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We propose a relativistic theory for spin density matrices of vector mesons based on Kadanoff-Baym equations in the closed-time-path formalism. The theory puts the calculation of spin observables such as the spin density matrix element ρ00 for vector mesons on a solid ground. Within the theory we formulate ρ00 for φ mesons into a factorization form in separation of momentum and spacetime variables. We argue that the main contribution to ρ00 at lower energies should be from the φ fields that can polarize the strange quark and antiquark in the same way as electromagnetic fields. The key observation is that there is correlation inside the φ meson wave function between the φ field that polarizes the strange quark and that polarizes the strange antiquark. This is reflected by the fact that the contributions to ρ00 are all in squares of fields that are nonvanishing even if the fields may strongly fluctuate in spacetime. The fluctuation of strong force fields can be extracted from ρ00 of unflavored vector mesons as links to fundamental properties of quantum chromodynamics.

Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.

Abstract Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.

Abstract Circular RNA (circRNA) plays a pivotal role in breast cancer onset and progression. Understanding the biological functions and underlying molecular mechanisms of dysregulated circRNAs in breast cancer is crucial for elucidating its pathogenesis and identifying potential therapeutic targets. In this study, we investigated the role and molecular mechanism of circGSK3β in breast cancer. We found that circGSK3β is highly expressed in breast cancer cell lines, where it promotes cell proliferation, migration, and invasion, thereby driving breast cancer progression. Furthermore, we observed a close association between circGSK3β expression levels and immune evasion in breast cancer cells. Mechanistically, circGSK3β acts as a competing endogenous RNA (ceRNA) by interacting with miR-338-3p, thereby promoting breast cancer cell proliferation, migration, and invasion. Additionally, circGSK3β positively regulates the expression of the target gene PRMT5 through its interaction with miR-338-3p. This, in turn, enhances H3K4me3 recruitment to the promoter region of PD-L1, resulting in upregulation of PD-L1 expression and consequent immune evasion in breast cancer. In summary, our findings underscore the significance of the circGSK3β-miR-338-3p-PRMT5-H3K4me3 axis in promoting breast cancer progression and immune evasion. CircGSK3β emerges as a critical player in breast cancer pathogenesis, potentially serving as a diagnostic and prognostic marker, and offering novel insights into the role of circRNAs in breast cancer progression.

Abstract Background Malaria is a serious public health concern. Artemisinin and its derivatives are first-line drugs for the treatment of Plasmodium falciparum malaria. In mammals, artemisinin exhibits potent anti-inflammatory and immunoregulatory properties. However, it is unclear whether artemisinin plays a regulatory role in the innate immunity of mosquitoes, thereby affecting the development of Plasmodium in Anopheles when artemisinin and its metabolites enter mosquitoes. This study aims to determine the effect of dihydroartemisinin (DHA), a first-generation semisynthetic derivative of artemisinin, on innate immunity and malaria vector competence of Anopheles stephensi. Methods Anopheles stephensi was fed Plasmodium-infected mice treated with DHA via gavage, Plasmodium-infected blood containing DHA in vitro, or DHA-containing sugar, followed by Plasmodium yoelii infection. The engorged female mosquitoes were separated and dissected 8 and 17 days after infection. Plasmodium oocysts and sporozoites were counted and compared between the control and DHA-treated groups. Additionally, total RNA and proteins were extracted from engorged mosquitoes 24 and 72 h post infection (hpi). Real-time polymerase chain reaction (PCR) and western blotting were performed to detect the transcriptional levels and protein expression of immune molecules in mosquitoes. Finally, the Toll signaling pathway was inhibited via RNA interference and the infection density was analyzed to confirm the role of the Toll signaling pathway in the effect of DHA on the vector competence of mosquitoes. Results DHA treatment via different approaches significantly reduced the number of Plasmodium oocysts and sporozoites in mosquitoes. The transcriptional levels of anti-Plasmodium immune genes (including TEP1, LRIM1, and APL1C), Toll pathway genes (including Tube, MyD88, and Rel1), and the effector defensin 1 were upregulated by DHA treatment at 24 and 72 hpi. TEP1 and Rel1 protein expression was significantly induced under DHA treatment. However, Rel1 knockdown in DHA-treated mosquitoes abrogated DHA-mediated refractoriness to Plasmodium infection. Conclusions DHA treatment effectively inhibited the development of P. yoelii in A. stephensi by upregulating mosquitoes’ Toll signaling pathway, thereby influencing the susceptibility of Anopheles to Plasmodium. Graphical Abstract

Abstract Immune checkpoint inhibitors (ICIs) immunotherapy facilitates new approaches to achieve precision cancer treatment. A growing number of patients with non-small cell lung cancer (NSCLC) have benefited from treatment with neoadjuvant ICIs combined with chemotherapy. However, the mechanisms and associations between the therapeutic efficacy of neoadjuvant pembrolizumab and chemotherapy (NAPC) and macrophage subsets are still unclear. We performed single-cell RNA sequencing (scRNA-seq) and identified a novel FABP4+C1q+ macrophage subtype, which exhibited stronger proinflammatory cytokine production and phagocytic ability. This subtype was found to be more abundant in tumor tissues and lymph nodes of major pathological response (MPR) patients compared to non-MPR patients, and was associated with a good efficacy of NAPC. Multiplex fluorescent immunohistochemical (mIHC) staining was subsequently used to verify our findings. Further mechanistic studies indicated that FABP4 and C1q regulate the expression of proinflammatory cytokines synergistically. In addition, FABP4 and C1q promote fatty acid synthesis, enhance anti-apoptosis ability and phagocytic ability of macrophage via the interaction of AMPK/JAK/STAT axis. This study provides novel insights into the underlying mechanisms and predictive biomarkers of NAPC. Our findings contribute to improving the prognosis of patients with NSCLC by potentially guiding more precise patient selection and treatment strategies. Novelty & Impact Statements We identified a group of macrophages (FABP4+C1q+ macrophages) related to the therapeutic efficacy of neoadjuvant chemoimmunotherapy. FABP4+C1q+ macrophages highly expressed proinflammatory cytokines-related genes and had a strong cytokine production and phagocytic ability. We believe that our study provides a novel insight into the synergistic mechanism of neoadjuvant ICI combined with chemotherapy and may lead to improved clinical outcomes in patients with NSCLC in the future.

Abstract Chronic hypobaric hypoxia at high altitudes can impair cognitive functions, especially causing deficits in learning and memory, which require therapeutic intervention. Here, we showed that mice subjected to hypobaric hypoxia (simulating an altitude of 5000 m) for one month experienced significant cognitive impairment, accompanied by increased biomarker levels of oxidative stress in the brain and blood. Oral administration of a novel formulation of edaravone, a free radical scavenger approved for the treatment of ischaemic stroke and amyotrophic lateral sclerosis, significantly alleviated oxidative stress and cognitive impairments caused by chronic hypobaric hypoxia. Furthermore, oral edaravone treatment also mitigated neuroinflammation and restored hippocampal neural stem cell exhaustion. Additionally, periostin (Postn) is vital in the cognitive deficits caused by chronic hypobaric hypoxia and may be a molecular target of edaravone. In conclusion, our results suggest that oxidative stress plays a crucial role in the cognitive deficits caused by chronic hypobaric hypoxia and that oral edaravone is a potential medicine for protecting against cognitive deficits caused by chronic hypobaric hypoxia in high-altitude areas.

Introduction: Posterior tibial slope (PTS) plays a vital role in knee stability. PTS of more than 12° may be considered with increased strain on the native anterior cruciate ligament (ACL) fibers. To handle the instability caused by changes in PTS degree, Proximal Tibial Anterior Closing Wedge Osteotomy (PT-ACWO) is adopted by surgeons. Methods: Between October 2015 and October 2019, our department conducted a retrospective analysis of patients who experienced anterior cruciate ligament reconstruction (ACLR) graft failures, with a particular focus on pathological PTS. The time from initial ACLR to revision ranged from 1 to 10 years, with a mean of 2.5 years. Radiological assessments of PTS were conducted, and outcomes were quantified using the International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity scale. The surgical technique and the use of 3D Patient-Specific Instrumentation (PSI) were outlined. Preoperative imaging included the use of Kirschner wires to establish tibial plateau reference points, and 3D-PSI was employed to guide the location and depth of the tibial osteotomy, which was performed obliquely. In a notable instance, a novel tibial tunnel was mapped out, and ortho-bridge system (OBS) fixation was utilized to ensure adequate space for the new tunnel. Results: In a cohort of seven patients with a mean follow-up of 28.1 months, a significant reduction in PTS was noted postoperatively (median [interquartile range, IQR], from 15.27° [13.46°, 16.60°] to 6.25° [5.89°, 6.78°]; P = 0.002). IKDC score improved to 85.10 (80.25, 88.10), P

Abstract Background In China, the problem of HIV infection among the older people has become increasingly prominent. This study aimed to analyze the pattern and influencing factors of HIV transmission based on a genomic and spatial epidemiological analysis among this population. Methods A total of 432 older people who were aged ≥ 50 years, newly diagnosed with HIV-1 between January 2018 and December 2021 and without a history of ART were enrolled. HIV-1 pol gene sequence was obtained by viral RNA extraction and nested PCR. The molecular transmission network was constructed using HIV-TRACE and the spatial distribution analyses were performed in ArcGIS. The multivariate logistic regression analysis was performed to analyze the factors associated with clustering. Results A total of 382 sequences were successfully sequenced, of which CRF07_BC (52.3%), CRF01_AE (32.5%), and CRF08_BC (6.8%) were the main HIV-1 strains. A total of 176 sequences entered the molecular network, with a clustering rate of 46.1%. Impressively, the clustering rate among older people infected through commercial heterosexual contact was as high as 61.7% and three female sex workers (FSWs) were observed in the network. The individuals who were aged ≥ 60 years and transmitted the virus by commercial heterosexual contact had a higher clustering rate, while those who were retirees or engaged other occupations and with higher education degree were less likely to cluster. There was a positive spatial correlation of clustering rate (Global Moran I = 0.206, P

Abstract This study investigates the unintended socioeconomic consequences of housing market regulations, focusing on the home purchase restriction (HPR) policy implemented in cities across China. While the primary aim of the HPR policy is to curb property prices by limiting the number of properties a household can purchase, its broader impact on family formation, particularly marriage and divorce patterns, remains underexplored. Applying Becker’s economic theory of marriage, which views marital decisions as rational choices influenced by socioeconomic factors, this study examines how the HPR policy affects family formation and dissolution across different city tiers and age groups in China. Our analysis reveals several key findings. First, the HPR policy effectively contributed to a decrease in house prices, aligning with its primary objective. However, it also led to delayed marriages among younger age groups, especially in first-tier cities, where housing affordability is a significant concern. Second, the policy inadvertently encouraged strategic divorces, allowing couples to circumvent purchase restrictions and acquire additional properties. This loophole undermines the policy’s effectiveness in reducing housing demand and stabilizing prices. These results highlight the complex interplay between housing market regulations and family demographics, emphasizing the need for policymakers to consider the broader societal impacts of non-family-oriented policies. As China, like many other societies, faces challenges related to the second demographic transition—such as declining marriage and fertility rates—the findings of this study serve as a cautionary tale. Housing policies, while effective in addressing market concerns, can have significant and sometimes counterproductive effects on family stability and formation, potentially exacerbating the demographic trends a society aims to mitigate.

Abstract Interannual global mean surface temperature (GMST) forecast provides critical insights into the economic and societal implications of climate variability. The pronounced GMST elevation in 2023–2024 indicates that the Earth may have accumulated enough heat to cause widespread disasters, underscoring the necessity for establishing accurate short-term GMST predictions to offer timely and sustainable public service. However, capturing high-frequency annual variability (ANV) component of GMST poses challenges due to its susceptibility to intraseasonal-to-interannual (ISI) noises, particularly across the Northern Hemisphere’s mid-to-high latitudes. Averaging these ISI variations in November and December effectively enhances signal clarity, especially over oceans, and masks unpredictable noises on land. By forecasting the average GMST for November and December to extract ANV predictability, a strategy for annual GMST prediction was established. This approach successfully advanced precise GMST hindcasts by up to 2-months during 1980–2022, exceeding performance of existing climate models and boosting early warning for interannual GMST shifts.

Abstract Nanocarriers (NCs) play a crucial role in delivering theranostic agents to tumors, making them a pivotal focus of research. However, the persistently low delivery efficiency of engineered NCs has been a significant challenge in the advancement of nanomedicine, stirring considerable debate. Transvascular transport is a critical pathway for NC delivery from vessels to tumors, yet a comprehensive understanding of the interactions between NCs and vascular systems remains elusive. In recent years, considerable efforts have been invested in elucidating the transvascular transport mechanisms of NCs, leading to promising advancements in tumor delivery and theranostics. In this context, we highlight various delivery mechanisms, including the enhanced permeability and retention effect, cooperative immune-driven effect, active transcytosis, and cell/bacteria-mediated delivery. Furthermore, we explore corresponding strategies aimed at enhancing transvascular transport of NCs for efficient tumor delivery. These approaches offer intriguing solutions spanning physicochemical, biological, and pharmacological domains to improve delivery and therapeutic outcomes. Additionally, we propose a forward-looking delivery framework that relies on advanced tumor/vessel models, high-throughput NC libraries, nano-bio interaction datasets, and artificial intelligence, which aims to guide the design of next-generation carriers and implementation strategies for optimized delivery.

Abstract This study aims to objectively assess the effect of three surgical approaches for posterior uterine fibroid resection: transumbilical laparoendoscopic single-site surgery (LESS), vaginal natural orifice transluminal endoscopic surgery (vNOTES) in prone position (vNOTES-P), and vNOTES in the lithotomy position (vNOTES-L). A retrospective analysis was conducted on data pertaining to all patients who underwent vNOTES and LESS for single posterior fibroids at our institution from January 2023 to July 2023. Patients were categorized into three groups based on the surgical approach: vNOTES-P group (n = 30), vNOTES-L group (n = 17), and LESS group (n = 32). Comparative analysis was performed on the demographic characteristics and perioperative outcomes among the three groups of patients. All 79 patients underwent surgery without the need for conversion to laparotomy. There were no statistically significant differences among the LESS group, vNOTES-P group, and vNOTES-L group in terms of operative time, intraoperative blood loss, and perioperative complication rates. In the vNOTES-L group, two patients required conversion to LESS during surgery. Patients had faster return of bowel function (less time to flatus) in the vNOTES group compared to the LESS group (P

Highlights Innovative synthesis method for nanoscale-based perovskites with enhanced stability and efficiency. Novel application of nanoscale-based perovskites in optoelectronics with superior performance metrics. Comprehensive analysis of the structure–property relationships in perovskite nanomaterials.

Abstract Background During wound healing, fibroblast to myofibroblast transition is required for wound contraction and remodeling. While hypoxia is an important biophysical factor in wound microenvironment, the exact regulatory mechanism underlying hypoxia and fibroblast-to-myofibroblast transition remains unclear. We previously found that tetraspanin CD9 plays an important role in oxygen sensing and wound healing. Herein, we investigated the effects of physiological hypoxia on fibroblast-to-myofibroblast transition and the biological function and mechanism of CD9 in it. Methods Human skin fibroblasts (HSF) and mouse dermis wounds model were established under physiological hypoxia (2% O2). The cell viability and contractility of HSF under hypoxia were evaluated by CCK8 and collagen gel retraction, respectively. The expression and distribution of fibroblast-to-myofibroblast transition markers and CD9 in HSF were detected by Western blotting and immunofluorescence. CD9 slicing and overexpressing HSFs were constructed to determine the role of CD9 by small interfering RNA and recombinant adenovirus vector. The association of TβR2 and TβR1 was measured by immunoprecipitation to explore the regulatory mechanism. Additionally, further validation was conducted on mouse dermis wounds model through histological analysis. Results Enhanced fibroblast-to-myofibroblast transition and upregulated CD9 expression was observed under hypoxia in vitro and in vivo. Besides, reversal of fibroblast-to-myofibroblast transition under hypoxia was observed when silencing CD9, suggesting that CD9 played a key role in this hypoxia-induced transition. Moreover, hypoxia increased fibroblast-to-myofibroblast transition by activating TGF-β1/Smad2/3 signaling, especially increased interaction of TβR2 and TβR1. Ultimately, CD9 was determined to directly affect TβR1–TβR2 association in hypoxic fibroblast. Conclusion Collectively, these findings suggest that CD9 promotes TβR2–TβR1 association, thus driving the transition of human dermal fibroblasts to myofibroblast under hypoxia.

Highlights The energy conversion mechanism is thoroughly analyzed, with a detailed quantitative characterization of the dissipation capacities of polarization, conduction, and magnetic loss. Inspired by DNA transcription, atom and geometry configurations co-modulating multi-scale helical converters achieve the RL min of −63.13 dB at 1.29 mm, and the maximum RCS reduction value reach 36.4 dB m2. Orbital coupling, spin and cross polarization synergize to realize a 6.08 GHz EAB, further expanding to ultrabroad electromagnetic wave absorption of 12.16 GHz through metamaterial design.

Abstract Background Aim to validate the diagnostic efficacy of radiomics models for predicting various degrees of cognitive impairment in patients with cerebral small vessel disease (CSVD). Methods Participants were divided into mild cognitive impairment group (mild-CSVD group) and sever cognitive impairment group (sever-CSVD group) according to Montreal Cognitive Assessment (MoCA) performance, 98 gender-age-education matched subjects served as normal controls. Radiomic features were extracted from the segmented hippocampus using PyRadiomics. The feature preprocessing involved replacing missing values with the mean, applying stratified random sampling to allocate subjects into training (80%) and testing (20%) sets, ensuring balance among the three classes (normal controls, mild-CSVD group, and sever-CSVD group). A feature selection method was applied to identify discriminative radiomic features, with the optimal texture feature chosen for developing diagnostic models. Performance was evaluated in both the training and testing sets using receiver operating characteristic (ROC) curve analysis. Results The radiomics model achieved an accuracy of 0.625, an AUC of 0.593, a sensitivity of 0.828, and a specificity of 0.316 in distinguishing mild-CSVD group from normal controls. When distinguishing mild-CSVD group from sever-CSVD group, the radiomics model reached an accuracy of 0.683, an AUC of 0.660, a sensitivity of 0.167, and a specificity of 0.897. Similarly, in distinguishing sever-CSVD group from normal controls, the radiomics model exhibited an accuracy of 0.781, an AUC of 0.818, a sensitivity of 0.538, and a specificity of 0.947. Conclusion Radiomics model based on hippocampal texture had disparities in the diagnostic efficacy of radiomics models in predicting various degrees of cognitive impairment in patients with CSVD.

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by the overproliferation of synovial fibroblast‐like synoviocytes (FLSs) in the lining, leading to chronic inflammation and progressive joint damage. RA pathogenesis involves lymphocyte infiltration, increased synovial cell proliferation, and impaired cell death. This study investigated the effects of rapamycin on RA‐FLSs and explored the underlying molecular mechanisms. Methods The optimal drug concentration and time for rapamycin administration were determined using a cell counting kit‐8 assay. The concentration of rapamycin varied from 1 to 25 nmol/L. The mRNA expression levels of protein kinase B (AKT), mammalian target of rapamycin (mTOR), B cell lymphoma 2 (Bcl‐2), and Bcl‐2‐associated X protein (Bax) were quantified by real‐time polymerase chain reaction. Protein expression (p‐AKT, AKT, p‐mTOR, mTOR, pS6 kinase [S6K], S6K, p‐4E‐binding protein 1 [4EBP1], 4EBP1, Bcl‐2, Bax, caspase 3, caspase 9, cyclin‐dependent kinase 2 [CDK2], and CD1) were detected by Western blotting analysis. Results Rapamycin suppresses RA‐FLS proliferation and induces apoptosis in a dose‐dependent manner. Rapamycin significantly elevated the protein expression of Bax (p