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Abstract Background Giant cell tumor of bone (GCTB) is a locally aggressive neoplasm with a high propensity for recurrence following intralesional curettage. The introduction of denosumab, a RANKL inhibitor, has shown potential in facilitating joint-sparing surgery. However, concerns exist regarding its impact on local recurrence rates. This study aimed to evaluate the efficacy and safety of combined preoperative denosumab with adjuvant microwave ablation (MWA) for the treatment of high-risk GCTB. Methods We conducted a retrospective review of 19 patients with high-risk GCTB who underwent preoperative denosumab treatment followed by curettage and adjuvant MWA. The primary outcome measure was the local recurrence rate, with secondary outcomes including functional status assessed by the Musculoskeletal Tumor Society (MSTS) score and safety profile of the treatment. Results In this retrospective analysis, we evaluated the outcomes of 19 patients with high-risk GCTB treated with preoperative denosumab and adjuvant MWA. The median follow-up duration was 33.1 months, 3 patients (15.8%) experienced local recurrence at a median of 21.6 months postoperatively and the local recurrence-free survival was 81.2% at two years. Notably, no patient developed lung metastasis, and all recurrences were successfully managed with repeat curettage and MWA, with a mean MSTS score of 27.3. No patient required joint replacement due to tumor recurrence, resulting in a 100% joint preservation rate. Conclusion The combination of preoperative denosumab and adjuvant MWA is a feasible and effective strategy for the management of high-risk GCTB, providing effective local control with preserved joint function. This approach may offer a surgical alternative for young patients where joint preservation is paramount.

Abstract Currently, the oncogenic mechanism of endoplasmic reticulum stress‐CAF (ERS‐CAF) subpopulation in chordoma remains unknown. Here, single‐cell RNA sequencing, spatial transcriptomics, GeoMx Digital Spatial Profiler, data‐independent acquisition proteomics, bulk RNA‐seq, and multiplexed quantitative immunofluorescence are used to unveil the precise molecular mechanism of how ERS‐CAF affected chordoma progression. Results show that hypoxic microenvironment reprograms CAFs into ERS‐CAF subtype. Mechanistically, this occurrs via hypoxia‐mediated transcriptional upregulation of IER2. Overexpression of IER2 in CAFs promotes chordoma progression, which can be impeded by IER2 knockdown or use of ERS inhibitors. IER2 also induces expression of ERS‐CAF marker genes and results in production of a pro‐tumorigenic paracrine GMFG signaling, which exert its biological function via directly binding to ITGB1 on tumor cells. ITGB1 inhibition attenuates tumor malignant progression, which can be partially reversed by exogenous GMFG intervention. Further analyses reveal a positive correlation between ITGB1high tumor cell counts and SPP1+ macrophage density, as well as the spatial proximity of these two cell types. Clinically, a significant correlation of high IER2/ITGB1 expression with tumor aggressive phenotype and poor patient survival is observed. Collectively, the findings suggest that ERS‐CAF regulates SPP1+ macrophage to aggravate chordoma progression via the IER2/GMFG/ITGB1 axis, which may be targeted therapeutically in future.

Drought tolerance and plant growth are critical factors affecting rice yield, and identifying genes that can enhance these traits is essential for improving crop resilience and productivity. Using a growth-depressed and drought-tolerant (gddt) mutant of the indica rice variety Huanghuazhan (HHZ) generated by radiation mutagenesis, we discovered a novel gene, GDDT, which plays a dual role in plant biology: it acts as a positive regulator of growth and development, but as a negative regulator of drought resistance. The gddt mutant displayed a marked reduction in plant growth and seed setting rate, yet exhibited an unexpected advantage in terms of drought tolerance. Our research revealed that the enhanced drought tolerance of the gddt mutant is primarily due to a decrease in stomatal size, density, and aperture, which reduces water loss, and an activation of the reactive oxygen species (ROS) scavenging system, which helps protect the plant from oxidative stress. These physiological changes are observed both under drought conditions and in normal growth conditions. This discovery highlights the importance of GDDT as a pleiotropic gene with significant implications for both plant growth and drought resistance. Through map-based cloning, we determined that the protein disulfide isomerase-like (PDIL) gene OsPDIL1-5 is the GDDT gene. The protein encoded by this gene was localized to the endoplasmic reticulum, consistent with its predicted function. Our findings provide new insights into the role of PDIL genes in rice and suggest that further study of GDDT could lead to a better understanding of how these genes contribute to the complex interplay between plant growth, development, and stress responses. This knowledge could pave the way for the development of rice varieties that are more resilient to drought, thereby increasing crop yields and ensuring food security in water-limited environments.

The study of creep models for concrete is of great significance in analyzing and predicting the long-term stability of concrete structures. Based on the theory of memory-dependent derivatives, memory-dependent viscous dashpots that can describe the characteristics of decaying creep and accelerating creep are constructed based on the varying characteristics of the creep process in different stages. The Kelvin body was replaced with a stable memory-dependent dashpot and the Newtonian dashpot in the visco-plastic body was transformed into an unstable memory-dependent dashpot by drawing on the component combination form of the Nishihara model. A three-dimensional concrete creep model based on memory-dependent derivatives was established. By adjusting the model parameters of stable and unstable memory-dependent viscous dashpots, the model can simulate the creep process of concrete with different decaying creep characteristics and accelerating creep characteristics, and it has good universality. Multiple sets of experimental data on concrete creep verify that the memory-dependent concrete creep model corresponds well to the experimental data. Compared with five other concrete creep models, this model has fewer parameters and higher fitting accuracy, especially in characterizing the accelerating creep characteristics of concrete.

The present study aimed to modify the structure of ginger peel polysaccharides (GPPs) with Cr (III) and to evaluate the in vivo anti-inflammatory activities of the GPPs and GPP-Cr (III) complexes and their underlying mechanisms. The response surface methodology optimized the preparation process to a GPPs-Cr (III) mass ratio of 1:0.06, a temperature of 60 °C, and a pH of 6.8, with the greatest chelation rate of 91.1%. The modification of Cr (III) increased the molecular weight and altered the glucose proportion of the GPPs, through targeting the O–H of hydroxyl groups and affecting the C–O/O–C–O structures. The GPP-Cr (III) complexes had a similar crystallinity and conformation to the parent polysaccharides, but were more thermally stable than the GPPs (in the region of < 130 °C and > 332 °C). In CuSO4-induced inflammation in zebrafish, the GPP-Cr (III) complexes (dose: 50 and 100 μg/mL) showed significantly stronger anti-inflammatory activity than the GPPs did via down-regulating the expression of relevant transcription factors and cytokines in the MyD88/NF-κB/MAPK/iNOS signaling pathway. Therefore, GPP-Cr (III) complexes might be promising dietary formulations with anti-inflammatory effects, Cr (III) supplements, or functional food components, which substantially facilitated the high-value utilization of ginger peel by-products.

Transcription factors (TFs) play essential roles in transcriptional reprogramming during activation of plant immune responses to pathogens. OsSPL10 (SQUAMOSA promoter binding protein-like10) is an important TF regulating trichome development and salt tolerance in rice. Here we report that knockout of OsSPL10 reduces whereas its overexpression enhances rice resistance to blast disease. OsSPL10 positively regulates chitin-induced immune responses including reactive oxygen species (ROS) burst and callose deposition. We show that OsSPL10 physically associates with OsJAmyb, an important TF involved in jasmonic acid (JA) signaling, and positively regulates its protein stability. We then prove that OsJAmyb positively regulates resistance to blast. Our results reveal a molecular module consisting of OsSPL10 and OsJAmyb that positively regulates blast resistance.

Aroma is a key criterion in evaluating aromatic coconut water. A comparison regarding key aroma compounds and sensory correlations was made between Thailand Aromatic Green Dwarf (THD) and Cocos nucifera L. cv. Wenye No. 4 coconut water using E-nose and GC × GC-O-TOF-MS combined with chemometrics. Twenty-one volatile components of coconut water were identified by GC × GC-O-TOF-MS, and 5 key aroma compounds were analyzed by relative odor activity value and aroma extract dilution analysis. Moreover, the combination of the E-nose with orthogonal partial least squares was highly effective in discriminating between the two coconut water samples and screened the key sensors responsible for this differentiation. Additionally, the correlation between volatile compounds and sensory properties was established using partial least squares. The key aroma compounds of coconut water exhibited positive correlations with the corresponding sensory properties.

Abstract Background Spatial epidemiology plays an important role in public health. Yet, it is unclear whether the current university education in spatial epidemiology in China could meet the competency-oriented professional demands. This study aimed to understand the current situation of education and training, practical application, and potential demands in spatial epidemiology among public health postgraduates in China, and to assess the critical gaps in a future emerging infectious diseases (EID) pandemic preparedness and response. Methods This study was divided into three parts. The first part was a comparative study on spatial epidemiology education in international public health postgraduate training. The second part was a cross-sectional survey conducted among public health professionals. The third part was a nationwide cross-sectional survey conducted among public health postgraduates at Chinese universities from October 2020 to February 2021. Data was collected by the WeChat-based questionnaire star survey system and analyzed using the SPSS software. Results International education institutions had required public health postgraduates to master the essential knowledge and capacity of spatial epidemiology. A total of 198 public health professionals were surveyed, and they had a median of 4.00 (IQR 3.13–4.53) in demand degree of spatial epidemiology. A total of 1354 public health postgraduates were surveyed from 51 universities. Only 29.41% (15/51) of universities offered spatial epidemiology course. Around 8.05% (109/1354) of postgraduates had learned spatial epidemiology, and had a median of 1.05 (IQR 1.00–1.29) in learning degree and a median of 1.91 (IQR 1.05–2.78) in practical application degree of spatial epidemiology. To enhance professional capacity, 65.95% (893/1354) of postgraduates hoped that universities would deliver a credit-course of spatial epidemiology. Conclusions A huge unmet education and training demand in spatial epidemiology existed in the current education system of public health postgraduates in China. To enhance the competency-oriented professional capacity in preparedness and response to a future pandemic, it is urgent to incorporate the teaching and training of spatial epidemiology into the compulsory curriculum system of public health postgraduates in China.

Milk thistle is one of the most popular ingredients in the liver protection products market. Silymarin is the main component of milk thistle and contains multiple isomers. There have been few studies focusing on the compositional ratios of silymarin isomers. In this study, we developed an HPLC method for the separation and quantification of silymarin isomers, thereby elucidating their compositional ratios. Through the analysis of more than 40 milk thistle extract products on the market, we found that the ratios, specifically Ratio 1 (the silybin B content to the silybin A content, SBNB/SBNA) and Ratio 2 (the sum of the contents of silybin B and isosilybin B to the sum of the contents of silybin A and isosilybin A, (SBNB + IBNB)/(SBNA + IBNA)), are highly consistent across milk thistle extracts, averaging approximately 1.58 and 1.28, respectively. Furthermore, such ratios were verified in milk thistle seed samples. This study introduces significant findings concerning the stable ratios among silymarin isomers in milk thistle extracts and seeds, thereby offering an innovative approach for quality assurance of milk thistle extracts.

Objectives A well-functioning health system ensures timely routine measles vaccinations for age-appropriate children, minimising measles risk. However, there is limited knowledge about the impact of the performance of immunisation programmes in health systems on the timeliness of measles vaccination. This study aimed to identify health system barriers to timely routine measles vaccination in rural southwest China, integrating the perspectives of township vaccination professionals and village doctors.Design, setting and participants Qualitative study among township vaccination professionals and village doctors in rural Guangxi, southwest China.Methods 20 focus group discussions (FGDs) at township level and 120 in-depth interviews (IDIs) at village level, based on a four-theme framework. We used convenience sampling to recruit 60 township vaccination professionals and 120 village doctors in 2015. Instruments used were a semistructured questionnaire and interview outlines. We collected township and village-level data focusing on themes of health resources allocation, pattern of vaccination services, management and supervision of vaccination services, and perceptions of vaccination policy. The FGDs and IDIs were audio-recorded and transcribed. Braun and Clarke’s thematic analysis approach was adopted to synthesise findings into meaningful subthemes, narrative text and illustrative quotations.Results The health system barriers to timely routine vaccinations were explored across four themes. Barriers in the health resources allocation theme comprised (1) inadequacy of vaccination-related human resources (eg, lack of township vaccination professionals and lack of young village doctors), and (2) incompatible and non-identical information system of vaccination services across regions. Barriers in the pattern of vaccination services theme included inflexible vaccination services models, for example, routine vaccination services being offered monthly on fixed vaccination days, limited numbers of vaccination days per month, vaccination days being set on non-local market days, vaccination days being clustered into a specific period and absence of formal vaccination appointments. Ineffective economic incentive mechanism was identified as a barrier in the management and supervision of vaccination services theme. Low-degree participation of village doctors in routine vaccination services was identified as a barrier in the perceptions of vaccination policy theme.Conclusions We encourage policymakers and stakeholders to apply these findings to improve the timeliness of routine vaccination. Barriers to timely routine vaccination include inadequate allocation of vaccination-related resources and inflexible vaccination service delivery models. Financial and non-financial incentives should be used to retain and recruit vaccination professionals and village doctors. Strengthening information systems with unified data standards enables cross-regional data exchange. Optimising immunisation services and rationalising vaccination days could eliminate health system barriers and improve vaccination timeliness in rural China.

ObjectiveTo explore the characteristics and risk factors for major mediastinal vessel invasion in different risk grades of thymic epithelial tumors (TETs) based on computed tomography (CT) imaging, and to develop prediction models of major mediastinal artery and vein invasion.MethodsOne hundred and twenty-two TET patients confirmed by histopathological analysis who underwent thorax CT were enrolled in this study. Clinical and CT data were retrospectively reviewed for these patients. According to the abutment degree between the tumor and major mediastinal vessels, the arterial invasion was divided into grade I, II, and III (< 25%, 25 – 49%, and ≥ 50%, respectively); the venous invasion was divided into grade I and II (< 50% and ≥ 50%). The degree of vessel invasion was compared among different defined subtypes or stages of TETs using the chi-square tests. The risk factors associated with TET vascular invasion were identified using multivariate logistic regression analysis.ResultsBased on logistic regression analysis, male patients (β = 1.549; odds ratio, 4.824) and the pericardium or pleural invasion (β = 2.209; odds ratio, 9.110) were independent predictors of 25% artery invasion, and the midline location (β = 2.504; odds ratio, 12.234) and mediastinal lymphadenopathy (β = 2.490; odds ratio, 12.06) were independent predictors of 50% artery invasion. As for 50% venous invasion, the risk factors include midline location (β = 2.303; odds ratio, 10.0), maximum tumor diameter larger than 5.9 cm (β = 4.038; odds ratio, 56.736), and pericardial or pleural effusion (β = 1.460; odds ratio, 4.306). The multivariate logistic model obtained relatively high predicting efficacy, and the area under the curve (AUC), sensitivity, and specificity were 0.944, 84.6%, and 91.7% for predicting 50% artery invasion, and 0.913, 81.8%, and 86.0% for 50% venous invasion in TET patients, respectively.ConclusionSeveral CT features can be used as independent predictors of ≥50% artery or venous invasion. A multivariate logistic regression model based on CT features is helpful in predicting the vascular invasion grades in patients with TET.

Rf(fa), a new restoring fertility gene in rice, was previously located to a large region on Chromosome 10. The large number of genes within the region made cloning of Rf(fa) difficult. To perform the cloning and further elucidate the molecular mechanism, we reconstructed a mapping segregation population (BC1F1) of 12 000 plants. Using the population and polymorphism of simple sequence repeat (SSR) molecular markers, we finally mapped Rf(fa) between the two SSR molecular markers MM2000 and RM25658, within a 78.87 kb region. By de novo sequencing of a restoring line of CMS-FA hybrid rice, we obtained the genomic sequence of the mapping region, which provided the basis for the prediction of the candidate gene(s) of the target gene and for the comparison of genomic sequence differences between wild and cultivated rice. Within the mapping region, the genomic sequence of the wild rice was significantly different from that of cultivated rice. There were ten genes in the final mapping region. A pentatricopeptide repeat (PPR) protein gene was predicted as the candidate gene of Rf(fa). Our results laid a solid foundation for the final cloning and molecular mechanism analysis of the gene. The identified molecular markers tightly linked to Rf(fa) will facilitate the marker assisted selection in breeding of CMS-FA hybrid rice.

Cannabidiol (CBD) is the major functional component in hemp and has a broad range of pharmacological applications, such as analgesic, anti-epileptic, anti-anxiety, etc. Currently, CBD is widely used in pharmaceuticals, cosmetics, and food. To ensure the quality and safety of the products containing CBD, more and more related sample testing is being conducted, and the demand for CBD-certified reference material (CRM) has also sharply increased. However, there is currently a lack of relevant reference materials. In this paper, a simple method for preparing CBD CRM was established based on preparative liquid chromatography using crude hemp extract as a raw material. A qualitative analysis of CBD was performed using techniques such as ultraviolet absorption spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), and differential scanning calorimetry (DSC). High-performance liquid chromatography (HPLC) was used for the homogeneity and stability tests, and the data were analyzed using an F-test and a T-test, respectively. Then, eight qualified laboratories were chosen for the determination of a certified value using HPLC. The results show that the CBD CRM had excellent homogeneity and good stability for 18 months. The certified value was 99.57%, with an expanded uncertainty of 0.24% (p = 0.95, k = 2). The developed CBD CRM can be used for the detection and quality control of cannabidiol products.

The J-TEXT capability is enhanced compared to two years ago with several upgrades of its diagnostics and the increase of electron cyclotron resonance heating (ECRH) power to 1 MW. With the application of electron cyclotron wave (ECW), the ECW assisted plasma startup is achieved; the tearing mode is suppressed; the toroidal injection of 300 kW ECW drives around 24 kA current; fast electrons are generated with toroidal injected ECW and the runaway current conversion efficiency increases with ECRH power. The mode coupling between 2/1 and 3/1 modes are extensively studied. The coupled 2/1 and 3/1 modes usually lead to major disruption. Their coupling can be either suppressed or avoided by external resonant magnetic perturbation fields and hence avoids the major disruption. It is also found that the 2/1 threshold of external field is significantly reduced by a pre-excited 3/1 mode, which can be either a locked island or an external kink mode. The disruption control is studied by developing prediction methods capable of cross tokamak application and by new mitigation methods, such as the biased electrode or electromagnetic pellet injector. The high-density operation and related disruptions are studied from various aspects. Approaching the density limit, the collapse of the edge shear layer is observed and such collapse can be prevented by applying edge biasing, leading to an increased density limit. The density limit is also observed to increase, if the plasma is operated in the poloidal divertor configuration or the plasma purity is increased by increasing the pre-filled gas pressure or ECRH power during the start-up phase.

The reversed field pinch (RFP) is a toroidal magnetic configuration in which plasmas can spontaneously transform into different self-organized states. Among various states, the ‘quasi-single-helical’ (QSH) state has a dominant component for the magnetic field and significantly improves confinement. Many theoretical and experimental efforts have investigated the transitions among different states. This paper employs the multi-region relaxed magnetohydrodynamic model to study the properties of QSH and other states. The stepped-pressure equilibrium code (SPEC) is used to compute MHD equilibria for the Keda Torus eXperiment (KTX). The toroidal volume of KTX is partitioned into two subvolumes by an internal transport barrier. The geometry of this barrier is adjusted to achieve force balance across the interface, ensuring that the plasma in each subvolume is force-free and that magnetic helicity is conserved. By varying the parameters, we generate distinct self-organized states in KTX. Our findings highlight the crucial role of magnetic helicity in shaping these states. In states with low magnetic helicity in both subvolumes, the plasma exhibits axisymmetric behavior. With increasing core helicity, the plasma gradually transforms from an axisymmetric state to a double-axis helical state and finally to a single-helical-axis state. Elevated core magnetic helicity leads to a more pronounced dominant mode of the boundary magnetic field and a reduced core magnetic shear. This is consistent with previous experimental and numerical results in other RFP devices. We find a linear relationship between the plasma current and helicity in different self-organized states. Our findings suggest that KTX may enter the QSH state when the toroidal current reaches 0.72 MA. This study demonstrates that the stellarator equilibrium code SPEC unveils crucial RFP equilibrium properties, rendering it applicable to a broad range of RFP devices and other toroidal configurations.

Since the last IAEA-FEC in 2021, significant progress on the development of long pulse steady state scenario and its related key physics and technologies have been achieved, including the reproducible 403 s long-pulse steady-state H-mode plasma with pure radio frequency (RF) power heating. A thousand-second time scale (∼1056 s) fully non-inductive plasma with high injected energy up to 1.73 GJ has also been achieved. The EAST operational regime of high β _P has been significantly extended ( H _98y2 > 1.3, β _P ∼ 4.0, β _N ∼ 2.4 and n _e / n _GW ∼ 1.0) using RF and neutral beam injection (NBI). The full edge localized mode suppression using the n = 4 resonant magnetic perturbations has been achieved in ITER-like standard type-I ELMy H-mode plasmas with q _95 ≈ 3.1 on EAST, extrapolating favorably to the ITER baseline scenario. The sustained large ELM control and stable partial detachment have been achieved with Ne seeding. The underlying physics of plasma-beta effect for error field penetration, where toroidal effect dominates, is disclosed by comparing the results in cylindrical theory and MARS-Q simulation in EAST. Breakdown and plasma initiation at low toroidal electric fields (

Deep pellet fueling depth is necessary to achieve a high-density high confinement operation and to conduct some pellet-related researches in current devices, such as trigger of internal transport barrier, and to achieve high fusion power and tritium burn-up fraction in future fusion devices. The newly developed PAM code which can make a fast evaluation on pellet ablation and deposition is applied to optimize injection parameters to achieve deep pellet fueling. Systematic scans on pellet injection parameters including pellet injection positions, injection angles, sizes and speeds are performed for optimization purpose, while at the same time demonstrating flexibility and time efficiency of the PAM code. Dependences of the pellet fueling depth on these injection parameters are revealed by simulation results and analyzed. Simulation results indicate that pellet penetration contributes more to the deep pellet deposition than the $\nabla B$ -induced plasmoid drifts in low temperature plasmas, while deep pellet fueling in reactor relevant high temperature plasmas has to rely on plasmoid drifts. Though a shallow penetration is expected in high temperature plasmas, the $\nabla B$ -induced plasmoid drift is expected to be larger than that in relatively low temperature plasmas.

The Langmuir probe observed an increase in density and floating potential fluctuations after the sawtooth crash at the edge of HL-2A neutral beam injection heated plasma. This process initiates fluctuating-induced radial inward particle transport once the plasma enters a period with strong sawtooth crash. The inward transport comprises broad-band fluctuations with varying scales, which occur uniquely in the immediate aftermath of the sawtooth crash-driven outflow, signifying a transient phenomenon confined to that specific interval. These results demonstrate that the sawtooth crash can significantly impact edge turbulence by modifying electrostatic fluctuations. This modification changes the direction of electric fluctuation-induced particle transport, thereby reducing the influence of the intense sawtooth crash-driven outflow. Furthermore, the observations support the existence of a damping mechanism for the outflow during the formation of inward flux after the sawtooth crash, which may be associated with the recovery process of sawtooth cycle.

The main building of Zone II of Zhanjiang Bay Laboratory R&D Building adopts a steel frame–core tube shear wall structure system, with a 53.4 m large-span and heavy-load-transfer truss on the fourth floor. In order to propose the optimal construction and installation scheme for the large-span and heavy-load-transfer truss, the simplified model, single model, and 3D model are utilized to compare Scheme 1 with rigid connection and Scheme 2 with elastic connection and rigid connection. After completing the construction of the underground layer and towers on both sides, in Scheme 1, the fourth-floor transfer truss is directly connected to the towers on both sides in a rigid manner. Subsequently, the support at the bottom of the transfer truss is removed, allowing for layer-by-layer construction. The transfer truss remains rigidly connected to both side towers throughout. On the other hand, in Scheme 2, initially, the transfer truss is connected to both side towers through upper chords and diagonal bars before being constructed upwards until reaching the sixth floor. Once formed as a whole with two floors above using large diagonal tie rods, lower chords of the large-span and heavy-load-transfer truss are then connected with another diagonal bar to establish a rigid connection between the transfer truss and towers; thereafter, upward construction continues. Following completion of constructing a seven-story large diagonal tie rod, whereupon removal of support at the bottom of the conversion truss occurs, subsequent layer-by-layer construction takes place accordingly. It has been observed that employing Scheme 2 can enhance stress distribution within core barrel shear walls as well as transfer trusses while ensuring deflection and stress levels meet requirements for the large-span and heavy-load-transfer truss, thereby rendering structural stress more rationalized, leading to significantly improved overall safety.

The Zhanjiang Bay Laboratory R&D Building project aims to create a favorable working, research, and living environment. Zone II of the Zhanjiang Bay Laboratory R&D Building is equipped with a large-span, heavy-load transfer truss to obtain a large space on the ground floor. The overall structure adopts a steel frame-core tube structure system. In order to reduce the deflection of the large-span, heavy-load transfer truss, eight diagonal pull rods are installed between the large-span, heavy-load transfer truss and the core tube. The Q235 cross-shaped replacement section can consume construction load energy. Adopting replacement methods can reduce the stress and damage of diagonal pull rods caused by construction loads. The structure adopts a performance-based seismic design method for seismic calculation and analysis. In addition, a special analysis was conducted on the single frame structure. The major results can be summarized as follows: during small earthquakes, all structural components are in the elastic stage; during large earthquakes, frame beams yield first, but frame columns and core tubes do not yield; even without considering out-of-plane constraints, the structure can still meet the requirements.

The R&D Building of Zhanjiang Bay Laboratory is a high-rise structure with multiple irregular items exceeding the specification limit, employing a steel frame-shear wall structural system. The outer frame consists of square steel tube concrete columns and solid-web steel beams, while the core shear wall uses a double steel plate concrete composite shear wall. This paper employs the architectural structural calculation software YJK-EP to perform a dynamic elastic-plastic time-history analysis under rare earthquake action. The shear and bending resistance of the shear wall at the maximum shear force and bending moment are checked to meet the requirements of the “Technical Specifications for Concrete Structures of High-rise Buildings”. The maximum inter-story displacement angle meets the requirements of the “Code for Seismic Design of Buildings”. The double steel plate concrete composite shear wall Wall-1, connected to a large-span and heavy-load transfer truss, was verified under significant seismic action using the ABAQUS software. The results indicate that Wall-1 can meet the design target requirements under major earthquake conditions. Finally, a dynamic nonlinear analysis method was employed using MIDAS-GEN software to study the structure’s anti-progressive collapse performance. The results show that under seven different scenarios, the maximum rotational angle of the remaining structural horizontal members is 2.02°, far less than the limit set by GSA, indicating that a progressive collapse did not occur. In the scenario where the corner column is removed, both the maximum shear and bending moment values for Wall-1 are far below its shear and bending resistance capacities, satisfying the load-bearing requirements. The removal of the corner column has a significant impact on the displacement of the columns on the same level nearby, with the peak displacement change rate reaching 702.65%.

Currently, the oncogenic mechanism of endoplasmic reticulum stress‐CAF (ERS‐CAF) subpopulation in chordoma remains unknown. Here, single‐cell RNA sequencing, spatial transcriptomics, GeoMx Digital Spatial Profiler, data‐independent acquisition proteomics, bulk RNA‐seq, and multiplexed quantitative immunofluorescence are used to unveil the precise molecular mechanism of how ERS‐CAF affected chordoma progression. Results show that hypoxic microenvironment reprograms CAFs into ERS‐CAF subtype. Mechanistically, this occurrs via hypoxia‐mediated transcriptional upregulation of IER2. Overexpression of IER2 in CAFs promotes chordoma progression, which can be impeded by IER2 knockdown or use of ERS inhibitors. IER2 also induces expression of ERS‐CAF marker genes and results in production of a pro‐tumorigenic paracrine GMFG signaling, which exert its biological function via directly binding to ITGB1 on tumor cells. ITGB1 inhibition attenuates tumor malignant progression, which can be partially reversed by exogenous GMFG intervention. Further analyses reveal a positive correlation between ITGB1high tumor cell counts and SPP1+ macrophage density, as well as the spatial proximity of these two cell types. Clinically, a significant correlation of high IER2/ITGB1 expression with tumor aggressive phenotype and poor patient survival is observed. Collectively, the findings suggest that ERS‐CAF regulates SPP1+ macrophage to aggravate chordoma progression via the IER2/GMFG/ITGB1 axis, which may be targeted therapeutically in future. [ABSTRACT FROM AUTHOR]

Environmental credit evaluation is essential for the establishment of an environmental financial system, but most studies have focused on the impact of green financial instruments such as green credit and green bonds, resulting in insufficient attention to this core aspect. This study examines the impact of environmental credit evaluation on firm ESG performance using a staggered difference‐in‐differences model based on China's environmental credit rating policy. By analyzing data from 2010 to 2020 on 1018 publicly listed firms in high‐pollution industries in China, this study finds that the implementation of the environmental credit rating policy significantly improves ESG performance. This positive impact is realized through enhancing environmental information transparency, strengthening external supervision, and alleviating financing constraints. [ABSTRACT FROM AUTHOR]

Abstract Background Measles outbreaks re-emerged in 2013–2014 in Guangxi Zhuang Autonomous Region of China, where measles immunisation coverage is high. The discrepancy between the vaccination coverage and outbreaks indicates that timeliness is crucial, yet there is limited knowledge on the health system barriers to timely vaccination. Using integrated evidence at the household, village clinic, and township hospital levels, this study aimed to identify the determinants of failure in receiving timely measles vaccinations among children in rural Guangxi. Methods A multi-stage stratified cluster sampling survey with a nested qualitative study was conducted among children aged 18–54 months in Longan, Zhaoping, Wuxuan, and Longlin counties of Guangxi from June to August 2015. The status of timely vaccinations for the first dose of measles-containing vaccine (MCV1) and the second dose of measles-containing vaccine (MCV2) was verified via vaccination certificates. Data on household-level factors were collected using structured questionnaires, whereas data on village and township-level factors were obtained through in-depth interviews and focus group discussions. Determinants of untimely measles vaccinations were identified using multilevel logistic regression models. Results A total of 1216 target children at the household level, 120 villages, and 20 township hospitals were sampled. Children were more likely to have untimely vaccination when their primary guardian had poor vaccination knowledge [MCV1, odds ratio (OR) = 1.72; MCV2, OR = 1.51], had weak confidence in vaccines (MCV1, OR = 1.28–4.58; MCV2, OR = 1.42–3.12), had few practices towards vaccination (MCV1, OR = 12.5; MCV2, OR = 3.70), or had low satisfaction with vaccination service (MCV1, OR = 2.04; MCV2, OR = 2.08). This trend was also observed in children whose village doctor was not involved in routine vaccination service (MCV1, OR = 1.85; MCV2, OR = 2.11) or whose township hospital did not provide vaccination notices (MCV1, OR = 1.64; MCV2, OR = 2.05), vaccination appointment services (MCV1, OR = 2.96; MCV2, OR = 2.74), sufficient and uniformly distributed sessions for routine vaccination (MCV1, OR = 1.28; MCV2, OR = 1.17; MCV1, OR = 2.08), or vaccination service on local market days (MCV1, OR = 2.48). Conclusions Guardians with poor knowledge, weak beliefs, and little practice towards vaccination; non-involvement of village doctors in routine vaccinations; and inconvenient vaccination services in township hospitals may affect timely measles vaccinations among children in rural China. Graphical abstract

Background: Type 2 diabetes mellitus (T2DM) and spinal degenerative disorders (SDD) are common diseases that frequently coexist. However, both traditional observational studies and recent Mendelian randomization (MR) studies have demonstrated conflicting evidence on the association between T2DM and SDD. This comparative study explored and compared the association between T2DM and SDD using observational and MR analyses. Methods: For observational analyses, cross-sectional studies (44,972 participants with T2DM and 403,095 participants without T2DM), case-control studies (38,234 participants with SDD and 409,833 participants without SDD), and prospective studies (35,550 participants with T2DM and 392,046 participants without T2DM with follow-up information until 2022) were performed to test the relationship between T2DM and SDD using individual-level data from the U.K. Biobankfrom 2006 to 2022. For MR analyses, the associations between single-nucleotide polymorphisms with SDD susceptibility obtained using participant data from the U.K. Biobank, which had 407,938 participants from 2006 to 2022, and the FinnGen Consortium, which had 227,388 participants from 2017 to 2022, and genetic predisposition to T2DM obtained using summary statistics from a pooled genome-wide association study involving 1,407,282 individuals were examined. The onset and severity of T2DM are not available in the databases being used. Results: Participants with T2DM were more likely to have SDD than their counterparts. Logistic regression analysis identified T2DM as an independent risk factor for SDD, which was confirmed by the Cox proportional hazard model results. However, using single-nucleotide polymorphisms as instruments, the MR analyses demonstrated no causal relationship between T2DM and SDD. The lack of such an association was robust in the sensitivity analysis, and no pleiotropy was seen. Conclusions: Our results suggest that the association between T2DM and SDD may be method-dependent. Researchers and clinicians should be cautious in interpreting the association, especially the causal association, between T2DM and SDD. Our findings provide fresh insights into the association between T2DM and SDD by various analysis methods and guide future research and clinical efforts in the effective prevention and management of T2DM and SDD. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the effects of 4-week tangeretin supplementation on the cortisol stress response induced by high-intensity resistance exercise.Methods: A randomized controlled trial of twenty-four soccer players was conducted during the winter training season. The experimental group (EG) took the oral supplement with tangeretin (200 mg/day) and the control group (CG) took placebo for 4 weeks. Before and after the 4-week intervention, all players performed a high intensity bout of resistance exercise to stimulate their cortisol stress responses. Serum cortisol, adreno-corticotropic hormone (ACTH) and superoxide dismutase (SOD) were obtained by collecting blood samples before (PRE), immediately after (P0), and 10 (P10), 20 (P20) and 30 minutes (P30) after the exercise.Results: The serum cortisol level (PRE, p = 0.017; P10, p = 0.010; P20, p = 0.014; P30, p = 0.007) and ACTH (P10, p = 0.037; P30, p = 0.049) of experimental group significantly decreased after the 4-week intervention. Compared with control group, EG displayed a significantly lower level of the serum cortisol (PRE, p = 0.036; P10, p = 0.031) and ACTH (P30, p = 0.044). Additionally, EG presented significantly higher superoxide dismutase activity level compared with CG at P30 (p = 0.044). The white blood cell of EG decreased significantly (PRE, p = 0.037; P30, p = 0.046) and was significantly lower than CG at P20 (p = 0.01) and P30 (p = 0.003).Conclusion: Four-week tangeretin supplementation can reduce serum cortisol and ACTH, which may ameliorate the cortisol stress response in soccer players during high-intensity resistance exercise training. It can also enhance antioxidant capacity, accelerate the elimination of inflammation throughout the body, and shorten recovery time after high-intensity exercise.

To date, the underlying mechanisms involved intervertebral disc degeneration (IDD) remain unclear, which has hindered the development of molecular biological therapy for IDD. Autophagy is vital for intracellular quality control and metabolic balance in intervertebral disc cells. Hence, autophagy homeostasis is important. Emerging evidence has implicated vitamin D (VD) and the vitamin D receptor (VDR) in IDD progression because of their effects on different autophagy steps. However, the results of clinical trials in which VD supplementation was assessed as a treatment for IDD are controversial. Furthermore, experimental studies on the interplay between VD/VDR and autophagy are still in their infancy. In view of the significance of the crosstalk between VD/VDR and autophagy components, this review focuses on the latest research on VD/VDR modulation in autophagy and investigates the possible regulatory mechanisms. This article will deepen our understanding of the relationship between VD/VDR and autophagy and suggests novel strategies for IDD prevention and treatment.

Abstract Background Intervertebral disc degeneration (IDD) is widely known as the main contributor to low back pain which has a negative socioeconomic impact worldwide. However, the underlying mechanism remains unclear. This study aims to analyze the dataset GSE23130 using bioinformatics methods to identify the pivotal genes and pathways associated with IDD. Material/methods The gene expression data of GSE23130 was downloaded, and differentially expressed genes (DEGs) were extracted from 8 samples and 15 controls. GO and KEGG pathway enrichment analyses were performed. Also, protein–protein interaction (PPI) network was constructed and visualized, followed by identification of hub genes and key module. Results A total of 30 downregulated and 79 upregulated genes were identified. The DEGs were mainly enriched in the regulation of protein catabolic process, extracellular matrix organization, collagen fibril organization, and extracellular structure organization. Meanwhile, we found that most DEGs were primarily enriched in the PI3K-Akt signaling pathway. The top 10 hub genes were FN1, COL1A2, SPARC, COL3A1, CTGF, LUM, TIMP1, THBS2, COL5A2, and TGFB1. Conclusions In summary, key candidate genes and pathways were identified by using integrated bioinformatics analysis, which may provide insights into the underlying mechanisms and offer potential target genes for the treatment of IDD.

Abstract Background Currently, the measurement of immune cells in previous studies is usually subjective, and no immune‐based prognostic model has been established for chordoma. In this study, we sought to simultaneously measure tumor‐infiltrating lymphocyte (TIL) subtypes in chordoma samples using an objective method and develop an immune risk score (IRS) model for survival prediction. Methods Multiplexed quantitative immunofluorescence staining was used to determine the TIL levels in the tumoral and stromal subareas of 114 spinal chordoma specimens (54 in the training and 60 in the validation cohort) for programmed death‐1 (PD‐1), CD3, CD8, CD20 (where CD is cluster of differentiation), and FOXP3. Flow cytometry was performed to validate the immunofluorescence assay for lymphocyte measurement on an additional five fresh chordoma specimens. Subsequently, the IRS model was built using the least absolute shrinkage and selection operator (LASSO) Cox regression method. Results Flow cytometry and quantitative immunofluorescence showed similar lymphocytic percentages and TIL subpopulation proportions in the fresh tumor specimens. With the training data, the LASSO model identified four immune features for IRS construction: tumoralFOXP3, tumoralPD‐1, stromalFOXP3, and stromalCD8. In both cohorts, a high IRS was significantly associated with tumoral programmed cell death‐1 ligand 1 expression, Enneking inappropriate tumor resection, and surrounding muscle invasion by tumor. Multivariate Cox regression and stratified analysis in the two cohorts revealed that the IRS was an independent predictor and could effectively separate patients with similar Enneking staging into different risk subgroups, with significantly different survival rates. Further receiver operating characteristic analysis found that the IRS classifier had a better prognostic value than the traditional clinicopathological factors and compensated for the deficiency of Enneking staging for outcome prediction. More importantly, a nomogram based on the IRS and clinical predictors showed adequate performance in estimating disease recurrence and survival of patients. Conclusions These data support the use of the IRS signature as a reliable prognostic tool in spinal chordoma and may facilitate individualized therapy decision making for patients.

BackgroundImmunotherapy only achieves efficacy in some cancer patients, and less is known about other immune checkpoint molecules in chordoma. Here, we aimed to determine the expression of PD-L1, HHLA2, B7H3, IDO-1 and Galectin-9 in spinal chordoma and evaluated their association with tumor infiltrating lymphocytes (TILs), clinicopathological characteristics and survival of patients.MethodsUsing multiplexed quantitative immunofluorescence (QIF), we simultaneously measured the levels of five different immune checkpoint molecules and major TIL subsets in 92 human spinal chordoma samples.ResultsTumor HHLA2 and PD-L1 were positive in 80.0% and 86.0% of cases, respectively. However, B7H3, IDO-1 and Galectin-9 positivity on tumor cells were only seen in 21.0% of cases, despite all showing predominantly stromal expression. Coexpression of these QIF markers in the tumor compartment was scarcely detected except for PD-L1 and HHLA2, which was observed in 69.6% of cases. While tumoral HHLA2 and stromal B7H3 expressions were associated with an aggressive tumor phenotype, suppressive immune response (specifically including elevated PD-1+ TILs level and decreased CD8+ TIL density) and poor prognosis, stromal levels of PD-L1 and Galectin-9 predicted the opposite outcomes. Importantly, HHLA2 and PD-L1 coexpression on tumor cells independently predicted both worse local recurrence-free survival and overall survival.ConclusionThese data provide a better understanding of the immunosuppressive mechanism in chordoma and may be useful for the development of combination or novel immunotherapy approaches aiming to improve therapeutic efficacy and survival.

Salinity is one of the major abiotic stress factors limiting rice production. Glabrousness is a trait of agronomic importance in rice (Oryza sativa L.). We previously found a single-gene recessive mutant sst, which displayed increased salt tolerance and glabrous leaf and glume without trichomes, and identified an SBP-box gene OsSPL10 as the candidate of the SST gene. In this study, OsSPL10-knockout and OsSPL10-overexpression mutants were created to check the function of the gene. The knockout mutants exhibited enhanced salt tolerance and glabrous leaves and glumes as expected, while the overexpression mutants showed opposite phenotypes, in which both salt sensitivity and trichome density on leaf and glume were increased. These results clearly confirmed that OsSPL10 is SST, and suggested that OsSPL10 controls the initiation rather than the elongation of trichomes. In addition, expression analysis indicated that OsSPL10 was preferentially expressed in young panicle and stem, and protein OsSPL10 was localized in nucleus. Taken together, OsSPL10 negatively controls salt tolerance but positively controls trichome formation in rice.