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Abstract This was a multicenter, single-arm, open-label, phase Ib/II study (NCT04255576), aimed to evaluate the efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone (GCTB). JMT103 (2 mg/kg) was administered subcutaneously every four weeks, with loading doses on days 8 and 15. The primary endpoint was the objective tumor response rate (OTR) based on best response, defined as the proportion of patients who achieved elimination of at least 90% of the giant cells or radiologic complete or partial response per the modified Inverse Choi density/size (mICDS) or modified European Organization for Research and Treatment of Cancer (mEORTC) within 12 weeks. Secondary endpoints included objective response rate (ORR) per mICDS and mEORTC, and safety. A total of 139 patients were enrolled, and 135 were analyzed for efficacy. OTR, determined by the independent review committee (IRC) was 93.3% (95% CI 87.7-96.9). Treatment-related adverse events occurred in 90 (64.7%) patients, with hypophosphatemia and hypocalcemia being the most common. No serious treatment-related adverse events were observed. Thus, JMT103 demonstrates potential as a therapeutic option for GCTB.

Abstract Objective Hepatocellular carcinoma (HCC) is fatal and poses great challenges to early diagnosis and effective treatment. This paper sought to expound the function of Zinc finger and SCAN domain-containing protein 16 (ZSCAN16) and TBC1 domain family member 31 (TBC1D31) in HCC progression. Methods ZSCAN16 and TBC1D31 levels were detected by RT-qPCR, Western blot, and immunohistochemistry. The transcriptional regulation of TBC1D31 by ZSCAN16 was demonstrated by ChIP-qPCR and dual-luciferase assay. Colony formation assay, migration and invasion assays, TUNEL staining, CCK-8 assay, flow cytometry, and western blot analysis were adopted to evaluate the biological activity of HCC cells. The role of the ZSCAN16/TBC1D31 axis in HCC was demonstrated by lentiviral gene intervention combined with functional rescue experiments. Hep3B cells were used to establish a nude mouse xenograft tumor model to study the role of the ZSCAN16/TBC1D31 axis in vivo. Results ZSCAN16 and TBC1D31 were highly expressed in HCC. Downregulation of ZSCAN16 repressed the proliferation, migration, and invasion of HCC cells while promoting apoptosis, as well as curbing tumor growth in vivo. Mechanistic studies showed that ZSCAN16 mediated the transcriptional activation of TBC1D31, which in turn led to tumor development. TBC1D31 overexpression reversed the inhibitory effect of ZSCAN16 knockdown on the malignant behavior and tumor growth of HCC cells and accelerated tumor development. Conclusion ZSCAN16 mediates transcriptional activation of TBC1D31 and promotes HCC progression.

Background: The reportedly high mutation rate of mitochondrial DNA (mtDNA) may be attributed to the absence of histone protection and complete repair mechanisms. Mitochondrial heteroplasmy refers to the coexistence of wild-type and mutant mtDNA. Most healthy individuals carry a low point mutation load (

Abstract High signal-to-noise ratio (SNR) seismic waveform data are conductive to various studies in seismology. Seismic denoising aims to enhance SNR by eliminating additive noise through signal processing while preserving important features of the seismic signal. Conventional parametric seismic denoising methods often require selecting appropriate parameters to achieve optimal results, which may be limiting when dealing with various types and scales of seismic data. Here, we develop an adaptive parameter-free denoising method by combining general cross-validation (GCV) thresholding and pixel connectivity in synchrosqueezed (SS) domain. In this denoising framework, the synchrosqueezed continuous wavelet transform (SS-CWT) is first applied to obtain a high-resolution time–frequency representation. Then, the GCV approach, which allows for choosing the (nearly) optimal threshold without relying on any prior knowledge about the noise level, is employed to attenuate most of the low-energy noise. After that, the relatively isolated high-energy residual noise remaining in the SS-CWT spectrum is removed using pixel connectivity thresholding. Finally, the inverse SS-CWT is applied to the thresholded spectrum to obtain the denoised seismic record. As the thresholds for GCV and pixel connectivity are derived from the spectrum characteristics of the data being analyzed, the proposed denoising approach is highly adaptive and parameter-free. We demonstrate the effectiveness and versatility of the proposed denoising framework using synthetic data and real seismic data from diverse monitoring scenarios, including land, ocean, and emerging distributed acoustic sensing (DAS). The results indicate that the method is a stable and efficient tool for seismic data denoising. Graphical Abstract

Abstract Clade A type 2C protein phosphatases (PP2Cs) are crucial components of the abscisic acid (ABA) signaling pathway. Research on clade A PP2Cs has focused more on their roles related to ABA signaling and stress responses than on the molecular mechanisms mediating their effects on plant growth and grain yield. Rice (Oryza sativa L.) is an important food crop worldwide. We previously determined that OsPP2C49, which encodes a rice clade A PP2C family member, negatively controls rice responses to drought, salt, and high-temperature stresses. In this study, we investigated the regulatory effects of OsPP2C49 on ABA responses and rice grain yield. By analyzing potential interactions with core ABA components, including pyrabactin resistance 1 (PYR1)/PYR1-like (PYL)/regulatory component of the ABA receptor (RCAR) and stress-activated protein kinases (SAPKs), we confirmed that OsPP2C49 is involved in the ABA signaling pathway. OsPP2C49 overexpression led to decreased ABA sensitivity and increased rice grain yield; the opposite phenotypes were observed in the ospp2c49 knockout mutants. Therefore, OsPP2C49 negatively regulates ABA responses, but positively modulates rice grain yield. Furthermore, we found that OsPP2C49 can interact with and dephosphorylate five OsSAPKs in vitro. Unlike OsPP2C49, these OsSAPKs positively modulate ABA responsiveness, but negatively affect rice yield. These findings indicate that OsPP2C49 may partially regulate ABA responses and rice grain production by dephosphorylating OsSAPKs. This study preliminarily explored the molecular basis of the regulatory effects of OsPP2C49 on rice plant growth and grain yield.

The article explores the digital transformation of State-Owned Enterprises (SOEs) through a bibliometric analysis. The study analyses the scientific literature to understand the current trends, challenges, and emerging themes surrounding the digitalization of SOEs across various industries. Digital transformation, which involves integrating technologies like AI, IoT, and big data, is crucial for improving operational efficiency, reducing costs, and ensuring sustainability in such key sectors as energy, transportation, and telecommunications, where SOEs often play a pivotal role. The research uses bibliometric tools, specifically Scopus and the Biblioshiny App, to map out the literature on digital transformation in SOEs, analyze keywords, and identify thematic clusters in the body of research. The study highlights the significant publication growth, particularly from 2018 onwards, and points to digital transformation, corporate governance, and green innovation as dominant research themes. These themes illustrate how SOEs leverage digital technologies to improve service delivery, increase transparency, and meet environmental targets. The study observed a rapid increase in research output related to SOE digital transformation, particularly from 2020 to 2023. The leading contributors were journals such as Finance Research Letters, Sustainability (Switzerland), and Technological Forecasting and Social Change. The central themes of the analyzed publications included digital transformation, corporate governance, green innovation, and environmental performance. These were classified as “motor themes” due to their high centrality and well-developed nature, indicating their pivotal role in SOE research. The analysis revealed strong links between keywords such as digital transformation, information asymmetry, and innovation. These connections highlight the critical role of digital technologies in enhancing transparency, efficiency, and sustainability within SOEs. The study reveals that the digital transformation of SOEs is a critical area of research, with a growing emphasis on sustainability and innovation. The analysis underscores the need for further studies on the financial impacts of digitalization, the role of government policies, and cross-country comparisons to fully understand how different regulatory and economic environments influence the digital transformation processes in SOEs. By leveraging emerging technologies, SOEs can better align with national digital strategies and contribute to broader policy goals such as energy efficiency and inclusive growth.

Abstract The aim of this study was to identify key genes and investigate the immunological mechanisms of atopic dermatitis (AD) at the molecular level via bioinformatics analysis. Gene expression profiles (GSE32924, GSE107361, GSE121212, and GSE230200) were obtained for screening common differentially expressed genes (co-DEGs) from the gene expression omnibus database. Functional enrichment analysis, protein–protein interaction network and module construction, and identification of common hub genes were performed. Hub genes were validated using receiver operating characteristic curve analysis based on GSE130588 and GSE16161. NetworkAnalyst was used to detect microRNAs (miRNAs) and transcription factors (TFs) associated with the hub genes. The immune cell infiltration was analyzed using the CIBERSORT algorithm to further analyze the correlation between hub genes and immune cells. A total of 146 co-DEGs were obtained, showing significant enrichment in cytokine–cytokine receptor interaction and JAK-STAT signaling pathway. Seven hub genes were identified by Cytoscape and validated with external datasets. Subsequent prediction of miRNAs and TFs targeting these hub genes revealed their regulatory roles. Analysis of immune cell infiltration and correlation revealed a significant positive correlation between CCL22 expression and the number of dendritic cells activated. The identified hub genes represent potential diagnostic and therapeutic targets in the immunological pathogenesis of AD.

Abstract Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio

Abstract Seed vigor is a complex trait encompassing seed germination, seedling emergence, growth, seed longevity, and stress tolerance, all are crucial for direct seeding in rice. Here, we report that the AP2/ERF transcription factor OsRAV1 (RELATED TO ABI3 AND VP1) positively regulates seed germination, vigor, and salt tolerance. Additionally, OsRAV1 was differently expressed in embryo and endosperm, with the OsRAV1 localized in the nucleus. Transcriptomic analysis revealed that OsRAV1 modulates seed vigor through plant hormone signal transduction and phenylpropanoid biosynthesis during germination. Haplotype analysis showed that rice varieties carrying Hap3 displayed enhanced salt tolerance during seed germination. These findings suggest that OsRAV1 is a potential target in breeding rice varieties with high seed vigor suitable for direct seeding cultivation.

ObjectiveTo understand the core information awareness of chronic disease prevention and control and its influencing factors among adult residents in Heilongjiang province, and to provide a reference for formulating chronic disease prevention and control strategies and intervention measures. MethodsFrom March to April 2021, a quota sampling method was used to select 5 238 adult residents aged ≥ 18 years old from 10 districts and counties in 8 cities in Heilongjiang province, including Nangang district and Daowai district in Harbin city, Yi’an county in Qiqihar city, Beilin district in Suihua city, Datong district in Daqing city, Luobei county in Hegang city, Huachuan county in Jiamusi city, Muling city and Ning′an city in Mudanjiang city, and Boli county in Qitaihe city, to conduct an online questionnaire survey and analyze the core information awareness of chronic disease prevention and control and its influencing factors among adult residents in Heilongjiang province. ResultsAmong the 5 226 adult residents in Heilongjiang province finally included in the analysis, 3 388 were aware of the core information of chronic disease prevention and control, with an awareness rate of 64.83%; the scoring rates of the dimensions of awareness of the severity of chronic diseases, healthy lifestyles for preventing chronic diseases, core knowledge of hypertension prevention and control, core knowledge of diabetes prevention and control, core knowledge of cardiovascular and cerebrovascular disease prevention and control, identification of cancer risk factors, and core knowledge of chronic respiratory disease prevention and control were 88.88%, 81.92%, 80.95%, 85.72%, 85.07%, 86.80%, and 83.02%, respectively; multivariate unconditional logistic regression analysis showed that adult residents in Heilongjiang province aged ≥ 25 years old and with a junior high school education or above had higher awareness rates of core information on chronic disease prevention and control, while adult residents in Heilongjiang province with occupations of manual labor had lower awareness rates of core information on chronic disease prevention and control. ConclusionThe awareness rate of core information on chronic disease prevention and control among adult residents in Heilongjiang province has reached the 60% target requirement for 2020 in the Medium- and Long-term Plan for the Prevention and Treatment of Chronic Diseases in China (2017 – 2025), but there is still a certain gap from the 70% target for 2025, and there are differences in the awareness levels of core knowledge of chronic diseases in different dimensions, with the lowest scoring rate in the dimension of core knowledge of hypertension prevention and treatment; age, education level, and occupation are the main influencing factors of core information awareness of chronic disease prevention and control among local adult residents.

Influenza A/H9 viruses circulate worldwide in wild and domestic avian species, continuing to evolve and posing a zoonotic risk. A substantial increase in human infections with A/H9N2 subtype avian influenza viruses (AIVs) and the emergence of novel reassortants carrying A/H9N2-origin internal genes has occurred in recent years. Different names have been used to describe the circulating and emerging A/H9 lineages. To address this issue, an international group of experts from animal and public health laboratories, endorsed by the WOAH/FAO Network of Expertise on Animal Influenza, has created a practical lineage classification and nomenclature system based on the analysis of 10,638 hemagglutinin sequences from A/H9 AIVs sampled worldwide. This system incorporates phylogenetic relationships and epidemiologic characteristics designed to trace emerging and circulating lineages and clades. To aid in lineage and clade assignment, an online tool has been created. This proposed classification enables rapid comprehension of the global spread and evolution of A/H9 AIVs.

Abstract Hyperactive Ras signalling is found in most cancers. Ras proteins are only active in membrane nanoclusters, which are therefore potential drug targets. We previously showed that the nanocluster scaffold galectin-1 (Gal1) enhances H-Ras nanoclustering via direct interaction with the Ras binding domain (RBD) of Raf. Here, we establish that the B-Raf preference of Gal1 emerges from the divergence of the Raf RBDs at their proposed Gal1-binding interface. We then identify the L5UR peptide, which disrupts this interaction by binding with low micromolar affinity to the B- and C-Raf-RBDs. Its 23-mer core fragment is sufficient to interfere with H-Ras nanoclustering, modulate Ras-signalling and moderately reduce cell viability. These latter two phenotypic effects may also emerge from the ability of L5UR to broadly engage with several RBD- and RA-domain containing Ras interactors. The L5UR-peptide core fragment is a starting point for the development of more specific reagents against Ras-nanoclustering and -interactors.

Abstract Background The weight-adjusted waist index (WWI) is a recently developed obesity metric, and the aim of this study was to investigate the relationship between physical activity (PA) and WWI and the homeostasis model assessment of insulin resistance (HOMA-IR) in adolescents, as well as the joint association of HOMA-IR. Methods This study was based on the National Health and Nutrition Survey conducted between 2013 and 2016 and included 1024 adolescents whose median age was 15.4. Multivariate linear regression was used to examine the associations between HOMA-IR and PA and WWI. Using generalized additive models, a potential nonlinear link between WWI and HOMA-IR was evaluated. Subgroup analysis was also carried out. Results The fully adjusted model revealed a positive association (β: 0.48, 95% CI: 0.43, 0.53) between the WWI and HOMA-IR. The HOMA-IR was lower in physically active (β: -0.16, 95% CI: -0.26, -0.05) participants versus inactive participants. Participants who had higher WWI and were not physically active (β: 0.69; 95% CI: 0.56, 0.82) had the highest levels of HOMA-IR compared to participants who had lower WWI and were physically active. Subgroup analysis revealed that these correlations were similar in males and females. Conclusion Our results demonstrated that higher WWI and PA were associated with a lower HOMA-IR and that WWI and PA had a combined association with HOMA-IR. The findings of this study are informative for the preventing insulin resistance in adolescents.

Objective Management of extensive acetabular bone defects in total hip arthroplasty (THA) remains challenging. This study aims to investigate the feasibility and preliminary outcomes of 3D‐printed personalized porous acetabular components for the reconstruction of acetabular defects in primary THA. Methods This retrospective study involved seven patients who received 3D‐printed acetabular components in primary THA between July 2018 and March 2021. Preoperatively, acetabular bone defects were evaluated by referencing the Paprosky classification. There were two "Paprosky type IIIA" defects and five "Paprosky type IIIB" defects. The acetabular components were custom‐made for each patient to reconstruct the extensive acetabular defects. The hip function was assessed according to the Harris hip score (HHS). Clinical and radiographic outcomes were assessed. Results The average follow‐up period was 40 months, ranging from 26 to 57 months. There were no patients lost to follow‐up. The HHS improved from 44 (range: 33–53) before the operation to 88 (range: 79–93) at the final follow‐up. Postoperative X‐rays showed that the 3D‐printed personalized components were properly fitted with the acetabulum. The average center of rotation (COR) discrepancy was 2.3 mm horizontally and 2.1 mm vertically, respectively. Tomosynthesis‐Shimadzu metal artifact reduction technology images showed that the implant was in close contact with the host bone. Moreover, no complications were observed during the follow‐up period, including loosening, dislocation, or component protrusion. Conclusion The implantation of 3D‐printed personalized acetabular components showed accurate reconstruction, stable mechanical support, and favorable function at short‐term follow‐up. This may be a viable alternative method for reconstructing extensive acetabular defects in THA.

This is an article in the field of mineral materials. The utilization of desulfurized gypsum (FGD) to prepare more widely used hemihydrate gypsum plays a very important role in the resource utilization of industrial by-product gypsum. It can not only avoid the large-scale exploitation of natural gypsum, but also realize the resource utilization of desulfurized gypsum. In the process of converting FGD gypsum into hemihydrate gypsum, appropriate concentration of additive and sodium chloride were used as the reaction solution, and the process was heated and stirred under normal pressure. The effects of sodium chloride concentration, additive concentration, solid-liquid ratio, rotation speed and reaction temperature on the phase conversion time and crystal size of dihydrate to hemihydrate gypsum were studied. The increase of additive and sodium chloride concentration not only sped up the phase conversion process but also had a certain inhibitory effect on the average length and average aspect ratio of hemihydrate gypsum crystals. Higher or lower rotation speed hindered the nucleation and growth of hemihydrate gypsum crystals and affected the collision frequency of Ca2+ and SO42- in the NaCl added solution, thus delaying the formation of hemihydrate gypsum. Decreasing the solid-liquid ratio and increasing the temperature had a certain promoting effect on the phase conversion process. At a lower temperature, due to the insufficient driving force of the phase conversion process, it was difficult to transform FGD gypsum into hemihydrate gypsum. The optimal process conditions for preparing hemihydrate gypsum from FGD gypsum were determined as follows: sodium chloride concentration 10%, additive concentration 10%, solid-liquid ratio 1∶5, rotating speed 300 r/min, reaction temperature 100 ℃. Under the best process conditions, the reaction could be completed in 60 min. The average length of the prepared hemihydrate gypsum crystals was as high as 127 μm, and the average aspect ratio was as high as 19. At the same time, the relationship between the activity of water molecules in the solution, the degree of supersaturation and the reaction temperature was studied, and it was determined that the phase conversion process was determined by the temperature and the degree of supersaturation.

Abstract This article addresses the phenomenon of Netspeak reductions with special reference to Mandarin computer-mediated communication. A tentative classification of Chinese Netspeak reductions is first provided, namely, two-, three-, or four-character reductions occurring at both the lexical and the syntactic levels and other atypical reductions. It is then proposed that Zipf’s Principle of Least Effort, which usually works at the lexical level, can work as well at the utterance level and can account for the increasing number of Netspeak reductions in daily communication, that is, the frequency of using Netspeak reduction determines its vitality and distribution.

Abstract Background The epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBECs) is essential for airway remodeling during asthma. Wnt5a has been implicated in various lung diseases, while its role in the EMT of HBECs during asthma is yet to be determined. This study sought to define whether Wnt5a initiated EMT, leading to airway remodeling through the induction of autophagy in HBECs. Methods Microarray analysis was used to investigate the expression change of WNT5A in asthma patients. In parallel, EMT models were induced using 16HBE cells by exposing them to house dust mites (HDM) or interleukin-4 (IL-4), and then the expression of Wnt5a was observed. Using in vitro gain- and loss-of-function approaches via Wnt5a mimic peptide FOXY5 and Wnt5a inhibitor BOX5, the alterations in the expression of the epithelial marker E-cadherin and the mesenchymal marker protein were observed. Mechanistically, the Ca2+/CaMKII signaling pathway and autophagy were evaluated. An autophagy inhibitor 3-MA was used to examine Wnt5a in the regulation of autophagy during EMT. Furthermore, we used a CaMKII inhibitor KN-93 to determine whether Wnt5a induced autophagy overactivation and EMT via the Ca2+/CaMKII signaling pathway. Results Asthma patients exhibited a significant increase in the gene expression of WNT5A compared to the healthy control. Upon HDM and IL-4 treatments, we observed that Wnt5a gene and protein expression levels were significantly increased in 16HBE cells. Interestingly, Wnt5a mimic peptide FOXY5 significantly inhibited E-cadherin and upregulated α-SMA, Collagen I, and autophagy marker proteins (Beclin1 and LC3-II). Rhodamine-phalloidin staining showed that FOXY5 resulted in a rearrangement of the cytoskeleton and an increase in the quantity of stress fibers in 16HBE cells. Importantly, blocking Wnt5a with BOX5 significantly inhibited autophagy and EMT induced by IL-4 in 16HBE cells. Mechanistically, autophagy inhibitor 3-MA and CaMKII inhibitor KN-93 reduced the EMT of 16HBE cells caused by FOXY5, as well as the increase in stress fibers, cell adhesion, and autophagy. Conclusion This study illustrates a new link in the Wnt5a-Ca2+/CaMKII-autophagy axis to triggering airway remodeling. Our findings may provide novel strategies for the treatment of EMT-related diseases.

Abstract Background Glyphosate is a commonly used herbicide worldwide and is purportedly associated with multiple health effects. Research assessing the association of glyphosate concentrations with glycosylated hemoglobin (HbA1c) levels and the prevalence of diabetes is scarce. We sought to evaluate the association between urinary glyphosate levels and HbA1c levels and the prevalence of diabetes. Methods A total of 2,745 adults in the National Health and Nutrition Examination Survey from 2013 to 2016 were included in this study. Generalized linear models (GLM) were applied to evaluate the associations of glyphosate concentrations with HbA1c levels and the prevalence of diabetes. The dose–response relationship was examined using restricted cubic splines (RCS). Results Significantly positive correlations of urinary glyphosate concentrations with HbA1c levels (percentage change: 1.45; 95% CI: 0.95, 1.96; P

Abstract The importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC.

Abstract Background To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia. Methods We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits. Results The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P

Abstract Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial–mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity. Graphical Abstract

Abstract CO2 reduction photocatalysts are favorable for obtaining renewable energy. Enriched active sites and effective photogenerated‐carriers separation are keys for improving CO2 photo‐reduction. A thulium (Tm) single atom tailoring strategy introducing carbon vacancies in porous tubular graphitic carbon nitride (g‐C3N4) surpassing the ever‐reported g‐C3N4 based photocatalysts, with 199.47 µmol g−1 h−1 CO yield, 96.8% CO selectivity, 0.84% apparent quantum efficiency and excellent photocatalytic stability, is implemented in this work. Results revealed that in‐plane Tm sites and interlayer‐bridged Tm‐N charge transfer channels significantly enhanced the aggregation/transfer of photogenerated electrons thus promoting CO2 adsorption/activation and contributing to *COOH intermediates formation. Meanwhile, Tm atoms and carbon vacancies both benefit for rich active sites and enhanced photogenerated‐charge separation, thus optimizing reaction pathway and leading to excellent CO2 photo‐reduction. This work not only provides guidelines for CO2 photo‐reduction catalysts design but also offers mechanistic insights into single‐atom based photocatalysts for solar fuel production.

Abstract The volatile aroma released from agricultural products is closely related to the health status and quality of their growth, thus endowing the related detection with great significance. For example, the dynamic variation of the volatile chemical composition of a banana during the growth process can reflect its ripeness. Also important for quality monitoring and storage is to precisely and swiftly identify volatile compounds produced by mildew in rice and wheat. In this endeavor, the current detection technologies such as gas chromatography‐mass spectrometry method (GC‐MS) cannot meet the pressing needs of smart agriculture in terms of real‐time monitoring, cost‐effectiveness, sensitivity, and detection speed, thereby necessitating alternative strategies to simultaneously satisfy these requirements. Aiming to provide an overall development trend in this field, this paper summarizes the existing detection technologies including GC‐MS, E‐nose, and sensory analysis with their respective shortcomings and challenges, and then proposes the application prospects. This work can effectively enrich the reliable monitoring methods for volatile agricultural fragrance while promoting the long‐run development of smart agriculture.

The universal contamination of arable land with potentially toxic elements (PTEs) poses a severe threat to food security and jeopardizes worldwide efforts to meet the United Nations Sustainable Development Goals (SDGs). How to obtain more reliable concentrations of PTEs in regional agricultural soils is a priority problem to be solved. Multispectral satellite remote sensing, with its advantages of high spatial and temporal resolution, broad coverage, and low cost, offers the potential to acquire spatial distribution of PTEs in agricultural soils over large areas. However, owing to the complexity of soil environments and the insufficiency of spectral information, the mechanism for retrieving concentrations of PTEs in agricultural soils via multispectral satellites is not yet clear, and the accuracy needs to be improved. In this study, we aimed to assess whether employing a fusion of spectral information and environmental covariates, results in more accurate retrievals of PTEs, specifically chromium (Cr) and mercury (Hg), in croplands than does employing spectral information alone. Three machine learning algorithms—kernel-based support vector machine (SVM), neural network-based back propagation neural network (BPNN), and tree-based extreme gradient boosting (XGBoost)—were developed to retrieve Cr and Hg concentrations in agricultural soils. The results showed that the fusion of spectral information and environmental covariates combined with the XGBoost model performed best in retrieving both Cr and Hg concentrations in agricultural soils with coefficient of determination (R2) values of 0.73 and 0.74, respectively. Environmental covariates were important variables for determining Cr and Hg concentrations in agricultural soils, but the ability to retrieve these element concentrations by utilizing spectral information alone was limited. High Cr concentrations occurred in central towns and southern hilly mountains. High Hg concentrations were detected in the northwestern region and southern hilly mountains. The potential of fusing spectral information and environmental covariates to precisely retrieve PTE concentrations in agricultural soils can serve as a reference for agricultural soil health information monitoring worldwide.

BackgroundSoft tissue sarcoma (STS) are heterogeneous and rare tumors, and few studies have explored predicting the prognosis of patients with STS. The Lung Immune Prognostic Index (LIPI), calculated based on baseline serum lactate dehydrogenase (LDH) and the derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR), was considered effective in predicting the prognosis of patients with pulmonary cancer and other malignancies. However, the efficacy of the LIPI in predicting the prognosis of patients with STS remains unclear.MethodsThis study retrospectively reviewed patients with STS admitted to our center from January 2016 to January 2021. Their hematological and clinical characteristics were collected and analyzed to construct the LIPI specific to STS. The correlations between various predictive factors and overall survival (OS) were examined using Kaplan–Meier and Cox regression analyses. Independent risk factors for OS were identified using univariate and multivariate analyses. Finally, a LIPI nomogram model for STS was established.ResultsThis study enrolled 302 patients with STS, of which 87 (28.9%), 162 (53.6%), and 53 (17.5%) were classified into three LIPI-based categories: good, moderate, and poor, respectively (P < 0.0001). The time-dependent operator curve showed that the LIPI had better prognostic predictive ability than other hematological and clinical characteristics. Univariate and multivariate analyses identified the Fédération Nationale des Centres de Lutte Contre le Cancer grade (FNCLCC/G), tumor size, and LIPI as independent risk factors. Finally, a nomogram was constructed by integrating the significant prognostic factors. Its C-index was 0.72, and the calibration curve indicated that it could accurately predict the three- and five-year OS of patients with STS. The decision and clinical impact curves also indicated that implementing this LIPI-nomogram could significantly benefit patients with STS.ConclusionThis study explored the efficacy of the LIPI in predicting the prognosis of 302 patients with STS, classifying them into three categories to evaluate the prognosis. It also reconstructed a LIPI-based nomogram to assist clinicians in predicting the three- and five-year OS of patients with STS, potentially enabling timely intervention and customized management.

BackgroundTo clarify the controversy between inflammatory or autoimmune skin diseases and thyroid diseases, we performed two-sample Mendelian randomization (MR) analyses.ParticipantsGenetic data on factors associated with atopic dermatitis (AD, n=40,835), seborrheic dermatitis (SD, n=339,277), acne (n=363,927), rosacea (n=299,421), urticaria (n=374,758), psoriasis (n=373,338), psoriasis vulgaris (n=369,830), systemic lupus erythematosus (SLE, n=14,267), vitiligo (n=353,348), alopecia areata (AA, n=361,822), pemphigus (n=375,929), bullous pemphigoid (BP, n=376,274), systemic sclerosis (SSc, n=376,864), localized scleroderma (LS, n=353,449), hypothyroidism (n=314,995 or n=337,159), and hyperthyroidism (n=281,683 or n=337,159) were derived from genome-wide association summary statistics of European ancestry.Main measuresThe inverse variance weighted method was employed to obtain the causal estimates of inflammatory or autoimmune skin diseases on the risk of thyroid diseases, complemented by MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO).Key resultsAD, SLE, SD, and psoriasis vulgaris were associated with an increased risk of hypothyroidism, whereas BP was associated with a lower risk of hypothyroidism (all with p < 0.05). The multivariable MR analyses showed that AD (OR = 1.053; 95%CI: 1.015-1.092; p = 0.006), SLE (OR = 1.093; 95%CI: 1.059-1.127; p < 0.001), and SD (OR = 1.006; 95%CI: 1.002-1.010; p = 0.006) independently and predominately contributed to the genetic causal effect on hypothyroidism after adjusting for smoking. The results showed no causal effects of inflammatory or autoimmune skin diseases on hyperthyroidism.ConclusionThe findings showed a causal effect of AD, SLE, SD on hypothyroidism, but further investigations should be conducted to explore the pathogenic mechanisms underlying these relationships.

The viral genome titer is a crucial indicator for the clinical dosing, manufacturing, and analytical testing of recombinant adeno-associated virus (rAAV) gene therapy products. Although quantitative PCR and digital PCR are the common methods used for quantifying the rAAV genome titer, they are limited by inadequate accuracy and robustness. The clustered regularly interspaced short palindromic repeat (CRISPR)-Cas12a biosensor is being increasingly used in virus detection; however, there is currently no report on its application in the titer determination of gene therapy products. In the present study, an amplification-free CRISPR-Cas12a assay was developed, optimized, and applied for rAAV genome titer determination. The assay demonstrated high precision and accuracy within the detection range of 4 × 109 and 1011 vg/mL. No significant difference was observed between the Cas12a and qPCR assay results (p

Abstract Abscisic acid (ABA) plays a crucial role in promoting plant stress resistance and seed dormancy. However, how ABA regulates rice quality remains unclear. This study identifies a key transcription factor SLR1-like2 (SLRL2), which mediates the ABA-regulated amylose content (AC) of rice. Mechanistically, SLRL2 interacts with NF-YB1 to co-regulate Wx, a determinant of AC and rice quality. In contrast to SLR1, SLRL2 is ABA inducible but insensitive to GA. In addition, SLRL2 exhibits DNA-binding activity and directly regulates the expression of Wx, bHLH144 and MFT2. SLRL2 competes with NF-YC12 for interaction with NF-YB1. NF-YB1 also directly represses SLRL2 transcription. Genetic validation supports that SLRL2 functions downstream of NF-YB1 and bHLH144 in regulating rice AC. Thus, an NF-YB1-SLRL2-bHLH144 regulatory module is successfully revealed. Furthermore, SLRL2 regulates rice dormancy by modulating the expression of MFT2. In conclusion, this study revealed an ABA-responsive regulatory cascade that functions in both rice quality and seed dormancy.

Cornus hongkongensis Hemsl. 1888, native to Hong Kong, belongs to the subgenus Syncarpea within the Cornus genus of the Cornaceae family. The complete chloroplast genome of C. hongkongensis spans 156,954 bp, comprising four subregions: a large single-copy region (86,290 bp), a small single-copy region (18,394 bp), and a pair of inverted repeats (26,135 bp). Within the chloroplast genome of C. hongkongensis, we identified 113 unique genes, including 80 protein-encoding genes, four ribosomal RNA (rRNA) genes, and 30 transfer RNA (tRNA) genes. Phylogenetic analysis based on the complete chloroplast genome of 30 related taxa of the Cornus genus indicates that C. hongkongensis has not formed a monophyletic lineage. Analyses of sequence divergence found three intergenic regions including rps19-rpl22, ccsA-ndhD, and atpH-atpI, exhibiting a high degree of variations. The first chloroplast genome of C. hongkongensis was reported in this work contributes to the enrichment of genomic data for the genus Cornus.