Search

Abstract Endo-periodontal lesions (EPLs) involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms, including unique anatomical and microbiological characteristics and multiple contributing factors. This etiological complexity leads to difficulties in determining patient prognosis, posing great challenges in clinical practice. Furthermore, EPL-affected teeth require multidisciplinary therapy, including periodontal therapy, endodontic therapy and others, but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy. By compiling the most recent findings on the etiology, pathogenesis, clinical characteristics, diagnosis, therapy, and prognosis of EPL-affected teeth, this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

Abstract Osteogenesis imperfecta (OI) is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding type I collagen. While it is well known that OI reflects defects in the activity of bone-forming osteoblasts, it is currently unclear whether OI also reflects defects in the many other cell types comprising bone, including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility. Here, we find that numbers of skeletal stem cells (SSCs) and skeletal arterial endothelial cells (AECs) are augmented in Col1a2 oim/oim mice, a well-studied animal model of moderate to severe OI, suggesting that disruption of a vascular SSC niche is a feature of OI pathogenesis. Moreover, crossing Col1a2 oim/oim mice to mice lacking a negative regulator of skeletal angiogenesis and bone formation, Schnurri 3 (SHN3), not only corrected the SSC and AEC phenotypes but moreover robustly corrected the bone mass and spontaneous fracture phenotypes. As this finding suggested a strong therapeutic utility of SHN3 inhibition for the treatment of OI, a bone-targeting AAV was used to mediate Shn3 knockdown, rescuing the Col1a2 oim/oim phenotype and providing therapeutic proof-of-concept for targeting SHN3 for the treatment of OI. Overall, this work both provides proof-of-concept for inhibition of the SHN3 pathway and more broadly addressing defects in the stem/osteoprogenitor niche as is a strategy to treat OI.

Abstract To explore the effect of different levels of systolic blood pressure (SBP) control on new-onset chronic kidney disease in hypertension multimorbidity. The hypertensive patients with multimorbidity information were enrolled from the Kailuan Study. The isolated hypertension patients undergoing physical examination during the same period were selected in a 1:1 ratio as control. Finally, 12,897 participants were divided into six groups: Group SBP

Abstract Dual emission from thermally activated delayed fluorescence (TADF) emitters is often difficult to observe, especially in solution, limited by Kasha’s rule. Two TADF dendrimers containing N-doped polycyclic aromatic hydrocarbons as acceptors are designed and synthesized. Compound 2GCzBPN, having a strongly twisted geometry, exhibits TADF, while 2GCzBPPZ, possessing a less twisted geometry, shows dual emission associated with the monomer and aggregate that is TADF. The demonstration reveals that 2GCzBPPZ can serve as a temperature sensor with excellent temperature sensitivity and remarkably wide emission color response in solution. By embedding 2GCzBPPZ in paraffin we demonstrate a spatial-temperature sensor that shows a noticeable emission shift from yellow to green and ultimately to blue as the temperature increases from 20 to 200 °C. We finally demonstrate the utility of these TADF dendrimers in solution-processed organic light-emitting diodes.

Abstract Lithium‐ion battery state‐of‐health (SOH) monitoring is essential for maintaining the safety and reliability of electric vehicles and efficiency of energy storage systems. When the SOH of lithium‐ion batteries reaches the end‐of‐life threshold, replacement and maintenance are required to avoid fire and explosion hazards. This paper provides a comprehensive literature review of lithium‐ion battery SOH estimation methods at the cell, module, and pack levels. Analysis and summary of the SOH definition based on the resistance, capacity, and energy indices are presented at each battery hierarchy level. A Comparison of SOH indices in terms of modelling complexity, required measurement time, and accuracy is provided. To the best of knowledge, a comprehensive classification of SOH estimation methods at different battery hierarchy levels is presented for the first time in this review. In addition, SOH estimation methods are further classified based on the applied methodologies, including direct measurement, model‐based methods, data‐driven methods, and hybrid model‐data methods. Advantages and disadvantages of SOH estimation methods are summarized and compared across different battery hierarchy levels. A detailed summary of typical SOH estimation methods is presented along with the battery topology, operating conditions, and performance. The challenges and research prospects of lithium‐ion battery SOH estimation are discussed from the cell to pack levels.

Abstract Purpose To investigate the repeatability and reproducibility of a new method for centration analysis after small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK (FS-LASIK). Methods This study comprised 29 eyes treated with SMILE and 24 with FS-LASIK. Decentrations were analyzed using tangential and pachymetry difference maps respectively. Both difference maps were generated with a Scheimpflug tomographer (Pentacam) for each eye, using preoperative and 3-month postoperative scans. Repeatability and reproducibility were evaluated by calculating the intraclass correlation coefficient (ICC), within-subject standard deviation (Sw), and coefficient of repeatability (CR). Results ICC, Sw, and CR showed good to excellent repeatability in locating the coordinates of the optical zone (OZ) center on both maps, with values ranging from 0.84 to 0.96, 0.03 to 0.13, and 0.08 to 0.36 respectively. The repeatability of the total decentration from the preoperative corneal vertex on the tangential curvature difference maps( $$d_{TC}$$ d TC ) and the pachymetry difference maps( $$d_{PC}$$ d PC ) were moderate and good, respectively. The ICC, Sw, and CR of $$d_{TC}$$ d TC were 0.63, 0.09, and 0.25, respectively. The ICC, Sw, and CR of $$d_{PC}$$ d PC were 0.77, 0.10, and 0.28, respectively. The reproducibility of the OZ center measurements was excellent for the tangential difference maps (ICC $$\ge 0.97$$ ≥ 0.97 ) and good for the pachymetry difference maps (ICC $$\ge$$ ≥ 0.86). ICC, Sw, and CR showed excellent reproducibility of $$d_{TC}$$ d TC , with values of 0.95, 0.03, and 0.08, respectively. ICC, Sw, and CR showed good reproducibility of $$d_{PC}$$ d PC , with values of 0.89, 0.06, and 0.17, respectively. Conclusion The centration analysis method used in this study showed good to excellent repeatability and reproducibility in locating the coordinates of the center of the OZ on the tangential and pachymetry difference maps.

Abstract The marine ecological red lines (MERLs) is an institutional innovation of the Chinese government to seek a balance between ecological protection and social development. China’s MERLs was designated in 2017, but there are problems such as insufficient consideration of areas of high ecological importance and lack of convergence with marine functional zoning. This paper carries out the adjustment of the MERLs in China by constructing the methods of marine ecological importance assessment and human activities disposal assessment, and the results show that after the adjustment, the type and distribution pattern of China’s MERLs is more reasonable, the areas of high ecological importance in the MERLs increases significantly, the intensity of human activities in the MERLs declines significantly, and the unification with the use of marine space is realized. China’s adjustment of the MERLs is based on scientific assessment and realizes the coordination of development and protection, which can provide a reference for global marine ecological protection.

Abstract Objective Neutrophil-to-lymphocyte ratio (NLR) has been shown to be an independent predictor for cardiovascular diseases and metabolic diseases. The role of NLR in metabolic syndrome (MS) has also been explored albeit with conflicting results. The objective of this study was to assess the predictive role of NLR in MS. Methods We conducted a meta-analysis of observational studies to evaluate the predictive role of NLR in MS. Cochrane library, PubMed, Medline, Embase, and Scopus were systematically searched from their inception to December 2023. The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines was followed. The statistical analysis was performed using RevMan 5.3 software. A randomeffect model was used. Results Twenty six studies enrolling 70,937 individuals were included in this meta-analysis. Compared with the individuals without MS, NLR value was significantly higher in the patients of MS (mean difference (MD) 0.40, 95% confidence intervals (CI): 0.27–0.52, P

Abstract Background The present study aimed to investigate physicians’ perspectives on the diagnosis and treatment decisions for patients with non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutations in a real-world setting in China using an online questionnaire. Methods This study was performed via the CAPTRA-Lung collaboration between December 9, 2022 and March 6, 2023. The questionnaire was distributed digitally to physicians around China and was comprised of three sections: basic characteristics of surveyed physicians, diagnosis and treatment status of NSCLC patients with the EGFR exon20ins-mutation, and physicians’ perspectives on treatment options. Physicians who treat more than 10 patients with advanced NSCLC every month and who have treated patients with advanced EGFR exon20ins-mutant NSCLC in the past six months were involved in this study. Results A total of 53,729 questionnaires were distributed and 390 valid ones were collected. The EGFR mutation test was performed in 80.9% and 59.9% of patients receiving first-line or second-line therapy and beyond (hereinafter “second-line”)therapy, respectively. In terms of treatment options, chemotherapy plus antiangiogenic therapy was the most common treatment option (30.0% of patients in first-line settings; 25.0% of patients in second-line settings), and a certain proportion of patients received novel EGFR exon20ins-targeted agents (including tyrosine kinase inhibitors [TKIs] and bispecific antibodies) in first- or second-line settings, which accounted for 11.9% and 15.7% of all treated patients, respectively. Additionally, physicians reported the highest satisfaction score for the efficacy and safety of targeted agents. Most physicians believed that EGFR exon20ins-targeted TKIs represented the most promising treatment option (80.2% in first-line treatment and 73.3% in second-line treatment). Among several novel agents under study, sunvozertinib has received the highest recognition for efficacy and safety. Conclusions This study investigated the current diagnosis and treatment status and physicians’ perspective, of patients with EGFR exon20ins-mutant NSCLC. The results highlight significant unmet clinical needs in this subgroup of patients. EGFR exon20ins-targeted TKIs were recognized as the most promising treatment regimen and may benefit more patients considering their awareness and acceptance of targeted therapy.

Abstract Intertidal algae may adapt to environmental challenges by acquiring genes from other organisms and relying on symbiotic microorganisms. Here, we obtained a symbiont-free and chromosome-level genome of Pyropia haitanensis (47.2 Mb), a type of intertidal algae, by using multiple symbiont screening methods. We identified 286 horizontal gene transfer (HGT) genes, 251 of which harbored transposable elements (TEs), reflecting the importance of TEs for facilitating the transfer of genes into P. haitanensis. Notably, the bulked segregant analysis revealed that two HGT genes, sirohydrochlorin ferrochelatase and peptide-methionine (R)-S-oxide reductase, play a significant role in the adaptation of P. haitanensis to heat stress. Besides, we found Pseudomonas, Actinobacteria, and Bacteroidetes are the major taxa among the symbiotic bacteria of P. haitanensis (nearly 50% of the HGT gene donors). Among of them, a heat-tolerant actinobacterial strain (Saccharothrix sp.) was isolated and revealed to be associated with the heat tolerance of P. haitanensis through its regulatory effects on the genes involved in proline synthesis (proC), redox homeostasis (ggt), and protein folding (HSP20). These findings contribute to our understanding of the adaptive evolution of intertidal algae, expanding our knowledge of the HGT genes and symbiotic microorganisms to enhance their resilience and survival in challenging intertidal environments.

Abstract Background This study aimed to assess the effectiveness of the BOPPPS model (bridge-in, learning objective, pre-test, participatory learning, post-test, and summary) in otolaryngology education for five-year undergraduate students. Methods A non-randomized controlled trial was conducted with 167 five-year undergraduate students from Anhui Medical University, who were allocated to an experimental group and a control group. The experimental group received instruction using the BOPPPS model, while the control group underwent traditional teaching methods. The evaluation of the teaching effectiveness was performed through an anonymous questionnaire based on the course evaluation questionnaire. Students’ perspectives and self-evaluations were quantified using a five-point Likert scale. Furthermore, students’ comprehension of the course content was measured through a comprehensive final examination at the end of the semester. Results Students in the experimental group reported significantly higher scores in various competencies compared to the control group: planning work (4.27 ± 0.676 vs. 4.03 ± 0.581, P

Abstract Introduction Inflammatory and immunological responses are reported involved in the pathogenesis and progression of obstructive nephropathy (ON). This study was designed to investigate the characteristics of peripheral immunity in patients with upper urinary tract urolithiasis and analyze the underlying associations with renal function. Methods Patients with unilateral upper urinary tract urolithiasis meeting the operation indications were prospectively enrolled. Preoperative circulating immune cells and inflammatory cytokines were detected in our clinical laboratory, and the indicators of renal function and calculi related parameters were particularly recorded. Patients were sectionalized into subgroups on the basis of the lesion of calculi. Characteristics of peripheral immunity in each subgroup were investigated by statistical approaches, and the underlying correlations with the degree of hydronephrosis (HN) and renal function were discussed in corresponding group. Results Patients with ureteral calculi presented severer HN compared with renal calculi, especial middle ureteral calculi, acting as the chief culprit of ON, exhibiting the highest serum creatine and blood urea nitrogen, most impaired estimated glomerular filtration rate, and severest HN. In addition, serum interleukin-8 (IL-8) and IL-6 were demonstrated presenting statistical differences between ureteral calculi and renal calculi patients, exhibiting underlying values in comprehending ON. However, circulating immune cells were demonstrated no obvious differences among groups. Conclusions Circulating inflammatory cytokines, referred in particular to serum IL-8 and IL-6 were partially associated with kidney injury in patients with upper urinary tract urolithiasis. But the specific influences and mechanisms between them needed to be investigated furthermore.

To enhance the aerodynamic performance of aero engine blades, simulations and experiments regarding microtextures to reduce the flow loss on the blade surfaces were carried out. First, based on the axisymmetric characteristics of the impeller, a new simulation method was proposed to determine the aerodynamic parameters of the blade model through the comparison of flow field characteristics and simulation results. Second, the placement position and geometrical parameters (height, width, and spacing) of microtextures with lower energy loss were determined by our simulation of microtextures on the blade surface, and the drag reduction mechanism was analyzed. Triangular ribs with a height of 0.2 mm, a width of 0.3 mm, and a spacing of 0.2 mm exhibited the best drag reduction, reducing the energy loss coefficient and drag by 1.45% and 1.31% for a single blade, respectively. Finally, the blades with the optimal microtexture parameters were tested in the wind tunnel. The experimental results showed that the microtexture decreased energy loss by 3.7% for a single blade under 57° angle of attack and 136.24 m/s, which was favorable regarding the drag reduction performance of the impeller with 45 blades.

Abstract Background Parent-child separation poses a significant challenge for left-behind children (LBC). However, limited empirical evidence exists regarding the correlation between left-behind characteristics and the psychological symptoms of LBC. This study investigated psychological symptoms among LBC and explored associations between left-behind characteristics and those symptoms. Methods Using stratified cluster sampling, 1,832 LBC aged 13–18 years from three cities in East China were selected for analysis. Participants’ depression and anxiety symptoms were assessed with the Patient Health Questionnaire 9 and the General Anxiety Disorder 7, respectively. Chi-square tests were used to compare differences in detection rates of psychological symptoms among LBC in different groups. Binary logistic regression analysis was used to infer associations between left-behind characteristics and psychological symptoms. Results Depression and anxiety symptoms were detected in 32.86% and 33.24%, respectively, of participating LBC. Univariate analysis showed statistically significant differences in detection rates of depression symptoms by sex, grade, and timing of parent-child separation. Statistically significant differences were observed in anxiety symptom rates by sex, grade, type of caregiver, and timing of mother-child separation. Multivariate analysis indicated a positive association between LBC’s anxiety symptoms and mother-child separation that occurred during post-primary school, and type of caregiver (father only or mother only). Our findings confirm a positive association between left-behind characteristics and anxiety symptoms among LBC. Conclusion The timing of mother-child separation and type of caregiver are potential risk factors for the development of anxiety symptoms in this population.

Abstract Purpose Cutaneous metastasis (CM) accounts for 5–30% of patients with breast cancer (BC) and presents unfavorable response to treatment and poor prognosis. A better understanding of the molecular alterations involved in metastasis is essential, which would help identify diagnostic and efficacy biomarkers for CM. Materials : We retrospectively reviewed a total of 13 patients with histological or cytological diagnosis of breast cancer and CM. Clinical information was extracted from the medical records. The mutational landscape of matched primary tumors with their lymph nodes or CM tissues were analyzed using next-generation sequencing (NGS) of 425 cancer-relevant genes. All tissues were also analyzed by immunohistochemistry (IHC). The association of prognosis with various clinical and molecular factors was also evaluated. Results More than half of the patients were Ki67 low ( 50%) showed significantly shorter T1 than the Ki67 low group (≤ 50%) (median 12.5 vs. 50.0 months, P = 0.036). TP53, PIK3CA mutations, and TERT amplification group were associated with inferior T2 (median 11 vs. 36 months, P = 0.065; 8 vs. 36 months, P = 0.013, 7 vs. 36 months, P = 0.003, respectively). All p values were not adjusted. Conclusion We compared the genomic features of primary breast cancer tissues with their corresponding CM tissues and discussed potential genes and pathways that may contribute to the skin metastasis of advanced breast cancers patients. TP53, PIK3CA mutant, and TERT amplification may serve as biomarkers for poor prognosis for CM patients.

Abstract A power system can be regarded as a cyber‐physical system with physical power networks and a cyber system based on increasing engagement with information communication technologies for smart grid functionalities for more efficient operations and control. Non‐intrusive load monitoring (NILM), an emerging smart‐grid technology, can be used to better understand the electricity usage profile and composition of smart meters using advanced data analysis algorithms. Although NILM enables various smart grid services, wider applications of NILM require addressing the challenges regarding cyber security and data privacy risks. Anomaly detection in appliance data is one of the most effective measures against potential cyber intrusions from a data perspective. This study proposes a framework of anomaly detection‐based learning algorithms to identify the anomalous periods of electricity loading data, which may be a subject for potential cyber‐attacks. Comparison studies with the hidden Markov model are performed to validate the proposed approaches. The simulation results show that these anomaly detection‐based learning algorithms work well and can precisely determine anomalous loading periods. Moreover, these trained models perform well on the testing dataset without prior knowledge of the data, providing the possibility of the real‐time assessment of power‐ loading states. The proposed framework can also be used to develop protective measures to ensure secure system operation and user data privacy.

Abstract Developing superporous hemostatic sponges with simultaneously enhanced permeability and mechanical properties remains challenging but highly desirable to achieve rapid hemostasis for non-compressible hemorrhage. Typical approaches to improve the permeability of hemostatic sponges by increasing porosity sacrifice mechanical properties and yield limited pore interconnectivity, thereby undermining the hemostatic efficacy and subsequent tissue regeneration. Herein, we propose a temperature-assisted secondary network compaction strategy following the phase separation-induced primary compaction to fabricate the superporous chitosan sponge with highly-interconnected porous structure, enhanced blood absorption rate and capacity, and fatigue resistance. The superporous chitosan sponge exhibits rapid shape recovery after absorbing blood and maintains sufficient pressure on wounds to build a robust physical barrier to greatly improve hemostatic efficiency. Furthermore, the superporous chitosan sponge outperforms commercial gauze, gelatin sponges, and chitosan powder by enhancing hemostatic efficiency, cell infiltration, vascular regeneration, and in-situ tissue regeneration in non-compressible organ injury models, respectively. We believe the proposed secondary network compaction strategy provides a simple yet effective method to fabricate superporous hemostatic sponges for diverse clinical applications.

Abstract Bacteriophages (phages) represent a unique category of viruses with a remarkable ability to selectively infect host bacteria, characterized by their assembly from proteins and nucleic acids. Leveraging their exceptional biological properties and modifiable characteristics, phages emerge as innovative, safe, and efficient delivery vectors. The potential drawbacks associated with conventional nanocarriers in the realms of drug and gene delivery include a lack of cell-specific targeting, cytotoxicity, and diminished in vivo transfection efficiency. In contrast, engineered phages, when employed as cargo delivery vectors, hold the promise to surmount these limitations and attain enhanced delivery efficacy. This review comprehensively outlines current strategies for the engineering of phages, delineates the principal types of phages utilized as nanocarriers in drug and gene delivery, and explores the application of phage-based delivery systems in disease therapy. Additionally, an incisive analysis is provided, critically examining the challenges confronted by phage-based delivery systems within the domain of nanotechnology. The primary objective of this article is to furnish a theoretical reference that contributes to the reasoned design and development of potent phage-based delivery systems. Graphical abstract

Abstract Background Research into the acute kidney disease (AKD) after acute ischemic stroke (AIS) is rare, and how clinical features influence its prognosis remain unknown. We aim to employ interpretable machine learning (ML) models to study AIS and clarify its decision-making process in identifying the risk of mortality. Methods We conducted a retrospective cohort study involving AIS patients from January 2020 to June 2021. Patient data were randomly divided into training and test sets. Eight ML algorithms were employed to construct predictive models for mortality. The performance of the best model was evaluated using various metrics. Furthermore, we created an artificial intelligence (AI)-driven web application that leveraged the top ten most crucial features for mortality prediction. Results The study cohort consisted of 1633 AIS patients, among whom 257 (15.74%) developed subacute AKD, 173 (10.59%) experienced AKI recovery, and 65 (3.98%) met criteria for both AKI and AKD. The mortality rate stood at 4.84%. The LightGBM model displayed superior performance, boasting an AUROC of 0.96 for mortality prediction. The top five features linked to mortality were ACEI/ARE, renal function trajectories, neutrophil count, diuretics, and serum creatinine. Moreover, we designed a web application using the LightGBM model to estimate mortality risk. Conclusions Complete renal function trajectories, including AKI and AKD, are vital for fitting mortality in AIS patients. An interpretable ML model effectively clarified its decision-making process for identifying AIS patients at risk of mortality. The AI-driven web application has the potential to contribute to the development of personalized early mortality prevention.

Abstract Prunus conradinae, a valuable flowering cherry belonging to the Rosaceae family subgenus Cerasus and endemic to China, has high economic and ornamental value. However, a high-quality P. conradinae genome is unavailable, which hinders our understanding of its genetic relationships and phylogenesis, and ultimately, the possibility of mining of key genes for important traits. Herein, we have successfully assembled a chromosome-scale P. conradinae genome, identifying 31,134 protein-coding genes, with 98.22% of them functionally annotated. Furthermore, we determined that repetitive sequences constitute 46.23% of the genome. Structural variation detection revealed some syntenic regions, inversions, translocations, and duplications, highlighting the genetic diversity and complexity of Cerasus. Phylogenetic analysis demonstrated that P. conradinae is most closely related to P. campanulata, from which it diverged ~ 19.1 million years ago (Mya). P. avium diverged earlier than P. cerasus and P. conradinae. Similar to the other Prunus species, P. conradinae underwent a common whole-genome duplication event at ~ 138.60 Mya. Furthermore, 79 MADS-box members were identified in P. conradinae, accompanied by the expansion of the SHORT VEGETATIVE PHASE subfamily. Our findings shed light on the complex genetic relationships, and genome evolution of P. conradinae and will facilitate research on the molecular breeding and functions of key genes related to important horticultural and economic characteristics of subgenus Cerasus.

Abstract The demand for larger and lighter mechanisms for next-generation space missions necessitates using deployable structures. High-strain fiber polymer composites show considerable promise for such applications due to their exceptional strength-to-weight ratio, manufacturing versatility, packaging efficiency, and capacity for self-deployment using stored strain energy. However, a significant challenge in using composite deployable structures for space applications arises from the unavoidable extended stowage periods before they are deployed into their operational configuration in orbit. During the stowage period, the polymers within the composites experience material degradation due to their inherent viscoelastic and/or plastic properties, causing stress relaxation and accumulation of plastic strains, thereby reducing the deployment capability and resulting in issues related to recovery accuracy. This paper aims to give a state-of-the-art review of recent advances in the design, modeling, and manufacturing of high-strain composites for deployable structures in space applications, emphasizing the long-term stowage effects. This review is intended to initiate discussion of future research to enable efficient, robust, and accurate design of composite deployable structures that account for the enduring challenges posed by long-term stowage effects.

In July 2021, a heavy rainstorm was sweeping across Henan Province, causing geological disasters such as floods, mudslides, and landslides, which seriously threatened the safety of human life and property. Precipitable water vapor (PWV) is related to the occurrence and scale of rainfall. Here, based on Global Navigation Satellite System (GNSS) observations, in-situ meteorological files (GMET), ephemeris products, ERA5 data, and weather station data, the relationship between PWV and rainstorm from July 1st to 30th was studied. The results show that GMET and ERA5 in July 2021 have high consistency in some stations, with a root mean square error (RMSE) for temperature below 1.6 °C, for pressure below 0.5 hPa, and for relative humidity below 9 %. During the week before the heavy rainstorm, the temperature dropped remarkably and the temperature difference decreased, while the relative humidity increased and the relative humidity difference decreased. Compared with ERA5 PWV, the RMSE of GNSS PWV retrieved using real-time ephemeris is 3.238 mm. Different from the normal rainfall, we found that the PWV variation during the Henan rainstorm experienced a unique “accumulation” period. We also observed a clear correlation between PWV and the rainstorm, both temporally and spatially. In addition, the PWV in the severely damaged area was 20 mm higher than the average value of the past decade. Ten days after the rainstorm, the surface of this area had subsided by 1.5–3 mm. Finally, we found that the topography of Henan, the low vortex, the north-biased subtropical high, and the double typhoons all played a role in the successful transport and deposition of water vapor.

ABSTRACTCapsule Robot Endoscope (CRE), as one of the widely used methods of gastrointestinal medical examination, has the characteristics of painless, non-cross infection, and no movement restriction, compared with other traditional endoscopes. To obtain the precise location of the lesion, positioning the capsule robot in the digestive tract has become a hot research topic in related fields. In recent decades, with the rapid advancement of indoor and outdoor positioning technologies, several well-established methods have emerged that enable the acquisition of high-precision real-time spatiotemporal integration data. These methods hold great potential for interdisciplinary applications in location services across various domains. The manuscript aims to draw inspiration from surveying and mapping positioning techniques by reviewing existing microspace positioning technologies to overcome inherent technical challenges. This article has reviewed more than 100 pieces of literature at home and abroad from four major academic search engines and has further studied the state of the art of several capsule robot positioning technologies commonly used. Microspace positioning technology in capsule robots is evaluated across eight factors: positioning accuracy, power consumption, portability, comfort, complexity, robustness, extensibility, and cost. We summarize the technical challenges associated with capsule robot positioning technology from each positioning technology’s limitations, finally proffering prospective avenues for future research. Our investigation reveals that the six identified capsule robot positioning technologies have distinct advantages and disadvantages. Among these, magnetic field-based positioning technology exhibited superior overall performance and is gradually advancing toward commercialization. Vision-based positioning technology, while significantly contributing to medical applications, particularly in enhancing augmented reality and surgical navigation, faces challenges related to the weak-textured and non-rigid characteristics of the gastrointestinal environment. Additionally, the limitation posed by the size and energy consumption of capsule robots make difficulties for single-source positioning techniques. We have proposed several promising future research directions by considering the capsule robot’s current positioning technological challenges and the advancements of cutting-edge indoor and outdoor positioning technologies. These include exploring new positioning sources, integrating multiple sensor fusion, and developing real-time three-dimensional gastrointestinal models. These new approaches are expected to enhance the safety and reliability of capsule robot positioning technology. They can potentially promote the development of capsule robots further and provide support for diagnosing and treating gastrointestinal diseases.

Abstract The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.

Abstract Despite the record speed of developing vaccines and therapeutics against the SARS-CoV-2 virus, it is not a given that such success can be secured in future pandemics. In addition, COVID-19 vaccination and application of therapeutics remain low in developing countries. Rapid and low cost mass production of antiviral IgY antibodies could be an attractive alternative or complementary option for vaccine and therapeutic development. In this article, we rapidly produced SARS-CoV-2 antigens, immunized hens and purified IgY antibodies in 2 months after the SARS-CoV-2 gene sequence became public. We further demonstrated that the IgY antibodies competitively block RBD binding to ACE2, neutralize authentic SARS-CoV-2 virus and effectively protect hamsters from SARS-CoV-2 challenge by preventing weight loss and lung pathology, representing the first comprehensive study with IgY antibodies. The process of mass production can be easily implemented in most developing countries and hence could become a new vital option in our toolbox for combating viral pandemics. This study could stimulate further studies, optimization and potential applications of IgY antibodies as therapeutics and prophylactics for human and animals.

Abstract Gastric cancer is one of the most common malignant tumors, and chemotherapy is the main treatment for advanced gastric cancer. However, chemotherapy resistance leads to treatment failure and poor prognosis in patients with gastric cancer. Multidrug resistance (MDR) is a major challenge that needs to be overcome in chemotherapy. According to recent research, ferroptosis activation is crucial for tumor therapeutic strategies. In this work, we explored the solution to chemoresistance in gastric cancer by investigating the effects of the Chinese medicine monomer baicalin on ferroptosis. Baicalin with different concentrations was used to treat the parent HGC27 and drug-resistant HGC27/L cells of gastric cancer. Cell viability was measured by CCK8, and synergistic effects of baicalin combined with oxaliplatin were evaluated using Synergy Finder software. The effects of baicalin on organelles and cell morphology were investigated using projective electron microscopy. Iron concentration, MDA production and GSH inhibition rate were measured by colorimetry. ROS accumulation was detected by flow cytometry. The ferroptosis-related genes (IREB2, TfR, GPX4, FTH1), P53, and SLC7A11 were analysed by Western blot, and the expression differences of the above proteins between pretreatment and pretreatment of different concentrations of baicalin, were assayed in both parental HGC27 cells and Oxaliplatin-resistant HGC27/L cells. Mechanically, Baicalin disrupted iron homeostasis and inhibits antioxidant defense, resulting in iron accumulation, lipid peroxide aggregation, and specifically targeted and activated ferroptosis by upregulating the expression of tumor suppressor gene p53, thereby activating the SLC7A11/GPX4/ROS pathway mediated by it. Baicalin activates ferroptosis through multiple pathways and targets, thereby inhibiting the viability of oxaliplatin-resistant gastric cancer HGC27/L cells and enhancing the sensitivity to oxaliplatin chemotherapy.

Abstract Growth differentiation factor 15 (GDF15) as a stress response cytokine is involved in the development and progression of several diseases associated with metabolic disorders. However, the regulatory role and the underlying mechanisms of GDF15 in sepsis remain poorly defined. Our study analyzed the levels of GDF15 and its correlations with the clinical prognosis of patients with sepsis. In vivo and in vitro models of sepsis were applied to elucidate the role and mechanisms of GDF15 in sepsis-associated lung injury. We observed strong correlations of plasma GDF15 levels with the levels of C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and lactate as well as Sequential Organ Failure Assessment (SOFA) scores in patients with sepsis. In the mouse model of lipopolysaccharide-induced sepsis, recombinant GDF15 inhibited the proinflammatory responses and alleviated lung tissue injury. In addition, GDF15 decreased the levels of cytokines produced by alveolar macrophages (AMs). The anti-inflammatory effect of glycolysis inhibitor 2-DG on AMs during sepsis was mediated by GDF15 via inducing the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α) and the expression of activating transcription factor 4 (ATF4). Furthermore, we explored the mechanism underlying the beneficial effects of GDF15 and found that GDF15 inhibited glycolysis and mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) signaling via promoting AMPK phosphorylation. This study demonstrated that GDF15 inhibited glycolysis and NF-κB/MAPKs signaling via activating AMP-activated protein kinase (AMPK), thereby alleviating the inflammatory responses of AMs and sepsis-associated lung injury. Our findings provided new insights into novel therapeutic strategies for treating sepsis.

Abstract Singapore's power sector has set targets of net‐zero emissions by 2050. Given the limited land space of the country, a key strategy to decarbonize the power grid is to import clean power from renewable energy resources such as photovoltaic (PV) plants installed at overseas locations. The present electricity market rules require such overseas PV plants to maintain constant power generation during each bidding period. To meet such requirements, energy storage systems (ESSs) are to be deployed in the PV plants to compensate for the PV power fluctuation. This paper proposes an optimal power bidding approach for maximizing the profit of the PV plant participating in the Singapore wholesale electricity market. The problem is formulated as a stochastic programming model, which takes the short‐term PV power forecasting as the input, maximizes the expected profit considering the PV power selling revenue and the penalty cost for power shortfall during each bidding cycle (30 min), and satisfies constraints of the ESS. The proposed method can also be used for determining the optimal size of the ESS. Simulation results have verified the effectiveness of the proposed method.

Abstract Heat shock protein 90 (HSP90) is overexpressed in numerous cancers, promotes the maturation of numerous oncoproteins and facilitates cancer cell growth. Certain HSP90 inhibitors have entered clinical trials. Although less than satisfactory clinical effects or insurmountable toxicity have compelled these trials to be terminated or postponed, these results of preclinical and clinical studies demonstrated that the prospects of targeting therapeutic strategies involving HSP90 inhibitors deserve enough attention. Nanoparticulate-based drug delivery systems have been generally supposed as one of the most promising formulations especially for targeting strategies. However, so far, no active targeting nano-formulations have succeeded in clinical translation, mainly due to complicated preparation, complex formulations leading to difficult industrialization, incomplete biocompatibility or nontoxicity. In this study, HSP90 and CD44-targeted A6 peptide functionalized biomimetic nanoparticles (A6-NP) was designed and various degrees of A6-modification on nanoparticles were fabricated to evaluate targeting ability and anticancer efficiency. With no excipients, the hydrophobic HSP90 inhibitor G2111 and A6-conjugated human serum albumin could self-assemble into nanoparticles with a uniform particle size of approximately 200 nm, easy fabrication, well biocompatibility and avoidance of hepatotoxicity. Besides, G2111 encapsulated in A6-NP was only released less than 5% in 12 h, which may avoid off-target cell toxicity before entering into cancer cells. A6 peptide modification could significantly enhance uptake within a short time. Moreover, A6-NP continues to exert the broad anticancer spectrum of Hsp90 inhibitors and displays remarkable targeting ability and anticancer efficacy both in hematological malignancies and solid tumors (with colon tumors as the model cancer) both in vitro and in vivo. Overall, A6-NP, as a simple, biomimetic and active dual-targeting (CD44 and HSP90) nanomedicine, displays high potential for clinical translation.

Abstract Background Sarcopenic obesity emerges as a risk factor for adverse clinical outcomes in non-hospitalized older adults, including physical disabilities, metabolic diseases, and even mortality. In this systematic review and meta-analysis, we investigated the overall SO prevalence in non-hospitalized adults aged ≥ 65 years and assessed the sociodemographic, clinicobiological, and lifestyle factors related to SO. Methods We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for studies reporting the prevalence of SO from database inception to October 2023. Two researchers independently screened the literature, evaluated the study quality, and extracted the data. Both fixed- and random-effects models were used in the meta-analysis to estimate the pooled SO prevalence and perform subgroup analyses. Publication and sensitivity bias analyses were performed to test the robustness of the associations. Results Among 46 studies eligible for review and a total of 71,757 non-hospitalized older adults, the combined prevalence of SO was 14% (95% CI:11–17%, I2 = 99.5%, P

Objective: To investigate the effect of Guangdong Shenqu (GSQ) on intestinal flora structure in mice with food stagnation through 16S rDNA sequencing. Methods: Mice were randomly assigned to control, model, GSQ low-dose (GSQL), GSQ medium-dose (GSQM), GSQ high-dose (GSQH), and lacidophilin tablets (LAB) groups, with each group containing 10 mice. A food stagnation and internal heat mouse model was established through intragastric administration of a mixture of beeswax and olive oil (1:15). The control group was administered normal saline, and the model group was administered beeswax and olive oil to maintain a state. The GSQL (2 g/kg), GSQM (4 g/kg), GSQH (8 g/kg), and LAB groups (0.625 g/kg) were administered corresponding drugs for 5 d. After administration, 16S rDNA sequencing was performed to assess gut microbiota in mouse fecal samples. Results: The model group exhibited significant intestinal flora changes. Following GSQ administration, the abundance and diversity index of the intestinal flora increased significantly, the number of bacterial species was regulated, and α and β diversity were improved. GSQ administration increased the abundance of probiotics, including Clostridia, Lachnospirales, and Lactobacillus, whereas the abundance of conditional pathogenic bacteria, such as Allobaculum, Erysipelotrichaceae, and Bacteroides decreased. Functional prediction analysis indicated that the pathogenesis of food stagnation and GSQ intervention were primarily associated with carbohydrate, lipid, and amino acid metabolism, among other metabolic pathways. Conclusion: The digestive mechanism of GSQ may be attributed to its role in restoring diversity and abundance within the intestinal flora, thereby improving the composition and structure of the intestinal flora in mice and subsequently influencing the regulation of metabolic pathways.

Abstract The strain clamps and leading wires are important components that connect conductors on overhead transmission lines and conduct current. During operation, poor contact between these components can cause abnormal overheating, leading to electric failures and threatening power system reliability. Recently, the use of unmanned aerial vehicles equipped with infrared thermal imagers for strain clamp and leading wire maintenance has become increasingly popular. Deep learning‐based image recognition shows promising prospects for intelligent fault diagnosis of overheating faults. A pre‐treatment method is proposed based on dynamic histogram equalisation to enhance the contrast of infrared images. The DeepLab v3+ network, loss function, and existing networks with different backbones are compared. The DeepLab v3+ network with ResNet101 and convolutional block attention module added, and the Focal Loss function achieved the highest performance with an average pixel accuracy of 0.614, an average intersection over union (AIoU) of 0.567, an F1 score of 0.644, and a frequency weighted intersection over union of 0.594 on the test set. The optimised Atrous rates has increased the AIoU by 12.91%. Moreover, an intelligent diagnosis scheme for evaluating the defect state of the strain clamps and leading wires is proposed and which achieves a diagnostic accuracy of 91.0%.

Abstract Background Early assessment of the risk of nonunion in osteoporotic vertebral compression fracture (OVCF) is beneficial to early clinical decision making. However, a comprehensive understanding of the risk factors for OVCF nonunion is lacking. Methods We conducted a case–control study to investigate risk factors for OVCF nonunion. Patients who underwent surgery for nonunited OVCFs between January 2011 and December 2021 were eligible for inclusion as cases. Patients with successful OVCF healing confirmed by MRI over the same period were identified as controls. Patient demographics, comorbidities, and fasting blood test data were extracted for analysis. Results A total of 201 patients with nonunited OVCFs and 1044 controls were included to evaluate the risk factors for nonunited OVCFs. There were statistically significant differences in sex, age, number of patients with hypertension, number of patients on bed rest after OVCF and T-score of BMD between the two groups. Logistic regression showed that female patients had a higher risk of OVCF nonunion than male patients and that smoking, drinking, diabetes, and hypertension were risk factors for nonunion of OVCFs, while bed rest and spinal support were protective factors against nonunion of OVCFs. We also found that age, BMD, FBG, and β-CTX were positively correlated with nonunited OVCFs, and that HGB and 1,25-(OH)2VitD3 level were negatively correlated with nonunited OVCFs. Conclusion Smoking, drinking, diabetes and hypertension were risk factors for nonunion of OVCFs, while bed rest and spinal support were protective factors against nonunion of OVCFs. Age, BMD, FBG and β-CTX were positively correlated with nonunited OVCFs, while HGB and 1,25-(OH)2VitD3 level were negatively correlated with nonunited OVCFs. Based on the results of our study, we suggest that bed rest or spinal support for at least 3 consecutive weeks is necessary to reduce the risk of OVCFs nonunion.

Abstract The factors influencing geogrid–soil interface characteristics are critical design parameters in some geotechnical designs. This study describes pull-out tests performed on gravelly soils commonly encountered in the Xinjiang region and reinforced with two types of geogrids. The factors affecting the geogrid–gravelly soil interface properties are investigated with different experimental loading methods (pull-out velocity, normal stress), geogrid types, and soil particle size distributions and water contents. The ultimate pull-out force increases with the normal stress and pull-out velocity. Furthermore, with increasing coarse particle content and water content, the ultimate pull-out force increases and then decreases sharply. Based on these research results, this paper provides reasonable parameters and recommendations for the design and pull-out testing of reinforced soil in engineering structures. In reinforced soil structure design, the grid depth should be increased appropriately, and the coarse particle content of the overlying soil should be between 30 and 40%. During construction, the gravelly soil should be compacted to the maximum compaction at the optimal water content, and the structure should have a reasonable waterproofing system. According to the calculation results of the interface strength parameters, the uniaxial geogrid–gravelly soil interface has a high cohesive force c sg, which should not be ignored in reinforced soil structure design.

Abstract Background Antral follicles consist of an oocyte cumulus complex surrounding by somatic cells, including mural granulosa cells as the inner layer and theca cells as the outsider layer. The communications between oocytes and granulosa cells have been extensively explored in in vitro studies, however, the role of oocyte-derived factor GDF9 on in vivo antral follicle development remains elusive due to lack of an appropriate animal model. Clinically, the phenotype of GDF9 variants needs to be determined. Methods Whole-exome sequencing (WES) was performed on two unrelated infertile women characterized by an early rise of estradiol level and defect in follicle enlargement. Besides, WES data on 1,039 women undergoing ART treatment were collected. A Gdf9 Q308X/S415T mouse model was generated based on the variant found in one of the patients. Results Two probands with bi-allelic GDF9 variants (GDF9 His209GlnfsTer6/S428T , GDF9 Q321X/S428T ) and eight GDF9 S428T heterozygotes with normal ovarian response were identified. In vitro experiments confirmed that these variants caused reduction of GDF9 secretion, and/or alleviation in BMP15 binding. Gdf9 Q308X/S415T mouse model was constructed, which recapitulated the phenotypes in probands with abnormal estrogen secretion and defected follicle enlargement. Further experiments in mouse model showed an earlier expression of STAR in small antral follicles and decreased proliferative capacity in large antral follicles. In addition, RNA sequencing of granulosa cells revealed the transcriptomic profiles related to defective follicle enlargement in the Gdf9 Q308X/S415T group. One of the downregulated genes, P4HA2 (a collagen related gene), was found to be stimulated by GDF9 protein, which partly explained the phenotype of defective follicle enlargement. Conclusions GDF9 bi-allelic variants contributed to the defect in antral follicle development. Oocyte itself participated in the regulation of follicle development through GDF9 paracrine effect, highlighting the essential role of oocyte-derived factors on ovarian response.

Abstract Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1. Our conclusions are supported by cold survival experiments with human cell models and zebrafish larvae. Promoting FOXO1 nuclear entry by the Exportin-1 inhibitor KPT-330 enhances cold tolerance in pre-diabetic obese mice, and greatly prolongs the shelf-life of human and mouse pancreatic tissues and islets. Transplantation of mouse islets cold-stored for 14 days reestablishes normoglycemia in diabetic mice. Our findings uncover a regulatory network and potential therapeutic targets to boost spontaneous cold adaptation.

Abstract Background Breast cancer is the most prevalent cancer among women globally, and surgical procedures continue to be the primary treatment. However, over 50% of patients experience preoperative anxiety due to the unknown and fear associated with surgery. Although drug therapy is commonly used to address this anxiety, its side effects have led to a heated debate regarding its effectiveness. Consequently, non-pharmacological therapies, such as preoperative education, have emerged as an alternative approach to alleviate anxiety. WeChat, a widely popular social media platform, offers a public platform that can potentially be utilized for effective preoperative education. This study aims to evaluate the use of WeChat public platform as a tool for preoperative education in patients undergoing breast surgery. Methods This is a prospective, randomized, and controlled trial will involve 392 adult women scheduled for breast cancer resection. Participants will be randomly assigned to either the WeChat education group or the regular group. In addition to regular preoperative visits, the WeChat education group will also watch science videos through the WeChat public platform. The regular group will only receive education from ward nurses during preoperative visits. The primary outcome measure will be the incidence of preoperative anxiety, defined by scores of the State Anxiety Inventory (SAI) exceeding 40 points. Secondary outcome measures include the incidence of severe anxiety (SAI > 44) on the day before surgery, incidence of anxiety 72 h after surgery, incidence of severe anxiety 72 h after surgery, NRS scores for pain at rest and during activity 24, 48, and 72 h after surgery, incidence of nausea and vomiting within 24 h after surgery, subjective sleep score at 1 week postoperatively, quality of life QoR-15 scores at 1 and 3 months postoperatively, incidence of chronic pain at 3 months postoperatively, bowel function recovery, length of hospital stay, and hospitalization expenses. Discussion This is the first clinical trial to investigate the use of WeChat public platform for delivering preoperative education on perioperative anxiety in breast cancer patients. By utilizing the renowned WeChat public platform, our study aims to improve patient outcomes by providing video education that explains the disease, surgery, and anesthesia in a more accessible manner, thereby reducing the incidence of perioperative anxiety. If our hypothesis is confirmed, this non-pharmacological approach can be universally acknowledged as a cost-effective and practical method in clinical care. Its application can also be extended to other medical fields beyond breast cancer. Trial registration ClinicalTrials.gov, NCT05291494. Registered on 29 December 2021.

Adenoid cystic carcinoma (ACC) is a rare type of breast cancer, and predominant adenoid cystic carcinomas are low grade and triple-negative by histology. Unlike other triple-negative breast carcinomas, ACC of the breast generally have a low propensity for recurrence and metastasis, with complete surgical excision alone being curative in most circumstances in early-stage disease. Here, we presents a case study detailing the clinical course of a 32-year-old female patient diagnosed with ACC of the breast. We emphasized the efficacy of standardized treatment protocols and highlighted recent advancements in research pertaining to this uncommon malignancy.

3-methyl-4-nitrophenol (PNMC), a degradation product of organophosphorus insecticides and a byproduct of fuel combustion, exerting endocrine-disrupting effects. However, its impact on the meiotic process of oocytes remains unclear. In the present study, we investigated the effects of PNMC on meiotic maturation of mouse oocytes in vitro and related mechanisms. Morphologically, PNMC-exposure affected germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) in mouse oocytes. Proteomic analysis suggested that PNMC-exposure altered oocyte protein expression that are associated with cytoskeleton, mitochondrial function and oxidative stress. Further studies demonstrated that PNMC-exposure disrupted spindle assembly and chromosome alignment, caused sustained activation of spindle assembly checkpoint (SAC), and arrested meiosis in oocytes. Specifically, PNMC-exposure interfered with the function of microtubule organizing centers (MTOCs) by significantly reducing phosphorylated mitogen activated protein kinase (p-MAPK) expression and disrupting the localization of Pericentrin and p-Aurora A, leading to spindle assembly failure. Besides, PNMC-exposure also increased α-tubulin acetylation, decreased microtubule stability. Moreover, PNMC-exposure impaired mitochondrial function, evidenced by abnormal mitochondrial distribution, decreased mitochondrial membrane potential and ATP levels, release of Cytochrome C into the cytoplasm, and elevated ROS levels. As a result, exposure to PNMC caused DNA damage and early apoptosis in oocytes. Fortunately, melatonin was able to promote oocyte maturation by removing the excessive ROS and enhancing mitochondrial function. These results highlight the adverse effects of PNMC on meiotic maturation, and underscore the protective role of melatonin against PNMC-induced damage.

Photoelectrochemical (PEC) water splitting presents a promising approach for harnessing solar energy and converting it into hydrogen energy. However, the limited water oxidation activity of semiconductor photoanodes has severely hampered the overall conversion efficiency. In this study, a hollow dodecahedral structure of NiCo-LDH (HD-NiCo-LDH) was designed using the metal-organic framework ZIF-67 as a precursor. HD-NiCo-LDH was employed to modify the BiVO4 photoanode, serving as an oxygen evolution cocatalyst. HD-NiCo-LDH can enhance light absorption, accelerate photogenic hole extraction, promote photogenic charge separation and improve the kinetics of water oxidation reaction. Significantly, the unique hollow dodecahedral structure of HD-NiCo-LDH possesses a larger specific surface areas, which provides additional active sites for the water oxidation reaction and facilitates the adsorption of water molecules. The photocurrent density of the optimized HD-NiCo-LDH/BiVO4 photoanode reaches 4.54 mA/cm2 at 1.23 V vs. RHE, which is 3.3 times greater than the bare BiVO4 photoanode. This presented work introduces an innovative design concept for photoanodes supported by oxygen evolution cocatalysts with multi-active sites.

Abstract Background Temporomandibular joint osteoarthritis (TMJOA) is a degenerative cartilage disease. 17β‐estradiol (E2) aggravates the pathological process of TMJOA; however, the mechanisms of its action have not been elucidated. Thus, we investigate the influence of E2 on the cellular biological behaviors of synoviocytes and the molecular mechanisms. Methods Primary fibroblast‐like synoviocytes (FLSs) isolated from rats were treated with TNF‐α to establish cell model, and phenotypes were evaluated using cell counting kit‐8, EdU, Tanswell, enzyme‐linked immunosorbent assay, and quantitative real‐time PCR (qPCR). The underlying mechanism of E2, FTO‐mediated NLRC5 m6A methylation, was assessed using microarray, methylated RNA immunoprecipitation, qPCR, and western blot. Moreover, TMJOA‐like rat model was established by intra‐articular injection of monosodium iodoacetate (MIA), and bone morphology and pathology were assessed using micro‐CT and H&E staining. Results The results illustrated that E2 facilitated the proliferation, migration, invasion, and inflammation of TNF‐α‐treated FLSs. FTO expression was downregulated in TMJOA and was reduced by E2 in FLSs. Knockdown of FTO promoted m6A methylation of NLRC5 and enhanced NLRC5 stability by IGF2BP1 recognition. Moreover, E2 promoted TMJ pathology and condyle remodeling, and increased bone mineral density and trabecular bone volume fraction, which was rescued by NLRC5 knockdown. Conclusion E2 promoted the progression of TMJOA.

BackgroundSystemic immune-inflammation index (SII) is associated with increased risk in a wide range of illnesses. However, few studies have explored the associations between SII and the risk of malnutrition. Therefore, this study aimed to investigate the association between SII and malnutrition in a nationwide, multicenter, cross-sectional study involving Chinese hospitalized patients.DesignFrom August 2020 to August 2021, a total of 40,379 hospitalized patients met the inclusion and exclusion criteria. Detailed demographic data, diagnoses, as well as physical and laboratory examination results were recorded. The diagnosis of malnutrition was used with two distinct methods: the Malnutrition Screening Tool 2002 (NRS 2002) + Global Leaders Initiative on Malnutrition (GLIM) criteria and the controlling nutritional status (CONUT) score. The risk factors for malnutrition were analyzed using binary logistic regression and multiple logistic regression to obtain odds ratios (OR) and 95% confidence intervals (CI). Restricted cubic spline (RCS), linear spline, and receiver operating characteristic (ROC) analysis were also used.ResultsThe prevalence of malnutrition diagnosed by the two methods was 13.4% and 14.9%, respectively. In the NRS 2002 + GLIM diagnostic model, lnSII showed statistical significance between the malnutrition and non-malnutrition group (6.28 ± 0.78 vs. 6.63 ± 0.97, p

The repair of secondary critical bone defects is an international medical challenge. Bone tissue engineering provides methods and technology for bone repair. The bone regeneration mechanism serves as inspiration for the material and structural design of bone tissue engineering scaffolds. In terms of materials, this review draws inspiration from the biological characteristics of host cells in the osteogenic microenvironment (including osteoblast lineage, vascular cell lineage, inflammatory cells, etc.), reviewing the regulatory mechanisms of bone self-healing and proposing autonomous living materials scaffolds which prepared by in-situ manufacturing. Autonomous living scaffolds regulate cell migration, proliferation and differentiation in real time by releasing living cells steadily for long-term. Regarding structure, we review the functional role of natural bone structures in bone homeostasis, providing insights into the design of bone-inspired scaffolds. Due to the conflict between the mechanical properties and bone regeneration ability, this review proposes assembled scaffolds. They can prolong the half-life of living cells, provide mechanical support and attachment points for new bone growth, and autonomously regulate osteogenic microenvironment. The assembled scaffolds have potential to advance the research progress in bone tissue engineering field and pave the way for novel clinical bone repair treatments.

Background: Cuproptosis may represent a potential biomarker for predicting prognosis and immunotherapy response, but the available evidence is insufficient. Methods: The multiple single-cell RNA sequencing (scRNA-seq) datasets were analyzed to investigate the specific occurrence of cuproptosis in distinct cell populations. Utilizing 28 scRNA-seq datasets, TCGA pan-cancer cohort, and 10 immunotherapy cohorts, we developed a cuproptosis signature (Cup.Sig). This signature was used to construct prediction models for immunotherapy response and identify potential prognostic biomarkers for pan-cancer using 11 different machine learning algorithms. Results: Malignant cells demonstrate the higher cuproptosis scores in comparison to other cell types across diverse cancer types. The Cup.Sig exhibits significant associations with cancer hallmarks and immune cell response in multiple cancer types. Leveraging the Cup.Sig, the robust pan-cancer immunotherapy prediction model and prognostic biomarker have been established and validated using diverse datasets from various platforms. Conclusions: We developed a pan-cancer cuproptosis signature for predicting survival and immunotherapy response.

IntroductionGrape is of high economic value. Colletotrichum viniferum, a pathogen causing grape ripe rot and leaf spot, threatens grape production and quality.MethodsThis study investigates the interplay between C. viniferum by Cytological study and transcriptome sequencing.ResultsDifferent grapevine germplasms, V. vinifera cv. Thompson Seedless (TS), V. labrusca accession Beaumont (B) and V. piasezkii Liuba-8 (LB-8) were classified as highly sensitive, moderate resistant and resistant to C. viniferum, respectively. Cytological study analysis reveals distinct differences between susceptible and resistant grapes post-inoculation, including faster pathogen development, longer germination tubes, normal appressoria of C. viniferum and absence of white secretions in the susceptible host grapevine. To understand the pathogenic mechanisms of C. viniferum, transcriptome sequencing was performed on the susceptible grapevine “TS” identifying 236 differentially expressed C. viniferum genes. These included 56 effectors, 36 carbohydrate genes, 5 P450 genes, and 10 genes involved in secondary metabolism. Fungal effectors are known as pivotal pathogenic factors that modulate plant immunity and affect disease development. Agrobacterium-mediated transient transformation in Nicotiana benthamiana screened 10 effectors (CvA13877, CvA01508, CvA05621, CvA00229, CvA07043, CvA05569, CvA12648, CvA02698, CvA14071 and CvA10999) that inhibited INF1 (infestans 1, P. infestans PAMP elicitor) induced cell death and 2 effectors (CvA02641 and CvA11478) that induced cell death. Additionally, transcriptome analysis of “TS” in response to C. viniferum identified differentially expressed grape genes related to plant hormone signaling (TGA, PR1, ETR, and ERF1/2), resveratrol biosynthesis genes (STS), phenylpropanoid biosynthesis genes (PAL and COMT), photosynthetic antenna proteins (Lhca and Lhcb), transcription factors (WRKY, NAC, MYB, ERF, GATA, bHLH and SBP), ROS (reactive oxygen species) clearance genes (CAT, GSH, POD and SOD), and disease-related genes (LRR, RPS2 and GST).DiscussionThis study highlights the potential functional diversity of C. viniferum effectors. Our findings lay a foundation for further research of infection mechanisms in Colletotrichum and identification of disease response targets in grape.

IntroductionAcute kidney injury (AKI) is a prevalent complication in older people, elevating the risks of acute kidney disease (AKD) and mortality. AKD reflects the adverse events developing after AKI. We aimed to develop and validate machine learning models for predicting the occurrence of AKD, AKI and mortality in older patients.MethodsWe retrospectively reviewed the medical records of older patients (aged 65 years and above). To explore the trajectory of kidney dysfunction, patients were categorized into four groups: no kidney disease, AKI recovery, AKD without AKI, or AKD with AKI. We developed eight machine learning models to predict AKD, AKI, and mortality. The best-performing model was identified based on the area under the receiver operating characteristic curve (AUC) and interpreted using the Shapley additive explanations (SHAP) method.ResultsA total of 22,005 patients were finally included in our study. Among them, 4,434 patients (20.15%) developed AKD, 4,000 (18.18%) occurred AKI, and 866 (3.94%) patients deceased. Light gradient boosting machine (LGBM) outperformed in predicting AKD, AKI, and mortality, and the final lite models with 15 features had AUC values of 0.760, 0.767, and 0.927, respectively. The SHAP method revealed that AKI stage, albumin, lactate dehydrogenase, aspirin and coronary heart disease were the top 5 predictors of AKD. An online prediction website for AKD and mortality was developed based on the final models.DiscussionThe LGBM models provide a valuable tool for early prediction of AKD, AKI, and mortality in older patients, facilitating timely interventions. This study highlights the potential of machine learning in improving older adult care, with the developed online tool offering practical utility for healthcare professionals. Further research should aim at external validation and integration of these models into clinical practice.

BackgroundThe interaction between the intestinal flora and gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remains poorly understood, despite the known effect of the gut microbiota on gastrointestinal adenocarcinomas. Hence, the present research aimed to determine the potential causal correlation between the intestinal flora and GEP-NENs by conducting a bidirectional Mendelian randomization (MR) analysis.MethodsTwo-sample MR analysis was conducted using the summary statistics of the gut microbiota from the MiBioGen consortium and those of GEP-NENs from the FinnGen research project. The inverse-variance weighted approach was utilized as the primary analytical method. To enhance the robustness of our findings, multiple sensitivity tests were performed, including Cochran’s Q test for evaluating heterogeneity, the MR-Egger intercept test to detect horizontal pleiotropy, and the MR-PRESSO test to identify outliers and assess pleiotropy bias. Additionally, a leave-one-out analysis was performed to validate the consistency of our findings. The MR-Steiger test was also utilized to determine the causal direction in the correlation between the gut microbiota and GEP-NENs. Finally, a reverse MR analysis was performed to assess reverse causality between the intestinal flora and GEP-NENs.ResultsWe identified 42 taxa of the gut microbiota that were potentially causally associated with GEP-NENs; of these taxa, 7, 8, 11, and 16 taxa were causally associated with pancreatic NENs, colorectal NENs, small intestinal NENs, and gastric NENs, respectively. After adjusting for false discovery rate (FDR) correction, we found significant causal links of Euryarchaeota with small intestinal NENs and Family XIII UCG-001 with gastric NENs. The sensitivity analyses confirmed the stability of these correlations. In the reverse MR analysis, colorectal NENs and small intestinal NENs were found to be associated with variations in 8 and 6 different taxa of the gut microbiota, respectively. After adjusting for FDR correction, no significant causal links were detected between GEP-NENs and the intestinal flora.ConclusionThe present study reveals a potential causal association between certain taxa of the intestinal flora and GEP-NENs, thus providing new perspectives regarding the role of the intestinal flora in the development of these tumors. These insights could provide innovative approaches to screen and prevent these diseases.

Background: The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been supported by various clinical studies. However, stem cell transplantation is limited in clinical application due to its low survival rate, low liver implantation rate, and possible carcinogenicity. Recently, there has been increasing interest in the use of MSC-exos due to their widespread availability, low immunogenicity, and non-carcinogenic properties. Numerous studies have demonstrated the potential of MSC-exos in treating liver fibrosis and preventing progression to end-stage liver disease.Objective: This study aimed to systematically investigate the efficacy of MSC-exos single administration in the treatment of hepatic fibrosis and the combined advantages of MSC-exos in combination with drug therapy (MSC-exos-drugs).Methods: Data sources included PubMed, Web of Science, Embase, and the Cochrane Library, which were built up to January 2024. The population, intervention, comparison, outcomes, and study design (PICOS) principle was used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Finally, the data from each study’s outcome indicators were extracted for a combined analysis.Results: After screening, a total of 18 papers (19 studies) were included, of which 12 involved MSC-exos single administration for the treatment of liver fibrosis and 6 involved MSC-exos-drugs for the treatment of liver fibrosis. Pooled analysis revealed that MSC-exos significantly improved liver function, promoted the repair of damaged liver tissue, and slowed the progression of hepatic fibrosis and that MSC-exos-drugs were more efficacious than MSC-exos single administration. Subgroup analyses revealed that the use of AD-MSC-exos resulted in more consistent and significant efficacy when MSC-exos was used to treat hepatic fibrosis. For MSC-exos-drugs, a more stable end result is obtained by kit extraction. Similarly, infusion through the abdominal cavity is more effective.Conclusion: The results suggest that MSC-exos can effectively treat liver fibrosis and that MSC-exos-drugs are more effective than MSC-exos single administration. Although the results of the subgroup analyses provide recommendations for clinical treatment, a large number of high-quality experimental validations are still needed.Systematic Review Registration: CRD42024516199.

Chorea-acanthocytosis (ChAc) is a rare, neurodegenerative disorder caused by mutations in the VPS13A gene. In this article, we report on a 32-year-old man diagnosed with ChAc, with involuntary movements of the mouth and trunk, drooling of the mouth, slurred speech, and abnormal vocalizations as the main clinical manifestations. Three weeks after implantation of globus pallidus internal (GPi)-deep brain stimulation (DBS), the patient’s symptoms improved significantly. For example, articulation is clear, involuntary trunk movements and salivation have largely disappeared, and abnormal vocalizations have been significantly reduced. After 1 year of follow-up, the improvement in involuntary movement symptoms is essentially the same as before. As far as we know, we are the first to report the relief of involuntary vocalizations in a patient with GPi-DBS treatment, and that salivation and involuntary trunk movements have almost disappeared, and all other symptoms are significantly relieved, which is rare in previous cases. All of the above proves that the treatment of our case with DBS was very successful and that longer term follow-up is critical. We also hope that our case will provide new references and therapeutic ideas for the future treatment of patients with ChAc.