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Abstract Background To investigate the role of antiphospholipid antibodies (aPLs) in the disease severity and prognosis of SLE-related thrombocytopenia (SLE-TP). Methods This multicenter prospective study was conducted based on data from the CSTAR registry. TP was defined as a platelet count

Aim Tripterygium wilfordii Hook F (TwHF) has been shown to substantially reduce proteinuria in patients with diabetic kidney disease (DKD); however, the effect of TwHF on renal outcomes in DKD remains unknown. Accordingly, we aimed to establish the effects of TwHF on renal outcomes in patients with DKD.Methods Overall, 124 patients with DKD, induced by type 2 diabetes mellitus, with 24-h proteinuria > 2 g, and an estimated glomerular filtration rate > 30 mL/min/1.73 m2 were retrospectively investigated. The renal outcomes were defined as doubling serum creatinine levels or end-stage kidney disease. Kaplan-Meier curves and Cox regression analyses were performed to analyze prognostic factors for renal outcomes.Results By the end of the follow-up, renal outcomes were observed in 23 and 11 patients in the non-TwHF and TwHF groups, respectively (p = 0.006). TwHF significantly reduced the risk of renal outcomes (adjusted hazard ratio [HR] 0.271, 95% confidence interval [CI] 0.111–0.660, p = 0.004) in patients with chronic kidney disease (CKD) G3 (adjusted HR 0.274, 95%CI 0.081–0.932, p = 0.039). Based on the Kaplan-Meier analysis, 1- and 3-year proportions of patients without renal outcomes were significantly lower in the non-TwHF group than those in the TwHF group (92.8% vs. 95.5% and 47.2% vs. 76.8%, respectively; p = 0.0018).Conclusion In DKD patients with severe proteinuria, TwHF could prevent DKD progression, especially in patients with CKD G3. A randomized clinical trial is needed to elucidate the benefits of TwHF on renal outcomes in patients with DKD.

Dimethyl sulfur compounds including dimethylsulfoniopropionate (DMSP), dimethyl sulfide (DMS), and dimethyl sulfoxide (DMSO), play a crucial part in global sulfur cycling. The eastern Indian Ocean (EIO), characterized by its remarkable diversity of biomes and climate dynamics, is integral to global climate regulation. However, the regulation mechanism of DMS (P, O) in the EIO remains to be elucidated in detail. This paper presented a field survey aimed at investigating the spatial distribution of DMS (P, O) and their relationships with environmental and biological factors in the EIO. The surface concentrations of DMS, DMSPt, and DMSOt varied from 0.07 to 7.37 nmol/L, 0.14 to 9.17 nmol/L, and 0.15 to 3.32 nmol/L, respectively, and their distributions are attributed to high Chl-a concentration near Sri Lanka and the influence of ocean currents (Wyrtki jets, Bay of Bengal runoff). Higher concentrations of DMS (P) and DMSOt were predominantly observed in water columns shallower than 75m and deeper than 75m deep, respectively. The monthly DMS fluxes in the study area peaked in August. Temperature and Dissolved Silica Index (DSI) were the key environmental determinants for DMS distribution, while nitrate (NO3-) was the primary factor for both DMSPt and DMSOt. In terms of biological factors, Prochlorococcus and Synechococcus were significant contributors to DMS (P, O) dynamics. Synechococcus was the dominant influence on the DMS source and DMSPt sink, whereas Prochlorococcus primarily consumed DMSOt. Furthermore, the structural equation modeling (SEM) revealed the relationship between DMS, DMSPt, DMSOt, and the key environmental/biological factors, as well as among them, and together they formed a co-regulatory network in the EIO. This contributes significantly to the advancement of global ecosystem models for DMS (P, O).

Abstract Processing can affect milk properties and alter the composition of milk metabolites, which has corresponding effects on milk flavor and quality. It is quite important to study the safe quality control of milk processing. Therefore, the purpose of this study was to identify metabolites at different steps of ultra‐high‐temperature‐sterilized (UHT) milk processing using gas chromatography–mass spectrometry (GC–MS). These steps included raw milk, pasteurized milk (80°C for 15 s), semi‐finished milk (after pasteurizing, it was homogenized at 75°C with pressure of 250 bar), UHT milk (at 140°C for 10 s), and finished milk (homogenized UHT milk). A total of 66 metabolites were identified across all samples, including 30 metabolites in the chloroform layers of the milk samples and 41 metabolites in the water layers; 5 metabolites were found in both layers. The metabolites were primarily fatty acids, amino acids, sugars, and organic acids. For example, pasteurized and ultra‐high‐temperature‐sterilized kinds of milk had lactose contents similar to those of raw milk, with increases in saturated fatty acids such as hexadecanoic acid and octadecanoic acid. Additionally, these findings indicated that these methods of processing can affect the contents of some components of milk. Therefore, from the perspective of milk's nutritional value and consumer health, the excessive heating of dairy products should be avoided and the milk heat treatment process should be standardized from the source.

Tooth enamel, which is a biological tissue mainly composed of well-aligned hydroxyapatite nanocrystals and an interlaced protein matrix, has remarkable mechanical and aesthetic behaviors. Nevertheless, it is challenging to regenerate enamel naturally, and potential pulp involvement and tooth loss may occur. As the hardest biogenic composite material, enamel has long been regarded as a promising load-bearing material. Thus, understanding the enamel formation process and enamel structural motif mechanisms is important for the design and engineering of high-performance biomimetic composites with high strength and physical resilience. Extensive studies have been conducted on mimicking the microstructure and mechanical properties of tooth enamel, and various enamel-like material synthesis protocols have been developed. In light of the engineering fabrication of enamel-like materials, this review focuses on recent progress in synthetic strategies for enamel-mimetic materials and provides a discussion of the potential applications of these materials.

PurposeIntravitreal vascular endothelial growth factor (VEGF) blockade is essential in many macular edema diseases treatment. However, intravitreal VEGF treatment has been reported to lead to deteriorated proteinuria and renal function. This study aimed to explore the relationship between renal adverse events (AEs) and the intravitreal use of VEGF inhibitors.MethodIn the FDA’s Adverse Event Reporting System (FAERS) database, we searched for renal AEs of patients receiving various anti-VEGF drugs. We performed statistics on renal AEs in patients treated with Aflibercept, Bevacizumab, Ranibizumab, and Brolucizumab (from January 2004 to September 2022) using disproportionate and Bayesian analysis. We also investigated the time to onset, fatality, and hospitalization rates of renal AEs.ResultsWe identified 80 reports. Renal AEs were most frequently associated with Ranibizumab (46.25%) and Aflibercept (42.50%). However, the association between intravitreal anti-VEGFs and renal AEs was insignificant since the reporting odds ratio of Aflibercept, Bevacizumab, Ranibizumab, and Brolucizumab were 0.23 (0.16, 0.32), 0.24 (0.11, 0.49), 0.37 (0.27, 0.51) and 0.15 (0.04, 0.61), respectively. The median time to renal AEs onsets was 37.5 (interquartile range 11.0–107.3) days. The hospitalization and fatality rates in patients who developed renal AEs were 40.24 and 9.76%, respectively.ConclusionThere are no clear signals for the risk of renal AEs following various intravitreal anti-VEGF drugs based on FARES data.

Abstract Backgroud To analyze the morphological changes of the anterior alveolar bone after the retraction of incisors in premolar extraction cases and the relationship between incisor retraction and remodeling of the alveolar base represented by points A and B displacements. Methods Pre- (T0) and post-treatment (T1) lateral cephalograms of 308 subjects in the maxilla and 154 subjects in the mandible who underwent the orthodontic treatment with extraction of 2 premolars in upper or lower arches were included. Alveolar bone width and height in both the maxillary and mandible incisor area were measured at T0 and T1 respectively. By superimposing the T0 and T1 cephalometric tracings, changes of points A and B, and the movement of the incisors were also measured. Then the correlation between incisor movement and the displacements of points A and B was analyzed. Results The alveolar bone width (ABW) showed a significant decrease in both maxilla and mandible (P 0.05). The alveolar bone height (ABH) showed a significant increase in the labial side of maxilla and a significant decrease in the lingual side of maxilla and mandible. A strong positive correlation was verified between incisor movement and position changes of points A and B in both horizontal and vertical directions. Conclusions Anterior alveolar bone width and height generally decreased after orthodontic treatment. Incisor retraction led to significant position changes of points A and B. The decrease of anterior alveolar bone due to significant incisor retraction should be taken into account in treatment planning.

Dimethyl sulfide (DMS) is one of the most important volatile biogenic sulfur compounds and plays a significant role in global climate change. Studying the seasonal variations and the environmental factors that affect the concentration of DMS would aid in understanding the biogeochemical cycle of sulfur compounds. Using benzene-assisted photoionization positive ion mobility spectrometry (BAPI-PIMS), the seasonal distribution and the key impact factors of DMS and dimethylsulfoniopropionate (DMSP) in the Bohai Sea and North Yellow Sea were investigated in the summer and autumn of 2019. The concentrations of DMS and its precursors, DMSPp and DMSPd, in the surface seawater were 0.11–23.90, 0.67–41.38, and 0.03–12.28 nmol/L, respectively, in summer, and 0.10–20.79, 0.39–13.51, and 0.18–20.58 nmol/L, respectively, in autumn. The air-to-sea exchange flux of DMS was 43.05 ± 44.52 and 34.06 ± 63.38 μmol/(m·d), respectively, in summer and autumn. The results demonstrated that the temperature was the most dominant environmental factor, and the abundance of dinoflagellates was the most dominant biological factor that affected the distribution of DMS and DMSP in summer. The abundance of diatoms was the most dominant biological factor, and the levels of PO43-, NO2-, NO3-, and SiO32- were the dominant environmental factors that affected the distribution of DMS and DMSP in autumn. These results of this study would be of great significance in understanding the biochemical cycle of DMS in BS and NYS.

With the rapid development of the three-dimensional (3D) printing technology in recent decades, precise and personalized manufacturing has been achieved gradually, bringing benefit to biomedical application, especially stomatology clinical practice. So far, 3D printing has been widely applied to prosthodontics, orthodontics, and maxillofacial surgery procedures, realizing accurate, efficient operation processes and promising treatment outcomes. Although the printing accuracy has improved, further exploration is still needed. Herein, we summarized the various additive manufacturing techniques and their applications in dentistry while highlighting the importance of accuracy (precision and trueness).

Objective The effectiveness and safety of sirolimus for SLE treatment have been shown in some uncontrolled studies. However, a comparison of sirolimus with other classic immunosuppressants has not been reported. We conducted the study to compare the effectiveness and safety of sirolimus versus tacrolimus for SLE treatment.Methods A real-world cohort study was conducted. Patients with clinically active SLE who were prescribed sirolimus or tacrolimus were enrolled. Propensity score matching was used to ensure equivalent disease conditions and background medications. SLE disease activity indices, serological parameters, steroid doses, modification of other immunosuppressants, renal effectiveness and adverse events were compared between the two groups at 3-month, 6-month, 9-month and 12-month follow-up visits.Results Data from 52 patients in each of the sirolimus and tacrolimus groups were analysed. Indices regarding the effectiveness of sirolimus, including Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores, physician’s global assessment (PhGA) scores, and proportion of patients with SLEDAI-2K reduction of ≥4 and PhGA increase of

FIP-fve, a fungal fruiting body protein from Flammulina velutipes, has potential immunomodulatory properties. Here, we investigated the immunomodulation mechanism of FIP-fve in Jurkat E6-1 cells by conducting a cell viability assay and IL-2 release assay. Kinase inhibitors experiment and proteomics analysis were also involved in the mechanism study. It was found that FIP-fve stimulated cell proliferation and enhanced IL-2 secretion in a dose-dependent manner in Jurkat E6-1 cells. Unbiased high-throughput proteomics analysis showed that 4 T cell immune activation markers, including ZAP-70, CD69, CD82, and KIF23, were upregulated in response to FIP-fve treatment. Further pathway analysis indicated that MAP2K3/p38 pathway-related proteins, including MAP2K, p38, ELK, AATF, FOS, and JUN-B, were unregulated. In addition, losmapimod (p38 inhibitor) and gossypetin (MAP2K3 inhibitor) inhibited FIP-fve enhanced cell proliferation and IL-2 release in Jurkat E6-1 cells. Our results demonstrate that FIP-fve stimulates cell proliferation and enhances IL-2 secretion through MAP2K3/p38α activation.

Abstract Background The symptoms of cool-temperature-induced chlorosis (CTIC) are widely existed in higher plants. Although many studies have shown that the genetic mechanism of CTIC is generally controlled by recessive genes in model plants, the dominant inheritance of albinism has not been reported thus far. Here, two CTIC mutants, Red Kamome and White Kamome, were utilized to analyse the inheritance of the albino trait in ornamental kale. The objective of this investigation is to fine-map the target locus and identify the most likely candidate genes for albinism. Results Genetic analysis revealed that the albinism in the inner leaves of ornamental kale followed semi-dominant inheritance and was controlled by a single locus in two segregating populations. BSR-seq in combination with linkage analysis was employed to fine-map the causal gene, named AK (Albino Kale), to an approximate 60 kb interval on chromosome C03. Transcriptome data from two extreme pools indicated that the differentially expressed gene of Bol015404, which encodes a cytochrome P450 protein, was the candidate gene. The Bol015404 gene was demonstrated to be upregulated in the albino leaves of ornamental kale by qPCR. Additionally, the critical temperature for the albinism was determined between 10 °C and 16 °C by gradient test. Conclusions Using two independent segregating populations, the albino mutants were shown to be controlled by one semi-dominant gene, AK, in ornamental kale. The Bol015404 gene was co-segregated with albinism phenotypes, suggesting this unknown function P450 gene as the most likely candidate gene. The albino trait appeared caused by the low temperatures rather than photoperiod. Our results lay a solid foundation on the genetic control of albinism in ornamental kale.

Aiming at shortage of metal materials, ceramic is increasingly applied in biomedicine due to its high strength, pleasing esthetics and good biocompatibility, especially for dental restorations and implants, artificial joints, as well as synthetic bone substitutes. However, the inherent brittleness of ceramic could lead to serious complications, such as fracture and disfunction of biomedical devices, which impede their clinical applications. Herein, several toughening strategies have been summarized in this review, including reinforcing phase addition, surface modification, and manufacturing processes improvement. Doping metal and/or non-metal reinforcing fillers modifies toughness of bulk ceramic, while surface modifications, mainly coating, chemical and thermal methods, regulate toughness on the surface layer. During fabrication, optimization should be practiced in powder preparation, green forming and densification processes. Various toughening strategies utilize mechanisms involving fine-grained, stress-induced phase transformation, and microcrack toughening, as well as crack deflection, bifurcation, bridging and pull-out. This review hopes to shed light on systematic combination of different toughening strategies and mechanisms to drive progress in biomedical devices.

Pyroptosis is a form of programmed cell death, and recently described as a new molecular mechanism of chemotherapy drugs in the treatment of tumors. Miltirone, a derivative of phenanthrene-quinone isolated from the root of Salvia miltiorrhiza Bunge, has been shown to possess anti-cancer activities. Here, we found that miltirone inhibited the cell viability of either HepG2 or Hepa1-6 cells, and induced the proteolytic cleavage of gasdermin E (GSDME) in each hepatocellular carcinoma (HCC) cell line, with concomitant cleavage of caspase 3. Knocking out GSDME switched miltirone-induced cell death from pyroptosis to apoptosis. Additionally, the induction effects of miltirone on GSDME-dependent pyroptosis were attenuated by siRNA-mediated caspase three silencing and the specific caspase three inhibitor Z-DEVD-FMK, respectively. Miltirone effectively elicited intracellular accumulation of reactive oxygen species (ROS), and suppressed phosphorylation of mitogen-activated and extracellular signal-regulated kinase (MEK) and extracellular regulated protein kinases 1/2 (ERK1/2) for pyroptosis induction. Moreover, miltirone significantly inhibited tumor growth and induced pyroptosis in the Hepa1-6 mouse HCC syngeneic model. These results provide a new insight that miltirone is a potential therapeutic agent for the treatment of HCC via GSDME-dependent pyroptosis.

The infant brain undergoes a remarkable period of neural development that is crucial for the development of cognitive and behavioral capacities (Hasegawa et al., 2018). Longitudinal magnetic resonance imaging (MRI) is able to characterize the developmental trajectories and is critical in neuroimaging studies of early brain development. However, missing data at different time points is an unavoidable occurrence in longitudinal studies owing to participant attrition and scan failure. Compared to dropping incomplete data, data imputation is considered a better solution to address such missing data in order to preserve all available samples. In this paper, we adapt generative adversarial networks (GAN) to a new application: longitudinal image prediction of structural MRI in the first year of life. In contrast to existing medical image-to-image translation applications of GANs, where inputs and outputs share a very close anatomical structure, our task is more challenging as brain size, shape and tissue contrast vary significantly between the input data and the predicted data. Several improvements over existing GAN approaches are proposed to address these challenges in our task. To enhance the realism, crispness, and accuracy of the predicted images, we incorporate both a traditional voxel-wise reconstruction loss as well as a perceptual loss term into the adversarial learning scheme. As the differing contrast changes in T1w and T2w MR images in the first year of life, we incorporate multi-contrast images leading to our proposed 3D multi-contrast perceptual adversarial network (MPGAN). Extensive evaluations are performed to assess the qualityand fidelity of the predicted images, including qualitative and quantitative assessments of the image appearance, as well as quantitative assessment on two segmentation tasks. Our experimental results show that our MPGAN is an effective solution for longitudinal MR image data imputation in the infant brain. We further apply our predicted/imputed images to two practical tasks, a regression task and a classification task, in order to highlight the enhanced task-related performance following image imputation. The results show that the model performance in both tasks is improved by including the additional imputed data, demonstrating the usability of the predicted images generated from our approach.

Nitrous oxide (N2O) is a powerful greenhouse gas that degrades ozone. Hypoxia and ocean acidification are becoming more intense as a result of climate change. The former stimulates N2O emissions, whereas the effects of the latter on N2O production vary by the ocean. Hypoxia and ocean acidification may play a critical role in the evolution of future oceanic N2O production. However, the interactive effects of hypoxia and ocean acidification on N2O production remain unclear. We conducted a research cruise in the Bohai Sea of China to assess the occurrence of ocean acidification in the seasonal oxygen minimum zone of the sea and further conducted laboratory incubation experiments to determine the effects of ocean acidification and hypoxia on N2O production. When pH decreased by 0.25, N2O production decreased by 50.77 and 72.38%, respectively. In contrast, hypoxia had a positive impact; when dissolved oxygen (DO) decreased to 3.7 and 2.4 mg L−1, N2O production increased by 49.72 and 278.68%, respectively. The incubation experiments demonstrated that the coupling of ocean acidification and hypoxia significantly increased N2O production, but, individually, there was an antagonistic relationship between the two. Structural equation modeling showed that the total effects of hypoxia treatment on N2O production changes weakened the effects of ocean acidification, with overall positive effects. Generally speaking, our results suggest that N2O production from the coastal waters of the Bohai Sea may increase under future climate change scenarios due to increasingly serious ocean acidification and hypoxia working in combination.

The objective of the study was to elucidate the stearoyl-coenzyme A desaturase (SCD1)-dependent gene network of c9, t11-CLA biosynthesis in MAC-T cells from an energy metabolism perspective. The cells were divided into the CAY group (firstly incubated with CAY10566, a chemical inhibitor of SCD1, then incubated with trans-11-octadecenoic acid, (TVA)), the TVA group (only TVA), and the control group (without CAY, TVA). The c9, t11-CLA, and TVA contents were determined by gas chromatography. The mRNA levels of SCD1 and candidate genes were analyzed via real-time PCR. Tandem mass tag (TMT)-based quantitative proteomics, bioinformatic analysis, parallel reaction monitoring (PRM), and small RNA interference were used to explore genes involved in the SCD1-dependent c9, t11-CLA biosynthesis. The results showed that the SCD1 deficiency led by CAY10566 blocked the biosynthesis of c9, t11-CLA. In total, 60 SCD1-related proteins mainly involved in energy metabolism pathways were primarily screened by TMT-based quantitative proteomics analysis. Moreover, 17 proteins were validated using PRM analysis. Then, 11 genes were verified to have negative relationships with SCD1 after the small RNA interference analysis. Based on the above results, we concluded that genes involved in energy metabolism pathways have an impact on the SCD1-dependent molecular mechanism of c9, t11-CLA biosynthesis.

Objective: To provide real-world data and summarize current clinical evidence on the efficacy and safety of sirolimus in active systemic lupus erythematosus (SLE) patients. Methods: This was a prospective real-world clinical study. Included SLE patients should have Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) ⩾ 2. They were treated with sirolimus and followed up regularly. The SLEDAI-2K, Physician Global Assessment (PGA), serological activity indices, and remission of organ manifestations were evaluated. We also performed a meta-analysis to integrate current evidence of sirolimus in SLE. Results: A total of 49 patients were included in the final analysis. After treatment, the SLEDAI-2K (6.2 ± 3.1 versus 4.0 ± 3.4, p = 0.001) decreased significantly, and the prednisone dosage was tapered successfully (9.9 ± 8.8 mg/day versus 5.9 ± 4.0 mg/day, p = 0.002). Serological activity indices also improved [complement 3 (C3): 0.690 ± 0.209 g/l versus 0.884 ± 0.219 g/l, p

Bone defects caused by injury, disease, or congenital deformity remain a major health concern, and efficiently regenerating bone is a prominent clinical demand worldwide. However, bone regeneration is an intricate process that requires concerted participation of both cells and bioactive factors. Mimicking physiological bone healing procedures, the sustained release of bioactive molecules plays a vital role in creating an optimal osteogenic microenvironment and achieving promising bone repair outcomes. The utilization of biomaterial scaffolds can positively affect the osteogenesis process by integrating cells with bioactive factors in a proper way. A high water content, tunable physio-mechanical properties, and diverse synthetic strategies make hydrogels ideal cell carriers and controlled drug release reservoirs. Herein, we reviewed the current advancements in hydrogel-based drug sustained release systems that have delivered osteogenesis-inducing peptides, nucleic acids, and other bioactive molecules in bone tissue engineering (BTE).

Repairing tooth defects with dental resin composites is currently the most commonly used method due to their tooth-colored esthetics and photocuring properties. However, the higher than desirable failure rate and moderate service life are the biggest challenges the composites currently face. Secondary caries is one of the most common reasons leading to repair failure. Therefore, many attempts have been carried out on the development of a new generation of antimicrobial and therapeutic dental polymer composite materials to inhibit dental caries and prolong the lifespan of restorations. These new antimicrobial materials can inhibit the formation of biofilms, reduce acid production from bacteria and the occurrence of secondary caries. These results are encouraging and open the doors to future clinical studies on the therapeutic value of antimicrobial dental resin-based restoratives. However, antimicrobial resins still face challenges such as biocompatibility, drug resistance and uncontrolled release of antimicrobial agents. In the future, we should focus on the development of more efficient, durable and smart antimicrobial dental resins. This article focuses on the most recent 5 years of research, reviews the current antimicrobial strategies of composite resins, and introduces representative antimicrobial agents and their antimicrobial mechanisms.

The oral cavity harbors complex microbial communities, which leads to biomaterial-associated infections (BAI) during dental and orthopedic treatments. Conventional antibiotic treatments have met great challenges recently due to the increasing emergency of drug-resistant bacteria. To tackle this clinical issue, antibacterial surface treatments, containing surface modification and coatings, of dental and orthopedic materials have become an area of intensive interest now. Among various antibacterial agents used in surface treatments, metallic agents possess unique properties, mainly including broad-spectrum antibacterial properties, low potential to develop bacterial resistance, relative biocompatibility, and chemical stability. Therefore, this review mainly focuses on underlying antibacterial applications and the mechanisms of metallic agents in dentistry and orthopedics. An overview of the present review indicates that much work remains to be done to deepen the understanding of antibacterial mechanisms and potential side-effects of metallic agents.