The involvement of Neuregulin-1 in the process of facial nerve injury repair through the utilization of dental pulp stem cells.

BACKGROUND: Facial nerve injury often results in poor prognosis due to the challenging process of nerve regeneration. Neuregulin-1, a human calmodulin, is under investigation in this study for its impact on the reparative capabilities of Dental Pulp Stem Cells (DPSCs) in facial nerve injury. METHODS: Lentivirus was used to transfect and construct Neuregulin-1 overexpressed DPSCs. Various techniques assessed the effects of Neuregulin-1: osteogenic induction, lipid induction, Reverse Transcription Polymerase Chain Reaction, Western Blot, Cell Counting Kit-8 assay, wound healing, immunofluorescence, Phalloidin staining, nerve stem action potential, Hematoxylin-eosin staining, transmission electron microscopy, and immunohistochemistry. RESULTS: Neuregulin-1 effectively enhanced the proliferation, migration, and cytoskeletal rearrangement of DPSCs, while simultaneously suppressing the expression of Ras homolog gene family member A (RhoA) and Microfilament actin (F-actin). These changes facilitated the neural differentiation of DPSCs. Additionally, in vivo experiments showed that Neuregulin-1 expedited the restoration of action potential in the facial nerve trunk, increased the thickness of the myelin sheath, and stimulated axon regeneration. CONCLUSION: Neuregulin-1 has the capability to facilitate the repair of facial nerve injuries by promoting the regenerative capacity of DPSCs. Thus, Neuregulin-1 is a significant potential gene in the reparative processes of nerve damage.

Fam20c regulates the calpain proteolysis system through phosphorylating Calpasatatin to maintain cell homeostasis.

BACKGROUND: The family with sequence similarity 20-member C (FAM20C) kinase, a Golgi casein kinase, which is responsible for phosphorylating the majority of the extracellular phosphoproteins within S-x-E/pS motifs, and is fundamentally associated with multiple biological processes to maintain cell proliferation, biomineralization, migration, adhesion, and phosphate homeostasis. In dissecting how FAM20C regulates downstream molecules and potential mechanisms, however, there are multiple target molecules of FAM20C, particularly many phenomena remain elusive, such as changes in cell-autonomous behaviors, incompatibility in genotypes and phenotypes, and others. METHODS: Here, assay for transposase-accessible chromatin using sequencing (ATAC-seq), RNA sequencing (RNA-seq), proteomics, and phosphoproteomics were performed in Fam20c-dificient osteoblasts and to facilitate an integrated analysis and determine the impact of chromatin accessibility, genomic expression, protein alterations, signaling pathway, and post translational modifcations. RESULTS: By combining ATAC-seq and RNA-seq, we identified TCF4 and Wnt signaling pathway as the key regulators in Fam20c-dificient cells. Further, we showed Calpastatin/Calpain proteolysis system as a novel target axis for FAM20C to regulate cell migration and F-actin cytoskeleton by integrated analysis of proteomics and phosphoproteomics. Furthermore, Calpastatin/Calpain proteolysis system could negatively regulate the Wnt signaling pathway. CONCLUSION: These observations implied that Fam20c knockout osteoblasts would cause cell homeostatic imbalance, involving changes in multiple signaling pathways in the conduction system.

Dynamic Fluctuation and Niche Differentiation of Fungal Pathogens Infecting Bell Pepper Plants.

The plant microbiome is shaped by plant development and microbial interaction. Fungal pathogens infecting bell pepper plants may fluctuate across the growing seasons. Dynamic fluctuation of the microbiome and fungal pathogens in bell pepper plants is poorly understood, and the origin of fungal pathogens causing fruit rot and leaf wilt has been barely investigated. In this study, we used amplicon sequencing (i.e., 16S rRNA and internal transcribed spacer [ITS] sequencing) to explore the compositional variations of the microbiome in bell pepper plants and studied the fluctuation of fungal pathogens across the growing seasons. Co-occurrence network analysis was applied to track the origin and dissemination route of fungal pathogens that infected bell pepper plants. ITS and 16S rRNA sequencing analyses demonstrated that fungal pathogens infecting fruits and leaves probably belonged to the Penicillium, Cladosporium, Fusarium, and unclassified_Sclerotiniaceae genera rather than one specific genus. The dominant fungal pathogens were different, along with the development of bell pepper plants. Both plant development and fungal pathogens shaped microbial communities in bell pepper plants across the growing seasons. Fungal pathogens decreased species richness and diversity of fungal communities in fungus-infected fruit and leaf tissues but not the uninfected stem tissues. Bacterial metabolic functions of xenobiotics increased in fungus-infected leaves at a mature developmental stage. Competitive interaction was present between fungal and bacterial communities in leaves. Co-occurrence network analysis revealed that the origins of fungal pathogens included the greenhouse, packing house, and storage room. Niche differentiation of microbes was discovered among these locations. IMPORTANCE Bell peppers are widely consumed worldwide. Fungal pathogen infections of bell peppers lead to enormous economic loss. To control fungal pathogens and increase economic benefit, it is essential to investigate the shifting patterns of the microbiome and fungal pathogens in bell pepper plants across the growing seasons. In this study, bell pepper plant diseases observed in fruits and leaves were caused by different fungal pathogens. Fungal pathogens originated from the greenhouse, packing house, and storage room, and niche differentiation existed among microbes. This study improves the understanding of dynamic fluctuation and source of fungal pathogens infecting bell pepper plants in the farming system. It also facilitates precise management of fungal pathogens in the greenhouse.

Electrical Dry Needling Plus Corticosteroid Injection for Osteoarthritis of the Knee: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of electrical dry needling (DN) plus corticosteroid injection (CSI) on pain, physical function, and global change in patients with osteoarthritis of the knee (KOA). DESIGN: A prospective, single-blinded, randomized controlled trial. SETTING: Pain treatment clinic. PARTICIPANTS: Sixty patients with KOA were randomly assigned to the electrical dry needling plus corticosteroid injection (electrical-DN+CSI) group or CSI group. INTERVENTIONS: The CSI group received glucocorticoid injection only once during the trial, and the electrical-DN+CSI group received glucocorticoid injection combined with 4 sessions of electrical-DN. MAIN OUTCOMES MEASURES: The primary outcome was the numerical rating scale at 3 months. The secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index, the time to complete the Timed Up and Go test, and the score of the global rating of change scale at 3 months. A generalized linear mixed-effects model was used to analyze the repeated measurement data. RESULTS: Baseline characteristics and measurements were similar in the 2 groups. The group by time interaction effect was significant for all variables (P<.05). The electrical-DN+CSI group obtained a more significant reduction in pain intensity and more significant improvement in dysfunction than the CSI group at 3 months (P<.05). The median global rating of change score for the CSI group was +3 (somewhat better), and that for the electrical-DN+CSI group was +4 (moderately better). CONCLUSION: Electrical-DN therapy at myofascial trigger points combined with CSI is more effective at alleviating pain, improving dysfunction, and creating global change than CSI alone for patients with KOA. Electrical-DN may be an essential part of treatment for KOA rehabilitation.

Prevalence and multilocus sequence typing of Clostridium perfringens isolated from different stages of a duck production chain.

Clostridium perfringens (C. perfringens) is a zoonotic microorganism and rarely reported in duck production chain. This study aimed to investigate prevalence, serotype distribution, antibiotic resistance and genetic diversity of C. perfringens at different stages of a duck production chain. In total, 319 samples were collected from a large-scale rearing and slaughter one-stop enterprise in Weifang, China, of which 42.95% of samples were positive for C. perfringens. All isolates were genotype A. Cpe and cpb2 genes were found in 2.54% and 24.87% of the isolates, respectively. Antimicrobial susceptibility testing revealed that 55.47% of the isolates resistant to at least 5 classes of commonly used antibiotics. Multilocus sequence typing (MLST) results showed that 65 representative isolates were divided into 47 sequences types (STs), 33.85% of them were included into four clonal complexes (CC). Some of isolates from breeding and slaughtering stages were distributed in the same CC or ST, indicating duck products may be contaminated by C. perfringens originated from the breeding stage. Part of duck isolates were distributed in the same CC as human isolates and systemically close with human isolates. The high contamination rates of duck products, the isolates with multi-drug antibiotic resistance or the cpe gene, and the close relationship between strains from human and ducks, indicated potential public health risks, not only control measures at slaughtering stage but also at rearing stage should be considered to reduce this risks.

Prevalence and characterization of Clostridium perfringens isolated from different chicken farms in China.

Clostridium perfringens (C. perfringens) is a common pathogenic microorganism present in nature, which can cause animal and human diseases, such as necrotizing enteritis (NE) in poultry. Little is known about the current prevalence status of C. perfringens from poultry farms of different types and regions in China. From December 2018 to August 2019, we investigated the prevalence, genotype distribution and drug resistance of C. perfringens from Guangdong, Pingyin, Tai'an and Weifang. A total of 622 samples were collected and processed for C. perfringens isolation, among which 239 (38.42%) samples were determined to be positive for C. perfringens. A total of 312 isolates of C. perfringens were recovered (1-5 strains were isolated for each positive sample), and 98.72% of the isolates were identified as type A, while the others were type F. Antimicrobial susceptibility testing revealed that 47.71% of the isolates were resistant to at least five classes of commonly used antibiotics. Multilocus sequence typing (MLST) showed that 74 representative isolates were divided into 63 sequence types (STs), and the Simpson's diversity index (Ds) of the STs for the five farms was 0.9799. 37.84% of the isolates were classified into seven clonal complexes (CC1-CC7), and the isolates from the same farm were more concentrated in the minimum spanning tree. In addition, some cloaca isolates and feed isolates were distributed in the same ST or CC; this result indicates that the C. perfringens in chicken can come from the environment (feed etc.).

Influence of incorporating beta zeolite nanoparticles on water permeability and ion selectivity of polyamide nanofiltration membranes.

A novel polyamide (PA) thin film nanocomposite (TFN) membrane modified with Beta (ß) zeolite was prepared by interfacial polymerization on a poly (ether sulfone) (PES) ultrafiltration membrane. Compared with the PA thin film composite (TFC) membrane, the introduction of ß zeolite with porous structure notably increased the water flux of TFN membrane. Because the ß zeolite with tiny-sized and well-defined inner-porous acted as prior flow channels for water molecules and a barrier for the sulfate ions. The successful introduction of ß zeolite into the (PA) selective layer and their dispersion in the corresponding layer were verified by scanning electron microscope (SEM) and atomic force microscopy (AFM). Water contact angle, zeta potential measurements were used to characterize the changes of membrane surface properties before and after incorporating the ß zeolite. With the ß zeolite introducing, the water contact angle of modified TFN membrane was decreased to 47.8°, which was benefited to improve the water flux. Meanwhile, the negative charges of the modified TFN membrane was increased, resulting in an enhancement of separation effect on SO42- and Cl-. In term of nanofiltration (NF) experiments, the highest pure water flux of the TFN membranes reached up to 81.22 L m-2 hr-1 under operating pressure of 0.2 MPa, which was 2.5 times as much as the pristine TFC membrane.

Natural variation in GmGBP1 promoter affects photoperiod control of flowering time and maturity in soybean.

The present study screened for polymorphisms in coding and non-coding regions of the GmGBP1 gene in 278 soybean accessions with variable maturity and growth habit characteristics under natural field conditions in three different latitudes in China. The results showed that the promoter region was highly diversified compared with the coding sequence of GmGBP1. Five polymorphisms and four haplotypes were closely related to soybean flowering time and maturity through association and linkage disequilibrium analyses. Varieties with the polymorphisms SNP_-796G, SNP_-770G, SNP_-307T, InDel_-242normal, SNP_353A, or haplotypes Hap-3 and Hap-4 showed earlier flowering time and maturity in different environments. The shorter growth period might be largely due to higher GmGBP1 expression levels in soybean that were caused by the TCT-motif with SNP_-796G in the promoter. In contrast, the lower expression level of GmGBP1 in soybean caused by RNAi interference of GmGBP1 resulted in a longer growth period under different day lengths. Furthermore, the gene interference of GmGBP1 also caused a reduction in photoperiod response sensitivity (PRS) before flowering in soybean. RNA-seq analysis on GmGBP1 underexpression in soybean showed that 94 and 30 predicted genes were significantly upregulated and downregulated, respectively. Of these, the diurnal photoperiod-specific expression pattern of three significant flowering time genes GmFT2a, GmFT5a, and GmFULc also showed constantly lower mRNA levels in GmGBP1-i soybean than in wild type, especially under short day conditions. Together, the results showed that GmGBP1 functioned as a positive regulator upstream of GmFT2a and GmFT5a to activate the expression of GmFULc to promote flowering on short days.

Expression of annexin A2 in adenomyosis and dysmenorrhea.

PURPOSE: To investigate the expression of annexin A2 (ANXA2) in ectopic and eutopic endometrium and serum of women with adenomyosis, and their relationships with adenomyosis-associated dysmenorrhea. METHODS: The expression of ANXA2 was detected by immunohistochemical S-P method in ectopic and eutopic endometrium tissues from 30 patients with adenomyosis who underwent hysterectomy. The correlation between ANXA2 expression and dysmenorrhea degree was evaluated. The endometrium tissues from 15 patients with uterine fibroids which underwent hysterectomy were used as controls. The preoperative serum level of ANXA2 was measured by enzyme-linked immunosorbent assay in 30 patients with adenomyosis and 15 patients with hysteromyoma. RESULT: The expression of ANXA2 in eutopic and ectopic endometrium of adenomyosis was higher than in normal endometrium (P < 0.05), but no significant difference of ANXA2 expression was observed between the eutopic endometrium and the ectopic endometrium (P > 0.05). In the ectopic endometrium, but not in the eutopic endometrium, of women with adenomyosis, ANXA2 expression was positively correlated with the severity of dysmenorrhea (R = 0.831, P = 0.000). The preoperative serum level of ANXA2 was markedly higher in patients with adenomyosis compared with the patients with hysteromyoma (P < 0.05). CONCLUSION: The increased ANXA2 may contribute to the occurrence and development of adenomyosis, and may play a important role in the dysmenorrhea. The present study may provide a new idea of diagnosis and treatment to adenomyosis-associated dysmenorrhea.

Clinical and Neuroimaging Features of Acute Ischemic Stroke in Cancer Patients.

BACKGROUND: The occurrence of acute ischemic stroke in cancer patients is not unusual. In clinical practice, acute ischemic stroke with cancer usually cannot be diagnosed promptly due to lack of specific markers. But for cancer patients, advanced prevention, accurate diagnosis and proper treatment of acute ischemic stroke are very important. The aim of the present study was to investigate the clinical and neuroimaging features of acute ischemic stroke in patients with cancer. METHODS: We conducted a retrospective review of all cancer-associated acute ischemic stroke patients (n = 46) admitted to the Affiliated Hospital of Academy of Military Medical Sciences between October 2011 and March 2015. A group of non-cancer acute ischemic stroke patients (n = 50) at the same period were selected randomly as control. The clinical and neuroimaging data were collected and compared between the 2 groups. RESULTS: Patients with cancer-associated stroke (CS) had a lower body mass index (23.26 ± 3.70 vs. 24.88 ± 2.83, p = 0.021) compared to non-cancer stroke (NC) patients. A lower proportion of CS patients suffered from hypertension (45.7 vs. 68.0%, p = 0.039) and hyperlipidemia (10.9 vs. 72.0%, p = 0.000) than the NC group. A higher proportion of CS patients had deep vein catheter (24.0 vs. 0%) before the onset of stoke than that of the NC group. Levels of hemoglobin, albumin and triglyceride were lower in CS groups compared with that of the NC group (p < 0.05). The prothrombin time, international normalized ratio, D-dimer and fibrinogen levels were significantly higher in the CS group than in the NC group (p < 0.05). As to the neuroimaging patterns, disperse lesions (OR 7.01; 95% CI 1.17-42.12; p < 0.05) was independently associated with CS. CONCLUSIONS: Cancer-associated ischemic stroke was different form conventional ischemic stroke in the aspect of clinical and neuroimaging manifestation. This phenomenon might be because of the embolic etiology of CS. These features together could become a clue to CS.

Characterization and multilocus sequence typing of Clostridium perfringens isolated from patients with diarrhoea and food poisoning in Tai'an region, China.

OBJECTIVES: Clostridium perfringens (C. perfringens) is a significant opportunistic pathogen. This study aims to examine the occurrence of C. perfringens in patients with diarrhoea and food poisoning and compare the genetic similarities with strains found in poultry retail markets and poultry farms in the same city (Tai'an, China). METHODS: Clostridium perfringens was isolated from 30 human faecal samples and genotyped using multiplex PCR. The antimicrobial susceptibility test was conducted using the Kirby-Bauer disk diffusion method. Genetic relationships were analysed through Multi-locus sequence typing (MLST) and Phylogenetic analysis. RESULTS: The positive rate of C. perfringens was found to be 96.67%. Among the positive samples, 91.67% of the faecal samples from patients with food poisoning contained type F strains of C. perfringens, while only 16.67% of the samples from diarrhoea cases contained type F. The drug susceptibility test revealed that the majority of isolates displayed broad-spectrum antimicrobial resistance. Out of the 57 isolates tested for drug susceptibility, 89.47% demonstrated resistance to at least three antibiotics. The MLST results indicated that strains originating from the same host and environment tended to be more closely related. However, certain strains associated with food poisoning and diarrhoea in patients shared the same ST and CC as some strains found in the retail market. These strains were also found to be phylogenetically similar to some retail market strains, suggesting potential risks to human health. CONCLUSIONS: Therefore, it is crucial to enhance the management of poultry retail markets in order to mitigate these associated risks.

Knocking out FAM20C in pre-osteoblasts leads to up-regulation of osteoclast differentiation to affect long bone development.

Family with sequence similarity 20 member C (FAM20C) is a Golgi casein kinase that phosphorylates extracellularly-secreted regulatory proteins involved in bone development and mineralization, but its specific role in bone development is still largely unknown. In this study, to examine the specific mechanisms that FAM20C influences bone development, we cross-bred Osx-Cre with FAM20Cflox/flox mice to establish a Osx-Cre; FAM20Cflox/flox knockout (oKO) mouse model; FAM20C was KO in pre-osteoblasts. oKO development was examined at 1-10 weeks, in which compared to control FAM20Cflox/flox, they had lower body weights and bone tissue mineralization. Furthermore, oKO had lower bone volume fractions, thickness, and trabecular numbers, along with higher degrees of trabecular separation. These mice also had decreased femoral metaphyseal cartilage proliferation layer, along with thickened hypertrophic layer and increased apoptotic cell counts. Transcriptomic analysis found that differentially-expressed genes in oKO were concentrated in the osteoclast differentiation pathway, in line with increased osteoclast presence. Additionally, up-regulation of osteoclast-related, and down-regulation of osteogenesis-related genes, were identified, in which the most up-regulated genes were signal regulatory protein ß-1 family (Sirpb1a-c) and mitogen-activated protein kinase 13. Overall, FAM20C KO in pre-osteoblasts leads to abnormal long bone development, likely due to subsequent up-regulation of osteoclast differentiation-associated genes.

Digital ray: enhancing cataractous fundus images using style transfer generative adversarial networks to improve retinopathy detection.

BACKGROUND/AIMS: The aim of this study was to develop and evaluate digital ray, based on preoperative and postoperative image pairs using style transfer generative adversarial networks (GANs), to enhance cataractous fundus images for improved retinopathy detection. METHODS: For eligible cataract patients, preoperative and postoperative colour fundus photographs (CFP) and ultra-wide field (UWF) images were captured. Then, both the original CycleGAN and a modified CycleGAN (C2ycleGAN) framework were adopted for image generation and quantitatively compared using Frechet Inception Distance (FID) and Kernel Inception Distance (KID). Additionally, CFP and UWF images from another cataract cohort were used to test model performances. Different panels of ophthalmologists evaluated the quality, authenticity and diagnostic efficacy of the generated images. RESULTS: A total of 959 CFP and 1009 UWF image pairs were included in model development. FID and KID indicated that images generated by C2ycleGAN presented significantly improved quality. Based on ophthalmologists' average ratings, the percentages of inadequate-quality images decreased from 32% to 18.8% for CFP, and from 18.7% to 14.7% for UWF. Only 24.8% and 13.8% of generated CFP and UWF images could be recognised as synthetic. The accuracy of retinopathy detection significantly increased from 78% to 91% for CFP and from 91% to 93% for UWF. For retinopathy subtype diagnosis, the accuracies also increased from 87%-94% to 91%-100% for CFP and from 87%-95% to 93%-97% for UWF. CONCLUSION: Digital ray could generate realistic postoperative CFP and UWF images with enhanced quality and accuracy for overall detection and subtype diagnosis of retinopathies, especially for CFP.\ TRIAL REGISTRATION NUMBER: This study was registered with ClinicalTrials.gov (NCT05491798).

Cost-effectiveness and cost-utility of a digital technology-driven hierarchical healthcare screening pattern in China.

Utilization of digital technologies for cataract screening in primary care is a potential solution for addressing the dilemma between the growing aging population and unequally distributed resources. Here, we propose a digital technology-driven hierarchical screening (DH screening) pattern implemented in China to promote the equity and accessibility of healthcare. It consists of home-based mobile artificial intelligence (AI) screening, community-based AI diagnosis, and referral to hospitals. We utilize decision-analytic Markov models to evaluate the cost-effectiveness and cost-utility of different cataract screening strategies (no screening, telescreening, AI screening and DH screening). A simulated cohort of 100,000 individuals from age 50 is built through a total of 30 1-year Markov cycles. The primary outcomes are incremental cost-effectiveness ratio and incremental cost-utility ratio. The results show that DH screening dominates no screening, telescreening and AI screening in urban and rural China. Annual DH screening emerges as the most economically effective strategy with 341 (338 to 344) and 1326 (1312 to 1340) years of blindness avoided compared with telescreening, and 37 (35 to 39) and 140 (131 to 148) years compared with AI screening in urban and rural settings, respectively. The findings remain robust across all sensitivity analyses conducted. Here, we report that DH screening is cost-effective in urban and rural China, and the annual screening proves to be the most cost-effective option, providing an economic rationale for policymakers promoting public eye health in low- and middle-income countries.

Overexpression of a GmGBP1 ortholog of soybean enhances the responses to flowering, stem elongation and heat tolerance in transgenic tobaccos.

Soybean is a typical short-day crop, and its photoperiodic and gibberellin (GA) responses for the control of flowering are critical to seed yield. The GmGBP1 mRNA abundance in leaves was dramatically increased in short-days (SDs) compared to that in long-days in which it was consistently low at all time points from 0 to 6 days (days after transfer to SDs). GmGBP1 was highly expressed in leaves and exhibited a circadian rhythm in SDs. Ectopic overexpression of GmGBP1 in tobaccos caused photoperiod-insensitive early flowering by increasing NtCO mRNA levels. GmGBP1 mRNA abundance was also increased by GAs. Transgenic GmGBP1 overexpressing (-ox) tobacco plants exhibited increased GA signaling-related phenotypes including flowering and plant height promotion. Furthermore, the hypocotyl elongation, early-flowering and longer internode phenotypes were largely accelerated by GA3 application in the GmGBP1-ox tobacco seedlings. Being consistent, overexpression of GmGBP1 resulted in significantly enhanced GA signaling (evidenced suppressed expression of NtGA20ox) both with and without GA treatments. GmGBP1 was a positive regulator of both photoperiod and GA-mediated flowering responses. In addition, GmGBP1-ox tobaccos were hypersensitive to ABA, salt and osmotic stresses during seed germination. Heat-inducible GmGBP1 also enhanced thermotolerance in transgenic GmGBP1-ox tobaccos during seed germination and growth. GmGBP1 protein was localized in the nucleus. Analyses of a series of 5'-deletions of the GmGBP1 promoter suggested that several cis-acting elements, including P-BOX, TCA-motif and three HSE elements necessary to induce gene expression by GA, salicic acid and heat stress, were specifically localized in the GmGBP1 promoter region.

Elucidating sulfate radical-induced oxidizing mechanisms of solid-phase pharmaceuticals: Comparison with liquid-phase reactions.

As a class of organic micropollutants of global concern, pharmaceuticals have prevalent distributions in the aqueous environment (e.g., groundwater and surface water) and solid matrices (e.g., soil, sediments, and dried sludge). Their contamination levels have been further aggravated by the annually increased production of expired drugs as emerging harmful wastes worldwide. Sulfate radicals (SO4•-)-based oxidation has attracted increasing attention for abating pharmaceuticals in the environment, whereas the transformation mechanisms of solid-phase pharmaceuticals remain unknown thus far. This investigation presented for the first time that SO4•-, individually produced by mechanical force-activated and heat-activated persulfate treatments, could effectively oxidize three model pharmaceuticals (i.e., methotrexate, sitagliptin, and salbutamol) in both solid and liquid phases. The high-resolution mass spectrometric analysis suggested their distinct transformation products formed by different phases of SO4•- oxidation. Accordingly, the SO4•--mediated mechanistic differences between the solid-phase and liquid-phase pharmaceuticals were proposed. It is noteworthy that the products from both systems were predicted with the remaining persistence, bioaccumulation, and multi-endpoint toxicity. Therefore, some post-treatment strategies need to be considered during practical applications of SO4•--based technologies in remediating different phases of micropollutants. This work has environmental implications for understanding the comparative transformation mechanisms of pharmaceuticals by SO4•- oxidation in remediating the contaminated solid and aqueous matrices.

UV cross-linked injectable non-swelling dihydrocaffeic acid grafted chitosan hydrogel for promoting wound healing.

Hydrogels are widely used as wound dressings for wound healing, but when hydrogels absorb wound exudate, swelling occurs and compresses the surrounding tissue, affecting healing. A chitosan injectable (CS/4-PA/CAT) hydrogel based on catechol and 4-glutenoic acid was prepared to avoid swelling and promote wound healing. After cross-linking by UV light, pentenyl groups formed hydrophobic alkyl chains which give the hydrogel a hydrophobic network and thus control its swelling. CS/4-PA/CAT hydrogels retained their non-swelling for a long time in PBS solution at 37 °C. CS/4-PA/CAT hydrogels had good injectable and adhesive properties, and had a good killing effect on E. coli and S. aureus and could remove the bacterial biofilms of E. coli and S. aureus. CS/4-PA/CAT hydrogels had good in vitro coagulation function by absorbing red blood cells and platelets. When used in a whole skin injury model, CS/4-PA/CAT-1 hydrogel stimulated fibroblast migration, promoted epithelialization and accelerated collagen deposition to promote defect healing, and showed good hemostatic effects in liver and femoral artery defects in mice. In summary, the non-swelling injectable hydrogel with free radical scavenging, rapid hemostasis, and antibacterial effects would be a promising treatment for defect repair.

Protocol to analyze fundus images for multidimensional quality grading and real-time guidance using deep learning techniques.

Data quality issues have been acknowledged as one of the greatest obstacles in medical artificial intelligence research. Here, we present DeepFundus, which employs deep learning techniques to perform multidimensional classification of fundus image quality and provide real-time guidance for on-site image acquisition. We describe steps for data preparation, model training, model inference, model evaluation, and the visualization of results using heatmaps. This protocol can be implemented in Python using either the suggested dataset or a customized dataset. For complete details on the use and execution of this protocol, please refer to Liu et al.1.

Epithelial-specific deletion of FAM20A leads to short root defects.

Short Root Defects defined by a reduced ratio of root to crown, may culminate in root resorption and subsequent tooth loss, in spite of the absence of apparent symptoms. Such defects present considerable impediments to orthodontic treatment and restoration. Recent identification of Fam20a, an emergent pseudokinase, has been associated with enamel development and tooth eruption, yet its definitive role in root formation and eruption remains ambiguous. In this research, we initially ascertained that the targeted knockout of Fam20a within the epithelium led to truncated tooth roots, irregular breaks in the epithelial root sheath initiation of the WNT signaling pathway, and decreased expression of the cell polarity-related transcription factor Cdc42 in murine models. This was concomitant with the participation of the associated epithelial root sheath developmental pathways BMP2, Gli1, and Nfic. Furthermore, we observed that Fam20a predominantly affects the intraosseous eruption phase of tooth emergence. During this phase, the osteoclast peak around the mandibular first molar in cKO mice is delayed, leading to a slower formation of the eruption pathway, ultimately resulting in delayed tooth eruption in mice. The findings of this study enrich the extant knowledge regarding the role of Fam20a, suggesting its potential regulatory function in tooth root development through the WNT/ß-catenin/Cdc42 pathway.

EE-Explorer: A Multimodal Artificial Intelligence System for Eye Emergency Triage and Primary Diagnosis.

PURPOSE: To develop a multimodal artificial intelligence (AI) system, EE-Explorer, to triage eye emergencies and assist in primary diagnosis using metadata and ocular images. DESIGN: A diagnostic, cross-sectional, validity and reliability study. METHODS: EE-Explorer consists of 2 models. The triage model was developed from metadata (events, symptoms, and medical history) and ocular surface images via smartphones from 2038 patients presenting to Zhongshan Ophthalmic Center (ZOC) to output 3 classifications: urgent, semiurgent, and nonurgent. The primary diagnostic model was developed from the paired metadata and slitlamp images of 2405 patients from ZOC. Both models were externally tested on 103 participants from 4 other hospitals. A pilot test was conducted in Guangzhou to evaluate the hierarchical referral service pattern assisted by EE-Explorer for unspecialized health care facilities. RESULTS: A high overall accuracy, as indicated by an area under the receiver operating characteristic curve (AUC) of 0.982 (95% CI, 0.966-0.998), was obtained using the triage model, which outperformed the triage nurses (P < .001). In the primary diagnostic model, the diagnostic classification accuracy (CA) and Hamming loss (HL) in the internal testing were 0.808 (95% CI 0.776-0.840) and 0.016 (95% CI 0.006-0.026), respectively. In the external testing, model performance was robust for both triage (average AUC, 0.988, 95% CI 0.967-1.000) and primary diagnosis (CA, 0.718, 95% CI 0.644-0.792; and HL, 0.023, 95% CI 0.000-0.048). In the pilot test in the hierarchical referral settings, EE-explorer demonstrated consistently robust performance and broad participant acceptance. CONCLUSION: The EE-Explorer system showed robust performance in both triage and primary diagnosis for ophthalmic emergency patients. EE-Explorer can provide patients with acute ophthalmic symptoms access to remote self-triage and assist in primary diagnosis in unspecialized health care facilities to achieve rapid and effective treatment strategies.