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Background: To determine the mechanism by which the flavonoid glycoside astragalin (AST) reduces ovarian failure in an aged rat model of menopause. Methods: The in vivo effect of AST on granulosa cell (GC) apoptosis in aged female rats was determined using flow cytometry. In vitro, the effects of AST on cultured GCs were investigated using the MTT proliferation assay and western blot assays. Results: Aged rats had significantly higher GC apoptosis as compared with young female rats. Treatment of aged rats with AST (all three doses; p < 0.01) or Progynova (p < 0.01) significantly reduced GC apoptosis as compared with the aged controls. The proportions of total apoptotic GCs was 25.70%, 86.65%, 47.04%, 27.02%, 42.09% and 56.42% in the normal, aged, 17β-estradiol (E2), high dose AST, medium dose AST, and low dose AST-treated groups, respectively. Significant increases of serum E2 and P4 levels, as well as altered levels of serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. In cultured rat GCs, AST stimulated GC proliferation, E2 and progesterone (P4) secretion, reduced apoptosis, reduced the level of the pro-apoptotic protein Bcl-2 (p < 0.01), but had no effect on BAX. Conclusions: AST enhanced ovarian function in aged female rats by increasing E2 and P4 levels, and reducing ovarian GC apoptosis via a mechanism involving Bcl-2. These data demonstrate a new pharmacological activity for AST, as well as a novel mechanism of action, and further suggest that AST may be a new therapeutic agent for the management of menopausal symptoms.

Free-electron lasers (FELs) are fourth-generation light sources that deliver extremely high intensity, ultrashort light pulses over a broad wavelength range from far-infrared to hard x ray. FELs based on the self-amplified spontaneous emission principle have been successfully operated with ultrahigh brightness and a broad wavelengths tuning range with good transverse coherence but poor temporal coherence. In contrast, the laser-seeded FELs have provided full coherence but at selected central wavelengths, usually the harmonics of the laser seeds, with relatively narrower tuning range. We report the experimental demonstration of a high-gain harmonic-generation (HGHG) FEL that is continuously tunable over a wide range using the combination of optical parametrical amplification, variable-gap undulator, and harmonic selection, where the temporal coherence is preserved as confirmed with the Michelson interferometry. In order to achieve higher photon energies, the first try of cascaded HGHG with a fresh-bunch technique is also made at the Shanghai Deep Ultraviolet Free-electron Laser test facility.

YpsR, a pivotal regulatory protein in the quorum-sensing (QS) of Yersinia pseudotuberculosis(Y. pstb), is essential for molecular signaling, yet its molecular mechanisms remain poorly understood. Herein, this study systematically investigates the interactions between YpsR and acyl-homoserine lactones (AHLs), shedding light on the selective mechanism of YpsR to various AHL molecules. Using molecular docking and surface plasmon resonance (SPR) analysis, we confirmed YpsR's binding affinities, with the strongest observed for 3OC6-HSL, which notably inhibited Y. pstb growth. Additionally, we engineered a whole-cell biosensor based on YpsR-AHL interaction, which exhibited sensitivity to the signal molecule 3OC6-HSL produced by Y. pstb. Furthermore, key YpsR residues (S32, Y50, W54, D67) involved in AHL binding were identified and validated. Overall, this research elucidates the mechanisms of QS signal recognition in Y. pstb, providing valuable insights that support the development of diagnostic tools for detecting Y. pstb infections.

Abstract Background In recent years, there have been many instances of negative sentiments expressed by and resignations observed from doctors working in the Ministry of Health (MOH), Malaysia. However, little is known about the perspectives of medical students and their career intentions. This study aims to determine the current Malaysian medical students’ career intentions immediately after graduation and upon completing the 2 years of housemanship and to establish the factors influencing these intentions. Methods This was a cross-sectional study of 859 Malaysian medical students from 21 medical schools who voluntarily completed a self-administered online questionnaire that was disseminated by representatives from medical schools nationwide and social media platforms of a national medical student society. Results 37.8% of the respondents were optimistic about a career with the Ministry of Health (MOH), Malaysia in the future. Most of the respondents (91.2%) plan to join and complete the MOH Housemanship programme as soon as possible after graduation, with the majority of them (66.2%) planning to complete it in their state of origin. After 2 years of Housemanship programme, only more than half of the respondents (63.1%) plan to continue their careers in MOH. Slightly more than a quarter (27.1%) of the total respondents plan to emigrate to practise medicine, with 80.7% of them planning to return to Malaysia to practise medicine after some years or after completing specialisation training. Combining the career intentions of Malaysian medical students immediately after graduation and upon completion of the 2 years housemanship programme, only a slight majority (57.5%) of the respondents plan to continue their career in MOH eventually. Most of the respondents (85.0%) intend to specialise. Conclusion A concerning number of Malaysian medical students plan to leave the Ministry of Health workforce, the main healthcare provider in Malaysia, in the future. Urgent government interventions are needed to address the underlying factors contributing to the potential exodus of future doctors to prevent further straining of the already overburdened healthcare system, posing a significant threat to public well-being. An annual national study to track medical students’ career intentions is recommended to gather crucial data for the human resources for health planning in Malaysia.

Abstract Background Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive degeneration of articular cartilage, leading to pain, stiffness, and loss of joint function. The pathogenesis of OA involves multiple factors, including increased intracellular reactive oxygen species (ROS), enhanced chondrocyte apoptosis, and disturbances in cartilage matrix metabolism. These processes contribute to the breakdown of the extracellular matrix (ECM) and the loss of cartilage integrity, ultimately resulting in joint damage and dysfunction. RNA interference (RNAi) therapy has emerged as a promising approach for the treatment of various diseases, including hATTR and acute hepatic porphyria. By harnessing the natural cellular machinery for gene silencing, RNAi allows for the specific inhibition of target genes involved in disease pathogenesis. In the context of OA, targeting key molecules such as matrix metalloproteinase-13 (MMP13), which plays a critical role in cartilage degradation, holds great therapeutic potential. Results In this study, we developed an innovative therapeutic approach for OA using a combination of liposome-encapsulated siMMP13 and NG-Monomethyl-L-arginine Acetate (L-NMMA) to form an injectable hydrogel. The hydrogel served as a delivery vehicle for the siMMP13, allowing for sustained release and targeted delivery to the affected joint. Experiments conducted on destabilization of the medial meniscus (DMM) model mice demonstrated the therapeutic efficacy of this composite hydrogel. Treatment with the hydrogel significantly inhibited the degradation of cartilage matrix, as evidenced by histological analysis showing preserved cartilage structure and reduced loss of proteoglycans. Moreover, the hydrogel effectively suppressed intracellular ROS accumulation in chondrocytes, indicating its anti-oxidative properties. Furthermore, it attenuated chondrocyte apoptosis, as demonstrated by decreased levels of apoptotic markers. Conclusion In summary, the injectable hydrogel containing siMMP13, endowed with anti-ROS and anti-apoptotic properties, may represent an effective therapeutic strategy for osteoarthritis in the future.

Abstract Wireless sensing of the wave propagation direction from radio sources lays the foundation for communication, radar, navigation, etc. However, the existing signal processing paradigm for the direction of arrival estimation requires the radio frequency electronic circuit to demodulate and sample the multichannel baseband signals followed by a complicated computing process, which places the fundamental limit on its sensing speed and energy efficiency. Here, we propose the super-resolution diffractive neural networks (S-DNN) to process electromagnetic (EM) waves directly for the DOA estimation at the speed of light. The multilayer meta-structures of S-DNN generate super-oscillatory angular responses in local angular regions that can perform the all-optical DOA estimation with angular resolutions beyond the diffraction limit. The spatial-temporal multiplexing of passive and reconfigurable S-DNNs is utilized to achieve high-resolution DOA estimation over a wide field of view. The S-DNN is validated for the DOA estimation of multiple radio sources over 5 GHz frequency bandwidth with estimation latency over two to four orders of magnitude lower than the state-of-the-art commercial devices in principle. The results achieve the angular resolution over an order of magnitude, experimentally demonstrated with four times, higher than diffraction-limited resolution. We also apply S-DNN’s edge computing capability, assisted by reconfigurable intelligent surfaces, for extremely low-latency integrated sensing and communication with low power consumption. Our work is a significant step towards utilizing photonic computing processors to facilitate various wireless sensing and communication tasks with advantages in both computing paradigms and performance over electronic computing.

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and the expression and function of an uncharacterized protein RNF214 in HCC are still unknown. Phase separation has recently been observed to participate in the progression of HCC. In this study, we investigated the expression, function, and phase separation of RNF214 in HCC. We found that RNF214 was highly expressed in HCC and associated with poor prognosis. RNF214 functioned as an oncogene to promote the proliferation, migration, and metastasis of HCC. Mechanically, RNF214 underwent phase separation, and the coiled-coil (CC) domain of RNF214 mediated its phase separation. Furthermore, the CC domain was necessary for the oncogenic function of RNF214 in HCC. Taken together, our data favored that phase separation of RNF214 promoted the progression of HCC. RNF214 may be a potential biomarker and therapeutic target for HCC.

Abdominal aortic aneurysm (AAA) is a life-threatening condition, but effective medications to prevent its progression and rupture are currently lacking. The nuclear receptor pregnane-X-receptor (PXR) plays a crucial role in vascular homeostasis. However, the role of PXR in AAA development remains unknown. We first detected the PXR expression in human and murine AAA tissues by RT-qPCR and Western blot. To investigate the potential role of PXR in the development of AAA, we used adeno-associated virus-mediated overexpression of PXR and pharmacological activation of PXR by ginkgolide A (GA) in mouse AAA models induced by both angiotensin II (AngII) and calcium phosphate [Ca3(PO4)2]. The underlying mechanism was further explored using RNA-sequencing and molecular biological analyses. We found a significant decrease in both mRNA and protein levels of PXR in both human and murine aortic smooth muscle cells from AAA tissues, accompanied with phenotypic switching of vascular smooth muscle cell and increased oxidative stress. PXR overexpression in abdominal aortas and GA treatment successfully suppressed AAA formation in both mouse AAA models. RNA-sequencing data revealed that PXR activation inhibited gamma-aminobutyric acid type A receptor subunit alpha3 (GABRA3) expression. Additional mechanistic studies identified that PXR suppressed AAA through mitigating GABRA3-induced reactive oxygen species (ROS) generation and subsequent phosphorylation of c-Jun N-terminal kinase (JNK). Interestingly, p-JNK was found to induce ubiquitin-proteasome degradation of PXR. In summary, our data unveiled, for the first time, the protective role of PXR against AAA pathogenesis by inhibiting oxidative stress. These findings suggested PXR as a promising therapeutic target for AAA.

Early-onset epilepsy following ischemic stroke is a severe neurological condition, the pathogenesis of which remains incompletely understood. Recent studies suggest that Neural stem/progenitor cells (NSPCs) play a crucial role in the disease process, yet the precise molecular mechanisms regulating NSPCs have not been thoroughly investigated. This study utilized single-cell transcriptome sequencing and bioinformatics analysis to identify disease-related genes, which were subsequently validated in both in vitro and in vivo experiments. The findings revealed that Hsp90aa1 (heat shock protein 90 kDa alpha, class A member 1), Jun proto-oncogene (JUN), and CC Motif Ligation 2 (Ccl2) constitute an important regulatory axis influencing the migration and differentiation of NSPCs, potentially impacting the onset and progression of early-onset epilepsy post-ischemic stroke. Additionally, the expression of Hsp90aa1 was found to influence the likelihood of seizure occurrence and the severity of brain ischemia.

A rapid, simple, effective, and green method for the determination of betaine and trigonelline from Lycium chinense Mill. (LCM) and the quantification of the trigonelline in coffee was proposed and validated by matrix-assisted laser desorption ionization time-of-flight mass spectrometric (MALDI-TOF MS) detection. Due to without chromatographic separation, the method greatly shortened the detection time. The detection of betaine and trigonelline concentration showed good linearity in the range of 1–100 μg/mL and 0.01–100 μg/mL, with correlation coefficients r2 = 0.9962 and 0.9946, respectively. The good reproducibility and reliability of the method were demonstrated by excellent intraday and interday precisions with RSD

PurposeStatins may have a protective effect against osteoarthritis (including knee osteoarthritis and hip osteoarthritis); however, the link between statins and osteoarthritis risk is incompletely established. The aim of this study was to explore the relationship between statins and osteoarthritis risk through Mendelian randomization analysis using pooled information from a large population-wide genome-wide association study (GWAS).MethodsStatin-related single-nucleotide polymorphisms (SNPs) were obtained from FinnGen’s latest 9th edition database, and data on osteoarthritis, knee osteoarthritis, and hip osteoarthritis were acquired from the IEU OpenGWAS, the UK Biobank, and Arthritis Research UK Osteoarthritis Genetics (ArcOGEN) database, respectively. The inverse-variance weighting method is an important analysis method to estimate the causal effect. Weighted median method, simple median method, weighted median estimator method, and MR–Egger regression were employed to supplement the explanation. Odds ratio and 95%CI were used to evaluate the causal relationship among statins and the osteoarthritis risk, osteoarthritis in the knee, and osteoarthritis in the hip. Second, sensitivity analysis was carried out to validate the reliability of the results. Cochran’s Q test was employed to test heterogeneity, MR–Egger intercept was employed to test whether horizontal pleiotropy existed, and single-nucleotide polymorphisms with potential influence were determined by the one-method analysis.Results(1) The results of the inverse variance weighting method showed Gene prediction indicated that statins were associated with osteoarthritis (OR = 0.998, 95% CI: 0.996–0.999, P = 0.01) and knee osteoarthritis (OR = 0.964, 95% CI: knee (0.940–0.989, P = 0.005) and hip osteoarthritis risk were associated (OR = 0.928, 95% CI: 0.901–0.955, P = 4.28 × 10−7). (2) MR–Egger intercept analysis did not detect potential horizontal pleiotropy (osteoarthritis: P = 0.658; knee osteoarthritis: P = 0.600; and hip osteoarthritis: P = 0.141). (3) The findings provide evidence that statins reduce osteoarthritis risk, osteoarthritis in the knee, and osteoarthritis in the hip, as described in observational studies, and the specific mechanisms by which statins treat osteoarthritis require further investigation.ConclusionThe results of this study, at the genetic level, reveal a negative causal relationship between statins and osteoarthritis, and this causal relationship is also present in knee and hip osteoarthritis. This study provides evidence against the potential of statins in the treatment of osteoarthritis, prompting the clinical treatment of osteoarthritis to consider improving the start and compliance of statins in the future.

Cancer immunotherapy, exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy, is revolutionizing cancer therapy. They induce long-term tumor regression and overall survival benefit in many types of cancer. With the advances in our knowledge about the tumor immune microenvironment, remarkable progress has been made in the development of small-molecule drugs for immunotherapy. Small molecules targeting PRR-associated pathways, immune checkpoints, oncogenic signaling, metabolic pathways, cytokine/chemokine signaling, and immune-related kinases have been extensively investigated. Monotherapy of small-molecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor resistance. Here, we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

Background Prescribing errors (PEs) cause significant avoidable harm globally. In Malaysia, despite the prevalence of PEs in government healthcare facilities, there is limited research on how pharmacist staffing levels influence intervention frequency and effectiveness. This study aims to address this gap by analysing intervention trends and assessing their association with staffing levels, highlighting the correlation between increased pharmacist presence and the frequency of interventions.Methods This retrospective cross-sectional study analysed data from the Ministry of Health's Pharmacy Management Form and the Pharmacy Board Registry from 2017 to 2019. Multivariate regression and two-way ANOVA assessed the association between the number of pharmacists, total prescriptions, and interventions on PEs in Health Clinic Outpatient Pharmacy, Hospital Outpatient Pharmacy, and Hospital Inpatient Pharmacy settings.Results Annually, pharmacists intervened in approximately 1.8% of total prescriptions, with the most common errors being wrong dose, wrong medication, and wrong dosing frequency. These interventions were consistent across all settings, highlighting the uniformity in pharmacists’ approach to managing PEs. The regression analysis revealed a significant positive correlation between the number of pharmacists, total prescriptions, and interventions on PEs, with an adjusted R-squared value of 0.899. Both the number of pharmacists and total prescriptions received were positively significant (p

Scandium aluminum nitride (ScAlN) has recently emerged as an attractive material for integrated photonics due to its favorable nonlinear optical properties and compatibility with complementary metal–oxide semiconductor (CMOS) fabrication. Despite the promising and versatile material properties, it is still an outstanding challenge to realize low-loss photonic circuits on thin-film ScAlN-on-insulator wafers. Here, we present a systematic study on the material quality of sputtered thin-film Sc0.1Al0.9N produced in a CMOS-compatible 200 mm line, including its crystallinity, roughness, and second-order optical nonlinearity, and developed an optimized fabrication process to yield 400 nm thick, fully etched waveguides. With surface polishing and annealing, we achieve micro-ring resonators with an intrinsic quality factor as high as 1.47 × 105, corresponding to a propagation loss of 2.4 dB/cm. These results serve as a critical step toward developing future large-scale, low-loss photonic integrated circuits based on ScAlN.

Polymer network is a crucial component of hydrogels, and network imperfection is a prominent feature of polymer networks, significantly influencing the performance of hydrogels. Two essential features of network imperfection are unequal chain lengths and dangling chains, both of which have a significant impact on the mechanical properties of single-network (SN) hydrogels. However, a theoretical framework considering network imperfection in SN hydrogels is still lacking. Here, we propose a theoretical model for SN hydrogels with network imperfection to study the damage behavior during deformation, in which we adopt different chain length distributions to accurately depict the real physical characteristics of the polymer network and incorporate the normalized critical chain force for a more precise measurement of network damage. To verify our theory, we discuss the effects of model parameters on the stress-stretch responses of SN hydrogels and predict the results of uniaxial loading-unloading tests of SN hydrogels, which agree well with experimentally measured stress-stretch behaviors. Finally, we implement the constitutive model into ABAQUS as a user subroutine to study the inhomogeneous deformation of hydrogels.

Summary: Resistance to chemotherapies such as temozolomide is a major hurdle to effectively treat therapy-resistant glioblastoma. This challenge arises from the activation of phosphatidylinositol 3-kinase (PI3K), which makes it an appealing therapeutic target. However, non-selectively blocking PI3K kinases PI3Kα/β/δ/γ has yielded undesired clinical outcomes. It is, therefore, imperative to investigate individual kinases in glioblastoma’s chemosensitivity. Here, we report that PI3K kinases were unequally expressed in glioblastoma, with levels of PI3Kβ being the highest. Patients deficient of O6-methylguanine-DNA-methyltransferase (MGMT) and expressing elevated levels of PI3Kβ, defined as MGMT-deficient/PI3Kβ-high, were less responsive to temozolomide and experienced poor prognosis. Consistently, MGMT-deficient/PI3Kβ-high glioblastoma cells were resistant to temozolomide. Perturbation of PI3Kβ, but not other kinases, sensitized MGMT-deficient/PI3Kβ-high glioblastoma cells or tumors to temozolomide. Moreover, PI3Kβ-selective inhibitors and temozolomide synergistically mitigated the growth of glioblastoma stem cells. Our results have demonstrated an essential role of PI3Kβ in chemoresistance, making PI3Kβ-selective blockade an effective chemosensitizer for glioblastoma.

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

Mobile phones are central to modern communication, yet for individuals with tremors, the precision required for touch-based interfaces is a significant hurdle. In pursuit of social equality and to empower those with tremors to interact more effectively with mobile technology, this study introduces an optical see-through Augmented Reality (AR) system equipped with a stabilized filter. This system is specially designed to assist individuals with tremors by stabilizing and translating shaky movements into precise virtual commands, allowing users with hand tremor to perform interactions with mobile more effectively and accurately. The first experiment assessed the stabilized filter’s effectiveness using a one-way Analysis of Variance (ANOVA), comparing task completion times with and without the filter. The results showed a statistically significant improvement in operation times with the filter. Subjective evaluations from participants further corroborated these findings, with users reporting a notably better interaction experience when the filter was applied. Feedback highlighted the filter’s stabilization capabilities and its facilitation of smoother interactions, leading to increased user satisfaction and comfort. The second phase of our research involved a comparative analysis, investigating the interactions of individuals with and without simulated tremors using two distinct interfaces within various environments. The experiment was structured around a matrix of conditions comprising two system types (Mobile and AR), two interface designs (Traditional and our Redesigned Interface), and two user states (Non-simulated and Tremor-simulated). Performance metrics focused on task completion times and user feedback via questionnaires revealed that the AR environment was deemed more conducive to operation by those with simulated tremors, due to improved accessibility and interaction quality. In conclusion, this research confirms that the AR system with the stabilized filter represents a meaningful advancement in assistive technologies for tremor patients. The positive response from the tremor community signals the AR system’s promise in fostering greater technological inclusivity and independence for individuals with motor impairment.

Abstract Introduction ‘Let’s Talk About Children’ is a brief family focused intervention developed to improve mental health outcomes of children of parents with mental illness (COPMI). This study aims to assess the efficacy of LTC in improving mental health of children of parents with schizophrenia or bipolar disorder in China. Methods The planned study is a multicentre parallel group randomized wait-list controlled trial. A total of 400 eligible families with children aged 8 to 18 years will be recruited, 200 each for families with parental schizophrenia or bipolar disorder. The intervention group will receive Let’s Talk About Children delivered by a trained therapist, while the control group will receive treatment as usual. The primary outcomes are child mental health measured by the strengths and difficulties questionnaire and parent–child communication measured using the parent-adolescent communication scale. Parental mental health and family functioning are secondary outcomes. This study also plans to explore mediating factors for the effect of Let’s Talk About Children on child mental health, as well as conduct a cost-effectiveness analysis on using Let’s Talk About Children in China. Conclusion The present study will provide evidence for the efficacy of Let’s Talk About Children in families with parental schizophrenia and bipolar disorder in China. In addition, it will evaluate potential mechanisms of action and cost-effectiveness of Let’s Talk About Children, providing a basis for future implementation. Trial registration ChiCTR2300073904.

Abstract Background Although cervical intervertebral disc (IVD) degeneration is closely associated with neck pain, its cause remains unclear. In this study, an animal model of cervical disc degeneration and discogenic neck pain induced by a low concentration of Propionibacterium acnes (P. acnes-L) is investigated to explore the possible mechanisms of cervical discogenic pain. Methods Cervical IVD degeneration and discitis was induced in 8-week-old male rats in C3–C6 IVDs through the anterior intervertebral puncture with intradiscal injections of low and high concentrations of P. acnes (P. acnes-L, n = 20 and P. acnes-H, n = 15) or Staphylococcus aureus (S. aureus, n = 15), compared to control (injection with PBS, n = 20). The structural changes in the cervical IVD using micro-CT, histological evaluation, and gene expression assays after MRI scans at 2 and 6 weeks post-modeling. The P. acnes-L induced IVD degeneration model was assessed for cervical spine MRI, histological degeneration, pain-like behaviors (guarding behavior and forepaw von Frey), nerve fiber growth in the IVD endplate region, and DRG TNF-α and CGRP. Results IVD injection with P. acnes-L induced IVD degeneration with decreased IVD height and MRI T2 values. IVD injection with P. acnes-H and S. aureus both lead to discitis-like changes on T2-weighted MRI, trabecular bone remodeling on micro-CT, and osseous fusion after damage in the cartilage endplate adjacent to the injected IVD. Eventually, rats in the P. acnes-L group exhibited significant nociceptive hypersensitivity, nerve fiber ingrowth was observed in the IVD endplate region, inflammatory activity in the DRG was significantly increased compared to the control group, and the expression of the pain neurotransmitter CGRP was significantly upregulated. Conclusion P. acnes-L was validated to induce cervical IVD degeneration and discogenic pain phenotype, while P. acnes-H induced was identified to resemble septic discitis comparable to those caused by S. aureus infection.

Developing low density and efficient dielectric loss materials has become a research hotspot, which can greatly meet the demands of modern radars and settle the problem of electromagnetic wave pollution. Herein, a series of N-doped ordered mesoporous carbon (OMC) materials with different nitrogen content were prepared via a modified self-assembly method and defect engineering in subsequent calcination treatment. It was discovered that the content and type of nitrogen doping can be effectively modulated by the amount of precursor dicyandiamide, resulting in the changes in porous structure, carbon defects, electromagnetic properties, microwave absorption (MA) performance and radar cross section (RCS) reduction values. Remarkably, as-fabricated OMC/N2.5 displays ideal MA performance, whose minimum reflection loss (RL(min)) value reaches −35.3 dB at 7.76 GHz (3.0 mm) and its effective absorption bandwidth reaches 3.52 GHz (10.64–14.16 GHz, 2.0 mm). Furthermore, the optimal RCS reduction values can be obtained as 12.01 dB·m2 when the detection theta is 30°, which validly reduces the chances of being detected by radar. Thus, this work opens up a novel way for the development of lightweight and high-efficiency MA materials.

AbstractThe authors carried out 1.5 T MRI examination without removing the CI magnet in two children with a cochlear implant (CI). In the first child, a conventional MRI scanning technique was used, which produced an image that was not clinically useful due to artifact size. He/she was scanned again using the ‘propeller technique’. This scan had a reduced artifact and was clinically useful. The second child was scanned using the propeller technique while asleep. The image was clinically useful. The authors conclude that the propeller technique is safe and of benefit to clinical diagnosis because it enables clinically useful images to be generated in a 1.5 T MRI without necessitating CI magnet removal and reimplantation surgeries.

To better construct an energy consumption model for the asphalt mixture production stage, this study divides the production process into four phases: aggregate dust removal, aggregate drying, asphalt heating, and mixture blending. Utilizing measured data from various regions in Anhui Province, the model considers factors such as season, mixture type, and energy consumption type. The study quantitatively compares and analyzes the energy consumption results obtained from three calculation methods: the theoretical method, the quota method, and the energy consumption model method. The results indicate that the total energy consumption shares of the aggregate dust removal, aggregate drying, asphalt heating, and mixture blending phases are 4.23%, 69.50%, 17.75%, and 8.52%, respectively. The primary energy consumption during the asphalt mixture production stage is concentrated in the aggregate drying and asphalt heating phases. The energy consumption model based on on-site measurements effectively reflects the actual energy consumption levels during the asphalt mixture production stage. Moreover, the total energy consumption calculated by the three methods follows the order quota method > energy consumption model method > theoretical method. By constructing an energy consumption model based on measured data, it is possible to more accurately assess the energy usage during the asphalt mixture production process. This helps optimize production techniques, reduce energy consumption and carbon emissions, and provide a scientific basis for sustainable road construction.

The theory of social-ecological systems (SESs) provides an ideal tool for understanding complex human-nature systems in protected areas. We adopt Ostrom’s SESs framework to analyze the complex interactions within Qilian Mountain National Park (QMNP), an essential ecological security barrier in China. Through qualitative and quantitative analyses of action situations, we identify the interactions among the resource system, resource units, governance system, and actors. The results show that applying the SESF in protected areas is feasible and operable; the development level of ecosystems in QMNP is better than that of the social systems; and the coupling coordination among the four subsystems is at primary coordination (0.6–0.7), indicating that the interaction between four subsystems needs to be strengthened. Moreover, the comprehensive evaluation index and the interactions between subsystems differ among townships, indicating the necessity for tailored management strategies. We emphasize integrating social components into protected areas management to achieve sustainable development and resilience in SESs.

In order to further enhance the erosion resistance of cement concrete pavement materials, this study constructed an apparent rough hydrophobic structure layer by spraying a micro-nano substrate coating on the surface layer of the cement concrete pavement. This was followed by a secondary spray of a hydroxy-silicone oil-modified epoxy resin and a low surface energy-modified substance paste, which combine to form a superhydrophobic coating. The hydrophobic mechanism of the coating was then analysed. Firstly, the effects of different types and ratios of micro-nano substrates on the apparent morphology and hydrophobic performance of the rough structure layer were explored through contact angle testing and scanning electron microscopy (SEM). Subsequently, Fourier transform infrared spectroscopy and permeation gel chromatography were employed to ascertain the optimal modification ratio, temperature, and reaction mechanism of hydroxy-silicone oil with E51 type epoxy resin. Additionally, the mechanical properties of the modified epoxy resin-low surface energy-modified substance paste were evaluated through tensile tests. Finally, the erosion resistance of the superhydrophobic coating was tested under a range of conditions, including acidic, alkaline, de-icer, UV ageing, freeze-thaw cycles and wet wheel wear. The results demonstrate that relying solely on the rough structure of the concrete surface makes it challenging to achieve superhydrophobic performance. A rough structure layer constructed with diamond micropowder and hydrophobic nano-silica is less prone to cracking and can form more “air chamber” structures on the surface, with better wear resistance and hydrophobic performance. The ring-opening reaction products that occur during the preparation of modified epoxy resin will severely affect its mechanical strength after curing. Controlling the reaction temperature and reactant ratio can effectively push the modification reaction of epoxy resin through dehydration condensation, which produces more grafted polymer. It is noteworthy that the grafted polymer content is positively correlated with the hydrophobicity of the modified epoxy resin. The superhydrophobic coating exhibited enhanced erosion resistance (based on hydrochloric acid), UV ageing resistance, abrasion resistance, and freeze-thaw damage resistance to de-icers by 19.41%, 18.36%, 43.17% and 87.47%, respectively, in comparison to the conventional silane-based surface treatment.

Beam-driven plasma wakefield acceleration (PWFA) is a promising technique to generate high-energy electron bunches for future electron-positron colliders. Longitudinal shaping of high-charge drive beam is highly desired for achieving high-transformer ratio and loading high-charge witness beam. However, the existing shaping schemes either focused on relatively low-charge bunch shaping or accompanied with significant charge-loss rate (typically over 50%). In this paper, a coherent-synchrotron-radiation-free shaping scheme based on velocity modulation is proposed to generate a high-charge beam with a linearly ramped profile. A >10 kA-peak-current shaped beam containing >50 nC charge with a low charge-loss rate is demonstrated by a start-to-end simulation, and the tunabilities of the beam charge and the peak current, and the robustness of the proposed shaping scheme are also discussed. When loaded by a 3 nC witness beam, a >GV/m accelerating electric field with a transformer ratio larger than 4 can be achieved in a uniform plasma for the shaped drive beam, providing the possibility of high-transformer-ratio PWFA for a high-charge beam.

Colorectal cancer is a common malignant tumor with high mortality, for which chemotherapy resistance is one of the main reasons. The high expression of ABCG2 in the cancer cells and expulsion of anticancer drugs directly cause multidrug resistance (MDR). Therefore, the development of new ABCG2 inhibitors that block the active causes of MDR may provide a strategy for the treatment of colorectal cancer. In this study, we find that dorsomorphin (also known as compound C or BML-275) potently inhibits the transporter activity of ABCG2, thereby preserving the chemotherapeutic agents mitoxantrone and doxorubicin to antagonize MDR in ABCG2-overexpressing colorectal cancer cells. Additionally, dorsomorphin does not alter ABCG2 protein expression. The results of molecular docking studies show that dorsomorphin is bound stably to the ABCG2-binding pocket, suggesting that dorsomorphin is a potent ABCG2 inhibitor that attenuates ABCG2-mediated MDR in colorectal cancer.

IntroductionPhosphorus (P) fertilizer is critical to maintain a high yield and quality of alfalfa (Medicago sativa L.). There are several fertilizer types and soil types in China, and the application of a single type of P fertilizer may not be suitable for present-day alfalfa production.MethodsIn order to select the optimal combination of alfalfa and soil type and fertilizer type for improving P utilization efficiency. We conducted a greenhouse pot experiment, calcium superphosphate (SSP), diammonium phosphate (DAP), ammonium polyphosphate (APP), potassium dihydrogen phosphate (KP), and no-fertilizer control treatments were applied to alfalfa in sandy and saline-alkali soils. The response of alfalfa root morphology and rhizosphere processes to different P fertilizers was investigated.Results and discussionThe results showed that shoot biomass of alfalfa was slightly higher in sandy soil than in saline–alkali soil. Shoot biomass of alfalfa increased by 223%-354% in sandy soil under P treatments compared with the control, and total root length increased significantly by 74% and 53% in DAP and SSP treatments, respectively. In saline–alkali soil, alfalfa shoot biomass was significantly increased by 229% and 275% in KP and DAP treatments, and total root length was increased by 109% only in DAP treatment. Net P uptake of alfalfa in DAP treatment was the highest in both soils, which were 0.73 and 0.54 mg plant-1, respectively. Alfalfa shoot P concentration was significantly positively correlated with shoot and root biomass (P < 0.05, 0.01 or 0.001) whereas negatively correlated with acid phosphatase concentration (P < 0.05). Improvement of plant growth and P uptake induced by P fertilizer application was greater in sandy soil than in saline–alkali soil. DAP and KP was the most efficient P fertilizers in both sandy soil and saline–alkali soil.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and healthcare burden worldwide. The progression of COPD is a combination of genetic predisposition and environmental factors, primarily cigarette smoking, and the underlying mechanisms are still unknown. Intestinal microecology impacts host immunity, metabolism, and resistance to pathogenic infections, which may be involved in pulmonary disease. Moreover, substantial interaction occurs between the intestinal and respiratory immune niches. After reviewing nearly 500 articles, we found the gut-lung axis plays an important role in the development of COPD. COPD patients often have dysbiosis of the intestinal microenvironment, which can affect host immunity through a series of mechanisms, exacerbating or protecting against COPD progression. This paper summarizes how the gut-lung axis influences COPD, including the alterations of intestinal microecology, the pathological mechanisms, and the involved immune responses. Finally, we summarize the latest research advances in COPD treatment from the perspective of regulating the gut-lung axis and intestinal immunity and evaluate the potential value of the gut-lung axis in improving COPD prognosis.

Radiation-induced lung injury (RILI) frequently occurs as a complication following radiotherapy for chest tumors like lung and breast cancers. However, the precise underlying mechanisms of RILI remain unclear. In this study, we generated RILI models in rats treated with a single dose of 20 Gy and examined lung tissues by single-cell RNA sequencing (scRNA-seq) 2 weeks post-radiation. Analysis of lung tissues revealed 18 major cell populations, indicating an increase in cell-cell communication following radiation exposure. Neutrophils, macrophages, and monocytes displayed distinct subpopulations and uncovered potential for pro-inflammatory effects. Additionally, endothelial cells exhibited a highly inflammatory profile and the potential for reactive oxygen species (ROS) production. Furthermore, smooth muscle cells (SMC) showed a high propensity for extracellular matrix (ECM) deposition. Our findings broaden the current understanding of RILI and highlight potential avenues for further investigation and clinical applications.

Abstract Soft ferromagnetic permalloy (NiFe) thin films are promising for applications in spintronic devices because of their constituent electrical and magnetic properties. Electron beam evaporation and sputtering techniques have been used to deposit NiFe thin films. For in situ stacking of NiFe with functional complex oxides, the pulsed laser deposition (PLD) method is highly desirable. However, the growth of high‐quality NiFe (and non‐oxide thin films in general) by PLD remains a formidable task. Here, high‐quality NiFe thin films of various thicknesses on oxide/non‐oxide substrates with desirable magnetic properties by PLD at room temperature are reported. The magnetic properties are found to be strongly dependent on the laser fluence of the deposition process. The laser fluence of 4 J cm−2 produces the highest magnetization of ≈547 emu cc−1. The small coercivity (few Oersted) and sharp ferromagnetic switching behavior indicate uniaxial anisotropy with an easy axis along the in‐plane direction. In addition, thickness‐dependent magnetodynamics characterizations are studied via ferromagnetic resonance. These results offer significant insight into the PLD‐based development of thin metal magnetic films.

Studying the dielectric response of topological insulators (TIs) can unveil their unique physical mechanisms such as charge transport and spin-orbit coupling effects. However, due to the manifestation of material's topological nature and band structure primarily in nanofilm, such thickness poses challenges for dielectric testing. To date, research on TI dielectric aspects remains relatively unexplored. Therefore, this paper successfully synthesizes nanofilm of quaternary topological insulator Bi1·2Sb0·8Te0·4Se2.6 (BSTS) using laser molecular beam epitaxy (LMBE) technique. Utilizing a wide-frequency dielectric spectrometer and a comprehensive physical properties measurement system (PPMS), we measured and thoroughly analyzed the dielectric polarization and charge transport characteristics of BSTS. We observed various polarization responses in the frequency range of 101–103 Hz, with the dipole orientation gradually failing to keep pace with the frequency increase in the range of 103–105 Hz, and the relaxation polarization unable to establish itself in the range of 105–107 Hz, with polarization primarily contributed by displacement polarization. Subsequently, we further analyzed the dependence of BSTS dielectric polarization response on temperature and film thickness, which will help reveal the influence of external factors on TI dielectric response, providing crucial insights for controlling TI materials' dielectric response. This not only deepens our understanding of the fundamental physical properties of this novel material but also offers important scientific basis and technological support for its applications in quantum computing, photonics, spintronics, and other fields.

Abstract Traditional Chinese medicine injections (TCMIs) is a new dosage form of Chinese medicine, which plays a unique role in rescuing patients with critical illnesses that are difficult to replace. With the rapid development and widespread application of TCMIs in recent years, their adverse events have emerged and attracted much attention. Among them, pseudo-allergic reactions, i.e., the most significant adverse reactions occurring with the first dose without immunoglobulin E mediated conditions. Currently, studies on the types of TCMIs and antibiotic mechanisms that cause pseudo-allergic reactions are incomplete, and standard models and technical guidelines for assessing TCMIs have not been established. First, this review describes the causes of pseudo-allergic reactions, in which the components and structures responsible for pseudo-allergic reactions are summarized. Second, the mechanisms by which pseudo-allergic reactions are discussed, including direct stimulation of mast cells and complement activation. Then, research models of pseudo-allergic reaction diseases are reviewed, including animal models and cellular models. Finally, the outlook and future challenges for the development of pseudo-allergic reactions in traditional Chinese medicine (TCM) are outlined. This shed new light on the assessment and risk prevention of pseudo-allergic reactions in TCM and the prevention of clinical adverse reactions in TCM.

Abstract Background Breast cancer is the most common malignant tumor among women worldwide. GREB1L is a protein-coding gene. Previous studies have shown that GREB1L plays a vital role in lung and gastric adenocarcinoma. Currently, there is no relevant report about its role in breast cancer. Methods The Cancer Genome Atlas database was used to compare the expression level of GREB1L between tumor and normal tissues. The TISIDB website was used for prognosis analysis. The LinkedOmics database was used to predict the potential biological mechanism of GREB1L in breast cancer. Immunohistochemistry was used to detect the GREB1L expression level in breast tissue. Western blotting was used to detect the GREB1L expression level in cell lines. Transwell assays, CCK-8 cell proliferation assays, and colony formation assays were used to detect the migration, invasion, proliferation, and colony formation abilities of cells. Subcutaneous xenograft models were used to detect the in vivo tumor formation abilities of cells. Results GREB1L is highly expressed in breast cancer tissues and breast cancer cells. KEGG enrichment analysis suggested that GREB1L participates in the regulation of the Hedgehog signaling pathway; changes in GREB1L expression affected the migration and invasion abilities of MCF7 and MDA-MB-231 cells. Although changes in GREB1L expression did not affect their proliferation and colony formation abilities in vitro and in vivo, they affected the expression of tumor metastasis-related genes in vivo. The overexpression of GREB1L in breast cancer predicted a favorable prognosis. Conclusion These results showed that GREB1L is involved in the development of breast cancer, and it may be a potential molecular marker for predicting the prognosis of breast cancer.