Hybrid Type I and II Polyketide Synthases Yield Distinct Aromatic Polyketides.

Bacterial aromatic polyketides are compounds with multiple aromatic rings synthesized by bacterial type II polyketide synthases (PKSs), some of which have been developed into clinical drugs. Compounds containing aromatic polyketides synthesized by hybrid type I and type II PKSs are extremely rare. Here, we report the discovery of a gene cluster encoding both modular type I and type II PKSs as well as KAS III through extensive bioinformatics analysis, leading to the characterization of the hybrid polyketide, spirocycline A. The structure of spirocycline A is rare among all aromatic polyketides, featuring a unique starter unit and four spirocycles and forming a dimer. Biosynthetic studies indicate that the starter unit of this molecule is synthesized by type I PKS in collaboration with two trans-acting ketoreductase (KR) and enoylreductase (ER). It is then transferred by KAS III to the type II PKS system, which synthesizes the tricyclic aromatic polyketide backbone. The subsequent formation of the spirocycle and dimerization are carried out by four redox enzymes encoded in the gene cluster. Overall, the discovery of spirocycline A provides a new approach for identifying novel aromatic polyketides and offers potential enzymatic tools for the bioengineering of these hybrid polyketides.

Ultrahigh Extinction Ratio Leaky-Guided Hollow Core Fiber Mach-Zehnder Interferometer Assisted by a Large Core Hollow Fiber Beam Splitter.

We proposed a novel fiber Mach-Zehnder interferometer (FMZI) that can perform an ultrahigh extinction ratio (ER), ultracompact, and ultra-broadband interference characteristics. The FMZI structure is based on an extremely tiny hollow core fiber (HCF) with a small diameter of 10 µm (named HCF10) connected with a beam splitter of a large core of 50 µm HCF (named HCF50). The refractive index (RI) of the air core is lower than that of the HCF cladding; a leaky-guided fiber waveguide (LGFW) occurs in such a short-section HCF10 waveguide to simultaneously have the core and cladding modes. To achieve better fringe visibility of the interference, the section of HCF50 assists in splitting the optical light into core and cladding beams launched into the HCF10 with appropriate intensities. Experimental and simulation results show that the optical characteristics of the proposed LGFW-FMZI are very similar. Based on the results of the study, the length of the HCF10 primarily influences the free spectral range (FSR) of the interference spectra, and the HCF50 splitter significantly controls the optimal extinction ratio (ER) of the interference fringes. By exactly adjusting the lengths of HCF10 and HCF50, the proposed fiber interferometers can perform the capability of an ultrahigh ER over 50 dB with the arbitrary FSR in the transmitted interference spectra over an ultra-broad wavelength range of 1250 nm to 1650 nm.

The Zpr-3 Antibody Recognizes the 320-354 Region of Rho and Labels Both Rods and Green Cones in Zebrafish.

Retinal markers with high quality and specificity are important for the observation of pathologic changes of retinal cells during retinal development, degeneration, and regeneration. The zpr-3 antibody is widely used to label rods in zebrafish, but the exact antigen is still unknown. In this study, we provided evidence to demonstrate that the antigen gene of zpr-3 is rho, which encodes the rod opsin, and the exact epitope of zpr-3 is the 320-354 region of Rho protein. More importantly, our immunofluorescence assays indicated that zpr-3 labels both the outer segments of rods and green cones on zebrafish retinal sections, probably due to the cross-reaction with the green-cone opsin. Our work is valuable for the scientific community to interpret the experimental data involving the zpr-3 antibody.

Framework-Induced Electrochemiluminescence Enhancement of an AIEgen-Based MOF Coupled with Heterostructured TiO2@Ag NPs as an Efficient Coreaction Accelerator for Sensitive Biosensing.

In conventional metal-organic framework (MOF) luminophore-involved electrochemiluminescence (ECL) systems, the aggregation-caused quenching commonly exists for the organic luminescent ligands, limiting the ECL efficiency and detection sensitivity. Herein, by employing the aggregation-induced emission luminogen (AIEgen) 1,1,2,2-tetra(4-carboxylbiphenyl)ethylene (H4TCBPE) as a ligand, one high-efficiency ECL emitter (Zr-MOF) was synthesized through a simple hydrothermal reaction. Compared with H4TCBPE monomers and their aggregates, the resultant Zr-MOF possesses the strongest ECL emission, which is mainly attributed to the framework-induced ECL enhancement. Specifically, the heterostructure was prepared by the deposition of silver nanoparticles on TiO2 microflowers and utilized as an efficient coreaction accelerator. Remarkably, the formative heterojunction can increase the interfacial charge transfer efficiency and promote the carrier separation, facilitating the oxidation of coreactant tripropylamine. In this way, a novel aptamer-mediated ECL sensing platform is constructed, achieving the sensitive analysis of adenosine triphosphate with a low detection limit of 0.17 nM. As a proof-of-concept study, this work may enlighten the rational design of new-type MOF-based ECL materials and expand the application scope of the ECL technology.

Boosting Electrochemical Nitrate Reduction to Ammonia by Fe Doped CuO/Co3O4 Nanosheet/Nanowire Heterostructures.

The electrochemical nitrate reduction reaction (NO3-RR) is a novel green method for ammonia synthesis. The development of outstanding NO3-RR performance is based on reasonable catalyst. Metal oxides have garnered significant attention due to their exceptional electrical conductivity and catalytic properties. Doping serves as an effective strategy for enhancing catalyst performance due to its ability to change the electron cloud distribution and energy levels. In this study, we develop a heterojunction catalyst Fe doped copper oxide nanosheet and cobalt tetroxide nanowire growing on carbon cloth simultaneously (Fe-CuO@Co3O4/CC) via hydrothermal method. The well-designed Fe-CuO@Co3O4/CC has excellent NH3 yield (470.9 µmol h-1 cm-2) and Faraday efficiency (FE: 84.4%) at -1.2 V versus reversible hydrogen electrode (vs. RHE). The heterostructure increases the specific surface area of the catalyst, and the possibility of contact between the catalyst and NO3- ions, enhances the catalytic efficiency. In addition, the catalyst has excellent stability and can stably carry out the electrocatalytic nitrate reduction reaction (NO3-RR), which provides a way for further research on the high-efficiency reduction of nitrate.

Aggregation-Induced Electrochemiluminescence of Ir(ppy)3-Functionalized ZIF-8 for Microcystin-LR Detection via the trans-Cleavage Activity of CRISPR-Cas12a.

An efficient electrochemiluminescence (ECL) emitter, Ir(ppy)3-based molecules has recently been reported to exhibit aggregation-induced electrochemiluminescence (AIECL) phenomenon. However, it remains a significant challenge to control the aggregation states of these molecules and achieve uniform aggregates with intense ECL emission. In this work, a biosensor was developed to detect microcystin-LR (MC-LR) based on Ir(ppy)3-functionalized zeolitic imidazolate framework-8 (Ir-ZIF-8) as the ECL emitter and the trans-cleavage activity of CRISPR-Cas12a as the methodological strategy. The Ir-ZIF-8, a functional metal-organic framework (MOF), exhibited the AIECL phenomenon via the spatial domain-limiting effect of encapsulating Ir(ppy)3 into the mesopores of ZIF-8, while the porosity and highly ordered topological structure of ZIF-8 effectively limited the molecular motion of Ir(ppy)3. CRISPR-Cas12a was employed to indiscriminately cleave double-stranded DNA decorated with carboxy tetramethylrhodamine (TAMRA), which quenched the ECL signal of Ir-ZIF-8 by resonance energy transfer and then separated the quencher from Ir-ZIF-8 to reactivate the signal. The concentration of MC-LR was designed to correlate with both the quencher amount and the activity of Cas12a. Then, two linear regression equations for MC-LR detection were constructed to improve the accuracy of the biosensor, and the constructed biosensor showed remarkable reproducibility, stability, and selectivity. The accurate detection of MC-LR with limits of detection of 1.2 and 5.9 pg/mL was made possible by the high quenching efficiency of TAMRA and the effective cutting ability of the editable CRISPR-Cas12a system.

Protein-driven interaction enhanced electrochemiluminescence biosensor of hydrogen-bonded biohybrid organic frameworks for sensitive immunoassay of disease markers.

The oriented design of reticular materials as emitters can significantly enhance the sensitivity of electrochemiluminescence (ECL) sensing analysis for disease markers. However, due to the structural fragility of hydrogen bonds, relational research on hydrogen-bonded organic frameworks (HOFs) has not been thoroughly conducted. Additionally, the modulation of luminescence behavior through HOFs has been rarely reported. In view of this, hydrogen-bonded biohybrid organic frameworks (HBOFs) were synthesized and recruited for ECL immunoassay applications. HBOFs was easily prepared using 6,6',6″,6‴-(pyrene-1,3,6,8-tetrayl)tetrakis(2-naphthoic acid) as linkers via bovine serum albumin (BSA) activated hydrogen-bonded cross-linking. The material exhibited good fluorescence emission characteristics. And the highly ordered topological structure and molecular motion limitation mediated by BSA overcome aggregation-caused quenching and generate strong aggregation induced emission, expressing hydrogen-bond interaction enhanced ECL (HIE-ECL) activity with the participation of tri-n-propylamine. Furthermore, a sandwich immunosensor was constructed employing cobalt-based metal-phenolic network (CMPN) coated ferrocene nanoparticles (FNPs) as quenchers (CMPN@FNPs). Signal closure can be achieved by annihilating the excited state through electron transfer from both CMPN and FNPs. Using a universal disease marker, carcinoembryonic antigen, as the analysis model, the signal-off sensor obtained a detection limit of 0.47 pg/mL within the detection range of 1 pg/mL - 50 ng/mL. The synthesis and application of highly stable HBOFs triggered by proteins provide a reference for the development of new reticular ECL signal labels, and electron transfer model provides flexible solutions for more sensitive sensing analysis.

Effective Enrichment of Free Radicals through Nanoconfinement Boosts Electrochemiluminescence of Carbon Dots Derived from Luminol.

Local enrichment of free radicals at the electrode interface may open new opportunities for the development of electrochemiluminescence (ECL) applications. The sensing platform was constructed by assembling ECL-emitting luminol derived carbon dots (Lu CDs) onto the heterojunction Tungsten disulfide/Covalent organic frameworks (WS2@COF) for the first time, establishing a nanoconfinement-reactor with significantly heightened ECL intensity and stability compared to the Lu CDs-H2O2 system. This enhanced performance is credited to the COF domain's restricted pore environment, where WS2@COF exhibits a more negative adsorption energy for H2O2, effectively enriching H2O2 in the catalytic edge sites of WS2. Furthermore, the internal electric field at the WS2 and COF interface accelerates electron flow, boosting WS2's catalytic activity and achieving domain-limited catalytic enhancement of ECL. Self-designed DNA nanomachines combined with cascading molecular keypad locking mechanisms are integrated into the biosensors, effectively guaranteeing the accuracy of the sensing process while providing crucial safeguards for molecular diagnostics and information security applications. In essence, this innovative approach represents the first system to enhance local free radical concentrations by enriching co-reactants on the electrode surface through nanoconfinement catalysis, yielding heightened ECL luminescence intensity. The potential impact of this novel strategy and sensing mechanism on real-bioanalysis applications is promising.

Room-Temperature Liquid Crystalline Tetraphenylethylene-Surfactant Complex with Chiral Supramolecular Structure and Tunable Circularly Polarized Luminescence.

A novel room-temperature liquid crystal of tetraphenylethylene derivative (TPE-DHAB) was synthesized using an ionic self-assembly strategy. The TPE-DHAB complex exhibits typical aggregation-induced emission properties and a unique helical supramolecular structure. Moreover, the generation and handedness inversion of circularly polarized luminescence (CPL) can be achieved through further chiral solvation, providing a facile approach to fabricate room-temperature liquid crystalline materials with controllable supramolecular structures and tunable CPL properties through a synergistic strategy of ionic self-assembly and chiral solvation process.

A sandwich-type photoelectrochemical sensor constructed with a signal amplification strategy based on the upconversion luminescence characteristics of Ag@N-CQDs for sensitive detection of neuron specific enolase.

In this paper, Bi2S3/AgBiS2 composite nanomaterials and PDA@Ag@N-CQDs were synthesized, and used as substrates and second antibody label respectively to construct a sandwich photoelectrochemical (PEC) sensor. The upconversion luminescence effect of N-CQDs can convert long wavelength light into short wavelength light that can be utilized by the substrate material, which can provide additional excitation light energy for the substrate material and further enhance the photoelectric response. Besides, Ag has SPR effect and can also promote electron transfer. The proposed sandwich immunosensor achieves detection of NSE in the concentration range of 0.001 ng mL-1 to 100 ng mL-1, with a detection limit of 0.28 pg mL-1 (S/N = 3). What's more, the proposed sensor also exhibits good stability, selectivity, as well as reproducibility, indicating its promising application prospects.

The prevalence of spontaneous resolution among pediatric trigger thumb: a systematic review and meta-analysis.

BACKGROUND: Trigger thumb is a prevalent hand condition observed in children, and its management remains a topic of considerable debate, ranging from mere observation to surgical intervention. In recent times, there has been a growing interest in exploring nonoperative treatments as alternatives to surgical procedures for managing pediatric trigger thumb. Gaining insight into the prevalence of spontaneous resolution in pediatric trigger thumb is of paramount importance. However, the literature presents a wide variation in estimates regarding the prevalence of this spontaneous resolution, highlighting the need for further investigation and consensus. The aim of this review was to estimate the overall prevalence of spontaneous resolution among pediatric trigger thumb. METHODS: This study meticulously followed the PRISMA guidelines and registered in the PROSPERO. The PubMed, Embase, and Cochrane Library databases were searched for all relevant studies up to May 2024.Inclusion criteria were studies reported only observation spontaneous resolution pediatric trigger thumb, aged up to 14 years, reported at least 10 thumbs and followed up time at least 3 months. Confounded intervention treatment measure studies were excluded. To synthesize the prevalence rates from individual studies, we employed a random-effects meta-analysis. In order to uncover the sources of heterogeneity and to compare prevalence estimates across different groups, we performed sensitivity and subgroup analyses. To meticulously evaluate the quality of the included studies, the Joanna Briggs Institute's quality assessment checklist was employed. Furthermore, to assess the heterogeneity among the studies, both Cochran's Q test and the I² statistic were utilized. RESULTS: A total of eleven studies were included for the final analysis, with 599 pediatric trigger thumbs. Our final meta-analysis showed that more than one-third of these pediatric trigger thumb cases resolved spontaneously, with a resolution rate of 43.5% (95% CI 29.6-58.6). Subgroup analyses showed that in terms of age at the first visit, the prevalence of spontaneous resolution in the less than 24 months group and in the 24 months or older group was 38.7%(95% CI 18.1-64.4)and 45.8%(95% CI 27.4-65.4), respectively. There was no significant difference between the two groups(P = 0.690). When analyzing follow up time, the prevalence of spontaneous resolution in the 24 months or longer group and in the less than 24 months group was 58.9%(95% CI 41.6-74.2)and 26.8%(95% CI 14.7-43.8), respectively.There was significant statistical differences between the two groups(P = 0.009). Based on the initial severity of interphalangeal (IP) joint flexion contracture, the prevalence of spontaneous resolution in the 30 degrees or less group and in the other measurements group was 54.1%(95% CI 31.5-75.1)and 37.1%(95% CI 21.9-55.4), respectively.There was no significant difference between the two groups(P = 0.259). CONCLUSION: Our study demonstrates that a significant proportion of pediatric trigger thumbs resolve spontaneously. This finding highlights the benefits of early observation in managing this condition. By prioritizing non-operative observation, both parents and surgeons are better equipped to make informed decisions regarding the treatment of pediatric trigger thumb, potentially reducing the need for surgical intervention.

Rheumatoid arthritis complicated with cervical actinomycosis and ureteral obstruction: A case report and literature review. / ç±»é£Žæ¹¿å ³èŠ‚ç‚Žåˆå¹¶å®«é¢ˆæ”¾çº¿èŒç— åŠè¾“å°¿ç®¡æ¢—é˜»1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Actinomycosis is a rare chronic granulomatous disease characterized by granuloma formation and tissue fibrosis with sinus tracts, often misdiagnosed due to its similarity to many infectious and non-infectious diseases. This report presents a case of a 60-year-old female with more than 10 years history of rheumatoid arthritis who developed actinomycosis infection after long-term treatment with immunosuppressants and biologics, including methotrexate, leflunomide, and infliximab, leading to recurrent joint pain, poorly controlled rheumatoid arthritis activity, and persistent elevation of white blood cell counts. Abdominal CT revealed a pelvic mass and right ureteral dilation. Pathological examination of cervical tissue showed significant neutrophil infiltration and sulfur granules, indicating actinomycosis. The patient received 18 months of doxycycline treatment for the infection and continued rheumatoid arthritis therapy with leflunomide, hydroxychloroquine sulfate, and tofacitinib, resulting in improved joint symptoms and normalized white blood cell counts. After 2 years of follow-up, the patient remained stable with no recurrence. This case highlights the importance of clinicians being vigilant for infections, particularly chronic, occult infections from rare pathogens, in rheumatoid arthritis patients on potent immunosuppressants and biologics, advocating for early screening and diagnosis.

Functional analysis of two caffeoyl-coenzyme 3 a-o-methyltransferase involved in pear lignin metabolism.

Caffeoyl-coenzyme 3 A-O-methyltransferase (CCoAOMT) plays a crucial role in the lignin synthesis in many higher plants. In this study, nine PbCCoAOMT genes in total were identified from pear, and classified into six categories. We treated pear fruits with hormones abscisic acid (ABA) and methyl jasmonate (MeJA) and salicylic acid (SA) and observed differential expression levels of these genes. Through qRT-PCR, we also preliminarily identified candidate PbCCoAOMT gene, potentially involved in lignin synthesis in pear fruits. Additionally, the overexpression of PbCCoAOMT1/2 in Arabidopsis and pear fruits increased in lignin content. Enzymatic assays showed that recombinant PbCCoAOMT1/2 proteins have similar enzymatic activity in vitro. The Y1H (Yeast one-hybrid) and dual luciferase (dual-LUC) experiments demonstrated that PbMYB25 can bind to the AC elements in the promoter region of the PbCCoAOMT1 gene. Our findings suggested that the PbCCoAOMT1 and PbCCoAOMT2 genes may contribute to the synthesis of lignin and provide insights into the mechanism of lignin biosynthesis and stone cell development in pear fruits.

Self-Assembled Perylene Diimide (PDI) Nanowire Sensitized In2O3@MgIn2S4 S-Scheme Heterojunction as Photoelectrochemical Biosensing Platform for the Detection of CA15-3.

Inorganic/organic heterojunctions show promising applications as high-performance sensing platforms for photoelectrochemical (PEC) immunosensors. This work reports constructing a PEC biosensor for CA15-3 based on a self-assembled perylene diimide (PDI) nanowire sensitized In2O3@MgIn2S4 S-scheme heterojunction platform. P-type semiconductor Cu2O nanoparticles were designed as a signal burst source and were used as immunoassay labels. The carboxyl group on self-assembled PDI nanowires eliminates the step of additional surface functionalization for covalent immobilization of the capture elements. The π-π stacking of PDI enhances electron generation efficiency, while the carboxylic acid groups on PDI promote electron transfer. The performance of the constructed sensor was validated using CA15-3 as a model. The experimental results showed that the sensor based on In2O3@MgIn2S4/PDI has excellent selectivity, stability, and reproducibility, and can sensitively detect CA15-3 in the range of 0.001-100 U·mL-1 with the detection limit of 0.00056 U·mL-1. The sensor has a broad application prospect. It is hoped that this research work based on the unique advantages of the organic compound PDI will inspire other researchers to design light-responsive materials and promote the development of the field of photoelectrochemical sensing.

Hyperglycemia-independent neonatal streptozotocin-induced retinopathy (NSIR) in rats.

Introduction: Chemicals, such as MNU (N-methyl-N-nitrosourea) and NaIO3 (sodium iodate), are widely used to induce retinal degeneration in rodents. Streptozotocin (STZ) is an analog of N-acetyl glucosamine in which an MNU moiety is linked to a hexose and has a special toxic effect on insulin-producing pancreatic ß-cells. It is commonly used to induce hyperglycemia to model diabetes. While intracerebroventricular injection of STZ can produce Alzheimer's disease independent of hyperglycemia, most retinal studies using STZ focus on the effects of hyperglycemia on the retina, but whether STZ has any impact on retinal cells independent of hyperglycemia is unknown. We aimed to investigate the role of cytotoxicity of STZ in rat retina. Methods: Intravitreal or subcutaneous injection of STZ was performed on newborn rats. Electroretinogram (ERG) and H&E staining investigated retinal function and morphological changes. Retinal cell types, cell death, proliferation, inflammation, and angiogenesis were studied by immunostaining. RNA sequencing was performed to examine the transcriptome changes of retinal cells after intravitreal injection of STZ. Results: Intravitreal (5 µg or 10 µg) or subcutaneous (30 mg/kg) injection of STZ at the early stage of newborn rats couldn't induce hyperglycemia but caused NSIR (Neonatal STZ-induced retinopathy), including reduced ERG amplitudes, retinal rosettes and apoptosis, cell cycle arrest, microglial activation, and delayed retinal angiogenesis. STZ did not affect the early-born retinal cell types but significantly reduced the late-born ones. Short-term and long-term hyperglycemia had no significant effects on the NSIR phenotypes. RNA sequencing revealed that STZ induces oxidative stress and activates the p53 pathway of retinal cells. Locally or systemically, STZ injection after P8 couldn't induce SINR when all retinal progenitors exit the cell cycle. Conclusion: NSIR in rats is independent of hyperglycemia but due to STZ's direct cytotoxic effects on retinal progenitor cells. NSIR is a typical reaction to STZ-induced retinal oxidative stress and DNA damage. This significant finding suggests that NSIR may be a valuable model for studying retinal progenitor DNA damage-related diseases, potentially leading to new insights and treatments.

Microbial synthesis of gallic acid and its glucoside ß-glucogallin.

Gallic acid (GA) and ß-glucogallin (BGG) are natural products with diverse uses in pharmaceutical, food, chemical and cosmetic industries. They are valued for their wide-ranging properties such as antioxidant, antibacterial, antidiabetic, and anticancer properties. Despite their significant importance, microbial production of GA and BGG faces challenges such as limited titers and yields, along with the incomplete understanding of BGG biosynthesis pathways in microorganisms. To address these challenges, we developed a recombinant Escherichia coli strain capable of efficiently producing GA. Our approach involved screening efficient pathway enzymes, integrating biosynthetic pathway genes into the genome while balancing carbon flux via adjusting expression levels, and strengthening the shikimate pathway to remove bottlenecks. The resultant strain achieved impressive results, producing 51.57 g/L of GA with a carbon yield of 0.45 g/g glucose and a productivity of 1.07 g/L/h. Furthermore, we extended this microbial platform to biosynthesize BGG by screening GA 1-O-glucosyltransferase, leading to the de novo production of 92.42 mg/L of BGG. This work establishes an efficient chassis for producing GA at an industrial level and provides a microbial platform for generating GA derivatives.

Berberine hydrochloride alleviates chronic prostatitis/chronic pelvic pain syndrome by modifying gut microbiome signaling.

ABSTRACT: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is highly prevalent worldwide and poses a significant threat to men's health, particularly affecting young men. However, the exact causes and mechanisms behind CP/CPPS remain unclear, leading to challenges in its treatment. In this research, a CP/CPPS rat model was established with complete Freund's adjuvant (CFA), and berberine hydrochloride was administered through daily gavage to assess its therapeutic effects. The alterations in the gut microbiome induced by CP/CPPS and berberine hydrochloride were investigated through 16S ribosomal RNA sequencing of cecum content and colonic epithelial cells. To investigate the impact of the gut microbiome on CP/CPPS, a pseudo germ-free rat model was established, and fecal microbiome transplantation (FMT) was performed on these rats. In all, berberine hydrochloride demonstrated effective reduction of inflammation and oxidative stress in the prostate, offering significant therapeutic advantages for CP/CPPS. Through analysis of the gut microbiome using 16S ribosome RNA sequencing, distinct differences were observed between CP/CPPS rats and control rats, and Clostridium butyricum was identified as a key bacteria. Pseudo germ-free rats that underwent FMT from CP/CPPS rats or rats treated with berberine hydrochloride displayed varying levels of inflammatory cytokine production, oxidative stress, and activity of associated signaling pathways. In conclusion, the therapeutic potential of berberine hydrochloride in addressing CP/CPPS is highly significant. The gut microbiome has emerged as a critical factor in the development of CP/CPPS and plays a pivotal role in mediating the therapeutic effects of berberine hydrochloride.

Cross-species single-cell landscapes identify the pathogenic gene characteristics of inherited retinal diseases.

Introduction: Inherited retinal diseases (IRDs) affect ∼4.5 million people worldwide. Elusive pathogenic variants in over 280 genes are associated with one or more clinical forms of IRDs. It is necessary to understand the complex interaction among retinal cell types and pathogenic genes by constructing a regulatory network. In this study, we attempt to establish a panoramic expression view of the cooperative work in retinal cells to understand the clinical manifestations and pathogenic bases underlying IRDs. Methods: Single-cell RNA sequencing (scRNA-seq) data on the retinas from 35 retina samples of 3 species (human, mouse, and zebrafish) including 259,087 cells were adopted to perform a comparative analysis across species. Bioinformatic tools were used to conduct weighted gene co-expression network analysis (WGCNA), single-cell regulatory network analysis, cell-cell communication analysis, and trajectory inference analysis. Results: The cross-species comparison revealed shared or species-specific gene expression patterns at single-cell resolution, such as the stathmin family genes, which were highly expressed specifically in zebrafish Müller glias (MGs). Thirteen gene modules were identified, of which nine were associated with retinal cell types, and Gene Ontology (GO) enrichment of module genes was consistent with cell-specific highly expressed genes. Many IRD genes were identified as hub genes and cell-specific regulons. Most IRDs, especially the retinitis pigmentosa (RP) genes, were enriched in rod-specific regulons. Integrated expression and transcription regulatory network genes, such as congenital stationary night blindness (CSNB) genes GRK1, PDE6B, and TRPM1, showed cell-specific expression and transcription characteristics in either rods or bipolar cells (BCs). IRD genes showed evolutionary conservation (GNAT2, PDE6G, and SAG) and divergence (GNAT2, MT-ND4, and PDE6A) along the trajectory of photoreceptors (PRs) among species. In particular, the Leber congenital amaurosis (LCA) gene OTX2 showed high expression at the beginning of the trajectory of both PRs and BCs. Conclusion: We identified molecular pathways and cell types closely connected with IRDs, bridging the gap between gene expression, genetics, and pathogenesis. The IRD genes enriched in cell-specific modules and regulons suggest that these diseases share common etiological bases. Overall, mining of interspecies transcriptome data reveals conserved transcriptomic features of retinas across species and promising applications in both normal retina anatomy and retina pathology.

Endophthalmitis: a bibliometric study and visualization analysis from 1993 to 2023.

Aims: This study is designed to generalize and depict the research hotspots of endophthalmitis through bibliometric methods and software and analyze the evolutive tendency of the work on this severe disease over the past 30 years. Methods: This study employed a rigorous bibliometric approach. We identified all endophthalmitis-related literature by conducting a comprehensive search of the Science Citation Index Expanded database under the Web of Science Core Collection. The data was then analyzed and visualized using CiteSpace and VOSviewer, two widely recognized software tools in the field of bibliometrics. CiteSpace was used to analyze the country distributions, dual map overlay of journals, keyword bursts, and co-cited references. VOSviewer was employed to describe the authors and co-cited authors, the journals, the co-cited journals, and the keywords co-occurrence network. This robust methodology ensures the reliability and validity of the study's findings. Results: A total of 2960 publications, including 2695 articles and 265 reviews, were included in this bibliometric study. There has been no shortage of endophthalmitis-related publications since 1993, with an apparent upward trend during recent years. Possible correlations with the COVID-19 pandemic are also analyzed. These studies were finished by 11,048 authors from 75 countries worldwide, with the United States in the lead. In the keyword co-occurrence network, except for the endophthalmitis term, cataract surgery becomes the keyword with the highest frequency. Different categories of endophthalmitis, including postoperative, post-injection, post-traumatic, and endogenous endophthalmitis, and antibacterial and anti-inflammatory therapies of infectious endophthalmitis, are discussed by categories. From the perspective of the timeline, postoperative and post-injection endophthalmitis were the dominant forms before and after the year 2000, respectively. Co-citation analyses reveal that the Endophthalmitis Vitrectomy Study (EVS) conducted in 1995 provides pivotal guidance for later research. Diverse pathogenic bacteria (e.g., Coagulase-negative Staphylococci, Propionibacterium acnes, Viridians Streptococci, and Bacillus cereus) or fungi (e.g., Candida, Aspergillus, and Fusarium) contribute to varying treatment principles and clinical prognosis, which should be taken seriously. In addition, intravitreal and intracameral antibiotics are the mainstay for treating and preventing infectious endophthalmitis, respectively. Conclusion: Our bibliometric analysis provides an overview of dynamic evolution and structural relationships in the research field of endophthalmitis. The displayed hotspots and developmental directions have reference values for future investigation.

Real time detection and identification of fish quality using low-power multimodal artificial olfaction system.

Single gas quantification and mixed gas identification have been the major challenges in the field of gas detection. To address the shortcomings of chemo-resistive gas sensors, sensor arrays have been the subject of recent research. In this work, the research focused on both optimization of gas-sensing materials and further analysis of pattern recognition algorithms. Four bimetallic oxide-based gas sensors capable of operating at room temperature were first developed by introducing different modulating techniques on the sensing layer, including constructing surface oxygen defects, polymerizing conducting polymers, modifying Nano-metal, and compositing flexible substrates. The signals derived from the gas sensor array were then processed to eliminate noise and reduce dimension with the feature engineering. The gases of were qualitatively identified by support vector machine (SVM) model with an accuracy of 98.86 %. Meanwhile, a combined model of convolutional neural network and long short-term memory network (CNN-LSTM) was established to remove the interference samples and quantitatively estimate the concentration of the target gases. The combined model based on deep learning, which avoids the overfitting with local optimal solutions, effectively boosts the performance of concentration recognition with the lowest root mean square error (RMSE) of 2.3. Finally, a low-power artificial olfactory system was established by merging the multi-sensor data and applied for real-time and accurate judgment of the food freshness.