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Abstract Background The role of triglyceride-glucose (TyG) index, an insulin resistance indicator, in glycemic management for diabetic patients with coronary artery disease (CAD) was still unknown. Therefore, we aimed to explore the association between glycemic control and cardiovascular (CV) outcomes in patients with diabetes and CAD according to different TyG index levels. Methods A total of 9996 diabetic patients with angiograph-proven CAD were consecutively recruited from 2017 to 2018 at Fuwai Hospital. Patients were assigned into 3 groups according to TyG index tertiles (T) (T1:

Abstract Background Spatial resolved transcriptomics (SRT) encompasses a rapidly developing set of technologies that enable the measurement of gene expression in tissue while retaining spatial localization information. SRT technologies and the enabled SRT studies have provided unprecedent insights into the structural and functional underpinnings of complex tissues. As SRT technologies have advanced and an increasing number of SRT studies have emerged, numerous sophisticated statistical and computational methods have been developed to facilitate the analysis and interpretation of SRT data. However, despite the growing popularity of SRT studies and the widespread availability of SRT analysis methods, analysis of large-scale and complex SRT datasets remains challenging and not easily accessible to researchers with limited statistical and computational backgrounds. Results Here, we present SRT-Server, the first webserver designed to carry out comprehensive SRT analyses for a wide variety of SRT technologies while requiring minimal prior computational knowledge. Implemented with cutting-edge web development technologies, SRT-Server is user-friendly and features multiple analytic modules that can perform a range of SRT analyses. With a flowchart-style interface, these different analytic modules on the SRT-Server can be dragged into the main panel and connected to each other to create custom analytic pipelines. SRT-Server then automatically executes the desired analyses, generates corresponding figures, and outputs results—all without requiring prior programming knowledge. We demonstrate the advantages of SRT-Server through three case studies utilizing SRT data collected from two common platforms, highlighting its versatility and values to researchers with varying analytic expertise. Conclusions Overall, SRT-Server presents a user-friendly, efficient, effective, secure, and expandable solution for SRT data analysis, opening new doors for researchers in the field. SRT-Server is freely available at https://spatialtranscriptomicsanalysis.com/ .

Abstract Background Among the safest procedures for anastomosis in pancreaticoduodenectomy, Blumgart pancreaticojejunostomy is associated with low rates of postoperative pancreatic fistula (POPF) and postoperative complications. However, this technique is difficult to perform during laparoscopic pancreaticoduodenectomy (LPD). This study presents a modified Blumgart method using a homemade crochet needle to facilitate laparoscopic pancreaticojejunostomy and evaluates its safety and reliability. Methods From February 2019 to October 2022, 96 LPD surgeries with the new technique were performed by the same surgeons in the Second Affiliated Hospital of Zhejiang University School of Medicine. The operative details (operative time, pancreaticojejunostomy time, POPF rate, postoperative complication rate, mortality rate) were analyzed along with clinical and pathological indicators (pancreatic duct diameter, pancreatic texture, and histopathological findings). Results There were 54 men and 42 women with a mean age of 63.38 ± 10.41 years. The intraoperative bleeding volume, operative time and postoperative length of hospital stay were 198.43 ± 132.97 mL, 445.30 ± 87.05 min and 13.68 ± 4.02 days, respectively. The operation time of pancreaticojejunostomy was 66.28 ± 10.17 min. Clinically relevant POPFs (grades B and C) occurred in 14.6% of patients. Only one patient had postoperative abdominal hemorrhage and was cured after reoperation. There were no operative or in-hospital deaths. With our proposed modification, the pancreatic duct and jejunal orifice are aligned correctly during duct-to-mucosa (DTM) after the application of external traction through the homemade crochet needle. The space between the posterior wall of pancreatic remnant and jejunal loop can be exposed by adjusting the tension of the external threads, which can facilitate DTM. Conclusions A modified Blumgart method using a homemade crochet needle could be technically feasible and safe during LPD. A randomized control trial is needed to confirm these findings.

Abstract Argonaute (Ago) proteins are ubiquitous across all kingdoms of life. Eukaryotic Agos (eAgos) use small RNAs to recognize transcripts for RNA silencing in eukaryotes. In contrast, the functions of prokaryotic counterparts (pAgo) are less well known. Recently, short pAgos in conjunction with the associated TIR or Sir2 (SPARTA or SPARSA) were found to serve as antiviral systems to combat phage infections. Herein, we present the cryo-EM structures of nicotinamide adenine dinucleotide (NAD+)-bound SPARSA with and without nucleic acids at resolutions of 3.1 Å and 3.6 Å, respectively. Our results reveal that the APAZ (Analogue of PAZ) domain and the short pAgo form a featured architecture similar to the long pAgo to accommodate nucleic acids. We further identified the key residues for NAD+ binding and elucidated the structural basis for guide RNA and target DNA recognition. Using structural comparisons, molecular dynamics simulations, and biochemical experiments, we proposed a putative mechanism for NAD+ hydrolysis in which an H186 loop mediates nucleophilic attack by catalytic water molecules. Overall, our study provides mechanistic insight into the antiphage role of the SPARSA system.

Abstract Background Frequent exposure to ultraviolet light has more detrimental and longer-term effects on the skin in early life than in adulthood. Teenagers with strong sun-seeking behaviors may be more likely to use an indoor tanning bed than those who seek less sun. We aimed to examine associations between sun-seeking behaviors and indoor tanning behavior during high school/college in US females. Methods In this cross-sectional study, we used data from The Nurses’ Health Study II, a large prospective cohort of US female nurses. We included a total of 81,746 white females who provided responses on the average annual frequency of indoor tanning during high school/college. Our study exposures were number of times/week spent outdoors in a swimsuit and percentage of time wearing sunscreen at the pool/beach as a teenager, weekly hours spent outdoors in direct sunlight during the daytime during high school/college, and number of severe sunburns that blistered between ages 15–20 years. The main outcome was annual frequency of indoor tanning bed usage during high school/college. Results In multivariable-adjusted logistic regression, we demonstrated positive associations between sun-seeking behaviors and indoor tanning use. Specifically, teenagers who spent 7 times/week outdoors in a swimsuit (adjusted odds ratio [aOR], 95% confidence interval [CI] for daily vs.

The complex thermo-fluid dynamics of the molten pool determine the dimension accuracy and mechanical properties of laser directed energy deposition (L-DED) components. In this work, a three-dimensional (3D) multiphase computational fluid dynamics (CFD) model based on the Volume of Fluid (VOF) method was proposed to establish the relationship between the thermo-fluid dynamics and the molten pool morphology evolution of René N5 nickel-based superalloy in L-DED. The single-track and ten-layer deposition processes under unidirectional and bidirectional scanning strategies were studied. Results show that the predicted deposition morphology and dimensions are in good agreement with the experimental samples. The heat accumulation in the multilayer deposition process increases the size of the molten pool, thereby increasing the width of the deposit. Different from the single-layer deposition driven by the Marangoni force, gravity is the key factor in the multilayer deposition process without the side support. The hump structure at the starting position under unidirectional scanning is attributed to the backward flow of the melt of the molten pool, while the decline structure at the end position is enhanced by the forward flow of the melt. At the starting position of each layer under bidirectional scanning, the expansion of the molten pool resulted from the heat accumulation and mass addition increases the width of the two ends and compensates for the deposition height. This work can provide a theoretical basis for understanding the uneven morphology characteristics and the dimensional accuracy control in L-DED.

Abstract Retrieval-based Clinical Decision Support (ReCDS) can aid clinical workflow by providing relevant literature and similar patients for a given patient. However, the development of ReCDS systems has been severely obstructed by the lack of diverse patient collections and publicly available large-scale patient-level annotation datasets. In this paper, we collect a novel dataset of patient summaries and relations called PMC-Patients to benchmark two ReCDS tasks: Patient-to-Article Retrieval (ReCDS-PAR) and Patient-to-Patient Retrieval (ReCDS-PPR). Specifically, we extract patient summaries from PubMed Central articles using simple heuristics and utilize the PubMed citation graph to define patient-article relevance and patient-patient similarity. PMC-Patients contains 167k patient summaries with 3.1 M patient-article relevance annotations and 293k patient-patient similarity annotations, which is the largest-scale resource for ReCDS and also one of the largest patient collections. Human evaluation and analysis show that PMC-Patients is a diverse dataset with high-quality annotations. We also implement and evaluate several ReCDS systems on the PMC-Patients benchmarks to show its challenges and conduct several case studies to show the clinical utility of PMC-Patients.

Abstract Background Liver stiffness (LS) is regarded as an indicator of the stages of liver fibrosis and liver cirrhosis. Numerous studies have investigated the relationship between body mass index (BMI) and LS; however, the conclusions remain controversial. In the current study, we utilized transient elastography (TE) technique, which could measure LS in a non-painful and noninvasive way, to explore the relationship between BMI and the risk of elevated LS in common community residents. Methods 5791 participants were included in the present study. To calculate BMI value, height and weight of the participants were carefully measured. Liver stiffness measurement (LSM) > 9.1 kPa was considered as a cutoff suggesting elevated LS. The relationship of BMI and risk of elevated LS was derived using generalized linear regression models, and the threshold effect was then analyzed by smooth curve fitting and segmented regression model. Results Elevated LS was detected in 230 participants (3.97%) using the TE technique. After potential confounders were adjusted according to the individual’s demographic variables, underlying comorbidities and blood biochemical test results, we observed a J-shaped relationship between BMI and the risk of elevated LS, with the inflection point at 23.05 kg/m2. The effect size (and confidence interval) was 0.84 (0.71, 0.98) on the left side of the inflection point, and 1.32 (1.24, 1.41) on the right side of it. Conclusions Our study found a novel J-shaped relationship between BMI and the risk of elevated LS assessed by TE technique. Abnormal BMI, either higher or lower, was associated with an increased risk of elevated LS.

Abstract Since the advent of COVID-19 vaccine, the long-term monitoring and evaluation of vaccine effectiveness worldwide has never stopped. Real-world research of the mainstream vaccines in China (BBIBP-CorV and CoronaVac) is extremely valuable as a supplement to clinical research data. Venous blood of this study was collected from 111 blood donors and from 6 volunteers, who had received 2 doses of SAR-CoV-2 vaccine. Cross-sectional study and cohort study was adopted. Venous blood of 11 COVID-19 convalescent plasma donors was collected as a positive control. The seroconversion rate of neutralizing antibodies in 111 vaccine recipients was 90.99% (101/111); The level of SAR-CoV-2 antibodies peaked around 28 days after inoculation, then fast descended followed by gentle descended until it was still detectable around 280 days later. The changes in antibody levels were similar to those of the 6 participants and those of convalescent plasma donors after infection. 5 of the 6 participants still maintained a high level of neutralizing antibodies (> 60% of the peak value) around 28 days after receiving 2 doses of vaccine; one participant had an antibody reaction that was almost always negative for 4 weeks. BBIBP-CorV and CoronaVac can produce good immune effects in most vaccinators aged 20 to 59 years in Nanjing area. Nevertheless, significant individual discrepancies of the humoral immunity are still existed.

Introduction: Scaffolds loaded with antibacterial agents and osteogenic drugs are considered essential tools for repairing bone defects caused by osteomyelitis. However, the simultaneous release of two drugs leads to premature osteogenesis and subsequent sequestrum formation in the pathological situation of unthorough antibiosis. Objectives: In this study, a spatiotemporal drug-release polydopamine-functionalized mesoporous silicon nanoparticle (MSN) core/shell drug delivery system loaded with antibacterial silver (Ag) nanoparticles and osteogenic dexamethasone (Dex) was constructed and introduced into a poly-l-lactic acid (PLLA) scaffold for osteomyelitis therapy. Methods: MSNs formed the inner core and were loaded with Dex through electrostatic adsorption (MSNs@Dex), and then polydopamine was used to seal the core through the self-assembly of dopamine as the outer shell (pMSNs@Dex). Ag nanoparticles were embedded in the polydopamine shell via an in situ growth technique. Finally, the Ag-pMSNs@Dex nanoparticles were introduced into PLLA scaffolds (Ag-pMSNs@Dex/PLLA) constructed by selective laser sintering (SLS). Results: The Ag-pMSNs@Dex/PLLA scaffold released Ag+ at the 12th hour, followed by the release of Dex starting on the fifth day. The experiments verified that the scaffold had excellent antibacterial performance against Escherichia coli and Staphylococcus aureus. Moreover, the scaffold significantly enhanced the osteogenic differentiation of mouse bone marrow mesenchymal stem cells. Conclusion: The findings suggested that this spatiotemporal drug release scaffold had promising potential for osteomyelitis therapy.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Accurate landslide extraction is significant for landslide disaster prevention and control. Remote sensing images have been widely used in landslide investigation, and landslide extraction methods based on deep learning combined with remote sensing images (such as U-Net) have received a lot of attention. However, because of the variable shape and texture features of landslides in remote sensing images, the rich spectral features, and the complexity of their surrounding features, landslide extraction using U-Net can lead to problems such as false detection and missed detection. Therefore, this study introduces the channel attention mechanism called the squeeze-and-excitation network (SENet) in the feature fusion part of U-Net; the study also constructs an attention U-Net landside extraction model combining SENet and U-Net, and uses Sentinel-2A remote sensing images for model training and validation. The extraction results are evaluated through different evaluation metrics and compared with those of two models: U-Net and U-Net Backbone (U-Net Without Skip Connection). The results show that proposed the model can effectively extract landslides based on Sentinel-2A remote sensing images with an F1 value of 87.94%, which is about 2% and 3% higher than U-Net and U-Net Backbone, respectively, with less false detection and more accurate extraction results.

The anomalous movements of glaciers cause disasters, such as debris flows and landslides. It is very important to assess the glacier movements and their future trends. Glacier velocity refers to movement process. The current research aims to analyse past and current spatiotemporal changes in glacier velocity. No study has used neural network model to conduct a spatiotemporal prediction for glacier velocity. Therefore, this paper selected typical mountain glaciers G2 and G5 along the Sichuan-Tibet Railway as research objects and constructed the Convolutional Gate Recurrent Unit (ConvGRU) spatiotemporal prediction model based on 1988–2018 Landsat data to predict velocities in 2019–2028, and analysed the future trends of G2 and G5. The evaluation indexes met the model requirements to a large extent, quantitatively showing that the model has high accuracy and can successfully capture the fluctuation changes in time series data of glacier velocity. The mean deviations of G2 and G5 were 0.09 and −0.47 m/yr, respectively, reflecting the high reliability of the model applied to extraction of glacier velocity. The velocities of G2 and G5 showed a slow downtrend with fluctuations; that is, they will not cause damage to the construction and operation of the Sichuan-Tibet Railway in the short term.

The attached microalgal–bacterial consortium (microalgae–bacteria biofilm, MBBF) has been increasingly recognized in wastewater treatment for its superior pollutant removal efficiency, resilience to toxic substances, and improved harvesting performance. This review initially discusses the advantages of MBBFs compared to activated sludge and suspended microalgal–bacterial consortia. These advantages stem from the coexistence of pollutant removal pathways for the bacteria and microalgae in MBBFs, as well as the synergistic interactions between the microalgae and bacteria that enhance pollutant removal and resilience capabilities. Subsequently, the establishment of the MBBF system is emphasized, covering the establishment process, influencing factors of MBBF formation, and the utilization of photobioreactors. Lastly, the challenges associated with implementing MBBFs in wastewater treatment are deliberated. This study aims to present a detailed and comprehensive overview of the application of MBBFs for wastewater treatment and biomass production.

Traditional drug development is a long and expensive process with high rates of failure. This has prompted the pharmaceutical industry to seek more efficient drug development frameworks, driving the emergence of organ-on-a-chip (OOC) based on microfluidic technologies. Unlike traditional animal experiments, OOC systems provide a more accurate simulation of human organ microenvironments and physiological responses, therefore offering a cost-effective and efficient platform for biomedical research, particularly in the development of new medicines. Additionally, OOC systems enable quick and real-time analysis, high-throughput experimentation, and automation. These advantages have shown significant promise in enhancing the drug development process. The success of an OOC system hinges on the integration of specific designs, manufacturing techniques, and biosensors to meet the need for integrated multiparameter datasets. This review focuses on the manufacturing, design, sensing systems, and applications of OOC systems, highlighting their design and sensing capabilities, as well as the technical challenges they currently face.

Multiple submerged breakwaters (MSBWs) are commonly used coastal protection structures due to their specific advantages over the emerged ones. Rip currents, as the inevitable natural hazard in the gaps of these constructions, are investigated numerically in the present study. A fully nonlinear mild-slope equation (NMSE) model possessing both fully nonlinear and fully dispersive properties is validated and adopted in the simulations. With four monochromatic wave conditions of different wave heights, periods and incidences representing low-energy, typical, storm and oblique waves tested, the flow patterns and the low-frequency oscillations of the rip currents are studied. For the convenience of risk assessment, the rip risk level is divided into three degrees according to the maximum rip flow speed. The effects of the configurations of the MSBWs on the rip current system as well as the rip risk level are examined, considering different breakwater widths, heights, forms, gap widths and gap numbers. Simulation results suggest that the cross-shore configurations of MSBWs influence the rip risk level by inducing different wave energy dissipations but the longshore configurations of MSBWs by changing flow field patterns.

Abstract Combining nutritional supplements to achieve synergistic benefit is a common practice in the nutraceutical industry. However, establishing added health benefit from a combination of natural ingredients is often assumed, [...]

Lake Okeechobee is a large and shallow freshwater body in south Florida. Due to the shallowness of Lake Okeechobee, the nutrient dynamics are strongly influenced by hydrodynamic processes (circulation and wind-induced waves) and sediment transport processes. To study water quality and the effects of hydrodynamic and sediment transport processes on nutrient dynamics in the lake, a three-dimensional simulation system that closely couples hydrodynamic and sediment transport processes with nutrient dynamics was developed and used. In this paper, we present a three-dimensional, coupled hydrodynamics-sediment-nutrient model for Lake Okeechobee. The coupled model was used to simulate a four-week survey conducted in spring 1989 in Lake Okeechobee. By comparing model results to measured field data, it is shown that the coupled model system is able to simulate weekly sediment and phosphorus dynamics in Lake Okeechobee. Model applications demonstrated that the resuspension flux of phosphorus from the lake bottom is significantly higher than the molecular flux during resuspension events and can cause increases of phosphorus concentrations in the water column. Sensitivity runs of the model show that both the advective/diffusive transport and the algal uptake promote the release of phosphorus from suspended sediments and thus affect the phosphorus budget in the lake and the net resuspension flux of phosphorus from the lake bottom. CE Database subject headings: Florida; Lakes; Three-dimensional models; Wind waves; Sediment transport; Settling velocity; Adsorption; Desorption.