PoWRKY69-PoVQ11 module positively regulates drought tolerance by accumulating fructose in Paeonia ostii.

Drought is a detrimental environmental factor that restricts plant growth and threatens food security throughout the world. WRKY transcription factors play vital roles in abiotic stress response. However, the roles of IIe subgroup members from WRKY transcription factor family in soluble sugar mediated drought response are largely elusive. In this study, we identified a drought-responsive IIe subgroup WRKY transcription factor, PoWRKY69, from Paeonia ostii. PoWRKY69 functioned as a positive regulator in response to drought stress with nucleus expression and transcriptional activation activity. Silencing of PoWRKY69 increased plants sensitivity to drought stress, whereas conversely, overexpression of PoWRKY69 enhanced drought tolerance in plants. As revealed by yeast one-hybrid, electrophoretic mobility shift assay, and luciferase reporter assays, PoWRKY69 could directly bind to the W-box element of fructose-1,6-bisphosphate aldolase 5 (PoFBA5) promoter, contributing to a cascade regulatory network to activate PoFBA5 expression. Furthermore, virus-induced gene silencing and overexpression assays demonstrated that PoFBA5 functioned positively in response to drought stress by accumulating fructose to alleviate membrane lipid peroxidation and activate antioxidant defense system, these changes resulted in reactive oxygen species scavenging. According to yeast two-hybrid, bimolecular fluorescence complementation, and firefly luciferase complementation imaging assays, valine-glutamine 11 (PoVQ11) physically interacted with PoWRKY69 and led to an enhanced activation of PoWRKY69 on PoFBA5 promoter activity. This study broadens our understanding of WRKY69-VQ11 module regulated fructose accumulation in response to drought stress and provides feasible molecular measures to create novel drought-tolerant germplasm of P. ostii.

Synergistic actions of three MYB transcription factors underpin blotch formation in tree peony.

Blotches in floral organs attract pollinators and promote pollination success. Tree peony (Paeonia suffruticosa Andr.) is an internationally renowned cut flower with extremely high ornamental and economic value. Blotch formation on P. suffruticosa petals is predominantly attributed to anthocyanin accumulation. However, the endogenous regulation of blotch formation in P. suffruticosa remains elusive. Here, we identified the regulatory modules governing anthocyanin-mediated blotch formation in P. suffruticosa petals, which involves the transcription factors PsMYB308, PsMYBPA2, and PsMYB21. PsMYBPA2 activated PsF3H expression to provide sufficient precursor substrate for anthocyanin biosynthesis. PsMYB21 activated both PsF3H and PsFLS expression and promoted flavonol biosynthesis. The significantly high expression of PsMYB21 in non-blotch regions inhibited blotch formation by competing for anthocyanin biosynthesis substrates, while conversely, its low expression in the blotch region promoted blotch formation. PsMYB308 inhibited PsDFR and PsMYBPA2 expression to directly prevent anthocyanin-mediated blotch formation. Notably, a smaller blotch area, decreased anthocyanin content, and inhibition of anthocyanin structural gene expression were observed in PsMYBPA2-silenced petals, while the opposite phenotypes were observed in PsMYB308-silenced and PsMYB21-silenced petals. Additionally, PsMYBPA2 and PsMYB308 interacted with PsbHLH1-3, and their regulatory intensity on target genes was synergistically regulated by the PsMYBPA2-PsbHLH1-3 and PsMYB308-PsbHLH1-3 complexes. PsMYB308 also competitively bound to PsbHLH1-3 with PsMYBPA2 to fine-tune the regulatory network to prevent overaccumulation of anthocyanin in blotch regions. Overall, our study uncovers a complex R2R3-MYB transcriptional regulatory network that governs anthocyanin-mediated blotch formation in P. suffruticosa petals, providing insights into the molecular mechanisms underlying blotch formation in P. suffruticosa.

Exploring the therapeutic potential of urine-derived stem cell exosomes in temporomandibular joint osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative ailment that causes slow cartilage degeneration, aberrant bone remodeling, and persistent discomfort, leading to a considerable reduction in the patient's life quality. Current treatment options for TMJOA have limited efficacy. This investigation aimed to explore a potential strategy for halting or reversing the progression of TMJOA through the utilization of exosomes (EXOs) derived from urine-derived stem cells (USCs). The USC-EXOs were obtained through microfiltration and ultrafiltration techniques, followed by their characterization using particle size analysis, electron microscopy, and immunoblotting. Subsequently, an in vivo model of TMJOA induced by mechanical force was established. To assess the changes in the cartilage of TMJOA treated with USC-EXOs, we performed histology analysis using hematoxylin-eosin staining, immunohistochemistry, and histological scoring. Our findings indicate that the utilization of USC-EXOs yields substantial reductions in TMJOA, while concurrently enhancing the structural integrity and smoothness of the compromised condylar cartilage surface. Additionally, USC-EXOs exhibit inhibitory effects on osteoclastogenic activity within the subchondral bone layer of the condylar cartilage, as well as attenuated apoptosis in the rat TMJ in response to mechanical injury. In conclusion, USC-EXOs hold considerable promise as a potential therapeutic intervention for TMJOA.

An R2R3-MYB network modulates stem strength by regulating lignin biosynthesis and secondary cell wall thickening in herbaceous peony.

Stem strength is an important agronomic trait affecting plant lodging, and plays an essential role in the quality and yield of plants. Thickened secondary cell walls in stems provide mechanical strength that allows plants to stand upright, but the regulatory mechanism of secondary cell wall thickening and stem strength in cut flowers remains unclear. In this study, first, a total of 11 non-redundant Paeonia lactiflora R2R3-MYBs related to stem strength were identified and isolated from cut-flower herbaceous peony, among which PlMYB43, PlMYB83 and PlMYB103 were the most upregulated differentially expressed genes. Then, the expression characteristics revealed that these three R2R3-MYBs were specifically expressed in stems and acted as transcriptional activators. Next, biological function verification showed that these P. lactiflora R2R3-MYBs positively regulated stem strength, secondary cell wall thickness and lignin deposition. Furthermore, yeast-one-hybrid and dual luciferase reporter assays demonstrated that they could bind to the promoter of caffeic acid O-methyltransferase gene (PlCOMT2) and/or laccase gene (PlLAC4), two key genes involved in lignin biosynthesis. In addition, the function of PlLAC4 in increasing lignin deposition was confirmed by virus-induced gene silencing and overexpression. Moreover, PlMYB83 could also act as a transcriptional activator of PlMYB43. The findings of the study propose a regulatory network of R2R3-MYBs modulating lignin biosynthesis and secondary cell wall thickening for improving stem lodging resistance, and provide a resource for molecular genetic engineering breeding of cut flowers.

Identification of key genes for triacylglycerol biosynthesis and storage in herbaceous peony (Paeonia lactifolra Pall.) seeds based on full-length transcriptome.

BACKGROUND: The herbaceous peony (Paeonia lactiflora Pall.) is extensively cultivated in China due to its root being used as a traditional Chinese medicine known as 'Radix Paeoniae Alba'. In recent years, it has been discovered that its seeds incorporate abundant unsaturated fatty acids, thereby presenting a potential new oilseed plant. Surprisingly, little is known about the full-length transcriptome sequencing of Paeonia lactiflora, limiting research into its gene function and molecular mechanisms. RESULTS: A total of 484,931 Reads of Inserts (ROI) sequences and 1,455,771 full-Length non-chimeric reads (FLNC) sequences were obtained for CDS prediction, TF analysis, SSR analysis and lncRNA identification. In addition, gene function annotation and gene structure analysis were performed. A total of 4905 transcripts were related to lipid metabolism biosynthesis pathway, belonging to 28 enzymes. We use these data to identify 10 oleosin (OLE) and 5 diacylglycerol acyltransferase (DGAT) gene members after de-redundancy. The analysis of physicochemical properties and secondary structure showed them similarity in gene family respectively. The phylogenetic analysis showed that the distribution of OLE and DGAT family members was roughly the same as that of Arabidopsis. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses revealed expression changes in different seed development stages, and showed a trend of increasing and then decreasing. CONCLUSION: In summary, these results provide new insights into the molecular mechanism of triacylglycerol (TAG) biosynthesis and storage during the seedling stage in Paeonia lactiflora. It provides theoretical references for selecting and breeding oil varieties and understanding the functions of oil storage as well as lipid synthesis related genes in Paeonia lactiflora.

Proton-Induced Reversible Spin-State Switching in Octanuclear FeIII Spin-Crossover Metal-Organic Cages.

Responsive spin-crossover (SCO) metal-organic cages (MOCs) are emerging dynamic platforms with potential for advanced applications in magnetic sensing and molecular switching. Among these, FeIII-based MOCs are particularly noteworthy for their air stability, yet they remain largely unexplored. Herein, we report the synthesis of two novel FeIII MOCs using a bis-bidentate ligand approach, which exhibit SCO activity above room temperature. These represent the first SCO-active FeIII cages and feature an atypical {FeN6}-type coordination sphere, uncommon for FeIII SCO compounds. Our study reveals that these MOCs are sensitive to acid/base variations, enabling reversible magnetic switching in solution. The presence of multiple active proton sites within these SCO-MOCs facilitates multisite, multilevel proton-induced spin-state modulation. This behavior is observed at room temperature through 1H NMR spectroscopy, capturing the subtle proton-induced spin-state transitions triggered by pH changes. Further insights from extended X-ray absorption fine structure (EXAFS) and theoretical analyses indicate that these magnetic alterations primarily result from the protonation and deprotonation processes at the NH active sites on the ligands. These processes induce changes in the secondary coordination sphere, thereby modulating the magnetic properties of the cages. The capability of these FeIII MOCs to integrate magnetic responses with environmental stimuli underscores their potential as finely tunable magnetic sensors and highlights their versatility as molecular switches. This work paves the way for the development of SCO-active materials with tailored properties for applications in sensing and molecular switching.

Kinetics of EBV antibody-based NPC risk scores in Taiwan NPC multiplex families.

Nasopharyngeal carcinoma (NPC) risk prediction models based on Epstein-Barr virus (EBV)-antibody testing have shown potential for screening of NPC; however, the long-term stability is unclear. Here, we investigated the kinetics of two EBV-antibody NPC risk scores within the Taiwan NPC Multiplex Family Study. Among 545 participants with multiple blood samples, we evaluated the stability of a 2-marker enzyme-linked immunosorbent assay score and 13-marker multiplex serology score using the intra-class correlation coefficient (ICC) by fitting a linear mixed model that accounted for the clustering effect of multiple measurements per subject and age. We also estimated the clustering of positive tests using Fleiss's kappa statistic. Over an average 20-year follow-up, the 2-marker score showed high stability over time, whereas the 13-marker score was more variable (p < .05). Case-control status is associated with the kinetics of the antibody response, with higher ICCs among cases. Positive tests were more likely to cluster within the same individual for the 2-marker score than the 13-marker score (p < .05). The 2-marker score had an increase in specificity from ~90% for single measurement to ~96% with repeat testing. The 13-marker score had a specificity of ~73% for a single measurement that increased to ~92% with repeat testing. Among individuals who developed NPC, none experienced score reversion. Our findings suggest that repeated testing could improve the specificity of NPC screening in high-risk NPC multiplex families. Further studies are required to determine the impact on sensitivity, establish optimal screening intervals, and generalize these findings to general population settings in high-risk regions.

The herbaceous peony transcription factor WRKY41a promotes secondary cell wall thickening to enhance stem strength.

Stem bending or lodging caused by insufficient stem strength is an important limiting factor for plant production. Secondary cell walls play a crucial role in plant stem strength, but whether WRKY transcription factors can positively modulate secondary cell wall thickness are remain unknown. Here, we characterized a WRKY transcription factor PlWRKY41a from herbaceous peony (Paeonia lactiflora), which was highly expressed in stems. PlWRKY41a functioned as a nucleus-localized transcriptional activator and enhanced stem strength by positively modulating secondary cell wall thickness. Moreover, PlWRKY41a bound to the promoter of the XYLOGLUCAN ENDOTRANSGLUCOSYLASE/HYDROLASE4 (PlXTH4) and activated the expression of PlXTH4. PlXTH4-overexpressing tobacco (Nicotiana tabacum) had thicker secondary cell walls, resulting in enhanced stem strength, while PlXTH4-silenced P. lactiflora had thinner secondary cell walls, showing decreased stem strength. Additionally, PlWRKY41a directly interacted with PlMYB43 to form a protein complex, and their interaction induced the expression of PlXTH4. These data support that the PlMYB43-PlWRKY41a protein complex can directly activate the expression of PlXTH4 to enhance stem strength by modulating secondary cell wall thickness in P. lactiflora. The results will enhance our understanding of the formation mechanism of stem strength and provide a candidate gene to improve stem straightness in plants.

Arabidopsis membrane protein AMAR1 interaction with type III effector XopAM triggers a hypersensitive response.

The efficient infection of plants by the bacteria Xanthomonas campestris pv. campestris (Xcc) depends on its type III effectors (T3Es). Although the functions of AvrE family T3Es have been reported in some bacteria, the member XopAM in Xcc has not been studied. As XopAM has low sequence similarity to reported AvrE-T3Es and different reports have shown that these T3Es have different targets in hosts, we investigated the functions of XopAM in the Xcc-plant interaction. Deletion of xopAM from Xcc reduced its virulence in cruciferous crops but increased virulence in Arabidopsis (Arabidopsis thaliana) Col-0, indicating that XopAM may perform opposite functions depending on the host species. We further found that XopAM is a lipase that may target the cytomembrane and that this activity might be enhanced by its membrane-targeted protein XOPAM-ACTIVATED RESISTANCE 1 (AMAR1) in Arabidopsis Col-0. The binding of XopAM to AMAR1 induced an intense hypersensitive response that restricted Xcc proliferation. Our results showed that the roles of XopAM in Xcc infection are not the same as those of other AvrE-T3Es, indicating that the functions of this type of T3E have differentiated during long-term bacterium‒host interactions.

PlWRKY47 Coordinates With Cytosolic Glyceraldehyde-3-Phosphate Dehydrogenase 2 Gene to Improve Thermotolerance Through Inhibiting Reactive Oxygen Species Generation in Herbaceous Peony.

Although WRKY transcription factors play crucial roles in plant responses to high-temperature stress, little is known about Group IIb WRKY family members. Here, we identified the WRKY-IIb protein PlWRKY47 from herbaceous peony (Paeonia lactiflora Pall.), which functioned as a nuclear-localized transcriptional activator. The expression level of PlWRKY47 was positively correlated with high-temperature tolerance. Silencing of PlWRKY47 in P. lactiflora resulted in the decreased tolerance to high-temperature stress by accumulating reactive oxygen species (ROS). Overexpression of PlWRKY47 improved plant high-temperature tolerance through decreasing ROS accumulation. Moreover, PlWRKY47 directly bound to the promoter of cytosolic glyceraldehyde-3-phosphate dehydrogenase 2 (PlGAPC2) gene and activated its transcription. PlGAPC2 was also positively regulated high-temperature tolerance in P. lactiflora by increasing NAD+ content to inhibit ROS generation. Additionally, PlWRKY47 physically interacted with itself to form a homodimer, and PlWRKY47 could also interact with one Group IIb WRKY family member PlWRKY72 to form a heterodimer, they all promoted PlWRKY47 to bind to and activate PlGAPC2. These data support that the PlWRKY47-PlWRKY47 homodimer and PlWRKY72-PlWRKY47 heterodimer can directly activate PlGAPC2 expression to improve high-temperature tolerance by inhibiting ROS generation in P. lactiflora. These results will provide important insights into the plant high-temperature stress response by WRKY-IIb transcription factors.

Early adopters of doxycycline as post-exposure prophylaxis to prevent bacterial sexually transmitted infections in a real-world clinical setting.

OBJECTIVES: Doxycycline as post-exposure prophylaxis (DoxyPEP) is a novel prevention approach which has demonstrated efficacy in preventing bacterial sexually transmitted infections (STIs) in men who have sex with men (MSM) and transgender women (TGW) including people who are living with HIV and those on HIV pre-exposure prophylaxis (PrEP). We evaluated patient knowledge and interest in DoxyPEP, as well as early adopters of its use. METHODS: In 2023, patients presenting for HIV and STI services at a primary care and sexual health clinic were asked about DoxyPEP knowledge, interest and use. Bivariate and multivariate analyses were used to evaluate demographics and behaviours associated with these outcomes. RESULTS: A total of n=421 people presented for care. Of these, 314 were MSM/TGW. Fifteen percent were Black/African-American, and 21% were Hispanic/Latino. A total of 50% of MSM/TGW had heard of DoxyPEP, 49% were interested and 18% reported prior DoxyPEP use. Having a history of STI infection ever (adjusted OR (aOR) 5.95, 95% CI 2.69 to 13.13) and in the past 12 months (aOR 2.99, 95% CI 1.56 to 5.72) were both associated with DoxyPEP use. Individuals who had ever used HIV PrEP had nearly three times the odds of ever taking DoxyPEP (aOR 2.88, 95% CI 1.56 to 5.30). There was no association between the use of DoxyPEP and race, ethnicity or HIV status. CONCLUSIONS: Among MSM and TGW, there is already significant awareness, interest and use of DoxyPEP to prevent bacterial STIs. Public health efforts should focus on improving access and delivery of this STI prevention intervention to MSM and TGW.

Implementation of Point of Care Sexually Transmitted Infections Testing in a Community Clinic Setting.

ABSTRACT: The rates of sexually transmitted infections (STIs) in the United States, including chlamydia and gonorrhea, are rising. Point-of-care (POC) testing could increase access to testing and treatment. This evaluation found POC STI testing to be concordant with the results of traditional laboratory testing for 100% of patients who were tested. Ninety-five percent of the patients reported being satisfied with the experience, and 66% preferred it to traditional laboratory testing. The most commonly reported reason for preferring the test was the short amount of time it took to receive results. However, insurance reimbursed less than 30% of what was billed for the POC tests. Low insurance reimbursement rates could be a barrier to implementation long-term financial sustainability of POC STI testing.

Development and analytical validation of a novel nasopharynx swab-based Epstein-Barr virus C promoter methylation quantitative assay for nasopharyngeal carcinoma detection.

OBJECTIVES: Epstein-Barr virus (EBV) C promoter (Cp) hypermethylation, a crucial factor for EBV latent infection of nasopharyngeal epithelial cells, has been recognized as a promising biomarker for nasopharyngeal carcinoma (NPC) detection. In this study, we develop a novel EBV Cp methylation quantification (E-CpMQ) assay and evaluate its diagnostic performance for NPC detection. METHODS: A novel qPCR assay for simultaneous quantification of methylated- and unmethylated EBV Cp was developed by the combinational modification of MethyLight and QASM, with an innovative calibrator to improve the detection accuracy and consistency. The NP swab samples and synthetic standards were used for the analytical validation of the E-CpMQ. The diagnostic efficacy of the developed E-CpMQ assay was validated in 137 NPC patients and 137 non-NPC controls. RESULTS: The E-CpMQ assay can detect the EBV Cp methylation ratio in one reaction system under 10 copies with 100 % recognition specificity, which is highly correlated to pyrosequencing with a correlation coefficient over 0.99. The calibrated E-CpMQ assay reduces the coefficient of variation by an average of 55.5 % with a total variance of less than 0.06 units standard deviation (SD). Linear methylation ratio detection range from 4.76 to 99.01 %. The sensitivity and specificity of the E-CpMQ respectively are 96.4 % (95 % CI: 91.7-98.8 %), 89.8 % (95 % CI: 83.5-94.3 %). CONCLUSIONS: The developed E-CpMQ assay with a calibrator enables accurate and reproducible EBV Cp methylation ratio quantification and offers a sensitive, specific, cost-effective method for NPC early detection.

A retrospective study of mineral and bone disorder in kidney transplant recipients: Single-center experience.

BACKGROUND: The status of mineral and bone disorder (MBD) after kidney transplantation is not fully understood, and the assessment of abnormal mineral and bone metabolism in kidney transplant recipients (KTRs) has not been standardized. MATERIALS AND METHODS: We performed a retrospective analysis of 292 KTRs in our center. The levels of biochemical markers of bone metabolism and bone mineral density (BMD) were assessed. We evaluated the influencing factors of BMD using linear regression analysis. And correlation test was used for the correlation analysis between bone metabolism indicators and other indicators. RESULTS: Postoperative MBD mainly manifested as hypercalcemia (8.9%), hypophosphatemia (27.1%), low levels of 25-hydroxyvitamin D(25(OH)vitD) (67.0%), hyperparathyroidism (50.6%), and high levels of bone turnover markers (BTMs). The prevalence of osteopenia/osteoporosis in the femoral neck (FN) and lumbar spine (LS) was 20.1%/2.8% and 26.1%/3.6%, respectively. Multivariate analysis indicated that FN BMD was positively associated with body mass index (BMI) and negatively associated with acute rejection history (p < 0.05); while LS BMD was positively associated with BMI, and negatively associated with intact parathyroid hormone (iPTH) (p < 0.05). Biochemical markers of bone metabolism were affected by age, sex, preoperative dialysis mode and time, postoperative time, transplanted kidney function, and iPTH levels. LS BMD was negatively correlated with iPTH and BTMs (p < 0.05). CONCLUSION: MBD persisted after kidney transplantation. Decreased bone mass was associated with persistent hyperparathyroidism, acute rejection history, low BMI, advanced age, and menopause. Dynamic monitoring of bone metabolism index and BMD helps to assess MBD after kidney transplantation.

Pgam5 aggravates hyperglycemia-induced myocardial dysfunction through disrupting Phb2-dependent mitochondrial dynamics.

This study aims to elucidate the roles of Phosphoglycerate Mutase Family Member 5 (Pgam5) and Prohibitin 2 (Phb2) in the context of hyperglycemia-induced myocardial dysfunction, a critical aspect of diabetic cardiomyopathy. The research employed primary cardiomyocytes, which were then subjected to hyperglycemia treatment to mimic diabetic conditions. We used siRNA transfection to knock down Pgam5 and overexpressed Phb2 using adenovirus transfection to assess their individual and combined effects on cardiomyocyte health. Mitochondrial function was evaluated through measurements of mitochondrial membrane potential using the JC-1 probe, and levels of mitochondrial reactive oxygen species (ROS) were assessed. Additionally, the study involved qPCR analysis to quantify the transcriptional changes in genes related to mitochondrial fission and mitophagy. Our findings indicate that hyperglycemia significantly reduces cardiomyocyte viability and impairs mitochondrial function, as evidenced by decreased mitochondrial membrane potential and increased ROS levels. Pgam5 knockdown was observed to mitigate these adverse effects, preserving mitochondrial function and cardiomyocyte viability. On the molecular level, Pgam5 was found to regulate genes associated with mitochondrial fission (such as Drp1, Mff, and Fis1) and mitophagy (including Parkin, Bnip3, and Fundc1). Furthermore, overexpression of Phb2 countered the hyperglycemia-induced mitochondrial dysfunction and normalized the levels of key mitochondrial antioxidant enzymes. The combined data suggest a protective role for both Pgam5 knockdown and Phb2 overexpression against hyperglycemia-induced cellular and mitochondrial damage. The study elucidates the critical roles of Pgam5 and Phb2 in regulating mitochondrial dynamics in the setting of hyperglycemia-induced myocardial dysfunction. By modulating mitochondrial fission and mitophagy, Pgam5 and Phb2 emerge as key players in preserving mitochondrial integrity and cardiomyocyte health under diabetic conditions. These findings contribute significantly to our understanding of the molecular mechanisms underlying diabetic cardiomyopathy and suggest potential therapeutic targets for mitigating myocardial dysfunction in diabetes.

Altered Gut Microbiota as a Potential Risk Factor for Coronary Artery Disease in Diabetes: A Two-Sample Bi-Directional Mendelian Randomization Study.

The current body of research points to a notable correlation between an imbalance in gut microbiota and the development of type 2 diabetes mellitus (T2D) as well as its consequential ailment, coronary artery disease (CAD). The complexities underlying the association, especially in the context of diabetic coronary artery disease (DCAD), are not yet fully understood, and the causal links require further clarification. In this study, a bidirectional Mendelian randomization (MR) methodology was utilized to explore the causal relationships between gut microbiota, T2D, and CAD. By analyzing data from the DIAGRAM, GERA, UKB, FHS, and mibioGen cohorts and examining GWAS databases, we sought to uncover genetic variants linked to T2D, CAD, and variations in gut microbiota and metabolites, aiming to shed light on the potential mechanisms connecting gut microbiota with DCAD. Our investigation uncovered a marked causal link between the presence of Oxalobacter formigenes and an increased incidence of both T2D and CAD. Specifically, a ten-unit genetic predisposition towards T2D was found to be associated with a 6.1% higher probability of an increase in the Oxalobacteraceae family's presence (ß = 0.061, 95% CI = 0.002-0.119). In a parallel finding, an augmented presence of Oxalobacter was related to an 8.2% heightened genetic likelihood of CAD (ß = 0.082, 95% CI = 0.026-0.137). This evidence indicates a critical pathway by which T2D can potentially raise the risk of CAD via alterations in gut microbiota. Additionally, our analyses reveal a connection between CAD risk and Methanobacteria, thus providing fresh perspectives on the roles of TMAO and carnitine in the etiology of CAD. The data also suggest a direct causal relationship between increased levels of certain metabolites - proline, lysophosphatidylcholine, asparagine, and salicylurate - and the prevalence of both T2D and CAD. Sensitivity assessments reinforce the notion that changes in Oxalobacter formigenes could pose a risk for DCAD. There is also evidence to suggest that DCAD may, in turn, affect the gut microbiota's makeup. Notably, a surge in serum TMAO levels in individuals with CAD, coinciding with a reduced presence of methanogens, has been identified as a potentially significant factor for future examination.

Experimental and theoretical studies on the compatibility of DNTF and typical hydrocarbon polymer binders.

3,4-bis(3-nitrofurazan-4-yl) furoxan (DNTF) is one of the third-generation energetic compounds with excellent comprehensive properties, which can be added to polymer bonded explosive (PBX) to improve energy levels and regulate sensitivity, so the compatibility of DNTF with other components in PBX, especially the binder, is the first question. Herein, two typical hydrocarbon polymers commonly used in PBX, which are hydroxyl-terminated polybutadiene (HTPB) and polyisobutylene (PIB), were selected as the binder, and the compatibility of HTPB and PIB with DNTF was investigated by differential scanning calorimetry (DSC), the vacuum stability test (VST), and in situ infrared spectroscopy (in situ IR). The results of compatibility experiments were verified by using the binding energy and solubility parameter criteria in molecular dynamics (MD). Experimental and MD simulation results showed that DNTF could be compatible with PIB but incompatible with HTPB. The frontier molecular orbital theory in quantum chemistry (QC) was adopted to explore the frontier orbital electron distribution and energy levels of DNTF/HTPB and DNTF/PIB composite systems to better understand the microscopic compatibility mechanism. The compatibility results of the two composite systems were explained from the perspective of electron transfer. All these can deduce that a hydrocarbon polymer binder with a saturated carbon-hydrogen bond at the end of the molecular chain has good compatibility with DNTF, compared with a hydroxyl group, which has bad compatibility with DNTF.

Long-term outcomes in rapamycin on renal allograft function: a 30-year follow-up from a single-center experience.

OBJECTIVES: To evaluate long-term renal graft prognosis and the role of rapamycin from a single-center in China over a 30-year follow-up. METHODS: This study enrolled a total of 654 patients who underwent kidney transplantation between 1989 and 2020. The basic characteristics of the included patients were collected. Graft survival was described and compared using Kaplan-Meier curves (K-M curves). Both continuous and categorical variables were included in a multivariate Cox proportional-hazards model. Patients were divided into rapamycin-based quadruple immunosuppression regimen group (rapa group, n = 41) and conventional tacrolimus-based triple immunosuppression regimen group (control group, n = 218). The indication biopsy results of the two groups were further reviewed to compare the incidence of rejection, acute rejection, and banff score. RESULTS: The overall 5, 10, 15, 20-year graft survival rate of our center is 87.5%, 62.4%, 46.4% and 20.9%, respectively. The median survival time after surgery is 14 years. Multiple Cox regression analysis identified BMI (p = 0.035), dialysis type (p < 0.001), immunosuppressants (p < 0.01), urine albumen (p < 0.001), globulin (p = 0.041), and blood glucose (p = 0.002) as risk factors. The 20-year, 10-year and 5-year AUC is 0.78, 0.75 and 0.75. The combination of FK506 and rapamycin was further suggested by the model to effectively improve the graft prognosis (p < 0.01, HR = 0.763). The K-M curve showed that the long-term survival rate of renal grafts in the rapa group was significantly better than that in the conventional group (p < 0.001). In addition, indication biopsy records revealed a lower possibility of immune rejection in the rapa group than that in the conventional group (p < 0.001). Banff score indicated that rapa group had less vascular inflammation in the transplanted kidney. CONCLUSIONS: In this study, a 30-year follow-up was performed in a single center, and a total graft 20-year survival rate of 20.9% was reported. The prognostic model and subgroup analysis suggested that FK506 combined with rapamycin could effectively improve the prognosis of renal transplantation, which could be explained by reduced acute rejection and less vascular inflammation.

Perspectives on a peer-driven intervention to promote pre-exposure prophylaxis (PrEP) uptake among men who have sex with men in southern New England: a qualitative study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a highly effective pharmaceutical intervention that prevents HIV infection, but PrEP uptake across the US has been slow among men who have sex with men (MSM), especially among Black/African American (B/AA) and Hispanic /Latino (H/L) MSM. This study investigates the acceptability and essential components of a peer-driven intervention (PDI) for promoting PrEP uptake among MSM, with a specific focus on B/AA and H/L communities. METHODS: We conducted 28 semi-structured, qualitative interviews with MSM in southern New England to explore the components of a PDI, including attitudes, content, and effective communication methods. A purposive sampling strategy was used to recruit diverse participants who reflect the communities with the highest burden of HIV infection. RESULTS: Of 28 study participants, the median age was 28 years (interquartile range [IQR]: 25, 35). The sample comprised B/AA (39%, n = 11) and H/L (50%, n = 14) individuals. Notably, nearly half of the participants (46%) were current PrEP users. We found that many participants were in favor of using a PDI approach for promoting PrEP. Additionally, several participants showed interest in becoming peer educators themselves. They emphasized the need for strong communication skills to effectively teach others about PrEP. Moreover, participants noted that peer education should cover key topics like how PrEP works, how effective it is, and any possible side effects. CONCLUSIONS: Our study shows that effective PDIs, facilitated by well-trained peers knowledgeable about PrEP, could enhance PrEP uptake among MSM, addressing health disparities and potentially reducing HIV transmission in B/AA and H/L communities.

Clinical application of a modified wiltse approach in middle and lower thoracic vertebrae: a case-control study of thoracic fracture patients.

BACKGROUND: The Wiltse approach has been extensively employed in thoracolumbar surgeries due to its minimal muscle damage. However, in the middle and lower thoracic spine, the conventional Wiltse approach necessitates the severance of the latissimus dorsi and trapezius muscles, potentially leading to muscular injury. Consequently, we propose a modified Wiltse approach for the middle and lower thoracic vertebrae, which may further mitigate muscular damage. METHODS: From May 2018 to April 2022, 60 patients with spinal fractures in the middle and lower thoracic vertebrae (T5-12) were enrolled in this study. Thirty patients underwent surgery using the modified Wiltse approach (Group A), while the remaining 30 patients received traditional posterior surgery (Group B). The observation indices included operation time, intraoperative blood loss, incision length, number of C-arm exposures, postoperative drainage, postoperative ambulation time, discharge time, as well as preoperative and postoperative Cobb's angle, percentage of anterior vertebral body height (PAVBH), visual analog scale (VAS) Score, and Oswestry disability index (ODI). RESULTS: Compared to the traditional posterior approach, the modified Wiltse approach demonstrated significant advantages in operation time, intraoperative blood loss, length of incision, postoperative ambulation time, postoperative drainage, and discharge time, as well as postoperative VAS and ODI scores. No significant differences were observed between the two groups in terms of number of C-arm exposures, postoperative Cobb's angle, or postoperative PAVBH. CONCLUSION: We propose a modification of the Wiltse approach for the middle and lower thoracic vertebral regions, which may further minimize muscular damage and facilitate the recovery of patients who have undergone surgery in the middle and lower thoracic vertebrae.