Photoinduced 1,5-HAT-enabled 1,7-hydrosulfonylation of allylic ethers and amides.

Herein, we report a photoinduced 1,7-hydrosulfonylation of allylic ethers and amides via a sequential Pd-mediated 1,5-HAT process and Pd-catalyzed allylic nucleophilic attack of arylsulfonates. This rationally designed synthetic protocol allows for facile construction of a series of structurally novel allylic sulfonated scaffolds, and features mild conditions, cheap and readily available raw materials and functional group compatibility.

Exploring the causal associations between diet-derived circulating antioxidants and the risk of endometriosis: a Mendelian randomization study.

Background: Numerous observational studies and randomized controlled trials have recently revealed the associations between circulating antioxidants and the risk of endometriosis, while the underlying causal relationship remains unclear. This study aimed to investigate the causal association between genetically determined circulating antioxidants and the risk of endometriosis using Mendelian randomization (MR). Methods: A two-sample MR analysis was conducted using publicly available summary data from genome-wide association studies (GWAS) to investigate the causal impact of genetically determined absolute circulating antioxidants (such as ascorbate, retinol, ß-carotene, and lycopene) and their metabolites (including α-and γ-tocopherol, ascorbate, and retinol) on the risk of endometriosis. The study used inverse variance weighted (IVW) or Wald ratio analyses as the primary estimation method and also conducted sensitivity analyses to assess heterogeneity and pleiotropy. Results: No significant causality was observed for genetically determined circulating antioxidants and the risk of endometriosis. The pooled odds ratios (ORs) for absolute circulating antioxidants were 0.62 (95% CI: 0.32-1.18, retinol), 0.95 (95% CI: 0.79-1.15, ß-carotene), 1.01 (95% CI: 0.95-1.08, lycopene), and 1.00 (95% CI: 0.99-1.02, ascorbate, expressed as a Wald ratio). The pooled ORs indicating the EM risk per unit increase in circulating antioxidant metabolites were 1.04 (95% CI: 0.82-1.33, γ-tocopherol), 0.91 (95% CI: 0.57-1.46, α-tocopherol), 1.03 (95% CI: 0.99-1.07, retinol), and 0.96 (95% CI: 0.87-1.06, ascorbate). Conclusion: Our study demonstrated that increased levels of diet-derived circulating antioxidants were not significantly associated with a reduced risk of endometriosis.

FRAME: flap endonuclease 1-engineered PAM module for precise and sensitive modulation of CRISPR/Cas12a trans-cleavage activity.

CRISPR/Cas12a system, renowned for its precise recognition and efficient nucleic acid cleavage capabilities, has demonstrated remarkable performance in molecular diagnostics and biosensing. However, the reported Cas12a activity regulation methods often involved intricate CRISPR RNA (crRNA) structural adjustments or costly chemical modifications, which limited their applications. Here, we demonstrated a unique enzyme activity engineering strategy using flap endonuclease 1 (FEN1) to regulate the accessibility of the protospacer adjacent motif (PAM) module in the double-stranded DNA activator (FRAME). By identifying the three-base overlapping structure between the target inputs and substrate, FEN1 selectively cleaved and released the 5'-flap containing the 'TTTN' sequence, which triggered the secondary cleavage of FEN1 while forming a nicked PAM, ultimately achieving the sensitive switching of Cas12a's activity. The FRAME strategy exemplified the 'two birds with one stone' principle, as it not only precisely programmed Cas12a's activity but also simultaneously triggered isothermal cyclic amplification. Moreover, the FRAME strategy was applied to construct a sensing platform for detecting myeloperoxidase and miR-155, which demonstrated high sensitivity and specificity. Importantly, it proved its versatility in detecting multiple targets using a single crRNA without redesign. Collectively, the FRAME strategy opens up a novel avenue for modulating Cas12a's activity, promising immense potential in the realm of medical diagnostics.

[Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use].

There are many kinds and dosage forms of Chinese patent medicines for external use on the market, which are widely used in clinical departments. The common adverse reactions of Chinese patent medicines for external use are skin reactions, and those for the rare severe diseases include palpitation, chest tightness, dyspnea, and anaphylactic shock. At present, World Health Organization(WHO), International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH),the United States, the European Union, and Asia-Pacific countries(such as Japan and South Korea) have not issued any pharmacovigilance guideline of Chinese patent medicines for external use. China has not issued any pharmacovigilance guideline for these medicines, only releasing the standard Evaluation of skin adverse reactions caused by Chinese patent medicines for external use(T/CACM 005-2017). To standardize the safe and reasonable use of Chinese patent medicines for external use, Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use was developed with the joint efforts of experts in diverse disciplines. The guideline provides guidance on the monitoring and reporting of adverse reactions/events, identification and assessment of risk signals, and risk control measures in the clinical application of Chinese patent medicines for external use to guide the rational use of these medicines in clinical practice. At the same time, the possible risks and risk control measures in clinical application of Chinese patent medicines for external use are listed for clinical reference. In addition, the guideline provides guidance for risk minimization plans and the standardization of activities related to pharmacovigilance of Chinese patent medicines for external use in China.

Exploring the efficacy of laser speckle contrast imaging in the stratified diagnosis of rosacea: a quantitative analysis of facial blood flow dynamics across varied regions.

Background: Rosacea has a high incidence, significantly impacts quality of life, and lacks sufficient diagnostic techniques. This study aimed to investigate the feasibility of laser speckle contrast imaging (LSCI) for measuring facial blood perfusion in patients with rosacea and to identify differences in blood flow among various facial regions associated with different rosacea subtypes. Methods: From June to December 2023, 45 patients were recruited, with 9 excluded, leaving 36 subjects: 12 with erythematotelangiectatic rosacea (ETR), 12 with papulopustular rosacea (PPR), and 12 healthy controls. The Think View multispectral imaging analyzer assessed inflammation via gray reading values across the full face and five facial areas: forehead, nose, cheeks, and chin. LSCI measured and analyzed blood perfusion in the same areas. Plasma biomarkers interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) were tested in different groups. Results: Both ETR and PPR groups showed increased average blood perfusion and facial inflammation intensity by gray values compared to controls, with statistically significant differences. Average blood perfusion of ETR and PPR groups showed increased values in the forehead, cheeks, and nose, compared to controls, and the values in the cheeks were statistically different between ETR and PPR. The facial inflammation intensity of the ETR group showed increased values in the forehead and cheeks, and the PPR group showed increased gray values in the forehead, cheeks, nose, and chin compared to controls, and the values for the cheeks, nose, and chin were statistically significantly different between ETR and PPR. Plasma biomarkers IL-6, IL-1ß, and TNF-α were significantly elevated in both ETR and PPR groups compared to controls. Conclusion: LSCI is a valuable, non-invasive tool for assessing blood flow dynamics in rosacea, providing a data foundation for clinical research. Different rosacea subtypes exhibit distinct lesion distribution and blood flow patterns, and both ETR and PPR could affect all facial areas, particularly the cheeks in ETR and the forehead, nose, and chin in PPR.

Effects of mycotoxin-producing fungi on the fitness and gut bacterial community of the soil springtail Folsomia candida.

Mycotoxin-producing fungi are widespread and their adverse effects on mammals have been investigated; however, their impacts on soil invertebrates are not fully understood. Folsomia candida is a model soil arthropod that represents an important part of the soil invertebrate community. This study investigated the consequences of F. candida grazing on mycotoxin-producing fungi Fusarium verticillioides, F. graminearum, Aspergillus ochraceus, and A. nidulans. Consuming mycotoxin-producing fungi affected the body size and reproductive ability of F. candida, and altered the gut bacterial composition, with decreased Proteobacteria and increased Actinobacteria (Microbacterium) abundances. Notably, the abundance of foodborne fungi can be detected. Furthermore, certain bacteria isolated from F. candida's gut inhibited the growth of corresponding mycotoxin-producing fungi. The gut bacteria that inhibited mycotoxin-producing fungi growth in Aspergillus groups were also associated with poor fitness parameters and larger disruption in gut microbiota. Importantly, switching back to yeast diets reversed both the fitness parameters and gut bacterial composition. Together, our study demonstrated that grazing of mycotoxin-producing fungi by F. candida resulted in reduced physiological parameters and disturbed the gut bacterial community, and those changes can be restored by switching back to yeast diets, which indicates a strong resilience of springtails to mycotoxin-producing fungi. IMPORTANCE: Mycotoxin-producing fungi are widespread in nature and raise concerns for human and livestock health. Although they share the same ecosystem, interactions between mycotoxin-producing fungi and soil arthropods are not well understood. In this study, we report an unexpected finding that the soil arthropod Folsomia candida is rather tolerant to these mycotoxin-producing fungi. F. candida can survive solely on mycotoxin-producing fungi as a food source with reduced physiological parameters. Moreover, the gut microbial community is disturbed by mycotoxin-producing fungi, and some of the bacteria isolated from F. candida's gut can inhibit the growth of corresponding fungi. Notably, the altered physiological parameters and gut microbiota are restored when a normal diet is reintroduced, suggesting F. candida's resilience to mycotoxin-producing fungi. These findings clarify the impact of toxin-producing diets on F. candida, shedding light on how organisms can build resilience to environmental stimuli.

Photoredox-Catalyzed Phosphine-Mediated Successive Deoxygenation of Sulfonyl Oxime Salts Enables Anti-Markovnikov Hydrothiolation of Alkenes.

Stable and easy-to-handle sodium salts of sulfonyl oximes were first identified to proceed via visible-light-driven phophine-mediated successive deoxygenation to realize the anti-Markovnikov hydrothiolation of alkenes, which could serve as an odorless sulfur source. Mechanistic studies revealed that the key thiyl radical intermediate could be generated in situ from the sulfonyl oxime anion via a phosphine-mediated fragmentation and a sequential deoxygenation process. Notably, a wide range of alkenes, including acrylamides, acrylates, vinyl ketones, vinyl sulfones, and acrylonitriles, are competent substrates for this protocol, which is highly beneficial for the construction of structurally diversified organosulfur compounds.

Cathepsin B modulates microglial migration and phagocytosis of amyloid ß in Alzheimer's disease through PI3K-Akt signaling.

The approval of anti-amyloid ß (Aß) monoclonal antibodies (lecanemab) for the treatment of patients with early preclinical stage of Alzheimer's disease (AD) by the Food and Drug Administration, suggests the reliability and importance of brain Aß clearance for AD therapy. Microglia are the main phagocytes that clear Aß in the brain, but the underlying regulatory mechanism is unclear. Here, we investigate the critical role of cathepsin B (CatB) in modulating microglial Aß clearance from mouse brain. Wild-type or CatB-/- mice were injected with Aß into the hippocampus from 1 to 3 weeks. Mice were evaluated for cognitive change, Aß metabolism, neuroinflammation. Microglia and neuron cultures were prepared to verify the in vivo results. The statistical analyses were performed by student's t test, one-way ANOVA with a post hoc Tukey's test using the GraphPad Prism software package. CatB deficiency significantly reduces Aß clearance efficiency and aggravates mouse cognitive decline. Exogenous Aß markedly increases CatB expression in activated microglia. Transcriptome analysis and in vitro cell culture experiments demonstrate that CatB is associated with gene clusters involved in migration, phagocytosis, and inflammation. In addition, transcriptome analysis and immunoblotting suggest that CatB modulates microglial Aß clearance via PI3K-AKT activation. Our study unveils a previously unknown role of CatB in promoting microglial functionality during Aß clearance.

Pioneering healthcare with soft robotic devices: A review.

Recent advancements in soft robotics have been emerging as an exciting paradigm in engineering due to their inherent compliance, safe human interaction, and ease of adaptation with wearable electronics. Soft robotic devices have the potential to provide innovative solutions and expand the horizons of possibilities for biomedical applications by bringing robots closer to natural creatures. In this review, we survey several promising soft robot technologies, including flexible fluidic actuators, shape memory alloys, cable-driven mechanisms, magnetically driven mechanisms, and soft sensors. Selected applications of soft robotic devices as medical devices are discussed, such as surgical intervention, soft implants, rehabilitation and assistive devices, soft robotic exosuits, and prosthetics. We focus on how soft robotics can improve the effectiveness, safety and patient experience for each use case, and highlight current research and clinical challenges, such as biocompatibility, long-term stability, and durability. Finally, we discuss potential directions and approaches to address these challenges for soft robotic devices to move toward real clinical translations in the future.

Bacterial and Archaeal Communities in Erhai Lake Sediments: Abundance and Metabolic Insight into a Plateau Lake at the Edge of Eutrophication.

The littoral zones of lakes are potential hotspots for local algal blooms and biogeochemical cycles; however, the microbial communities within the littoral sediments of eutrophic plateau lakes remain poorly understood. Here, we investigated the taxonomic composition, co-occurrence networks, and potential functional roles of both abundant and rare taxa within bacterial and archaeal communities, as well as physicochemical parameters, in littoral sediments from Erhai Lake, a mesotrophic lake transitioning towards eutrophy located in the Yunnan-Guizhou Plateau. 16S rRNA gene sequencing revealed that bacterial communities were dominated by Proteobacteria, Bacteroidetes, and Chloroflexi, while Euryarchaeota was the main archaeal phylum. Co-occurrence network analysis revealed that keystone taxa mainly belonged to rare species in the bacterial domain, but in the archaeal domain, over half of keystone taxa were abundant species, demonstrating their fundamental roles in network persistence. The rare bacterial taxa contributed substantially to the overall abundance (81.52%), whereas a smaller subset of abundant archaeal taxa accounted for up to 82.70% of the overall abundance. Functional predictions highlighted a divergence in metabolic potentials, with abundant bacterial sub-communities enriched in pathways for nitrogen cycling, sulfur cycling, and chlorate reduction, while rare bacterial sub-communities were linked to carbon cycling processes such as methanotrophy. Abundant archaeal sub-communities exhibited a high potential for methanogenesis, chemoheterotrophy, and dark hydrogen oxidation. Spearman correlation analysis showed that genera such as Candidatus competibacter, Geobacter, Syntrophobacter, Methanocella, and Methanosarcina may serve as potential indicators of eutrophication. Overall, this study provides insight into the distinct roles that rare and abundant taxa play in the littoral sediments of mesotrophic plateau lakes.

A phosphodiesterase CpdB in Yersinia pseudotuberculosis degrades CDNs to inhibit innate immune response.

Yersinia pseudotuberculosis (Yptb) is a pathogenic gram-negative bacterium that can colonize the intestines of different animals. Its infection leads to the activation of the host's innate immunity. Both host and bacterial-derived cyclic dinucleotides (CDNs) could activate the innate immune response of host cells. In bacteria, CDNs like c-di-AMP, c-di-GMP, or 3'3'-cGAMP can be hydrolyzed by different hydrolases. Recent studies showed that the degradation of those second messengers helps the pathogen evade immune detection. In this study, we identified a hydrolase, YPK_3776, namely CpdB in Yptb. CpdB is predicted to bind bacterial-derived c-di-AMP, c-di-GMP, 3'3'-cGAMP and host-derived 2'3'-cGAMP. Surprisingly, by using high-performance liquid chromatography (HPLC), we found that CpdB could only degrade bacterial-derived CDNs but not host-derived 2'3'-cGAMP. In addition, CpdB has 2'3'-cNMP activity. Consistently, the Yptb mutant lacking the cpdB gene exhibited a higher level of intracellular c-di-GMP. Furthermore, the ∆cpdB mutant elicited stronger innate immune responses during Yptb infection in macrophages, suggesting CpdB enables Yptb to evade host immune surveillance. Furthermore, CpdB inhibited the Yptb-induced innate immune response in a STING-dependent manner. Finally, we showed the ∆cpdB infection in mice model exhibited in lower bacterial burden, as compared to wild-type strain infection, indicating CpdB is important for bacterial survival in the host. Together, we identified a cyclic dinucleotide hydrolase CpdB in Yptb that could degrade bacterial-derived CDNs which help the pathogen to evade immune detection via the STING pathway.

BSA-stabilized selenium nanoparticles ameliorate intracerebral hemorrhage's-like pathology by inhibiting ferroptosis-mediated neurotoxicology via Nrf2/GPX4 axis activation.

Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH.

Specific reference interval for high-sensitivity cardiac troponin I among healthy children in Wuhan, China.

Background: Troponin (Tn) is of an important biomarker for the diagnosis and prognosis of myocardial injury and for evaluating the severity of cardiac involvement due to other systemic diseases in children. Unfortunately, high-sensitivity cardiac troponin I (hs-cTnI) specific reference intervals (RIs) are extremely limited. This study aimed to establish a preliminary pediatric hs-cTnI RI for newborns, children, and adolescents in Wuhan, China. Methods: A total of 1,355 healthy participants (1 day to 19 years) were recruited from a cross-sectional study implemented in Wuhan Children's Hospital from September 2022 to August 2023. Serum hs-cTnI levels were detected via the Mindray automated chemiluminescence immunoassay analyzer (CL-6000i). Specific serum hs-cTnI RIs were established according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The RIs were defined by the nonparametric median (P50), and 2.5th, 97.5th [P50 (P2.5-P97.5)] intervals. Results: Of the 1,355 pediatric participants, serum hs-cTnI concentrations of 1,332 children were measured. The serum overall P50 and 95% interval range (P2.5-P97.5) of serum hs-cTnI was 0.41 (0.00, 44.31) ng/L. This was higher in males of 0.47 (0.00, 44.90) ng/L than in females of 0.36 (0.00, 44.17) ng/L (P<0.01). Age- and sex-specific differences in hs-cTnI levels were observed. The levels were highly variable in children under 1 year of age (especially in newborns), deriving a P50 (P2.5-P97.5) of 22.06 (1.04, 154.22) ng/L, and gradually narrowed and decreased with increasing age, with a markedly lower established P50 (P2.5-P97.5) of 0.36 (0.00, 2.16) ng/L. However, the levels began to increase slightly at the age of 9-12 years and reached a small peak at the age range of 15 to 18 years in males with 0.71 (0.03, 3.29) ng/L, while females were less affected by puberty. Sex- and age-specific RIs for hs-cTnI were established: 5 age-specific RIs in males, 1 day-1 month: 30.16 (8.67, 171.81) ng/L; >1-12 months: 13.20 (0.63, 61.91) ng/L; >1-15 years: 0.36 (0.00, 1.86) ng/L; >15-18 years: 0.71 (0.03, 3.29) ng/L; >18-19 years: 0.52 (0.00, 1.92) ng/L; and 4 age-specific RIs in females, 1 day-1 month: 43.93 (18.82, 146.38) ng/L; >1-12 months: 5.22 (0.92, 42.54) ng/L; >1-6 years: 0.54 (0.00, 2.74) ng/L; >6-19 years: 0.23 (0.00, 1.56) ng/L. Conclusions: This study preliminarily established age- and sex-specific serum hs-cTnI RIs using the Mindray CL-6000i system in healthy children in Wuhan, China.

Fermentation of Polygonati Rhizoma aqueous extract using Lactiplantibacillus plantarum under the condition of eutrophication.

In this experiment, the eutrophication system was established by adding sucrose and yeast powder, and the pH and dissolved oxygen were measured in a bioreactor in real time to study the effect of aerobic environment on the fermentation process of Polygonati Rhizoma extract by Lactiplantibacillus plantarum. To further analyze metabolic changes, UPLC-Q-Exactive MS was used for metabolomic analysis and metabolic profiling. Multivariate analysis was performed using principal component analysis and Orthogonal projections to latent structures discriminant analysis. Finally, 313 differential metabolites were selected, 196 of which were annotated through database matching. After fermentation, the content of short-chain fatty acids, lactic acid, and their derivatives increased significantly, and there were 13 kinds and 4 kinds, respectively. Both compounds and their derivatives are beneficial to the intestinal flora. Consequently, incorporating L. plantarum into the aerobic fermentation process of Polygonati Rhizoma extract within the eutrophic system is potentially advantageous in enhancing the impact of its fermentation solution on the gut microbiota and its effects on human health. Our findings for this kind of edible and medicinal material research and development offer useful insights.

Exploring the inverse relationship between serum total bilirubin and systemic immune-inflammation index: insights from NHANES data (2009-2018).

BACKGROUND: Bilirubin is known for its multifaceted attributes, including antioxidant, anti-inflammatory, immunomodulatory, and antiapoptotic properties. The systemic immune-inflammation index (SII) is a recent marker that reflects the balance between inflammation and immune response. Despite the wealth of information available on bilirubin's diverse functionalities, the potential correlation between the total bilirubin (TB) levels and SII has not been investigated so far. METHODS: Leveraging data from the National Health and Nutrition Examination Survey spanning 2009-2018, the TB levels were categorized using tertiles. Employing the chi-squared test with Rao and Scott's second-order correction and Spearman's rank correlation analysis, the association between TB and SII was examined. The potential nonlinearities between TB and SII were evaluated using restricted cubic spline (RCS) analysis. Weighted linear regression, adjusted for covariates, was used to explore the correlation between TB and SII, with further subgroup analyses. RESULTS: A total of 16,858 participants were included, and the findings revealed significant SII variations across TB tertiles (p < 0.001). The third tertile (Q3) exhibited the lowest SII level at 495.73 (295.00) 1000 cells/µL. Spearman rank correlation disclosed the negative association between TB and SII. RCS analysis exposed the lack of statistically significant variations in the nonlinear relationship (p > 0.05), thereby providing support for a linear relationship. Weighted linear regression analysis underscored the negative correlation between TB and SII (ß 95% CI - 3.9 [- 5.0 to - 2.9], p < 0.001). The increase in the TB levels is associated with a significant linear trend toward decreasing SII. After controlling for relative covariates, this negative correlation increased (p < 0.001). Subgroup analysis confirmed the significant negative TB-SII association. CONCLUSION: A notable negative correlation between TB and SII implies the potential protective effects of bilirubin in inflammation-related diseases.

Extracellular Matrix Remodeling Alleviates Memory Deficits in Alzheimer's Disease by Enhancing the Astrocytic Autophagy-Lysosome Pathway.

Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer's disease (AD) risk; however, the underlying mechanisms are not fully understood. Here, it is found that the injection of chondroitinase ABC (ChABC), mimicking ECM remodeling, into the medial prefrontal cortex (mPFC) reversed short-term memory loss and reduced amyloid-beta (Aß) deposition in 5xFAD mice. ECM remodeling also reactivated astrocytes, reduced the levels of aggrecan in Aß plaques, and enhanced astrocyte recruitment to surrounding plaques. Importantly, ECM remodeling enhanced the autophagy-lysosome pathway in astrocytes, thereby mediating Aß clearance and alleviating AD pathology. ECM remodeling also promoted Aß plaque phagocytosis by astrocytes by activating the astrocytic phagocytosis receptor MERTK and promoting astrocytic vesicle circulation. The study identified a cellular mechanism in which ECM remodeling activates the astrocytic autophagy-lysosomal pathway and alleviates AD pathology. Targeting ECM remodeling may represent a potential therapeutic strategy for AD and serve as a reference for the treatment of this disease.

Unveil cis-acting combinatorial mRNA motifs by interpreting deep neural network.

SUMMARY: Cis-acting mRNA elements play a key role in the regulation of mRNA stability and translation efficiency. Revealing the interactions of these elements and their impact plays a crucial role in understanding the regulation of the mRNA translation process, which supports the development of mRNA-based medicine or vaccines. Deep neural networks (DNN) can learn complex cis-regulatory codes from RNA sequences. However, extracting these cis-regulatory codes efficiently from DNN remains a significant challenge. Here, we propose a method based on our toolkit NeuronMotif and motif mutagenesis, which not only enables the discovery of diverse and high-quality motifs but also efficiently reveals motif interactions. By interpreting deep-learning models, we have discovered several crucial motifs that impact mRNA translation efficiency and stability, as well as some unknown motifs or motif syntax, offering novel insights for biologists. Furthermore, we note that it is challenging to enrich motif syntax in datasets composed of randomly generated sequences, and they may not contain sufficient biological signals. AVAILABILITY AND IMPLEMENTATION: The source code and data used to produce the results and analyses presented in this manuscript are available from GitHub (https://github.com/WangLabTHU/combmotif).

Screening of reference genes for gene expression study in different tissues from the transcriptome data of the vector leafhopper Psammotettix striatus.

Selecting appropriate reference genes is crucial for ensuring the accuracy and reliability of gene expression study using reverse transcription-quantitative PCR (RT-qPCR). To screen the optimal reference genes for analyzing gene expression in different tissues of the vector leafhopper Psammotettix striatus which causes extensive damage to a wide range of crops by vectoring multiple plant pathogenic microorganisms, the transcriptome data from Malpighian tubules (MTs) of P. striatus were mined. Twenty alternative candidate reference genes were initially selected for screening, among which seven genes with diverse Gene Ontology (GO) annotations were choosed as candidate reference genes, i.e., ribosomal protein L7A (RPL7A), ribosomal protein S28 (RPS28), ribosomal protein L22 (RPL22), ribosomal protein LP2 (RPLP2), H3 histone family 3A (H3F3A), elongation factor 1γ (EF-1γ), and elongation factor 1α (EF-1α). Gene expression levels in different tissues of P. striatus adults were examined using RT-qPCR, and their expression stability was analyzed using multiple reference gene screening software. This study revealed EF-1α as the most abundantly expressed gene, while RPL22 exhibited the lowest expression levels. EF-1α showed the most stable expression, whereas RPS28 showed the least stability. Various software tools confirmed EF-1α as the most stable single reference gene, and EF-1α and RPLP2 an optimal combination. This study provides a foundation for future investigation of the transmission of pathogenic microorganisms mediated by the vector leafhoppers, the function of the MTs, the biosynthesis of brochosomes, the coevolutionary processes and nutritional interactions of symbionts and host insects, and the gene expression study of other sap-sucking insects.

The impact of physical therapy on dysphagia in neurological diseases: a review.

A neurogenic dysphagia is dysphagia caused by problems with the central and peripheral nervous systems, is particularly prevalent in conditions such as Parkinson's disease and stroke. It significantly impacts the quality of life for affected individuals and causes additional burdens, such as malnutrition, aspiration pneumonia, asphyxia, or even death from choking due to improper eating. Physical therapy offers a non-invasive treatment with high efficacy and low cost. Evidence supporting the use of physical therapy in dysphagia treatment is increasing, including techniques such as neuromuscular electrical stimulation, sensory stimulation, transcranial direct current stimulation, and repetitive transcranial magnetic stimulation. While initial studies have shown promising results, the effectiveness of specific treatment regimens still requires further validation. At present, there is a lack of scientific evidence to guide patient selection, develop appropriate treatment regimens, and accurately evaluate treatment outcomes. Therefore, the primary objectives of this review are to review the results of existing research, summarize the application of physical therapy in dysphagia management, we also discussed the mechanisms and treatments of physical therapy for neurogenic dysphagia.