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Abstract With a small short‐circuit ratio (SCR), the grid‐connected inverter is prone to low‐frequency oscillation instability due to the dynamic interaction between the phase‐locked loop (PLL) and the weak grid. To this end, an active‐disturbance‐rejection‐controller‐based symmetric PLL (ADRC‐based SyPLL) is proposed in this article to simplify the system modelling and improve the low‐frequency stability of the inverter system. Specifically, the ADRC technique is applied to phase‐regulated feedback control of a PLL, where an extended state observer (ESO) is used to estimate the lumped disturbance of the controlled system. A control loop symmetric to the q‐axis is further designed on the d‐axis of the PLL, and the d‐axis information is then added at the reference generation side to eliminate the coupled frequency term in the small‐signal model. A simple and accurate single‐input single‐output (SISO) model is thus obtained. The impedance stability analysis for grid‐connected inverters shows that the proposed ADRC‐based SyPLL can significantly improve the low‐frequency stability margin of the system compared with the conventional PI‐regulated PLL. Finally, the experimental results validate the effectiveness and superiority of the proposed method.

Abstract The thermal Hall effect recently provided intriguing probes to the ground state of exotic quantum matters. These observations of transverse thermal Hall signals lead to the debate on the fermionic versus bosonic origins of these phenomena. The recent report of quantum oscillations (QOs) in Kitaev spin liquid points to a possible resolution. The Landau level quantization would most likely capture only the fermionic thermal transport effect. However, the QOs in the thermal Hall effect are generally hard to detect. In this work, we report the observation of a large oscillatory thermal Hall effect of correlated Kagome metals. We detect a 180-degree phase change of the oscillation and demonstrate the phase flip as an essential feature for QOs in the thermal transport properties. More importantly, the QOs in the thermal Hall channel are more profound than those in the electrical Hall channel, which strongly violates the Wiedemann–Franz (WF) law for QOs. This result presents the oscillatory thermal Hall effect as a powerful probe to the correlated quantum materials.

Abstract Objectives Lung cancer is one of the most common malignant tumors threatening human life and health. At present, low‐dose computed tomography (LDCT) screening for the high‐risk population to achieve early diagnosis and treatment of lung cancer has become the first choice recommended by many authoritative international medical organizations. To further optimize the lung cancer screening method, we conducted a real‐world study of LDCT lung cancer screening in a large sample of a healthy physical examination population, comparing differences in lung nodules and lung cancer detection between thin and thick‐slice LDCT scanning. Methods A total of 29 296 subjects who underwent low‐dose thick‐slice CT scanning (5 mm thickness) from January 2015 to December 2015 and 28 058 subjects who underwent low‐dose thin‐slice CT scanning (1 mm thickness) from January 2018 to December 2018 in West China Hospital were included. The positive detection rate, detection rate of lung cancer, pathological stage of lung cancer, and mortality rate of lung cancer were analyzed and compared between the two groups. Results The positive rate of LDCT screening in the thin‐slice scanning group was significantly higher than that in the thick‐slice scanning group (20.1% vs. 14.4%, p

Objectives The etiology of flatfoot and cavus foot is multicausal and controversial. So far, no literature reports the relationship between the sagittal morphology of subtalar joint and the alignment of foot. The purpose of this study was to explore whether the subtalar alignment would influence the configuration of foot. Methods From January 2017 to January 2020, we included 109 feet in the flatfoot group, 95 feet in the cavus group, and 104 feet in the control group in this retrospective comparative study. The Gissane angle and calcaneal posterior articular surface inclination angle represented the sagittal morphology of the subtalar joint. Meary's angle, calcaneal pitch angle, and talar pitch angle reflected the alignment of foot. They were measured in the weightbearing foot X‐rays. The angles in different groups were compared via Mann–Whitney U test. We calculated the correlation between the sagittal alignment of subtalar joint and the alignment of foot using Spearman's correlation analysis. Interobserver and intraobserver reliability were calculated. Results The Gissane angle, calcaneal posterior articular surface inclination angle, Meary's angle, talar pitch angle, and calcaneal pitch angle were significantly different in the three groups. The Gissane angle had an excellent correlation with the Meary's angle (r = 0.850, p

Abstract Background Skin barrier alterations play a crucial function in melasma development. Past researches have demonstrated variations in lipid content between the epidermis of melasma lesions and normal tissues, along with the varied expression of lipid-related genes in melasma. This study aimed to analyze the lipidome profiles of skin surface lipids (SSL) in patients with melasma before and after treatment to understand associated abnormalities. Methods Melasma was treated with tranexamic acid orally and hydroquinone cream topically. Disease was assessed using the Melasma Area and Severity Index (MASI), and the impact to life was evaluated with Melasma Quality of Life (MELASQoL) score. Epidermal melanin particles were observed using reflection confocal microscopy (RCM), whereas epidermal pigment and blood vessel morphology were observed using dermoscopy, and SSL samples were collected. Specific information regarding alterations in lipid composition was obtained through multivariate analysis of the liquid chromatography-mass spectrometry data. Results After treatment, patients with melasma exhibited decreased MASI and MELASQoL scores (P

Atherosclerosis is featured as chronic low-grade inflammation in the arteries, which leads to the formation of plaques rich in lipids. M2 macrophage-derived extracellular vesicles (M2EV) have significant potential for anti-atherosclerotic therapy. However, their therapeutic effectiveness has been hindered by their limited targeting capability in vivo. The objective of this study was to create the P-M2EV (platelet membrane-modified M2EV) using the membrane fusion technique in order to imitate the interaction between platelets and macrophages. P-M2EV exhibited excellent physicochemical properties, and microRNA (miRNA)-sequencing revealed that the extrusion process had no detrimental effects on miRNAs carried by the nanocarriers. Remarkably, miR-99a-5p was identified as the miRNA with the highest expression level, which targeted the mRNA of Homeobox A1 (HOXA1) and effectively suppressed the formation of foam cells in vitro. In an atherosclerotic low-density lipoprotein receptor-deficient (Ldlr−/−) mouse model, the intravenous injection of P-M2EV showed enhanced targeting and greater infiltration into atherosclerotic plaques compared to regular extracellular vesicles. Crucially, P-M2EV successfully suppressed the progression of atherosclerosis without causing systemic toxicity. The findings demonstrated a biomimetic platelet-mimic system that holds great promise for the treatment of atherosclerosis in clinical settings.

Abstract Accumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs (such as exosomes). The osteoinductive effect of MSC-apoVs is attributed to their diverse contents, especially enriched proteins or microRNAs (miRNAs). To optimize their osteoinduction activity, it is necessary to determine the unique cargo profiles of MSC-apoVs. We previously established the protein landscape and identified proteins specific to MSC-apoVs. However, the features and functions of miRNAs enriched in MSC-apoVs are unclear. In this study, we compared MSCs, MSC-apoVs, and MSC-exosomes from two types of MSC. We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes, which we classified as apoV-specific miRNAs. Among these seven specific miRNAs, hsa-miR-4485-3p was the most abundant and stable. Next, we explored its function in apoV-mediated osteoinduction. Unexpectedly, hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway. Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs. Like releasing the brake, we acquired more powerful osteoinductive apoVs. In summary, we identified the miRNA cargos, including miRNAs specific to MSC-apoVs, and generated tailored apoVs with high osteoinduction activity, which is promising in apoV-based therapies for bone regeneration.

Carbon-doped copper ferrite (C–CuFe2O4) was synthesized by a simple two-step hydrothermal method, which showed enhanced tetracycline hydrochloride (TCH) removal efficiency as compared to the pure CuFe2O4 in Fenton-like reaction. A removal efficiency of 94% was achieved with 0.2 g L−1 catalyst and 20 mmol L−1 H2O2 within 90 min. We demonstrated that 5% C–CuFe2O4 catalyst in the presence of H2O2 was significantly efficient for TCH degradation under the near-neutral pH (5–9) without buffer. Multiple techniques, including SEM, TEM, XRD, FTIR, Raman, XPS Mössbauer and so on, were conducted to investigate the structures, morphologies and electronic properties of as-prepared samples. The introduction of carbon can effectively accelerate electron transfer by cooperating with Cu and Fe to activate H2O2 to generate ·OH and ·O2−. Particularly, theoretical calculations display that the p, p, d orbital hybridization of C, O, Cu and Fe can form C–O–Cu and C–O–Fe bonds, and the electrons on carbon can transfer to metal Cu and Fe along the C–O–Fe and C–O–Cu channels, thus forming electron-rich reactive centers around Fe and Cu. This work provides lightful reference for the modification of spinel ferrites in Fenton-like application.

Background: Acute heart failure necessitates intensive care, and arterial catheterization is a commonly performed invasive procedure in the intensive care unit (ICU). We aimed to investigate the association between arterial catheterization and outcomes in acute heart failure patients without shock. Methods: We utilized MIMIC-IV database records for acute heart failure patients at Beth Israel Deaconess Medical Center from 2008 to 2019. Employing doubly robust estimation, we examined the relationship between arterial catheterization and outcomes, including 28-day, 90-day, in-hospital mortality, and ICU-free days within 28 days. Results: Of 6936 patients identified, 2078 met inclusion criteria; 347 underwent arterial catheterization during their ICU stay. We observed no significant difference in 28-day mortality (odds ratio [OR]: 0.61, 95 % confidence interval [CI]: 0.31–1.21, P = 0.155), though catheterization was associated with reduced in-hospital mortality (OR: 0.41, 95 % CI: 0.14–0.65, P = 0.02). No significant effects were observed on 90-day mortality or ICU-free days within 28 days. Conclusion: Our findings suggest that arterial catheterization is not associated with 28- and 90-day mortality rates in acute heart failure patients without shock but is linked to lower in-hospital mortality. Additional research and consensus are required to determine the appropriate utilization of arterial catheterization in patients.

This study introduces an Integrated Carbon Capture and Utilisation-Reverse Water Gas Shift (ICCU-RWGS) approach, a novel method for in situ CO2 adsorption and conversion, leveraging the synergistic effects of CaO within a NaCl-CaCl2 molten salt blend to enhance CO2 capture and conversion efficiency. Building upon this foundation, we optimize CaO concentration and operating temperature to maximize CO2 uptake and conversion performance. The research focuses on integrating CaO with a NaCl-CaCl2 molten salt blend (mass ratio 4:6) to improve CO2 sorption and conversion performance. Findings show significant enhancements in CO2 uptake and CO yield with the presence of molten salt compared to systems without it. The optimal operating temperature and CaO concentration are identified for maximum CO yield. Characterisation techniques like in-situ infrared spectroscopy, XRD, and SEM provide insights into the behavior of CaO in the molten salt, revealing the solubility of the partial carbonate formed from CO2 and CaO, dispersion of CaO particles, and their morphological characteristics. Overall, the study demonstrates the potential of CaO-molten salt integration in improving ICCU-RWGS process efficiency and contributes to the development of more effective and sustainable ICCU technologies.

The United States has emerged as a prominent actor in the international fight against transnational terrorism in the Sahel region of Africa since 2002, exerting significant political influence on regional affairs. Under the leadership of the United States, a coalition of Sahel countries has collaboratively established security programs, notably including the Trans-Saharan Counterterrorism Partnership (TSCTP). However, the U.S. counterterrorism strategy in the Sahel region has not only proven ineffective in containing the deterioration of regional security, but also has exacerbated the vulnerability to coups in recipient countries. The observed deterioration can be attributed to various driving factors, such as deviations in the willingness and ability to involve and the security traffic jam. We contend that the U.S.-Sahel counterterrorism partnership is fundamentally misaligned and plagued by a securitization problem. Firstly, a significant impediment to international cooperation lies in the United States’ pursuit of consolidating its dominant role in Sahel security affairs, which usually overlooks the pragmatic principle of ‘African solutions to African problems’. In the counterterrorism process, there is a misalignment between U.S. national interests and those of Sahel states. Furthermore, the United States’ extensive reliance on military strategies indicates a significant securitization of non-violent civil affairs in certain Sahel states, inadvertently creating an opportunity for genuine terrorist organizations to recruit members. In addition, U.S. interference in the internal affairs of Sahel states heightens the risk of coups, thereby undermining the legitimacy of U.S. leadership in the region. Currently, with both the withdrawal of the United Nations Stabilization Mission in Mali (MINUSMA) and France withdrawing their security forces from the Sahel region, there has a significant weakening effect on regional security capabilities. Therefore, it is imperative for the international community to collaborate with African nations and adopt more proactive measures to safeguard regional security and maintain order.

Summary: Erythropoietin-producing hepatoma (Eph) receptors, comprising the largest family of receptor tyrosine kinases (RTKs), exert profound influence on diverse biological processes and pathological conditions such as cancer. Interacting with their corresponding ligands, erythropoietin-producing hepatoma receptor interacting proteins (Ephrins), Eph receptors regulate crucial events like embryonic development, tissue boundary formation, and tumor cell survival. In addition to their well-established roles in embryonic development and cancers, emerging evidence highlights the pivotal contribution of the Ephrin/Eph family to cardiovascular physiology and pathology. Studies have elucidated their involvement in cardiovascular development, atherosclerosis, postnatal angiogenesis, and, more recently, cardiac fibrosis and calcification, suggesting a promising avenue for therapeutic interventions in cardiovascular diseases. There remains a need for a comprehensive synthesis of their collective impact in the cardiovascular context. By exploring the intricate interactions between Eph receptors, ephrins, and cardiovascular system, this review aims to provide a holistic understanding of their roles and therapeutic potential in cardiovascular health and diseases.

Reactive oxygen species play a vital role in tissue repair, and nonequilibrium of redox homeostasis around bone defect can compromise osteogenesis. However, insufficient antioxidant capacity and weak osteogenic performance remain major obstacles for bone scaffold materials. Herein, integrating the mussel-inspired polydopamine (PDA) coating and 3D printing technologies, we utilized the merits of both osteogenic bredigite and antioxidative fullerol to construct 3D-printed porous, biodegradable acid-buffering, reactive oxygen species (ROS) -scavenging and robust osteogenic bio-scaffold (denoted “FPBS”) for in situ bone defect restoration under oxidative stress microenvironment. Initially, fullerol nanoparticles were attached to the surface of the bredigite scaffold via covalently inter-crosslinking with PDA. Upon injury, extracellular ROS capturing triggered the oxidative degradation of PDA, releasing fullerol nanoparticles to enter into cells for further intracellular ROS scavenging. In vitro, FPBS had good biocompatibility and excellent antioxidative capability. Furthermore, FPBS promoted the osteogenesis of stem cells with significant elevation of osteogenic markers. Finally, in vivo implantation of FPBS remarkably enhanced new bone formation in a rat critical calvarial defect model. Overall, with amelioration of the ROS microenvironment of injured tissue and enhancement of osteogenic differentiation of stem cells simultaneously, FPBS may hold great potential towards bone defect repair.

The hydrothermal performance of the microchannel heat sinks with different pin fins (PF-MCHS) is studied experimentally and numerically. Five pin fins, namely rectangular pin fin (RPF), backward triangular pin fin (BTPF), forward triangular pin fin (FTPF), diamond pin fin (DPF) and ellipsoidal pin fin (EPR) are integrated in the microchannel for enhancing heat transfer. The results show that the PF-MCHSs possess 51.8–94.8 % higher average Nusselt number than the conventional microchannel (CMC) without pin fins, which indicates that these pin fins all can cause significant heat enhancement in the microchannels. Among all finned microchannels, the MC- RPF and MC-BTPF can offer the larger Nusselt number than the other microchannels. In addition to the improved thermal performance, the pin fins also result in the larger apparent friction factor. Furthermore, taking the MC-RPF and MC-BTPF as examples, three non-dimensional parameters α = P/L, β = wp/hc and γ = lp/hc are proposed for optimizing the global characteristics of microchannels. The rise of Nussle number and apparent friction factor is often accompanied by a decrease in α, or an increase in β and γ.

In bone tissue engineering, polycaprolactone (PCL) is a promising material with good biocompatibility, but its poor degradation rate, mechanical strength, and osteogenic properties limit its application. In this study, we developed an Mg-1Ca/polycaprolactone (Mg-1Ca/PCL) composite scaffolds to overcome these limitations. We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5, 10, and 20 wt%. Porous scaffolds with controlled macro- and microstructure were printed using the fused deposition modeling method. We explored the mechanical strength, biocompatibility, osteogenesis performance, and molecular mechanism of the Mg-1Ca/PCL composites. The 5 and 10 wt% Mg-1Ca/PCL composites were found to have good biocompatibility. Moreover, they promoted the mechanical strength, proliferation, adhesion, and osteogenic differentiation of human bone marrow stem cells (hBMSCs) of pure PCL. In vitro degradation experiments revealed that the composite material stably released Mg2+ ions for a long period; it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth. Microcomputed tomography and histological analysis showed that both 5 and 10 wt% Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects. Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect. Therefore, Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application. Statement of significance: Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects. However, there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds. This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities. Furthermore, the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold. The obtained porous scaffolds can significantly promote the regeneration of bone defects.

Abstract Background The objective of the current study was to investigate the correlation between trajectories of maternal perinatal depression (PND) spanning from early pregnancy to one year postpartum and developmental delays observed in one-year-old children. Methods The dataset under examination encompassed 880 women who took part in a mother-child birth study conducted in China. Latent class growth analysis (LCGA) was employed to identify patterns in Edinburgh Postnatal Depression Scale (EPDS) scores of women, spanning from early pregnancy to one year postpartum. To assess the neurodevelopment of one-year-old children, a Chinese version of the Bayley Scale of Infant Development (BSID-CR) was employed. Logistic regression was employed to explore the association between PND trajectories and developmental delays in children, with appropriate covariate adjustments. Results The trajectories of maternal PND identified in this study included a minimal-stable symptom group (n = 155), low-stable symptom group (n = 411), mild-stable symptom group (n = 251), and moderate-stable symptom group (n = 63). Logistic regression analysis revealed that mothers falling into the moderate-stable symptom group exhibited a notably heightened risk of having a child with psychomotor developmental delays at the age of one year. Conclusions The findings drawn from a representative sample in China provide compelling empirical evidence that bolsters the association between maternal PND and the probability of psychomotor developmental delays in children. It is imperative to develop tailored intervention strategies and meticulously design mother-infant interactive intervention programs for women with PND.

Abstract Background Inflammatory diseases may occur within the crypt beside the preputial frenulum in men. This study was performed to gain an understanding of the etiology, clinical manifestations, and management methods of cryptitis beside the preputial frenulum in men. Results Thirteen patients treated for cryptitis beside the preputial frenulum served as the observation group, and 40 healthy individuals served as the control group. The patients’ clinical manifestation was the presence of a yellowish oily substance embedded in the crypt. Wiping off the substance revealed a conical blind cavity-like structure with an opening diameter of 1 to 5 mm (2.8 ± 1.3 mm) and depth of 1 to 4 mm (2.5 ± 1.1 mm). No blind cavity-like structures in the crypt were found in the control group. The shortest distance between the opening edges of the bilateral crypts in the observation and control groups was 6 to 14 mm (10.3 ± 2.4 mm) and 2 to 10 mm (3.9 ± 1.9 mm), respectively, with a statistically significant difference. Examination for pathogens in the secretions from skin lesions showed that the three most common pathogens were Candida albicans, Staphylococcus aureus, and Escherichia coli. All patients recovered after antibiotic treatment. Conclusions A blind cavity-like structure in the crypt may be related to excessive width of the preputial frenulum. Cryptitis may be a secondary infection caused by smegma trapped in the blind cavity-like structure. Maintaining cleanliness in the frenulum area may help to prevent the occurrence of cryptitis. Antibiotic treatment is effective.

The preparation of carbon nanotubes (CNTs) from plastics is of great significance for realizing high value utilization of waste and reducing carbon emission. Here, several kinds of real waste plastics were introduced into catalytic pyrolysis, and the process was also optimized. The results showed that the presence of impurities (e.g., adhesive labels) reduced the initial activation energy of the pyrolysis reaction, and the pyrolysis process was extended and could be divided into two stages. During the catalytic process, impurities play a toxic role on the catalyst at higher temperatures and result in the agglomeration of catalyst particles and a decrease in catalytic activity. Less than 10 wt.% carbon fibers were collected from milk cup waste. However, after experimental optimization, the influence of the impurity component was greatly reduced. The toxic effect of organic impurity volatiles on a catalyst was avoided by employing a segmented catalytic pyrolysis process, which led to an increase in solid carbon content of more than 20 % for express package waste. Simultaneously, more uniform and smoother CNTs can be found in the obtained solid carbon. The process of preparing carbon nanotubes with higher yield and better quality is feasible and has important application prospects in the utilization of waste plastics.

Non-typhoidal Salmonella infection is among the most frequent foodborne diseases threatening human health worldwide. The host circadian clock orchestrates daily rhythms to adapt to environmental changes, including coordinating immune function in response to potential infections. However, the molecular mechanisms underlying the interplay between the circadian clock and the immune system in modulating infection processes are incompletely understood. Here, we demonstrate that NLRP6, a novel nucleotide-oligomerization domain (NOD)-like receptor (NLR) family member highly expressed in the intestine, is closely associated with the differential day–night response to Salmonella infection. The core clock component REV-ERBα negatively regulates NLRP6 transcription, leading to the rhythmic expression of NLRP6 and the secretion of IL-18 in intestinal epithelial cells, playing a crucial role in mediating the differential day–night response to Salmonella infection. Activating REV-ERBα with agonist SR9009 in wild-type mice attenuated the severity of infection by decreasing the NLRP6 level in intestinal epithelial cells. Our findings provide new insights into the association between the host circadian clock and the immune response to enteric infections by revealing the regulation of Salmonella infection via the inhibitory effect of REV-ERBα on NLRP6 transcription. Targeting REV-ERBα to modulate NLRP6 activation may be a potential therapeutic strategy for bacterial infections.

Summary: Programmed cell death (PCD) is tightly orchestrated by molecularly defined executors and signaling pathways. NLRP6, a member of cytoplasmic pattern recognition receptors, has a multifaceted role in host resistance to bacterial infection. However, whether and how NLRP6 may contribute to regulate host PCD during Gram-negative bacterial infection remain to be illuminated. Here, we report that NLRP6 promotes RIP1 kinase-mediated necroptosis, a form of lytic PCD, in both an in vitro and in vivo model of Salmonella typhimurium infection. By downregulating TAK1-mediated p38MAPK/MK2 phosphorylation, NLRP6 decreased RIP1 phosphorylation at residue S321 and subsequently increased RIP1 kinase-dependent MLKL phosphorylation. Suppression of p38MAPK/MK2 cascade not only reduced the number of dead cells caused by NLRP6 but also decreased the systemic dissemination of S. typhimurium resulting from NLRP6. Taken together, our findings provide new insights into the role and regulatory mechanism of NLRP6-associated antimicrobial responses by revealing a function for NLRP6 in regulating necroptosis.

Abstract Rituximab has been incorporated into the standard treatment regimen for diffuse large B-cell lymphoma (DLBCL), and induces the death of tumor cells via complement-dependent cytotoxicity (CDC). Unfortunately, the resistance of DLBCL cells to Rituximab limits its clinical usefulness. It remains unclear whether the complement system is related to Rituximab resistance in DLBCL. A Rituximab-resistant DLBCL cell line (Farage/R) was generated under the stress of Rituximab. Constituent proteins of the complement system in wild-type Farage cells (Farage/S) and Farage/R cells were analyzed by qPCR, western blotting, and immunofluorescence. In vitro and in vivo knockdown and overexpression studies confirmed that the complement 1Q subcomponent A chain (C1qA) was a regulator of Rituximab resistance. Finally, the mechanism by which C1qA is regulated by m6A methylation was explored. The reader and writer were identified by pull-down studies and RIP-qPCR. Activity of the complement system in Farage/R cells was suppressed. C1qA expression was reduced in Farage/R cells due to post-transcriptional regulation. Furthermore, in vitro and in vivo results showed that C1qA knockdown in Farage/S cells decreased their sensitivity to Rituximab, and C1qA overexpression in Farage/R cells attenuated the Rituximab resistance of those cells. Moreover, METTL3 and YTHDF2 were proven to be the reader and writer for m6A methylation of C1qA, respectively. Knockdown of METTL3 or YTHDF2 in Farage/R cells up-regulated C1qA expression and reduced their resistance to Rituximab. In summary, the aberrant downregulation of C1qA was related to Rituximab resistance in DLBCL cells, and C1qA was found to be regulated by METTL3- and YTHDF2-mediated m6A methylation. Enhancing the response of the complement system via regulation of C1qA might be an effective strategy for inhibiting Rituximab resistance in DLBCL.

Abstract In the recently discovered kagome metal CsV3Sb5, an intriguing proposal invoking a doped Chern insulator state suggests the presence of small Chern Fermi pockets hosting spontaneous orbital-currents and large orbital magnetic moments. While the net thermodynamic magnetization is nearly insensitive to these moments, due to their antiferromagnetic alignment, their presence can be revealed by the Zeeman effect, which shifts electron energies in magnetic fields with a proportionality given by the effective g−factor. Here, we determine the g-factor using the spin-zero effect in magnetic quantum oscillations. A large g-factor enhancement is visible only in magnetic breakdown orbits between conventional and concentrated Berry curvature Fermi pockets that host large orbital moments. Such Berry-curvature-generated large orbital moments are almost always concealed by other effects. In this system, however, magnetic breakdown orbits due to the proximity to a conventional Fermi-surface section allow them to be visibly manifested in magnetic quantum oscillations. Our results provide a remarkable example of the interplay between electronic correlations and more conventional electronic bands in quantum materials.

To utilize wheat bran by-products in high value, wheat bran raw materials were pretreated with ultrafine grinding (for 0, 10, 20, and 30 min) and wheat bran polysaccharide was obtained by water extraction and alkali extraction. The effects of ultrafine grinding pretreatment on the physicochemical properties of wheat bran polysaccharides were analyzed based on yield, chemical composition (arabinoxylan, total sugar, protein, and ferulic acid), infrared spectrum, monosaccharide composition, potential, particle size, solubility, and microstructure. The results showed that the yield of alkali-extracted and water-extracted wheat bran polysaccharide increased from 6.6% and 1.34% to 15.03% and 6.28%, respectively. The content of arabxylan (AX) obtained by alkali extraction and water extraction increased from 53.13% and 33.32% to 73.35% and 37.52%, respectively. The particle size of alkali-extracted and water-extracted wheat bran polysaccharide decreased from 308.47 and 919.23 nm to 203.8 and 168.03 nm, respectively. The results from infrared spectroscopy and monosaccharide composition analysis showed that the ultrafine grinding pretreatment had little effect on the structure of the functional group of polysaccharide extracted from wheat bran by alkali and water extraction. However, the pretreatment could destroy the ordered structure of the wheat bran polysaccharide. The total content and proportion of arabinose and xylose, which were the main components of wheat bran polysaccharide, increased significantly after ultrafine grinding (P

Abstract Background Accurate prediction of response to neoadjuvant chemoradiotherapy (nCRT) is very important for treatment plan decision in locally advanced rectal cancer (LARC). The aim of this study was to investigate whether self-attention mechanism based multi-sequence fusion strategy applied to multiparametric magnetic resonance imaging (MRI) based deep learning or hand-crafted radiomics model construction can improve prediction of response to nCRT in LARC. Methods This retrospective analysis enrolled 422 consecutive patients with LARC who received nCRT before surgery at two hospitals. All patients underwent multiparametric MRI scans with three imaging sequences. Tumor regression grade (TRG) was used to assess the response of nCRT based on the resected specimen. Patients were separated into 2 groups: poor responders (TRG 2, 3) versus good responders (TRG 0, 1). A self-attention mechanism, namely channel attention, was applied to fuse the three sequence information for deep learning and radiomics models construction. For comparison, other two models without channel attention were also constructed. All models were developed in the same hospital and validated in the other hospital. Results The deep learning model with channel attention mechanism achieved area under the curves (AUCs) of 0.898 in the internal validation cohort and 0.873 in the external validation cohort, which was the best performed model in all cohorts. More importantly, both the deep learning and radiomics model that applied channel attention mechanism performed better than those without channel attention mechanism. Conclusions The self-attention mechanism based multi-sequence fusion strategy can improve prediction of response to nCRT in LARC.

Increasing oil production is crucial for multilayer co-production. When there are significant differences in the permeability of each layer, an interlayer contradiction arises that can impact the recovery efficiency. After a number of tests and the establishment of a mathematical model, the effects of permeability contrast on oil production for water flooding were revealed. In the meantime, the developed mathematical model was solved using the Buckley–Lever seepage equation. Ultimately, the accuracy of the established model was confirmed by comparing the simulated outcomes of the mathematical model with the experimental results. The findings indicate that when permeability contrast increases, the production ratio of the high-permeability layer will improve. This is primarily due to the low-permeability layer’s production contribution rate decreasing. The accuracy of the established model is ensured by an error of less than 5% between the results of the experiment and the simulation. When the permeability contrast is less than three, the low-permeability layer can be effectively used for three-layer commingled production. However, when the permeability contrast exceeds six, the production coefficient of the low-permeability layer will be less than 5%, which has a significant impact on the layer’s development.

Most visual simultaneous localization and mapping (SLAM) systems are based on the assumption of a static environment in autonomous vehicles. However, when dynamic objects, particularly vehicles, occupy a large portion of the image, the localization accuracy of the system decreases significantly. To mitigate this challenge, this paper unveils DOT-SLAM, a novel stereo visual SLAM system that integrates dynamic object tracking through graph optimization. By integrating dynamic object pose estimation into the SLAM system, the system can effectively utilize both foreground and background points for ego vehicle localization and obtain a static feature points map. To rectify the inaccuracies in depth estimation from stereo disparity directly on the foreground points of dynamic objects due to their self-similarity characteristics, a coarse-to-fine depth estimation method based on camera–road plane geometry is presented. This method uses rough depth to guide fine stereo matching, thereby obtaining the 3 dimensions (3D)spatial positions of feature points on dynamic objects. Subsequently, by establishing constraints on the dynamic object’s pose using the road plane and non-holonomic constraints (NHCs) of the vehicle, reducing the initial pose uncertainty of dynamic objects leads to more accurate dynamic object initialization. Finally, by considering foreground points, background points, the local road plane, the ego vehicle pose, and dynamic object poses as optimization nodes, through the establishment and joint optimization of a nonlinear model based on graph optimization, accurate six degrees of freedom (DoFs) pose estimations are obtained for both the ego vehicle and dynamic objects. Experimental validation on the KITTI-360 dataset demonstrates that DOT-SLAM effectively utilizes features from the background and dynamic objects in the environment, resulting in more accurate vehicle trajectory estimation and a static environment map. Results obtained from a real-world dataset test reinforce the effectiveness.

Cancer poses a significant public health challenge worldwide, and timely screening has the potential to mitigate cancer progression and reduce mortality rates. Currently, early identification of most tumors relies on imaging techniques and tissue biopsies. However, the use of low-cost, highly sensitive, non-invasive detection methods for early cancer screening has become more attractive. Extracellular Vesicles (EVs) released by all living cells contain distinctive biological components, such as nucleic acids, proteins, and lipids. These vesicles play crucial roles in the tumor microenvironment and intercellular communication during tumor progression, rendering liquid biopsy a particularly suitable method for diagnosis. Nevertheless, challenges related to purification methods and validation of efficacy currently hinder its widespread clinical implementation. These limitations underscore the importance of refining isolation techniques and conducting comprehensive investigations on EVs. This study seeks to evaluate the potential of liquid biopsy utilizing blood-derived EVs as a practical, cost-effective, and secure approach for early cancer detection.

BackgroundThe latest census data show that people over 60 years of age account for about 18.7% of the total population in China, and the aging of the population has become an irreversible trend in the 21st century. This study aimed to investigate the current status and factors influencing the care of the elderly in community day care centers in order to lay the foundation for the development of better services in community day care centers.MethodsThis study was a cross-sectional survey using convenience sampling in Nanjing, China. The survey instrument was the Day care and Elderly Care Service Needs Questionnaire, which included the Ability of Daily Living Assessment (ADL), the Xiao Shuiyuan Social Support Rating Scale (SSRS) and the Day care Elderly Care Service Needs Survey Form, and a general information survey.ResultsA total of 450 elderly people in day care centers were surveyed. The elderly had different levels of demand for day care services, especially regarding daily care. Correlation analyses indicated that age (r = 0.619), education level (r = 0.616), source of income (r = 0.582), caregiver (r = 0.557), satisfaction with care service (r = 0.603), and degree of ADL (r = 0.629) were correlated with the need for elderly day care services (all p

Abstract Background and purpose To explore the association of systemic inflammatory index (SIRI), systemic immune-inflammatory index (SII) and inflammatory prognosis index (IPI) with 90d outcomes in patients with acute ischemic stroke (AIS) after intravenous thrombolysis. Methods The patients who underwent intravenous thrombolysis were enrolled in the present study from September 2019 to December 2022. According to the relevant blood indexes obtained in 24 h after admission, the corresponding values of SIRI, SII and IPI were calculated. The correlation among SIRI, SII, IPI, and admission NIHSS scores was examined by Spearman correlation analysis. ROC curve analysis was conducted to determine the optimal cut-off value of SIRI, SII, IPI, and their corresponding sensitivity and specificity to evaluate their predictive value on admission for poor prognosis. To investigate whether high SIRI, SII, and IPI were independent predictors of poor outcomes within 90 days, variables with P-value

Intrauterine adhesion (IUA) is the fibrosis within the uterine cavity. It is the second most common cause of female infertility, significantly affecting women's physical and mental health. Current treatment strategies fail to provide a satisfactory therapeutic outcome for IUA patients, leaving an enormous challenge for reproductive science. A self-healing adhesive hydrogel with antioxidant properties will be highly helpful in IUA prevention. In this work, we prepare a series of self-healing hydrogels (P10G15, P10G20, and P10G25) with antioxidant and adhesive properties. Those hydrogels exhibit good self-healing properties and can adapt themselves to different structures. They possess good injectability and fit the shape of the human uterus. Moreover, the hydrogels exhibit good tissue adhesiveness, which is desirable for stable retention and therapeutic efficacy. The in vitro experiments using P10G20 show that the adhesive effectively scavenges ABTS+, DPPH, and hydroxyl radicals, rescuing cells from oxidative stress. In addition, P10G20 offers good hemocompatibility and in vitro and in vivo biocompatibility. Furthermore, P10G20 lowers down the in vivo oxidative stress and prevents IUA with less fibrotic tissue and better endometrial regeneration in the animal model. It can effectively downregulate fibrosis-related transforming growth factor beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF). Altogether, these adhesives may be a good alternative for the clinical treatment of intrauterine adhesion.

Facing the significant challenge of 3D object detection in complex weather conditions and road environments, existing algorithms based on single-frame point cloud data struggle to achieve desirable results. These methods typically focus on spatial relationships within a single frame, overlooking the semantic correlations and spatiotemporal continuity between consecutive frames. This leads to discontinuities and abrupt changes in the detection outcomes. To address this issue, this paper proposes a multi-frame 3D object detection algorithm based on a deformable spatiotemporal Transformer. Specifically, a deformable cross-scale Transformer module is devised, incorporating a multi-scale offset mechanism that non-uniformly samples features at different scales, enhancing the spatial information aggregation capability of the output features. Simultaneously, to address the issue of feature misalignment during multi-frame feature fusion, a deformable cross-frame Transformer module is proposed. This module incorporates independently learnable offset parameters for different frame features, enabling the model to adaptively correlate dynamic features across multiple frames and improve the temporal information utilization of the model. A proposal-aware sampling algorithm is introduced to significantly increase the foreground point recall, further optimizing the efficiency of feature extraction. The obtained multi-scale and multi-frame voxel features are subjected to an adaptive fusion weight extraction module, referred to as the proposed mixed voxel set extraction module. This module allows the model to adaptively obtain mixed features containing both spatial and temporal information. The effectiveness of the proposed algorithm is validated on the KITTI, nuScenes, and self-collected urban datasets. The proposed algorithm achieves an average precision improvement of 2.1% over the latest multi-frame-based algorithms.

This article reports on the recent mining and production status of ruby in Longido, Tanzania. Faceted-grade rubies and their matrix from Longido Area, Tanzania, were investigated by standard gemological testing, including FTIR, UV-VIS, Raman spectra, and LA-ICP-MS. Microscopic observations revealed dense needle-like and triangular inclusions, distinct growth lines, and color banding as typical inclusions. In agreement with the Raman results, the transmission FTIR spectrum confirmed the presence of aluminum hydroxide. The Raman spectra identified associated minerals and inclusions, including zoisite, parasites, feldspar within the matrix, rutile, and diaspore in the ruby host. The chemistry analysis revealed a high amount of Cr and relatively low iron as a good indicator of geographic origin.

Abstract Objective The optimal blood pressure (BP) targets for acute ischemic stroke are unclear. We aimed to assess the relationship between Mean BP and clinical outcomes during hospitalization. Materials and methods We included 649 patients with Acute ischemic stroke (AIS) from December 2020 to July 2021. BP was measured daily, and mean blood pressure was calculated. Clinical events recorded within 90 days of randomization were: recurrent ischemic stroke, symptomatic intracranial hemorrhage, and death. The modified Rankin Scale (mRS) was used to measure primary outcomes 3 months after AIS. Logistic multiple regression analysis was performed by statistical software R. Result There is a nonlinear U-shaped relationship between SBP and poor outcomes. This means higher SBP and lower SBP will increase the incidence of poor outcomes. The optimal mean SBP during hospitalization was 135-150 mmHg, and patients with SBP 150mmhg OR 2.04 [95% Cl, 1.02 ~ 4.08], p = 0.045 had a higher probability of poor outcomes. Conclusion Our study shows that the optimal SBP of patients with AIS during hospitalization was 135-150 mmHg. The findings suggest that the relationship between mean SBP and 3-month functional outcome after AIS was U-shaped. Both higher SBP and lower SBP lead to poor prognosis in AIS patients.

Abstract Most existing template matching algorithms are global matching between the template target and the search region, which makes the matching process retain a lot of unfavourable background information and ignore the structure and local information of the template target. To address this problem, a template matching algorithm based on bipartite graph and graph attention mechanism is proposed in this paper. The algorithm models the similarity matching problem between template features and search region features as a complete bipartite graph, realises local‐to‐local information transfer between the two, and uses the graph attention mechanism to apply weights between local information to obtain a learnable embedding network module. In addition, in terms of feature representation, a multi‐level feature fusion module based on CNN is introduced, which improves the representation of a target by fusing features with different representational meanings of the target. Experimental results on several typical datasets show that the proposed algorithm achieves leading performance in terms of accuracy and efficiency compared to the two state‐of‐the‐art CNN‐based template matching algorithms, Deep‐DIM and QATM.

Brusatol (Bru), a bioactive compound found in Brucea sumatrana, exerts antitumour effects on several malignancies. However, the role and molecular mechanism of Bru in squamous cell carcinoma of the oesophagus (ESCC) remain unclear. Here, we found that Bru decreased the survival of ESCC cells. Subsequently, the ferroptosis inhibitors, deferoxamine and liproxstatin-1, rescued Bru-induced cell death, indicating that ferroptosis plays a major role in Bru-induced cell death. Furthermore, Bru promoted lipid peroxidation, glutathione (GSH) depletion, and ferrous iron overload in vitro. Consistent with these in vitro results, Bru significantly inhibited tumour growth in KYSE150 xenograft nude mice by triggering ferroptosis. Mechanistically, nuclear factor E2-related factor 2 (NRF2) inactivation via increased ubiquitin-proteasome degradation was found to be a vital determinant of ferroptosis induced by Bru. Notably, Bru significantly decreases GSH synthesis, iron storage, and efflux by downregulating the expression of NRF2 target genes (glutamate-cysteine ligase catalytic subunit (GCLC), solute carrier family 7 member 11 (SLC7A11), ferritin heavy chain 1 (FTH1), and solute carrier family 40 member 1 (SLC40A1)), resulting in the accumulation of lethal lipid-based reactive oxygen species (ROS) and intracellular enrichment of chelated iron. Taken together, our findings indicate that ferroptosis is a novel mechanism underlying Bru-induced antitumour activity and will hopefully provide a valuable compound for ESCC treatment.

Heavy metal contamination poses a significant environmental threat to wildlife on global scale, making accurate assessment of exposure risk crucial for conservation efforts, particularly for vulnerable species. Existing risk assessment models have been widely used, but their construction process lacks comprehensive considerations. In this study, we constructed an optimized health risk assessment model based on the well-established ''Liu's model'' and ''ADI model'', and applied the pollution allocation factor (AF) to accurately assess the risk of heavy metal exposure to wildlife. Our model was applied to assess exposure risk of heavy metal for the black-necked crane(Grus nigricollis), a flagship species in the alpine wetland ecosystem of Caohai Wetland. Soil, plant and black-necked crane fecal samples were collected from the Caohai Wetland and surrounding areas in Guizhou, China. We revealed varying degrees of As, Cd, Cr, Ni, Pb, and Zn contamination in soil and plants from different habitats, exceeding the background or plant limit values. This indicated that the black-necked crane and other waterbirds living in Caohai Wetland are suffering with the multi-elemental heavy metal contamination, especially in the gutterway and grassland. The exposure dose of As, Cd, Cr, Ni, Cu, and Zn toward black-necked cranes differed significantly in soil and plant pathways (P 0.5). The risk assessment model identified Cr and Pb were the highest risk elements for black-necked cranes, with exposure risk simulated through feces exceeding those through food. These findings suggested that current Liu's model may underestimate the effects of other pathways and medium. Therefore, we proposed a more comprehensive and accurate model for evaluating the exposure risk of black-necked cranes, incorporating AF to quantify the contribution of risk sources to black-necked cranes and understand their overall health risk. This model can serve as a useful tool for the conservation and habitat quality improvement of the black-necked cranes and other waterbirds.

Both estrogen deficiency and aging may lead to osteoporosis. Developing novel drugs for treating osteoporosis is a popular research direction. We screened several potential therapeutic agents through a new deep learning-based efficacy prediction system (DLEPS) using transcriptional profiles for osteoporosis. DLEPS screening led to a potential novel drug examinee, ataluren, for treating osteoporosis. Ataluren significantly reversed bone loss in ovariectomized mice. Next, ataluren significantly increased human bone marrow-derived mesenchymal stem cell (hBMMSC) osteogenic differentiation without cytotoxicity, indicated by the high expression index of osteogenic differentiation genes (OCN , BGLAP, ALP, COL1A, BMP2, RUNX2). Mechanistically, ataluren exerted its function through the BMP-SMAD pathway. Furthermore, it activated SMAD phosphorylation but osteogenic differentiation was attenuated by BMP2-SMAD inhibitors or small interfering RNA of BMP2. Finally, ataluren significantly reversed bone loss in aged mice. In summary, our findings suggest that the DLEPS-screened ataluren may be a therapeutic agent against osteoporosis by aiding hBMMSC osteogenic differentiation.

Abstract Background Heme has attracted much attention because of its wide applications in medicine and food. The products of genes hemBCDEFY convert 5-aminolevulinic acid to protoporphyrin IX (PPIX; the immediate precursor of heme); protoporphyrin ferrochelatase (FECH) inserts Fe2+ into PPIX to generate heme. Biosynthesis of heme is limited by the need for optimized expression levels of multiple genes, complex regulatory mechanisms, and low enzymatic activity; these problems need to be overcome in metabolic engineering to improve heme synthesis. Results We report a heme biosensor-guided screening strategy using the heme-responsive protein HrtR to regulate tcR expression in Escherichia coli, providing a quantifiable link between the intracellular heme concentration and cell survival in selective conditions (i.e., the presence of tetracycline). This system was used for rapid enrichment screening of heme-producing strains from a library with random ribosome binding site (RBS) variants and from a FECH mutant library. Through up to four rounds of iterative evolution, strains with optimal RBS intensities for the combination of hemBCDEFY were screened; we obtained a PPIX titer of 160.8 mg/L, the highest yield yet reported in shaken-flask fermentation. A high-activity FECH variant was obtained from the saturation mutagenesis library. Fed-batch fermentation of strain SH20C, harboring the optimized hemBCDEFY and the FECH mutant, produced 127.6 mg/L of heme. Conclusion We sequentially improved the multigene biosynthesis pathway of PPIX and performed in vivo directed evolution of FECH, based on a heme biosensor, which demonstrated the effectiveness of the heme biosensor-based pathway optimization strategy and broadens our understanding of the mechanism of heme synthesis.

Abstract Glycolytic flux is a fundamental index in microbial cell factories. A glycolytic flux biosensor that can monitor glucose metabolism efficiency is a promising strategy in rewiring metabolic flux to balance growth and biosynthesis. A key design feature of the glycolytic flux biosensors is the interaction between the global transcriptional factor Cra and its regulated promoters. However, overexpression and mutation of Cra has unpredictable effects on global metabolism in Escherichia coli. Therefore, new orthogonal biosensor design strategies should be developed to circumvent metabolic issues. In this report, the promoters in glycolytic flux biosensor were replaced with synthetic promoters of varying strengths or phage‐derived promoters, and the Cra DNA‐binding sites were deployed into promoters at different positions and distances to yield biosensors. The de nova biosensors that depended on Cra could sense Fructose‐1,6‐diphosphate (FBP) with broad dynamic ranges and low basal leakage. Then the negative‐response biosensors were applied to fine‐tune the target ATP synthesis gene, leading to the desired increase in pyruvate production (the highest 9.66 g/L) and cell growth. Moreover, the membrane synthesis gene plsC was also dynamically activated by the positive‐response biosensor, leading to effective accumulation of lycopene in the cell membrane and a 50‐fold increase in lycopene titre (100.3 mg/L) when compared with the control strain, demonstrating the effective and broader usages of our biosensors.

Abstract This study aimed to investigate the characteristics and prognosis of distant metastasis (DM) after primary treatment for early‐stage extranodal nasal‐type natural killer (NK)/T‐cell lymphoma (ENKTCL). A total of 1619 patients from the China Lymphoma Collaborative Group database were retrospectively reviewed. The cumulative incidence of DM was assessed using Fine and Gray's competing risk analysis. The correlation between DM sites was evaluated using phi coefficients, while DM sites were classified using hierarchical clustering. Regression analysis was used to assess the linear correlation between DM‐free survival (DMFS) and overall survival (OS). The 5‐year cumulative DM rate was 26.2%, with the highest annual hazard rate being in the first year (14.9%). The most frequent DM sites were the skin and soft tissues (SSTs, 32.4%) and distant lymph nodes (LNs, 31.3%). DM sites were categorized into four subgroups of distinct prognosis — distant LN, SST, extracutaneous site, and lymphoma‐associated hemophagocytic lymphohistiocytosis. SST or distant LN, solitary metastasis, and late‐onset DM demonstrated a relatively favorable prognosis. Contemporary chemotherapy significantly decreased DM rates and improved DMFS. Decreased DM rates were further associated with increased OS probabilities. Our findings improve the understanding of the variable clinical behaviors of early‐stage ENKTCL based on four distinct DM sites and thus provide guidance for future therapeutic decisions, metastatic surveillance, and translational trial design.

Abstract Purpose Studies of the association between body mass index (BMI) at diagnosis and treatment outcome in children with acute lymphoblastic leukemia (ALL) have yielded inconsistent results. Hence, we conducted a retrospective study in a large cohort of Chinese children with ALL treated with contemporary protocols. Patients and Methods A total of 1437 children (62.1% male; median age at diagnosis 5.7 years, range: 2.3–16.3 years) were enrolled in two consecutive clinical trials at the Shanghai Children's Medical Center. The rates of overall survival, event‐free survival, relapse, treatment‐related mortality, and adverse events were compared among patients who were underweight (BMI 85th to

Abstract Background Astronauts undergo significant microgravity-induced bone loss during space missions, which has become one of the three major medical problems hindering human's long-term space flight. A risk-free and antiresorptive drug is urgently needed to prevent bone loss during space missions. D-mannose is a natural C-2 epimer of D-glucose and is abundant in cranberries. This study aimed to investigate the protective effects and potential mechanisms of D-mannose against bone loss under weightlessness. Methods The hind legs of tail-suspended (TS) rats were used to mimic weightlessness on Earth. Rats were administered D-mannose intragastrically. The osteoclastogenic and osteogenic capacity of D-mannose in vitro and in vivo was analyzed by micro-computed tomography, biomechanical assessment, bone histology, serum markers of bone metabolism, cell proliferation assay, quantitative polymerase chain reaction, and western blotting. RNA-seq transcriptomic analysis was performed to detect the underlying mechanisms of D-mannose in bone protection. Results The TS rats showed lower bone mineral density (BMD) and poorer bone morphological indices. D-mannose could improve BMD in TS rats. D-mannose inhibited osteoclast proliferation and fusion in vitro, without apparent effects on osteoblasts. RNA-seq transcriptomic analysis showed that D-mannose administration significantly inhibited the cell fusion molecule dendritic cell-specific transmembrane protein (DC-STAMP) and two indispensable transcription factors for osteoclast fusion (c-Fos and nuclear factor of activated T cells 1 [NFATc1]). Finally, TS rats tended to experience dysuria-related urinary tract infections (UTIs), which were suppressed by treatment with D-mannose. Conclusion D-mannose protected against bone loss and UTIs in rats under weightlessness. The bone protective effects of D-mannose were mediated by inhibiting osteoclast cell fusion. Our findings provide a potential strategy to protect against bone loss and UTIs during space missions.

Osteoporosis is a common degenerative bone disease. The treatment of osteoporosis remains a clinical challenge in light of the increasing aging population. Human dental pulp stem cells (DPSCs), a type of mesenchymal stem cells (MSCs), are easy to obtain and have a high proliferation ability, playing an important role in the treatment of osteoporosis. However, MSCs undergo apoptosis within a short time when used in vivo; therefore, apoptotic vesicles (apoVs) have attracted increasing attention. Currently, the osteogenic effect of DPSC-derived apoVs is unknown; therefore, this study aimed to determine the role of DPSC-derived apoVs and their potential mechanisms in bone regeneration. We found that MSCs could take up DPSC-derived apoVs, which then promoted MSC osteogenesis in vitro. Moreover, apoVs could increase the trabecular bone count and bone mineral density in the mouse osteoporosis model and could promote bone formation in rat cranial defects in vivo. Mechanistically, apoVs promoted MSC osteogenesis by activating the extracellular regulated kinase (ERK)1/2 signaling pathway. Consequently, we propose a novel therapy comprising DPSC-derived apoVs, representing a promising approach to treat bone loss and bone defects.

The escalating thermal power density in electronic devices necessitates advanced thermal management technologies. Polymer-based materials, prized for their electrical insulation, flexibility, light weight, and strength, are extensively used in this field. However, the inherent low thermal conductivity of polymers requires enhancement for effective heat dissipation. This work proposes a novel paradigm, emphasizing ordered structures with functional units, to create triple-level, ordered, low-filler loading of multi-walled carbon nanotube (MWCNT)/poly(vinyl alcohol)(PVA) nanofibrous films. By addressing interfacial thermal resistance through –OH groups, the coupling between polymer and MWCNT is strengthened. The triple-level ordered structure comprises aligned PVA chains, aligned MWCNTs, and aligned MWCNT/PVA composite fibers. Focusing on the filler’s impact on thermal conductivity and chain orientation, the thermal transport mechanisms have been elucidated level by level. Our MWCNT/PVA composite, with lower filler loadings (10 wt.%), achieves a remarkable TC exceeding 35.4 W/(m·K), surpassing other PVA composites with filler loading below 50 wt.%.

Intelligent vehicles are constrained by road, resulting in a disparity between the assumed six degrees of freedom (DoF) motion within the Visual Simultaneous Localization and Mapping (SLAM) system and the approximate planar motion of vehicles in local areas, inevitably causing additional pose estimation errors. To address this problem, a stereo Visual SLAM system with road constraints based on graph optimization is proposed, called RC-SLAM. Addressing the challenge of representing roads parametrically, a novel method is proposed to approximate local roads as discrete planes and extract parameters of local road planes (LRPs) using homography. Unlike conventional methods, constraints between the vehicle and LRPs are established, effectively mitigating errors arising from assumed six DoF motion in the system. Furthermore, to avoid the impact of depth uncertainty in road features, epipolar constraints are employed to estimate rotation by minimizing the distance between road feature points and epipolar lines, robust rotation estimation is achieved despite depth uncertainties. Notably, a distinctive nonlinear optimization model based on graph optimization is presented, jointly optimizing the poses of vehicle trajectories, LPRs, and map points. The experiments on two datasets demonstrate that the proposed system achieved more accurate estimations of vehicle trajectories by introducing constraints between the vehicle and LRPs. The experiments on a real-world dataset further validate the effectiveness of the proposed system.

BackgroundProgressive supranuclear palsy (PSP) is a clinically heterogenous atypical parkinsonian syndrome. Therefore, early recognition and correct diagnosis of PSP is challenging but essential. This study aims to characterize the clinical manifestations, magnetic resonance imaging (MRI), and longitudinal MRI changes of PSP in China.MethodClinical and MRI presentations were compared among 150 cases with PSP. Then the longitudinal MRI changes among 20 patients with PSP were further explored. Additionally, a series of midbrain-based MRI parameters was compared between PSP-P and PD.ResultsThroughout the course of the disease, there were differences in the symptoms of the fall and hand tremor between the PSP-RS and PSP-P. There were significant differences in the six midbrain-based MRI parameters between the PSP-RS and the PSP-P, including hummingbird sign, midbrain diameter, midbrain to pons ratio (MTPR), midbrain area, midbrain area to pons area ratio (Ma/Pa), and midbrain tegmental length (MBTegm). Longitudinal MRI studies revealed that the annual rel.ΔMTPR and rel.Δ (Ma/Pa) for PSP were 5.55 and 6.52%, respectively; additionally, PSP-RS presented a higher decline rate than PSP-P. Moreover, MTPR ≤0.56, midbrain diameter ≤ 0.92, midbrain area ≤ 1.00, and third ventricle width ≤ 0.75 could identify PSP-P from PD.ConclusionPSP-P differs from PSP-RS regarding clinical manifestations, MRI, and longitudinal MRI changes. MRI parameters could be potential imaging markers to identify PSP-P from PD.

BackgroundMental health literacy (MHL) is crucial to address issues related to mental illness. Nurses’ MHL is even more important because they are expected to deal with both the physical and psychological consequences of mental disorders.ObjectiveThis study investigated the level, discrepancy, and characteristics of MHL among Chinese nurses from both public general and psychiatric hospitals; identified influential factors; and explored the relationship between MHL and mental health status.MethodsUsing a stratified cluster sampling method to select participants, a cross-sectional survey was conducted to describe the MHL of 777 nurses from 13 general and 12 psychiatric hospitals using the Chinese version of the Mental Health Literacy Scale, Patient Health Questionnaire-2, Generalized Anxiety Disorder-2, and a demographic questionnaire. A multiple regression analysis was used to determine the factors influencing MHL among the nurses recruited.ResultsThe participants’ total score on the Chinese version of the Mental Health Literacy Scale was 93.25 (SD = 10.52). Multiple regression analysis revealed that nurses who worked in psychiatric or higher-level hospitals, with higher professional titles or higher education had higher levels of overall MHL and core MHL, while those working in general hospitals, with shorter work duration, or who were unmarried had higher social acceptance of patients. Nurses’ MHL was closely correlated with their mental health status.ConclusionThe overall and core MHL of Chinese nurses were at a moderate level, with social acceptance remaining at a relatively low level. There is an urgent need for MHL promotion programs to improve the MHL of clinical nurses. The focus must be given to overall MHL, especially core MHL, for non-psychiatric nurses to enhance their competence in mental health promotion and identification; more emphasis should be placed on the social acceptance of patients with mental illnesses for psychiatric nurses to improve their provision of professional services. Better MHL would be a formula for improving nurses’ own mental health and their mental health service competence.

Abstract Background Ginsenosides are Panax plant-derived triterpenoid with wide applications in cardiovascular protection and immunity-boosting. However, the saponins content of Panax plants is fairly low, making it time-consuming and unsustainable by direct extraction. Protopanaxadiol (PPD) is a common precursor of dammarane-type saponins, and its sufficient supply is necessary for the efficient synthesis of ginsenoside. Results In this study, a combinational strategy was used for the construction of an efficient yeast cell factory for PPD production. Firstly, a PPD-producing strain was successfully constructed by modular engineering in Saccharomyces cerevisiae BY4742 at the multi-copy sites. Then, the INO2 gene, encoding a transcriptional activator of the phospholipid biosynthesis, was fine-tuned to promote the endoplasmic reticulum (ER) proliferation and improve the catalytic efficiency of ER-localized enzymes. To increase the metabolic flux of PPD, dynamic control, based on a carbon-source regulated promoter P HXT1 , was introduced to repress the competition of sterols. Furthermore, the global transcription factor UPC2-1 was introduced to sterol homeostasis and up-regulate the MVA pathway, and the resulting strain BY-V achieved a PPD production of 78.13 ± 0.38 mg/g DCW (563.60 ± 1.65 mg/L). Finally, sugarcane molasses was used as an inexpensive substrate for the first time in PPD synthesis. The PPD titers reached 1.55 ± 0.02 and 15.88 ± 0.65 g/L in shake flasks and a 5-L bioreactor, respectively. To the best of our knowledge, these results were new records on PPD production. Conclusion The high-level of PPD production in this study and the successful comprehensive utilization of low-cost carbon source -sugarcane molassesindicate that the constructed yeast cell factory is an excellent candidate strain for the production of high-value-added PPD and its derivativeswith great industrial potential. Graphical Abstract