LAMTOR1/mTORC1 promotes CD276 to induce immunosuppression via PI3K/Akt/MMP signaling pathway in Clostridium perfringens-induced necrotic enteritis of laying hens.

Clostridium perfringens (C. perfringens) causes avian necrotic enteritis, leading to huge economic losses to the poultry industry. This pathogen induces host immunosuppression; however, the molecular mechanism is still unclear. Thus, we established a laying hen infection model to explore this mechanism. We randomly divided 20 one-old-day laying hens into the control and infection groups. The infection group was infected intragastrically with 1 × 109 colony-forming units of C. perfringens in 1 mL of sterile phosphate-buffered saline (PBS) once a day from d 17 to 20; the control group received the same volume of PBS without the bacterium. Twenty-four hours after the last challenge, we sacrificed the laying hens and collected the jejunum for analysis. The infection group presented alterations in blood biochemical parameters and necrotic lesion scores as well as damage to the jejunum. Proteomics revealed 427 upregulated and 291 downregulated proteins in the infection group. In the infection group, CD3, CD4, and CD8 messenger RNA expression (mRNA) expression was decreased; LAMTOR1 and mTORC1 mRNA expression was increased; CD276 protein expression was enhanced; and the PI3K/Akt/MMP pathway was activated in jejunum of laying hens. This is the first study to report CD276 expression in the jejunum related to immunosuppression in a laying hen model of necrotic enteritis. It provides some new key targets to potentially control avian necrotic enteritis.

Cancer Prevention and Treatment on Chinese Social Media: Machine Learning-Based Content Analysis Study.

BACKGROUND: Nowadays, social media plays a crucial role in disseminating information about cancer prevention and treatment. A growing body of research has focused on assessing access and communication effects of cancer information on social media. However, there remains a limited understanding of the comprehensive presentation of cancer prevention and treatment methods across social media platforms. Furthermore, research comparing the differences between medical social media (MSM) and common social media (CSM) is also lacking. OBJECTIVE: Using big data analytics, this study aims to comprehensively map the characteristics of cancer treatment and prevention information on MSM and CSM. This approach promises to enhance cancer coverage and assist patients in making informed treatment decisions. METHODS: We collected all posts (N=60,843) from 4 medical WeChat official accounts (accounts with professional medical backgrounds, classified as MSM in this paper) and 5 health and lifestyle WeChat official accounts (accounts with nonprofessional medical backgrounds, classified as CSM in this paper). We applied latent Dirichlet allocation topic modeling to extract cancer-related posts (N=8427) and identified 6 cancer themes separately in CSM and MSM. After manually labeling posts according to our codebook, we used a neural-based method for automated labeling. Specifically, we framed our task as a multilabel task and utilized different pretrained models, such as Bidirectional Encoder Representations from Transformers (BERT) and Global Vectors for Word Representation (GloVe), to learn document-level semantic representations for labeling. RESULTS: We analyzed a total of 4479 articles from MSM and 3948 articles from CSM related to cancer. Among these, 35.52% (2993/8427) contained prevention information and 44.43% (3744/8427) contained treatment information. Themes in CSM were predominantly related to lifestyle, whereas MSM focused more on medical aspects. The most frequently mentioned prevention measures were early screening and testing, healthy diet, and physical exercise. MSM mentioned vaccinations for cancer prevention more frequently compared with CSM. Both types of media provided limited coverage of radiation prevention (including sun protection) and breastfeeding. The most mentioned treatment measures were surgery, chemotherapy, and radiotherapy. Compared with MSM (1137/8427, 13.49%), CSM (2993/8427, 35.52%) focused more on prevention. CONCLUSIONS: The information about cancer prevention and treatment on social media revealed a lack of balance. The focus was primarily limited to a few aspects, indicating a need for broader coverage of prevention measures and treatments in social media. Additionally, the study's findings underscored the potential of applying machine learning to content analysis as a promising research approach for mapping key dimensions of cancer information on social media. These findings hold methodological and practical significance for future studies and health promotion.

TgMIC6 inhibition of autophagy is partially responsible for the phenotypic differences between Chinese 1 Toxoplasma gondii strains.

Chinese1 is the predominant Toxoplasma gondii lineage in China, and significant phenotypic differences are observed within the lineage. WH3 and WH6 are two representative strains of Chinese 1, which exhibit divergent virulence and pathogenicity in mice. However, virulence determinants and their modulating mechanisms remain elusive. A global genome expression analysis of the WH3 and WH6 transcriptional profiles identified microneme secretory protein 6 (MIC6), which may be associated with the phenotypic difference observed in WH3. In the present study, the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome-editing technique was used to generate a T. gondii microneme secretory protein (TgMIC6) knockout in WH3. Wild-type mice and different mouse and human cell lines were infected with the WH3, WH3-Δmic6, and WH6 strains. The survival rate of mice, related cytokine levels in serum, and the proliferation of parasites were observed. These results suggested that TgMIC6 is an important effector molecule that determines the differential virulence of WH3 in vivo and in vitro. Furthermore, MIC6 may enhance WH3 virulence via inhibition of host cell autophagy and activation of key molecules in the epidermal growth factor receptor (EGFR)-Akt-mammalian target of rapamycin (mTOR) classical autophagy pathway. CD40L was cleared in vivo by i.p injection of CD40L monoclonal antibody, and it was found that the virulence of WH3-Δmic6 to mice was restored to a certain extent in the absence of CD40L. This study elucidates the virulence determinants and immune escape strategies of Toxoplasma gondii in China. Moreover, these data will aid the development of effective strategies for the prevention and control of toxoplasmosis.

Design of Three-Dimensional Mesoporous Adamantane-Based Covalent Organic Framework with Exceptionally High Surface Areas.

The development of three-dimensional (3D) covalent organic frameworks (COFs) with large pores and high specific surface areas is of critical for practical applications. However, it remains a tremendous challenge to reconcile the contradiction between high porosity and high specific surface areas, and increasing the length of building blocks leads to structural interpenetration in 3D COFs. Here, we report the preparation of mesoporous three-dimensional COF by a new steric hindrance engineering method. By incorporating adamantane into the monomers instead of carbon centers, we successfully achieve 2-fold interpenetrated diamondoid-structured 3D COFs, featuring permanent mesopores (up to 33 Å), exceptionally high surface areas (>3400 m2 g-1), and low crystal densities (0.123 g cm-3). These properties far surpass those of most conventional 3D COFs with similar topologies. This work not only aims to construct 3D COFs with low interpenetration but also to establish a foundation for the systematic design and structural control of 3D COFs.

Analysis of hemorrhagic drug-drug interactions between P-gp inhibitors and direct oral anticoagulants from the FDA Adverse Event Reporting System.

BACKGROUND: Limited understanding exists regarding the hemorrhagic risk resulting from potential interactions between P-glycoprotein (P-gp) inhibitors and direct oral anticoagulants (DOACs). Utilizing the Food and Drug Administration Adverse Event Reporting System (FAERS) data, we analyzed hemorrhagic adverse events (AEs) linked with the co-administration of P-gp inhibitors and DOACs, aiming to offer guidance for their safe and rational use. METHODS: Hemorrhagic events associated with P-gp inhibitors in combination with DOACs were scrutinized from the FAERS database. Hemorrhagic signals mining was performed by estimating the reported odds ratios (RORs), corroborated by additive and multiplicative models and a combination risk ratio (PRR) model. RESULTS: Our analysis covered 4,417,195 cases, revealing 11,967 bleeding events associated with P-gp inhibitors. We observed a significantly higher risk of bleeding with the combination of apixaban and felodipine (ROR 118.84, 95% CI 78.12-180.79, additive model 0.545, multiplicative model 1.253, PRR 22.896 (2450.141)). Moreover, consistent associations were found in the co-administration analyzes of rivaroxaban with dronedarone and diltiazem, and apixaban with losartan, telmisartan, and simvastatin. CONCLUSION: Our FAERS data analysis unveils varying degrees of bleeding risk associated with the co-administration of P-gp inhibitors and DOACs, underscoring the importance of vigilance about them in clinical practice.

The male germ unit association is independently regulated of GUM in Arabidopsis thaliana.

Cytoplasmic projections (CPs) formed by the generative and sperm cells link the male gametes with the vegetative cell (VC) nucleus, which are required to build the male germ unit (MGU) assemblage in the angiosperm pollen grain. As molecular and genetic controls underlying CP development and formation of the MGU are unknown, it was hypothesized that physical association between germ cells and the VC nucleus might be lost in germ unit malformed (gum) mutants or in those which either block generative cell (GC) division or that additionally prevent gamete differentiation. In vivo, analysis of marked cellular components demonstrated a linkage of sperm cells (SCs) and the VC nucleus in gum mutant alleles despite their increased physical separation. Similarly, for several independent classes of bicellular pollen mutants, undivided GCs were associated with the VC nucleus like GCs in wild-type pollen. We conclude that the early formation of GC CPs to establish the MGU is regulated independently of DUO1-DAZ1 and DUO3 transcription factors as well as cyclin-dependent kinase function (CDKA;1). As the absence of cytoplasmic protrusion was expected in the gum mutants in Arabidopsis, early histological studies reported temporal disappearance of cytoplasmic protrusion in several organisms. Our findings demonstrated the striking importance of live imaging to verify the broad conservation of the persistent MGU contact in all the angiosperms and its important role in successful double fertilization.

Anemoside B4 attenuates necrotic enteritis of laying hens induced by Clostridium perfringens via inhibiting NF-κB and PI3K/Akt/mTOR signalling pathways.

Poultry necrotic enteritis is an important enteric disease which might be controlled by antibiotics. However, with the excessive use of antibiotics, the phenomenon of drug resistance of Clostridium perfringens is becoming increasingly prominent. Anemoside B4 exhibits important anti-inflammatory, antioxidant and immunomodulatory effects. This study was performed to estimate the effect of Anemoside B4 on chicken necrotic enteritis induced by C. perfringens in vivo and in vitro. In the in vivo experiment we investigated the efficacy of Anemoside B4 on the growth curve, biofilm formation, haemolytic activity, virulence-related gene expression and NF-κB and PI3K/AKT/mTOR activation in Caco-2 cells induced by C. perfringens. The results showed that 12.5-50 µg/mL Anemoside B4 had no antibacterial activity but could inhibit biofilm formation, attenuate haemolytic activity and virulence-related gene expression of C. perfringens and weaken NF-κB and PI3K/Akt/mTOR activation triggered by C. perfringens in Caco-2 cells. In the in vivo experiment, 60 17-day-old healthy White Leghorns were randomly divided into six groups. The growing laying hens of the control group were fed a basic diet, and those of the five challenged groups were fed a basic diet (infection group), added 0.43 g/kg Anemoside B4 (0.43 g/kg Ane group), 0.86 g/kg Anemoside B4 (0.86 g/kg Ane group), 1.72 g/kg Anemoside B4 (1.72 g/kg Ane group) and 40 mg/kg lincomycin (lincomycin group), respectively. All challenged laying hens were infected with 1 × 109 CFU C. perfringens from day 17-20. Blood and intestinal samples were obtained, and the data demonstrated that Anemoside B4 improved the blood biochemical parameters, attenuated jejunum tissue injury, increased the spleen, thymus, bursa of fabricius index, and decreased lesion scores of the jejunum and the ileum. In the jejunum, Anemoside B4 and lincomycin downregulated the expression of IL-1ß, IL-6, IL-10, TNF-α and IFN-γ at mRNA levels. Moreover, Anemoside B4 significantly enhanced both mRNA and protein levels of tight junctions ZO-1, Claudin-1 and MUC-2 in the jejunum. Anemoside B4 weakened p-P65, p-PI3K, p-Akt and p-mTOR protein expression in the jejunum infected by C. perfringens. Diets supplemented with Anemoside B4 alleviated C. perfringens-induced necrotic enteritis in laying hens by inhibiting NF-κB and PI3K/Akt/mTOR signalling pathways and improving intestinal barrier functions.

Construction and application of medication reminder system: intelligent generation of universal medication schedule.

BACKGROUND: Patients with chronic conditions need multiple medications daily to manage their condition. However, most patients have poor compliance, which affects the effectiveness of treatment. To address these challenges, we establish a medication reminder system for the intelligent generation of universal medication schedule (UMS) to remind patients with chronic diseases to take medication accurately and to improve safety of home medication. METHODS: To design medication time constraint with one drug (MTCOD) for each drug and medication time constraint with multi-drug (MTCMD) for each two drugs in order to better regulate the interval and time of patients' medication. Establishment of a medication reminder system consisting of a cloud database of drug information, an operator terminal for medical staff and a patient terminal. RESULTS: The cloud database has a total of 153,916 pharmaceutical products, 496,708 drug interaction data, and 153,390 pharmaceutical product-ingredient pairs. The MTCOD data was 153,916, and the MTCMD data was 8,552,712. An intelligent UMS medication reminder system was constructed. The system can read the prescription information of patients and provide personalized medication guidance with medication timeline for chronic patients. At the same time, patients can query medication information and get remote pharmacy guidance in real time. CONCLUSIONS: Overall, the medication reminder system provides intelligent medication reminders, automatic drug interaction identification, and monitoring system, which is helpful to monitor the entire process of treatment in patients with chronic diseases.

Optimizing medication guidance support for patients with cancer pain: development and evaluation of a pharmaceutical care system for healthcare professionals.

BACKGROUND: Effective management of cancer pain critically depends on timely medication administration and adherence to precise medication guidelines. In the context of limited time and a busy healthcare environment, tailoring the optimal medication schedule for each patient with cancer pain presents a significant challenge for physicians and clinical pharmacists. METHODS: To address this challenge, we conducted a comprehensive analysis of healthcare professionals' needs in guiding cancer pain medication. By developing core features based on key user needs and continuously updating them, we have created the Universal Medication Schedule System (UMSS). We invited 20 physicians and pharmacists specializing in oncology or cancer pain to trial the system and assessed UMSS usage through distributed questionnaires. RESULTS: We identified five key needs of healthcare professionals in cancer pain medication guidance. Based on these needs, we (1) constructed a comprehensive drug information database, including basic information for 1135 drugs, 130,590 drug interaction data entries, and 1409 individual medication timing constraints, and (2) developed a web-based system that provides essential reference information such as drug interactions and dietary restrictions. It can create medication schedules and provide medication education tailored to the patient's daily routine. Participating evaluators unanimously agreed (100%) that the system aids in accurately assessing the risks of polypharmacy and quickly scheduling medication regimens. CONCLUSION: UMSS, by offering personalized medication schedule support, assists healthcare professionals in better managing patients' medication treatment plans. However, further improvements are needed in the automation of database updates and maintenance, as well as in integrating it with electronic health records.

Baicalin attenuates PD-1/PD-L1 axis-induced immunosuppression in piglets challenged with Glaesserella parasuis by inhibiting the PI3K/Akt/mTOR and RAS/MEK/ERK signalling pathways.

Infection of piglets with Glaesserella parasuis (G. parasuis) induces host immunosuppression. However, the mechanism underlying the immunosuppression of piglets remains unclear. Activation of the PD-1/PD-L1 axis has been shown to trigger host immunosuppression. Baicalin possesses anti-inflammatory and immunomodulatory functions. However, whether baicalin inhibits PD-1/PD-L1 activation and thus alleviates host immunosuppression has not been investigated. In this study, the effect of baicalin on the attenuation of piglet immunosuppression induced by G. parasuis was evaluated. Seventy piglets were randomly divided into the control group, infection group, levamisole group, BMS-1 group, 25 mg/kg baicalin group, 50 mg/kg baicalin group and 100 mg/kg baicalin group. Following pretreatment with levamisole, BMS-1 or baicalin, the piglets were challenged with 1 × 108 CFU of G. parasuis. Our results showed that baicalin, levamisole and BMS-1 modified routine blood indicators and biochemical parameters; downregulated IL-1ß, IL-10, IL-18, TNF-α and IFN-γ mRNA expression; and upregulated IL-2 and IL-8 mRNA expression in blood. Baicalin, levamisole and BMS-1 increased the proportions of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD3-CD21+ B cells in the splenocyte population, increased the proportions of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells in the blood, and inhibited PD-1/PD-L1 and TIM-3 activation. Baicalin, levamisole and BMS-1 reduced p-PI3K, p-Akt, and p-mTOR expression, the p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 ratios and increased RAS expression. Baicalin, levamisole and BMS-1 provided substantial protection against G. parasuis challenge and relieved tissue histopathological damage. Our findings might provide new strategies for controlling G. parasuis infection and other immunosuppressive diseases.

Baicalin and probenecid protect against Glaesserella parasuis challenge in a piglet model.

Glaesserella parasuis (G. parasuis) induces vascular damage and systemic inflammation. However, the mechanism by which it causes vascular damage is currently unclear. Baicalin has important anti-inflammatory, antibacterial and immunomodulatory functions. In this study, we explored the ability of baicalin and probenecid to protect against G. parasuis challenge in a piglet model. Sixty piglets were randomly divided into a control group; an infection group; a probenecid group; and 25 mg/kg, 50 mg/kg and 100 mg/kg baicalin groups. The probenecid group and the 25 mg/kg, 50 mg/kg and 100 mg/kg baicalin groups were injected intramuscularly with 20 mg/kg body weight (BW) probenecid and 25 mg/kg BW, 50 mg/kg BW and 100 mg/kg BW baicalin, respectively. All piglets except those from the control group were injected intraperitoneally with 1 × 108 CFU of G. parasuis. The control group was injected intraperitoneally with TSB. The results showed baicalin and probenecid protected piglets against G. parasuis challenge, improved body weight and decreased temperature changes in piglets. Baicalin and probenecid attenuated IL-1ß, IL-10, IL-18, TNF-α and IFN-γ mRNA levels in the blood for 48 h, inhibited the production of the nucleosides ATP, ADP, AMP and UMP from 24 to 72 h, reduced Panx-1/P2Y6/P2X7 expression, weakened NF-kB, AP-1, NLRP3/Caspase-1 and ROCK/MLCK/MLC signalling activation, and upregulated VE-cadherin expression in the blood vessels of piglets challenged with G. parasuis. Baicalin and probenecid alleviated pathological tissue damage in piglets induced by G. parasuis. Our results might provide a promising strategy to control and treat G. parasuis infection in the clinical setting.

Ethnopharmacology, chemical composition and functions of Cymbopogon citratus.

Cymbopogon citratus in the gramineous family, also known as lemongrass (LG), is a perennial herb. LG, a drug and food homologous medicine, has a widely recorded medicinal value and food applications. To date, 158 LG compounds have been reported, including terpenoids, flavonoids, phenolic acids. Pharmacological and clinical studies have indicated that LG has antibacterial, neuroprotective, hypoglycemic, hypotensive, anti-inflammatory, and anti-tumor effects. This article reviews LG in ethnopharmacology, chemical composition, pharmacology, food, medicine, and daily chemical applications to provide a basis for the subsequent development of food and medicine.

Rapid and Sustained Effect of Ixekizumab on Patient Global, Spinal Pain, Stiffness, and Fatigue in Chinese Patients with Radiographic Axial Spondyloarthritis.

INTRODUCTION: Ixekizumab, an interleukin 17A (IL-17A) inhibitor, has demonstrated rapid and sustained improvement in the signs and symptoms in patients with active radiographic axial spondyloarthritis (r-axSpA) in global and Chinese populations. We studied the effect of ixekizumab on patient-reported outcomes (PROs) (including patient global, spinal pain, stiffness, and fatigue) and overall health-related quality of life (HRQoL) of ixekizumab in the phase 3 study in China. METHODS: In this Chinese phase 3, randomized, double-blind, placebo-controlled study, patients with r-axSpA were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg) or placebo for 16 weeks. At week 16, patients receiving placebo were switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. Data for patient global, spinal pain, spinal pain at night, stiffness, and fatigue were collected through week 52. Minimally clinical important differences (MCIDs) were determined for spinal pain and spinal pain at night. The subgroup analyses by baseline disease duration since diagnosis and baseline C-reactive protein (CRP) level were conducted post hoc. RESULTS: Compared with placebo, patients treated with IXEQ4W reported significantly greater improvement with a rapid onset in changes from baseline of PROs (patient global, spinal pain, spinal pain at night, stiffness, and fatigue) through week 16. Improvements were maintained through week 52. A similar trend of improvement was also observed in MCID response in spinal pain and spinal pain at night. The improvement in overall HRQoL was supported by EQ-5D-5L assessment. Subgroup analyses demonstrated that IXEQ4W provided significantly greater efficacy at week 16 compared with placebo, irrespective of baseline disease duration or baseline CRP level. CONCLUSION: IXEQ4W provided rapid and sustained improvement in clinically relevant PROs and overall HRQoL through 1-year treatment in Chinese patients with r-axSpA. Regardless of the baseline disease duration or baseline CRP level, consistent efficacy was observed. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04285229.

Synergistic effect of combining umami substances enhances perceived saltiness.

Umami substances have the potential to enhance the perception of saltiness and thus reduce sodium intake. Two sensory evaluation experiments were conducted, involving participants tasting salt solutions, and solutions with added umami substances at equal sodium concentrations. Umami substances included sodium glutamate (MSG), disodium inosinate (IMP), and the combination of them which has a synergistic effect and is a closer match to commonly-consumed foods. In Experiment 1, using the two-alternative forced-choice (2-AFC) method by 330 consumers, paired comparisons were conducted at three different sodium concentrations. The combination of MSG and IMP enhanced the perception of saltiness (p < .001 in the difference test), whereas presenting either umami substance in isolation failed to do so (p > .05 in the similarity test). Significant order effects occurred in paired comparisons. In Experiment 2, a two-sip time-intensity (TI) analysis with trained panellists verified these results and found that tasting MSG and IMP either simultaneously or successively enhanced saltiness perception at equal sodium concentrations. These findings indicate that the synergistic effect of umami substances may be the cause of saltiness enhancement, and represents a potential strategy for sodium reduction while satisfying the consumer demand for saltiness perception. Considering the application in food processing and in food pairing, umami substances can potentially be used to help to reduce salt intake in food consumption.

The phosphate starvation response regulator PHR2 antagonizes arbuscule maintenance in Medicago.

Phosphate starvation response (PHR) transcription factors play essential roles in regulating phosphate uptake in plants through binding to the P1BS cis-element in the promoter of phosphate starvation response genes. Recently, PHRs were also shown to positively regulate arbuscular mycorrhizal colonization in rice and lotus by controlling the expression of many symbiotic genes. However, their role in arbuscule development has remained unclear. In Medicago, we previously showed that arbuscule degradation is controlled by two SPX proteins that are highly expressed in arbuscule-containing cells. Since SPX proteins bind to PHRs and repress their activity in a phosphate-dependent manner, we investigated whether arbuscule maintenance is also regulated by PHR. Here, we show that PHR2 is a major regulator of the phosphate starvation response in Medicago. Knockout of phr2 showed reduced phosphate starvation response, symbiotic gene expression, and fungal colonization levels. However, the arbuscules that formed showed less degradation, suggesting a negative role for PHR2 in arbuscule maintenance. This was supported by the observation that overexpression of PHR2 led to enhanced degradation of arbuscules. Although many arbuscule-induced genes contain P1BS elements in their promoters, we found that the P1BS cis-elements in the promoter of the symbiotic phosphate transporter PT4 are not required for arbuscule-containing cell expression. Since both PHR2 and SPX1/3 negatively affect arbuscule maintenance, our results indicate that they control arbuscule maintenance partly via different mechanisms. While PHR2 potentiates symbiotic gene expression and colonization, its activity in arbuscule-containing cells needs to be tightly controlled to maintain a successful symbiosis in Medicago.

The Immunomodulatory effect of exosomes in diabetes: a novel and attractive therapeutic tool in diabetes therapy.

Exosomes carry proteins, metabolites, nucleic acids and lipids from their parent cell of origin. They are derived from cells through exocytosis, are ingested by target cells, and can transfer biological signals between local or distant cells. Therefore, exosomes are often modified in reaction to pathological processes, including infection, cancer, cardiovascular diseases and in response to metabolic perturbations such as obesity and diabetes, all of which involve a significant inflammatory aspect. Here, we discuss how immune cell-derived exosomes origin from neutrophils, T lymphocytes, macrophages impact on the immune reprogramming of diabetes and the associated complications. Besides, exosomes derived from stem cells and their immunomodulatory properties and anti-inflammation effect in diabetes are also reviewed. Moreover, As an important addition to previous reviews, we describes promising directions involving engineered exosomes as well as current challenges of clinical applications in diabetic therapy. Further research on exosomes will explore their potential in translational medicine and provide new avenues for the development of effective clinical diagnostics and therapeutic strategies for immunoregulation of diabetes.

Transcription directionality is licensed by Integrator at active human promoters.

A universal characteristic of eukaryotic transcription is that the promoter recruits RNA polymerase II (RNAPII) to produce both precursor mRNAs (pre-mRNAs) and short unstable promoter upstream transcripts (PROMPTs) toward the opposite direction. However, how the transcription machinery selects the correct direction to produce pre-mRNAs is largely unknown. Here, through multiple acute auxin-inducible degradation systems, we show that rapid depletion of an RNAPII-binding protein complex, Integrator, results in robust PROMPT accumulation throughout the genome. Interestingly, the accumulation of PROMPTs is compensated by the reduction of pre-mRNA transcripts in actively transcribed genes. Consistently, Integrator depletion alters the distribution of polymerase between the sense and antisense directions, which is marked by increased RNAPII-carboxy-terminal domain Tyr1 phosphorylation at PROMPT regions and a reduced Ser2 phosphorylation level at transcription start sites. Mechanistically, the endonuclease activity of Integrator is critical to suppress PROMPT production. Furthermore, our data indicate that the presence of U1 binding sites on nascent transcripts could counteract the cleavage activity of Integrator. In this process, the absence of robust U1 signal at most PROMPTs allows Integrator to suppress the antisense transcription and shift the transcriptional balance in favor of the sense direction.

Role of calcium nutrition in plant Physiology: Advances in research and insights into acidic soil conditions - A comprehensive review.

Plant mineral nutrition has immense significance for crop productivity and human well-being. Soil acidity plays a major role in determining the nutrient availability that influences plant growth. The importance of calcium (Ca) in biological processes, such as signaling, metabolism, and cell growth, underlines its critical role in plant growth and development. This review focuses on soil acidification, a gradual process resulting from cation leaching, fertilizer utilization, and drainage issues. Soil acidification significantly hampers global crop production by modifying nutrient accessibility. In acidic soils, essential nutrients, such as nitrogen (N), phosphorus (P), potassium (K), magnesium (Mg), and Ca become less accessible, establishing a correlation between soil pH and plant nutrition. Cutting-edge Ca nutrition technologies, including nanotechnology, genetic engineering, and genome sequencing, offer the potential to deliver Ca and reduce the reliance on conventional soluble fertilizers. These fertilizers not only contribute to environmental contamination but also impose economic burdens on farmers. Nanotechnology can enhance nutrient uptake, and Ca nanoparticles improve nutrient absorption and release. Genetic engineering enables the cultivation of acid-tolerant crop varieties by manipulating Ca-related genes. High-throughput technologies such as next-generation sequencing and microarrays aid in identifying the microbial structures, functions, and biosynthetic pathways involved in managing plant nutritional stress. The ultimate goal is to shed light on the importance of Ca, problems associated with soil acidity, and potential of emerging technologies to enhance crop production while minimizing the environmental impact and economic burden on farmers.

PD-1/PD-L1 axis induced host immunosuppression via PI3K/Akt/mTOR signalling pathway in piglets infected by Glaesserella Parasuis.

Glaesserella parasuis, an important respiratory bacterial pathogen, causes Glässer's disease in piglets, with potential immunosuppression. We established a piglet infection model and explored the immunosuppression mechanism to improve our understanding of the host immune response to G. parasuis. Twenty piglets were randomly divided into two groups (n = 10). The infection group was intraperitoneally challenged with 2 × 108 CFU of G. parasuis in 2 mL TSB. The control group was intraperitoneally injected with equivalent TSB. After 72 h, the piglets were sacrificed, and spleen tissue was collected. PD-1/PD-L1 expression was determined. The splenocytes were isolated to detect CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3-CD21+cell differentiation. Via data-independent acquisition (DIA), we compared the proteomics of healthy and infected spleen tissues. Glaesserella parasuis modified CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3-CD21+ cell differentiation and PD-1/PD-L1 expression in the spleen. The infection group had 596 proteins with significant differences in expression, of which 301 were significantly upregulated and 295 downregulated. Differentially expressed proteins (DEPs) were mainly related to immune responses. This is the first study on PD-1/PD-L1 expression in the spleen associated with immunosuppression in a piglet model to explore the protein changes related to immune responses via DIA.

Biomimetic Structure and Surface for Grasping Tasks.

Under water, on land, or in the air, creatures use a variety of grasping methods to hunt, avoid predators, or carry food. Numerous studies have been conducted to construct a bionic surface for grasping tasks. This paper reviews the typical biomimetic structures and surfaces (wedge-shaped surface, suction cup surface and thorn claw surface) for grasping scenarios. Initially, progress in gecko-inspired wedge-shaped adhesive surfaces is reviewed, encompassing the underlying mechanisms that involve tuning the contact area and peeling behavior. The applications of grippers utilizing this adhesive technology are also discussed. Subsequently, the suction force mechanisms and applications of surfaces inspired by octopus and remora suction cups are outlined. Moreover, this paper introduces the applications of robots incorporating the principles of beetle-inspired and bird-inspired thorn claw structures. Lastly, inspired by remoras' adhesive discs, a composite biomimetic adhesive surface is proposed. It integrates features from wedge-shaped, suction cup, and claw thorn surfaces, potentially surpassing the adaptability of basic bioinspired surfaces. This surface construction method offers a potential avenue to enhance adhesion capabilities with superior adaptability to surface roughness and curvature.