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Abstract The main cause of corneal blindness worldwide is keratitis, especially the infectious form caused by bacteria, fungi, viruses, and Acanthamoeba. The key to effective management of infectious keratitis hinges on prompt and precise diagnosis. Nevertheless, the current gold standard, such as cultures of corneal scrapings, remains time-consuming and frequently yields false-negative results. Here, using 23,055 slit-lamp images collected from 12 clinical centers nationwide, this study constructed a clinically feasible deep learning system, DeepIK, that could emulate the diagnostic process of a human expert to identify and differentiate bacterial, fungal, viral, amebic, and noninfectious keratitis. DeepIK exhibited remarkable performance in internal, external, and prospective datasets (all areas under the receiver operating characteristic curves > 0.96) and outperformed three other state-of-the-art algorithms (DenseNet121, InceptionResNetV2, and Swin-Transformer). Our study indicates that DeepIK possesses the capability to assist ophthalmologists in accurately and swiftly identifying various infectious keratitis types from slit-lamp images, thereby facilitating timely and targeted treatment.

Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate. However, most new chemical entities exhibit poor water solubility, and hence are exempt from such benefits. Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility, like other supersaturating systems, the problem of drug recrystallization has yet to be resolved, particularly within the dosage form. Here, we explored the potential of an emerging, non-leachable terpolymer nanoparticle (TPN) pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion (CRASD) beads comprising a poorly soluble drug (celecoxib) reservoir and insoluble polymer (ethylcellulose) membrane. Compared to conventional pore former, polyvinylpyrrolidone (PVP), TPN-containing membranes exhibited superior structural integrity, less crystal formation at the CRASD bead surface, and greater extent of celecoxib release. All-atom molecular dynamics analyses revealed that in the presence of TPN, intra-molecular bonding, crystal formation tendency, diffusion coefficient, and molecular flexibility of celecoxib were reduced, while intermolecular H-bonding was increased as compared to PVP. This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.

Smartphone-based artificial intelligence (AI) diagnostic systems could assist high-risk patients to self-screen for corneal diseases (e.g., keratitis) instead of detecting them in traditional face-to-face medical practices, enabling the patients to proactively identify their own corneal diseases at an early stage. However, AI diagnostic systems have significantly diminished performance in low-quality images which are unavoidable in real-world environments (especially common in patient-recorded images) due to various factors, hindering the implementation of these systems in clinical practice. Here, we construct a deep learning-based image quality monitoring system (DeepMonitoring) not only to discern low-quality cornea images created by smartphones but also to identify the underlying factors contributing to the generation of such low-quality images, which can guide operators to acquire high-quality images in a timely manner. This system performs well across validation, internal, and external testing sets, with AUCs ranging from 0.984 to 0.999. DeepMonitoring holds the potential to filter out low-quality cornea images produced by smartphones, facilitating the application of smartphone-based AI diagnostic systems in real-world clinical settings, especially in the context of self-screening for corneal diseases.

Key Clinical Message Using the Senhance robotic system and Senhance ultrasonic energy device for robotic‐assisted radical nephrectomy with hilum lymph node dissection demonstrated safety and feasibility in managing a large renal tumor without the need for open conversion or transfusion, offering a cost‐effective solution.

BackgroundMycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL). Comprehensive analysis of MF cells in situ and ex vivo is complicated by the fact that is challenging to distinguish malignant from reactive T cells with certainty.MethodsTo overcome this limitation, we performed combined single-cell RNA (scRNAseq) and T-cell receptor TCR sequencing (scTCRseq) of skin lesions of cutaneous MF lesions from 12 patients. A sufficient quantity of living T cells was obtained from 9 patients, but 2 had to be excluded due to unclear diagnoses (coexisting CLL or revision to a fixed toxic drug eruption).ResultsFrom the remaining patients we established single-cell mRNA expression profiles and the corresponding TCR repertoire of 18,630 T cells. TCR clonality unequivocally identified 13,592 malignant T cells. Reactive T cells of all patients clustered together, while malignant cells of each patient formed a unique cluster expressing genes typical of naive/memory, such as CD27, CCR7 and IL7R, or cytotoxic T cells, e.g., GZMA, NKG7 and GNLY. Genes encoding classic CTCL markers were not detected in all clusters, consistent with the fact that mRNA expression does not correlate linearly with protein expression. Nevertheless, we successfully pinpointed distinctive gene signatures differentiating reactive malignant from malignant T cells: keratins (KRT81, KRT86), galectins (LGALS1, LGALS3) and S100 genes (S100A4, S100A6) being overexpressed in malignant cells.ConclusionsCombined scRNAseq and scTCRseq not only allows unambiguous identification of MF cells, but also revealed marked heterogeneity between and within patients with unexpected functional phenotypes. While the correlation between mRNA and protein abundance was limited with respect to established MF markers, we were able to identify a single-cell gene expression signature that distinguishes malignant from reactive T cells.

T cell development in the thymus is dependent on the thymic microenvironment, in which thymic epithelial cells (TECs) are the major component. However, TECs undergo both a qualitative and quantitative loss during aging, which is believed to be the major factor responsible for age-dependent thymic atrophy. FOXN1 plays a critical role in TEC development and adult TECs maintenance. We have previously reported that intrathymic injection of a recombinant (r) protein containing murine FOXN1 and a protein transduction domain increases the number of TECs in mice, leading to enhanced thymopoiesis. However, intrathymic injection may not be an ideal choice for clinical applications. In this study, we produced a rFOXN1 fusion protein containing the N-terminal of CCR9, human FOXN1 and a protein transduction domain. When injected intravenously into 14-month-old mice, the rFOXN1 fusion protein enters the thymus and TECs, and enhances thymopoiesis, resulting in increased T cell generation in the thymus and increased number of T cells in peripheral lymphoid organ. Our results suggest that the rFOXN1 fusion protein has the potential to be used in preventing and treating T cell immunodeficiency in older adults.

Summary: Identifying the atlas of immune cells from coronary sinus circulation (CSC) of patients with persistent atrial fibrillation (PerAF) may provide new insights into the role of immune cells in the progression of AF. Single-cell sequencing revealed substantial alterations in immune cells from CSCs of patients with PerAF, especially a markedly elevated abundance of T cells, after which we identified a T cell subset: FGFBP2(+)TRDC(−)CD4(−) T cells (Ftc-T cells), which can promote the proliferation of cardiac fibroblasts (CFs),and the proportion of Ftc-T had a positive linear with AF recurrence post catheter ablation (CA). Moreover, IFI27 was found to be highly enriched in Ftc-T cells and promoted CFs proliferation and collagen expression. Altogether, our findings represent a unique resource providing in-depth insights into the heterogeneity of the immune cell from CSC of patients with PerAF and highlight the potential role of Ftc-T cells and IFI27 for AF progression.

Pterocarpan glucosides are biologically active natural products, in which the glucosyl group plays an important role. However, specific pterocarpan glycosyltransferases have rarely been reported. In this study, two highly efficient glycosyltransferases, AmGT28 and AmGT44, from Astragalus membranaceus, catalyzing the conversion of medicarpin (1) to medicarpin 3-O-glucoside (1a) were identified. They could also use other pterocarpans and isoflavonoids as substrates, showing a preference for pterocarpans over isoflavonoids. A new isoflavone 7-O-glucoside 5a was prepared through a scaled-up enzymatic reaction. Furthermore, AmGT44 was expressed in E. coli to establish a whole-cell biocatalytic system (500 μL with 0.1 mM substrate), which could glucosylate pterocarpans 1-3 with a conversion rate of up to 100% and a titer of 30-38 μg/mL within 25 h. The titer of maackiain 3-O-glucoside (2a) could reach 78.66 μg/mL in a 10-mL system. The study provides efficient catalytic tools for the biosynthesis of pterocarpan glycosides.

Abstract Natural products possess significant therapeutic potential but remain underutilized despite advances in genomics and bioinformatics. While there are approaches to activate and upregulate natural product biosynthesis in both native and heterologous microbial strains, a comprehensive strategy to elicit production of natural products as well as a generalizable and efficient method to interrogate diverse native strains collection, remains lacking. Here, we explore a flexible and robust integrase-mediated multi-pronged activation approach to reliably perturb and globally trigger antibiotics production in actinobacteria. Across 54 actinobacterial strains, our approach yielded 124 distinct activator-strain combinations which consistently outperform wild type. Our approach expands accessible metabolite space by nearly two-fold and increases selected metabolite yields by up to >200-fold, enabling discovery of Gram-negative bioactivity in tetramic acid analogs. We envision these findings as a gateway towards a more streamlined, accelerated, and scalable strategy to unlock the full potential of Nature’s chemical repertoire.

Abstract Based on our fieldwork in Yunnan Province and Ningxia Hui Autonomous Region, this paper explores the different ways in which Chinese rural women engage with the rising industry of e-commerce livestreaming related to agricultural products and villages. Our analytical framework is informed by feminist political economy, which pays heed to the gendered social settings, operation of power, and entanglement between women’s domesticity and productivity that underpin people’s economic activities. We argue that Chinese rural women’s simultaneous empowerment and disempowerment by e-commerce livestreaming are characterized by “mobile immobility”, a term inspired by Wallis’s (2013) research on rural women’s technological empowerment by mobile phones a decade ago. On the one hand, this latest form of e-commerce has created an apparently accessible path for rural women, who tend to be geographically immobile, to achieve social mobility by becoming professional webcasters and/or vloggers. On the other hand, this enablement is in fact classed, aged, and preconditioned on in-laws’ support and willingness to share these women’s domestic duties, which are not guaranteed. The urban-oriented digital economy of e-commerce livestreaming capitalizes on rural young women’s femininity, docile bodies and labor as well as the reproductive labor performed by their family members at the microlevel, reinforcing the urban–rural disparity at the macrolevel. The paper ends with reflections on the role of information and communication technologies and e-commerce in the development of rural China.

Background: Pulmonary vein isolation (PVI) is a foundational treatment for persistent atrial fibrillation (PeAF), but the effectiveness of adding posterior wall isolation (PWI) and selective complex fractionated atrial electrogram (CFAE) ablation in the roof and anterior wall remains debated. The potential of these additional ablation techniques to improve long-term outcomes for PeAF patients is still uncertain. Methods: This retrospective study included 151 PeAF patients who underwent first-time catheter ablation at our center. The choice of ablation strategy was based on the operator’s clinical judgment, taking into account the patient’s specific condition and anatomical features. Patients were divided into two groups: the PVI group, which received PVI alone, and the modified PWI (MPWI) group, which received PVI along with additional PWI and selective CFAEs ablation in the roof and anterior wall. The primary endpoint was the absence of atrial arrhythmia lasting more than 30 s, without antiarrhythmic drugs, at 12 months. Results: At the 12-month follow-up, 77.3% of the patients in the MPWI group and 52.1% of the patients in the PVI group remained in sinus rhythm without an atrial arrhythmia recurrence (p = 0.001). The BIC-based Cox regression analysis identified the ablation strategy and atrial fibrillation (AF) duration as independent predictors of recurrence across the cohort. It was found that MPWI significantly reduced the risk of recurrence, while a longer AF duration increased it. In the MPWI group, AF duration, left ventricular internal diameter in systole (LVIDs), and moderate or greater tricuspid regurgitation were independent predictors of recurrence. In the PVI group, only the left atrial low voltage area (LVA) index was a significant predictor. Conclusion: The addition of PWI and selective CFAE ablation to PVI significantly improves 12-month arrhythmia-free survival compared to PVI alone, demonstrating the superiority of this combined approach in improving long-term outcomes for patients with persistent AF.

Abstract Metal–organic frameworks (MOF) derived nitrogen‐doped carbon‐supported monodisperse Fe (Fe–N–C) catalysts are intensively studied, but great challenges remain in understanding the relationship between the coordination structure and the performance of Fe–N–C nanozymes. Herein, a novel nanocluster ligand‐bridging strategy is proposed for constructing Fe‐S1N4 structures with axially coordinated S and Au nanoclusters on ZIF‐8 derived Fe–N–C (labeled Aux/Fe‐S1N4‐C). The axial Au nanoclusters facilitate electron transfer to Fe active sites, utilizing the bridging ligand S as a medium, thereby enhancing the oxygen adsorption capacity of composite nanozymes. Compared to Fe‐N‐C, Aux/Fe‐S1N4‐C exhibits high oxidase‐like specificity and activity, and holds great potential for detecting acetylcholinesterase activity with a detection limit of 5.1 µU mL−1, surpassing most reported nanozymes.

Abstract Background The role of PPAR signaling and its associated genes in the pathogenesis and progression of chronic heart failure (CHF) remains elusive. Methods We accessed the gene expression profile and relevant baseline information of CHF samples from the Gene Expression Omnibus (GEO) database, specifically from the GSE57338 project. Results From GSE57338 project, we derived the expression value of 126 PPAR-related genes. A protein-protein interaction network was then established to illustrate potential protein interactions. ClueGO analysis results revealed that these genes predominantly participate in functions such as export across plasma membrane, regulation of lipid metabolic process, fatty acid metabolism, circulatory system vascular processes, alcohol metabolism, triglyceride metabolism and regulation of lipid localization and response to nutrient. Using the cytohubba plug-in in Cytoscape, we pinpointed ACADM, PPARG and CPT2 as potential central molecules in HF pathogenesis and progression. Subsequent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis delved into the potential biological role of these three genes in CHF. Immune infiltration analysis suggested that the infiltration level of neutrophils and M2 macrophages might be notably influenced by these genes, thereby playing a role in the CHF mechanism. Conclusions Our research provides a comprehensive insight into the significance of PPAR associated genes in CHF development. Notably, the genes ACADM, PPARG and CPT2 emerged as potential targets for clinical interventions.

We assessed tecovirimat treatment equity for 3,740 mpox patients in New York, New York, USA, during the 2022 mpox emergency; 32.4% received tecovirimat. Treatment rates by race/ethnicity were 38.8% (White), 31.3% (Black/African American), 31.0% (Hispanic/Latino), and 30.1% (Asian/Pacific Islander/other). Future public health emergency responses must prioritize institutional and structural racism mitigation.

Abstract Apiose is a natural pentose containing an unusual branched-chain structure. Apiosides are bioactive natural products widely present in the plant kingdom. However, little is known on the key apiosylation reaction in the biosynthetic pathways of apiosides. In this work, we discover an apiosyltransferase GuApiGT from Glycyrrhiza uralensis. GuApiGT could efficiently catalyze 2″-O-apiosylation of flavonoid glycosides, and exhibits strict selectivity towards UDP-apiose. We further solve the crystal structure of GuApiGT, determine a key sugar-binding motif (RLGSDH) through structural analysis and theoretical calculations, and obtain mutants with altered sugar selectivity through protein engineering. Moreover, we discover 121 candidate apiosyltransferase genes from Leguminosae plants, and identify the functions of 4 enzymes. Finally, we introduce GuApiGT and its upstream genes into Nicotiana benthamiana, and complete de novo biosynthesis of a series of flavonoid apiosides. This work reports an efficient phenolic apiosyltransferase, and reveals mechanisms for its sugar donor selectivity.

Abstract Acetylation contributes to the bioactivity of numerous medicinally important natural products. However, little is known about the acetylation on sugar moieties. Here we report a saponin acetyltransferase from Astragalus membranaceus. AmAT7-3 is discovered through a stepwise gene mining approach and characterized as the xylose C3′/C4′-O-acetyltransferse of astragaloside IV (1). To elucidate its catalytic mechanism, complex crystal structures of AmAT7-3/1 and AmAT7-3A310G/1 are obtained, which reveal a large active pocket decided by a specific sequence AADAG. Combining with QM/MM computation, the regiospecificity of AmAT7-3 is determined by sugar positioning modulated by surrounding amino acids including #A310 and #L290. Furthermore, a small mutant library is built using semi-rational design, where variants A310G and A310W are found to catalyze specific C3′-O and C4′-O acetylation, respectively. AmAT7-3 and its variants are also employed to acetylate other bioactive saponins. This work expands the understanding of saponin acetyltransferases, and provide efficient catalytic tools for saponin acetylation.

Abstract Objective This study aimed to explore the knowledge, self-efficacy, and attitudes toward suicide prevention among nurses with different demographic characteristics. Methods A cross-sectional descriptive design was adopted, and the study was conducted between August and September 2020. The content of the questionnaire included basic demographics, knowledge, self-efficacy, and attitudes toward suicide prevention. Correlation analysis was performed to determine nurses’ knowledge, self-efficacy, and attitudes toward suicide prevention. Results The sample comprised 778 nursing staff from a medical center in southern Taiwan. The results showed that age, years of nursing experience, department type, education on suicide prevention, and care experience of nursing staff were associated with their knowledge, self-efficacy, and attitudes toward suicide prevention in general hospital patients. Younger and less experienced nurses demonstrated superior knowledge, self-efficacy, and attitudes toward suicide prevention. Nurses who received suicide-related education and training exhibited better self-efficacy and attitudes than those who did not. Nurses with care experience had better knowledge of suicide prevention than those without experience. Knowledge and self-efficacy in suicide prevention were both significantly and positively correlated with attitudes. Conclusion Younger, less experienced, psychiatric nurses demonstrated superior knowledge, self-efficacy, and attitudes toward suicide prevention. Therefore, education on suicide prevention should be strengthened for older, experienced, and non-psychiatric nurses.

The widespread use of per- and polyfluoroalkyl substances (PFASs) with different physico–chemical properties poses a great threat to the environment and human health. Simultaneous detection of different classes of PFASs is a difficult task, especially for rapid analysis of polluted water samples in environmental forensic cases. In this study, a simple sample preparation ultrahigh-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was established for the detection of PFASs in a wide range of water matrices. By optimizing the conditions of pretreatment and the parameters of the instrument, the developed method provided good linearity of calibration standards (R2 > 0.99), and demonstrated excellent MLOQ (0.008–1.2 µg/L), with spiked recoveries ranging from 57.7% to 151% for 47 targets in surface water samples, and from 45.7 to 165% for 46 targets in ground and waste water samples, respectively. This method required an injection volume of 3 µL and an analysis time of only 18 min per sample. The validation method was successfully applied to the analysis of 20 environmental water samples, in which 15 target substances with different concentrations were detected, with total concentrations of 0.082 to 262.455 μg/L. The method is simple and exclusive, and can rapidly confirm the occurrence of PFASs in different water samples, providing a convenient and fast high-throughput analysis, which is especially suitable for the application in the environmental forensic investigation of PFASs pollution.

C-Glycosides are important natural products with various bioactivities. In plant biosynthetic pathways, the C-glycosylation step is usually catalyzed by C-glycosyltransferases (CGTs), and most of them prefer to accept uridine 5′-diphosphate glucose (UDP-Glc) as sugar donor. No CGTs favoring UDP-rhamnose (UDP-Rha) as sugar donor has been reported, thus far. Herein, we report the first selective C-rhamnosyltransferase VtCGTc from the medicinal plant Viola tricolor. VtCGTc could efficiently catalyze C-rhamnosylation of 2-hydroxynaringenin 3-C-glucoside, and exhibited high selectivity towards UDP-Rha. Mechanisms for the sugar donor selectivity of VtCGTc were investigated by molecular dynamics (MD) simulations and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) binding free energy calculations. Val144 played a vital role in recognizing UDP-Rha, and the V144T mutant could efficiently utilize UDP-Glc. This work provides a new and efficient approach to prepare flavonoid C-rhamnosides such as violanthin and iso-violanthin.

Recently, biomacromolecules have received considerable attention in hemostatic materials. Collagen, an ideal candidate for hemostatic sponges due to its involvement in the clotting process, has been facing challenges in extraction from raw materials, which is time-consuming, expensive, and limited by cultural and religious restrictions associated with traditional livestock and poultry sources. To address these issues, this study explored a new shortcut method that using wild Halocynthia roretzi (HR), a marine fouling organism, as a raw material for developing HR collagen fiber sponge (HRCFs), which employed urea to disrupt hydrogen bonds between collagen fiber aggregates. This method simplifies traditional complex manufacturing processes while utilized marine waste, thus achieving dual green in terms of raw materials and manufacturing processes. FTIR results confirmed that the natural triple-helical structure of collagen was preserved. HRCFs exhibit a blood absorption ratio of 2000–3500 %, attributed to their microporous structure, as demonstrated by kinetic studies following a capillary model. Remarkably, the cytotoxicity and hemolysis ratio of HRCFs are negligible. Furthermore, during in vivo hemostasis tests using rabbit ear and kidney models, HRCFs significantly reduce blood loss and shorten hemostasis time compared to commercial gelatin sponge and gauze, benefiting from the capillary effect and collagen's coagulation activity. This study provides new insights into the design of collagen-based hemostatic biomaterials, especially in terms of both raw material and green manufacturing processes.

The solubility and transformation of cadmium (Cd) are controlled by paddy soil pH, whereas paddy soil pH varies during flooding and drainage and is significantly controlled by flooding durations. However, there is still a lack of modeling approaches for simulating the impact of flooding durations on pH fluctuation and concomitant Cd effectiveness in Cd-polluted acidic paddy soils. Herein, laboratory findings combined with a process-based numerical modeling method were used to quantify the observed key geochemical processes of Fe/C/N/S and the accompanying Cd partitioning dynamics during flooding and drainage. During flooding stage, the number of protons consumed by Fe(III), NO3−, and SO42− reduction increased with flooding durations, resulting in an increase of pH, which enhanced Cd immobilization and reduced Cd potential risk. After entering drainage stage, the number of protons released from Fe(II), NH4+, and S2− oxidation increased with flooding time, leading to pH decrease, which increased Cd release. A process-based kinetic model fitting results showed that Fe(III) reduction and Fe(II) oxidation were key processes that increased and decreased pH, respectively, and that increasing flooding durations were not beneficial to Cd immobilization during flooding and drainage processes. The results of this study shed light on the impact of redox state of paddy soil on Cd dynamics under different flooding durations and provide a theoretical approach to quantify the contribution of key processes controlling changes in metal species, which can be used to simulate the dynamic behavior of heavy metals in paddy soil under different natural conditions by coupling other significant processes.

Abstract Biosurfactants are attracting much interest due to their potential application as therapeutic agents in the medical and cosmetic field. Previous studies have demonstrated that biosurfactant such as sophorolipid (SL) exhibits immunomodulatory effects. In this article, we found the potential of sophorolipid for inhibiting histamine-induced itch and preliminarily explored its molecular basis. First, behavioral tests indicated that SL can remit the histamine-induced scratching behaviors of mice. Second, SL can suppress the the calcium influx induced by histamine, HTMT and VUF8430 in HaCaT cells. RT-PCR analysis showed that the histamine-induced upregulation of mRNA levels of phospholipase Cγ1, 1,4,5-trisphosphate receptor (IP3R), and protein kinase Cα can be inhibted by SL, suggesting that SL may impede the PLC/IP3R signaling pathway activated by histamine. In further tests, the capsaicin-induced calcium influx can also be inhibited by SL. The immunofluorescence and molecular docking analysis indicated that SL acts as an inhibitor of transient receptor potential vanilloid-1 (TRPV1) activation to decrease calcium influx against stimuli. In summary, these results revealed that SL may inhibit histamine-induced itch by decreasing PLC/IP3R signaling pathway activation and modulating TRPV1 activity. This paper indicates that SL can be a useful treatment for histamine-dependent itch.

Abstract Aims Limited data are available on the outcomes of cryoballoon ablation (CBA)‐based pulmonary vein isolation (PVI) for atrial fibrillation (AF) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF). The present study aimed to evaluate the safety and effectiveness of CBA in such patients. Methods and results Consecutive patients with AF referred for CBA‐based PVI from two highly experienced electrophysiology centres were included in this retrospective study. Of 651 patients undergoing CBA, 471 cases were divided into four groups: No HF (n = 255), HFpEF (n = 101), HFmrEF (n = 78), and HF with reduced ejection fraction (n = 37). Similar early recurrence of atrial arrhythmia was found among groups (16.2% vs. 15.4% vs. 14.9% vs. 12.2%, P = 0.798), and no significant difference of long‐term sinus rhythm (SR) maintenance was identified among the HFmrEF, HFpEF, and No HF groups (71.8% vs. 75.2% vs. 79.6%, P = 0.334). CBA is safe for patients with HFmrEF and HFpEF with similar complications compared with the No HF group (3.8% vs. 4.0% vs. 3.1%, P = 0.814). The reassessment of cardiac function after CBA showed that patients with HF indicated beneficial outcomes. Left atrial diameter (LAD) and left ventricular ejection fraction were significantly improved in the HFmrEF group. There were 41.6% of patients in the HFpEF group who were completely relieved from HF. LAD and New York Heart Association (NYHA) were associated with recurrence in the HFpEF and HFmrEF groups, and the maintenance of SR was an independent predictor of NYHA improvement for all HF groups. Conclusions Patients with HFmrEF and HFpEF could benefit from CBA with high SR maintenance and significant HF improvement.

Introduction: Triterpenoids and saponins have a broad range of pharmacological activities. Unlike most legumes which contain mainly oleanane-type scaffold, Astragalus membranaceus contains not only oleanane-type but also cycloartane-type saponins, for which the biosynthetic pathways are unknown. Objectives: This work aims to study the function and catalytic mechanism of oxidosqualene cyclases (OSCs), one of the most important enzymes in triterpenoid biosynthesis, in A. membranaceus. Methods: Two OSC genes, AmOSC2 and AmOSC3, were cloned from A. membranaceus. Their functions were studied by heterologous expression in tobacco and yeast, together with in vivo transient expression and virus-induced gene silencing. Site-directed mutagenesis and molecular docking were used to explain the catalytic mechanism for the conserved motif. Results: AmOSC2 is a β-amyrin synthase which showed higher expression levels in underground parts. It is associated with the production of β-amyrin and soyasaponins (oleanane-type) in vivo. AmOSC3 is a cycloartenol synthase expressed in both aerial and underground parts. It is related to the synthesis of astragalosides (cycloartane-type) in the roots, and to the synthesis of cycloartenol as a plant sterol precursor. From AmOSC2/3, conserved triad motifs VFM/VFN were discovered for β-amyrin/cycloartenol synthases, respectively. The motif is a critical determinant of yield as proved by 10 variants from different OSCs, where the variant containing the conserved motif increased the yield by up to 12.8-fold. Molecular docking and mutagenesis revealed that Val, Phe and Met residues acted together to stabilize the substrate, and the cation-π interactions from Phe played the major role. Conclusion: The study provides insights into the biogenic origin of oleanane-type and cycloartane-type triterpenoids in Astragalus membranaceus. The conserved motif offers new opportunities for OSC engineering.

Here, the authors investigate naphthalimide-based compounds with cold triplet excitons utilized by triplet-triplet annihilation-mediated high-lying reverse intersystem crossing, and realize rate constant of over 109 s−1 with exciton utilization efficiency of 46.7% in organic light-emitting diodes.

The Internet brings convenience and happiness to consumers. The government must guide food safety standards. The government must provide implementation details, schedule planning, description-of-use documents, relevant regulations on food safety, and address matters needing attention and critical points of on-site counseling and inspection, the formulation of pertinent form documents, the evaluation of the feasibility of the form, and the time required. The Taichung City Government mainly conducts this research to investigate and guide online food sale companies. The industries are food manufacturing, online sales, and catering. The information was surveyed from major website platforms, comprising 640 incidents. These sites include Shopee, PC Home, MOMO, PChome, eBay, and Gomaji. This study uses corporate interview surveys and narrative statistics. The research results show that there are ten food safety issues. The most common ones are the items that should and should not be recorded in the stereotypical food or catering service contract stipulated by communication transactions. That is the most common food safety violation by businesses. This research provides academic and practical references for the positive message transmission of online sales.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease distinguished by synovial hyperplasia and a progressive destruction of joints. T cells are critical players in the pathogenesis of RA. We have previously identified a novel immune checkpoint molecule, TAPBPL, that inhibits T cell functions in vitro. As a model for human RA, we investigated the ability of the TAPBPL protein to ameliorate collagen type II (CII)-induced arthritis (CIA) in mice that were injected with recombinant TAPBPL or a control protein. The mice were analyzed for CIA development, immune cells, and their responses. We found that TAPBPL protein significantly decreased CIA incidence and reduced clinical and pathological arthritis scores, which were related to a lower number of activated CD4 T cells but a greater number of regulatory T cells (Tregs) in the spleen, and a reduction of Th1/Th17 inflammatory cytokines in the joints and serum. Importantly, TAPBPL protein inhibited CII-specific T cell growth and Th1 and Th17 cytokine expression and reduced the production of CII autoantibodies in the serum. Our results suggest that TAPBPL protein can ameliorate CIA in mice and has the potential to be used in the treatment of patients with RA.

Light-sheet fluorescent microscopy has become the leading technique for in vivo imaging in the fields of disease, medicine, and cell biology research. However, designing proper illumination for high image resolution and optical sectioning is challenging. Another issue is geometric constraints arising from the multiple bulky components for illumination and detection. Here, we demonstrate that those issues can be well addressed by integrating nanophotonic meta-lens as the illumination component for LSFM. The meta-lens is composed of 800-nm-thick GaN nanostructures and is designed for a light-sheet well-adapted to biological specimens such as the nematode Caenorhabditis elegans (C. elegans). With the meta-lens, the complexity of the LSFM system is significantly reduced, and it is capable of performing multicolor fluorescent imaging of live C. elegans with cellular resolution. Considering the miniature size and plane geometry of the meta-lens, our system enables a new design for LSFM to acquire in vivo images of biological specimens with high resolution.

Abstract Background The depth of cervical stromal invasion is one of the important prognostic factors affecting decision-making for early stage cervical cancer (CC). This study aimed to develop and validate a T2-weighted imaging (T2WI)-based radiomics model and explore independent risk factors (factors with statistical significance in both univariate and multivariate analyses) of middle or deep stromal invasion in early stage CC. Methods Between March 2017 and March 2021, a total of 234 International Federation of Gynecology and Obstetrics IB1-IIA1 CC patients were enrolled and randomly divided into a training cohort (n = 188) and a validation cohort (n = 46). The radiomics features of each patient were extracted from preoperative sagittal T2WI, and key features were selected. After independent risk factors were identified, a combined model and nomogram incorporating radiomics signature and independent risk factors were developed. Diagnostic accuracy of radiologists was also evaluated. Results The maximal tumor diameter (MTD) on magnetic resonance imaging was identified as an independent risk factor. In the validation cohort, the radiomics model, MTD, and combined model showed areas under the curve of 0.879, 0.844, and 0.886. The radiomics model and combined model showed the same sensitivity and specificity of 87.9% and 84.6%, which were better than radiologists (sensitivity, senior = 75.7%, junior = 63.6%; specificity, senior = 69.2%, junior = 53.8%) and MTD (sensitivity = 69.7%, specificity = 76.9%). Conclusion MRI-based radiomics analysis outperformed radiologists for the preoperative diagnosis of middle or deep stromal invasion in early stage CC, and the probability can be individually evaluated by a nomogram.

Abstract Background The transfer of the behaviors of a human’s upper limbs to an avatar is widely used in the field of virtual reality rehabilitation. To perform the transfer, movement tracking technology is required. Traditionally, wearable tracking devices are used for tracking; however, these devices are expensive and cumbersome. Recently, non-wearable upper-limb tracking solutions have been proposed, which are less expensive and more comfortable. However, most products cannot track the upper limbs, including the arms and all the fingers at the same time, which limits the limb parts for tracking in a virtual environment and may lead to a limited rehabilitation effect. Methods In this paper, a novel virtual reality rehabilitation system (VRRS) was developed for upper-limb rehabilitation. The VRRS could track the motion of both upper limbs, integrate fine finger motion and the range of motion of the entire arm and map the motion to an avatar. To test the performance of VRRS, two experiments were designed. In the first experiment, we investigated the effect of VRRS on virtual body ownership, agency and location of the body and usability in 8 healthy participants by comparing it with a partial upper-limb tracking method based on a Leap Motion controller (LP) in the same virtual environments. In the second experiment, we examined the feasibility of VRRS in upper-limb rehabilitation with 27 stroke patients. Results VRRS improved the users’ senses of body ownership, agency, and location of the body. The users preferred using the VRRS to using the LP. In addition, we found that although the upper limb motor function of patients from all groups was improved, the difference between the FM scores tested on the first day and the last day of the experimental group was more significant than that of the control groups. Conclusions A VRRS with motion tracking of the upper limbs and avatar control including the arms and all the fingers was developed. It resulted in an improved user experience of embodiment and effectively improved the effects of upper limb rehabilitation in stroke patients. Trial registration The study was registered at the First Affiliated Hospital of Jinan University Identifier: KY-2020–036; Date of registration: June 01, 2020.

The present study investigated the molecular phylogeny, antimicrobial and cytotoxic activities of fungal endophytes obtained from the A*STAR Natural Organism Library (NOL) and previously isolated from Sungei Buloh Wetland Reserve, Singapore. Phylogenetic analysis based on ITS2 gene suggests that these isolates belong to 46 morphotypes and are affiliated to 23 different taxa in 17 genera of the Ascomycota phylum. Colletotrichum was the most dominant fungal genus accounting for 37% of all the isolates, followed by Diaporthe (13%), Phyllosticta (10.9%) and Diplodia (8.7%). Chemical elicitation using 5-azacytidine, a DNA methyltransferase inhibitor and suberoylanilide hydroxamic acid, a histone deacetylase inhibitor resulted in an increase in the number of active strains. Bioassay-guided isolation and structural elucidation yielded pestahivin and two new analogues from Bartalinia sp. F9447. Pestahivin and its related analogues did not exhibit antibacterial activity against Staphylococcus aureus but displayed strong antifungal activities against Candida albicans and Aspergillus brasiliensis, with IC50 values ranging from 0.46 ± 0.06 to 144 ± 18 µM. Pestahivin and its two analogues furthermore exhibited cytotoxic activity against A549 and MIA PACA-2 cancer cell lines with IC50 values in the range of 0.65 ± 0.12 to 42 ± 5.2 µM. The finding from this study reinforces that chemical epigenetic induction is a promising approach for the discovery of bioactive fungal secondary metabolites encoded by cryptic gene clusters.

Pulmonary hypertension (PH) is featured by pulmonary vascular and cardiac remodeling. Rehabilitation exercise can improve patients’ quality of life. We previously pinpointed a potential glutamine metabolism dysfunction in PH. Hence, we aim to investigate whether rehabilitation exercise could mitigate right ventricular and pulmonary vascular remodeling and its effect on glutaminase (GLS). We collected clinical indicators of PH patients and analyzed their correlation with GLS. Rehabilitation exercise (moderate intensity swimming exercise) was performed in monocrotaline-induced PH (MCT-PH) rats. We found that plasma GLS1 level in patients was lower than healthy subjects, and it was negatively correlated with end-systolic stage eccentricity index, right atrial transverse dimension and right atrial longitudinal dimension. MCT-PH rats displayed pulmonary vascular remodeling and right ventricular hypertrophy. Compared to control rats, higher levels of GLS1 and GLS2 mRNA in lung and lower levels of these two isoforms of GLS in right ventricle (RV) were displayed in MCT-PH rats. After swimming exercise, GLS mRNA levels in the lung and RV were significantly upregulated, and the cross-sectional area of right ventricular cardiomyocytes was significantly decreased although the percentage of pulmonary arteriolar medial wall thickness was not significantly changed. Therefore, we hold the opinion that plasma GLS1 level was decreased in PH. The transcriptional levels of GLS1 and GLS2 were increased in the lung tissues in PH, but were decreased in the RV tissues. Meanwhile, the changes of GLS levels indicated the pulmonary vascular and right ventricular remodeling. Whereas moderate intensity swimming exercise might improve the right ventricular remodeling by regulating the levels of GLS.

Lophiotrema is a genus of ascomycetous fungi within the family Lophiotremataceae. Members of this genus have been isolated as endophytes from a wide range of host plants and also from plant debris within terrestrial and marine habitats, where they are thought to function as saprobes. Lophiotrema sp. F6932 was isolated from white mangrove (Avicennia officinalis) in Pulau Ubin Island, Singapore. Crude extracts from the fungus exhibited strong antibacterial activity, and bioassay-guided isolation and structure elucidation of bioactive constituents led to the isolation of palmarumycin C8 and a new analog palmarumycin CP30. Whole-genome sequencing analysis resulted in the identification of a putative type 1 iterative PKS (iPKS) predicated to be involved in the biosynthesis of palmarumycins. To verify the involvement of palmarumycin (PAL) gene cluster in the biosynthesis of these compounds, we employed ribonucleoprotein (RNP)-mediated CRISPR-Cas9 to induce targeted deletion of the ketosynthase (KS) domain in PAL. Double-strand breaks (DSBs) upstream and downstream of the KS domain was followed by homology-directed repair (HDR) with a hygromycin resistance cassette flanked by a 50 bp of homology on both sides of the DSBs. The resultant deletion mutants displayed completely different phenotypes compared to the wild-type strain, as they had different colony morphology and were no longer able to produce palmarumycins or melanin. This study, therefore, confirms the involvement of PAL in the biosynthesis of palmarumycins, and paves the way for implementing a similar approach in the characterization of other gene clusters of interest in this largely understudied fungal strain.

Introduction: During the COVID-19 epidemic in Singapore, there was an urgent demand to train more nurses within a short timeframe to perform the Water Swallow Test (WST). The previous training model involved training with actual patients and was time-consuming. Hence, the model was revamped and standardised patients (SPs) were engaged for nurses’ training. This study further investigated nurses’ feedback about the new training model and compared the efficiency and learner-reported outcomes of the previous and new models. Methods: Nurses who completed WST training from January 2018 to July 2020 were enrolled. Training records were accessed to determine the number of nurses trained under the previous and new models. Nurses were invited to complete post-training evaluation forms and their responses were analysed. Descriptive statistics and the Mann-Whitney U test were used for data analysis. Results: Under the previous model, 52 nurses were trained over 2 years, whereas under the new model, 112 nurses were trained over two months. From the evaluation form responses, the majority of nurses trained under the new model agreed that they achieved the learning objectives and were confident in performing the WST. There was also no significant difference (p>0.05) found between learner-reported outcomes for both training models. Conclusion: Our findings demonstrated that the new model that engaged SPs was more efficient in training more nurses. Nurses were also satisfied with the new training model, which achieved similar learner-reported outcomes as the previous model.

Keratitis is the main cause of corneal blindness worldwide, but most vision loss caused by keratitis can be avoidable via early detection and treatment, which are challenging in resource-limited settings. Here, the authors develop a deep learning system for the automated classification of keratitis and other cornea abnormalities.

Endophytic microorganisms are an important source of bioactive secondary metabolites. In this study, fungal endophytes obtained from A*STAR’s Natural Product Library (NPL) and previously isolated from different habitats of Singapore were investigated for their diversity, antimicrobial, and cytotoxic activities. A total of 222 fungal strains were identified on the basis of sequence analysis of ITS region of the rDNA gene. The identified fungal strains belong to 59 genera distributed in 20 orders. Majority of the identified strains (99%; 219 strains) belong to the phylum Ascomycota, while two strains belonged to the phylum Basidiomycota, and only one strain was from Mucoromycota phylum. The most dominant genus was Colletotrichum accounting for 27% of all the identified strains. Chemical elicitation using 5-azacytidine and suberoylanilide hydroxamic acid (SAHA) and variation of fermentation media resulted in the discovery of more bioactive strains. Bioassay-guided isolation and structure elucidation of active constituents from three prioritized fungal strains: Lophiotrema sp. F6932, Muyocopron laterale F5912, and Colletotrichum tropicicola F10154, led to the isolation of a known compound; palmarumycin C8 and five novel compounds; palmarumycin CP30, muyocopronol A-C and tropicicolide. Tropicicolide displayed the strongest antifungal activity against Aspergillus fumigatus with an IC50 value of 1.8 μg/ml but with a weaker activity against the Candida albicans presenting an IC50 of 7.1 μg/ml. Palmarumycin C8 revealed the best antiproliferative activity with IC50 values of 1.1 and 2.1 μg/ml against MIA PaCa-2 and PANC-1 cells, respectively.

The presence of a swallow-tail sign in the nigrosome-1 with hyperintense signal shown on the susceptibility-weighted imaging (SWI) has been shown to be sensitive in detecting the abnormal iron deposits in this area. A systematic evaluation in healthy subjects is required before this tool can be recommended in a widespread application. We evaluated a simple and practical SWI approach using a multiecho gradient-echo sequence with an improved contrast-to-noise ratio (CNR). We also evaluated the association of the neuromelanin imaging contrast behavior with the susceptibility and relaxation measurements. Twenty-five older and 23 young healthy adults were evaluated. The CNRs of the nigrosome-1 were compared along with method and group. Correlations of the nigrosome-1 neuromelanin signal in the neuromelanin-sensitive imaging with CNRs in the susceptibility, T1 and T2 mappings were examined. Two different coils were used to confirm the reproducibility. Compared with the single-echo, multiecho SWI can improve the CNR of the swallow-tail sign. We found significant correlations between neuromelanin signal and CNRs in the susceptibility and T2 mappings, and T1 value. The older subjects exhibited increased CNRs compared with the young adults. No significant difference was observed in the measurements between 20 and 64 channels. The multiecho technique allows the high-quality nigrosome-1 images in SWI and allows for a joint analysis of T2* and quantitative-susceptibility mapping at high spatial resolution. The correlations of neuromelanin-sensitive imaging with susceptibility and T2 imply that the iron content in the nigrosome-1 may have significant influences on the hyperintensity of neuromelanin in the magnetization transfer-related contrast.

Abstract Using an established CRISPR-Cas mediated genome editing technique for streptomycetes, we explored the combinatorial biosynthesis potential of the auroramycin biosynthetic gene cluster in Streptomyces roseosporous. Auroramycin is a potent anti-MRSA polyene macrolactam. In addition, auroramycin has antifungal activities, which is unique among structurally similar polyene macrolactams, such as incednine and silvalactam. In this work, we employed different engineering strategies to target glycosylation and acylation biosynthetic machineries within its recently elucidated biosynthetic pathway. Auroramycin analogs with variations in C-, N- methylation, hydroxylation and extender units incorporation were produced and characterized. By comparing the bioactivity profiles of five of these analogs, we determined that unique disaccharide motif of auroramycin is essential for its antimicrobial bioactivity. We further demonstrated that C-methylation of the 3, 5-epi-lemonose unit, which is unique among structurally similar polyene macrolactams, is key to its antifungal activity.

BackgroundCOVID-19 vaccination is essential. However, no study has reported adverse events (AEs) after ChAdOx1 nCoV-19 vaccination in patients with end-stage renal disease (ESRD) on hemodialysis (HD). This study investigated the AEs within 30-days after the first dose of ChAdOx1 nCoV19 (Oxford-AstraZeneca) in ESRD patients on HD.Methods and findingsA total of 270 ESRD patients on HD were enrolled in this study. To determine the significance of vascular access thrombosis (VAT) post vaccination, we performed a self-controlled case study (SCCS) analysis. Of these patients, 38.5% had local AEs; local pain (29.6%), tenderness (28.9%), and induration (15.6%) were the most common. Further, 62.2% had systemic AEs; fatigue (41.1%), feverishness (20%), and lethargy (19.9%) were the most common. In addition, post-vaccination thirst affected 18.9% of the participants with female predominance. Younger age, female sex, and diabetes mellitus were risk factors for AEs. Five patients had severe AEs, including fever (n = 1), herpes zoster (HZ) reactivation (n = 1), and acute VAT (n = 3). However, the SCCS analysis revealed no association between vaccination and VAT; the incidence rate ratio (IRR)-person ratio was 0.56 (95% CI 0.13-2.33) and 0.78 (95% CI 0.20-2.93) [IRR-event ratio 0.78 (95% CI 0.15-4.10) and 1.00 (95% CI 0.20-4.93)] in the 0-3 months and 3-6 months period prior to vaccination, respectively.ConclusionsThough some ESRD patients on HD had local and systemic AEs after first-dose vaccination, the clinical significance of these symptoms was minor. Our study confirmed the safety profile of ChAdOx1 nCoV-19 in HD patients and presented a new viewpoint on vaccine-related AEs. The SCCS analysis did not find an elevated risk of VAT at 1 month following vaccination. Apart from VAT, other vaccine-related AEs, irrespective of local or systemic symptoms, had minor clinical significance on safety issues. Nonetheless, further coordinated, multi-center, or registry-based studies are needed to establish the causality.

Bioavailability of weakly basic drugs may be disrupted by dramatic pH changes or unexpected pH alterations in the gastrointestinal tract. Conventional organic acids or enteric coating polymers cannot address this problem adequately because they leach out or dissolve prematurely, especially during controlled release applications. Thus, a non-leachable, multifunctional terpolymer nanoparticle (TPN) made of cross-linked poly(methacrylic acid) (PMAA)-polysorbate 80-grafted-starch (PMAA-PS 80-g-St) was proposed to provide pH transition-independent release of a weakly basic drug, verapamil HCl (VER), by a rationally designed bilayer-coated controlled release bead formulation. The pH-responsive PMAA and cross-linker content in the TPN was first optimized to achieve the largest possible increase in medium uptake alongside the smallest decrease in drug release rate at pH 6.8, relative to pH 1.2. Such TPNs maintained an acidic microenvironmental pH (pHm) when loaded in ethylcellulose (EC) films, as measured using pH-indicating dyes. Further studies of formulations revealed that with the 1:2 VER:TPN ratio and 19% coating weight gain, bilayer-coated beads maintained a constant release rate over the pH transition and exhibited extended release up to 18 h. These results demonstrated that the multifunctional TPN as a pHm modifier and pH-dependent pore former could overcome the severe pH-dependent solubility of weakly basic drugs.

Adding organically modified bentonite into impervious wall materials may improve the adsorption of organic pollutants. In this study, cetyltrimethylammonium bromide organically modified bentonite (CTMAB bentonite) was mixed with sodium bentonite and kaolin to obtain two materials, which were then used as cut-off walls for typical pollutants. Soil column consolidation tests, diffusion tests, and breakdown tests were conducted to study migration of organic pollutants in soil columns. The parameter sensitivity of pollutant transport in the cut-off wall was analysed by numerical simulation. The sodium bentonite mixed with 10% CTMAB bentonite and kaolin-CTMAB bentonite showed the greatest impermeability: with a consolidation pressure of 200 kPa, the permeability coefficients were 1.03 × 10−8 m/s and 3.49 × 10−9 m/s, respectively. The quantity of phenol adsorbed on sodium bentonite-CTMAB bentonite increased with increasing water head height. The kaolin-CTMAB bentonite column showed the best rhodamine B adsorption performance, and the adsorption rate reached 98.9% on day 67. The numerical results showed that the permeability coefficient was positively correlated with the diffusion of pollutants in the soil column. The quantity adsorbed on the soil column was positively correlated with the retardation factor, and the extent of pollutant diffusion was negatively correlated with the retardation factor. This study provides a technical means for the optimal design of organic pollutant cut-off walls.

Atrial fibrillation (AF) is the most common arrhythmia worldwide and has a significant impact on human health and substantial costs. Currently, there is a lack of accurate biomarkers for the diagnosis and prognosis of AF. Moreover, the long-term efficacy of the catheter ablation in the AF is unsatisfactory. Therefore, it is necessary to explore new biomarkers and treatment strategies for the mechanism-based AF. Exosomes are nano-sized biovesicles released by nearly all types of cells. Since the AF would be linked to the changes of the atrial cells and their microenvironment, and the AF would strictly influence the exosomal non-coding RNAs (exo-ncRNAs) expression, which makes them as attractive diagnostic and prognostic biomarkers for the AF. Simultaneously, the exo-ncRNAs have been found to play an important role in the mechanisms of the AF and have potential therapeutic prospects. Although the role of the exo-ncRNAs in the AF is being actively investigated, the evidence is still limited. Furthermore, there is a lack of consensus regarding the most appropriate approach for exosome isolation and characterization. In this article, we reviewed the new methodologies available for exosomes biogenesis, isolation, and characterization, and then discussed the mechanism of the AF and various levels and types of exosomes relevant to the AF, with the special emphasis on the exo-ncRNAs in the diagnosis, prognosis, and treatment of the mechanism-based AF.

Background: Cholinergic deficiency has been suggested to associate with the abnormal accumulation of Aβ and tau for patients with Alzheimer's disease (AD). However, no studies have investigated the effect of APOE-ε4 and group differences in modulating the cholinergic basal forebrain–amygdala network for subjects with different levels of cognitive impairment. We evaluated the effect of APOE-ε4 on the cholinergic structural association and the neurocognitive performance for subjects with different levels of cognitive impairment.Methods: We used the structural brain magnetic resonance imaging scans from the Alzheimer's Disease Neuroimaging Initiative dataset. The study included cognitively normal (CN, n = 167) subjects and subjects with significant memory concern (SMC, n = 96), early mild cognitive impairment (EMCI, n = 146), late cognitive impairment (LMCI, n = 138), and AD (n = 121). Subjects were further categorized according to the APOE-ε4 allele carrier status. The main effects of APOE-ε4 and group difference on the brain volumetric measurements were assessed. Regression analyses were conducted to evaluate the associations among cholinergic structural changes, APOE-ε4 status, and cognitive performance.Results: We found that APOE-ε4 carriers in the disease group showed higher brain atrophy than non-carriers in the cholinergic pathway, while there is no difference between carriers and non-carriers in the CN group. APOE-ε4 allele carriers in the disease groups also exhibited a stronger cholinergic structural correlation than non-carriers did, while there is no difference between the carriers and non-carriers in the CN subjects. Disease subjects exhibited a stronger structural correlation in the cholinergic pathway than CN subjects did. Moreover, APOE-ε4 allele carriers in the disease group exhibited a stronger correlation between the volumetric changes and cognitive performance than non-carriers did, while there is no difference between carriers and non-carriers in CN subjects. Disease subjects exhibited a stronger correlation between the volumetric changes and cognitive performance than CN subjects did.Conclusion: Our results confirmed the effect of APOE-ε4 on and group differences in the associations with the cholinergic structural changes that may reflect impaired brain function underlying neurocognitive degeneration in AD.

Chemical treatments of hair such as dyeing, perming and bleaching could cause mechanical damage to the hair, which weakens the hair fibers and makes the hair break more easily. In this work, hyaluronate (HA) with different molecular weight (MW) was investigated for its effects on restoring the mechanical properties of damaged hair. It was found that low-MW HA (average MW~42 k) could significantly improve the mechanical properties, specifically the elastic modulus, of overbleached hair. The fluorescent-labeling experiments verified that the low-MW HA was able to penetrate into the cortex of the hair fiber, while high-MW HA was hindered. Fourier transform infrared spectrometry (FT-IR) results implied the formation of additional intermolecular hydrogen bonds in the HA-treated hair. Thermos gravimetric analysis (TGA) indicated that the HA-treated hair exhibited decreased content of loosely bonded water, and differential scanning calorimetry (DSC) characterizations suggested stronger water bonding inside the HA-treated hair, which could alleviate the weakening effect of loosely bonded water on the hydrogen bond networks within keratin. Therefore, the improved elastic modulus and mechanical strength of the HA-treated hair could be attributed to the enhanced formation of hydrogen bond networks within keratin. This study illustrates the capability of low-MW HA in hair damage repair, implying an enormous potential for other moisturizers to be used in hair care products.

Limonin is a natural compound which is rich in the fruit of various plants of the Rutaceae family and demonstrated to have a wide range of biological activities. In this work, seven limonin derivatives were successfully synthesized by hydrogenation of limonin, using different reducing agents (sodium cyanoborohydride, lithium aluminum hydride, and sodium borohydride). The chemical structure of the seven derivatives was characterized and identified by a series of techniques, including HR-ESI-MS, 1H-NMR, 13C-NMR, 2D-NMR, and IR. Among the seven limonin derivatives, six limonin derivatives were found to be new compounds which have not been previously reported. Then, the anti-inflammatory activities of the seven synthesized limonin derivatives, as well as the anti-inflammatory activities of eight known natural limonins, were evaluated and compared. Natural limonins, 30-O-Acetylhainangranatumin E and Xylogranatin A, presented significantly better anti-inflammatory activity. Xylogranatin A could inhibit LPS-induced RAW264.7 cell inflammatory factors, with a 90.0% inhibition ratio of TNF-α and 63.77% inhibition ratio of NO release in LPS-induced BV2 cells at 10 μM. Other natural limonins showed poor anti-inflammatory activity. In comparison, all the synthetic limonin derivatives showed decent anti-inflammatory activities, with the highest inhibition ratio of TNF-α of 37.8% and inhibition ratio of NO release of 12.5% in LPS-induced BV2 cells at 10 μM.

Organic dye rhodamine B is one of the common organic pollutants in the water and soil environment. This study investigated the feasibility of removing rhodamine B from an aqueous solution through adsorption by kaolin, kaolin-sodium bentonite, and kaolin-organic bentonite. Batch adsorption test results showed that the maximum adsorption quantities of kaolin, kaolin-sodium bentonite, and kaolin-organic bentonite were 7.76 mg/g, 11.26 mg/g, and 12.68 mg/g, respectively, implying that the addition of bentonite to kaolin can effectively improve its adsorption capacity for rhodamine B. Moreover, the Langmuir isotherm model is suitable to describe the adsorption of rhodamine B by kaolin and kaolin-sodium bentonite, while it is preferable to use the Freundlich isotherm model in the case of kaolin-organic bentonite. The adsorption kinetic characteristics of rhodamine B, by these three adsorbents, are suitable to be described with a pseudo-second order kinetic model. Furthermore, the characteristics of the above three adsorbents were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The above results indicated that kaolin and organic bentonite can be used to design efficient adsorbents for organic pollutants similar to rhodamine B.

Soil salinization and alkalization greatly restrict crop growth and yield. In this study, NaCl (8 g kg−1) and Na2CO3 (8 g kg−1) were used to create saline stress and alkaline stress on cotton in pot cultivation in the field, and organic polymer compound material (OPCM) and stem girdling were applied before cotton sowing and at flowering and boll-forming stage, respectively, aiming to determine the effects of OPCM on K+ and Na+ absorption and transport and physiological characteristics of cotton leaf and root. The results showed that after applying the OPCM, the Na+ content in leaf of cotton under saline stress and alkaline stress were decreased by 7.72 and 6.49%, respectively, the K+/Na+ ratio in leaf were increased by 5.65 and 19.10%, respectively, the Na+ content in root were decreased by 9.57 and 0.53%, respectively, the K+/Na+ ratio in root were increased by 65.77 and 55.84%, respectively, and the transport coefficients of K+ and Na+ from leaf to root were increased by 39.59 and 21.38%, respectively. The activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), and the relative electrical conductivity (REC) in cotton leaf were significantly increased, while the content of malondialdehyde (MDA) was decreased; but the changes in those in root were not significant. The boll weights were increased by 11.40 and 13.37%, respectively, compared with those for the control. After stem girdling, the application of OPCM still promoted the ion transport of cotton organs; moreover, the CAT activity in root was increased by 25.09% under saline stress, and the SOD activity in leaf and CAT in root were increased by 42.22 and 6.91%, respectively under alkaline stress. Therefore, OPCM can significantly change the transport of K+ and Na+ to maintain the K+ and Na+ homeostasis in leaf and root, and regulate physiological and biochemical indicators to alleviate the stress-induced damage. Besides, the regulation effect of OPCM on saline stress was better than that on alkaline stress.

Abstract Nanotechnology‐basedin vitro diagnostics (nanoIVDs) are widely studied for disease diagnostics with promising sensitivity, specificity, and convenience. However, it is still a major challenge for both regulatory authorities and scientific researchers to accelerate the clinical translation of such an innovative technology. Herein, this perspective discussed the benefits and challenges of nanoIVDs as well as the administration considerations on the distinguish features of nanoIVDs by regulatory authorities, so as to further achieve the evaluation, translation, and application of nanoIVD products.