The SiaA/B/C/D signaling network regulates biofilm formation in Pseudomonas aeruginosa.

Bacterial cyclic-di-GMP (c-di-GMP) production is associated with biofilm development and the switch from acute to chronic infections. In Pseudomonas aeruginosa, the diguanylate cyclase (DGC) SiaD and phosphatase SiaA, which are co-transcribed as part of a siaABCD operon, are essential for cellular aggregation. However, the detailed functions of this operon and the relationships among its constituent genes are unknown. Here, we demonstrate that the siaABCD operon encodes for a signaling network that regulates SiaD enzymatic activity to control biofilm and aggregates formation. Through protein-protein interaction, SiaC promotes SiaD diguanylate cyclase activity. Biochemical and structural data revealed that SiaB is an unusual protein kinase that phosphorylates SiaC, whereas SiaA phosphatase can dephosphorylate SiaC. The phosphorylation state of SiaC is critical for its interaction with SiaD, which will switch on or off the DGC activity of SiaD and regulate c-di-GMP levels and subsequent virulence phenotypes. Collectively, our data provide insights into the molecular mechanisms underlying the modulation of DGC activity associated with chronic infections, which may facilitate the development of antimicrobial drugs.

Integrated Multi-Omics Landscape of Liver Metastases.

BACKGROUND & AIMS: Lack of thorough knowledge about the complicated immune microenvironment (IM) within a variety of liver metastases (LMs) leads to inappropriate treatment and unsatisfactory prognosis. We aimed to characterize IM subtypes and investigate potential mechanisms in LMs. METHODS: Mass cytometry was applied to characterize immune landscape of a primary liver cancers and liver metastases cohort. Transcriptomic and whole-exome sequencing were used to explore potential mechanisms across distinct IM subtypes. Single-cell transcriptomic sequencing, multiplex fluorescent immunohistochemistry, cell culture, mouse model, Western blot, quantitative polymerase chain reaction, and immunohistochemistry were used for validation. RESULTS: Five IM subtypes were revealed in 100 LMs and 50 primary liver cancers. Patients featured terminally exhausted (IM1) or rare T-cell-inflamed (IM2 and IM3) immune characteristics showed worse outcome. Increased intratumor heterogeneity, enriched somatic TP53, KRAS, APC, and PIK3CA mutations and hyperactivated hypoxia signaling accounted for the formation of vicious subtypes. SLC2A1 promoted immune suppression and desert via increasing proportion of Spp1+ macrophages and their inhibitory interactions with T cells in liver metastatic lesions. Furthermore, SLC2A1 promoted immune escape and LM through inducing regulatory T cells, including regulatory T cells and LAG3+CD4+ T cells in primary colorectal cancer. CONCLUSIONS: The study provided integrated multi-omics landscape of LM, uncovering potential mechanisms for vicious IM subtypes and confirming the roles of SLC2A1 in regulating tumor microenvironment remodeling in both primary tumor and LM lesions.

FlhF affects the subcellular clustering of WspR through HsbR in Pseudomonas aeruginosa.

In bacteria, the second messenger cyclic di-GMP (c-di-GMP) is synthesized and degraded by multiple diguanylate cyclases (DGCs) and phosphodiesterases. A high level of c-di-GMP induces biofilm formation and represses motility. WspR, a hybrid response regulator DGC, produces c-di-GMP when it is phosphorylated. FlhF, a signal recognition particle-type GTPase, is initially localized to the cell poles and is indispensable for polar flagellar localization in Pseudomonas aeruginosa. In this study, we report that deletion of flhF affected biofilm formation and the c-di-GMP level in P. aeruginosa. Phenotypic analysis of a flhF knockout mutant revealed increased biofilm formation, wrinkled colonies on Congo red agar, and an elevated c-di-GMP level compared to the wild-type strain, PAO1. Yeast and bacterial two-hybrid systems showed that FlhF binds to the response regulator HsbR, and HsbR binds to WspR. Deletion of hsbR or wspR in the ΔflhF background abolished the phenotype of ΔflhF. In addition, confocal microscopy demonstrated that WspR-GFP was distributed throughout the cytoplasm and formed a visible cluster at one cell pole in PAO1 and ΔhsbR, but it was mainly distributed as visible clusters at the lateral side of the periplasm and with visible clusters at both cell poles in ΔflhF. These findings suggest that FlhF influences the subcellular cluster and localization of WspR and negatively modulates WspR DGC activity in a manner dependent on HsbR. Together, our findings demonstrate a novel mechanism for FlhF modulating the lifestyle transition between motility and biofilm via HsbR to regulate the DGC activity of WspR.IMPORTANCECyclic di-GMP (c-di-GMP) is a second messenger that controls flagellum biosynthesis, adhesion, virulence, motility, exopolysaccharide production, and biofilm formation in bacteria. Recent research has shown that distinct diguanylate cyclases (DGCs) or phosphodiesterases (PDEs) produce highly specific outputs. Some DGCs and PDEs contribute to the total global c-di-GMP concentration, but others only affect local c-di-GMP in a microenvironment. However, the underlying mechanisms are unclear. Here, we report that FlhF affects the localization and DGC activity of WspR via HsbR and is implicated in local c-di-GMP signaling in Pseudomonas aeruginosa. This study establishes the link between the c-di-GMP signaling system and the flagellar localization and provides insight for understanding the complex regulatory network of c-di-GMP signaling.

A novel mutation in intron 1 of Wnt1 causes developmental loss of dopaminergic neurons in midbrain and ASD-like behaviors in rats.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic liability. Despite extensive studies, however, the underlying pathogenic mechanism still remains elusive. In the present study, we identified a homozygous mutation in the intron 1 of Wnt1 via large-scale screening of ASD risk/causative genes and verified that this mutation created a new splicing donor site in the intron 1, and consequently, a decrease of WNT1 expression. Interestingly, humanized rat models harboring this mutation exhibited robust ASD-like behaviors including impaired ultrasonic vocalization (USV), decreased social interactions, and restricted and repetitive behaviors. Moreover, in the substantia nigra compacta (SNpc) and the ventral tegmental area (VTA) of mutant rats, dopaminergic (DAergic) neurons were dramatically lost, together with a comparable decrease in striatal DAergic fibers. Furthermore, using single-cell RNA sequencing, we demonstrated that the decreased DAergic neurons in these midbrain areas might attribute to a shift of the boundary of the local pool of progenitor cells from the hypothalamic floor plate to the midbrain floor plate during the early embryonic stage. Moreover, treatments of mutant rats with levodopa could attenuate the impaired USV and social interactions almost completely, but not the restricted and repetitive behaviors. Our results for the first time documented that the developmental loss of DAergic neurons in the midbrain underlies the pathogenesis of ASD, and that the abnormal progenitor cell patterning is a cellular underpinning for this developmental DAergic neuronal loss. Importantly, the effective dopamine therapy suggests a translational significance in the treatment of ASD.

Postoperative EEG abnormalities in relation to neurodevelopmental outcomes after pediatric cardiac surgery.

BACKGROUND: We had reported that postoperative EEG background including sleep-wake cycle (SWC) and discharge (seizures, spikes/sharp waves) abnormalities were significantly correlated with adverse early outcomes in children after cardiac surgery. We aimed to analyze the relations between these EEG abnormalities and neurodevelopmental outcomes at about 2 years after cardiac surgery. METHODS: We enrolled 121 patients undergoing cardiac surgery at 3.3 months (0.03 ~ 28 months). EEG abnormalities described above during the first postoperative 48 h were evaluated. Griffiths Mental Development Scales-Chinese was used to evaluate the quotients of overall development and 5 subscales of the child's locomotor, language, personal-social, eye-hand coordination and performance skills at 16 ~ 31 months of age. RESULTS: EEG background abnormalities occurred in 59/121 (48.8%) patients and 33 (55.9%) unrecovered to normal by 48 h. Abnormal SWC occurred in 15 (12.4%) patients and 7 (5.8%) unrecovered to normal by 48 h. EEG seizures occurred in 11 (9.1%) patients with frontal lobe seizures in 4. Spikes/sharp waves occurred in 100 (82.6%). EEG background abnormalities, number of spikes/sharp waves and frontal lobe seizures were significantly associated with neurodevelopmental impairment at about 1 ~ 2 year after surgery (Ps ≤ 0.05). CONCLUSIONS: Most parameters of EEG abnormalities were significantly associated with neurodevelopmental impairment after cardiac surgery. IMPACT: Neurodevelopmental impairment in children with congenital heart disease remain poorly understood. Previous studies had reported that either EEG seizures or background abnormalities were associated with worse neurodevelopmental outcomes. Our present study showed that all the EEG background and discharge abnormalities including EEG background, seizures and spikes/sharp waves in the early postoperative period were significantly associated with neurodevelopmental impairment at about 1 ~ 2 years after cardiac surgery. Comprehensive evaluation of early postoperative EEG may provide further insights about postoperative brain injury, its relation with neurodevelopmental impairment, and guide to improve clinical management.

Dual regulatory actions of LncBMP4 on BMP4 promote chicken primordial germ cell formation.

The unique characteristics of chicken primordial germ cells (PGCs) provide potential strategies for transgenic animal generation; however, insufficient PGC availability has limited their application. Regulation of bone morphogenic protein 4 (BMP4), a crucial factor for PGCs formation, may provide new strategies for PGC generation. We here identify a long noncoding RNA (lncRNA) that targets BMP4 (LncBMP4). LncBMP4 has similar functions as BMP4, in that it facilitates the formation and migration of PGCs. LncBMP4 promotes BMP4 expression by adsorbing the miRNA gga-mir-12211, thus reducing its inhibitory effect on BMP4 expression. In addition, the small peptide EPC5 encoded by LncBMP4 promotes the transcription of BMP4. The competing endogenous RNA (ceRNA) effect of LncBMP4 requires N6-methyladenosine (m6A) modification, in a dose-dependent manner, and high levels of m6A modification hinder EPC5 translation. Understanding the molecular mechanisms through which LncBMP4 promotes BMP4 expression during PGC formation may provide new avenues for efficient PGC generation.

[Correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy].

OBJECTIVE: To explore the correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy (DEE). METHODS: Clinical data of 46 children with DEE and SCN1A variants identified at the Guangzhou Women and Children's Medical Center between January 2018 and June 2022 were collected. The children were grouped based on their age of onset, clinical manifestations, neurodevelopmental status, and results of genetic testing. The correlation between SCN1A genotypes and clinical phenotypes was analyzed. RESULTS: Among the 46 patients, 2 children (4.35%) had developed the symptoms before 3 months of age, 42 (91.30%) were between 3 to 9 months, and 2 cases (4.35%) were after 10 months. Two cases (4.35%) presented with epilepsy of infancy with migrating focal seizures (EIMFS), while 44 (95.7%) had presented with Dravet syndrome (DS), including 28 cases (63.6%) with focal onset (DS-F), 13 cases (29.5%) with myoclonic type (DS-M), 1 case (2.27%) with generalized type (DS-G), and 2 cases (4.55%) with status epilepticus type (DS-SE). Both of the two EIMFS children had severe developmental delay, and among the DS patients, 7 cases had normal development, while the remaining had developmental delay. A total of 44 variants were identified through genetic sequencing, which included 16 missense variants and 28 truncating variants. All EIMFS children had carried the c.677C>T (p.Thr226Met) missense variant. In the DS group, there was a significant difference in the age of onset between the missense variants group and the truncating variants group (P < 0.05). Missense variants were more common in D1 (7/15, 46.7%) and pore regions (8/15, 53.3%), while truncating variants were more common in D1 (12/28, 42.9%). Children with variants outside the pore region were more likely to develop myoclonic seizures. CONCLUSION: The clinical phenotypes of DEE are diverse. There is a difference in the age of onset between individuals with truncating and missense variants in the SCN1A gene. Missense variants outside the pore region are associated with a higher incidence of myoclonic seizures.

Identification of key events and regulatory networks in the formation process of primordial germ cell based on proteomics.

Currently, studies have analyzed the formation mechanism of primordial germ cell (PGC) at the transcriptional level, but few at the protein level, which made the mechanism study of PGC formation not systematic. Here, we screened differential expression proteins (DEPs) regulated PGC formation by label-free proteomics with a novel sampling strategy of embryonic stem cells and PGC. Analysis of DEPs showed that multiple key events were involved, such as the transition from glycolysis to oxidative phosphorylation, activation of autophagy, low DNA methylation ensured the normal formation of PGC, beyond that, protein ubiquitination also played an important role in PGC formation. Importantly, the progression of such events was attributed to the inconsistency between transcription and translation. Interestingly, MAPK, PPAR, Wnt, and JAK signaling pathways not only interact with each other but also interact with different events to participate in the formation of PGC, which formed the PGC regulatory network. According to the regulatory network, the efficiency of PGC formation in induction system can be significantly improved. In conclusion, our results indicate that chicken PGC formation is a complex process involving multiple events and signals, which provide technical support for the specific application in PGC research.

BMP4 activates the Wnt-Lin28A-Blimp1-Wnt pathway to promote primordial germ cell formation via altering H3K4me2.

The unique developmental characteristics of chicken primordial germ cells (PGCs) enable them to be used in recovery of endangered bird species, gene editing and the generation of transgenic birds, but the limited number of PGCs greatly limits their application. Studies have shown that the formation of mammalian PGCs is induced by BMP4 signal, but the mechanism underlying chicken PGC formation has not been determined. Here, we confirmed that Wnt signaling activated via BMP4 activates transcription of Lin28A by inducing ß-catenin to compete with LSD1 for binding to TCF7L2, causing LSD1 to dissociate from the Lin28A promoter and enhancing H3K4me2 methylation in this region. Lin28A promotes PGC formation by inhibiting gga-let7a-3p maturation to initiate Blimp1 expression. Interestingly, expression of Blimp1 helped sustain Wnt5A expression by preventing LSD1 binding to the Wnt5A promoter. We thus elucidated a positive feedback pathway involving Wnt-Lin28A-Blimp1-Wnt that ensures PGC formation. In summary, our data provide new insight into the development of PGCs in chickens.

UDP-Galactopyranose Mutase Mediates Cell Wall Integrity, Polarity Growth, and Virulence in Fusarium graminearum.

CHY1 is a zinc finger protein unique to microorganisms that was found to regulate polarized tip growth in Fusarium graminearum, an important pathogen of wheat and barley. To further characterize its functions, in this study we identified CHY1-interacting proteins by affinity purification and selected UDP-galactofuranose (Galf) mutase (UGMA) for detailed characterization, because UGMA and UDP-Galf are unique to fungi and bacteria and absent in plants and animals. The interaction between CHY1 and UGMA was confirmed by yeast two-hybrid assays. Deletion of UGMA in F. graminearum resulted in significant defects in vegetative growth, reproduction, cell wall integrity, and pathogenicity. Infection with the ΔugmA mutant was restricted to the inoculated floret, and no vomitoxin was detected in kernels inoculated with the ΔugmA strain. Compared to the wild type, the ΔugmA mutant produced wide, highly branched hyphae with thick walls, as visualized by transmission electron microscopy. UGMA tagged with green fluorescent protein (GFP) mainly localized to the cytoplasm, consistent with the synthesis of Galf in the cytoplasm. The Δchy1 mutant was more sensitive, while the ΔugmA mutant was more tolerant, to cell wall-degrading enzymes. The growth of the ΔugmA mutant nearly ceased upon caspofungin treatment. More interestingly, nocodazole treatment of the ΔugmA strain attenuated its highly branched morphology, while caspofungin inhibited the degree of the twisted Δchy1 mycelia, indicating that CHY1 and UGMA probably have opposite effects on cell wall architecture. In conclusion, UGMA is an important pathogenic factor that is specific to fungi and bacteria and required for cell wall architecture, radial growth, and caspofungin tolerance, and it appears to be a promising target for antifungal agent development. IMPORTANCE The long-term use of chemical pesticides has had increasingly negative impacts on the ecological environment and human health. Low-toxicity, high-efficiency and environmentally friendly alternative pesticides are of great significance for maintaining the sustainable development of agriculture and human and environmental health. Using fungus- or microbe-specific genes as candidate targets provides a good foundation for the development of low-toxicity, environmentally friendly pesticides. In this study, we characterized a fungus- and bacterium-specific UDP-galactopyranose mutase gene, ugmA, that contributes to the synthesis of the cell wall component Galf and is required for vegetative growth, cell wall integrity, deoxynivalenol (DON) production, and pathogenicity in F. graminearum. The ugmA deletion mutant exhibited increased sensitivity to caspofungin. These results demonstrate the functional importance of UGMA in F. graminearum, and its absence from mammals and higher plants constitutes a considerable advantage as a low-toxicity target for the development of new anti-Fusarium agents.

Discovery of Isojacareubin as a covalent inhibitor of SARS-CoV-2 main protease using structural and experimental approaches.

The ongoing pandemic with the emergence of immune evasion potential and, particularly, the current omicron subvariants intensified the situation further. Although vaccines are available, the immune evasion capabilities of the recent variants demand further efficient therapeutic choices to control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Hence, considering the necessity of the small molecule inhibitor, we target the main protease (3CLpro), which is an appealing target for the development of antiviral drugs against SARS-CoV-2. High-throughput molecular in silico screening of South African natural compounds database reported Isojacareubin and Glabranin as the potential inhibitors for the main protease. The calculated docking scores were reported to be -8.47 and -8.03 kcal/mol, respectively. Moreover, the structural dynamic assessment reported that Isojacareubin in complex with 3CLpro exhibit a more stable dynamic behavior than Glabranin. Inhibition assay indicated that Isojacareubin could inhibit SARS-CoV-2 3CLpro in a time- and dose-dependent manner, with half maximal inhibitory concentration values of 16.00 ± 1.35 µM (60 min incubation). Next, the covalent binding sites of Isojacareubin on SARS-CoV-2 3CLpro was identified by biomass spectrometry, which reported that Isojacareubin can covalently bind to thiols or Cysteine through Michael addition. To evaluate the inactivation potency of Isojacareubin, the inactivation kinetics was further investigated. The inactivation kinetic curves were plotted according to various concentrations with gradient-ascending incubation times. The KI value of Isojacareubin was determined as 30.71 µM, whereas the Kinact value was calculated as 0.054 min-1 . These results suggest that Isojacareubin is a covalent inhibitor of SARS-CoV-2 3CLpro .

Discovery of the covalent SARS-CoV-2 Mpro inhibitors from antiviral herbs via integrating target-based high-throughput screening and chemoproteomic approaches.

The main proteases (Mpro ) are highly conserved cysteine-rich proteins that can be covalently modified by numerous natural and synthetic compounds. Herein, we constructed an integrative approach to efficiently discover covalent inhibitors of Mpro from complex herbal matrices. This work begins with biological screening of 60 clinically used antiviral herbal medicines, among which Lonicera japonica Flos (LJF) demonstrated the strongest anti-Mpro effect (IC50 = 37.82 µg/mL). Mass spectrometry (MS)-based chemical analysis and chemoproteomic profiling revealed that LJF extract contains at least 50 constituents, of which 22 exhibited the capability to covalently modify Mpro . We subsequently verified the anti-Mpro effects of these covalent binders. Gallic acid and quercetin were found to potently inhibit severe acute respiratory syndrome coronavirus 2 Mpro in dose- and time- dependent manners, with the IC50 values below 10 µM. The inactivation kinetics, binding affinity and binding mode of gallic acid and quercetin were further characterized by fluorescence resonance energy transfer, surface plasmon resonance, and covalent docking simulations. Overall, this study established a practical approach for efficiently discovering the covalent inhibitors of Mpro from herbal medicines by integrating target-based high-throughput screening and MS-based assays, which would greatly facilitate the discovery of key antiviral constituents from medicinal plants.

Jun-mediated lncRNA-IMS promotes the meiosis of chicken spermatogonial stem cells via gga-miR-31-5p/stra8.

Meiosis, a key step in spermatogenesis, is affected by many factors. Current studies have shown that long noncoding RNAs (lncRNAs) are potential factors regulating meiosis, and their regulatory mechanisms have received much attention. However, little research has been done on its regulatory mechanism in the spermatogenesis of roosters. Here, we found that lncRNA involved in meiosis and spermatogenesis (lncRNA-IMS) was involved in the regulation of Stra8 by gga-miR-31-5p and hindered the inhibition of Stra8 by gga-miR-31-5p. The acquisition and loss of function experiments demonstrated that lncRNA-IMS was involved in meiosis and spermatogenesis. In addition, we predicted and determined the core promoter region of lncRNA-IMS. Prediction of transcription factors, deletion/overexpression of binding sites, knockdown/overexpression of Jun, and dual-luciferase reporter analysis confirmed that Jun positively activated transcription of lncRNA-IMS. Our findings further enrich the TF-lncRNA-miRNA-mRNA regulatory network during male meiosis and provide new ideas for studying the molecular mechanism of meiosis and spermatogenesis in chicken spermatogonial stem cells.

Altered expression of the L-arginine/nitric oxide pathway in ovarian cancer: metabolic biomarkers and biological implications.

MOTIVATION: Ovarian cancer (OC) is a highly lethal gynecological malignancy. Extensive research has shown that OC cells undergo significant metabolic alterations during tumorigenesis. In this study, we aim to leverage these metabolic changes as potential biomarkers for assessing ovarian cancer. METHODS: A functional module-based approach was utilized to identify key gene expression pathways that distinguish different stages of ovarian cancer (OC) within a tissue biopsy cohort. This cohort consisted of control samples (n = 79), stage I/II samples (n = 280), and stage III/IV samples (n = 1016). To further explore these altered molecular pathways, minimal spanning tree (MST) analysis was applied, leading to the formulation of metabolic biomarker hypotheses for OC liquid biopsy. To validate, a multiple reaction monitoring (MRM) based quantitative LCMS/MS method was developed. This method allowed for the precise quantification of targeted metabolite biomarkers using an OC blood cohort comprising control samples (n = 464), benign samples (n = 3), and OC samples (n = 13). RESULTS: Eleven functional modules were identified as significant differentiators (false discovery rate, FDR < 0.05) between normal and early-stage, or early-stage and late-stage ovarian cancer (OC) tumor tissues. MST analysis revealed that the metabolic L-arginine/nitric oxide (L-ARG/NO) pathway was reprogrammed, and the modules related to "DNA replication" and "DNA repair and recombination" served as anchor modules connecting the other nine modules. Based on this analysis, symmetric dimethylarginine (SDMA) and arginine were proposed as potential liquid biopsy biomarkers for OC assessment. Our quantitative LCMS/MS analysis on our OC blood cohort provided direct evidence supporting the use of the SDMA-to-arginine ratio as a liquid biopsy panel to distinguish between normal and OC samples, with an area under the ROC curve (AUC) of 98.3%. CONCLUSION: Our comprehensive analysis of tissue genomics and blood quantitative LC/MSMS metabolic data shed light on the metabolic reprogramming underlying OC pathophysiology. These findings offer new insights into the potential diagnostic utility of the SDMA-to-arginine ratio for OC assessment. Further validation studies using adequately powered OC cohorts are warranted to fully establish the clinical effectiveness of this diagnostic test.

Two-way focal stack fusion for light field saliency detection.

To improve the accuracy of saliency detection in challenging scenes such as small objects, multiple objects, and blur, we propose a light field saliency detection method via two-way focal stack fusion. The first way extracts latent depth features by calculating the transmittance of the focal stack to avoid the interference of out-of-focus regions. The second way analyzes the focused distribution and calculates the background probability of the slice, which can distinguish the foreground from the background. Extracting the potential cues of the focal stack through the two different ways can improve saliency detection in complex scenes. Finally, a multi-layer cellular automaton optimizer is utilized to incorporate compactness, focus, center prior, and depth features to obtain the final salient result. Comparison and ablation experiments are performed to verify the effectiveness of the proposed method. Experimental results prove that the proposed method demonstrates effectiveness in challenging scenarios and outperforms the state-of-the-art methods. They also verify that the depth and focus cues of the focal stack can enhance the performance of previous methods.

Research Challenges, Recent Advances, and Popular Datasets in Deep Learning-Based Underwater Marine Object Detection: A Review.

Underwater marine object detection, as one of the most fundamental techniques in the community of marine science and engineering, has been shown to exhibit tremendous potential for exploring the oceans in recent years. It has been widely applied in practical applications, such as monitoring of underwater ecosystems, exploration of natural resources, management of commercial fisheries, etc. However, due to complexity of the underwater environment, characteristics of marine objects, and limitations imposed by exploration equipment, detection performance in terms of speed, accuracy, and robustness can be dramatically degraded when conventional approaches are used. Deep learning has been found to have significant impact on a variety of applications, including marine engineering. In this context, we offer a review of deep learning-based underwater marine object detection techniques. Underwater object detection can be performed by different sensors, such as acoustic sonar or optical cameras. In this paper, we focus on vision-based object detection due to several significant advantages. To facilitate a thorough understanding of this subject, we organize research challenges of vision-based underwater object detection into four categories: image quality degradation, small object detection, poor generalization, and real-time detection. We review recent advances in underwater marine object detection and highlight advantages and disadvantages of existing solutions for each challenge. In addition, we provide a detailed critical examination of the most extensively used datasets. In addition, we present comparative studies with previous reviews, notably those approaches that leverage artificial intelligence, as well as future trends related to this hot topic.

Ultra-High Sensitivity Terahertz Microstructured Fiber Biosensor for Diabetes Mellitus and Coronary Heart Disease Marker Detection.

Diabetes Mellitus (DM) and Coronary Heart Disease (CHD) are among top causes of patient health issues and fatalities in many countries. At present, terahertz biosensors have been widely used to detect chronic diseases because of their accurate detection, fast operation, flexible design and easy fabrication. In this paper, a Zeonex-based microstructured fiber (MSF) biosensor is proposed for detecting DM and CHD markers by adopting a terahertz time-domain spectroscopy system. A suspended hollow-core structure with a square core and a hexagonal cladding is used, which enhances the interaction of terahertz waves with targeted markers and reduces the loss. This work focuses on simulating the transmission performance of the proposed MSF sensor by using a finite element method and incorporating a perfectly matched layer as the absorption boundary. The simulation results show that this MSF biosensor exhibits an ultra-high relative sensitivity, especially up to 100.35% at 2.2THz, when detecting DM and CHD markers. Furthermore, for different concentrations of disease markers, the MSF exhibits significant differences in effective material loss, which can effectively improve clinical diagnostic accuracy and clearly distinguish the extent of the disease. This MSF biosensor is simple to fabricate by 3D printing and extrusion technologies, and is expected to provide a convenient and capable tool for rapid biomedical diagnosis.

Analysis of the Promoter Regions of gga-miR-31 and Its Regulation by RA and C-jun in Chicken.

The role of gga-miR-31 in chicken germ cell differentiation and spermatogenesis is of significant importance. The transcriptional properties of gga-miR-31 are crucial in establishing the foundation for the formation of chicken spermatogonia stem cells and spermatogenesis. In this study, a series of recombinant vectors including varying lengths of the gga-miR-31 promoter were predicted and constructed. Through the utilization of the dual luciferase reporting system, the upstream -2180~0 bp region of gga-miR-31 was identified as its promoter region. Furthermore, it was predicted and confirmed that the activity of the gga-miR-31 promoter is increased by retinoic acid (RA). The binding of RA to the gga-miR-31 and Stra8 promoter regions was found to be competitive. Through the deletion of C-jun binding sites and the manipulation of C-jun expression levels, it was determined that C-jun inhibits the activity of the gga-miR-31 promoter. Furthermore, the combined treatment of C-jun and RA demonstrated that the positive regulatory effect of RA on the gga-miR-31 promoter is attenuated in the presence of high levels of C-jun. Overall, this study establishes a foundation for further investigation into the regulatory mechanisms of gga-miR-31 action, and provides a new avenue for inducing chicken embryonic stem cells (ESC) to differentiate into spermatogonial stem cells (SSC), and sperm formation.

Napyradiomycin A4 and Its Relate Compounds, a New Anti-PRV Agent and Their Antibacterial Activities, from Streptomyces kebangsaanensis WS-68302.

Two new napyradiomycins derivatives, napyradiomycin A4 (1) and A80915 H (2), along with five known ones, were isolated from the ethyl acetate extract of fermentation culture of Streptomyces kebangsaanensis WS-68302. Their structures were elucidated by extensive spectroscopic analysis, including HR-MS, 1D and 2D NMR, CD spectrum, as well as comparison with literature data. Compound 1 exhibited significant antiviral activity against PRV (Pseudorabies virus) with an IC50 value of 2.056 µM and therapeutic ratio at 14.98, suggesting that it might have potential for development of an antiviral agent. Moreover, compound 1 displayed the strongest inhibition against PRV protein among the tested napyradiomycins in the indirect immunofuorescence assay. Compounds 3 and 4 showed higher activities against swine pathogenic Streptococcus suis than the positive control penicillin G sodium salt, with MIC values of 3.125 and 6.25 µg/mL, respectively. Compounds 1 and 3-6 exhibited moderate antibacterial activity against the swine pathogenic Erysipelothrix rhusiopathiae, with MIC values ranging from 25 to 50 µg/mL.

Antiviral Activity of Benzoheterocyclic Compounds from Soil-Derived Streptomyces jiujiangensis NBERC-24992

Pseudorabies virus (PRV) is a pathogen that causes Aujeszky's disease (AD) in animals, leading to huge economic losses to swine farms. In order to discover anti-PRV compounds, we studied the extracts of the strain Streptomyces jiujiangensis NBERC-24992, which showed significant anti-PRV activity. Eight benzoheterocyclic secondary metabolites, including three new compounds (1-3, virantmycins D-G) and five known compounds (4-8, virantmycin, A-503451 D, A-503451 D acetylate, A-503451 A, and A-503451 B), were isolated from the broth of NBERC-24992. The structures of the new compounds were identified by using extensive spectroscopic data, including mass spectrometry (MS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD). Compound 1 was found to be a novel heterocyclic compound with a tricyclic skeleton from natural product. All compounds were tested for antiviral activity, and 4 (virantmycin) showed an excellent effect against PRV and was better than ribavirin and acyclovir. Our study revealed that chlorine atom and tetrahydroquinoline skeleton were important active moiety for antiviral activity. Virantmycin could be a suitable leading compound for an antiviral drug against PRV.