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Abstract Despite the pivotal role of stannum doping in achieving ultrahigh piezoelectric performance in barium titanate-based ceramics, the fundamental mechanisms underlying this enhancement remain elusive. Here, we introduce a single variable nonstoichiometric stannum strategy in lead-free barium titanate-based ceramics with giant piezoelectricity, revealing that stannum doping contributes intrinsically and extrinsically to enhance piezoelectricity. Density functional theory calculations elucidate the intrinsic enhancement of polarization arising from lattice distortion and increased space for titanium-oxygen bonds induced by optimal stannum doping, which is corroborated by Rayleigh analysis. A phase transition from ferroelectric multiphase coexistence to paraelectric phase is observed, alongside a rapid miniaturized and eventually disappeared domains with increasing stannum doping. This evolution in phase structure and domain configuration induces a nearly vanishing polarization anisotropy and low domain wall energy, facilitating easy polarization rotation and domain wall motion, thereby significantly contributing to the extrinsic piezoelectric response. Consequently, the origins of ultrahigh performance can be attributed to the synergistic effect of stannum-induced intrinsic and extrinsic contributions in barium titanate-based ceramics. This study provides fundamental insights into the role of doping elements and offers guidance for the design of high-performance piezoelectrics.

Objectives: Femtosecond laser technology has become the primary method for micropore processing due to its high precision and low energy consumption. However, during the process, it is easy to cause microcracks and burrs in the micropores. Additionally, due to the small size, low structural stability and weak wear resistance of the micropores, conventional methods are ineffective in polishing them. To address the challenge of polishing femtosecond laser-processed micropores, the abrasive water jet polishing method is employed. This method leverages the stable removal function and strong adaptability of the abrasive water jet to improve the quality of femtosecond laser-processed micropores. Methods: Computational fluid dynamics (CFD) simulations of the abrasive water jet micropore polishing process under different process parameters were carried out by using Fluent software. A finite element model of abrasive water jet polishing for femtosecond laser-processed micropores was established under various working conditions. The flow field distribution, the erosion rate and the wall shear force under different parameters were analyzed. Corresponding experiments were conducted for each variable discussed in the Fluent simulation, and the variation patterns of micropore inner wall roughness were summarized. Subsequently, optimization experiments were conducted on the three factors, namely jet target distance, jet pressure and abrasive particle size, using the response surface method. The mean square error of shear force on the inner wall of the hole was taken as the response value Y, and the response surface equation was established. The optimal polishing parameter combination was obtained through the response surface equation and experimentally verified. Results: A jet impact angle of 90° is suitable for polishing the inner wall of the micropore, as wall erosion is uniform and the shear force distribution is concentrated at this angle. At a target distance of 4.2 to 6.0 mm, the jet on the end face enters the deceleration stage, and the jet velocity decreases as the target distance increases. The shear force increases with increasing jet pressure. When the jet pressure is 0.80 MPa, the shear force is the smallest, concentrated in the range of 1 500 to 3 500 Pa. At a jet pressure of 1.50 MPa, the shear force is the largest, concentrated in the range of 3 500 to 5 500 Pa. When jet pressure increases from 0.80 to 1.50 MPa, the shear force on the inner wall of the hole increases more than twice. The effects of abrasive particle size and jet pressure on wall shear force are similar. When the abrasive particle size is 1.0 μm, the shear force is the smallest, concentrated in the range of 1 000 to 2 500 Pa. At an abrasive particle size of 30.0 μm, the shear force reaches its maximum, concentrated between 3 000 and 5 500 Pa. Corresponding tests are carried out for each variable discussed in the simulation, and the minimum roughness Ra of the inner wall of the micropore was 0.386 μm. The optimal process parameter combination obtained through response surface analysis is as follows: jet impact angle of 90°, jet target distance of 3.5 mm, jet pressure of 1.10 MPa, and abrasive particle size of 15.0 μm. Under the optimal parameter combination, with an abrasive mass fraction of 5% and a polishing time of 5.0 minutes, the surface roughness Ra of the polished micropore inner wall surface was reduced to 0.354 µm, which is better than the minimum roughness of 0.386 µm observed in the simulation. Polishing efficiency is improved by about 3%, and the quality of the micropore inner wall surface is further enhanced. Conclusions: When the impact angle is constant, the shear force on the inner wall of the hole increases with increasing jet pressure and abrasive particle size. It increases first and then decreases with the increase in jet target distance, with jet pressure having the greatest influence on the wall shear force. Different structural segments of the jet can be applied to different working conditions due to different properties. Additionally, the simulation and experimental results are in good agreement, and the improvement in roughness is significant. This indicates that abrasive water jet polishing significantly enhances the quality of micropore walls, and the data model for response surface prediction has high accuracy.

AgNbO3 (AN) and modified AgNbO3 have been extensively investigated as promising lead-free antiferroelectric (AFE) energy storage materials. Previous studies have focused mainly on the use of an ion dopant at the A/B site to obtain a stabilized AFE phase; however, simultaneous improvements in the recoverable energy storage density (Wrec) and efficiency (η) are still difficult to realize. Herein, we innovatively constructed a AgNbO3–NaNbO3–(Sr0.7Bi0.2)TiO3 (AN–NN–SBT) ternary solid solution to achieve a relaxor AFE in AgNbO3-based materials. The coexistence of antiferroelectric (M3) and paraelectric (O) phases in 0.8(0.7AgNbO3–0.3NaNbO3)–0.2(Sr0.7Bi0.2)TiO3 confirms the successful realization of a relaxor AFE, attributed to multiple ion occupation at the A/B sites. Consequently, a high Wrec of 7.53 J·cm−3 and η of 74.0% are acquired, together with superior stability against various temperatures, frequencies, and cycling numbers. Furthermore, a high power density (298.7 MW·cm−3) and fast discharge speed (41.4 ns) are also demonstrated for the AgNbO3-based relaxor AFE. This work presents a promising energy storage AgNbO3-based ternary solid solution and proposes a novel strategy for AgNbO3-based energy storage via the design of relaxor AFE materials.

Abstract Background Adverse atherogenic lipid profile is associated with an increased risk of major adverse cardiac events in patients after acute coronary syndrome (ACS). Knowledge regarding the impact of statins on lipid profile remains limited. Methods We retrospectively analysed multicenter, real-world data from the Chinese Cardiovascular Association Database-iHeart Project. Patients with a primary diagnosis of ACS from 2014 to 2021 during index hospitalisation and having at least one lipid panel record after discharge within 12 months were enrolled. We analysed target achievement of atherogenic lipid profile, including apolipoprotein B (

Abstract Drought is a major abiotic stress affecting crop yields. Mapping quantitative trait loci (QTLs) and mining genes for drought tolerance in rice are important for identifying gene functions and targets for molecular breeding. Here, we performed linkage analysis of drought tolerance using a recombinant inbred line population derived from Jileng 1 (drought sensitive) and Milyang 23 (drought tolerant). An ultra-high-density genetic map, previously constructed by our research team using genotype data from whole-genome sequencing, was used in combination with phenotypic data for rice grown under drought stress conditions in the field in 2017–2019. Thirty-nine QTLs related to leaf rolling index and leaf withering degree were identified, and QTLs were found on all chromosomes except chromosomes 6, 10, and 11. qLWD4-1 was detected after 32 days and 46 days of drought stress in 2017 and explained 7.07–8.19% of the phenotypic variation. Two loci, qLRI2-2 and qLWD4-2, were identified after 29, 42, and 57 days of drought stress in 2018. These loci explained 10.59–17.04% and 5.14–5.71% of the phenotypic variation, respectively. There were 281 genes within the QTL interval. Through gene functional annotation and expression analysis, two candidate genes, Os04g0574600 and OsCHR731, were found. Quantitative reverse transcription PCR analysis showed that the expression levels of these genes were significantly higher under drought stress than under normal conditions, indicating positive regulation. Notably, Os04g0574600 was a newly discovered drought tolerance gene. Haplotype analysis showed that the RIL population carried two haplotypes (Hap1 and Hap2) of both genes. Lines carrying Hap2 exhibited significantly or extremely stronger drought tolerance than those carrying Hap1, indicating that Hap2 is an excellent haplotype. Among rice germplasm resources, there were two and three haplotypes of Os04g0574600 and OsCHR731, respectively. A high proportion of local rice resources in Sichuan, Yunnan, Anhui, Guangdong and Fujian provinces had Hap of both genes. In wild rice, 50% of accessions contained Hap1 of Os04g0574600 and 50% carried Hap4; 13.51%, 59.46% and 27.03% of wild rice accessions contained Hap1, Hap2, and Hap3, respectively. Hap2 of Os04g0574600 was found in more indica rice resources than in japonica rice. Therefore, Hap2 has more potential for utilization in future drought tolerance breeding of japonica rice.

Abstract Background Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ. Methods GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration. Results The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P

Abstract The time-dependent effects in steel-concrete composite beam bridges can intensify track irregularities, subsequently leading to amplified train-bridge coupling vibrations. This phenomenon may increase the stress amplitudes in the bridge steel, thereby impacting the fatigue performance of the composite structures. This paper employs multiple rigid body dynamics to construct a high-speed train model and utilizes the finite element method to develop a steel-concrete composite beam element model that accounts for time-dependent effects, interfacial slip, and shear hysteresis. This approach enables the computational analysis of the train-bridge coupling system, facilitating an investigation into the influence of concrete’s time-dependent effects on the fatigue performance of railway steel-concrete composite bridges. Focusing on a 40-m simply supported composite bridge, the train-bridge coupling dynamic responses were computed for each operational year within a decade of the completion of construction. Applying the P-M linear fatigue damage accumulation theory, statistical analysis of stress history data across various operational periods was conducted to quantify the fatigue damage induced by a single eight-car high-speed train on the lower flange of the mid-span steel beam and the beam-end studs. The findings reveal that the beam-end studs sustain greater damage than the mid-span steel beam. Moreover, the detrimental impact of time-dependent effects diminishes with the increase of operational years. Notably, compared to the initial year, the fatigue damage to the lower flange of the mid-span steel beam by an eight-car train in the tenth year has surged by 39.3%. Conversely, the damage to the beam-end studs has decreased by 47.5%.

Abstract Background The determining effect of facial hard tissues on soft tissue morphology in orthodontic patients has yet to be explained. The aim of this study was to clarify the hard-soft tissue relationships of the lower 1/3 of the face in skeletal Class II-hyperdivergent patients compared with those in Class I-normodivergent patients using network analysis. Methods Fifty-two adult patients (42 females, 10 males; age, 26.58 ± 5.80 years) were divided into two groups: Group 1, 25 subjects, skeletal Class I normodivergent pattern with straight profile; Group 2, 27 subjects, skeletal Class II hyperdivergent pattern with convex profile. Pretreatment cone-beam computed tomography and three-dimensional facial scans were taken and superimposed, on which landmarks were identified manually, and their coordinate values were used for network analysis. Results (1) In sagittal direction, Group 2 correlations were generally weaker than Group 1. In both the vertical and sagittal directions of Group 1, the most influential hard tissue landmarks to soft tissues were located between the level of cemento-enamel junction of upper teeth and root apex of lower teeth. In Group 2, the hard tissue landmarks with the greatest influence in vertical direction were distributed more forward and downward than in Group 1. (2) In Group 1, all the correlations for vertical-hard tissue to sagittal-soft tissue position and sagittal-hard tissue to vertical-soft tissue position were positive. However, Group 2 correlations between vertical-hard tissue and sagittal-soft tissue positions were mostly negative. Between sagittal-hard tissue and vertical-soft tissue positions, Group 2 correlations were negative for mandible, and were positive for maxilla and teeth. Conclusion Compared with Class I normodivergent patients with straight profile, Class II hyperdivergent patients with convex profile had more variations in soft tissue morphology in sagittal direction. In vertical direction, the most relevant hard tissue landmarks on which soft tissue predictions should be based were distributed more forward and downward in Class II hyperdivergent patients with convex profile. Class II hyperdivergent pattern with convex profile was an imbalanced phenotype concerning sagittal and vertical positions of maxillofacial hard and soft tissues.

Abstract Histone lysine methyltransferase 2D (KMT2D) is the most frequently mutated epigenetic modifier in head and neck squamous cell carcinoma (HNSCC). However, the role of KMT2D in HNSCC tumorigenesis and whether its mutations confer any therapeutic vulnerabilities remain unknown. Here we show that KMT2D deficiency promotes HNSCC growth through increasing glycolysis. Additionally, KMT2D loss decreases the expression of Fanconi Anemia (FA)/BRCA pathway genes under glycolytic inhibition. Mechanistically, glycolytic inhibition facilitates the occupancy of KMT2D to the promoter/enhancer regions of FA genes. KMT2D loss reprograms the epigenomic landscapes of FA genes by transiting their promoter/enhancer states from active to inactive under glycolytic inhibition. Therefore, combining the glycolysis inhibitor 2-DG with DNA crosslinking agents or poly (ADP-ribose) polymerase (PARP) inhibitors preferentially inhibits tumor growth of KMT2D-deficient mouse HNSCC and patient-derived xenografts (PDXs) harboring KMT2D-inactivating mutations. These findings provide an epigenomic basis for developing targeted therapies for HNSCC patients with KMT2D-inactivating mutations.

Abstract Background This study quantitatively analyzed the anatomic structure of the alveolar bone in the maxillary molar region at three potential locations for Temporary Anchorage Device (TAD) placement. Additionally, the study compared the variability in this region across different age groups, sagittal skeletal patterns, vertical facial types, and sexes. Methods In this retrospective cone-beam computed tomography study, the buccal alveolar bone was analyzed in the posterior molar area of 200 patients, the measurement items include buccal alveolar bone height, alveolar bone thickness, interradicular distance, and maxillary retromolar space. Results Buccal alveolar height was greatest in the U56 region. The interradicular space was largest in the U56 region and increased from the alveolar crest to the sinus floor. Buccal alveolar bone thickness was highest in the U67 region and generally increased from the alveolar crest to the sinus floor. The maxillary retromolar space gradually increased from the alveolar crest to the root apex. Conclusions TADs are safest when placed in the buccal area between the maxillary second premolar and the first molar, particularly at the 9 mm plane. The U67 region is the optimal safe zone for TAD placement for maxillary dentition distalization. TADs placement in adolescents can be challenging. Maxillary third molar extraction can be considered for maxillary dentition distalization.

Abstract Background The potentially fatal attacks experienced by porphyria carriers are triggered by various porphyrinogenic drugs. However, determining the safety of particular drugs is challenging. Methods We retrospectively used the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) to identify drugs associated with porphyria as an adverse event (AE) extracted from data from January 2004 to March 2022. The associated search terms included “Porphyria,” “Porphyria screen,” “Porphyria non-acute,” “Porphyria acute,” “Acquired porphyria,” and “Pseudoporphyria.” Signal mining analysis was performed to identify the association between drugs and AEs by four algorithms, namely the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker. Results FAERS reported 1470 cases of porphyria-related AEs, and 406 drugs were screened after combining trade and generic names. All four algorithms identified 52 drugs with signals. The characteristics of all the reports and signaling drugs were analyzed. Conclusions This is the first report of drug-associated porphyria that provides critical information on drug porphyrogenicity, facilitating rational and evidence-based drug prescription and improving the accuracy of porphyrogenicity prediction based on model algorithms. Moreover, this study serves a reference for clinicians to ensure that porphyrinogenic drugs are not prescribed to carriers of porphyria genetic mutations.

Abstract Compared with teenage patients, adult patients generally show a slower rate of tooth movement and more pronounced alveolar bone loss during orthodontic treatment, indicating the maladaptation of alveolar bone homeostasis under orthodontic force. However, this phenomenon is not well-elucidated to date, leading to increased treatment difficulties and unsatisfactory treatment outcomes in adult orthodontics. Aiming to provide a comprehensive knowledge and further inspire insightful understanding towards this issue, this review summarizes the current evidence and underlying mechanisms. The age-related abatements in mechanosensing and mechanotransduction in adult cells and periodontal tissue may contribute to retarded and unbalanced bone metabolism, thus hindering alveolar bone reconstruction during orthodontic treatment. To this end, periodontal surgery, physical and chemical cues are being developed to reactivate or rejuvenate the aging periodontium and restore the dynamic equilibrium of orthodontic-mediated alveolar bone metabolism. We anticipate that this review will present a general overview of the role that aging plays in orthodontic alveolar bone metabolism and shed new light on the prospective ways out of the impasse.

Abstract In the digital era, digital platforms are gradually changing the ways of life and social production and are becoming the centre of digital services in various industries. Additionally, they break the established institutional framework of social recognition and promote technological change and innovation. Thus, examining the quality of innovation facilitated by digital platforms has become an important area of research. This paper utilises China’s 2011–2021 provincial panel data and examines digital platforms, resource mismatches and innovation quality within the same research framework. The direct, indirect and nonlinear effects of digital platforms on innovation quality are explored using the fixed effects model, intermediary effect model and dynamic threshold regression model. The findings indicate that digital platforms have a significant positive direct effect on innovative quality, and resource mismatches play intermediary and threshold roles in the process. These findings offer policy guidance for constructing robust digital platform ecosystems and enhancing innovation quality.

Abstract Background Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone. Case presentation A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic. Conclusions In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.

Abstract Background Exercise has been identified as a promising non-pharmacological therapy for the management of depression, but there is still controversy over which type is most effective. We aimed to compare and rank the types of exercise that improve depression in postmenopausal women by quantifying information from randomized controlled trials (RCTs). Methods The PubMed, Web of Science, SPORTDiscus, CNKI, The Cochrane Library, PsycINFO, EMBASE, and CINAHL Plus databases were searched to identify articles published from inception to 1 March 2024 reporting RCTs that examined the effectiveness of exercise on depression in postmenopausal women. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for RCTs. The quality of the evidence for each comparison was graded using the online confidence in network meta-analysis tool (CINeMA). Standardized mean differences (SMDs) were calculated using the mean and standard deviation of pre-to-post intervention changes and then pooled using a random effects model in a pairwise meta-analysis using Review Manager 5.4. Then, a frequentist network meta-analysis was conducted using a random effects model was conducted to evaluate the efficacy of different exercise types using the network package of Stata 15. Results This study included 26 studies involving 2,170 participants. The pairwise meta-analysis revealed that exercise had a significant positive effect on depression in postmenopausal women (SMD = -0.71, 95% confidence interval [CI] = -0.94 to -0.48; I 2 = 78%). The network meta-analysis revealed that mind-body exercise (SMD = -0.97, 95% CI = -1.28 to -0.67), aerobic exercise (SMD = -0.58, 95% CI = -0.88 to -0.27) and multicomponent exercise (SMD = -0.57, 95% CI = -1.15 to -0.002) significantly reduced depression compared to the control intervention. Mind-body exercise had the highest probability of being the most effective intervention. Exercise interventions also showed positive effects on anxiety. Most studies were judged to have some concerns regarding their risk of bias, and the confidence in evidence was often very low according to CINeMA. Conclusion For postmenopausal women, there is very low to moderate quality evidence that exercise interventions are an effective antidepressant therapy, with mind-body exercise most likely being the optimal type. Trial registration This meta-analysis was prospectively registered with PROSPERO (registration number: CRD42024505425).

Background/purpose: Quantitative in vitro research was conducted on the learning process of a dynamic navigation system. This study provides guidance for the promotion and application of dynamic navigation technology in the endodontic apical surgery field. Materials and methods: Standardized models were designed and 3D printed to form the approach operation of endodontic apical surgery. 6 clinicians with no experience in dynamic navigation performed the operation. The distance deviation tolerance was set as 0.6 mm, and the angle deviation tolerance was set as 5°. Fifteen mm deep approach operation was completed using dynamic navigation. Each operator performed 10 consecutive exercises on the models. The positioning deviation and operation time of each operator for each practice were recorded. Based on this, the learning curve of the dynamic navigation of every operator was mapped. The learning difficulty of dynamic navigation was evaluated. Results: The learning curves of all operators reached a stable level after the 7th practice, which can ensure that the distance and angle deviations are maintained within the deviation tolerances (0.6 mm, 5°). Conclusion: Operators with no experience in dynamic navigation technology need practice to master dynamic navigation operations. For this navigation system, operators with no operational experience can master dynamic navigation operations after 7 exercises.

Abstract Background Mediterranean diet rich in polyphenolic compounds holds great promise to prevent and alleviate multiple sclerosis (MS), a central nervous system autoimmune disease associated with gut microbiome dysbiosis. Health-promoting effects of natural polyphenols with low bioavailability could be attributed to gut microbiota reconstruction. However, its underlying mechanism of action remains elusive, resulting in rare therapies have proposed for polyphenol-targeted modulation of gut microbiota for the treatment of MS. Results We found that oral ellagic acid (EA), a natural polyphenol rich in the Mediterranean diet, effectively halted the progression of experimental autoimmune encephalomyelitis (EAE), the animal model of MS, via regulating a microbiota-metabolites-immunity axis. EA remodeled the gut microbiome composition and particularly increased the relative abundances of short-chain fatty acids -producing bacteria like Alloprevotella. Propionate (C3) was most significantly up-regulated by EA, and integrative modeling revealed a strong negative correlation between Alloprevotella or C3 and the pathological symptoms of EAE. Gut microbiota depletion negated the alleviating effects of EA on EAE, whereas oral administration of Alloprevotella rava mimicked the beneficial effects of EA on EAE. Moreover, EA directly promoted Alloprevotella rava (DSM 22548) growth and C3 production in vitro. The cell-free supernatants of Alloprevotella rava co-culture with EA suppressed Th17 differentiation by modulating acetylation in cell models. C3 can alleviate EAE development, and the mechanism may be through inhibiting HDAC activity and up-regulating acetylation thereby reducing inflammatory cytokines secreted by pathogenic Th17 cells. Conclusions Our study identifies EA as a novel and potentially effective prebiotic for improving MS and other autoimmune diseases via the microbiota-metabolites-immunity axis. Video Abstract

While the impact of the house purchase restriction (HPR) policy on the housing market in China has been deeply examined, there is still little known about how the housing market varies when such policy is abandoned. To fill this gap, we first theoretically propose two hypotheses concerning the relationship between abandoning HPR policy and housing price and transaction based on the housing literature. We then examine the hypotheses by taking Jinan, China as empirical case that offer an excellent policy setting of some districts having discarded the policy while the other remains. The results derived from Synthetic Control Method (SCM) showed that the cancellation of the HPR policy plays a vital role in increasing the transaction volume, but it fails to promote house prices. The findings remain reliable after a series of placebo and robustness tests. This article adds new insight to the debate on efficacy of government intervention via more granular quantitative data, and further contributes to policy implications regarding housing market development.

Abstract The design and preparation of efficient catalysts for ammonia production under mild conditions is a desirable but highly challenging target. Here, we report a series of single-atom catalysts [M-SACs, M = Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Mo(II)] derived from UiO-66 containing structural defects and their application to electrochemical reduction of nitrate (NO3 -) to ammonia (NH3). Cu-SAC and Fe-SAC exhibit remarkable yield rates for NH3 production of 30.0 and 29.0 mg h−1 cm−2, respectively, with a high Faradaic efficiency (FENH3) of over 96% at −1.0 V versus the reversible hydrogen electrode. Importantly, their catalytic performance can be retained in various simulated wastewaters. Complementary experiments confirmed the nature of single-atom sites within these catalysts and the binding domains of NO3 - in UiO-66-Cu. In situ spectroscopic techniques, coupled with density functional theory calculations confirm the strong binding of NO3 - and the formation of reaction intermediates, thus facilitating the catalytic conversion to NH3.

Abstract Background Cervical cancer is one of the most common gynecological malignancies. Previous studies have shown that the ethanol extract of Sophora moorcroftiana seeds (EESMS) possesses an antiproliferative effect on several tumors in vitro. Therefore, in this study, we assessed the impact of EESMS on human cervical carcinoma (HeLa) cell proliferation. Methods The proliferation and apoptotic effects of HeLa cells treated with EESMS were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, dual acridine orange/ethidium bromide double staining, flow cytometry, and western blotting. Single-cell level atomic force microscopy (AFM) was conducted to detect the mechanical properties of HeLa cells, and proteomics and bioinformatics methods were used to elucidate the molecular mechanisms of EESMS. Results EESMS treatment inhibited HeLa cell proliferation by blocking the G0/G1 phase, increasing the expression of Caspase-3 and affecting its mechanical properties, and the EESMS indicated no significant inhibitory effect on mouse fibroblasts L929 cell line. In total, 218 differentially expressed proteins were identified using two-dimensional electrophoresis, and eight differentially expressed proteins were successfully identified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. The differentially expressed proteins were involved in various cellular and biological processes. Conclusion This study provides a perspective on how cells change through biomechanics and a further theoretical foundation for the future application of Sophora moorcroftiana as a novel low-toxicity chemotherapy medication for treating human cervical cancer.

Abstract Background Palliative care and the integration of health and social care have gradually become the key direction of development to address the aging of the population and the growing burden of multimorbidity at the end of life in the elderly. Aims To explore the benefits/effectiveness of the availability and stability of palliative care for family members of terminally ill patients in an integrated institution for health and social care. Methods This prospective observational study was conducted at an integrated institution for health and social care. 230 patients with terminal illness who received palliative care and their family members were included. Questionnaires and scales were administered to the family members of patients during the palliative care process, including quality-of-life (SF-8), family burden (FBSD, CBI), anxiety (HAMA), and distress (DT). We used paired t-tests and correlation analyses to analyze the data pertaining to our research questions. Results In the integrated institution for health and social care, palliative care can effectively improve quality of life, reduce the family’s burden and relieve psychological impact for family members of terminally ill patients. Palliative care was an independent influencing factor on the quality of life, family burden, and psychosocial status. Independently of patient-related and family-related factors, the results are stable and widely applicable. Conclusion The findings underline the availability and stability of palliative care and the popularization of an integrated service model of health and social care for elder adults.

Abstract Background Pharmacist clinics offer professional pharmaceutical services that can improve public health outcomes. However, primary healthcare staff in China face various barriers and challenges in implementing such clinics. To identify existing problems and provide recommendations for the implementation of pharmacist clinics, this study aims to assess the knowledge, attitudes, and practices of pharmacist clinics among primary healthcare providers. Methods A cross-sectional survey based on the Knowledge-Attitude-Practice (KAP) model, was conducted in community health centers (CHCs) and private hospitals in Shanghai, China in May, 2023. Descriptive analytics and the Pareto principle were used to multiple-answer questions. Chi-square test, Fisher’s exact test, and binary logistic regression models were employed to identify factors associated with the knowledge, attitudes, and practices of pharmacist clinics. Results A total of 223 primary practitioners participated in the survey. Our study revealed that most of them had limited knowledge (60.1%, n = 134) but a positive attitude (82.9%, n = 185) towards pharmacist clinics, with only 17.0% (n = 38) having implemented them. The primary goal of pharmacist clinics was to provide comprehensive medication guidance (31.5%, n = 200), with medication education (26.3%, n = 202) being the primary service, and special populations (24.5%, n = 153) identified as key recipients. Logistic regression analysis revealed that education, age, occupation, position, work seniority, and institution significantly influenced their perceptions. Practitioners with bachelor’s degrees, for instance, were more likely than those with less education to recognize the importance of pharmacist clinics in medication guidance (aOR: 7.130, 95%CI: 1.809–28.099, p-value = 0.005) and prescription reviews (aOR: 4.675, 95% CI: 1.548–14.112, p-value = 0.006). Additionally, practitioners expressed positive attitudes but low confidence, with only 33.3% (n = 74) feeling confident in implementation. The confidence levels of male practitioners surpassed those of female practitioners (p-value = 0.037), and practitioners from community health centers (CHCs) exhibited higher confidence compared to their counterparts in private hospitals (p-value = 0.008). Joint physician-pharmacist clinics (36.8%, n = 82) through collaboration with medical institutions (52.0%, n = 116) emerged as the favored modality. Daily sessions were preferred (38.5%, n = 86), and both registration and pharmacy service fees were considered appropriate for payment (42.2%, n = 94). The primary challenge identified was high outpatient workload (30.9%, n = 69). Conclusions Although primary healthcare practitioners held positive attitudes towards pharmacist clinics, limited knowledge, low confidence, and high workload contributed to the scarcity of their implementation. Practitioners with diverse sociodemographic characteristics, such as education, age, and institution, showed varying perceptions and practices regarding pharmacist clinics.

Abstract Background The operation accuracy and efficiency of dynamic navigated endodontic surgery were evaluated through in vitro experiments. This study provides a reference for future clinical application of dynamic navigation systems in endodontic surgery. Materials and methods 3D-printed maxillary anterior teeth were used in the preparation of models for endodontic surgery. Endodontic surgery was performed with and without dynamic navigation by an operator who was proficient in dynamic navigation technology but had no experience in endodontic surgery. Optical scanning data were applied to evaluate the length and angle deviations of root-end resection. And the operation time was recorded. T tests were used to analyze the effect of dynamic navigation technology on the accuracy and duration of endodontic surgery. Results With dynamic navigation, the root-end resection length deviation was 0.46 ± 0.06 mm, the angle deviation was 2.45 ± 0.96°, and the operation time was 187 ± 22.97 s. Without dynamic navigation, the root-end resection length deviation was 1.20 ± 0.92 mm, the angle deviation was 16.20 ± 9.59°, and the operation time was 247 ± 61.47 s. Less deviation was achieved and less operation time was spent with than without dynamic navigation (P

Carbon emissions from China’s forest products industry were considered based on the data of 2001-2020. Then a carbon emissions Kuznets curve was constructed to judge the relationship between the economic development level and carbon emissions. The logarithmic mean Divisia index (LMDI) was used to analyze the influencing factors of carbon emissions. The carbon emissions from China’s forest products industry showed a trend of rapid growth in the early stage and slow decline in the later stage, increasing from 19.46 million tonnes in 2001 to 54.18 million tonnes in 2020. Consumption of raw coal was the main reason for the increase in carbon emissions. There was an inverted-U relationship between the economic development level and carbon emissions, and the industry output value of CNY 3306.56 billion was the theoretical inflection point. The current economic development level of the industry was in the left-half part of the inverted “U” shape, indicating that carbon emissions from this industry will continue to increase with the increase of industrial output. Economic development was the key factor driving the increase of carbon emissions in the forest products industry, while the energy intensity was the key factor inhibiting the growth of carbon emissions.

Abstract The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation in hgfa and two missense mutations in met by positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation in hgfa or met. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes. Moreover, HGF promotes thyrocyte migration, which is probably mediated by downregulation of E-cadherin expression. The delayed bifurcation of the thyroid primordium is also observed in thyroid-specific Met knockout mice. Together, our findings reveal that HGF/Met is indispensable for the bifurcation of the thyroid primordium during thyroid development mediated by downregulation of E-cadherin in thyrocytes via MAPK-snail pathway.

The N6-methyladenosine (m6A) modification is the most prevalent modification of eukaryotic mRNAs and plays a crucial role in various physiological processes by regulating the stability or function of target mRNAs. Accumulating evidence has suggested that m6A methylation may be involved in the pathological process of major depressive disorder (MDD), a common neuropsychiatric disorder with an unclear aetiology. Here, we found that the levels of the circular RNA HECW2 (circHECW2) were significantly increased in the plasma of both MDD patients and the chronic unpredictable stress (CUS) mouse model. Notably, the downregulation of circHECW2 attenuated astrocyte dysfunction and depression-like behaviors induced by CUS. Furthermore, we demonstrated that the downregulation of circHECW2 increased the expression of the methylase WTAP, leading to an increase in Gng4 expression via m6A modifications. Our findings provide functional insight into the correlation between circHECW2 and m6A methylation, suggesting that circHECW2 may represent a potential target for MDD treatment.

Amid the escalating conflicts between urban demography, resource availability, and environmental constraints, there is an accelerating demand for emergency medical services prompted by a spectrum of factors including diseases, natural calamities, and unforeseen events. This growth is further accentuated by an imbalance in the allocation of emergency facilities, amplifying public anxiety and underscoring the urgent necessity for scientifically informed optimization of pre-hospital emergency facilities. To this end, the present study articulates specific optimization goals for facility deployment and introduces a nuanced set coverage optimization model that integrates spatiotemporal determinants of emergency service requirements. The model is fortified with a constellation of constraints, including spatial constraint, temporal constraint, and coverage constraint. For spatial constraints, we use the Monte Carlo simulation to predict the spatial distribution of emergency demands. Temporal constraints involve determining the actual travel time matrix from predicted demand points to candidate sites. Coverage constraints specify the effective demand coverage rate. This study uses Nanjing as a case example, utilizing multisource big data, including ambulance GPS logs from June 2016 to May 2017, Amap traffic congestion indicators, and survey data on existing emergency facilities in Nanjing City. By preprocessing and analyzing the existing data, this study thoroughly investigates the spatiotemporal distribution of emergency demands and the impact of traffic congestion on emergency service effectiveness. Consequently, the model incorporates constraints that ensure, under the specified planning and actual traffic conditions, 95 % of the simulated emergency demands can be met within an 8-minute on-route time. Locations for pre-hospital emergency stations are optimized using a genetic algorithm, achieving the best solution at the 120th iteration. Verification confirms 134 optimal sites; after excluding 52 existing sites, 82 potential sites are identified. The new layout plan has reduced Nanjing’s average emergency response time from 18.6 min to 12 min. Additionally, under peak and average traffic conditions, emergency demand coverage rates improved from 76.92 % and 83.18 % at 15 min to 95.61 % and 98.10 % at 12 min, respectively. These results demonstrate that the new layout significantly enhances practical application effectiveness. The approach presented in this paper addresses the previously overlooked randomness of emergency incidents and traffic conditions, offering innovative strategies for improving the efficiency and effectiveness of emergency station planning and site selection models.

Vitamin D binding protein (VDBP) serves as a key transporter protein responsible for binding and delivering vitamin D and its metabolites to target organs. VDBP plays a crucial part in the inflammatory reaction following tissue damage and is engaged in actin degradation. Recent research has shed light on its potential role in various diseases, leading to a growing interest in understanding the implications of VDBP in psychiatric and neurological disorders. The purpose of this review was to provide a summary of the existing understanding regarding the involvement of VDBP in neurological and psychiatric disorders. By examining the intricate interplay between VDBP and these disorders, this review contributes to a deeper understanding of underlying mechanisms and potential therapeutic avenues. Insights gained from the study of VDBP could pave the way for novel strategies in the diagnosis, prognosis, and treatment of psychiatric and neurological disorders.

Abstract Switchable adhesion, a phenomenon characterized by the ability to transition between attachment and detachment states under external stimuli, has recently gained popularity in various advanced devices. The realization of the desired functionalities on such surfaces relies on intricate interfacial designs. A general understanding of the commonalities and distinctions among these designs can foster the development of refined switchable adhesion interfaces (SAIs). To address this, this review first examines adhesion interfaces by focusing on the fundamental interactions at the atomic/molecular level, adhesion models, and their correlation with the diverse forces/bonds that dominate the adhesion behaviors. The latest progress in SAIs based on various forces/bonds, including electrostatic force, van der Waals force, capillary force, chemical bond, and suction force, is then discussed with regard to their specific design strategies, such as structures, components, and triggers. Additionally, an extensive overview of the broad applications of SAIs in fields ranging from space to biomedicine is provided, along with an exploration of the prevailing challenges and potential opportunities. With the rapid progress that has been made in state‐of‐the‐art mechanisms and design strategies, SAIs are expected to undergo booming development in the foreseeable future.

Abstract A comprehensive immune landscape for Brucella infection is crucial for developing new treatments for brucellosis. Here, we utilized single‐cell RNA sequencing (scRNA‐seq) of 290,369 cells from 35 individuals, including 29 brucellosis patients from acute (n = 10), sub‐acute (n = 9), and chronic (n = 10) phases as well as six healthy donors. Enzyme‐linked immunosorbent assays were applied for validation within this cohort. Brucella infection caused a significant change in the composition of peripheral immune cells and inflammation was a key feature of brucellosis. Acute patients are characterized by potential cytokine storms resulting from systemic upregulation of S100A8/A9, primarily due to classical monocytes. Cytokine storm may be mediated by activating S100A8/A9‐TLR4‐MyD88 signaling pathway. Moreover, monocytic myeloid‐derived suppressor cells were the probable contributors to immune paralysis in acute patients. Chronic patients are characterized by a dysregulated Th1 response, marked by reduced expression of IFN‐γ and Th1 signatures as well as a high exhausted state. Additionally, Brucella infection can suppress apoptosis in myeloid cells (e.g., mDCs, classical monocytes), inhibit antigen presentation in professional antigen‐presenting cells (APCs; e.g., mDC) and nonprofessional APCs (e.g., monocytes), and induce exhaustion in CD8+ T/NK cells, potentially resulting in the establishment of chronic infection. Overall, our study systemically deciphered the coordinated immune responses of Brucella at different phases of the infection, which facilitated a full understanding of the immunopathogenesis of brucellosis and may aid the development of new effective therapeutic strategies, especially for those with chronic infection.

Background: The prognosis and therapeutic response of patients with liver hepatocellular carcinoma (LIHC) can be predicted based on programmed cell death (PCD) as PCD plays a crucial role during tumor progression. We developed a PCD-related gene signature to evaluate the therapeutic response and prognosis for patients with LIHC. Methods: Molecular subtypes of LIHC were classified using ConsensusClusterPlus according to the gene biomarkers related to PCD. To predict the prognosis of high- and low-risk LIHC patients, a risk model was established by LASSO regression analysis based on the prognostic genes. Functional enrichment analysis was conducted using clusterProfiler package, and relative abundance of immune cells was quantified applying CIBERSORT package. Finally, to determine drug sensitivity, oncoPredict package was employed. Results: PCD was correlated with the clinicopathologic features of LIHC. Then, we defined four molecular subtypes (C1–C4) of LIHC using PCD-related prognostic genes. Specifically, subtype C1 had the worst prognosis with enriched T cells regulatory (Tregs) and Macrophage_M0 and higher expression of T cell exhaustion markers, meanwhile, C1 also had a relatively higher TIDE score and metastasis potential. A risk model was established using 5 prognostic genes. High-risk patients tended to have higher expression of T cell exhaustion markers and TIDE score and unfavorable outcomes, and they were more sensitive to small molecule drug 5.Fluorouracil. Conclusion: A PCD-related gene signature was developed and verified to be able to accurately predict the prognosis and drug sensitivity of LIHC patients.

Efficiency, safety and cost are three major evaluation indexes of warehouse operation. However, the uncertainty of efficiency, safety and cost factors will lead to economic losses and waste of resources. The purpose of this study is to propose a novel parameterized neutrosophic objective–proportionate genetic algorithm model (PNO–PGA) to optimize the above three objectives. There are three main contributions of this study. Firstly, a novel score function of neutrosophic sets (NSs) is proposed to effectively integrate the fuzziness of efficiency, safety and cost to avoid the evaluation result being too idealized. Secondly, a novel proportionate genetic algorithm is applied to adaptively realize the iteration and inheritance processes. Finally, two parameters are proposed to make the algorithm model flexibly adapt to different types of environments and problems. Then, an example is used to compare the new method with genetic algorithm (GA). The result shows that PNO-PGA has better problem-solving ability in warehouse operation than GA.

Summary: The oxidative-stress-related protein Kelch-like ECH-associated protein 1 (KEAP1) is a substrate articulator of E3 ubiquitin ligase, which plays an important role in the ubiquitination modification of proteins. However, the function of KEAP1 in breast cancer and its impact on the survival of patients with breast cancer remain unclear. Our study demonstrates that KEAP1, a positive prognostic factor, plays a crucial role in regulating cell proliferation, apoptosis, and cell cycle transition in breast cancer. We investigate the underlying mechanism using human tumor tissues, high-throughput detection technology, and a mouse xenograft tumor model. KEAP1 serves as a key regulator of cellular metabolism, the reprogramming of which is one of the hallmarks of tumorigenesis. KEAP1 has a significant effect on mitochondrial biogenesis and oxidative phosphorylation by regulating HSPA9 ubiquitination and degradation. These results suggest that KEAP1 could serve as a potential biomarker and therapeutic target in the treatment of breast cancer.

Condyloma acuminatum (CA) is a sexually transmitted disease characterized by proliferative lesions in the anogenital region, and its pathogenesis is mainly related to HPV infection and disturbed immune responses. Studies have shown that the incidence of CA is higher in women than in men, and the incidence of CA during pregnancy is higher than that during non-pregnancy. Sex hormones may be related to the occurrence and development of CA. This article reviews the association of estrogen and progesterone with CA, and discusses the possible link of estrogen and CA to the balance of Th1/Th2 and Th17/Treg in cellular immunity during HPV infection, in addition to exploration of the role of estrogen and progesterone in the pathogenesis and recurrence of CA, in order to provide new ideas for the clinical diagnosis and treatment of CA.

Abstract Despite the dominance of lead-based piezoelectric materials with ultrahigh electric-field-induced strain in actuating applications, seeking eco-friendly substitutes with an equivalent performance remains an urgent demand. Here, a strategy of regulating the irreversible non-180° domain via phase engineering is introduced to optimize the available strain (the difference between the maximum strain and the remnant strain in a unipolar strain curve) in the lead-free potassium–sodium niobate-based piezoelectric ceramics. In situ synchrotron X-ray diffraction and Rayleigh analysis reveal the contribution of the non-180° domain to available strain in the tetragonal–orthorhombic–rhombohedral phase boundary. The reducing orthorhombic phase and increasing rhombohedral/tetragonal phase accompanied by the reduced irreversible non-180° domain are obtained with increasing doping of Sb5+, resulting in an enlarged available strain due to the significantly lowered remnant strain. This optimization is mainly attributed to the reduced irreversible non-180° domain wall motion and the increased lattice distortion, which are beneficial to decrease extrinsic contribution and enhance intrinsic contribution. The mesoscopic structure of miniaturized nanosized domain with facilitated domain switching also contributes to the enhancement of available strain due to the improved random field and decreased energy barrier. The study will shed light on the design of lead-free high-performance piezoelectric ceramics for actuator applications.

Background: Information on the association between physical activity (PA) and the risk of chronic kidney disease (CKD) is limited. We aimed to explore the associations of total, domain-specific, and intensity-specific PA with CKD and its subtypes in China. Methods: The study included 475,376 adults from the China Kadoorie Biobank aged 30–79 years during 2004–2008 at baseline. An interviewer-administered questionnaire was used to collect the information about PA, which was quantified as metabolic equivalent of task hours per day (MET-h/day) and categorized into 4 groups based on quartiles. Cox regression was used to analyze the association between PA and CKD risk. Results: During a median follow-up of 12.1 years, 5415 incident CKD cases were documented, including 1159 incident diabetic kidney disease (DKD) cases and 362 incident hypertensive nephropathy (HTN) cases. Total PA was inversely associated with CKD risk, with an adjusted hazard ratio (HR, 95% confidence interval (95%CI)) of 0.83 (0.75–0.92) for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile. Similar results were observed for risk of DKD and HTN, and the corresponding HRs (95%CIs) were 0.75 (0.58–0.97) for DKD risk and 0.56 (0.37–0.85) for HTN risk. Increased nonoccupational PA, low-intensity PA, and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD, with HRs (95%CIs) of 0.80 (0.73–0.88), 0.85 (0.77–0.94), and 0.85 (0.76–0.95) in the highest quartile, respectively. Conclusion: PA, including nonoccupational PA, low-intensity PA, and moderate-to-vigorous-intensity PA, was inversely associated with the risk of CKD, including DKD, HTN, and other CKD, and such associations were dose dependent.

Abstract Background Acute ischemic stroke is a common neurological disease with a significant financial burden but lacks effective drugs. Hypoxia-inducible factor (HIF) and prolyl hydroxylases (PHDs) participate in the pathophysiological process of ischemia. However, whether FG4592, the first clinically approved PHDs inhibitor, can alleviate ischemic brain injury remains unclear. Methods The infarct volumes and behaviour tests were first analyzed in mice after ischemic stroke with systemic administration of FG4592. The knockdown of HIF-1α and pretreatments of HIF-1/2α inhibitors were then used to verify whether the neuroprotection of FG4592 is HIF-dependent. The targets predicting and molecular docking methods were applied to find other targets of FG4592. Molecular, cell biological and gene knockdown methods were finally conducted to explore the potential neuroprotective mechanisms of FG4592. Results We found that the systemic administration of FG4592 decreased infarct volume and improved neurological defects of mice after transient or permanent ischemia. Meanwhile, FG4592 also activated autophagy and inhibited apoptosis in peri-infarct tissue of mice brains. However, in vitro and in vivo results suggested that the neuroprotection of FG4592 was not classical HIF-dependent. 2-oxoglutarate and iron-dependent oxygenase domain-containing protein 1 (OGFOD1) was found to be a novel target of FG4592 and regulated the Pro-62 hydroxylation in the small ribosomal protein s23 (Rps23) with the help of target predicting and molecular docking methods. Subsequently, the knockdown of OGFOD1 protected the cell against ischemia/reperfusion injury and activated unfolded protein response (UPR) and autophagy. Moreover, FG4592 was also found to activate UPR and autophagic flux in HIF-1α independent manner. Blocking UPR attenuated the neuroprotection, pro-autophagy effect and anti-apoptosis ability of FG4592. Conclusion This study demonstrated that FG4592 could be a candidate drug for treating ischemic stroke. The neuroprotection of FG4592 might be mediated by inhibiting alternative target OGFOD1, which activated the UPR and autophagy and inhibited apoptosis after ischemic injury. The inhibition of OGFOD1 is a novel therapy for ischemic stroke.

Abstract Background This study assessed the effect of standardized efficacy markers on prognosis in patients with newly diagnosed multiple myeloma (MM) during the induction phase of treatment with bortezomib, cyclophosphamide, and dexamethasone (BCD). Methods We retrospectively analyzed clinical data in 197 newly diagnosed MM patients treated with BCD as front‐line regimen at Peking Union Medical College Hospital from January 1, 2013 to December 31, 2018. Results There were 107 patients with International Staging System (ISS) III and 51 with paraprotein of light chain. Of these, 77 completed nine cycles of the BCD regimen. As the number of treatment cycles increased, the proportions of serum and urine immunofixation electrophoresis (IFE) tests elevated from 40.39% to 62.22% and 16.75% to 37.78%, respectively. More than 90% of intact immunoglobulin chain MM patients were evaluated for blood M protein per cycle, but that of urinary M protein was less than 60%. The detection rate of urinary M protein in light chain MM was more than 70% per cycle. Patients with a very good partial response (VGPR) had longer progression‐free survival (PFS) than those with uncertain VGPR (32 vs. 26 months, p = 0.0336). Of the 141 patients who completed at least four cycles without undergoing autologous hematopoietic stem cell transplantation, those who were regularly assessed at every other cycle showed more favorable PFS than those who visited irregularly (27 vs. 22 months, p = 0.059). Conclusion Urinary M protein detection rate is significantly lower than that in serum, leading to an overestimation of efficacy, premature reduction of treatment intensity, and shortened PFS. Precise response assessments are critical to treatment decisions and clinical diagnoses.

Abstract Abnormal lipid metabolism promotes hepatocellular carcinoma (HCC) progression, which engenders therapeutic difficulties owing to unclear mechanisms of the phenomenon. We precisely described a special steatotic HCC subtype with HBV-related cirrhosis and probed its drivers. Hematoxylin-eosin (HE) staining of 245 HCC samples revealed a special HCC subtype (41 cases) characterized by HBV-related cirrhosis and intratumoral steatosis without fatty liver background, defined as steatotic HCC with HBV-related cirrhosis (SBC-HCC). SBC-HCC exhibits a larger tumor volume and worse prognosis than non-SBC-HCC. Screening for driver genes promoting fatty acid (FA) biosynthesis in the Gao’s HBV-related cirrhosis HCC cases and GSE121248’ HBV-related HCC cases revealed that high expression of SOCS5 predicts increased FA synthesis and that SOCS5 is upregulated in SBC-HCC. Through proteomics, metabolomics, and both in vivo and in vitro experiments, we demonstrated that SOCS5 induces lipid accumulation to promote HCC metastasis. Mechanistically, through co-IP and GST-pulldown experiments, we found that the SOCS5-SH2 domain, especially the amino acids Y413 and D443, act as critical binding sites for the RBMX-RRM domain. SOCS5-RBMX costimulates the promoter of SREBP1, inducing de novo lipogenesis, while mutations in the SH2 domain, Y413, and D443 reverse this effect. These findings precisely identified SBC-HCC as a special steatotic HCC subtype and highlighted a new mechanism by which SOCS5 promotes SBC-HCC metastasis.

ObjectiveAiming at the area coverage problem of multiple autonomous surface vehicles (ASVs), this paper investigates a coverage path planning (CPP) strategy based on an electronic chart display and information system (ECDIS). MethodFirst, according to the information of sea, land and water depth from ECDIS, an environmental model for the area coverage of ASVs is established based on the grid method. Second, an area division method based on the roulette wheel selection method is proposed to solve the problem of irregular area division in divided areas based on the robots' initial position method, and achieve the reasonable area division of ASVs in the grid map. Finally, a template-based area coverage path planning method is proposed to solve the problem of generating too many turns in paths generated by the spanning tree coverage agorithm.ResultsA human-machine interactive simulation platform for ASVs based on ECDIS is established to verify the effectiveness of the proposed area coverage path planning method based on the roulette wheel method and template method in optimizing the number of turns in the planning path. ConclusionThe proposed area coverage path planning method for ASVs based on ECDIS can be used to achieve coverage path planning in target mission areas at sea.

The monocular camera can both perceive the surroundings and measure the motion states of an unmanned surface vehicle (USV) by imitating the functions of human vision, such that the monocular visual servo is an important means of improving the navigation perception and control autonomy of USVs. Starting from basic principles, the classification of visual servo methods, perspective projection model of the camera and mathematical model of the USV are briefly described so as to provide a fundamental framework for the literature review. According to task complexity, the research progress and challenges of monocular visual servo-based USV control are then summarized in four typical scenarios, namely course control, stabilization control, trajectory tracking control and swarm control. Finally, the future trends of the monocular visual servo-based autonomous control of USVs are systematically summarized.

In order to explore the influence of various process parameters in the pressing stage of magnetic abrasive grain bodies on their forming quality, optimize the sintering preparation parameters of magnetic abrasive grains, and prepare high-quality magnetic abrasive grains, the dispersion element model of dry pressing forming of magnetic abrasive grains was established with iron-based alumina magnetic abrasive grains as the research object. By changing the pressing force, pressing mode, friction coefficient, die height-diameter ratio and other process parameters, the influence of each process parameter on the forming quality of the magnetic abrasive grain bodies was explored, and the optimization of process parameters in the pressing process was realized. The results show that the larger the pressing force, the smaller the porosity of the green body. However, if the pressing force is too large, cracks will appear on the outer surface of the green body, affecting the integrity of the surface morphology of the green body. Therefore, a pressing force of 75 to 125 MPa should be selected. The density of the green body obtained by two-way pressing is more uniform, and the mechanical properties are better. The higher the height-diameter ratio of the mold, the higher the porosity of the green body, and the smaller the axial stress of the green body. The smaller the friction coefficient between particles and between the side wall and particles, the smaller the porosity, the better the density and the better the homogeneity of the green body. When adding an appropriate amount of lubricant in the mixing stage of the magnetic abrasive particles, the friction coefficient between the magnetic abrasive particles and between the particles and the side wall of the mold can be appropriately reduced, thereby improving the quality of the abrasive body.

Abstract Background Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective and sometimes cause serious side effects. There is an urgent need for the development of more effective drugs with relatively low toxicity. Methods The effect of tylosin on the viability of host cells was measured using CCK8 assays. To assess the inhibition of tylosin on T. gondii proliferation, a real-time PCR targeting the B1 gene was developed for T. gondii detection and quantification. Total RNA was extracted from parasites treated with tylosin and then subjected to transcriptome analysis by RNA sequencing (RNA-seq). Finally, murine infection models of toxoplasmosis were used to evaluate the protective efficacy of tylosin against T. gondii virulent RH strain or avirulent ME49 strain. Results We found that tylosin displayed low host toxicity, and its 50% inhibitory concentration was 175.3 μM. Tylsoin also inhibited intracellular T. gondii tachyzoite proliferation, with a 50% effective concentration of 9.759 μM. Transcriptome analysis showed that tylosin remarkably perturbed the gene expression of T. gondii, and genes involved in “ribosome biogenesis (GO:0042254)” and “ribosome (GO:0005840)” were significantly dys-regulated. In a murine model, tylosin treatment alone (100 mg/kg, i.p.) or in combination with sulfadiazine sodium (200 mg/kg, i.g.) significantly prolonged the survival time and raised the survival rate of animals infected with T. gondii virulent RH or avirulent ME49 strain. Meanwhile, treatment with tylosin significantly decreased the parasite burdens in multiple organs and decreased the spleen index of mice with acute toxoplasmosis. Conclusions Our findings suggest that tylosin exhibited potency against T. gondii both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis. Graphical Abstract

Abstract Aim of this comparative cross-sectional study was to evaluate the effect of anterior teeth retraction and related hard and soft tissue change under physiologic anchorage control in patients with chief complain of protrusive teeth. 68 Class I or II orthodontic patients undergoing four-premolar extraction and requiring maximum or medium anchorage were included. Patients were treated with physiologic anchorage control technique (PASS group, n = 34, 18.6 ± 7.7 years, 10 male and 24 female) and self-ligation technique (Damon group, n = 34, 17.5 ± 5.4 years, 13 male and 21 female), respectively. TADs were used for anchorage reinforcement in Damon group. Pre- and post-treatment cephalograms were collected. Twenty-six skeletal, dental and soft tissue items were measured and analyzed using a blinded method. T test and paired rank-sum test were used for statistical analysis. The baseline characteristics were similar between groups (P > 0.05). After treatment, inter-group comparison showed statistically significant differences in the decrease of skeletal measurements ∠ANB (− 0.73 ± 1.05° in PASS group and − 0.25 ± 0.84° in the Damon group), Wits value (− 2.56 ± 2.29 mm in PASS group and − 0.47 ± 2.15 mm in Damon group) and soft tissue measurement UL-E (− 2.75 ± 1.36 mm in PASS group and − 2.03 ± 1.30 mm in Damon group) and the increase of FCA and Z angle, which was 2.03 ± 2.12°and 9.52 ± 4.78°in PASS group and 0.97 ± 2.12°and 6.96 ± 4.43°in Damon group, respectively (P

Synthetic Aperture Radar (SAR) finds widespread applications in environmental monitoring, disaster management, ship surveillance, and military intelligence. However, existing target detection methods are ineffective in SAR scenes due to the intricate background environments, small target displays, and irregular appearances. To address these challenges, this thesis introduces a target detection model named YOLOv8-FDF, tailored for SAR scenes based on the YOLOv8 architecture. The model effectively incorporates the FADC module to distinguish targets from complex backgrounds and integrates a deformable feature adaptive mechanism to focus on irregular targets. Additionally, this thesis devised a specialized detection head designed to identify small targets in SAR-wide scenes, thereby improving the effectiveness of detecting such targets. The proposed YOLOv8-FDF model is evaluated on the HRSID dataset. Experiment results show a 3.6% improvement in Map75 on both the training and test sets. Furthermore, under the COCO standard, the model achieves improvements of 4.1%, 2.9%, and 5.5% on AP, AP50, and AP75, along with 6.8%, 1.2%, and 1.2% improvements on small, medium, and large-sized ship detection. An accuracy enhancement of 6.8%, 1.0%, and 14.9% is achieved. These experimental findings validate the efficacy of the proposed YOLOv8-FDF model in SAR scenarios.

Traditional pattern mining algorithms are based on tree and linked list structures. However, they often only consider a single factor of frequency or utility and have to deal with exponential search spaces as well as generate numerous candidates. Thus, we propose a frequent closed high-utility itemset mining (FCHUIM) algorithm based on Leiden community detection and a compact genetic algorithm (LcGA). This algorithm first employs Leiden community detection to decompose a dataset into several highly related transaction communities and then uses an approximate or exact strategy to mine frequent itemsets. Subsequently, it checks for closures in the mined frequent itemsets and finally employs the compact genetic algorithm to efficiently mine high-utility patterns from the frequent closed itemsets. Experimental results on four real datasets, namely Retail, Chainstore, Chess, Accidents,among which the datatype of the former two is Sparse and that of the latter two is Dense, demonstrate that compared with modified traditional closed high-utility mining algorithms, including CHUI-Miner-S, CLS-Miner-S and the most advanced algorithms for mining frequent closed high-utility mining algorithms called FCHUIM, the average runtime of LcGA-FCHUIM is lower by 40.5% than the optimal contrastive algorithm. Moreover, LcGA-FCHUIM can mine an average of 96% of frequent closed high-utility itemsets, making it an effective algorithm for frequent closed high-utility itemset mining and suitable for most scenarios.

High-resolution multi-color printing relies upon pixelated optical nanostructures, which is crucial to promote color display by producing nonbleaching colors, yet requires simplicity in fabrication and dynamic switching. Antimony trisulfide (Sb2S3) is a newly rising chalcogenide material that possesses prompt and significant transition of its optical characteristics in the visible region between amorphous and crystalline phases, which holds the key to color-varying devices. Herein, we proposed a dynamically switchable color printing method using Sb2S3-based stepwise pixelated Fabry-Pérot (FP) cavities with various cavity lengths. The device was fabricated by employing a direct laser patterning that is a less time-consuming, more approachable, and low-cost technique. As switching the state of Sb2S3 between amorphous and crystalline, the multi-color of stepwise pixelated FP cavities can be actively changed. The color variation is due to the profound change in the refractive index of Sb2S3 over the visible spectrum during its phase transition. Moreover, we directly fabricated sub-50 nm nano-grating on ultrathin Sb2S3 laminate via microsphere 800-nm femtosecond laser irradiation in far field. The minimum feature size can be further decreased down to ~45 nm (λ/17) by varying the thickness of Sb2S3 film. Ultrafast switchable Sb2S3 photonic devices can take one step toward the next generation of inkless erasable papers or displays and enable information encryption, camouflaging surfaces, anticounterfeiting, etc. Importantly, our work explores the prospects of rapid and rewritable fabrication of periodic structures with nano-scale resolution and can serve as a guideline for further development of chalcogenide-based photonics components.

Abstract Purpose Benign skin lesions in zygomatic-infraorbital regions severely influence pediatric patients’ appearance as well as mental health. Treatments are difficult for the high requirements of patients’ guardians in both function and aesthetics. The present study aims to introduce a surgical method, Expanded Multi-Lobe Cervicofacial Flap, which combines the advantages of the classical cervicofacial advancement rotation flap and the tissue expansion technique. Methods A total of 21 pediatric patients were enrolled. The treatment process included 2 stages: implantation of the skin tissue expander and flap transfer. The excessive skin created by tissue expansion extended the coverage area of the multi-lobe flap. Results In this retrospective study, follow-up periods were all more than 12 months (20.8 ± 6.7). In the last follow-ups, the flaps were all in good condition, and No facial organ displacement was observed. The patients’ guardians were satisfied with the outcomes. Conclusions Using the expanded multi-lobe cervicofacial flap for the zygomatic-infraorbital benign skin lesion repair is effective, and this method is especially applicable to the pediatric population.

Abstract Background Orthodontic tooth movement (OTM) in a region containing alveolar bone defects with insufficient height and width is hard to achieve. Bovine bone mineral (Bio-Oss) is available to restore the alveolar defect; however, whether the region augmented with a bovine bone mineral graft (BG) is feasible for OTM, and the mechanisms by which macrophages remodel the BG material, is uncertain under the mechanical force induced by OTM. Material and methods Rats were divided into three groups: OTM (O), OTM + BG material (O + B), and Control (C). First molars were extracted to create bone defects in the O and O + B groups with bovine bone mineral grafting in the latter. Second molars received OTM towards the bone defects in both groups. After 28 days, maxillae were analyzed using microfocus-computed tomography (μCT) and scanning-electron-microscopy (SEM); and macrophages (M1/M2) were stained using immunofluorescence. THP-1 cell-induced macrophages were cultured under mechanical force (F), BG material (B), or both (F + B). Phagocytosis-related signaling molecules (cAMP/PKA/RAC1) were analyzed, and conditioned media was analyzed for MMP-9 and cytokines (IL-1β, IL-4). Results Our study demonstrated that alveolar defects grafted with BG materials are feasible for OTM, with significantly increased OTM distance, bone volume, and trabecular thickness in this region. SEM observation revealed that the grafts served as a scaffold for cells to migrate and remodel the BG materials in the defect during OTM. Moreover, the population of M2 macrophages increased markedly both in vivo and in cell culture, with enhanced phagocytosis via the cAMP/PKA/RAC1 pathway in response to mechanical force in combination with BG particles. By contrast, M1 macrophage populations were decreased under the same circumstances. In addition, M2 macrophage polarization was also indicated by elevated IL-4 levels, reduced IL-1β levels, and less active MMP-9 in cell culture. Conclusion This study explored the mechanisms of mechanical force-induced alveolar bone remodeling with bovine bone mineral grafts during OTM. The results might provide molecular insights into the related clinical problems of whether we can move teeth into the grafted materials; and how these materials become biologically remodeled and degraded under mechanical force.

As an exogenous pollutant, the microplastics accumulated in soil could alter microbial activity. The use of plastic mulch in greenhouse vegetable planting not only enhances vegetable yield and quality, but also leads to the formation and accumulation of microplastics in the soil over time. It is essential to determine the characteristics of microplastics and microorganisms in soils with varying years of planting is crucial for ensuring vegetable quality and quantity. Therefore, this study investigated the abundance and particle size of microplastics, the concentration of phthalates (PAEs), and the dynamics of soil microbial activity in greenhouse soils with different planting years (5, 10, 15, 20, 25, and 30 years). Results showed that microplastics increased in abundance, particle size, and PAEs concentration as planting years progressed. Specifically, the abundance of microplastics rose from 70.0 ± 8.7 to 224.0 ± 10.4 items/kg, with the proportion of microplastics sized 0–2 mm increasing from 14.02 to 69.11 %, and the total PAEs concentration in the soil escalating from 0.31 to 1.89 mg/kg. Additionally, Bacteroidetes and Actinobacteria levels increased, correlating with organic matter degradation. Metabolic pathway linked to degradation were enriched according to KEGG analysis. Correlation analysis revealed that microplastics notably decreased soil pH, creating an acidic environment that boosted urease activity and the relative abundance of Nitrospirae. This study sheds light on the accumulation characteristics of microplastics and their impact on soil microbial activity following prolonged planting.