectional survey.

OBJECTIVES: To investigate the latent class of psychological resilience in patients with rheumatoid arthritis (RA) and examine the factors influencing various latent types. METHODS: A cross-sectional survey design was used in this study. A total of 480 patients with RA were enrolled from two tertiary care institutions in Chengdu, Sichuan Province, between May and November 2023, using the convenience sample approach. The General Information Questionnaire, CD-RISC-10, SSRS, ASES-8, and BRAF-MDQ were used to analyze the latent classes of psychological resilience in the respondents, and the factors influencing the latent classes were explored using one-way analysis of variance, analysis of variance, and multi-categorical logistic regression analysis. RESULTS: Overall, 423 valid questionnaires were returned, indicating an 88.13% effective return rate. A latent class analysis revealed that RA patients were divided into three classes of psychological resilience: low-level (20.3%), moderate-level (31.0%), and high-level (48.7%) psychological resilience. A multi-categorical logistic regression analysis found that social support, self-efficacy, weariness, age, work status, and somatic pain all significantly influenced psychological resilience in RA patients. CONCLUSION: Three classes of RA patients' psychological resilience were identified by this study, and these classes were strongly correlated with individual treatment components. It is crucial to take into account the psychological resiliency of female RA patients who do not have a job. In order to improve psychological resilience, healthcare staff should first increase their comprehension of treat-to-target. Furthermore, people with RA may become more psychologically resilient if they receive more social support. Key Points • Preliminary research found that psychological resilience in RA patients was associated with three latent classes. • In RA patients, psychological resilience was significantly influenced by self-efficacy, fatigue, age, work status, physical pain, and social support. • The fundamental goal of bolstering RA patients' psychological resilience is to reaffirm their place in the treatment process, for example, by improving patient compliance and achieving treat-to-target earlier.

Pentanary Oxythiogermanates Ba3MGe3O2S8 (M = Ca, Zn) Featuring [Ge3O2S8]8- Trimers and {[MGe3O2S8]6-}∞ Chains: Structural Chemistry and Physical Properties.

Oxychalcogenides are increasingly attracting wide attention because they contain multiple anions that may combine the advantages of oxides and chalcogenides. In this work, two new pentanary oxythiogermanates, Ba3MGe3O2S8 [M = Ca (1), Zn (2)], were synthesized by a high-temperature solid-state reaction. They crystallize in the orthorhombic space group Pnma, and their structures contain isolated [Ge3O2S8]8- units constructed by one [GeO2S2] and two [GeOS3] tetrahedra that link with M2+ ions to build the {[MGe3O2S8]6-}∞ chain, representing a new type of oxythiogermanate. Notably, a [ZnS5] square pyramid exists in 2. Their structural chemistry and relationship with relevant structures are analyzed. 1 and 2 exhibit wide band gaps of 3.93 and 2.63 eV, birefringences of 0.100 and 0.089 at 2100 nm, respectively, and also obvious photocurrent responses. This work may be extended to a family of AE3MIIMIV3O2Q8 (AE = alkali-earth metal; MII = Ca, Zn, Cd, Hg; MIV = Si, Ge, Sn; Q = S, Se), and further systematic survey on them can be performed to enrich the study of multifunctional oxychalcogenides.

Molecular mechanisms underlying structural plasticity of electroconvulsive therapy in major depressive disorder.

Although previous studies reported structural changes associated with electroconvulsive therapy (ECT) in major depressive disorder (MDD), the underlying molecular basis of ECT remains largely unknown. Here, we combined two independent structural MRI datasets of MDD patients receiving ECT and transcriptomic gene expression data from Allen Human Brain Atlas to reveal the molecular basis of ECT for MDD. We performed partial least square regression to explore whether/how gray matter volume (GMV) alterations were associated with gene expression level. Functional enrichment analysis was conducted using Metascape to explore ontological pathways of the associated genes. Finally, these genes were further assigned to seven cell types to determine which cell types contribute most to the structural changes in MDD patients after ECT. We found significantly increased GMV in bilateral hippocampus in MDD patients after ECT. Transcriptome-neuroimaging association analyses showed that expression levels of 726 genes were positively correlated with the increased GMV in MDD after ECT. These genes were mainly involved in synaptic signaling, calcium ion binding and cell-cell signaling, and mostly belonged to excitatory and inhibitory neurons. Moreover, we found that the MDD risk genes of CNR1, HTR1A, MAOA, PDE1A, and SST as well as ECT related genes of BDNF, DRD2, APOE, P2RX7, and TBC1D14 showed significantly positive associations with increased GMV. Overall, our findings provide biological and molecular mechanisms underlying structural plasticity induced by ECT in MDD and the identified genes may facilitate future therapy for MDD.

Progressive thalamic nuclear atrophy in blepharospasm and blepharospasm-oromandibular dystonia.

The thalamus is considered a key region in the neuromechanisms of blepharospasm. However, previous studies considered it as a single, homogeneous structure, disregarding potentially useful information about distinct thalamic nuclei. Herein, we aimed to examine (i) whether grey matter volume differs across thalamic subregions/nuclei in patients with blepharospasm and blepharospasm-oromandibular dystonia; (ii) causal relationships among abnormal thalamic nuclei; and (iii) whether these abnormal features can be used as neuroimaging biomarkers to distinguish patients with blepharospasm from blepharospasm-oromandibular dystonia and those with dystonia from healthy controls. Structural MRI data were collected from 56 patients with blepharospasm, 20 with blepharospasm-oromandibular dystonia and 58 healthy controls. Differences in thalamic nuclei volumes between groups and their relationships to clinical information were analysed in patients with dystonia. Granger causality analysis was employed to explore the causal effects among abnormal thalamic nuclei. Support vector machines were used to test whether these abnormal features could distinguish patients with different forms of dystonia and those with dystonia from healthy controls. Compared with healthy controls, patients with blepharospasm exhibited reduced grey matter volume in the lateral geniculate and pulvinar inferior nuclei, whereas those with blepharospasm-oromandibular dystonia showed decreased grey matter volume in the ventral anterior and ventral lateral anterior nuclei. Atrophy in the pulvinar inferior nucleus in blepharospasm patients and in the ventral lateral anterior nucleus in blepharospasm-oromandibular dystonia patients was negatively correlated with clinical severity and disease duration, respectively. The proposed machine learning scheme yielded a high accuracy in distinguishing blepharospasm patients from healthy controls (accuracy: 0.89), blepharospasm-oromandibular dystonia patients from healthy controls (accuracy: 0.82) and blepharospasm from blepharospasm-oromandibular dystonia patients (accuracy: 0.94). Most importantly, Granger causality analysis revealed that a progressive driving pathway from pulvinar inferior nuclear atrophy extends to lateral geniculate nuclear atrophy and then to ventral lateral anterior nuclear atrophy with increasing clinical severity in patients with blepharospasm. These findings suggest that the pulvinar inferior nucleus in the thalamus is the focal origin of blepharospasm, extending to pulvinar inferior nuclear atrophy and subsequently extending to the ventral lateral anterior nucleus causing involuntary lower facial and masticatory movements known as blepharospasm-oromandibular dystonia. Moreover, our results also provide potential targets for neuromodulation especially deep brain stimulation in patients with blepharospasm and blepharospasm-oromandibular dystonia.

Incommensurate Spin Density Wave in Antiferromagnetic RuO_{2} Evinced by Abnormal Spin Splitting Torque.

Since the discovery of antiferromagnetism, metallic oxide RuO_{2} has exhibited numerous intriguing spintronics properties such as the anomalous Hall effect and anisotropic spin splitting effect. However, the microscopic origin of its antiferromagnetism remains unclear. By investigating the spin splitting torque in RuO_{2}/Py, we found that metallic RuO_{2} exhibits a spatially periodic spin structure which interacts with the spin waves in Py through interfacial exchange coupling. The wavelength of such structure is evaluated within 14-20 nm depending on the temperature, which is evidence of an incommensurate spin density wave state in RuO_{2}. Our work not only provides a dynamics approach to characterize the antiferromagnetic ordering in RuO_{2}, but also offers fundamental insights into the spin current generation due to anisotropic spin splitting effect associated with spin density wave.

Drug recommendation for optimization on treatment outcome for MDR/RR-TB based on a multi-center, large scale, retrospective cohort study in China.

OBJECTIVE: With the change in drug-resistant pattern, MDR/RR-TB was faced with underlying changes in regimens. A multi-center, large-scale, retrospective study performed aims to provide a recommendation of drug selection on optimization of outcome for the patients. METHOD: The study was conducted in six TB-specialized hospitals in China. Patients were included from 2018-2021 and followed up throughout the treatment. Using a multivarariable and propensity score-matched logistic regression analysis, we evaluated associations between outcomes and drug use, as well as clinical characteritics. RESULTS: Of 3112 patients, 74.29% had treatment sucess, 14.52% lost to follow-up, 9.67% failure, and 1.51% died. Treatment success was positively associated with Bedaquiline(Bdq), Linezolid(Lzd), and Cycloserin(Cs). Capreomycin(Cm) increased the risk of unfavorable outcomes. other drugs such as Amikacin(Amk) and clofazimine had no significant effect on outcomes. If isolates were susceptible to fluoroquinolones(FQs), FQs could decrease the risk of unfavorable outcomes. CONCLUSIONS: The recommendation order for the treatment of MDR/RR-TB is Bdq, Lzd, and Cs. FQs were decreased in use intensity. Injection drugs, whether Amk or Cm, are not recommended.

Application of multidisciplinary in situ simulation training in the treatment of acute ischemic stroke: a quality improvement project.

BACKGROUND: Ischemic stroke refers to a disorder in the blood supply to a local area of brain tissue for various reasons and is characterized by high morbidity, mortality, and disability. Early reperfusion of brain tissue at risk of injury is crucial for the treatment of acute ischemic stroke. The purpose of this study was to evaluate comfort levels in managing acute stroke patients with hypoxemia who required endotracheal intubation after multidisciplinary in situ simulation training and to shorten the door-to-image time. METHODS: This quality improvement project utilized a comprehensive multidisciplinary in situ simulation exercise. A total of 53 participants completed the two-day in situ simulation training. The main outcome was the self-reported comfort levels of participants in managing acute stroke patients with hypoxemia requiring endotracheal intubation before and after simulation training. A 5-point Likert scale was used to measure participant comfort. A paired-sample t-test was used to compare the mean self-reported comfort scores of participants, as well as the endotracheal intubation time and door-to-image time on the first and second days of in situ simulation training. The door-to-image time before and after the training was also recorded. RESULTS: The findings indicated that in situ simulation training could enhance participant comfort when managing acute stroke patients with hypoxemia who required endotracheal intubation and shorten door-to-image time. For the emergency management of hypoxemia or tracheal intubation, the mean post-training self-reported comfort score was significantly higher than the mean pre-training comfort score (hypoxemia: 4.53±0.64 vs. 3.62±0.69, t= -11.046, P<0.001; tracheal intubation: 3.98±0.72 vs. 3.43±0.72, t= -6.940, P<0.001). We also observed a decrease in the tracheal intubation and door-to-image time and a decreasing trend in the door-to-image time, which continued after the training. CONCLUSION: Our study demonstrates that the implementation of in situ simulation training in a clinical environment with a multidisciplinary approach may improve the ability and confidence of stroke team members, optimize the first-aid process, and effectively shorten the door-to-image time of stroke patients with emergency complications.

QUIZ: An arbitrary volumetric point matching method for medical image registration.

Rigid pre-registration involving local-global matching or other large deformation scenarios is crucial. Current popular methods rely on unsupervised learning based on grayscale similarity, but under circumstances where different poses lead to varying tissue structures, or where image quality is poor, these methods tend to exhibit instability and inaccuracies. In this study, we propose a novel method for medical image registration based on arbitrary voxel point of interest matching, called query point quizzer (QUIZ). QUIZ focuses on the correspondence between local-global matching points, specifically employing CNN for feature extraction and utilizing the Transformer architecture for global point matching queries, followed by applying average displacement for local image rigid transformation.We have validated this approach on a large deformation dataset of cervical cancer patients, with results indicating substantially smaller deviations compared to state-of-the-art methods. Remarkably, even for cross-modality subjects, it achieves results surpassing the current state-of-the-art.

Knockdown of fat mass and obesity alleviates the ferroptosis in Parkinson's disease through m6A-NRF2-dependent manner.

Emerging evidence has suggested that N6 -methyladenosine (m6 A) regulates the pathology of Parkinson's disease (PD). Nevertheless, the function of demethylase fat mass and obesity (FTO) associated pathogenesis is still not fully elucidated. Here, this research findings revealed that m6 A-modification was decreased in PD models, meanwhile, the FTO level upregulated in the PD models. Functionally, in N-methyl-4-phenylpyridinium (MPP+) treated SH-SY5Y cells, the ferroptosis significantly upregulated and FTO silencing mitigated the ferroptosis phenotype. Moreover, in silico assays indicated that nuclear factor erythroid 2-related factor-2 (NRF2) acted as the target of FTO, and FTO demethylated the m6 A modification from NRF2 mRNA. Furthermore, FTO impaired the NRF2 mRNA stability via m6 A-dependent pathway. Thus, our findings illustrated an important role of FTO on PD through m6 A-NRF2-ferroptosis manner. Taken together, the study revealed the potential function of FTO on PD nervous system diseases.

A novel pyrosequencing strategy for RHD zygosity for predicting risk of hemolytic disease of the fetus and newborn.

OBJECTIVE: The aim of this study was the development of an accurate and quantitative pyrosequence (PSQ) method for paternal RHD zygosity detection to help risk management of hemolytic disease of the fetus and newborn (HDFN). METHODS: Blood samples from 96 individuals were genotyped for RHD zygosity using pyrosequencing assay. To validate the accuracy of pyrosequencing results, all the samples were then detected by the mismatch polymerase chain reaction with sequence-specific primers (PCR-SSP) method and Sanger DNA sequencing. Serological tests were performed to assess RhD phenotypes. RESULTS: Serological results revealed that 36 cases were RhD-positive and 60 cases were RhD-negative. The concordance rate between pyrosequencing assay and mismatch PCR-SSP assay was 94.8% (91/96). There were 5 discordant results between pyrosequencing and the mismatch PCR-SSP assay. Sanger sequencing confirmed that the pyrosequencing assay correctly assigned zygosity for the 5 samples. CONCLUSION: This DNA pyrosequencing method accurately detect RHD zygosity and will help risk management of pregnancies that are at risk of HDFN.

Early Diagnosing and Transformation Prediction of Alzheimer's Disease Using Multi-Scaled Self-Attention Network on Structural MRI Images with Occlusion Sensitivity Analysis.

BACKGROUND: Structural magnetic resonance imaging (sMRI) is vital for early Alzheimer's disease (AD) diagnosis, though confirming specific biomarkers remains challenging. Our proposed Multi-Scale Self-Attention Network (MUSAN) enhances classification of cognitively normal (CN) and AD individuals, distinguishing stable (sMCI) from progressive mild cognitive impairment (pMCI). OBJECTIVE: This study leverages AD structural atrophy properties to achieve precise AD classification, combining different scales of brain region features. The ultimate goal is an interpretable algorithm for this method. METHODS: The MUSAN takes whole-brain sMRI as input, enabling automatic extraction of brain region features and modeling of correlations between different scales of brain regions, and achieves personalized disease interpretation of brain regions. Furthermore, we also employed an occlusion sensitivity algorithm to localize and visualize brain regions sensitive to disease. RESULTS: Our method is applied to ADNI-1, ADNI-2, and ADNI-3, and achieves high performance on the classification of CN from AD with accuracy (0.93), specificity (0.82), sensitivity (0.96), and area under curve (AUC) (0.95), as well as notable performance on the distinguish of sMCI from pMCI with accuracy (0.85), specificity (0.84), sensitivity (0.74), and AUC (0.86). Our sensitivity masking algorithm identified key regions in distinguishing CN from AD: hippocampus, amygdala, and vermis. Moreover, cingulum, pallidum, and inferior frontal gyrus are crucial for sMCI and pMCI discrimination. These discoveries align with existing literature, confirming the dependability of our model in AD research. CONCLUSION: Our method provides an effective AD diagnostic and conversion prediction method. The occlusion sensitivity algorithm enhances deep learning interpretability, bolstering AD research reliability.

Current advances in the structural biology and molecular engineering of PETase.

Poly(ethylene terephthalate) (PET) is a highly useful synthetic polyester plastic that is widely used in daily life. However, the increase in postconsumer PET as plastic waste that is recalcitrant to biodegradation in landfills and the natural environment has raised worldwide concern. Currently, traditional PET recycling processes with thermomechanical or chemical methods also result in the deterioration of the mechanical properties of PET. Therefore, it is urgent to develop more efficient and green strategies to address this problem. Recently, a novel mesophilic PET-degrading enzyme (IsPETase) from Ideonella sakaiensis was found to streamline PET biodegradation at 30°C, albeit with a lower PET-degrading activity than chitinase or chitinase-like PET-degrading enzymes. Consequently, the molecular engineering of more efficient PETases is still required for further industrial applications. This review details current knowledge on IsPETase, MHETase, and IsPETase-like hydrolases, including the structures, ligand‒protein interactions, and rational protein engineering for improved PET-degrading performance. In particular, applications of the engineered catalysts are highlighted, including metabolic engineering of the cell factories, enzyme immobilization or cell surface display. The information is expected to provide novel insights for the biodegradation of complex polymers.

Construction and validation of a novel ferroptosis-related prognostic signature for lung adenocarcinoma.

Background: Lung cancer has the highest prevalence and mortality of all cancers, and lung adenocarcinoma (LUAD) occupies the largest proportion of lung cancers. Herein, this study is aimed at constructing a ferroptosis-related prognostic signature for LUAD and conducting functional analysis based on the signature, highlighting the importance of ferroptosis in LUAD. Methods: We employed RNA-sequencing (RNA-seq) and clinical data from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis were conducted to build the ferroptosis-related genes (FRGs) prognostic signature. The efficacy of this FRG signature was further analyzed with Kaplan-Meier (KM) plot, multivariate Cox regression, and the receiver operating characteristic (ROC) curves. Enrichment analysis was used to evaluate key pathways. The expression of immunomodulators, immune infiltration status, and drug sensitivity correlation were explored to predict the response to various therapies. The expression of FRGs was validated in LUAD samples with western blot (WB) and immunohistochemistry (IHC) staining. Cell viability assay and lipid peroxidation detection were measured after small interfering RNA (siRNA) knockdown of two FRGs in lung cancer cell lines. Results: A seven-gene signature was constructed and used to divide LUAD patients into high- and low-risk groups. High-risk patients were notably related to shorter overall survival (OS), and multivariate Cox regression demonstrated that our signature was an independent predictor of OS. ROC curve analysis presented a maximum area under the curve (AUC) value of 0.740 for the experimental cohort and 0.705 for the validation cohort. The low-risk group showed higher levels of plasma cell infiltration and higher expression of programmed cell death protein 1 (PDCD1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Ferroptosis inducers such as talazoparib or cisplatin had lower IC50 values in the high-risk group, while navitoclax (BCL-2 gene family inhibition and apoptosis inducer) had higher IC50 values in the high-risk group. Additionally, peroxiredoxin-6 (PRDX6) and acyl-CoA synthetase long chain family member 3 (ACSL3) were upregulated in LUAD tissues. Lipid peroxide assay showed that silencing PRDX6 or ACSL3 promoted lipid peroxidation and ferroptosis in lung cancer cells. Conclusions: Our novel ferroptosis-related signature shows potential clinical and functional importance in LUAD patients, and further research on ferroptosis as a therapeutic target in LUAD is warranted.