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As a result of globalization, Chinese young adults who transit to adulthood currently are being exposed to a combination of traditional Chinese values such as collectivism and Confucian philosophy, as well as Western individualism. We analyzed the trends in depression prevalence within an 8-year period using panel data derived from young adults in China. The investigation further delved into the multifaceted correlates of depression, including demographic profiles, health-related parameters, and consequential life events. Data were obtained from five cycles, 2010 to 2018, of the China Family Panel Studies (CFPS). Participants included adults aged 18 to 24 years (total analytic sample N = 15,442). Depression symptoms increased in prevalence in Chinese young adults over the eight years; therefore, depression screening should be regularly conducted in this demographic. This study highlights the issue's gravity and suggests potential correlations with cultural, regional economic development level, gender, religion, hukou (household registration), lifestyle, chronic health conditions, on-going school attendance, and marital factors.

We investigate the dynamic characteristics of Covid-19 daily infection rates in Taiwan during its initial surge period, focusing on 79 districts within the seven largest cities. By employing computational techniques, we extract 18 features from each district-specific curve, transforming unstructured data into structured data. Our analysis reveals distinct patterns of asymmetric growth and decline among the curves. Utilizing theoretical information measurements such as conditional entropy and mutual information, we identify major factors of order-1 and order-2 that influence the peak value and curvature at the peak of the curves, crucial features characterizing the infection rates. Additionally, we examine the impact of geographic and socioeconomic factors on the curves by encoding each of the 79 districts with two binary characteristics: North-vs-South and Urban-vs-Suburban. Furthermore, leveraging this data-driven understanding at the district level, we explore the fine-scale behavioral effects on disease spread by examining the similarity among 96 age-group-specific curves within urban districts of Taipei and suburban districts of New Taipei City, which collectively represent a substantial portion of the nations population. Our findings highlight the implicit influence of human behaviors related to living, traveling, and working on the dynamics of Covid-19 transmission in Taiwan.

Zanthoxylum bungeanum, as a vital spice, the presence of its bitter components has a notable impact on the overall flavor of the food. To deeply explore the formation mechanism of the bitter components in Z. bungeanum and correlated influencing factors, this study used bitterness intensity as an indicator and employed sensory evaluation to optimize the processing conditions of Z. bungeanum during boiling and frying through single-factor optimization. Furthermore, organic solvent extraction, solid-phase extraction, and preparative high-performance liquid chromatography were used to isolate and concentrate the bitter fractions from Z. bungeanum water and oil. Subsequently, taste dilution analysis was employed to evaluate the contribution of these bitter fractions to the sensory characteristics of food. Additionally, high-performance liquid chromatography-mass spectrometry was adopted to identify the bitter components in Z. bungeanum water and oil. The results indicated that during the boiling process, increasing the amount of Z. bungeanum and extending the boiling time intensified the bitterness, while the bitterness of Z. bungeanum during frying process increased with raised temperature, extended frying time, and increased amount of Z. bungeanum. The recommended conditions for consumption and processing of Z. bungeanum water and Z. bungeanum oil were as follows: Z. bungeanum water was recommended to be boiled at 100 ℃ for 5 min, and the dosage of Z. bungeanum could be controlled at less than 2 g to reduce the bitter flavor. Z. bungeanum oil was recommended to be fried at 105~120 ℃ for 10~30 min, and the amount of Z. bungeanum could be added moderately to keep the bitter flavor low. The main bitter substances in Z. bungeanum water might be quercetin-3-rhamnose gentiobioside, quercetin-3,7-di-O-β-D-glucopyranoside, quercetin-3-O-robinobioside, and nuciferine, while the primary bitter compounds in Z. bungeanum oil were hydroxy-α-sanshool and hydroxy-β-sanshool. This study provides data reference and theoretical basis for the processing, quality control, and bitterness reduction of Z. bungeanum.

This paper analyzes the current status, technological developments, academic exchange platforms, and future challenges and solutions in the field of intelligent ophthalmology (IO) in China. In terms of technology, significant progress has been made in various areas, including diabetic retinopathy, fundus image analysis, quality assessment of medical artificial intelligence products, clinical research methods, technical evaluation, and industry standards. Researchers continually enhance the safety and standardization of IO technology by formulating a series of clinical application guidelines and standards. The establishment of domestic and international academic exchange platforms provides extensive collaboration opportunities for professionals in various fields, and various academic journals serve as publication platforms for IO research. However, challenges such as technological innovation, data privacy and security, lagging regulations, and talent shortages still pose obstacles to future development. To address these issues, future efforts should focus on strengthening technological research and development, regulatory framework construction, talent cultivation, and increasing patient awareness and acceptance of new technologies. By comprehensively addressing these challenges, IO in China is poised to further lead the industry's development on a global scale, bringing more innovation and convenience to the field of ophthalmic healthcare.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant neoplasm, and up to now, the role of long non-coding RNA (lncRNA) AP001885.4 in cancer, including ESCC, is absolutely unclear. The GEPIA database was applied to identify differentially expressed and prognosis-associated genes in esophageal cancer (ESCA). CCK-8, colony formation, Western blot, and qRT-PCR methods were harnessed to investigate the role and mechanism of AP001885.4 in esophageal carcinogenesis. By analyzing TCGA data in the GEPIA database, two lncRNAs were selected. AP001885.4 was overexpressed and positively associated with the unfavorable outcome of ESCC patients, and LINC001786 was under-expressed and negatively linked with the poor prognosis. Knockdown of AP001885.4 suppressed the proliferation and colony formation of ESCC cells. Importantly, the silence of AP001885.4 downregulated c-myc. Mechanically, the knockdown of AP001885.4 reduced METTL3 expression and m6A modification in c-myc mRNA, and METTL3 positively regulated c-myc. Furthermore, the knockdown of AP001885.4 diminished histone lactylation and NF-κB (p65) expression, and the protein lactylation inhibitors (2-DG, 2-deoxy-D-glucose and oxamate) and the NF-κB inhibitor (JSH-23) also lessened c-myc expression. Consequently, our findings suggested that AP001885.4 promoted the proliferation of esophageal squamous cell carcinoma cells by histone lactylation- and NF-κB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc.

ABSTRACTThe role of ferroptosis-associated gene SLC7A11 in esophageal cancer progression is largely unknown, therefore, the effects of blocking SLC7A11 on esophageal squamous cell carcinoma (ESCC) cells are evaluated. Results showed that SLC7A11 was overexpressed in ESCC tissues both in mRNA and protein levels. Blocking SLC7A11 using Erastin suppressed the proliferation and colony formation of ESCC cells, decreased cellular ATP levels, and improved ROS production. Sixty-three SLC7A11-binding proteins were identified using the IP-MS method, and these proteins were enriched in four signaling pathways, including spliceosome, ribosome, huntington disease, and diabetic cardiomyopathy. The deubiquitinase inhibitors PR-619, GRL0617, and P 22077 could reduce at least 40% protein expression level of SLC7A11 in ESCC cells, and PR-619 and GRL0617 exhibited suppressive effects on the cell viability and colony formation ability of KYSE30 cells, respectively. Erastin downregulated GPX4 and DHODH and also reduced the levels of β-catenin, p-STAT3, and IL-6 in ESCC cells. In conclusion, SLC7A11 was overexpressed in ESCC, and blocking SLC7A11 using Erastin mitigated malignant phenotypes of ESCC cells and downregulated key ferroptosis-associated molecules GPX4 and DHODH. The therapeutic potential of targeting SLC7A11 should be further evaluated in the future.

Abstract Photothermal catalysis is a promising strategy to combine the advantages of both thermal-catalysis and photocatalysis. Herein we achieve the protolignin conversion to aromatics via the photothermal catalytic transfer hydrogenolysis process intensified by the in-situ protection strategy. The Pd/TiO2 at 140 °C with UV irradiation can catalyze the reforming of primary alcohols to aldehydes and active H* species, which further participate in the acetalation protection of the 1,3-diol group of β-O-4 linkage and mediate the hydrogenolysis of Cβ–OAr bonds, respectively. The conversion of birch sawdust with ethanol as the hydrogen donor provides a 40 wt% yield of phenolic monomers, compared with an 11 wt% monomer yield obtained from the conversion of extracted 1,3-diol-protected lignin under the same conditions. The synergistic effect of photocatalysis and thermal-catalysis contributes to the prior cleavage of the Cβ–OAr bond before other C–O bonds. The feasibility of solar-light-driven photothermal catalytic system is demonstrated.

Metabolic abnormalities in mammalian joint tissues are closely linked to various diseases, including rheumatoid arthritis and osteoarthritis. The variations of small molecule metabolites within bone joint tissues can affect cell proliferation, drive the secretion of inflammatory mediators, mediate leukocyte infiltration, and consequently induce synovial inflammation and cartilage damage. Therefore, the development of novel mass spectrometry imaging (MSI) methods for visualizing metabolites in joint tissues is crucial for comprehensively understanding the metabolic characteristics of different microregions under both physiological and pathological conditions. In this study, an airflow-assisted desorption electrospray ionization (AFADESI)-MSI was used to establish an ambient MSI method for rat joint tissues. To ensure the effectiveness of the method, dynamic range, sensitivity, and imaging effect were selected as the primary evaluation criteria. The tissue preparation, section thickness, and spray solvent systems were systematically optimized. Compared to the AB glue transfer method, the tape adhesion method can obtain complete bone joint tissue sections and clearer images. A section thickness of 20 μm, as opposed to 15 μm, provides higher ion intensity in the m/z 600-900 range. Among the tested spray solvent systems, compared with methanol-water (8:2, V/V), acetonitrile-water (8:2, V/V), and the acetonitrile-isopropanol-water (6:2:2, V/V/V), the acetonitrile-isopropanol-water (4:4:2, V/V/V) prove to be the most effective, detecting the highest number of metabolites and lipids when employed as the spray solvent. The precision of this method was evaluated on six adjacent rat knee sections under positive and negative ion modes, with the relative standard deviation (RSD) for the ion intensity of representative metabolites being less than 20%. Subsequently, this method was utilized for spatially resolved metabolomics analysis of rat knee tissues. A total of 613 metabolites are annotated in the overall knee tissues. Based on the optical images, the rat knee tissues were segmented into three microregions for bone, marrow, and cartilage. 452, 418, and 451 metabolites in these microregions are identified, respectively. In bone, the pentose phosphate pathway, glyoxylate and dicarboxylate metabolism, and the TCA cycle are more prominent. In bone marrow, ascorbate and purine metabolism pathways are more significant. In cartilage, arginine and proline metabolism, as well as lysine degradation, are more pronounced. These findings highlight significant metabolic heterogeneity across different microregions of rat knee joint tissues. Overall, this study develops an AFADESI-MSI method for in-depth profiling of metabolites within rat joint tissues, providing a powerful tool for in situ visualization of metabolites in metabolic studies of joint tissues.

Abstract Background Conventional management (CM), substantial fertilization and flooding irrigation, has led to soil acidification, the decrease in soil bacterial diversity in bamboo forests. Integration of water and fertilizer management (IWF) can effectively improve the efficiency of water and fertilizer use, but its effect on soil environment, especially on microbial community, is still unclear. Methods Here, we used next-generation high-throughput sequencing to compare soil properties and bacterial communities through different fertilization and irrigation methods under IWF and CM. Results Compared to the control group, CM significantly reduced soil pH and bacterial diversity, while IWF improved soil nutrition status, increased soil bacterial diversity and soil pH to a level similar to the control group. Compared with CM, IWF also improved the relative abundance of beneficial bacteria and copiotrophic bacteria community in the soil, and the bacterial community in IWF was similar to CK. The structure of the bacterial community was also significantly correlated with soil organic matter, total nitrogen, hydrolyzable nitrogen, and available potassium, while soil bacterial diversity was mainly associated with soil hydrolyzable nitrogen. Conclusions IWF can play an important role in preventing soil acidification, the loss of soil bacterial diversity, and improving the structure of the bacterial community under specific conditions.

Abstract Background Previous research has identified a positive relationship between problematic social media use and depression. However, with the increasing diversification and personalization of social media platforms, the impact of different platforms on college students varies significantly. It is necessary to examine the specific symptom network of problematic use in certain platforms and its relationship with depression. Therefore, this study aims to address these gaps by investigating the symptom network of problematic WeChat use among college students and identifying bridge symptoms linking problematic WeChat use to depression. Method A total of 6,060 Chinese college students (Mean age = 18.32; range 16–21; 60.66% male, 39.34% female) were recruited and provided self-reports on their problematic WeChat use and depression levels. Latent profile analysis was employed to identify the profiles of problematic WeChat users. Subsequently, four network structures relating to problematic WeChat use and its association with depression were constructed among problematic users. Results The analysis revealed three heterogeneous groups of college students regarding their WeChat use, with 11.4% classified as problematic users. Network analysis indicated that the central symptoms of problematic WeChat use were “I feel the need to use WeChat with increasing amounts of time to achieve satisfaction” and “I have used WeChat to relieve of loneliness and stress”. No significant gender differences were found in the network structure of problematic WeChat use; the network strength was significantly higher among male students compared to female students. Within the combined network, the central symptoms included “self-dislike,” “pessimism,” “I feel happy and satisfied when I am on WeChat,” and “guilt.” A strong association was observed between problematic WeChat use and depressive symptoms. Conclusion The findings of this study further elucidate the impact of problematic WeChat use on depression among college students, providing both theoretical and practical insights for developing interventions targeting WeChat use and depression within this demographic.

Taking the mining of II-3 coal seam in Gongniergaigou area of 231 mining area of Zhuanlongwan Coal Mine as the research background, based on the key strata theory of strata control, the similar physical simulation experiment is used to study the failure field, displacement field and mining-induced fissures evolution law of overburden strata in shallow coal seam mining. The results show that the periodic breaking distance of the main key strata decreases with the increase of the thickness of the load layer due to the influence of the valley terrain load distribution. The periodic breaking distance of the main key strata in model 1, model 2 and model 3 is 7-17 cm, 12-20 cm and 11-23 cm, respectively. The maximum vertical displacement of the main key strata in model 1, model 2 and model 3 is 22.77 mm, 24.42 mm and 20.98 mm, respectively. It is not easy to form a stable “masonry beam” bearing structure after the key strata of the missing structure is broken, which is the main reason why the maximum vertical displacement of the main key stratum of model 2 is greater than that of model 1 and model 3. With the advancement of the working face, the influence range of overburden migration gradually increases in the vertical and horizontal directions. The main key stratum is in the stage of periodic breaking, and the development and formation of mining-induced fissures enter the active period. The number and spacing of mining-induced fissures are related to the breaking law of the main key stratum. The mining-induced fissures have dynamic change characteristics. The mining-induced fissures at the bottom of the valley and the slope foot on both sides are easily affected by extrusion. The fissures width is small or even closed, and the fissure morphology in the flat surface area is relatively stable.

Abstract Translational research in toxicology has significantly benefited from transcriptomic profiling, particularly in drug safety. However, its application has predominantly focused on limited organs, notably the liver, due to resource constraints. This paper presents TransTox, an innovative AI model using a generative adversarial network (GAN) method to facilitate the bidirectional translation of transcriptomic profiles between the liver and kidney under drug treatment. TransTox demonstrates robust performance, validated across independent datasets and laboratories. First, the concordance between real experimental data and synthetic data generated by TransTox was demonstrated in characterizing toxicity mechanisms compared to real experimental settings. Second, TransTox proved valuable in gene expression predictive models, where synthetic data could be used to develop gene expression predictive models or serve as “digital twins” for diagnostic applications. The TransTox approach holds the potential for multi-organ toxicity assessment with AI and advancing the field of precision toxicology.

Abstract Especially, the processing and utilization of biomass-based material is closely related to the vessel, e.g. the flow of vapour and additive. It is conventional that vessels in most plants can influence on water and nutrients transport between adjacent cells, which could just infer to be important in the wood-based panel industries. In this work, a complete characterization of vessels and pits is presented for three conventional biomasses in wood-based panel: poplar (Populus deltoides) (P), moso bamboo (Phyllostachys edulis) (B), and the fruit shell of oil camellia (Camellia Oleifera) (FS_OC). Every material is analyzed by combining several techniques including: light microscopy, scanning electron microscopy and surveying calculations from resin casting. The results show that among the three biomass materials, B has a significantly larger vessel width (164.8 ± 6.0 μm for B, 2.2 ± 6.2 μm for P, 10.0 ± 0.8 μm for FS_OC) and smaller inclination angle of the perforation plates (6.8° for B, 44.7° for P), which is more conductive to improving moisture transfer between the vessels. The vessel length of P varies widely from 676.8 μm to 1025.2 μm, which is related to its seasonal growth. By resin casting analysis, more differences in the morphology and distribution of pits in the vessel walls were observed between the three species. Such as, For B, there are numerous pits between vessel cells, while very few to none between vessel and parenchyma cells or fiber. In addition to pits, B and FS_OC also have spiral thickening structures on their vessel walls. The pit membrane is an elliptical shape in P, while slit-like shape in FS_OC and a combination of both elliptical and slit-like shape in bamboo. The unique microstructural characteristics of vessels is related to the individual plant growth traits, which is the basis for biomass-based material processing and utilization.

Abstract Ligusticum sinense cv. Chuanxiong (L. Chuanxiong), one of the widely used traditional Chinese medicines (TCM), is currently facing the problem of excessive cadmium (Cd) content. This problem has significantly affected the quality and safety of L. Chuanxiong and become a vital factor restricting its clinical application and international trade development. Currently, to solve the problem of excessive Cd, it is essential to research the response mechanisms of L. Chuanxiong to Cd stress. However, there are few reports on its physiological and biochemical responses under Cd stress. In this study, we conducted the hydroponic experiment under 25 μM Cd stress, based on the Cd content of the genuine producing areas soil. The results showed that 25 μM Cd stress not only had no significant inhibitory effect on the growth of L. Chuanxiong seedlings but also significantly increased the chlorophyll a content (11.79%) and root activity (51.82%) compared with that of the control, which might be a hormesis effect. Further results showed that the absorption and assimilation of NH4 + increased in seedlings under 25 μM Cd stress, which was associated with high photosynthetic pigments. Here, we initially hypothesized and confirmed that Cd exceedance in the root system of L. Chuanxiong was due to the thickening of the root cell wall, changes in the content of the cell wall components, and chelation of Cd by GSH. There was an increase in cell wall thickness (57.64 %) and a significant increase in cellulose (25.48%) content of roots under 25 μM Cd stress. In addition, L. Chuanxiong reduced oxidative stress caused by 25 μM Cd stress mainly through the GSH/GSSG cycle. Among them, GSH-Px (48.26%) and GR (42.64%) activities were significantly increased, thereby maintaining a high GSH/GSSG ratio. This study preliminarily reveals the response of L. Chuanxiong to Cd stress and the mechanism of Cd enrichment. It provides a theoretical basis for solving the problem of Cd excessive in L. Chuanxiong. Graphical Abstract Physiological and biochemical mechanisms of L. Chuanxiong seedlings under Cd stress.

Abstract Excessive alarmins S100A8/A9 escalate the inflammation and even exacerbate immune-driven thrombosis and multi-organ damage. However, the regulatory mechanisms of S100A8/A9 expression in infectious diseases remain unclear. In this study, high-dimensional transcriptomic data analyses revealed a high proportion of CD14+FCN1hi macrophages within the pulmonary niche post-severe SARS-CoV-2 infection. By constructing the S100-coexpression gene list and supervised module scoring, we found that CD14+FCN1hi macrophages presented the highest scores of alarmin S100, and possibly served as the trigger and amplifier of inflammation in severe COVID-19. These CD14+FCN1hi cells lacked the positive regulatory activity of transcription factor PPARγ, and lost their differentiation ability towards mature macrophages. Ex vivo experiments further validated that the epithelial cells with high ORF-3a expression promoted the expression and secretion of S100A8/A9 through ANXA1/SAA1-FPR1 signaling. S100A8/A9 heterodimers, as well as the co-localization of S100A8/A9 with microtubules, were both diminished by the FPR1 inhibitor. Phospho-kinase protein array indicated that STAT3 promoted transcription, and PLC-γ and ERK1/2 pathways were involved in the hetero-dimerization and unconventional secretion of S100A8/A9. Our study highlights the pivotal role of FPR1 signaling in the excessive production of S100A8/A9 and provides a promising target for the prevention and control of severe COVID-19 and post-acute COVID-19 sequelae.

Abstract Background We previously developed a nanobody targeting CTLA-4 and demonstrated that it can boost antitumour T-cell responses in vitro; however, the resulting responses after the injection of T cells into cancer models are usually weak and transient. Here, we explored whether fusing our nanobody to IL-12 would enable it to induce stronger, longer-lasting T-cell immune responses after exposure to immature dendritic cell and tumour cell fusions. Results The fusion protein enhanced the response of CD8+ T cells to tumour antigens in vitro and led to stronger, more persistent immune responses after the T cells were injected into mice bearing different types of xenografts. Conclusion Our in vitro and in vivo results suggest the anticancer potential of our nanobody-interleukin fusion system and support the clinical application of this fusion approach for various nanobodies.

Abstract Background Multidrug- or rifampicin-resistant tuberculosis (TB; MDR/RR-TB) is a significant public health threat. However, the mechanisms involved in its transmission in Sichuan, China are unclear. To provide a scientific basis for MDR/RR-TB control and prevention, we investigated the drug-resistance characteristics, genetic diversity, and transmission dynamics and analyzed the demographic and clinical characteristics of patients to identify risk factors for the acquisition of MDR/RR-TB in Sichuan, Western China. Methods Whole-genome sequencing was performed using a sample comprised of all MDR/RR-TB strains isolated from patients with pulmonary TB (≥ 15 years) at the 22 surveillance sites in Sichuan province between January 2019 and December 2021, to analyze genotypic drug resistance and genetic diversity. Moreover, we performed statistical analyses of the epidemiological characteristics and risk factors associated with the transmission dynamics of MDR/RR-TB. Results The final analysis included 278 MDR/RR TB strains. Lineage 2.2, the major sub-lineage, accounted for 82.01% (228/278) of isolates, followed by lineage 4.5 (9.72%, 27/278), lineage 4.4 (6.83%, 19/278), and lineage 4.2 (1.44%, 4/278). The drug resistance rates, ranging from high to low, were as follows: isoniazid (229 [82.37%]), streptomycin (177 [63.67%]), ethambutol (144 [51.80%]), pyrazinamide (PZA, 119 [42.81%]), fluoroquinolones (FQs, 93 [33.45%]). Further, the clofazimine, bedaquiline, and delamanid resistance rates were 2.88, 2.88, and 1.04%, respectively. The gene composition cluster rate was 32.37% (90/278). In addition, 83.81% (233/278) of MDR/RR-TB cases were determined to be likely caused by transmission. Finally, patients infected with lineage two strains and strains with the KatG S315T amino acid substitution presented a higher risk of MDR/RR-TB transmission. Conclusion Transmission plays a significant role in the MDR/RR-TB burden in Sichuan province, and lineage 2 strains and strains harboring KatG S315T have a high probability of transmission. Further, high levels of FQ and PZA drug resistance suggest an urgent need for drug susceptibility testing prior to designing therapeutic regimens. New anti-TB drugs need to be used standardly and TB strains should be regularly monitored for resistance to these drugs.

Abstract Objectives To explore the role of nodule-pleural relationship, including nodule with pleural tail sign (PTS), nodule with pleural contact and nodule with pleural unrelated in CT-guided percutaneous transthoracic needle biopsy (PTNB)-induced pneumothorax, and whether employing different puncture routes has an impact on the incidence of pneumothorax in PTNB of nodules with PTS. Methods Between April 1, 2019, to June 30, 2021, 775 consecutive PTNB procedures of pulmonary nodules in the Peking University Cancer Hospital were retrospectively reviewed. The univariate and multivariate regression analysis were used to identify the risk factors for pneumothorax in PTNB. Results The nodule with pleural contact group has a lower incidence of pneumothorax than the nodule with PTS group (p = 0.001) and the nodule with pleural unrelated group (p = 0.002). It was observed that a higher incidence of pneumothorax caused by crossing PTS compared with no crossing PTS (p

Abstract Background Few studies quantified the influence of the coronavirus disease 2019 (COVID-19) pandemic on medical teaching and scientific research activities in China. This is the first national study to investigate such topics from the viewpoint of physicians practicing obstetrics and gynecology in China. Methods This is a national questionnaire survey with online interviews for respondents. This two-stage, stratified, cluster sampling method was applied based on city categories (categories 1 to 3 correspond to 30,000 beds, respectively), hospital levels (primary, secondary, and tertiary), and hospital types (general and specialized) in China among physicians practicing obstetrics and gynecology. Physicians documented notable alterations in both overall and specialized teaching and research engagements. Comparative analyses were conducted across diverse municipal and hospital attributes. Results Data were collected from a representative sample of 11,806 physicians from 779 hospitals across 157 cities and 31 provinces. Notably, except for online seminars, a minimum reduction of 20% in both overall and specialized teaching and research activities was observed among physicians. Up to 61.7% (95% confidence interval 59.3–64.0) of physicians reported either a complete termination or a > 50% decline in resident training. Compared with category 1 cities and primary hospitals, category 3 cities and tertiary hospitals experienced greater reductions in items of resident or graduate education, visiting scholar, clinical trials, and laboratory studies (adjusted p values

To solve problems of the low yields and dark color of Sargassum horneri polysaccharides which were produced according to the traditional extraction method under the high-temperature and alkalic condition, this study attempted to produce S. horneri polysaccharides at a lower alkaline treatment temperature of 60 ℃ and optimize the process parameters by the response surface methodology. The combined scores of alginate and fucoidan yields and whiteness index (WI) were used as assessment indices to identify the optimal process condition. Under the optimal extraction condition, the concentration of NaClO addition was changed to investigate its effect on various characteristics of the produced alginate and fucoidan. The results showed that the polysaccharide comprehensive score was significantly correlated with the alkaline concentration, the extraction time, and the dosage of NaClO (P

Objective This study investigated the impact of Aspergillus niger lysing polysaccharide monooxygenase (AnLPMO) on in vitro rumen microbial fermentation of rice straw. Methods AnLPMO was heterologously expressed in Escherichia coli. Fourier transform infrared spectrometry and X-ray photoelectron spectroscopy analyzed the surface structure of rice straw after AnLPMO treatment. Two in vitro experiments, coupled with 16S high-throughput sequencing and quantitative real–time polymerase chain reaction techniques, assessed the influence of AnLPMO on rumen microbial fermentation of rice straw. Results AnLPMO exhibited peak activity at 40°C and pH 6.5, with a preference for rice straw xylan hydrolysis, followed by Avicel. AnLPMO application led to the fractional removal of cellulose and hemicelluloses and a notable reduction in the levels of carbon elements and C–C groups present on the surface of rice straw. Compared to the control (no AnLPMO), supplementing AnLPMO at 1.1 to 2.0 U significantly enhanced in vitro digestibility of dry matter (IVDMD, p

Abstract Fresh‐cut pineapple is highly popular with consumers, but it is also susceptible to quality deterioration during storage or shelf life. This study aimed to explore the effects of caffeic acid on the quality of fresh‐cut pineapple, specifically in relation to epigenetic regulation. The application of caffeic acid efficiently maintained fruit quality of pineapple slices stored at 4°C. Interestingly, caffeic acid treatment resulted in the increased accumulation of flavonoids in fresh‐cut pineapple. Moreover, the expression of several flavonoids biosynthesis‐related genes (AcPAL, AcF3’H, AcCHI, AcCHS2, Ac4CL, and AcFLS) was upregulated by caffeic acid. Furthermore, caffeic acid increased the methylation levels of H3K4me3, a gene‐activated epigenetic marker, at the loci of AcF3’H, AcCHI, AcCHS2, Ac4CL, and AcFLS. Overall, these findings suggest that the treatment with caffeic acid leads to increased levels of H3K4me3 and activates the expression of flavonoids biosynthesis‐related genes, thereby promoting the accumulation of flavonoids and maintaining the quality of pineapple slices.

Abstract Rosacea is a chronic inflammatory skin disease that typically affects the central facial area. Its main clinical symptoms include paroxysmal flushing, telangiectasia, and non-temporary erythema. Cell-free adipose tissue extracts (ATEs) are liquid components extracted from human adipose tissue that contain large amounts of growth factors. Despite the scar-reducing, anti-aging, and wound-healing effects of ATEs, the efficacy of ATEs in rosacea remains unknown. Therefore, the anti-rosacea effects of ATEs were investigated in human cathelicidin peptide (LL-37) induced rosacea mice and capsaicin (CAP)-stimulated HaCaT keratinocytes. In vitro, ATEs significantly reduced TRPV1 expression, intracellular calcium ions influx and the release of inflammatory factors (such as KLK5, IL-6, IL-8 and TNF-α) after intervening in CAP-stimulated cells. The in vivo results revealed that ATEs alleviated rosacea symptoms, such as erythema score, erythema area, transepidermal water loss, abnormal epidermal thickness, mast cell infiltration and telangiectasia upon downregulating TRPV1 and CD31 expression. Moreover, the up-regulated TRPV1 protein expression was also recovered by ATEs administration in vivo and in vitro. Meanwhile, ATEs demonstrated good biocompatibility. In summary, ATEs could be a potential therapeutic agent for rosacea by regulating inflammation and alleviating telangiectasia.

Abstract In this paper, a flexural Mikaelian lens in thin plate is designed by using conformation transformation. The propagation characteristics of flexural waves in the lens are investigated through rays trajectory equation, simulation analyses, and experimental tests, confirming the self-focusing properties of the Mikaelian lens. Additionally, the study explores the Talbot effect for flexural waves, revealing through simulation studies that the Talbot effect within the Mikaelian lens exhibits nearly diffraction-free properties. Building on the non-diffractive nature of the Talbot effect within the Mikaelian lens, we explore the potential for encoding flexural waves using active interference sources. The simulation and experiment results demonstrate the good performance of the designed active encoding system. This work opens up new avenues for the encoding of flexural waves, presenting promising implications for applications in communication such as structural health monitoring, wireless communication in solid media and data transmission in robotics and other areas related to flexural wave technology.

Abstract Backgroud The relationship between serum uric acid (SUA) and 25-hydroxyvitamin D (25(OH)D) has been variably characterized in existing literature, with inconsistent results regarding its nature and implications in the Chinese population. This study aims to clarify this association, considering the potential impact of vitamin D levels on SUA. Methods This cross-sectional study involved 7,086 individuals from the Second Affiliated Hospital of Zhejiang University School of Medicine, screened throughout 2020. We collected data on 25(OH)D, SUA, and other metabolic markers. Logistic regression models adjusted for confounding factors were utilized to analyze the relationships. Results Our findings illustrate a statistically significant inverted U-shaped relationship between 25(OH)D and SUA. The identified threshold effect at 28.82 ng/ml is pivotal; with 25(OH)D levels below this point associated with an increased risk of hyperuricemia (odds ratio: 1.0146, p = 0.0148), and levels above it offering protective benefits (odds ratio: 0.9616, p = 0.0164). Conclusions Our findings confirm a nonlinear, inverted U-shaped correlation between 25(OH)D and SUA, emphasizing the importance of maintaining vitamin D levels within a specific range to effectively manage hyperuricemia. These results support the implementation of personalized vitamin D supplementation strategies to optimize metabolic health outcomes, highlighting the complex interplay between vitamin D status and uric acid levels.

Abstract Background Transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC. Methods Clinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed. Results Patients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment. Conclusions Patients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead.

Abstract Background Natural products have a long history in drug discovery. Lycorine is an alkaloid derived from Amaryllidaceae plants, demonstrating significant pharmacological potential. Lycorine and its hydrochloride salt, lycorine hydrochloride, have shown outstanding anticancer effects both in vitro and in vivo. Purpose This review aims to comprehensively summarize recent research advancements regarding the anticancer potential of lycorine and lycorine hydrochloride. It intends to elucidate current research limitations, optimization strategies, and future research directions to guide clinical translation. Methods Various databases, e.g., Web of Science, PubMed, and Chinese National Knowledge Infrastructure, are systematically searched for relevant articles using keywords such as lycorine, cancer, pharmacokinetics, and toxicity. The retrieved literature is then categorized and summarized to provide an overview of the research advancements in the anticancer potential of lycorine and lycorine hydrochloride. Results Lycorine and lycorine hydrochloride demonstrate significant anticancer activities against various types of cancer both in vitro and in vivo, employing diverse mechanisms such as inducing cell cycle arrest, triggering cellular senescence, regulating programmed cell death, inhibiting angiogenesis, suppressing metastasis, and modulating immune system. Furthermore, pharmacokinetic profiles and toxicity data are summarized. Additionally, this review discusses the druggability, limitations, optimization strategies, and target identification of lycorine, offering insights for future preclinical studies. Conclusion The anticancer effects and safety profile of lycorine and lycorine hydrochloride suggest promising potential for clinical applications. Further research on their in-depth mechanisms and optimization strategies targeting their limitations will enhance the understanding and druggability of lycorine and lycorine hydrochloride. Graphical Abstract

Abstract Recent studies have identified a correlation between chronic viral hepatitis and cognitive impairment, yet the underlying mechanisms remain unclear. This study investigated the influence of TGFB1 genetic polymorphisms on cognitive function in individuals with and without hepatitis infections, hypothesizing that these polymorphisms and the viral hepatitis‐induced inflammatory environment interact to affect cognitive abilities. Participants (173 with viral hepatitis and 258 healthy controls) were recruited. Genotyping of TGFB1 SNPs was performed using the C2‐58 Axiom Genome‐Wide TWB 2.0 Array Plate. Cognitive function was assessed using the MMSE and MoCA tests. Our results showed that healthy individuals carrying the C allele of rs2241715 displayed better performance in sentence writing (p = 0.020) and language tasks (p = 0.022). Notably, viral hepatitis was found to moderate the impact of the rs2241715 genotype on language function (p = 0.002). Similarly, those carrying the T allele of rs10417924 demonstrated superior orientation to time (p = 0.002), with viral hepatitis modifying the influence of the SNP on this particular cognitive function (p = 0.010). Our findings underscore the significant role of TGFβ1 in cognitive function and the moderating impact of viral hepatitis on TGFB1 SNP effects. These findings illuminate the potential of TGFB1 as a therapeutic target for cognitive impairment induced by viral hepatitis, thus broadening our understanding of TGFβ1 functionality in the pathogenesis of neurodegeneration.

Background/purpose: Zirconia has been a popular material in dental implantology with good biocompatibility. But few research focused on its application in implant drills. This study aimed to investigate the physical, thermal, and biological effects on using the zirconia and stainless-steel drills for implant bone site preparation. Methods: We performed a series of experiments to evaluate the physical wearing properties of zirconia and stainless-steel drills of identical diameter and similar shape. During the implant site preparation thermal test, we subjected both drills onto a resin-embedded bone, utilizing a thermal couple device without irrigation. Moreover, we conducted a cell study by collecting bone cells in vivo while preparing the implant site with both tested drills. The cell activity was evaluated through cell proliferation colorimetric analysis (XTT) and alkaline phosphatase (ALP) activity measurements. Results: The zirconia drill outperforms the stainless-steel drill in terms of requiring less force, maintaining stability over repeated cutting tests, and generating lower temperatures during drilling (stainless-steel drill: 45.48 ± 1.31 °C; zirconia-coated drill: 32.98 ± 1.21 °C, P = 0.000247). Meanwhile, both types of drills show similar results in XTT colorimetric analysis and ALP activity test. Conclusion: The thermal effect study is more favorable for using the zirconia drill than the stainless-steel drill for bone preparation. Cytological analysis indicate that the zirconia drill produces a similar impact on bone cells activity as the stainless-steel drill. Therefore, we conclude that the zirconia drills offer a good cutting effect similar to currently available stainless-steel drills in various aspects.

Although serving as the workhorse, MS/MS cannot fully satisfy the analytical requirements of quantitative sub-metabolome characterization. Because more information intrinsically correlates to more structural and concentration clues, here, efforts were devoted to comprehensively tracing and deciphering MS/MS behaviors through constructing triple three-dimensional (3×3D)-MS/MS spectrum. Ginsenosides-targeted metabolomics of notoginseng, one of the most famous edible medicinal plants, was employed as a proof-of-concept. Serial authentic ginsenosides were deployed to build the correlations between 3×3D-MS/MS spectra and structure/concentration features. Through assaying ginsenosides with progressive concentrations using QTOF-MS to configure 1st 3D spectrum, the generations of MS1 spectral signals, particularly multi-charged multimer anions, e.g., [2M–2H]2– and [2M+2HCOO]2– ions, relied on both concentration and the amount of sugar chains. By programming progressive collision energies to the front collision cell of Qtrap-MS device to gain 2nd 3D spectrum, optimal collision energy (OCE) corresponding to the glycosidic bond fission was primarily correlated with the masses of precursor and fragment ions and partially governed by the glycosidation site. The quantitative relationships between OCEs and masses of precursor and fragment ions were utilized to build large-scale quantitative program for ginsenosides. After applying progressive exciting energies to the back collision chamber to build 3rd 3D spectrum, the fragment ion and the decomposition product anion exhibited identical dissociation trajectories when they shared the same molecular geometry. After ginsenosides-focused quantitative metabolomics, significant differences occurred for sub-metabolome amongst different parts of notoginseng. The differential ginsenosides were confirmatively identified by applying the correlations between 3×3D-MS/MS spectra and structures. Together, 3×3D-MS/MS spectrum covers all MS/MS behaviors and dramatically facilitates sub-metabolome characterization from both quantitative program development and structural identification.

Abstract Background To investigate the relationship between preoperative low serum albumin and perioperative blood transfusion in patients undergoing total joint arthroplasty (TJA). Methods We enrolled 2,772 TJA patients from our hospital between January 1, 2017, and January 1, 2022. Clinical data were extracted from electronic medical records, including patient ID, sex, BMI (Body Mass Index), age, and diagnoses. Receiver operating characteristic curves were constructed to establish thresholds for serum albumin levels categorization. Propensity score matching (PSM) was developed with preoperative serum albumin as the dependent variable and perioperative blood transfusion-related factors as covariates, including BMI grade, age grade, sex, diagnosis, hypertension, diabetes, coronary heart disease, chronic obstructive pulmonary disease, chronic bronchitis, cerebral infarction, major surgeries within the last 12 months, renal failure, cancer, depression, corticosteroid use, smoking, drinking, and blood type. The low serum albumin group was matched with the normal albumin group at a 1:2 ratio, employing a caliper value of 0.2. Binary logistic regression was employed to analyze the outcomes. Results An under the curve of 0.601 was discovered, indicating a cutoff value of 37.3 g/L. Following PSM, 892 cases were successfully paired in the low serum (

Abstract The Ideal Plant Architecture 1 (IPA1) transcription factor promotes rice yield and immunity through phosphorylation at its amino acid residue Ser163 as a switch. Although phosphorylated IPA1 mimic, IPA1(S163D), directly targets the promoter of immune response gene WRKY45, it cannot activate its expression. Here, we identified a co-activator of IPA1(S163D), a RING-finger E3 ligase IPA1 interactor 7 (IPI7), which fine-tunes the transcriptional activity of IPA1 to timely promote plant immunity and simultaneously maintain growth for yield. IPI7 interacts with IPA1 and promotes K29-polyubiquitination of IPA1 in vitro and in vivo. However, the stability of IPA1 protein is not affected by IPI7-mediated ubiquitination. The IPI7-promoted K29-polyubiquitination of IPA1 is induced by Magnaporthe oryzae infection and required for phosphorylated IPA1 to transactivate WRKY45 expression for immune response but not for plain IPA1 to transactivate DENSE AND ERECT PANICLES 1 (DEP1) expression for panicle development. IPI7 knockout impairs IPA1-mediated immunity but not yield. Our study reveals that plants utilize non-proteolytic K29-ubiquitination as a response to pathogen infection to fine-tune IPA1 transactivation activity for promoting immunity.

Staircase choice is one of the most critical factors leading to the difference in pedestrian flow and evacuation routes in buildings with multiple staircases. Neither the shortest path to the building exit nor the locally quickest path to the nearest staircase can represent the natural mode of evacuation path choices for an authentic evacuation simulation. Thus, a prediction-based approach is established to predict and simulate evacuation choices, which helps to address three key issues: (1) extracting evacuation data through a controlled experiment; (2) establishing a Logit model for staircase choice prediction based on experimental data; (3) developing a prediction-based cellular automaton model. The proposed approach has achieved the coupling between choice prediction and evacuation simulation. A comparison with Pathfinder software is conducted to reveal the superiority of the prediction-based CA model for simulating staircase choice.

The hybrids (BY) derived from blunt snout bream (Megalobrama amblycephala, BSB, ♀) and Bleeker's yellow tai (Xenocypris davidi Bleeker, YT, ♂) have a fast growth rate and body thickness. However, the molecular mechanisms underlying the growth advantage of BY are still unclear. MSTN, a member of the TGF-β superfamily, is a negative regulator of muscle growth and development. MYOD, a member of the myogenic regulatory factor family (MRFs), is a positive regulator of muscle growth and development. MSTN and MYOD interact to co-regulate muscle growth and development. In this study, we cloned the full-length cDNAs of mstn and myod in BY, analyzed differential expression of the two genes in muscle of BY and its parents, and observed the localization of the two genes during embryonic development of BY. Multiple sequence alignment of amino acids and phylogenetic analysis showed that mstn and myod were highly conserved in BY, BSB, YT, and other carp family fishes. Quantitative Real-time PCR (qRT-PCR) showed that mstn and myod were primarily expressed in muscle of BY, and there were significant differences in the expression of the two genes in the red and white muscles of BY, BSB, and YT at different age. The results of in situ hybridization of embryos showed an overlap in the temporal and spatial expression of mstn and myod in BY embryo development, suggesting that the two genes might interact to co-regulate embryo growth and development. This study provides a theoretical basis for further research on the mechanisms of mstn and myod in muscle growth of hybrid fishes.

Abstract Developing a regional damage function to quickly estimate direct economic losses (DELs) caused by heavy rain and floods is crucial for providing scientific supports in effective disaster response and risk reduction. This study investigated the factors that influence regional rainfall-induced damage and developed a calibrated regional rainfall damage function (RDF) using data from the 2016 extreme rainfall event in Hebei Province, China. The analysis revealed that total precipitation, asset value exposure, per capita GDP, and historical geological disaster density at both the township and county levels significantly affect regional rainfall-induced damage. The coefficients of the calibrated RDF indicate that doubling the values of these factors leads to varying increases or decreases in rainfall-induced damage. Furthermore, the study demonstrated a spatial scale dependency in the coefficients of the RDF, with increased elasticity values for asset value exposure and per capita GDP at the county level compared to the township level. The findings emphasize the challenges of applying RDFs across multiple scales and highlight the importance of considering socioeconomic factors in assessing rainfall-induced damage. Despite the limitations and uncertainties of the RDF developed, this study contributes to our understanding of the relationship between physical and socioeconomic factors and rainfall-induced damage. Future research should prioritize enhancing exposure estimation and calibrating RDFs for various types of rainfall-induced disasters to improve model accuracy and performance. The study also acknowledges the variation in RDF performance across different physical environments, especially concerning geological disasters and slope stability.

Abstract Transcranial temporal interference stimulation (tTIS) is a promising brain stimulation method that can target deep brain regions by delivering an interfering current from surface electrodes. Most instances of tTIS stimulate the brain with a single-frequency sinusoidal waveform generated by wave interference. Theta burst stimulation is an effective stimulation scheme that can modulate neuroplasticity by generating long-term potentiation- or depression-like effects. To broaden tTIS application, we developed a theta burst protocol using tTIS technique to modulate neuroplasticity in rats. Two cannula electrodes were unilaterally implanted into the intact skull over the primary motor cortex. Electrical field of temporal interference envelopes generated by tTIS through cannula electrodes were recorded from primary motor cortex. Theta burst schemes were characterized, and motor activation induced by the stimulation was also evaluated simultaneously by observing electromyographic signals from the corresponding brachioradialis muscle. After validating the stimulation scheme, we further tested the modulatory effects of theta burst stimulation delivered by tTIS and by conventional transcranial electrical stimulation on primary motor cortex excitability. Changes in the amplitude of motor evoked potentials, elicited when the primary motor cortex was activated by electrical pulses, were measured before and after theta burst stimulation by both techniques. Significant potentiation and suppression were found at 15 to 30 min after the intermittent and continuous theta burst stimulation delivered using tTIS, respectively. However, comparing to theta burst stimulations delivered using conventional form of transcranial electrical stimulation, using tTIS expressed no significant difference in modulating motor evoked potential amplitudes. Sham treatment from both methods had no effect on changing the motor evoked potential amplitude. The present study demonstrated the feasibility of using tTIS to achieve a theta burst stimulation scheme for motor cortical neuromodulation. These findings also indicated the future potential of using tTIS to carry out theta burst stimulation protocols in deep-brain networks for modulating neuroplasticity.

Abstract Systems theory and complex science, especially knowledge of social–ecological interdependencies, are urgently needed in planning and decision-making on sustainable urban development due to the intensification of the contradiction between human development and nature conservation. Here, we present an analytical framework, the “social–ecological coupling trajectory”, that integrates the social–ecological coupling, multi-stability, causal feedbacks and sustainable management through understanding the evolution of the urban social–ecological system (SES). This framework is applied to a typical urban SES, i.e., China’s rapidly prosperous Pearl River Delta (PRD). Our results indicate that the SES evolution in the PRD is a phased process, which is accompanied by a continuous decline in major ecosystem services (ESs) and the disproportionate decline of ecological management performance. Further analysis shows that social and economic policies have a decisive role in driving the evolution of SES and the cumulative effect of sustained human interference is directly linked to the disproportionate increase in sustainability challenges. The findings of critical slowing down and evolution patterns of SES in the PRD may provide evidence for the threshold recognition and regime shift prediction in SES. In sum, this study expands the theoretical framework and empirical knowledge of SES evolution and provides a pathway for sustainable development of regions seeking prosperity from the social–ecological coupling perspective.

Abstract Background This study aimed to investigate the potential variance in the prevalence of early‐onset scoliosis among children aged 4–7 years and analyze the influencing factors. The goal was to establish a crucial reference point for monitoring and evaluating spinal curvature development in preschoolers, ultimately to reduce the occurrence of adverse health outcomes. Methods Children aged 4–7 years within the main urban area of Nanjing were selected using a stratified random sampling method. A team of four senior therapists conducted screenings for spinal curvature among children using visual inspection, the Adams forward bending test, and an electronic scoliometer to measure the angle of trunk rotation (ATR) and identify children displaying signs of scoliosis. Children with suspected scoliosis in the initial screening underwent X‐ray Cobb angle assessment for confirmation. The prevalence of early‐onset scoliosis was then determined from the screening results. R version 4.2.0 software was used to analyze the factors associated with scoliosis among children using partial least squares structural equation modeling. Results A total of 2281 children were included in this study, consisting of 1211 boys and 1070 girls, with a mean age of 5.44 ± 0.81 years (ranging from 4 to 7 years). Among them, 7.58% exhibited positive signs of scoliosis, 5.87% had early‐onset scoliosis, and the positive predictive value was 77.5%. Significant differences in ATR were observed among children in different age groups (Kruskal–Wallis = 15, p = 0.0104) and by sex (t = 3.17, p = 0.00153). Significant variations in ATR were noted in children with scoliosis (t = −22.7, p

Abstract Protein complexes are fundamental to all cellular processes, so understanding their evolutionary history and assembly processes is important. Gene duplication followed by divergence is considered a primary mechanism for diversifying protein complexes. Nonetheless, to what extent assembly of present-day paralogous complexes has been constrained by their long evolutionary pathways and how cross-complex interference is avoided remain unanswered questions. Subunits of protein complexes are often stabilized upon complex formation, whereas unincorporated subunits are degraded. How such cooperative stability influences protein complex assembly also remains unclear. Here, we demonstrate that subcomplexes determined by cooperative stabilization interactions serve as building blocks for protein complex assembly. We further develop a protein stability-guided method to compare the assembly processes of paralogous complexes in cellulo. Our findings support that oligomeric state and the structural organization of paralogous complexes can be maintained even if their assembly processes are rearranged. Our results indicate that divergent assembly processes by paralogous complexes not only enable the complexes to evolve new functions, but also reinforce their segregation by establishing incompatibility against deleterious hybrid assemblies.

Abstract Background Extracellular vesicles (EVs) are membrane-enclosed structures containing lipids, proteins, and RNAs that play a crucial role in cell-to-cell communication. However, the precise mechanism through which circulating EVs disrupt hepatic glucose homeostasis in gestational diabetes mellitus (GDM) remains unclear. Results Circulating EVs isolated from human plasma were co-cultured with mammalian liver cells to investigate the potential induction of hepatic insulin resistance by GDM-EVs using glucose output assays, Seahorse assays, metabolomics, fluxomics, qRT-PCR, bioinformatics analyses, and luciferase assays. Our findings demonstrated that hepatocytes exposed to GDM-EVs exhibited increased gluconeogenesis, attenuated energy metabolism, and upregulated oxidative stress. Particularly noteworthy was the discovery of miR-1299 as the predominant miRNA in GDM-EVs, which directly targeting the 3′-untranslated regions (UTR) of STAT3. Our experiments involving loss- and gain‐of‐function revealed that miR-1299 inhibits the insulin signaling pathway by regulating the STAT3/FAM3A axis, resulting in increased insulin resistance through the modulation of mitochondrial function and oxidative stress in hepatocytes. Moreover, experiments conducted in vivo on mice inoculated with GDM-EVs confirmed the development of glucose intolerance, insulin resistance, and downregulation of STAT3 and FAM3A. Conclusions These results provide insights into the role of miR-1299 derived from circulating GDM-EVs in the progression of insulin resistance in hepatic cells via the STAT3/FAM3A axis and downstream metabolic reprogramming.

Abstract Background A combination of prone positioning (PP) and venovenous extracorporeal membrane oxygenation (VV-ECMO) is safe, feasible, and associated with potentially improved survival for severe acute respiratory distress syndrome (ARDS). However, whether ARDS patients, especially non-COVID-19 patients, placed in PP before VV-ECMO should continue PP after a VV-ECMO connection is unknown. This study aimed to test the hypothesis that early use of PP during VV-ECMO could increase the proportion of patients successfully weaned from ECMO support in severe ARDS patients who received PP before ECMO. Methods In this prospective observational study, patients with severe ARDS who were treated with VV-ECMO were divided into two groups: the prone group and the supine group, based on whether early PP was combined with VV-ECMO. The proportion of patients successfully weaned from VV-ECMO and 60-day mortality were analyzed before and after propensity score matching. Results A total of 165 patients were enrolled, 50 in the prone and 115 in the supine group. Thirty-two (64%) and 61 (53%) patients were successfully weaned from ECMO in the prone and the supine groups, respectively. The proportion of patients successfully weaned from VV-ECMO in the prone group tended to be higher, albeit not statistically significant. During PP, there was a significant increase in partial pressure of arterial oxygen (PaO2) without a change in ventilator or ECMO settings. Tidal impedance shifted significantly to the dorsal region, and lung ultrasound scores significantly decreased in the anterior and posterior regions. Forty-five propensity score-matched patients were included in each group. In this matched sample, the prone group had a higher proportion of patients successfully weaned from VV-ECMO (64.4% vs. 42.2%; P = 0.035) and lower 60-day mortality (37.8% vs. 60.0%; P = 0.035). Conclusions Patients with severe ARDS placed in PP before VV-ECMO should continue PP after VV-ECMO support. This approach could increase the probability of successful weaning from VV-ECMO. Trial Registration ClinicalTrials.Gov: NCT04139733. Registered 23 October 2019.

To solve the current problems of fermented glutinous rice wine produced with traditional Jiuqu as a fermentation starter such as unstable quality, weak aroma and high alcohol content, this study selected non-Saccharomyces yeast strains with ester-producing and aroma-enhancing characteristics from traditional Jiuqu by analyzing the structure of its fungal community, and explored the effects of co-fermentation with each selected strain and Rhizopus arrhizus on the volatile flavor components of fermented glutinous rice wine. The results showed that Ascomycota and Mucoromycota were the dominant fungal phyla in Jiuqu and Rhizopus and Saccharomycopsis were the major fungal genera. Four non-Saccharomyces yeast strains, JLY1–JLY4, were obtained, and JLY1 and JLY2 were identified by sequencing as Saccharomycopsis fibuligera, while JLY3 and JLY4 as Torulaspora delbrueckii and Wickerhamomyces anomalus, respectively. Co-fermentation with JLY2 and Rhizopus arrhizus increased the number of volatile components from 46 to 62 compared with the control group, increasing the numbers of esters and alcohols and significantly increasing the relative contents of major flavor compounds such as isoamyl alcohol, phenylethanol, and phenylethyl acetate. Partial least squares-discriminant analysis (PLS-DA) was performed on 40 volatile flavor components shared by fermented glutinous rice wines, and 20 differential flavor substances were selected using the cut-off of variable importance for the projection (VIP) value ≥ 1, including 5 alcohols, 10 esters, 3 acids, 1 aldehyde or ketone, and 1 alkane. Differential substance analysis and sensory evaluation indicated that JLY1 and JLY2 were better than the other strains in terms of ester production and aroma enhancement, and synergistic fermentation significantly enhanced the contents of volatile flavor substances in fermented glutinous rice wine and consequently improved its quality.

Abstract The emulation of tactile sensory nerves to achieve advanced sensory functions in robotics with artificial intelligence is of great interest. However, such devices remain bulky and lack reliable competence to functionalize further synaptic devices with proprioceptive feedback. Here, we report an artificial organic afferent nerve with low operating bias (−0.6 V) achieved by integrating a pressure-activated organic electrochemical synaptic transistor and artificial mechanoreceptors. The dendritic integration function for neurorobotics is achieved to perceive directional movement of object, further reducing the control complexity by exploiting the distributed and parallel networks. An intelligent robot assembled with artificial afferent nerve, coupled with a closed-loop feedback program is demonstrated to rapidly implement slip recognition and prevention actions upon occurrence of object slippage. The spatiotemporal features of tactile patterns are well differentiated with a high recognition accuracy after processing spike-encoded signals with deep learning model. This work represents a breakthrough in mimicking synaptic behaviors, which is essential for next-generation intelligent neurorobotics and low-power biomimetic electronics.

Abstract Pressure ulcers (PU) are caused by persistent long-term pressure, which compromises the integrity of the epidermis, dermis, and subcutaneous adipose tissue layer by layer, making it difficult to heal. Platelet products such as platelet lysate (PL) can promote tissue regeneration by secreting numerous growth factors based on clinical studies on skin wound healing. However, the components of PL are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel that has lately emerged as a promising material for tissue engineering and regenerative medicine. The PL liquid was extracted, flow cytometrically detected for CD41a markers, and evenly dispersed in the GelMA hydrogel to produce a surplus growth factor hydrogel system (PL@GM). The microstructure of the hydrogel system was observed under a scanning electron microscope, and its sustained release efficiency and biological safety were tested in vitro. Cell viability and migration of human dermal fibroblasts, and tube formation assays of human umbilical vein endothelial cells were applied to evaluate the ability of PL to promote wound healing and regeneration in vitro. Real-time polymerase chain reaction (PCR) and western blot analyses were performed to elucidate the skin regeneration mechanism of PL. We verified PL’s therapeutic effectiveness and histological analysis on the PU model. PL promoted cell viability, migration, wound healing and angiogenesis in vitro. Real-time PCR and western blot indicated PL suppressed inflammation and promoted collagen I synthesis by activating STAT3. PL@GM hydrogel system demonstrated optimal biocompatibility and favorable effects on essential cells for wound healing. PL@GM also significantly stimulated PU healing, skin regeneration, and the formation of subcutaneous collagen and blood vessels. PL@GM could accelerate PU healing by promoting fibroblasts to migrate and secrete collagen and endothelial cells to vascularize. PL@GM promises to be an effective and convenient treatment modality for PU, like chronic wound treatment.