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In order to improve the gel properties of surimi, the surimi gel was prepared by adding Laminaria japonica powder (LJP) with a mass fraction of 2%~10% in silver carp surimi. The effect of amount of LJP on the gel strength, texture, water holding capacity, rheological properties, chemical forces, myofibrillar protein (MP) secondary structure, color and microstructure of the surimr gel were analyzed. Thus, the intrinsic cause of LJP improving the surimi gel quality was explored. Results showed that the addition of LJP significantly improved (P

Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered ‘truck’ (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

Abstract Background: Clinically, the ability to distinguish which Crohn’s disease patients can benefit from Adalimumab is limited. Aims: This study aimed to develop a model for predicting clinical remission probability for Crohn’s disease patients with Adalimumab at 12 weeks. The model assists clinicians in identifying which Crohn’s disease patients are likely to benefit from Adalimumab treatment before starting therapy, thus optimizing individualized treatment strategies. Methods: Demographic and clinical characteristics of Crohn’s disease patients were utilized to develop a model for clinical remission probability. LASSO regression was used to select predictive factors, and predictions were made using a logistic regression model. The model was internally validated using the bootstrap method (resampling 1000 times). Results: 68 patients with Crohn’s disease were enrolled in this study. Clinical remission was observed in 55.9% at 12 weeks. Three variables were selected through the least absolute shrinkage and selection operator regression method, including Adalimumab-positive cell count, disease duration, and neutrophil count of Crohn’s disease patients. A predictive model was constructed by multivariate logistic regression (Adalimumab-positive cell count (OR, 1.143; 95%CI, 1.056–1.261), disease duration (OR, 0.967; 95%CI, 0.937–0.986), and neutrophil count (×109/L) (OR, 1.274; 95%CI,1.014–1.734)). The predictive model yielded an area under the curve of 0.866 (95%CI, 0.776–0.956), and in the internal validation, the area under the curve was 0.870 (95%CI, 0.770–0.940). Conclusions: This model provides a convenient tool to assess the likelihood of patient remission prior to Adalimumab treatment, thereby supporting the development of personalized treatment plans.

Abstract Background Different anesthetic drugs and techniques may affect survival outcomes for gastric cancer (GC) after surgery. In this study, we investigated the association between sedated and unsedated gastroscopy on survival outcomes in patients with GC after surgery. Methods This was a retrospective study of patients who were diagnosed with GC by gastroscopy and underwent gastrectomy from January 2013 to December 2017. They were grouped based on the examination modality: propofol-based sedated gastroscopy or unsedated gastroscopy. Propensity score matching (PSM) was used to balance the baseline variables. Survival outcomes and distant metastases were compared between these two groups. Results Finally, 673 patients were enrolled, 160 in the sedated gastroscopy group and 513 in the unsedated gastroscopy group. After PSM, there were 160 patients in each group. There was no significant difference in overall survival outcomes in the sedated gastroscopy group compared to the unsedated gastroscopy group before PSM (HR = 0.761, 95% CI: 0.531–1.091, P = 0.139) or after PSM (HR = 0.874, 95% CI: 0.564–1.355, P = 0.547). There was no significant difference in the incidence of distant metastases between the two groups before PSM (16.9% vs. 20.7%, P = 0.294) or after PSM (16.9% vs. 23.8%, P = 0.126). To confirm that our patients behaved similarly to other studies, we performed a multivariate analysis and the results showed that sex, pathological TNM stage, Borrmann type, adjuvant treatment, and surgical resection range were all independent factors affecting survival outcomes in our patients. Conclusion Our results showed no significant difference in the effects of sedated gastroscopy vs. unsedated gastroscopy on survival outcomes or distant metastases of patients after gastrectomy for GC.

Abstract Background context As lumbar degenerative diseases become more prevalent in an aging population, there is an increasing demand for surgical interventions, such as posterior lumbar interbody fusion (PLIF). However, cage subsidence (CS), observed in 23.9–54% of cases postoperatively, remains a significant complication. Several factors, including age, bone quality, and endplate damage, contribute to the risk of CS, with bone quality being among the most critical determinants. Although DEXA and QCT are widely employed to assess bone density, their routine use in preoperative evaluations is restricted by cost considerations and radiation exposure. Recent studies suggest that MRI-based vertebral body quality (VBQ) and endplate bone quality (EBQ) score offer a viable, non-invasive alternative for evaluating bone quality; however, there is limited research comparing their predictive value for CS. Methods In this retrospective study, 165 patients undergoing single-level PLIF surgery were included. MRI-based VBQ and EBQ score were calculated using T1-weighted images, and preoperative QCT was employed as a clinical standard. Cage subsidence was assessed based on postoperative imaging at 12-month follow-up. Statistical analyses, including t-tests, chi-square tests, and ROC curve analyses, were used to evaluate the predictive accuracy of VBQ and EBQ for CS. Results The study’s findings demonstrated that both VBQ and EBQ scores were significantly correlated with QCT measurements, thereby validating their utility as indicators of bone quality. ROC analysis revealed that VBQ had superior predictive value for CS (AUC = 0.814) compared to EBQ (AUC = 0.719), with both scores demonstrating significant clinical utility in identifying patients at risk for CS. Notably, VBQ exhibited a stronger correlation with preoperative clinical outcomes compared to EBQ, underscoring its greater reliability as a predictor. Conclusions This study highlights the effectiveness of MRI-based VBQ and EBQ score as practical, non-invasive tools for assessing bone quality preoperatively, with VBQ demonstrating superior predictive performance for CS risk. The findings underscore the potential of integrating these MRI-based assessments into routine preoperative planning to improve patient outcomes and minimize complications associated with PLIF surgery.

Abstract Study design Retrospective Case-Control Study. Background There have been some previous studies on the risk factors associated with lumbar spondylolisthesis, but there are few studies on the risk factors for disease progression in mild degenerative lumbar spondylolisthesis (DLS). To analyze the risk factors associated with aggravation of spondylolisthesis in patients with grade I degenerative spondylolisthesis and construct a prediction model. Methods We conducted a retrospective analysis of 220 patients diagnosed with DLS who were admitted to our hospital between January 2019 and January 2023. Data collected included gender, age, body mass index (BMI), diabetes, hypertension, occupation, and imaging parameters. Results A total of 220 patients were included in this study, including 111 males and 109 females; 178 patients with no aggravation of lumbar spondylolisthesis (group A) and 42 patients with aggravation of lumbar spondylolisthesis (group B). Progression of grade I DLS was associated with single factors such as age, BMI, Occupation, vertebral CT value, facet joint angle (FJA), Modic change (MC), Pfirrmann grade of intervertebral disc (PG), Facet joint effusion (FJE), osteophyte formation, and Percentage of the Fat Infiltration (FIA%) of multifidus muscle (MM). BMI, FJA, PG, and FI% of MM had a significant impact on disease progression in lumbar spondylolisthesis. Conclusion BMI, FJA, PG, and FIA% of MM were independent risk factors for the progression of degenerative spondylolisthesis. The risk prediction model was established by including the above four variables and nomograms were drawn. The internal validation proved that the model had good discrimination, calibration, and clinical practicability.

Abstract Background There is currently no consensus on the surgical treatment of lumbar spondylolysis in young adults, and the nonunion rate remains relatively high even after surgery. Therefore, in this study, we proposed a modified intravertebral screw-rod fixation technique within a single vertebral segment and investigated the clinical efficacy of this modified fixation system combined with autologous cancellous bone grafting in the treatment of lumbar spondylolysis in young adults. Methods This study included 28 young adults with lumbar spondylolysis who were treated at our center between 2021 and 2023. All patients underwent modified intravertebral screw-rod fixation within a single vertebral segment combined with autologous cancellous bone grafting. We performed postoperative follow-ups regularly to assess the patient’s pain status using the visual analog scale (VAS), Oswestry Disability Index (ODI), and radiological findings. Results All 28 patients successfully underwent the surgery with an average operation time and blood loss volume of 96.01 ± 21.3 min and 186.78 ± 63.43 mL, respectively. Postoperatively, patients experienced significant symptom relief, with notable decreases in VAS scores and ODI indices at 1, 3, 6, and 12 months compared with preoperative conditions. These differences were statistically significant (P

Abstract The present study examined optimal dietary patterns of eight plant-based foods for preventing chronic diseases, including hypertension, stroke, myocardial infarction, and diabetes, using data from the China Health and Nutrition Survey (CHNS). We applied generalized estimating equations to assess time-based changes and gender differences, using residual balancing weights to control time-varying confounders, and employed a restricted cubic spline model to explore dose-response relationships by gender. The findings suggested that a high intake of vegetables and whole grains, along with moderate amounts of fruits, fungi and algae, could help reduce the risk of developing these four chronic diseases simultaneously. Additionally, men could benefit from moderate refined grain consumption, while women should consider increasing their intake of nuts and seeds. Our results indicated that adopting a plant-based diet could provide non-linear protective effects against chronic diseases, with the magnitude of this protection varying by gender.

Abstract Background The accelerated aging process worldwide is placing a heavy burden on countries. PM2.5 particulate matter exposure is a significant factor affecting human health and is crucial in the aging process. Methods We utilized data from China Health and Retirement Longitudinal Study (CHARLS) and the Survey of Health, Aging, and Retirement in Europe (SHARE) to study the relationship between PM2.5 exposure and the frailty index. Acquire PM2.5 exposure data for China and Europe, match them according to geographic location within the database. Our study used frailty index to evaluate frailty, which comprises 29 items. We examined the association between PM2.5 and frailty index using fixed-effects regression models and Mendelian randomization (MR) analysis. Results We first examined the association between PM2.5 and frailty index using fixed-effects regression models, revealing a notable positive link across populations in China (coefficient = 0.0003, P = 0.0380) and Europe (Coefficient = 0.0019, P

Abstract Bacterial lipid branched glycerol dialkyl glycerol tetraethers (brGDGTs) are a valuable tool for reconstructing past temperatures. However, a gap remains regarding the influence of bacterial communities on brGDGT profiles. Here, we identified two distinct patterns of brGDGTs from the surface sediments of 38 Tibetan Plateau lakes using an unsupervised clustering technique. Further investigation revealed that salinity and pH significantly change bacterial community composition, affecting brGDGT profiles and causing brGDGT-based temperatures to be overestimated by up to 2.7 ± 0.7 °C in haloalkaline environments. We subsequently used the trained clustering model to examine the patterns of bacterial assemblages in the global lacustrine brGDGT dataset, confirming the global applicability of our approach. We finally applied our approach to Holocene brGDGT records from the Tibetan Plateau, showing that shifts in bacterial clusters amplified temperature variations over timescales. Our findings demonstrate that microbial ecology can robustly diagnose and constrain site-specific discrepancies in temperature reconstruction.

To achieve efficient immobilization of papain (PAP), this study constructed a hydrophilic three-dimensional matrix for easy magnetic separation of the immobilized enzyme. The immobilization conditions were optimized using single-factor and response methodology. A core-shell structured nano-magnetic bead Fe3O4@PMMA was prepared by coating the magnetic Fe3O4 with poly(methyl methacrylate) (PMMA), followed by grafting polyethyleneimine (PEI) of different molecular weights. PAP was physically adsorbed onto the PEI, and then cross-linked using glutaraldehyde (GA) to construct an easily magnetically separable hydrophilic three-dimensional immobilization matrix Fe3O4@PMMA-PEI. The cross-linked encapsulation of PAP and its microstructure and physicochemical properties were characterized. Using the immobilization capacity of the nano-magnetic beads as the evaluation criterion, the optimal cross-linking time, glutaraldehyde concentration, cross-linking temperature, and cross-linking speed for immobilizing PAP were investigated. The results indicated that the carboxyl group content formed after the ester hydrolysis of the PMMA on the surface of the magnetic beads was 0.95 mmol/g. Following the grafting of PEI with different molecular weights, the amino group content on the surface of the magnetic beads was 0.16~0.48 mmol/g. The loading capacity of PAP on the nano-magnetic beads could be modulated by the molecular weight of the grafted PEI. When the molecular weight of PEI was 1800, the loading capacity reached 120.71 mg/g. PEI 1800 was selected as the grafting spacer arms. The nanomagnetic spheres exhibited well-defined morphology, uniform particle size distribution in the range of approximately 150~200 nm. Through response surface experiments, the best conditions were optimized: Cross-linking time of 32 minutes, glutaraldehyde concentration of 0.02%, cross-linking temperature of 25 ℃, and cross-linking speed of 90 revolutions per minute. Under these conditions, Fe3O4@PMMA-PEI 1800 achieved a PAP loading capacity of 139.80 mg/g. Importantly, even after five cycles of reuse, Fe3O4@PMMA-PEI 1800-PAP retained 80.35% of its relative enzyme activity. This study presents the design and synthesis of a nanomagnetic sphere structure tailored for the efficient immobilization of PAP, providing experimental evidence for the research and application of immobilized PAP.

Bioactive ceramics have been used in bone tissue repair and regeneration. However, because of the complex in vivo osteogenesis process, long cycle, and difficulty of accurately tracking, the mechanism of interaction between materials and cells has yet to be fully understood, hindering its development. The ceramic microbridge microfluidic chip system may solve the problem and provide an in vitro method to simulate the microenvironment in vivo. Nevertheless, the complex microenvironment parameters of the chip system need to be studied in detail. Computer simulation bionics can provide clues for the setting of microenvironment parameters. This study used a computational bionic model to simulate the bone growth process in the presence of immune-related factors. The osteoblast differentiation of mesenchymal stem cells of calcium phosphate ceramics in a macrophage-dominated immune microenvironment was studied using a microfluidic chip system. The computational biomimetic model and microfluidic chip findings were basically consistent with the reported results of the animal experiments. These findings suggest that studying the osteogenic behavior of calcium phosphate ceramics using a microfluidic chip model is feasible. The method model provided in this study can be extended to other biomaterials, providing a viable path for their research and evaluation.

Abstract Objective This study aimed to compare the clinical efficacy of thoracoscopy combined with transforaminal endoscopy and thoracoscopy alone in the treatment of thoracic tuberculosis. Methods Patients with thoracic tuberculosis who visited our hospital from February 2018 to October 2022 were retrospectively analyzed. The patients were divided into thoracoscopic combined transforaminal endoscopic surgery group (group A) and thoracoscopic surgery alone group (group B) according to the surgical methods. Surgery-related information, VAS score, ODI score, degree of spinal cord function improvement, fusion time, and progression of kyphotic deformity were compared. Results A total of 37 patients were included, 16 in group A and 21 in group B. Postoperative follow-up time was 10–48 months, with an average of 28.62 ± 10.53 months. All patients had significant improvement in chest and back pain and spinal cord function after the operation. There were statistical differences in operation time, intraoperative blood loss, incidence rate of complications, and JOA score at 1 week and 3 months after operation between the two groups (P0.05). All patients had no recurrence of thoracic tuberculosis during follow-up. Conclusion Thoracoscopy combined with transforaminal endoscopy produce equivalent long-term results with shorter operation time, less intraoperative blood loss, less complications and higher surgical safety comparing to thoracoscopy alone. And thoracoscopy combined with transforaminal endoscopy can fully decompress and facilitate the early recovery of spinal cord function.

Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) that sequentially drives macrophage phenotypic polarization (M0 to M1, then to M2) was constructed by integrating anti-inflammatory components and proinflammatory solvents. In vitro experiments demonstrated that the proinflammatory solvent ethanol stabilized the hydrogel structure, maintained the phenolic hydroxyl group activity, and achieved macrophages' proinflammatory transition (M0 to M1) to enhance antibacterial effects. With ethanol depletion, the hydrogel's cations and phenolic hydroxyl groups synergistically regulated macrophages' anti-inflammatory transition (M1 to M2) to initiate regeneration. In the anti-contraction full-thickness wound model with infection, this hydrogel effectively eliminated bacteria and even achieved anti-inflammatory M2 macrophage accumulation at three days post-surgery, accelerated angiogenesis and collagen deposition. By sequentially driving macrophage phenotypic polarization, this injectable immunoregulatory hydrogel will bring new guidance for the care and treatment of infected wounds.

Abstract Multivalent antigen display on nanoparticles can enhance the immunogenicity of nanovaccines targeting viral moieties, such as the receptor binding domain (RBD) of SARS-CoV-2. However, particle morphology and size of current nanovaccines are significantly different from those of SARS-CoV-2. Additionally, surface antigen patterns are not controllable to enable the optimization of B cell activation. Herein, we employ an icosahedral DNA origami (ICO) as a display particle for RBD nanovaccines, achieving morphology and diameter like the virus (91 ± 11 nm). The surface addressability of DNA origami permits facile modification of the ICO surface with numerous RBD antigen clusters (ICO-RBD) to form various antigen patterns. Using an in vitro screening system, we demonstrate that the antigen spacing, antigen copies within clusters and cluster number parameters of the surface antigen pattern all impact the ability of the nanovaccines to activate B cells. Importantly, the optimized ICO-RBD nanovaccines evoke stronger and more enduring humoral and T cell immune responses in female mouse models compared to soluble RBD antigens, and the multivalent display broaden the protection range of B cell responses to more mutant strains. Our vaccines activate similar humoral immunity, observable stronger cellular immunity and more memory immune cells compared to trimeric mRNA vaccines.

Abstract Background To study the risk factors associated with misplacement of freehand pedicle screws through a posterior approach for degenerative scoliosis. Methods A total of 204 patients who underwent posterior pedicle screw-rod system surgery for degenerative scoliosis in our hospital from December 2020 to December 2023 were retrospectively analyzed. Patient demographics, radiographic accuracy, and surgery-related information were recorded. Results A total of 204 patients were included. A total of 2496 screws were placed. 2373 (95.07%) were in good position. Misplacement screws were 123 (4.93%). None of the patients had postoperative spinal nerve symptoms due to screw malposition. The misplacement rate of thoracic (T10-T12) pedicle screws was 11.11% (60/540). Misplacement of pedicle screws in the lumbar spine (L1-L5) was 3.22% (63/1956). Age, gender, surgeon, and operation time had no significant effect on misplacement of pedicle screws (P>0.05). Body mass index, Hu value, number of screw segments, Cobb angle, vertebral rotation, and spinal canal morphology had some correlation with pedicle screw misplacement. Among them, BMI, Hu value, number of screw segments, Cobb angle, and vertebral rotation grade were independent risk factors for PS misplacement (P

Converting carbohydrates into 5-hydroxymethylfurfural (5-HMF) is an attractive and promising route for value-added utilization of agricultural and forestry biomass resource. As an important platform compound, 5-HMF possesses high active furan structure with hydroxymethyl and aldehyde group for production of various bio-chemicals and materials, meanwhile, which suffer from low stability and poor yield during the industrial biorefinery process. Hence, selective production of 5-HMF with high-yield and low-cost has attracted extensive attention from scientific and industrial researchers. This review sorted and described the latest advanced research on solvent and catalyst system, as well as energy field effect for production of 5-HMF with different feedstock in detail, emphatically discussing the solvent effect and its synergistic effect with other aspects. Besides, the future prospects and challenges for production of 5-HMF from carbohydrates were also presented, which provide a profound insight into industrial 5-HMF process with economic and environmental feature.

Abstract CT and MR tools are commonly used to diagnose lumbar fractures (LF). However, numerous limitations have been found in practice. The aims of this study were to innovate and develop a spinal disease-specific neural network and to evaluate whether synthetic MRI of the LF affected clinical diagnosis and treatment strategies. A total of 675 LF patients who met the inclusion and exclusion criteria were included in the study. For each participant, two mid-sagittal CT and T2-weighted MR images were selected; 1350 pairs of LF images were also included. A new Self-pix based on Pix2pix and Self-Attention was constructed. A total of 1350 pairs of CT and MR images, which were randomly divided into a training group (1147 pairs) and a test group (203 pairs), were fed into Pix2pix and Self-pix. The quantitative evaluation included PSNR and SSIM (PSNR1 and SSIM1: real MR images and Pix2pix-generated MR images; PSNR2 and SSIM2: real MR images and Self-pix-generated MR images). The qualitative evaluation, including accurate diagnosis of acute fractures and accurate selection of treatment strategies based on Self-pix-generated MRI, was performed by three spine surgeons. In the LF group, PSNR1 and PSNR2 were 10.884 and 11.021 (p

Abstract Background The coexistence of cardiovascular disease and chronic kidney disease, termed chronic cardiovascular-kidney disorder (CCV-KD), is increasingly prevalent. However, limited studies have assessed the association between cardiovascular health (CVH), assessed by the American Heart Association’s Life’s Essential 8 (LE8), and CCV-KD. Methods We conducted a prospective cohort study using data from UK Biobank. Participants without cardiovascular disease and chronic kidney disease at baseline and having complete data on metrics of LE8 were included (N = 125,986). LE8 included eight metrics, and the aggregate score was categorized as low (

Abstract Background Patient navigators, whose value has become increasingly apparent, still face significant challenges, including a lack of support, funding, and recognition. These challenges have been exacerbated in the wake of COVID‐19 pandemic. Methods This study explored the potential use of artificial intelligence (AI) in patient navigation. Data were collected through structured surveys and individual interviews with patient navigators from a variety of institutions and professional backgrounds. The data were analyzed to understand the current state of patient navigation, identify existing gaps, and suggest best practices for the future. Results The findings showed that patient navigators (a) have diverse backgrounds and responsibilities, (b) lack technology support for their work, (c) are at risk for burnout, with the extent varying based on the level of technical support received, and (d) report significant overlap between current barriers and those that could potentially be addressed with AI‐driven technologies. Conclusion A novel intervention, that is enabled by AI and other technologies and tailored to individual needs, has the potential to reduce burnout, increase capacity, and help ensure the sustainability of patient navigation and other areas of healthcare. By addressing the specific needs of individual patients, this type of intervention could help improve the overall effectiveness of patient navigation and support the long‐term sustainability of the role.

Abstract Human hands can envelop the surface of an object and recognize its shape through touch. However, existing stretchable haptic sensors exhibit limited flexibility and stability to detect pressure during deformation, while also solely achieving recognition of planar objects. Inspired by the structure of skin tissue, an embedded construction‐enabled liquid metal‐based e‐skin composed of a liquid metal microstructured electrode (LM‐ME) array is fabricated for curved pressure mapping. The embedded LM‐ME‐based sensor elements are fabricated by using femtosecond laser‐induced micro/nanostructures and water/hydrogel assisted patterning method, which enables high sensitivity (7.42 kPa−1 in the range of 0–0.1 kPa) and high stability through an interlinked support isolation structure for the sensor units. The sensor array with a high interfacial toughness of 1328 J m−2 can maintain pressure sensation under bending and stretching conditions. Additionally, the embedded construction and laser‐induced bumps effectively reduce crosstalk from 58 to 7.8% compared to conventional flexible sensors with shared surfaces. The stretchable and mechanically stable sensor arrays possess shape‐adaptability that enables pressure mapping on non‐flat surfaces, which has great potential for object recognition in robotic skins and human‐computer interaction.

Abstract Electrocatalytic H2 production from seawater, recognized as a promising technology utilizing offshore renewables, faces challenges from chloride-induced reactions and corrosion. Here, We introduce a catalytic surface where OH– dominates over Cl– in adsorption and activation, which is crucial for O2 production. Our NiFe-based anode, enhanced by nearby Cr sites, achieves low overpotentials and selective alkaline seawater oxidation. It outperforms the RuO2 counterpart in terms of lifespan in scaled-up stacks, maintaining stability for over 2500 h in three-electrode tests. Ex situ/in situ analyses reveal that Cr(III) sites enrich OH–, while Cl– is repelled by Cr(VI) sites, both of which are well-dispersed and close to NiFe, enhancing charge transfer and overall electrode performance. Such multiple effects fundamentally boost the activity, selectively, and chemical stability of the NiFe-based electrode. This development marks a significant advance in creating durable, noble-metal-free electrodes for alkaline seawater electrolysis, highlighting the importance of well-distributed catalytic sites.

Abstract Background and objective Complex acetabular fractures involving quadrilateral areas are more challenging to treat during surgery. To date, there has been no ideal internal fixation for these acetabular fractures. The purpose of this study was to evaluate the biomechanical stability of complex acetabular fractures using a dynamic anterior titanium-plate screw system of the quadrilateral area (DAPSQ) by simulating the standing and sitting positions of pelvic specimens. Materials and methods Eight formal in-preserved cadaveric pelvises aged 30–50 years were selected as the research objects. First, one hip of the normal pelvises was randomly used as the control model (group B) for measurement, and then one hip of the pelvises was randomly selected to make the fracture model in the 8 intact pelvises as the experimental model (group A) for measurement. In group A, acetabular both-column fractures in the quadrilateral area were established, and the fractures were fixed by DAPSQ. The biomechanical testing machine was used to load (simulated physiological load) from 400 N to 700 N at a 1 mm/min speed for 30 s in the vertical direction when the specimens were measured at random in simulated standing or sitting positions in groups. The horizontal displacement and longitudinal displacement of the acetabular fractures in the quadrilateral area were measured in both the standing and sitting simulations. Results As the load increased, no dislocation or internal fixation breakage occurred during the measurements. In the standing position, the horizontal displacement of the quadrilateral area fractures in group A and group B appeared to be less than 1 mm with loads ranging from 400 N to 700 N, and there was no significant difference between group A and group B (p > 0.05). The longitudinal displacement appeared to be greater than 1 mm with a load of 700 mm in group A (700 N, 2 cases), and the difference was significant between group A and group B (p 0.05). Conclusion For complex acetabular fractures in the quadrilateral area, DAPSQ fixation may provide early sitting stability, but it is inappropriate for patients to stand too early.

Abstract Background Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent–offspring trios and proband only analysis. Methods We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation. Results Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications. Conclusion CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.

Abstract The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8+ T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting.

Abstract It is vital to explore effective ways for prolonging electrode lifespans under harsh electrolysis conditions, such as high current densities, acid environment, and impure water source. Here we report alternating electrolysis approaches that realize promptly and regularly repair/maintenance and concurrent bubble evolution. Electrode lifespans are improved by co-action of Fe group elemental ions and alkali metal cations, especially a unique Co2+-Na+ combo. A commercial Ni foam sustains ampere-level current densities alternatingly during continuous electrolysis for 93.8 h in an acidic solution, whereas such a Ni foam is completely dissolved in ~2 h for conventional electrolysis conditions. The work not only explores an alternating electrolysis-based system, alkali metal cation-based catalytic systems, and alkali metal cation-based electrodeposition techniques, and beyond, but demonstrates the possibility of prolonged electrolysis by repeated deposition-dissolution processes. With enough adjustable experimental variables, the upper improvement limit in the electrode lifespan would be high.

Abstract The interior environment of articular cartilage in osteoarthritis (OA) presents substantial hurdles, leading to the malfunction of chondrocytes and the breakdown of collagen II-enriched hyaline cartilage matrix. Despite this, most clinical treatments primarily provide temporary relief from OA discomfort without arresting OA progression. This study aimed to alleviate OA by developing intra-articular injectable dECM-enhanced hyaluronic (HE) microgels. The HE hydrogel was engineered and shaped into uniformly sized microgels using microfluidics and photopolymerization techniques. These microgels provided a spatiotemporal cascade effect, facilitating the rapid release of growth factors and a slower release of ECM macromolecules and proteins. This process assisted in the recovery of OA chondrocytes’ function, promoting cell proliferation, matrix synthesis, and cartilage-specific gene expression in vitro. It also effectively aided repair of the collagen II-enriched hyaline cartilage and significantly reduced the severity of OA, as demonstrated by radiological observation, gross appearance, histological/immunohistochemical staining, and analysis in an OA rat model in vivo. Collectively, the HE injectable microgels with spatiotemporal release of cartilage-specific molecules have shown promise as a potential candidate for a cell-free OA therapy approach. Graphical Abstract

Abstract The objective of regenerative wound healing dressings is to accelerate skin tissue regeneration and restore normal physiological function at wound sites. Achieving this goal requires biomaterials capable of repairing distinct phases of wound healing in a way that balances material function, degradation, safety, and tissue growth. In this study, we introduced a novel dual-stage wound dressing system comprising methacrylic anhydride-modified recombinant humanized type III collagen (rhCol III-MA) and methacrylic anhydride-modified dopamine (DMA) (RMDM), which was synthesized through free radical polymerization and π-π stacking. Within this system, RMDM was formulated into two forms with identical compositions: hydrogel and sponge, tailored for application across various stages of wound repair. These materials displayed favorable hemocompatibility, biocompatibility, antioxidant properties, and angiogenic potential in vitro. Moreover, the in vivo experiments also demonstrated that sponges could rapidly stop the bleeding of wounds in mouse tail amputation and liver incision models. Notably, the sponge/gel (S/G) system accelerated wound healing compared to individual sponge and gel treatments in a rat full-thickness skin wound model, underscoring the synergistic benefits of combining sponge and gel materials for wound repair at different stages. Therefore, this research provides valuable insights into designing advanced biomaterials that can be tailored to specific stages of wound healing, which may have significant potential for biomedical applications. Graphical Abstract

Abstract Background posterior pedicle screw fixation is common method, one of the most severe complications is iatrogenic vascular damage, no report investigated association of different introversion angles (INTAs) and length of pedicle screw. The aims were to investigate the optimal introversion angle and length of pedicle screw for improving the safety of the operation, and to analyze the differences of vascular damage types at L1-S1. Methods Lumbar CT imaging data from110 patients were analyzed by DICOM software, and all parameters were measured by new Cartesian coordinate system, INTAs (L1-L5:5°,10°,15°,S1: 0°, 5°,10°,15°), DO−AVC (the distance between the origin (O) with anterior vertebral cortex (AVC)), DAVC−PGVs (the distance between AVC and the prevertebral great vessels (PGVs)), DO−PGVs (the distance between the O and PGVs). At different INTAs, DAVC−PGVs were divided into four grades: Grade III: DAVC−PGVs ≤ 3 mm, Grade II: 3 mm 5 mm, and N: the not touching PGVs. Results The optimal INTA was 5° at L1-L3, the left was 5° and the right was 15° at L4, and screw length was less than 50 mm at L1-L4. At L5, the left optimal INTA was 5° and the right was 10°, and screw length was less than 45 mm. The optimal INTA was 15° at S1, and screw length was less than 50 mm. However, screw length was less than 40 mm when the INTA was 0° or 5° at S1. Conclusions At L5-S1, the risk of vascular injury is the highest. INTA and length of the pedicle screw in lumbar operation are closely related. 3 mm interval of screw length may be more preferable to reduce vascular damage.

To improve the microstructure and properties of Cu-Sn-Ti brazing alloy through component control, the effect of Si on the microstructure and properties of Cu-20Sn-15Ti brazing filler metals was studied using scanning electron microscopy, X-ray diffraction, and EDS energy spectrum analysis. The results show that the microstructure of Cu-20Sn-15Ti brazing filler metal is composed of large-sized polygonal CuSn3Ti5 phase, eutectic structure and α-Cu phase. A small amount of Si (≤ 2.0wt%) refines the polygonal-shaped CuSn3Ti5 phase in the brazing filler metal and generates small-sized Si3Ti5 phase. In contrast, a larger amount of Si (≥ 3.0wt%) differentiates the polygonal-shape CuSn3Ti5 phase, reduces the proportion of eutectic structure, and increases the content and size of the Si3Ti5 phase. When the Si content increases to 5.0wt%, the filler metal no longer generates polygonal-shaped CuSn3Ti5 phase and eutectic structure. Instead, Ti primarily forms Ti5Si3 phase, and the microstructure mainly consists of Ti5Si3 phase, α- Cu phase, Cu41Sn11 phase, and a small amount of strip-shaped CuSn3Ti5 phase. Compared with Cu and Sn, Si has a stronger chemical affinity with Ti and preferentially reacts with Ti to form Ti5Si3 phase. The three-dimensional structure of Ti5Si3 phase is prismatic and exhibits agglomerated growth characteristics. The coarse strip Ti5Si3 phase has central or lateral pore defects, which are mainly related to the growth mechanism. As the Si content increases, the shear strength of the filler metals shows a trend of “increasing-decreasing-increasing”, and the fracture morphology transitions from a mixed morphology of quasi-cleavage fracture and cleavage fracture to cleavage fracture. The CuSn3Ti5 phase is prone to breakage and cracking, becoming the source of cracking. The presence of coarse CuSn3Ti5 phase in different states can deteriorate the shear strength of the brazing filler metals to some extent.

BackgroundComputer-aided design/manufacturing (CAD/CAM) materials are widely used in resin-bonded fixed partial dentures (RBFPDs), but their suitability across different designs has not been fully assessed. This study compares the stress distribution and failure probability of mandibular incisors restored by RBFPDs with various CAD/CAM materials.Materials and methodsFinite-element models of single- and double-ended RBFPDs were created using cone-beam computed tomography (CBCT) data. Five CAD/CAM materials (IPS e.max CAD, IPS e.max ZirCAD, Vita Enamic, Lava Ultimate, Vitablocs MarkII) were tested under vertical and oblique (45°) loading with a 100 N force. Stress distribution and failure risk were evaluated for each material and design.ResultsOblique loading produced the highest stress and displacement for single-ended RBFPDs. Lava Ultimate had the largest displacement and principal stress, while IPS e.max ZirCAD showed the highest equivalent stress. IPS e.max CAD exhibited the lowest displacement and principal stress among double-ended RBFPDs under oblique loading.ConclusionThis study demonstrated that double-ended RBFPDs experience lower stress and strain compared to single-ended designs, particularly under oblique loading. Vita Enamic had the highest failure risk, while IPS e.max ZirCAD had the lowest. These insights into stress distribution and material performance offer valuable guidance for material selection and restoration design, aiming to improve the longevity and success of RBFPDs in mandibular incisor restorations.

Background This study aimed to examine whether baseline atherosclerosis was associated with subsequent short‐term domain‐specific cognitive decline. Methods and Results This research was based on the BRAVE (Beijing Research on Aging and Vessel) study, a population‐based prospective cohort study of adults aged 40 to 80 years, free of dementia. At baseline (wave 1, 2019), cognitive assessments and atherosclerosis measures, including carotid intima‐media thickness, carotid plaques, coronary artery calcification, and brachial–ankle pulse wave velocity were conducted. Cognitive function was reassessed in wave 2 (2022–2023) using linear mixed models for analysis. A total of 932 participants (63.7% women; mean age, 60.0±6.9 years) were included. Compared with the lowest tertile of carotid intima‐media thickness, carotid plaques, and brachial–ankle pulse wave velocity, or a coronary artery calcification score=0, the highest tertile of carotid intima‐media thickness (β=−0.065 SD/y [95% CI, −0.112 to −0.017]; P=0.008), carotid plaques (β=−0.070 SD/y [95% CI, −0.130 to −0.011]; P=0.021), and brachial–ankle pulse wave velocity (β=−0.057 SD/y [95% CI, −0.105 to −0.010]; P=0.018), and a coronary artery calcification score≥400 (β=−0.081 SD/y [95% CI, −0.153 to −0.008]; P=0.029) were significantly associated with a faster decline in semantic fluency after multivariable adjustment. Moreover, greater carotid intima‐media thickness, coronary artery calcification, and brachial–ankle pulse wave velocity were significantly associated with a faster decline in global cognition. Conclusions More significant atherosclerosis was associated with faster semantic fluency and global cognition declines.

Aim: The aim of this study was to evaluate the potential protective effect of Qiju Granule in a rat model of age-related macular degeneration (AMD) and investigate the underlying mechanisms involved. Methods: Rats were injected intravenously with 40 mg/kg of sodium iodate (SI) to induce a dry AMD model. The rats in the treatment group received three different doses of Qiju Granule once a day via gavage, while the rats in the control group were given an equal volume of physiological saline. On day 14 and day 28 following the intervention, various methods were employed to evaluate retinal function and structure, including electroretinography (ERG), optical coherence tomography (OCT), and histological examination. The expression of glial fibrillary acidic protein (GFAP), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF) was assessed via immunofluorescence. Beyond immunofluorescence, the mRNA levels of bFGF, BDNF, and CNTF were quantitatively determined using real-time polymerase chain reaction (qRT-PCR). Results: Rats treated with Qiju Granule exhibited significant improvements in both retinal function and structure compared to the model group. The most noteworthy effects were observed at a high dose of Qiju Granule. Furthermore, the expression levels of bFGF, BDNF, and CNTF were significantly unregulated in the treated groups compared to the model group. Conclusions: Qiju Granule demonstrated a protective effect on the retina in the SI-induced rat model of AMD. The protective mechanism may be attributed to the upregulation of retinal neurotrophic factors expression.

ObjectiveSARS-CoV-2 transmission has become a serious worldwide public health concern. However, there is currently insufficient data to determine whether SARS-CoV-2 infection would affect opportunistic infections in inflammatory bowel disease (IBD) patients.MethodsA retrospective study included 451 IBD patients (294 UC and 157 CD). The IBD patients were divided into two groups: before SARS-CoV-2 infection and after SARS-CoV-2 infection, and outcomes were measured for these groups. The primary outcome was the presence and distribution of opportunistic infections. The secondary outcomes included factors associated with opportunistic infections, based on which a nomogram prediction model was developed and validated.ResultsAfter SARS-CoV-2 infection, the proportion of IBD patients with opportunistic infections by Clostridium difficile (21.31% vs. 14.01%, p = 0.044) and Epstein–Barr virus (13.93% vs. 4.35%, p = 0.001) was significantly higher compared to that before. Conversely, the proportion of patients with hepatitis B virus (3.69% vs. 10.14%, p = 0.006) and herpes simplex virus type I (1.23% vs. 4.35%, p = 0.04) infections was significantly lower after the infection. Additionally, pre-SARS-CoV-2 infection factors associated with opportunistic infections in IBD include duration of illness, red blood cell count, the presence of comorbid chronic illnesses, and alcohol consumption, while post-SARS-CoV-2 infection, the primary risk factors involve corticosteroid use, red blood cell count, protein level, and high-sensitivity C-reactive protein.ConclusionAfter the SARS-CoV-2 infection, there has been a shift in the occurrence of opportunistic infections among IBD patients. It might be attributed to the use of corticosteroids and also the strengthening of containment measures, heightened public health awareness, and widespread vaccination.

Objective To systematically assess the risk prediction models for preoperative deep vein thrombosis in older patients with hip fractures. Method We searched four databases for literature through November 17, 2023. We included patients aged ≥60 with hip fractures and considered English-language case-control or cohort studies that focused on developing and/or validating risk prediction models for DVT in this population. Excluded were studies that solely analyzed risk factors without constructing a prediction model, had fewer than 2 predictive variables, or were not available in full-text or were duplicate publications. The Predictive Model Bias Risk Assessment tool was utilized to evaluate risk of bias. The area under the curve (AUC) values were meta-analyzed using R Studio software. The I 2 index and Cochrane q test were employed to assess heterogeneity. Additionally, sensitivity analysis was performed by systematically removing individual studies to explore the sources of heterogeneity. Results A total of 1880 studies were gathered. Out of these, seven studies were included, encompassing 8 models. The most commonly utilized factors in the models were D-dimer and the time from injury to admission. The pooled AUC value for the validation of 8 models was 0.84 (95% confidence interval: 0.80-0.87), indicating robust model performance. Conclusion Current risk prediction models for preoperative DVT in elderly hip fracture patients are still in the developmental phase. Future research should focus on developing new models with larger sample sizes, robust study designs, and multicenter external validation.

Abstract Furin primarily localizes to the trans‐Golgi network (TGN), where it cleaves and activates a broad range of immature proproteins that play critical roles in cellular homeostasis, disease progression, and infection. Furin is retrieved from endosomes to the TGN after being phosphorylated, but it is still unclear how furin exits the TGN to initiate the post‐Golgi trafficking and how its activity is regulated in the TGN. Here three membrane‐associated RING‐CH finger (MARCHF) proteins (2, 8, 9) are identified as furin E3 ubiquitin ligases, which catalyze furin K33‐polyubiquitination. Polyubiquitination prevents furin from maturation by blocking its ectodomain cleavage inside cells but promotes its egress from the TGN and shedding. Further ubiquitin‐specific protease 32 (USP32) is identified as the furin deubiquitinase in the TGN that counteracts the MARCHF inhibitory activity on furin. Thus, the furin post‐Golgi trafficking is regulated by an interplay between polyubiquitination and phosphorylation. Polyubiquitination is required for furin anterograde transport but inhibits its proprotein convertase activity, and phosphorylation is required for furin retrograde transport to produce fully active furin inside cells.

Abstract Seawater electroreduction is attractive for future H2 production and intermittent energy storage, which has been hindered by aggressive Mg2+/Ca2+ precipitation at cathodes and consequent poor stability. Here we present a vital microscopic bubble/precipitate traffic system (MBPTS) by constructing honeycomb-type 3D cathodes for robust anti-precipitation seawater reduction (SR), which massively/uniformly release small-sized H2 bubbles to almost every corner of the cathode to repel Mg2+/Ca2+ precipitates without a break. Noticeably, the optimal cathode with built-in MBPTS not only enables state-of-the-art alkaline SR performance (1000-h stable operation at –1 A cm−2) but also is highly specialized in catalytically splitting natural seawater into H2 with the greatest anti-precipitation ability. Low precipitation amounts after prolonged tests under large current densities reflect genuine efficacy by our MBPTS. Additionally, a flow-type electrolyzer based on our optimal cathode stably functions at industrially-relevant 500 mA cm−2 for 150 h in natural seawater while unwaveringly sustaining near-100% H2 Faradic efficiency. Note that the estimated price (~1.8 US$/kgH2) is even cheaper than the US Department of Energy’s goal price (2 US$/kgH2).

Abstract Abnormal hemoglobin anti-Lepore Hong Kong is a rare βδ fusion variants resulting from non-homologous crossover during meiosis. Anti-Lepore Hong Kong is known to consistently exhibit significantly increased level of HbA2. In this study, we used multiplex ligation-dependent probe amplification (MLPA) and single molecular real-time (SMRT) sequencing, as well as Sanger sequencing, to identify variants in five unrelated families with abnormal elevated HbA2 level. All probands in these five families were found to be heterozygous for anti-Lepore Hong Kong. Among them, two families showed co-occurrence of β0-thalassemia and α-thalassemia (–SEA/ or αCSα/). Heterozygotes for anti-Lepore Hong Kong displayed an average HbA2 level of 17.7% and behaved normal. However, when combined with β0-thalassemia and α-thalassemia, the probands exhibited higher HbA2 level (30.2–40.8%) and behaved with β-thalassemia trait. Furthermore, determination of the α/β-mRNA ratio revealed a slight downregulation of β-globin, similar to that of β-thalassemia minor. Our study is the first to identify compound heterozygotes for anti-Lepore Hong Kong, β0-thalassemia and α-thalassemia, provide valuable information for prenatal counseling.

A Bottom Simulating Reflector (BSR) is a seismic feature closely related to marine gas hydrate as it is usually regarded as the seismic response of the base of the gas hydrate stability zone in seismic profiles. BSRs are widely distributed in the Makran accretionary wedge, and double BSRs are observed at some locations. Double BSRs usually appear on seismic profiles as two layers of BSRs located at distinct depths but with large lateral seismic amplitude variations. Based on the multi-channel seismic reflection data acquired over the Makran accretionary wedge, this work studies the origin of the double BSR in the Makran accretionary wedge and its association with fluid escape events. Our modeling suggests that double BSRs correspond to both the paleo-seafloor and modern seafloor caused by late sedimentary activities. Also, the residual paleo-BSR migrates upward due to the increase in local geothermal gradient caused by diapirs and gas chimney thermal fluids.

Pitch is a fundamental element in music. While most previous studies on musical pitch have focused on musicians, our understanding of musical pitch perception in non-musicians is still limited. This study aimed to explore how Mandarin-speaking listeners who did not receive musical training perceive and categorize musical pitch. Two experiments were conducted in the study. In Experiment 1, participants were asked to discriminate musical tone pairs with different intervals. The results showed that the nearer apart the tones were, the more difficult it was to distinguish. Among adjacent note pairs at major 2nd pitch distance, the A4–B4 pair was perceived as the easiest to differentiate, while the C4–D4 pair was found to be the most difficult. In Experiment 2, participants completed a tone discrimination and identification task with the C4–D4 and A4–B4 musical tone continua as stimuli. The results revealed that the C4–D4 tone continuum elicited stronger categorical perception than the A4–B4 continuum, although the C4–D4 pair was previously found to be more difficult to distinguish in Experiment 1, suggesting a complex interaction between pitch perception and categorization processing. Together, these two experiments revealed the cognitive mechanism underlying musical pitch perception in ordinary populations and provided insights into future musical pitch training strategies.

Organophosphorus pesticides are the most extensively utilized agrichemicals in the world. They play a crucial role in regulating crop growth, immunizing against pests, and improving yields, while their unregulated residues exert serious detrimental effects on both the environment and human health. Many efforts have been made in the world to monitor organophosphorus pesticides and solve the issues caused by them. Nanozymes, as one kind of enzyme mimic that is artificially designed to simulate the function of natural enzymes, have aroused a lot of attention due to their unparalleled advantages. Nanozymes inherit both the unique properties of nanomaterials and catalytic functions, which could overcome the limitations inherent in natural enzymes and have great versatile and adaptable application prospects. This review presents a recent advancement in synthesizing multifunctional nanozymes with enzymatic-like activities by using various nanomaterials to degrade and detect organophosphorus pesticides. It mainly encompasses metal-based nanozymes, carbon-based nanozymes, metal–organic-framework-based nanozymes, and single-atom-based nanozymes. Additionally, this paper discusses the potential of nanozymes as novel functional environmental materials.

Background: The associations of age at diagnosis of breast cancer with incident myocardial infarction (MI) and heart failure (HF) remain unexamined. Addressing this problem could promote understanding of the cardiovascular impact of breast cancer. Methods: Data were obtained from the UK Biobank. Information on the diagnosis of breast cancer, MI, and HF was collected at baseline and follow-ups (median = 12.8 years). The propensity score matching method and Cox proportional hazards models were employed. Results: A total of 251,277 female participants (mean age: 56.8 ± 8.0 years), of whom 16,241 had breast cancer, were included. Among breast cancer participants, younger age at diagnosis (per 10-year decrease) was significantly associated with elevated risks of MI (hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.19–1.56, p

BackgroundTo investigate whether the novel mutation of PKHD1 could cause polycystic kidney disease by affecting splicing with a recessive inheritance pattern.MethodsA nonconsanguineous Chinese couple with two recurrent pregnancies showed fetal enlarged echogenic polycystic kidney and oligoamnios were recruited. Pedigree WES, minigene splicing assay experiment and following bioinformatics analysis were performed to verify the effects, and inheritance pattern of diseasing-causing mutations.ResultsWES revealed that both fetuses were identified as carrying the same novel mutation c.3592_3628 + 45del, p.? and c.11207 T>C, p.(Ile3736Thr) in the PKHD1 gene (NM_138694.4), which inherited from the father and mother respectively. Both bioinformatic method prediction and minigene splicing assay experience results supported the mutation c.3592_3628 + 45del, p.? affects the splicing of the PKHD1 transcript, resulting in exon 31 skipping. Another missense mutation c.11207 T>C, p.(Ile3736Thr) has a low frequency in populations and is predicted to be deleterious by bioinformatic methods.ConclusionThese findings provide a direct clinical and functional evidence that the truncating mutations of the PKHD1 gene could lead to more severe phenotypes, and cause ARPKD as a homozygous or compound heterozygous pattern. Our study broadens the variant spectrum of the PKHD1 gene and provides a basis for genetic counseling and diagnosis of ARPKD.

Evaluating environmental flow (EF) is pivotal for conserving and restoring riverine ecosystems. Yet, prevalent EF evaluations presume that a river reach's hydraulic conditions are exclusively governed by inflow discharge, presupposing a state of equilibrium in the river channel. This presumption narrows the scope of EF evaluations in expansive alluvial rivers like the Middle Yangtze River (MYR), characterized by marked channel alterations. Here we show the profound channel erosion process and its impact on EF requirements for riparian habitats within the MYR. Our research unveils that: (i) pronounced erosion has led to a mean reduction of 1.0–2.7 m in the riverbed across four sub-reaches of the MYR; (ii) notwithstanding a 37–107% increase in minimal discharges post the Three Gorges Project, the lowest river stages at some hydrometric stations diminished owing to bed erosion, signifying a notable transformation in MYR's hydraulic dynamics; (iii) a discernible rightward shift in the correlation curve between the weighted useable area and discharge from 2002 to 2020 in a specific sub-reach of the MYR, instigated by alterations in hydraulic conditions, necessitated an increase of 1500–2600 m³ s−1 in the required EF for the sub-reach; (iv) it is deduced that macroinvertebrate biomass rapidly decreases as the flow entrains the riverbed substrate, with the maximum survivable velocity for macroinvertebrates being contingent on their entrainment threshold. These findings highlight the importance of incorporating channel morphological changes in devising conservation strategies for the MYR ecosystem.

Abstract Ratios of glycerol dialkyl glycerol tetraethers (GDGT), which are membrane lipids of bacteria and archaea, are at the base of several paleoenvironmental proxies. They are frequently applied to soils as well as lake‐ and marine sediments to generate records of past temperature and soil pH. To derive meaningful environmental information from these reconstructions, high analytical reproducibility is required. Based on submitted results by 39 laboratories from across the world, which employ a diverse range of analytical and quantification methods, we explored the reproducibility of brGDGT‐based proxies (MBT′5ME, IR, and #ringstetra) measured on four soil samples and four soil lipid extracts. Correct identification and integration of 5‐ and 6‐methyl brGDGTs is a prerequisite for the robust calculation of proxy values, but this can be challenging as indicated by the large inter‐interlaboratory variation. The exclusion of statistical outliers improves the reproducibility, where the remaining uncertainty translates into a temperature offset from median proxy values of 0.3–0.9°C and a pH offset of 0.05–0.3. There is no apparent systematic impact of the extraction method and sample preparation steps on the brGDGT ratios. Although reported GDGT concentrations are generally consistent within laboratories, they vary greatly between laboratories. This large variability in brGDGT quantification may relate to variations in ionization efficiency or specific mass spectrometer settings possibly impacting the response of brGDGTs masses relative to that of the internal standard used. While ratio values of GDGT are generally comparable, quantities can currently not be compared between laboratories.

Scutellaria baicalensis Georgi is a medicinal herb with a rich history of use in traditional Chinese medicine. This review concentrates on the chemical constituents of Scutellaria baicalensis Georgi, with a particular emphasis on flavonoids such as baicalin, baicalein, and wogonin. Additionally, it examines the effects of probiotic fermentation on the plant’s chemical profile and pharmacological actions. Evidence suggests that probiotic fermentation markedly modifies the bioactive components of Scutellaria baicalensis Georgi, thereby augmenting its medicinal potency. The paper delves into the mechanisms by which the primary active constituents of Scutellaria baicalensis Georgi are altered during fermentation and how these changes influence its pharmacological properties. This review aims to lay a theoretical groundwork for the clinical utilization of Scutellaria baicalensis Georgi and the formulation of innovative therapeutic approaches.

Soybean production, integral to sustainable agriculture and reliant on imports, faces vulnerability to international risk factors impacting domestic food security. The 2021 Central Rural Work Conference advocated strategic adjustments for sustainable soybean production amidst resource constraints, trade conflicts, and the lingering impact of COVID-19. This study scrutinizes the developmental framework of China’s soybean industry within current domestic policies. This paper uses the soybean sown area and soybean production in each province of China from 1995 to 2020 to measure China’s soybean concentration, production layout, and comparative advantage of regional scale, to analyze in depth the overall situation of China’s soybean production as well as the differences between regions, and to pave the way for the subsequent soybean production forecast. Further, taking the domestic soybean supply and demand situation in China in 2020 as the base period, while considering the growth values of soybean production under different scenarios, the potential forecasting model is utilized to estimate China’s soybean production under different scenarios. The results show that, in terms of inter-annual variability, revealing an upward trajectory from 1995 to 2020, with a shift to major soybean producing areas, notably in the northeast and the Huanghe-Huaihe-Haihe area. From inter-provincial changes, Soybean production on the left and right sides of the “Hu-Huanyong line” has significant heterogeneity; specifically, east of the “Hu-Huanyong line,” soybean production advantages are more obvious. Additionally, the study considered the actual planting situation of soybeans and envisaged two scenarios of compound planting and strip planting. The soybean production range in 2030 is expected to be 20.73–22.32 million tons and 21.15–27.55 million tons, with self-sufficiency rates varying from 18.57 to 19.98% and 18.95 to 24.68%, respectively. The research aims to provide a comprehensive understanding of China’s soybean industry and its potential trajectories, employing a model combining historical trends, policy analysis, and technological advancements. Results suggest a promising future with strategic adjustments in planting structures. Recommendations emphasize policymakers’ prioritization of technological investments and sustainable planting practices to achieve projected production targets. Policy interventions must address challenges tied to resource limitations, trade conflicts, and the ongoing COVID-19 effects, ensuring soybean industry resilience.

Summary: This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.

Abstract The assembly of oligopeptide and polypeptide molecules can reconstruct various ordered advanced structures through intermolecular interactions to achieve protein-like biofunction. Here, we develop a “molecular velcro”-inspired peptide and gelatin co-assembly strategy, in which amphiphilic supramolecular tripeptides are attached to the molecular chain of gelatin methacryloyl via intra-/intermolecular interactions. We perform molecular docking and dynamics simulations to demonstrate the feasibility of this strategy and reveal the advanced structural transition of the co-assembled hydrogel, which brings more ordered β-sheet content and 10-fold or more compressive strength improvement. We conduct transcriptome analysis to reveal the role of co-assembled hydrogel in promoting cell proliferation and chondrogenic differentiation. Subcutaneous implantation evaluation confirms considerably reduced inflammatory responses and immunogenicity in comparison with type I collagen. We demonstrate that bone mesenchymal stem cells-laden co-assembled hydrogel can be stably fixed in rabbit knee joint defects by photocuring, which significantly facilitates hyaline cartilage regeneration after three months. This co-assembly strategy provides an approach for developing cartilage regenerative biomaterials.