A full-length glycoprotein mRNA vaccine confers complete protection against severe fever with thrombocytopenia syndrome virus, with broad-spectrum protective effects against bandaviruses.

Highly pathogenic viruses from family Phenuiviridae, which are mainly transmitted by arthropods, have intermittently sparked epidemics worldwide. In particular, tick-borne bandaviruses, such as severe fever with thrombocytopenia syndrome virus (SFTSV), continue to spread in mountainous areas, resulting in an average mortality rate as high as 10.5%, highlighting the urgency and importance of vaccine development. Here, an mRNA vaccine developed based on the full-length SFTSV glycoprotein, containing both the receptor-binding domain and the fusion domain, was shown to confer complete protection against SFTSV at a very low dose by triggering a type 1 helper T cell-biased cellular immune response in rodents. Moreover, the vaccine candidate elicited long-term immunity and protection against SFTSV for at least 5 months. Notably, it provided complete cross-protection against other bandaviruses, such as the Heartland virus and Guertu virus, in lethal challenge models. Further research revealed that the conserved epitopes among bandaviruses within the full-length SFTSV glycoprotein may facilitate broad-spectrum protection mediated by the cellular immune response. Collectively, these findings demonstrate that the full-length SFTSV glycoprotein mRNA vaccine is a promising vaccine candidate for SFTSV and other bandaviruses, and provide guidance for the development of broad-spectrum vaccines from conserved antigens and epitopes. IMPORTANCE: Tick-borne bandaviruses, such as SFTSV and Heartland virus, sporadically trigger outbreaks in addition to influenza viruses and coronaviruses, yet there are no specific vaccines or therapeutics against them. mRNA vaccine technology has advantages in terms of enabling in situ expression and triggering cellular immunity, thus offering new solutions for vaccine development against intractable viruses, such as bandaviruses. In this study, we developed a novel vaccine candidate for SFTSV by employing mRNA vaccination technology and using a full-length glycoprotein as an antigen target. This candidate vaccine confers complete and durable protection against SFTSV at a notably low dose while also providing cross-protection against Heartland virus and Guertu virus. This study highlights the prospective value of full-length SFTSV-glycoprotein-based mRNA vaccines and suggests a potential strategy for broad-spectrum bandavirus vaccines.

Effect of oxidized starch on the storage stability of frozen raw noodles: Water distribution, protein structure, and quality attributes.

Freezing is a popular method of food preservation with multiple advantages. However, it may change the internal composition and quality of food. This study aimed to investigate the effect of modified starch on the storage stability of frozen raw noodles (FRNs) under refrigerated storage conditions. Oxidized starch (OS), a modified starch, is widely used in the food industry. In the present study, texture and cooking loss rate analyses showed that the hardness and chewiness of FRNs with added OS increased and the cooking loss rate decreased during the frozen storage process. Low-field nuclear magnetic resonance characterization confirmed that the water-holding capacity of FRNs with OS was enhanced. When 6% OS was added, the maximum freezable water content of FRNs was lower than the minimum freezable water content (51%) of FRNs without OS during freezing. Fourier-transform infrared spectroscopy showed that after the addition of OS, the secondary structures beneficial for structural maintenance were increased, forming a denser protein network and improving the microstructure of FRNs. In summary, the water state, protein structure, and quality characteristics of FRNs were improved by the addition of OS within an appropriate range.

NETs contribute to psoriasiform skin inflammation: A novel therapeutic approach targeting IL-36 cytokines by a small molecule tetrahydroxystilbene glucoside.

BACKGROUND: Psoriasis, a chronic immune-mediated skin disease with pathological features such as aberrant differentiation of keratinocytes, dermal-epidermal inflammation, and angiogenesis. 2,3,5,4'-Tetrahydroxy stilbene 2-Ο-ß-d-glucoside (2354Glu) is a natural small molecule polyhydrostilbenes isolated from Polygonum multiglorum Thunb. The regulation of IL-36 subfamily has led to new pharmacologic strategies to reverse psoriasiform dermatitis. PURPOSE: Here we investigated the therapeutic potential of 2354Glu and elucidated the underlying mechanism in psoriasis. METHODS: The effects of 2354Glu on IL-36 signaling were assessed by psoriasiform in vivo, in vitro and ex vivo model. The in vivo mice model of psoriasis-like skin inflammation was established by applying imiquimod (IMQ), and the in vitro and ex vitro models were established by stimulating mouse primary keratinocyte, human keratinocytes cells (HaCaT) and ex vivo skin tissue isolated from the mice back with Polyinosine-polycytidylic acid (Poly(I:C)), IMQ, IL-36γ and Lipopolysaccharide (LPS) respectively. Moreover, NETs formation was inhibited by Cl-amidine to evaluate the effect of NETs in psoriatic mouse model. The effects of 2354Glu on skin inflammation were assessed by western blot, H&E, immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assay and real-time quantitative PCR. RESULTS: In Poly(I:C)-stimulated keratinocytes, the secretion of IL-36 was inhibited after treatment with 2354Glu, similar to the effects of TLR3, P2X7R and caspase-1 inhibitors. In aldara (imiquimod)-induced mice, 2354Glu (100 and 25 mg/kg) improved immune cell infiltration and hyperkeratosis in psoriasis by directly targeting IL-36 in keratinocytes through P2X7R-caspase-1. When treatment with 2354Glu (25 mg/kg) was insufficient to inhibit IL-36γ, NETs reduced pathological features and IL-36 signaling by interacting with keratinocytes to combat psoriasis like inflammation. CONCLUSION: These results indicated that NETs had a beneficial effect on psoriasiform dermatitis. 2354Glu alleviates psoriasis by directly targeting IL-36/P2X7R axis and NET formation, providing a potential candidate for the treatment of psoriasis.

Cerebrospinal fluid mesencephalic astrocyte-derived neurotrophic factor: A moderating effect on sleep time and cognitive function.

BACKGROUND: Sleeping late has been associated with cognitive impairment, and insufficient sleep can affect the secretion of feeding-related cytokines. Feeding-related cytokines may contribute to cognitive deficits resulting from delayed bedtime. Glial cell line-derived neurotrophic factor (GDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF), which are feeding-related neurotrophic factors, have been associated with improved cognitive function and neuroprotective abilities. Enhanced expression of GDNF and MANF is linked to increased energy expenditure and hyperphagia, respectively. AIMS: This study aimed to investigate the association between cerebrospinal fluid (CSF) GDNF, MANF, cognition, and sleep time and to explore the moderating effects of GDNF and MANF on cognitive impairment in individuals who sleep late. METHOD: This cross-sectional study included participants (mean age 31.76 ± 10.22 years) who were categorized as ≤23 o'clock sleepers (n = 66) and >23 o'clock sleepers (n = 125) based on sleep time. Cognition was assessed using Montreal Cognitive Assessment (MoCA), and GDNF and MANF levels in CSF were measured. RESULTS: MANF may play a moderating role in the relationship between sleep time and cognition (R2 = 0.06, ß = 0.59, p = 0.031). Age showed a negative correlation with MoCA scores (R2 = 0.08, ß = -0.18), while education exhibited a positive correlation (ß = 0.17, both p < 0.05). Only ≤23 o'clock sleepers exhibited a negative correlation between MANF levels and BMI (r = -0.35, p = 0.005). CONCLUSIONS: This study provides hitherto undocumented evidence of the potential protective effect of CSF MANF on cognitive impairment of late sleepers, which suggests that maintaining a regular sleep schedule may contribute to cognition and overall health, with MANF playing a role in this process.

Patients' needs and experiences of telerehabilitation after total hip and knee arthroplasty: A qualitative systematic review and meta-synthesis.

Background: The number of patients undergoing joint replacement procedures is continuously increasing. Tele-equipment is progressively being employed for postrehabilitation of total hip and knee replacements. Gaining a comprehensive understanding of the experiences and requirements of patients undergoing total hip and knee arthroplasty who participate in telerehabilitation can contribute to the enhancement of telerehabilitation programs and the overall rehabilitation and care provided to this specific population. Objective: To explore the needs and experiences of total hip and knee arthroplasty patients with telerehabilitation. Design: Systematic review and qualitative synthesis. Methods: Electronic databases PubMed, Web of Science, The Cochrane Library, Embase, CINAHL, Scopus, ProQuest, CNKI, Wanfang Data, VIP, and SinoMed were systematically searched for information on the needs and experiences of telerehabilitation for patients with total hip arthroplasty and total knee arthroplasty in qualitative studies. The search period was from the creation of the database to March 2024. Literature quality was assessed using the 2016 edition of the Australian Joanna Briggs Institute Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research. A pooled integration approach was used to integrate the findings inductively. Results: A total of 11 studies were included and 4 themes were identified: the desire to communicate and the need to acquire knowledge; accessible, high-quality rehabilitation services; positive psychological experiences; the dilemmas of participating in telerehabilitation. Conclusions: This study's findings emphasize that the practical needs and challenges of total hip and knee arthroplasty patients' participation in telerehabilitation should be continuously focused on, and the advantages of telerehabilitation should be continuously strengthened to guarantee the continuity of patients' postoperative rehabilitation and to promote their postoperative recovery.

Intervention with fructooligosaccharides, Saccharomyces boulardii, and their combination in a colitis mouse model.

Objective: To examine the effects of an intervention with fructooligosaccharides (FOS), Saccharomyces boulardii, and their combination in a mouse model of colitis and to explore the mechanisms underlying these effects. Methods: The effects of FOS, S. boulardii, and their combination were evaluated in a DSS-induced mouse model of colitis. To this end, parameters such as body weight, the disease activity index (DAI), and colon length were examined in model mice. Subsequently, ELISA was employed to detect the serum levels of proinflammatory cytokines. Histopathological analysis was performed to estimate the progression of inflammation in the colon. Gas chromatography was used to determine the content of short-chain fatty acids (SCFAs) in the feces of model mice. Finally, 16S rRNA sequencing technology was used to analyze the gut microbiota composition. Results: FOS was slight effective in treating colitis and colitis-induced intestinal dysbiosis in mice. Meanwhile, S. boulardii could significantly reduced the DAI, inhibited the production of IL-1ß, and prevented colon shortening. Nevertheless, S. boulardii treatment alone failed to effectively regulate the gut microbiota. In contrast, the combined administration of FOS/S. boulardii resulted in better anti-inflammatory effects and enabled microbiota regulation. The FOS/S. boulardii combination (109 CFU/ml and 107 CFU/ml) significantly reduced the DAI, inhibited colitis, lowered IL-1ß and TNF-α production, and significantly improved the levels of butyric acid and isobutyric acid. However, FOS/S. boulardii 109 CFU/ml exerted stronger anti-inflammatory effects, inhibited IL-6 production and attenuated colon shortening. Meanwhile, FOS/S. boulardii 107 CFU/ml improved microbial regulation and alleviated the colitis-induced decrease in microbial diversity. The combination of FOS and S. boulardii significantly increased the abundance of Parabacteroides and decreased the abundance of Escherichia-Shigella. Additionally, it promoted the production of acetic acid and propionic acid. Conclusion: Compared with single administration, the combination can significantly increase the abundance of beneficial bacteria such as lactobacilli and Bifidobacteria and effectively regulate the gut microbiota composition. These results provide a scientific rationale for the prevention and treatment of colitis using a FOS/S. boulardii combination. They also offer a theoretical basis for the development of nutraceutical preparations containing FOS and S. boulardii.

Immunomodulatory poly(L-lactic acid) nanofibrous membranes promote diabetic wound healing by inhibiting inflammation, oxidation and bacterial infection.

Background: Given the significant impact on human health, it is imperative to develop novel treatment approaches for diabetic wounds, which are prevalent and serious complications of diabetes. The diabetic wound microenvironment has a high level of reactive oxygen species (ROS) and an imbalance between proinflammatory and anti-inflammatory cells/factors, which hamper the healing of chronic wounds. This study aimed to develop poly(L-lactic acid) (PLLA) nanofibrous membranes incorporating curcumin and silver nanoparticles (AgNPs), defined as PLLA/C/Ag, for diabetic wound healing. Methods: PLLA/C/Ag were fabricated via an air-jet spinning approach. The membranes underwent preparation and characterization through various techniques including Fourier-transform infrared spectroscopy, measurement of water contact angle, X-ray photoelectron spectroscopy, X-ray diffraction, scanning electron microscopy, assessment of in vitro release of curcumin and Ag+, testing of mechanical strength, flexibility, water absorption and biodegradability. In addition, the antioxidant, antibacterial and anti-inflammatory properties of the membranes were evaluated in vitro, and the ability of the membranes to heal wounds was tested in vivo using diabetic mice. Results: Loose hydrophilic nanofibrous membranes with uniform fibre sizes were prepared through air-jet spinning. The membranes enabled the efficient and sustained release of curcumin. More importantly, antibacterial AgNPs were successfully reduced in situ from AgNO3. The incorporation of AgNPs endowed the membrane with superior antibacterial activity, and the bioactivities of curcumin and the AgNPs gave the membrane efficient ROS scavenging and immunomodulatory effects, which protected cells from oxidative damage and reduced inflammation. Further results from animal studies indicated that the PLLA/C/Ag membranes had the most efficient wound healing properties, which were achieved by stimulating angiogenesis and collagen deposition and inhibiting inflammation. Conclusions: In this research, we successfully fabricated PLLA/C/Ag membranes that possess properties of antioxidants, antibacterial agents and anti-inflammatory agents, which can aid in the process of wound healing. Modulating wound inflammation, these new PLLA/C/Ag membranes serve as a novel dressing to enhance the healing of diabetic wounds.

Bispecific antibodies targeting two glycoproteins on SFTSV exhibit synergistic neutralization and protection in a mouse model.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high fatality rate of up to 30% caused by SFTS virus (SFTSV). However, no specific vaccine or antiviral therapy has been approved for clinical use. To develop an effective treatment, we isolated a panel of human monoclonal antibodies (mAbs). SF5 and SF83 are two neutralizing mAbs that recognize two viral glycoproteins (Gn and Gc), respectively. We found that their epitopes are closely located, and we then engineered them as several bispecific antibodies (bsAbs). Neutralization and animal experiments indicated that bsAbs display more potent protective effects than the parental mAbs, and the cryoelectron microscopy structure of a bsAb3 Fab-Gn-Gc complex elucidated the mechanism of protection. In vivo virus passage in the presence of antibodies indicated that two bsAbs resulted in less selective pressure and could efficiently bind to all single parental mAb-escape mutants. Furthermore, epitope analysis of the protective mAbs against SFTSV and RVFV indicated that they are all located on the Gn subdomain I, where may be the hot spots in the phleboviruses. Collectively, these data provide potential therapeutic agents and molecular basis for the rational design of vaccines against SFTSV infection.

Patient Self-Management Scale after Total Knee Arthroplasty (PSMS-TKA): Instrument Development and Cross-Sectional Validation Study.

BACKGROUND: Effective self-management after total knee arthroplasty not only improves patients' knee pain and physical function, but also improves quality of life. However, there is no assessment tool that can be targeted to evaluate the self-management level of patients after total knee arthroplasty. This study aimed to develop and validate a scale to specifically assess the level of self-management in patients after total knee arthroplasty. METHODS: The study was conducted in two steps: (1) instrument development; and (2) psychological tests (n = 428). For the instrument development portion, scale items were generated through a literature review and semi-structured interviews, then reviewed and revised by a panel of experts, and assessed for content validity and pilot testing. For the psychometric tests component, items were analyzed using corrected item-total scale correlations, the critical ratio method, and Cronbach's α. Construct validity was evaluated using exploratory factor analysis and validation factor analysis. Criterion correlation validity was checked by calculating Pearson's correlation coefficient using the Arthritis Self-Efficacy Scale-8 and the scale developed in this study. Internal consistency reliability was evaluated using Cronbach's α and fold-half reliability, and retest reliability was assessed using intragroup correlation coefficients. RESULTS: The Patient Self-Management Scale after Total Knee Arthroplasty (PSMS-TKA) comprises 4 factors and 23 items that assess daily behavior management, disease information management, psychosocial management, and exercise rehabilitation management. Exploratory factor analysis and validation factor analysis yielded a stable 4-factor model for the 23 items. The PSMS-TKA demonstrated good criterion-related validity when using the Arthritis Self-Efficacy-8 as a criterion. The Cronbach's α of the PSMS-TKA was 0.903, the split-half reliability was 0.934, and the test-retest reliability correlation coefficient was 0.887 (P < 0.01); thus, the reliability of the scale is good. CONCLUSION: The PSMS-TKA developed in this study has good validity and reliability and can be used to assess the level of self-management in patients after total knee arthroplasty. The scale helps healthcare professionals understand the level of self-management of patients undergoing total knee arthroplasty.

MMP13-targeted siRNA-loaded micelles for diagnosis and treatment of posttraumatic osteoarthritis.

Posttraumatic osteoarthritis (PTOA) patients are often diagnosed by X-ray imaging at a middle-late stage when drug interventions are less effective. Early PTOA is characterized by overexpressed matrix metalloprotease 13 (MMP13). Herein, we constructed an integrated diagnosis and treatment micelle modified with MMP13 enzyme-detachable, cyanine 5 (Cy5)-containing PEG, black hole quencher-3 (BHQ3), and cRGD ligands and loaded with siRNA silencing MMP13 (siM13), namely ERMs@siM13. ERMs@siM13 could be cleaved by MMP13 in the diseased cartilage tissues to detach the PEG shell, causing cRGD exposure. Accordingly, the ligand exposure promoted micelle uptake by the diseased chondrocytes by binding to cell surface αvß3 integrin, increasing intracellular siM13 delivery for on-demand MMP13 downregulation. Meanwhile, the Cy5 fluorescence was restored by detaching from the BHQ3-containing micelle, precisely reflecting the diseased cartilage state. In particular, the intensity of Cy5 fluorescence generated by ERMs@siM13 that hinged on the MMP13 levels could reflect the PTOA severity, enabling the physicians to adjust the therapeutic regimen. Finally, in the murine PTOA model, ERMs@siM13 could diagnose the early-stage PTOA, perform timely interventions, and monitor the OA progression level during treatment through a real-time detection of MMP13. Therefore, ERMs@siM13 represents an appealing approach for early-stage PTOA theranostics.

Morphological and molecular characterization of Heterodera ripae, a new record cyst nematode in the rhizosphere soil of Fagopyrum esculentum.

Numerous plant parasitic nematodes (PPNs) have the potential to inflict considerable damage on agricultural crops. Through a comprehensive survey aimed at identifying PPNs affecting crops, cyst nematodes were isolated from the rhizosphere soil of buckwheat (Fagopyrum esculentum). Employing both molecular and morphological techniques, this cyst nematode was conclusively identified as Heterodera ripae. Notably, this represents the first documented occurrence of this particular cyst nematode species within the rhizosphere soil of F. esculentum.

Advancing Tissue Damage Repair in Geriatric Diseases: Prospects of Combining Stem Cell-Derived Exosomes with Hydrogels.

Geriatric diseases are a group of diseases with unique characteristics related to senility. With the rising trend of global aging, senile diseases now mainly include endocrine, cardiovascular, neurodegenerative, skeletal, and muscular diseases and cancer. Compared with younger populations, the structure and function of various cells, tissues and organs in the body of the elderly undergo a decline as they age, rendering them more susceptible to external factors and diseases, leading to serious tissue damage. Tissue damage presents a significant obstacle to the overall health and well-being of older adults, exerting a profound impact on their quality of life. Moreover, this phenomenon places an immense burden on families, society, and the healthcare system.In recent years, stem cell-derived exosomes have become a hot topic in tissue repair research. The combination of these exosomes with biomaterials allows for the preservation of their biological activity, leading to a significant improvement in their therapeutic efficacy. Among the numerous biomaterial options available, hydrogels stand out as promising candidates for loading exosomes, owing to their exceptional properties. Due to the lack of a comprehensive review on the subject matter, this review comprehensively summarizes the application and progress of combining stem cell-derived exosomes and hydrogels in promoting tissue damage repair in geriatric diseases. In addition, the challenges encountered in the field and potential prospects are presented for future advancements.

Practice and Effect Evaluation of Preoperative Management Strategy for Patients Undergoing Day Arthroscopic Surgery Based on Evidence-Based Concept.

Objective: To improve the preoperative management of patients undergoing day arthroscopy. Methods: Based on the evidence-based concept, the preoperative management strategy of daytime arthroscopic surgery was practiced, and the implementation effect of patients undergoing daytime arthroscopic surgery before and after evidence application was compared. The evidence-based strategies adopted in this study include: informed consent,seven aspects: anesthesia assessment, health education, prohibition of drinking and eating, preoperative medication guidance, surgical arrangement, and emergency management. Results: After applying evidence-based strategies, significant improvements were observed in various quality indicators, including reduced waiting time, reduced surgical cancellations, increased patient satisfaction, and reduced unplanned hospitalization rates. Conclusion: Based on the evidence-based concept, the practice of preoperative management strategies for patients undergoing daytime arthroscopic surgery optimizes the daytime surgical process from the strict implementation of patient health education and evaluation, as well as the establishment of compliant and reasonable surgical schedules and emergency mechanisms. This improves the preoperative management behavior of daytime surgery, enhances the patient's medical experience, and enhances the quality of daytime surgical care, providing a good basis for management and decision-making.

Transparent and Efficient Wood-Based Triboelectric Nanogenerators for Energy Harvesting and Self-Powered Sensing.

Wood possesses several advantageous qualities including innocuity, low cost, aesthetic appeal, and excellent biocompatibility, and its naturally abundant functional groups and diverse structural forms facilitate functionalization modification. As the most sustainable bio-based material, the combination of wood with triboelectric nanogenerators (TENGs) stands poised to significantly advance the cause of green sustainable production while mitigating the escalating challenges of energy consumption. However, the inherent weak polarizability of natural wood limits its development for TENGs. Herein, we present the pioneering development of a flexible transparent wood-based triboelectric nanogenerator (TW-TENG) combining excellent triboelectrical properties, optical properties, and wood aesthetics through sodium chlorite delignification and epoxy resin impregnation. Thanks to the strong electron-donating groups in the epoxy resin, the TW-TENG obtained an open-circuit voltage of up to ~127 V, marking a remarkable 530% enhancement compared to the original wood. Furthermore, durability and stability were substantiated through 10,000 working cycles. In addition, the introduction of epoxy resin and lignin removal endowed the TW-TENG with excellent optical characteristics, with optical transmittance of up to 88.8%, while preserving the unique texture and aesthetics of the wood completely. Finally, we show the application prospects of TW-TENGs in the fields of self-power supply, motion sensing, and smart home through the demonstration of a TW-TENG in the charging and discharging of capacitors and the output of electrical signals in different scenarios.

Polygenic risk-stratified screening for nasopharyngeal carcinoma in high-risk endemic areas of China: a cost-effectiveness study.

Background: Nasopharyngeal carcinoma (NPC) has an extremely high incidence rate in Southern China, resulting in a severe disease burden for the local population. Current EBV serologic screening is limited by false positives, and there is opportunity to integrate polygenic risk scores for personalized screening which may enhance cost-effectiveness and resource utilization. Methods: A Markov model was developed based on epidemiological and genetic data specific to endemic areas of China, and further compared polygenic risk-stratified screening [subjects with a 10-year absolute risk (AR) greater than a threshold risk underwent EBV serological screening] to age-based screening (EBV serological screening for all subjects). For each initial screening age (30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 years), a modeled cohort of 100,000 participants was screened until age 69, and then followed until age 79. Results: Among subjects aged 30 to 54 years, polygenic risk-stratified screening strategies were more cost-effective than age-based screening strategies, and almost comprised the cost-effectiveness efficiency frontier. For men, screening strategies with a 1-year frequency and a 10-year absolute risk (AR) threshold of 0.7% or higher were cost-effective, with an incremental cost-effectiveness ratio (ICER) below the willingness to pay (¥203,810, twice the local per capita GDP). Specifically, the strategies with a 10-year AR threshold of 0.7% or 0.8% are the most cost-effective strategies, with an ICER ranging from ¥159,752 to ¥201,738 compared to lower-cost non-dominated strategies on the cost-effectiveness frontiers. The optimal strategies have a higher probability (29.4-35.8%) of being cost-effective compared to other strategies on the frontier. Additionally, they reduce the need for nasopharyngoscopies by 5.1-27.7% compared to optimal age-based strategies. Likewise, for women aged 30-54 years, the optimal strategy with a 0.3% threshold showed similar results. Among subjects aged 55 to 69 years, age-based screening strategies were more cost-effective for men, while no screening may be preferred for women. Conclusion: Our economic evaluation found that the polygenic risk-stratified screening could improve the cost-effectiveness among individuals aged 30-54, providing valuable guidance for NPC prevention and control policies in endemic areas of China.

Shexiang Tongxin Dropping Pill Promotes Angiogenesis through VEGF/eNOS Signaling Pathway on Diabetic Coronary Microcirculation Dysfunction.

OBJECTIVE: To study the effect of Shexiang Tongxin Dropping Pill (STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction (CMD). METHODS: According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve (CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot. RESULTS: Compared with the model group, medium- and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening (P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level (all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS (P<0.05 or P<0.01). CONCLUSION: STDP has a definite therapeutic effect on diabetic CMD, and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway.

Elucidation of the beneficial role of co-fermented whole grain quinoa and black barley with Lactobacillus on rats fed a western-style diet via a multi-omics approach.

Long-term consumption of Western-style diet (WSD) can lead to metabolic disorders and dysbiosis of gut microbiota, presenting a critical risk factor for various chronic conditions such as fatty liver disease. In the present study, we investigated the beneficial role of co-fermented whole grain quinoa and black barley with Lactobacillus kisonensis on rats fed a WSD. Male Sprague-Dawley (SD) rats, aged six weeks and weighing 180 ± 10 g, were randomly assigned to one of three groups: the normal control group (NC, n = 7), the WSD group (HF, n = 7), and the WSD supplemented with a co-fermented whole grain quinoa with black barley (FQB) intervention group (HFF, n = 7). The findings indicated that FQB was effective in suppressing body weight gain, mitigating hepatic steatosis, reducing perirenal fat accumulation, and ameliorating pathological damage in the livers and testicular tissues of rats. Additionally, FQB intervention led to decreased levels of serum uric acid (UA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). These advantageous effects can be ascribed to the regulation of FQB on gut microbiota dysbiosis, which includes the restoration of intestinal flora diversity, reduction of the F/B ratio, and promotion of probiotics abundance, such as Akkermansia and [Ruminococcus] at the genus level. The study employed the UPLC-Q-TOF-MSE technique to analyze metabolites in fecal and hepatic samples. The findings revealed that FQB intervention led to a regression in the levels of specific metabolites in feces, including oxoadipic acid and 20a, 22b-dihydroxycholesterol, as well as in the liver, such as pyridoxamine, xanthine and xanthosine. The transcriptome sequencing of liver tissues revealed that FQB intervention modulated the mRNA expression of specific genes, including Cxcl12, Cidea, and Gck, known for their roles in anti-inflammatory and anti-insulin resistance mechanisms in the context of WSD. Our findings indicate that co-fermented whole-grain quinoa with black barley has the potential to alleviate metabolic disorders and chronic inflammation resulting from the consumption of WSD.

Three-dimensional liquid metal-based neuro-interfaces for human hippocampal organoids.

Human hippocampal organoids (hHOs) derived from human induced pluripotent stem cells (hiPSCs) have emerged as promising models for investigating neurodegenerative disorders, such as schizophrenia and Alzheimer's disease. However, obtaining the electrical information of these free-floating organoids in a noninvasive manner remains a challenge using commercial multi-electrode arrays (MEAs). The three-dimensional (3D) MEAs developed recently acquired only a few neural signals due to limited channel numbers. Here, we report a hippocampal cyborg organoid (cyb-organoid) platform coupling a liquid metal-polymer conductor (MPC)-based mesh neuro-interface with hHOs. The mesh MPC (mMPC) integrates 128-channel multielectrode arrays distributed on a small surface area (~2*2 mm). Stretchability (up to 500%) and flexibility of the mMPC enable its attachment to hHOs. Furthermore, we show that under Wnt3a and SHH activator induction, hHOs produce HOPX+ and PAX6+ progenitors and ZBTB20+PROX1+ dentate gyrus (DG) granule neurons. The transcriptomic signatures of hHOs reveal high similarity to the developing human hippocampus. We successfully detect neural activities from hHOs via the mMPC from this cyb-organoid. Compared with traditional planar devices, our non-invasive coupling offers an adaptor for recording neural signals from 3D models.

An epigenome-wide association study of waist circumference in Chinese monozygotic twins.

OBJECTIVES: Central obesity poses significant health risks because it increases susceptibility to multiple chronic diseases. Epigenetic features such as DNA methylation may be associated with specific obesity traits, which could help us understand how genetic and environmental factors interact to influence the development of obesity. This study aims to identify DNA methylation sites associated with the waist circumference (WC) in Northern Han Chinese population, and to elucidate potential causal relationships. METHODS: A total of 59 pairs of WC discordant monozygotic twins (ΔWC >0) were selected from the Qingdao Twin Registry in China. Generalized estimated equation model was employed to estimate the methylation levels of CpG sites on WC. Causal relationships between methylation and WC were assessed through the examination of family confounding factors using FAmiliaL CONfounding (ICE FALCON). Additionally, the findings of the epigenome-wide analysis were corroborated in the validation stage. RESULTS: We identified 26 CpG sites with differential methylation reached false discovery rate (FDR) < 0.05 and 22 differentially methylated regions (slk-corrected p < 0.05) strongly linked to WC. These findings provided annotations for 26 genes, with notable emphasis on MMP17, ITGA11, COL23A1, TFPI, A2ML1-AS1, MRGPRE, C2orf82, and NINJ2. ICE FALCON analysis indicated the DNA methylation of ITGA11 and TFPI had a causal effect on WC and vice versa (p < 0.05). Subsequent validation analysis successfully replicated 10 (p < 0.05) out of the 26 identified sites. CONCLUSIONS: Our research has ascertained an association between specific epigenetic variations and WC in the Northern Han Chinese population. These DNA methylation features can offer fresh insights into the epigenetic regulation of obesity and WC as well as hints to plausible biological mechanisms.