Generation of genuine entanglement up to 51 superconducting qubits.

Scalable generation of genuine multipartite entanglement with an increasing number of qubits is important for both fundamental interest and practical use in quantum-information technologies1,2. On the one hand, multipartite entanglement shows a strong contradiction between the prediction of quantum mechanics and local realization and can be used for the study of quantum-to-classical transition3,4. On the other hand, realizing large-scale entanglement is a benchmark for the quality and controllability of the quantum system and is essential for realizing universal quantum computing5-8. However, scalable generation of genuine multipartite entanglement on a state-of-the-art quantum device can be challenging, requiring accurate quantum gates and efficient verification protocols. Here we show a scalable approach for preparing and verifying intermediate-scale genuine entanglement on a 66-qubit superconducting quantum processor. We used high-fidelity parallel quantum gates and optimized the fidelitites of parallel single- and two-qubit gates to be 99.91% and 99.05%, respectively. With efficient randomized fidelity estimation9, we realized 51-qubit one-dimensional and 30-qubit two-dimensional cluster states and achieved fidelities of 0.637 ± 0.030 and 0.671 ± 0.006, respectively. On the basis of high-fidelity cluster states, we further show a proof-of-principle realization of measurement-based variational quantum eigensolver10 for perturbed planar codes. Our work provides a feasible approach for preparing and verifying entanglement with a few hundred qubits, enabling medium-scale quantum computing with superconducting quantum systems.

Combining full-length gene assay and SpliceAI to interpret the splicing impact of all possible SPINK1 coding variants.

BACKGROUND: Single-nucleotide variants (SNVs) within gene coding sequences can significantly impact pre-mRNA splicing, bearing profound implications for pathogenic mechanisms and precision medicine. In this study, we aim to harness the well-established full-length gene splicing assay (FLGSA) in conjunction with SpliceAI to prospectively interpret the splicing effects of all potential coding SNVs within the four-exon SPINK1 gene, a gene associated with chronic pancreatitis. RESULTS: Our study began with a retrospective analysis of 27 SPINK1 coding SNVs previously assessed using FLGSA, proceeded with a prospective analysis of 35 new FLGSA-tested SPINK1 coding SNVs, followed by data extrapolation, and ended with further validation. In total, we analyzed 67 SPINK1 coding SNVs, which account for 9.3% of the 720 possible coding SNVs. Among these 67 FLGSA-analyzed SNVs, 12 were found to impact splicing. Through detailed comparison of FLGSA results and SpliceAI predictions, we inferred that the remaining 653 untested coding SNVs in the SPINK1 gene are unlikely to significantly affect splicing. Of the 12 splice-altering events, nine produced both normally spliced and aberrantly spliced transcripts, while the remaining three only generated aberrantly spliced transcripts. These splice-impacting SNVs were found solely in exons 1 and 2, notably at the first and/or last coding nucleotides of these exons. Among the 12 splice-altering events, 11 were missense variants (2.17% of 506 potential missense variants), and one was synonymous (0.61% of 164 potential synonymous variants). Notably, adjusting the SpliceAI cut-off to 0.30 instead of the conventional 0.20 would improve specificity without reducing sensitivity. CONCLUSIONS: By integrating FLGSA with SpliceAI, we have determined that less than 2% (1.67%) of all possible coding SNVs in SPINK1 significantly influence splicing outcomes. Our findings emphasize the critical importance of conducting splicing analysis within the broader genomic sequence context of the study gene and highlight the inherent uncertainties associated with intermediate SpliceAI scores (0.20 to 0.80). This study contributes to the field by being the first to prospectively interpret all potential coding SNVs in a disease-associated gene with a high degree of accuracy, representing a meaningful attempt at shifting from retrospective to prospective variant analysis in the era of exome and genome sequencing.

Informing the Need for a SARS-CoV-2 Booster Based Upon the Immune Responses among Young Healthy Adults to Variants Circulating in Late 2023.

BACKGROUND: COVID-19 remains a global public health challenge due to new immune-evasive SARS-CoV-2 variants and heterogeneous immunity. METHODS: In this cross-sectional study, we evaluated the adaptive immune responses in U.S. active-duty personnel who completed a COVID-19 primary vaccine series and with heterogenous SARS-CoV-2 vaccination and infection histories to 3 previously dominant variants (Ancestral, Delta, BA.5) and 3 circulating variants (XBB.1.5, EG.5, and BA.2.86) in late 2023. Analyses were performed based upon timing (within or beyond 12 months) and type (vaccine or infection) of the most recent exposure. RESULTS: Significant reduction was observed in binding antibodies, neutralization antibodies, memory B cells, and CD8+ T cells against circulating variants compared to previous variants. The reduction in antibody response was more pronounced in those whose most recent exposure was greater than 12 months from enrollment. In contrast, the CD4+ T cell response was largely consistent across all tested variants. The type of most recent exposure was not a significant factor in determining the magnitude of current immune responses. CONCLUSIONS: Administration of the XBB.1.5-based booster is likely to enhance cross-reactive humoral responses against SARS-CoV-2 circulating lineages. Ongoing surveillance of immune responses to emerging variants is needed for informing vaccine composition and timing.

Organelle Proximity Analysis for Enhanced Quantification of Mitochondria-Endoplasmic Reticulum Interactions in Single Cells via Super-Resolution Microscopy.

Mitochondria (MT) and the endoplasmic reticulum (ER) maintain lipid and calcium homeostasis through membrane contacts, particularly MT-ER contacts (MERCs), spanning distances from 10 to 50 nm. However, the variation of different distance ranges and the metabolic factors influencing this variation remain poorly understood. This study employed microfluidic chip-based super-resolution microscopy in conjunction with a Moore-Neighbor tracing-incorporated organelle proximity analysis algorithm. This approach enabled precise three-dimensional localization of single-fluorescence protein molecules within narrow and irregular membrane proximities. It achieved lateral localization precision of less than 20 nm, resulting in a minimum MERC distance of approximately 8 nm in spatial and mean distances across multiple threshold ranges. Additionally, we demonstrated that the MERC distance variation was correlated with MT size rather than ER width. The proportion of each distance range varied significantly after the stimuli. Free cholesterol showed a negative correlation with various distances, while distances of 10-30 nm were associated with glucose, glutamine, and pyruvic acid. Furthermore, the 30-40 nm range was influenced by citric acid. These results underscore the role of advanced subcellular organelle analysis in elucidating the single-molecule behavior and organelle morphology in single-cell studies.

One-Shot Dual-Detection-Based Single-Molecule Super-Resolution Imaging Method for Real-Time Observation of Spatiotemporal Catalytic Activity Variations on the Plasmonic Gold Nanoparticle Surface.

Understanding the relationship between the surface properties of a single plasmonic nanoparticle and its catalytic performance is critical for developing highly efficient nanocatalysts. In this study, a one-shot dual-detection-based single-molecule super-resolution imaging method in the evanescent field was developed to observe real-time spatiotemporal catalytic activity on a single plasmonic gold nanoparticle (AuNP) surface. The scattering intensity of AuNPs and the fluorescence of resorufin molecules produced on the AuNP surface were obtained simultaneously to investigate the relationship between nanoparticles and catalytic reactions at a single-molecule level. Chemisorbed adsorbates (i.e., catalytic product and resorufin) changed the electron density of individual AuNPs throughout the catalytic cycle, resulting in the fluctuation of the scattering intensity of individual AuNPs, which was attributed to the electron transfer between reactant resazurin molecules and AuNPs. The increase in the electron density of individual AuNPs affected the catalytic reaction rate. Furthermore, sequential mapping of individual catalytic events at the subdiffraction limit resolution was completed for real-time surface dynamics and spatiotemporal activity variations on the single AuNP surface. The developed method can aid in understanding surface-property-dependent catalytic kinetics and facilitate the development of nanoparticle-based heterogeneous catalysts at subdiffraction limit resolution.

Fabrication and Performance of Bubble-Containing Multicompartmental Particles: Novel Self-Orienting Carriers.

In this work, a class of bubble-containing multicompartmental particles with self-orienting capability is developed, where a single bubble is enclosed at the top of the super-segmented architecture. Such bubbles, driven by potential energy minimization, cause the particles to have a bubble-upward preferred orientation in liquid, enabling efficient decoding of their high-density signals in an interference-resistant manner. The particle preparation involves bubble encapsulation via the impact of a multicompartmental droplet on the liquid surface and overall stabilization via rational crosslinking. The conditions for obtaining these particles are systematically investigated. Methodological compatibility with materials is demonstrated by different hydrogel particles. Finally, by encapsulating cargoes of interest, these particles have found broad applications in actuators, multiplexed detection, barcodes, and multicellular systems.

Gravity-Oriented Microfluidic Device for Biocompatible End-to-End Fabrication of Cell-Laden Microgels.

Droplet microfluidics are extensively utilized to generate monodisperse cell-laden microgels in biomedical applications. However, maintaining cell viability is still challenging due to overexposure to harsh conditions in subsequent procedures that recover the microgels from the oil phase. Here, a gravity-oriented microfluidic device for end-to-end fabrication of cell-laden microgels is reported, which integrates dispersion, gelation, and extraction into a continuous workflow. This innovative on-chip extraction, driven by native buoyancy and kinetically facilitated by pseudosurfactant, exhibits 100% retrieval efficiency for microgels with a wide range of sizes and stiffnesses. The viability of encapsulated cells is perfectly maintained at ≈98% with minimal variations within and between batches. The end-to-end fabrication remarkably enhances the biocompatibility and practicality of microfluidics-based cell encapsulation and is promising to be compatible with various applications ranging from single-cell analysis to clinical therapy.

Optical transmission of microwave control signal towards large-scale superconducting quantum computing.

With the rapid development of superconducting quantum computing and the implementation of surface code, large-scale quantum computing is emerging as an urgent demand. In a superconducting computing system, the qubit is maintained in a cryogenic environment to avoid thermal excitation. Thus, the transmission of control signals, which are generated at room temperature, is needed. Typically, the transmission of these signals to the qubit relies on a coaxial cable wiring approach. However, in a large-scale computing system with hundreds or even thousands of qubits, the coaxial cables will pose great space and heat load to the dilution refrigerator. Here, to tackle this problem, we propose and demonstrate a direct-modulation-based optical transmission line. In our experiment, the average single-qubit XEB error and control error are measured as 0.139% and 0.014% separately, demonstrating the feasibility of the optical wiring approach and paving the way for large-scale superconducting quantum computing.

The silk gland proteome of Stenopsyche angustata provides insights into the underwater silk secretion.

Caddisworms (Trichoptera) spin adhesive silks to construct a variety of underwater composite structures. Many studies have focused on the fibroin heavy chain of caddisworm silk and found that it contains heavy phosphorylation to maintain a stable secondary structure. Besides fibroins, recent studies have also identified some new silk proteins within caddisworm silk. To better understand the silk composition and its secretion process, this study reports the silk gland proteome of a retreat-building caddisworm, Stenopsyche angustata Martynov (Trichoptera, Stenopsychidae). Using liquid chromatography tandem mass spectrometry (LC-MS/MS), 2389 proteins were identified in the silk gland of S. angustata, among which 192 were predicted as secreted silk proteins. Twenty-nine proteins were found to be enriched in the front silk gland, whereas 109 proteins were enriched in the caudal silk gland. The fibroin heavy chain and nine uncharacterized silk proteins were identified as phosphorylated proteins. By analysing the sequence of the fibroin heavy chain, we found that it contains 13 Gly/Thr/Pro-rich regions, 12 Val/Ser/Arg-rich regions and a Gly/Arg/Thr-rich region. Three uncharacterized proteins were identified as sericin-like proteins due to their larger molecular weights, signal peptides and repetitive motifs rich in serine. This study provides valuable information for further clarifying the secretion and adhesion of underwater caddisworm silk.

Sub-inhibitory concentrations of tetrabromobisphenol A induce the biofilm formation of methicillin-resistant Staphylococcus aureus.

Biofilm formation by methicillin-resistant Staphylococcus aureus (MRSA) on indwelling medical devices complicates the treatment of infection. Tetrabromobisphenol A (TBBPA), a synthetic, lipophilic, halogenated aromatic compound widely used as an additive in plastics and electronic products, has raised environmental concerns due to its potential for bioaccumulation. This study investigated the impact of sub-inhibitory concentrations of TBBPA on MRSA biofilm formation. Crystal violet staining and confocal laser scanning microscopy analysis demonstrated that 1/8 MIC (0.5 µg/mL) of TBBPA significantly stimulated MRSA biofilm formation (P < 0.0001). MTT assays indicated that the metabolic activity within the biofilms increased by 15.60-40.85% compared to untreated controls. Dot blot immunoassay, autolysis assay, and extracellular DNA (eDNA) quantification further revealed TBBPA enhanced the production of polysaccharide intercellular adhesin (PIA) and eDNA, which are key biofilm components. Additionally, TBBPA was found to enhance the production of staphyloxanthin, facilitating MRSA survival under oxidative conditions and in human whole blood. RT-qPCR analysis showed that TBBPA significantly upregulated genes associated with biofilm formation (icaA, atlA, sarA), staphyloxanthin biosynthesis (crtM and sigB), and oxidative stress responses (sodA and katA). These findings suggest that TBBPA promotes MRSA biofilm development and enhances bacterial resistance to adverse conditions, thereby potentially exacerbating risks to human health.

The association of serum uric acid with all-cause and cardiovascular mortality among adults with rheumatoid arthritis: a cohort study.

OBJECTIVES: Serum uric acid (SUA) is associated with poor outcomes in patients with numerous types of disease. However, the association between SUA and the outcomes of patients with rheumatoid arthritis (RA) remains to be fully elucidated. Thus, the present study aimed to determine the associations between SUA and all-cause or cardiovascular disease (CVD)-associated mortality in adults with RA. METHODS: The data of patients with RA were collected from the National Health and Nutrition Examination Survey from 2001 to 2018. All-cause and CVD-associated mortality were identified using national death records through 31 December 2019. Weighted survival curves, Cox proportional hazards regression models, restricted cubic splines (RCS) and stratified analyses were used to assess the association between SUA levels and mortality. RESULTS: Among 2,312 patients with RA, a total of 597 all-cause deaths and 198 CVD-associated deaths were recorded during 19,133 person-years of follow-up. The results of the Kaplan-Meier curves for long-term all-cause and CVD-associated mortality demonstrated that increased levels of SUA were associated with a higher incidence of mortality. In the fully adjusted models, the highest SUA quartile exhibited hazard ratios [(HRs); 95% confidence intervals (CIs)] of 1.53 (1.10, 2.14) for all-cause mortality and 1.93 (1.14, 3.27) for CVD-associated mortality, compared with the lowest SUA quartile. The results of the RCS analysis confirmed a strong linear association between SUA levels and the HR of all-cause mortality, while a U-shaped association was observed between SUA and CVD-associated mortality. CONCLUSIONS: The results of the present study demonstrated that high SUA levels were significantly associated with increased risks of all-cause and CVD-associated mortality in patients with RA. Further studies are required to elucidate the potential impact of treatments on reducing SUA levels.

Ruthenium Complexes with NNN-Pincer Ligands for N-Methylation of Amines Using Methanol.

A series of ruthenium complexes (Ru1-Ru4) bearing new NNN-pincer ligands were synthesized in 58-78% yields. All of the complexes are air and moisture stable and were characterized by IR, NMR, and high-resolution mass spectra (HRMS). In addition, the structures of Ru1-Ru3 were confirmed by X-ray crystallographic analysis. These Ru(II) complexes exhibited high catalytic efficiency and broad functional group tolerance in the N-methylation reaction of amines using CH3OH as both the C1 source and solvent. Experimental results indicated that the electronic effect of the substituents on the ligands considerably affects the catalytic reactivity of the complexes in which Ru3 bearing an electron-donating OMe group showed the highest activity. Deuterium labeling and control experiments suggested that the dehydrogenation of methanol to generate ruthenium hydride species was the rate-determining step in the reaction. Furthermore, this protocol also provided a ready approach to versatile trideuterated N-methylamines under mild conditions using CD3OD as a deuterated methylating agent.

Translation, cultural adaptation, and validation of the Chinese standardized outcomes in nephrology-hemodialysis fatigue (C-SONG-HD fatigue) scale: a study of Chinese patients undergoing hemodialysis.

OBJECTIVE: This study aimed to translate and culturally adapt the standardized outcomes in nephrology-hemodialysis fatigue (SONG-HD fatigue) scale and to assess the psychometric properties of the Chinese version of the SONG-HD fatigue (C-SONG-HD fatigue) scale. METHODS: Forward and back translations were used to translate the SONG-HD fatigue scale into Chinese. We used the C-SONG-HD fatigue scale to survey Chinese patients undergoing hemodialysis (HD) in China. We examined the distribution of responses and floor and ceiling effects. Cronbach's alpha and McDonald's omega coefficient, intraclass coefficients, and Spearman correlations were used to assess internal consistency reliability, test-retest reliability, and convergent validity, respectively. Responsiveness was also evaluated. RESULTS: In total, 489 participants across southeast China, northwest China, and central China completed the study. The C-SONG-HD fatigue scale had good internal consistency (Cronbach's alpha coefficient 0.861, omega coefficient 0.916), test-retest reliability (intraclass correlation coefficient 0.695), and convergent validity (Spearman correlation 0.691). The analysis of all first-time HD patients did not show notable responsiveness, and only patients with temporary vascular access had good responsiveness with an effect size (ES) of 0.54, a standardized response mean (SRM) of 0.85, and a standard error of measurement (SEM) of 0.77. CONCLUSION: The Chinese version of the SONG-HD fatigue scale showed satisfactory reliability and validity in patients undergoing hemodialysis (HD) in China. It could be used as a tool to measure the fatigue of Chinese HD patients.

Eucalyptol-loaded microcapsules combined with Cynanchum komarovii extracts provide long-term and low-risk management of Chinese wolfberry (Lycium barbarum L.).

Realizing eco-friendly, long-term, and low-risk aphid control on Lycium barbarum (medicinal cash crop) using a Cynanchum komarovii extracts and eucalyptus oil-loaded microcapsules (EOMCs) formulation compositions is viable. In this study, the aim is to optimize the composition of Cynanchum komarovii extracts and EOMCs formulation for effective control of aphids, the release of EOMCs was controlled by changing the cross-linking degree of the shell to match the aphid control characteristics of Cynanchum komarovii extracts. Four types of polyamines were used as cross-linking agents for the preparation of EOMCs by interfacial polymerization. The bioactivity, wettability, and field application efficacy of Cynanchum komarovii extracts and different EOMCs formulation compositions were evaluated. These EOMCs exhibited an encapsulation efficiency exceeding 85 %. The control efficiency of the formulation compositions of microcapsules with a moderate release rate and Cynanchum komarovii extracts on aphids remained at 62.86 %, while the control efficiency of the combination of microcapsules with the fastest and slowest rates with Cynanchum komarovii extracts was only 48.62 % and 57.11 %, respectively. The formulation compositions of Cynanchum komarovii extracts with all four types of EOMCs were found to be safe for Chinese wolfberry plants. Overall, by selecting appropriate polyamines during fabrication, the release rate can be effectively controlled to achieve sustainable and low-risk aphid control in Lycium barbarum through compounding with selected microcapsules.

Prenatal diagnosis and appearance of nasal chondromesenchymal hamartoma in a fetus: A case report.

We report a case of fetal nasal chondromesenchymal hamartoma (NCMH) first noted on prenatal ultrasound at 34 weeks. A solid-cystic mass which predominantly hyperechoicgenic and relatively clear margin, was located on the left nasal cavity and pharynx, with anterior extension and moderate blood flow. Further follow-up ultrasound examination depicted an enlargement of the tumor. Fetal magnetic resonance imaging (MRI) showed an inhomogeneous signal lesion involving the ethmoid sinuses, nasal cavity, and pharynx. The infant, delivered via cesarean section at 37 + 5 weeks, required urgent neonatology intervention due to respiratory difficulties. Neonatal MRI and computer tomography were subsequently performed at 1 day after birth. Surgical excision occurred at 7 days, confirming NCMH via histological examination. Awareness of this entity, is essential to avoid potentially harmful therapies, especially in prenatal period. Considered NCMH in diagnosis when fetal nasal masses presenting with predominantly high-level echo, well-defined margins and moderate vascularity.

Impact of Sjögren's syndrome on maternal and fetal outcomes following pregnancy: a systematic review and meta-analysis of studies published between years 2007-2022.

OBJECTIVE: To show the impact of Sjögren's syndrome (SS) on maternal and fetal outcomes following pregnancy. METHODS: We performed a literature search based on PubMed, Web of science, Wan fang, China National Knowledge Infrastructure and ProQuest databases from 1 January 2007 to 6 November 2022. Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the certainty of the evidence. Systematic reviews and meta-analyses were performed using RevMan 5.3 software. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Trial sequential analyses were performed by TSA 0.9. RESULTS: Nine studies with 2341 patients and 2472 pregnancies with SS were included in our analysis. This current analysis showed pregnancy hypertension and preeclampsia/eclampsia to be significantly higher in pregnant women with SS compared to pregnant women without SS (OR: 1.65, 95% CI: 1.04-2.63; P = 0.03), (OR: 2.06, 95% CI: 1.16-3.65; P = 0.01) respectively. Cesarean section, thromboembolic disease, premature rupture of membranes, and spontaneous abortion were also significantly higher in the SS women with OR: 2.07, 95% CI: 1.48-2.88; P < 0.0001, OR: 9.45, 95% CI: 1.99-44.87; P = 0.005, OR: 1.36, 95% CI: 1.13-1.64; P = 0.001, OR: 9.30, 95% CI: 4.13-20.93; P < 0.00001, respectively. Significantly higher premature births were observed with infants who were born from SS mothers (OR: 2.19, 95% CI: 1.54-3.12; P < 0.0001). Infants defined as 'small for gestational age/intrauterine growth restriction' and 'weighing < 2500 g' were also significantly higher in patients suffering from SS (OR: 2.26, 95% CI: 1.38-3.70; P = 0.001), (OR: 3.84, 95% CI: 1.39-10.61; P = 0.009) respectively. In addition, live birth significantly favored infants who were born from mothers without SS (OR: 21.53, 95% CI: 8.36-55.44; P < 0.00001). Subgroup analysis by sample size revealed that pregnancy hypertension risk has significantly increased in small cohort (OR: 2.74, 95%CI: 1.45-5.18), and a slight increase was found in population-based studies (OR: 1.14, 95%CI: 0.91-1.43). In both small cohorts and population-based researches, cesarean section was significantly higher in SS (OR: 2.13, 95% CI: 1.29, 3.52; OR: 1.85, 95% CI: 1.29-2.64, respectively). The number of infants with intrauterine growth restriction did not grow in the population-based researches (OR: 2.07, 95%CI: 0.92-4.66) although there has been an increase in small reports (OR: 2.53, 95%CI: 1.16-5.51). Subgroup analysis was conducted on the basis of study location (not Asian vs. Asian countries) indicated that cesarean section was significantly higher in SS in both countries (OR: 1.69, 95% CI: 1.31-2.18; OR: 3.37, 95% CI: 2.39-4.77, respectively). CONCLUSION: This meta-analysis has shown SS to have a high impact on maternal and fetal outcomes following pregnancy.

Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis. METHODS: PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software. RESULTS: A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (ß2-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or ß2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias. CONCLUSIONS: The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly used to treat diabetic neuropathy (DN) and Astragalus membranaceus components are known to improve DN symptoms.We aimed to establish the efficacy and safety of using Astragalus combined with RAAS inhibitors.Astragalus combined with RAAS inhibitors enhances the total effective rate of diabetic neuropathy response to treatment and reduces urinary protein excretion rate, serum creatinine, blood urea nitrogen and HbAlc.Sensitivity analysis affirms study stability, while publication bias was detected for total effective rate, serum creatinine, and 24 h urinary protein levels.

Role of Trace Cadmium Exposure on the Development of Occlusal Traumatic Temporomandibular Arthritis.

OBJECTIVE: To investigate whether heavy metal cadmium acts as a risk factor for temporomandibular joint disorder disease and to study its pathogenic mechanism. METHODS: A total of 57 rats were allocated into 6 distinct groups, distinguished by 2 interventions: occlusal elevation and cadmium water gavage. These groups included a blank control group, occlusal elevation group, occlusal elevation + 0.42 mg/mL cadmium water gavage group, occlusal elevation + 4.2 mg/mL cadmium water gavage group, no occlusal elevation + 0.42 mg/mL cadmium water gavage group, and no occlusal elevation + 4.2 mg/mL cadmium water gavage group. The impact of cadmium exposure on cartilage oxidative stress was evaluated through the assessment of SOD, CAT, GST, and GSH-Px enzyme activities. In addition, the influence of cadmium exposure on alterations in the extracellular matrix and inflammatory mediators was examined by analyzing the expression levels of type II collagen, protein aggregation polysaccharide, glycosaminoglycan, IL1ß, IL-6, and TNF-α. Histologic examination of the condylar process cartilage of rats in the occlusal elevation + cadmium water gavage group was conducted to ascertain the occurrence of osteoarthritis. RESULTS: The variance in the expression levels of inflammatory factors did not demonstrate statistical significance between the occlusal elevation group and the blank control group; however, statistical significance was observed between the occlusal elevation + cadmium water gavage group and both the control and occlusal elevation groups. CONCLUSION: The severity of inflammation and condylar lesions correlates directly with the concentration of cadmium.

Integrated Methylome and Transcriptome Analysis between Wizened and Normal Flower Buds in Pyrus pyrifolia Cultivar 'Sucui 1'.

Here, cytosine methylation in the whole genome of pear flower buds was mapped at a single-base resolution. There was 19.4% methylation across all sequenced C sites in the Pyrus pyrifolia cultivar 'Sucui 1' flower bud genome. Meantime, the CG, CHG, and CHH sequence contexts (where H = A, T or C) exhibited 47.4%, 33.3%, and 11.9% methylation, respectively. Methylation in different gene regions was revealed through combining methylome and transcriptome analysis, which presented various transcription trends. Genes with methylated promoters exhibited lower expression levels than genes with non-methylated promoters, while body-methylated genes displayed an obvious negative correlation with their transcription levels. The methylation profiles of auxin- and cytokinin-related genes were estimated. And some of them proved to be hypomethylated, with increased transcription levels, in wizened buds. More specifically, the expression of the genes PRXP73, CYP749A22, and CYP82A3 was upregulated as a result of methylation changes in their promoters. Finally, auxin and cytokinin concentrations were higher in wizened flower buds than in normal buds. The exogenous application of paclobutrazol (PP333) in the field influenced the DNA methylation status of some genes and changed their expression level, reducing the proportion of wizened flower buds in a concentration-dependent manner. Overall, our results demonstrated the relationship between DNA methylation and gene expression in wizened flower buds of P. pyrifolia cultivar 'Sucui 1', which was associated with changes in auxin and cytokinin concentrations.

A systematic analysis on global epidemiology and burden of foot fracture over three decades.

PURPOSE: To comprehensively analyze the geographic and temporal trends of foot fracture, understand its health burden by age, sex, and sociodemographic index (SDI), and explore its leading causes from 1990 to 2019. METHODS: The datasets in the present study were generated from the Global Burden of Diseases Study 2019, which included foot fracture data from 1990 to 2019. We extracted estimates along with the 95% uncertainty interval (UI) for the incidence and years lived with disability (YLDs) of foot fracture by location, age, gender, and cause. The epidemiology and burden of foot fracture at the global, regional, and national level was exhibited. Next, we presented the age and sex patterns of foot fracture. The leading cause of foot fracture was another focus of this study from the viewpoint of age, sex, and location. Then, Pearson's correlations between age-standardized rate (ASR), SDI, and estimated annual percentage change were calculated. RESULTS: The age-standardized incidence rate was 138.68 (95% UI: 104.88 - 182.53) per 100,000 persons for both sexes, 174.24 (95% UI: 134.35 - 222.49) per 100,000 persons for males, and 102.19 (95% UI: 73.28 - 138.00) per 100,000 persons for females in 2019. The age-standardized YLDs rate was 5.91 (95% UI: 3.58 - 9.25) per 100,000 persons for both genders, 7.35 (95% UI: 4.45 - 11.50) per 100,000 persons for males, and 4.51 (95% UI: 2.75 - 7.03) per 100,000 persons for females in 2019. The global incidence and YLDs of foot fracture increased in number and decreased in ASR from 1990 to 2019. The global geographical distribution of foot fracture is uneven. The incidence rate for males peaked at the age group of 20 - 24 years, while that for females increased with advancing age. The incidence rate of older people was rising, as younger age incidence rate declined from 1990 to 2019. Falls, exposure to mechanical forces, and road traffic injuries were the 3 leading causes of foot fracture. Correlations were observed between ASR, estimated annual percentage change, and SDI. CONCLUSIONS: The burden of foot fracture remains high globally, and it poses an enormous public health challenge, with population ageing. It is necessary to allocate more resources to the high-risk populations. Targeted realistic intervention policies and strategies are warranted.