Hypoxia promotes histone H3K9 lactylation to enhance LAMC2 transcription in esophageal squamous cell carcinoma.

Hypoxia promotes tumorigenesis and lactate accumulation in esophageal squamous cell carcinoma (ESCC). Lactate can induce histone lysine lactylation (Kla, a recently identified histone marks) to regulate transcription. However, the functional consequence of histone Kla under hypoxia in ESCC remains to be explored. Here, we reveal that hypoxia facilitates histone H3K9la to enhance LAMC2 transcription for proliferation of ESCC. We found that global level of Kla was elevated under hypoxia, and thus identified the landscape of histone Kla in ESCC by quantitative proteomics. Furthermore, we show a significant increase of H3K9la level induced by hypoxia. Next, MNase ChIP-seq and RNA-seq analysis suggest that H3K9la is enriched at the promoter of cell junction genes. Finally, we demonstrate that the histone H3K9la facilitates the expression of LAMC2 for ESCC invasion by in vivo and in vitro experiments. Briefly, our study reveals a vital role of histone Kla triggered by hypoxia in cancer.

Gas Molecule Assisted All-Inorganic Dual-Interface Passivation Strategy for High-Performance Perovskite Solar Cells.

The trap states at both the upper and bottom interfaces of perovskite layers significantly impact non-radiative carrier recombination. The widely used solvent-based passivation methods result in the disordered distribution of surface components, posing challenges for the commercial application of large-area perovskite solar cells (PSCs). To address this issue, a novel NH3 gas-assisted all-inorganic dual-interfaces passivation strategy is proposed. Through the gas treatment of the perovskite surface, NH3 molecules significantly enhanced the iodine vacancy formation energy (1.54 eV) and bonded with uncoordinated Pb2+ to achieve non-destructive passivation. Meanwhile, the reduction of the film defect states is accompanied by a decrease in the work function, which promotes carrier transport between the interface. Further, a stable passivation layer is constructed to manage the bottom interfacial defects using inorganic potassium tripolyphosphate (PT), whose ─P═O group effectively mitigated the charged defects and lowered the carrier transport barriers and nucleation barriers of PVK, while the gradient distribution of K+ improved the crystalline quality of PVK film. Based on the dual-interface synergistic effect, the optimal MA-contained PSCs with an effective area of 0.1 cm2 achieved an efficiency of 24.51% and can maintain 90% of the initial value after aging (10-20% RH and 20 °C) for 2000 h.

IL-27 Gene Therapy Ameliorates IPEX Syndrome Caused by Germline Mutation of Foxp3 Gene: A Major Role for Induction of IL-10.

Inactivating mutations of Foxp3, the master regulator of regulatory T cell development and function, lead to immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome in mice and humans. IPEX is a fatal autoimmune disease, with allogeneic stem cell transplant being the only available therapy. In this study, we report that a single dose of adeno-associated virus (AAV)-IL-27 to young mice with naturally occurring Foxp3 mutation (Scurfy mice) substantially ameliorates clinical symptoms, including growth retardation and early fatality. Correspondingly, AAV-IL-27 gene therapy significantly prevented naive T cell activation, as manifested by downregulation of CD62L and upregulation of CD44, and immunopathology typical of IPEX. Because IL-27 is known to induce IL-10, a key effector molecule of regulatory T cells, we evaluated the contribution of IL-10 induction by crossing IL-10-null allele to Scurfy mice. Although IL-10 deficiency does not affect the survival of Scurfy mice, it largely abrogated the therapeutic effect of AAV-IL-27. Our study revealed a major role for IL-10 in AAV-IL-27 gene therapy and demonstrated that IPEX is amenable to gene therapy.

Identification of formation mechanism and key elements of quality geriatric care behavior of nursing assistants in nursing homes: a grounded theory study.

Objectives: This study aimed to identify the key elements and develop a formation mechanism model of quality geriatric care behavior for nursing assistants. Methods: This qualitative research employed the strategy of grounded theory proposed by Strauss and Corbin. Furthermore, the data was collected by participatory observation and semi-structured interviews. A total of 12 nursing managers, 63 nursing assistants, and 36 older people from 9 nursing homes in 6 cities were interviewed, whereas for the observatory survey, participants were recruited from 2 nursing homes. Results: The comparative and analysis process revealed 5 key elements of quality geriatric care behavior, including holistic care, personalized care, respect, positive interaction, and empowerment. Based on the Capability-Opportunity-Motivation-Behavior (COM-B) model, key elements and the 3 stages of quality geriatric care behavior (negative behavior cognition stage, practice exchange run-in stage, and positive behavior reinforcement stage), the theoretical framework of the formation mechanism was established. Conclusion: The results indicated that nursing assistants' capabilities, motivation, and organizational and environmental support are vital for quality care behaviors. The theoretical framework established in this study provides theoretical support and practical reference to policymakers, institutional administrators, and healthcare professionals for improving nursing assistant's care behaviors.

Resistance mechanisms of cereal plants and rhizosphere soil microbial communities to chromium stress.

Agricultural soils contaminated with heavy metals poison crops and disturb the normal functioning of rhizosphere microbial communities. Different crops and rhizosphere microbial communities exhibit different heavy metal resistance mechanisms. Here, indoor pot studies were used to assess the mechanisms of grain and soil rhizosphere microbial communities on chromium (Cr) stress. Millet grain variety 'Jingu 21' (Setaria italica) and soil samples were collected prior to control (CK), 6 hours after (Cr_6h), and 6 days following (Cr_6d) Cr stress. Transcriptomic analysis, high-throughput sequencing and quantitative polymerase chain reaction (qPCR) were used for sample determination and data analysis. Cr stress inhibited the expression of genes related to cell division, and photosynthesis in grain plants while stimulating the expression of genes related to DNA replication and repair, in addition to plant defense systems resist Cr stress. In response to chromium stress, rhizosphere soil bacterial and fungal community compositions and diversity changed significantly (p < 0.05). Both bacterial and fungal co-occurrence networks primarily comprised positively correlated edges that would serve to increase community stability. However, bacterial community networks were larger than fungal community networks and were more tightly connected and less modular than fungal networks. The abundances of C/N functional genes exhibited increasing trends with increased Cr exposure. Overall, these results suggest that Cr stress primarily prevented cereal seedlings from completing photosynthesis, cell division, and proliferation while simultaneously triggering plant defense mechanisms to resist the toxic effects of Cr. Soil bacterial and fungal populations exhibited diverse response traits, community-assembly mechanisms, and increased expression of functional genes related to carbon and nitrogen cycling, all of which are likely related to microbial survival during Cr stress. This study provides new insights into resistance mechanisms, microbial community structures, and mechanisms of C/N functional genes responses in cereal plants to heavy metal contaminated agricultural soils. Portions of this text were previously published as part of a preprint (https://www.researchsquare.com/article/rs-2891904/v1).

Ginsenoside Rh4 inhibits colorectal cancer via the modulation of gut microbiota-mediated bile acid metabolism.

INTRODUCTION: Dysbiosis of the gut microbiota is emerging as a pivotal factor in the pathogenesis of colorectal cancer (CRC). Ginsenoside Rh4 (Rh4) is an active compound isolated from ginseng with beneficial effects in modulating intestinal inflammation and gut microbiota dysbiosis, but how Rh4 regulates the gut microbiota to alleviate CRC remains underexplored. OBJECTIVES: We investigated the impact of Rh4 on CRC and the mechanism of its action in inhibiting CRC via modulation of gut microbiota. METHODS: We used the AOM/DSS model and employed transcriptomics, genomics and metabolomics techniques to explore the inhibitory impact of Rh4 on CRC. Furthermore, we employed experiments involving antibiotic treatment and fecal microbiota transplantation (FMT) to investigate the role of the gut microbiota. Finally, we elucidated the pivotal role of key functional bacteria and metabolites regulated by Rh4 in CRC. RESULTS: Our research findings indicated that Rh4 repaired intestinal barrier damage caused by CRC, alleviated intestinal inflammation, and inhibited the development of CRC. Additionally, Rh4 inhibited CRC in a gut microbiota-dependent manner. Rh4 increased the diversity of gut microbiota, enriched the probiotic Akkermansia muciniphila (A. muciniphila), and alleviated gut microbiota dysbiosis caused by CRC. Subsequently, Rh4 regulated A. muciniphila-mediated bile acid metabolism. A. muciniphila promoted the production of UDCA by enhancing the activity of 7α-hydroxysteroid dehydrogenase (7α-HSDH). UDCA further activated FXR, modulated the TLR4-NF-κB signaling pathway, thus inhibiting the development of CRC. CONCLUSION: Our results confirm that Rh4 inhibits CRC in a gut microbiota-dependent manner by modulating gut microbiota-mediated bile acid metabolism and promoting the production of UDCA, which further activates the FXR receptor and regulates the TLR4-NF-κB signaling pathway. Our results confirm that Rh4 has the potential to be used as a modulator of gut microbiota for preventing and treatment of CRC.

Vaginal microbiota are associated with in vitro fertilization during female infertility.

The vaginal microbiome plays an essential role in the reproductive health of human females. As infertility increases worldwide, understanding the roles that the vaginal microbiome may have in infertility and in vitro fertilization (IVF) treatment outcomes is critical. To determine the vaginal microbiome composition of 1411 individuals (1255 undergoing embryo transplantation) and their associations with reproductive outcomes, clinical and biochemical features are measured, and vaginal samples are 16S rRNA sequenced. Our results suggest that both too high and too low abundance of Lactobacillus is not beneficial for pregnancy; a moderate abundance is more beneficial. A moderate abundance of Lactobacillus crispatus and Lactobacillus iners (~80%) (with a pregnancy rate of I-B: 54.35% and III-B: 57.73%) is found beneficial for pregnancy outcomes compared with a higher abundance (>90%) of Lactobacillus (I-A: 44.81% and III-A: 51.06%, respectively). The community state type (CST) IV-B (contains a high to moderate relative abundance of Gardnerella vaginalis) shows a similar pregnant ratio (48.09%) with I-A and III-A, and the pregnant women in this CST have a higher abundance of Lactobacillus species. Metagenome analysis of 71 samples shows that nonpregnant women are detected with more antibiotic-resistance genes, and Proteobacteria and Firmicutes are the main hosts. The inherent differences within and between women in different infertility groups suggest that vaginal microbes might be used to detect infertility and potentially improve IVF outcomes.

Prevalence and Molecular Characterization of Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi in Cattle in Heilongjiang Province, Northeast China.

Crytosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi are important diarrheal pathogens with a global distribution that threatens the health of humans and animals. Despite cattle being potential transmission hosts of these protozoans, the associated risks to public health have been neglected. In the present study, a total of 1155 cattle fecal samples were collected from 13 administrative regions of Heilongjiang Province. The prevalence of Cryptosporidium spp., G. duodenalis, and E. bieneusi were 5.5% (64/1155; 95% CI: 4.2-6.9), 3.8% (44/1155; 95% CI: 2.7-4.9), and 6.5% (75/1155; 95% CI: 5.1-7.9), respectively. Among these positive fecal samples, five Cryptosporidium species (C. andersoni, C. bovis, C. ryanae, C. parvum, and C. occultus), two G. duodenalis assemblages (E and A), and eight E. bieneusi genotypes (BEB4, BEB6, BEB8, J, I, CHS7, CHS8, and COS-I) were identified. Phylogenetic analysis showed that all eight genotypes of E. bieneusi identified in the present study belonged to group 2. It is worth noting that some species/genotypes of these intestinal protozoans are zoonotic, suggesting a risk of zoonotic disease transmission in endemic areas. The findings expanded our understanding of the genetic composition and zoonotic potential of Cryptosporidium spp., G. duodenalis, and E. bieneusi in cattle in Heilongjiang Province.

Supramolecular assembly activated single-molecule phosphorescence resonance energy transfer for near-infrared targeted cell imaging.

Pure organic phosphorescence resonance energy transfer is a research hotspot. Herein, a single-molecule phosphorescence resonance energy transfer system with a large Stokes shift of 367 nm and near-infrared emission is constructed by guest molecule alkyl-bridged methoxy-tetraphenylethylene-phenylpyridines derivative, cucurbit[n]uril (n = 7, 8) and ß-cyclodextrin modified hyaluronic acid. The high binding affinity of cucurbituril to guest molecules in various stoichiometric ratios not only regulates the topological morphology of supramolecular assembly but also induces different phosphorescence emissions. Varying from the spherical nanoparticles and nanorods for binary assemblies, three-dimensional nanoplate is obtained by the ternary co-assembly of guest with cucurbit[7]uril/cucurbit[8]uril, accompanying enhanced phosphorescence at 540 nm. Uncommonly, the secondary assembly of ß-cyclodextrin modified hyaluronic acid and ternary assembly activates a single intramolecular phosphorescence resonance energy transfer process derived from phenyl pyridines unit to methoxy-tetraphenylethylene function group, enabling a near-infrared delayed fluorescence at 700 nm, which ultimately applied to mitochondrial targeted imaging for cancer cells.

Sources of stress and coping strategies among Chinese medical graduate students: a qualitative study.

BACKGROUND: The incidence of mental health problems among medical graduate students is much higher than among students of other disciplines. This can have adverse consequences for the medical students themselves as well as their future patients. This study aims to understand the pressures faced by Chinese medical students and the current status of mental health education. It also propose recommendations for the current situation and prospects for the future. METHOD: The authors conducted in-depth semi-structured interviews with 22 master's students from five medical schools during November 2023. All interview sessions were recorded and transcribed verbatim. The transcriptions were analyzed using the Colaizzi's seven-step method. RESULT: Three main themes were extracted from the students' statements: sources of psychological stress, ways to cope with stress, and perspectives on mental health education. The study showed that current mental health education in China is mostly in the form of printed mental health education manuals and mental health lectures, and there is no active tiered intervention for students at different levels. It is suggested that reforms should be made to shift to a model where the school proactively identifies problems and intervenes based on feedback. CONCLUSION: This study reveals the widespread psychological stress and shortcomings in current education methods. To address these challenges, institutions should develop tailored interventions, including tiered support systems, open dialogue promotion, and resilience training. Future research should focus on evaluating innovative interventions' effectiveness, ultimately fostering a supportive environment that enhances students' success and contributes to a healthier healthcare workforce.

[Prophylaxis of migraine without aura of liver yang hyperactivity treated with acupuncture at the points selected using the "seven lines of the neck" method: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of prophylaxis on migraine without aura differentiated as liver yang hyperactivity undergoing acupuncture at the points selected using the "seven lines of the neck" method. METHODS: Fifty-eight patients with migraine without aura of liver yang hyperactivity at remission stage were randomly divided into an observation group (29 cases, 3 cases dropped out) and a control group (29 cases, 4 cases dropped out). In the observation group, acupuncture was delivered at Dazhui (GV 14), Fengfu (GV 16), bilateral Fengchi (GB 20), Gongxue (Extra), etc., selected using the "seven lines of the neck" method. In the control group, conventional acupuncture was applied to ashi point, Sizhukong (TE 23), Shuaigu (GB 8), Taiyang (EX-HN 5) and others on the affected side. The treatment was given once every other day or every two days, 3 interventions weekly, for consecutive 8 weeks. Before treatment, after 4 and 8 weeks of treatment, and after 4 weeks of treatment completion (follow-up visit), the days of migraine episodes, the frequency of migraine episodes, the score of visual analogue scale (VAS) for pain intensity, and the score of migraine specific quality of life questionnaire (MSQ) were observed in the patients of the two groups. Before treatment and after 8 weeks of treatment, the score of TCM syndrome was observed. After 4 and 8 weeks of treatment and after 4 weeks of treatment completion (follow-up visit), the response rates of 50% reduction in the days and the frequency of migraine episodes were calculated in the two groups. RESULTS: After 4 and 8 weeks of treatment and during follow-up visit, the days and the frequency of migraine episodes were decreased (P<0.01) and VAS scores were declined (P<0.01) when compared with those before treatment in the two groups. The days and the frequency of migraine episodes in the observation group were lower during the follow-up visit (P<0.05) and VAS scores were lower after 8 weeks of treatment and during the follow-up visit (P<0.05) when compared with those in the control group. After 4 and 8 weeks of treatment, and during follow-up visit, the scores of "role function-preventive" and "emotional function" of MSQ were increased in comparison with those before treatment in the observation group (P<0.05). After 8 weeks of treatment and during the follow-up visit, the scores of "role function-restrictive" of MSQ were increased in comparison with those before treatment in the observation group (P<0.05), and the scores of "role function-restrictive" "role function-preventive" and "emotional function" were higher when compared with those before treatment in the control group (P<0.05). After 8 weeks of treatment, the scores of TCM syndrome were decreased in comparison with those before treatment in the two groups (P<0.01). In the observation group, the response rate of 50% reduction in the days of migraine episodes after 8 weeks of treatment and that of the frequency of migraine episodes during the follow-up visit were higher than those of the control group (P<0.05). CONCLUSION: Acupuncture at the points selected using the "seven lines of the neck" method can reduce the days and frequency of migraine episodes and pain intensity, ameliorate the syndrome of TCM and improve the quality of life of the patients with migraine without aura of liver yang hyperactivity.

Water scarcity footprint and water saving potential for large-scale green hydrogen generation: Evidence from coal-to-hydrogen substitution in China.

Green hydrogen generated via water electrolysis using photovoltaics or wind has begun to scale up in the process of achieving the global net-zero goal, but there is a lack of research on its impact on the scarcity of water resources and water saving potential. A water resources impact assessment framework for green hydrogen scale-up development is established, integrating the product water footprint and regional water footprint scarcity impacts and advancing the study of the water resources impacts on green hydrogen from water conservation as well as from a sustainable context. The research framework specifies the cradle-to-gate life cycle water consumption of hydrogen production, establishes the water scarcity footprint based on the available water remaining (AWARE) model, quantifies the water saving intensity and potential of the green hydrogen alternative to traditional hydrogen production, and proposes quantitative indicators of the water saving benefit. Taking the regions of 31 provinces in China as a case study, the wind-to­hydrogen scenario and the solar-to­hydrogen scenario will generate approximately 68.86×108 m3 and 126.10×108 m3 water scarcity footprints, respectively. Under the coal-to­hydrogen baseline scenario, approximately 1.68×108 m3 and - 0.57×108 m3 of water saving potential will be generated. In addition, the water saving intensity decreases from west to east. According to the adjusted quantitative indicators of water saving benefits, the wind-to­hydrogen scenario in China can reach 40.22×108 m3eq and the water saving benefit is more obvious in northern regions such as Hebei, Ningxia and Inner Mongolia. The methodological framework can be applied to other countries or regions to assess the sustainable impacts of green hydrogen production on water resources in a given region.

A systematic review and meta-analysis of the effectiveness of social support on turnover intention in clinical nurses.

Background: Nurse turnover has become a salient issue in healthcare system worldwide and seriously compromises patient outcomes. Social support is considered an effective contributor to alleviate nurse turnover intention (TI). However, the degree of correlation between social support and nurse TI remains elusive. Aims: This study aims to evaluate the strength of the effectiveness of social support on TI among nurses as well as its potential moderators. Design: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Methods: To obtained qualified studies, two researchers searched Embase, PubMed, Web of science, CINAHL, CNKI, WanFang, and Chinese Medical Journal Full Text Database from inception to January 6, 2024. Meta-analysis, publication bias, and sensitivity analysis were carried out on the included studies using CMA 3.0 software, and the moderating effect was verified through meta-analysis of variance (ANOVA). Results: A total of 38 studies were obtained, involving 63,989 clinical nurses. The comprehensive effect size of the random effect model showed a significant medium negative correlation between social support and TI among nurses (p < 0.001). The sample size and TI measurement tools significantly moderated the correlation between social support and TI (p < 0.050). However, nurse department, gender, data collection time, and social support measurement tools did not moderate the correlation between the two variables. Conclusion: Social support is negatively associated with TI in nurses. Nursing administrators and the medical community should fully recognize the importance of social support for nurses and take corresponding measures to enhance it, thereby reducing TI and ensuring the stability of the nursing team.

Impact of previous COVID-19 infection on postoperative complications and functional recovery: a one-year follow-up ambispective cohort study.

BACKGROUND: It's necessary to reassess the patients' short-term and long-term postoperative outcome in the post-COVID-19 era. This study aims to provide more comprehensive evidence regarding the timing of surgery after COVID-19 infection among the vaccinated population upon Omicron variant, considering the duration after acute COVID-19 infection, severity of COVID-19, patients' comorbidities, and the full course quality of postoperative recovery. MATERIALS AND METHODS: This is a single-center cohort study. Patients diagnosed with preoperative COVID-19 infection were consecutively included before surgery. Patients' demographics, surgical characteristics, and COVID-19 related factors were documented. Exposure was the time interval from COVID-19 infection to surgery. The primary outcome was postoperative complications within 30 days. The secondary outcomes included postoperative mortality within 30 days, functional disability at 6 and 12 months after surgery. RESULTS: A total of 4953 patients were included, and postoperative complications occurred in 353 patients (7.1%) within 30 days after surgery. Time interval from COVID-19 infection to surgery was associated with postoperative complications within 30 days after surgery (adjusted odds ratio [aOR] per day: 0.99; 95% CI, 0.99-1.00; P<0.01), as well as postoperative 6- and 12-month functional disability ([aOR]: 1.00; 95% CI, 0.99-1.00; P<0.01; and [aOR] 0.99; 95% CI, 0.98-1.00; P=0.01, respectively). Delaying surgery beyond a time interval of 2 weeks was associated with reduced postoperative 30-day complications ([aOR]: 0.63; 95% CI, 0.43-0.91; P=0.01) and mortality ([aOR]: 0.07; 95% CI, 0.01-0.38; P<0.01). Meanwhile, delaying surgery beyond a time interval of 7 weeks was associated with reduced functional disability at both 6-month ([aOR]: 0.67; 95% CI, 0.58-0.79; P<0.01) and 12-month postoperatively ([aOR]: 0.71; 95% CI, 0.53-0.95; P=0.02). CONCLUSION: A 2 weeks delay after COVID-19 infection is necessary for decreasing short-term postoperative risks, and a longer waiting period could be beneficial for long-term functional recovery.

Self-Assembled PD-L1 Downregulator to Boost Photodynamic Activated Tumor Immunotherapy Through CDK5 Inhibition.

The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient. Nanoscale CeSe exhibits an increased stability and drug delivery efficiency, contributing to intracellular production of reactive oxygen species (ROS) for robust photodynamic therapy (PDT). The PDT of CeSe can not only suppress the primary tumor growth, but also induce the immunogenic cell death (ICD) to release tumor associated antigens. More importantly, the CDK5 inhibition by CeSe can downregulate PD-L1 to re-activate the systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. This work provides an antibody free strategy to activate systemic immune response for metastatic tumor treatment, which may accelerate the development of translational nanomedicine with sophisticated mechanism.

The dominant influencing factors of desertification and ecological risk changes in Qinghai Area of Qilian Mountains National Park: Climate change or human activity?

Transitional features of desert environments partially determine the risks associated with ecosystems. Influenced by climate change and human activities, the variability and uncertainty of desertification levels and ecological risks in the Qinghai Area of Qilian Mountain National Park (QMNPQA) has become increasingly prominent. As a critical ecological barrier in northwest China, monitoring desertification dynamics and ecological risks is crucial for maintaining ecosystem stability. This study identifies the optimal monitoring model from four constructed desertification monitoring models and analyzes spatiotemporal changes in desertification. The spatial and temporal changes in ecological risks and their primary driving factors were analyzed using methods such as raster overlay calculation, geographic detector, cloud model, and trend analysis. The main conclusions are as follows: The desertification feature spatial model based on GNDVI-Albedo demonstrates better applicability in the study area, with an inversion accuracy of 81.24%. The levels of desertification and ecological risks in QMNPQA exhibit significant spatial heterogeneity, with a gradual decrease observed from northwest to southeast. From 2000 to 2020, there is an overall decreasing trend in desertification levels and ecological risks, with the decreasing trend area accounting for 89.82% and 85.71% respectively, mainly concentrated in the southeastern and northwestern parts of the study area. The proportion of areas with increasing trends is 4.49% and 7.05% respectively, scattered in patches in the central and southern edge areas. Surface temperature (ST), Digital Elevation Map (DEM), and Green normalized difference vegetation index (GNDVI) are the most influential factors determining the spatial distribution of ecological risks in QMNPQA. The effects of management and climatic factors on ecological risks demonstrate a significant antagonistic effect, highlighting the positive contributions of human activities in mitigating the driving effects of climate change on ecological risks. The research results can provide reference for desertification prevention and ecological quality improvement in QMNPQA.

Molecular network mechanism of Shexiang Huayu Xingnao granules in treating intracerebral hemorrhage.

We aim to explore the pharmacological efficacy and molecular network mechanism of Shexiang Huayu Xingnao granules (SX granules) in the treatment of intracerebral hemorrhage (ICH) based on experiments and network pharmacology. After the ICH model establishment, the behavioral functions of rats were assessed by the modified neurological severity score (mNSS), the wire suspension test, and the rotarod test. Brain histomorphological changes were observed using 2,3,5-triphenyl tetrazolium chloride (TTC), hematoxylin-eosin (HE), Nissl, and TdT-mediated dUTP nick end labeling (TUNEL) combined with neuronal nuclear (NEUN) immunofluorescence staining. The cross-targets of SX granules and ICH were obtained using network pharmacology, gene ontology (GO) enrichment analysis, and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis were performed. Then, the obtained Hub genes were verified using real-time quantitative polymerase chain reaction (RT-qPCR). The mNSS score was reduced and the duration to remain wire suspended increased in the SX group. In the morphological experiment, SX granules reduced brain tissue damage, neuronal apoptosis, and the number of astrocytes in the ICH rats. Moreover, 607 targets of drug-disease intersection were obtained by network pharmacology, and 10 Hub genes were found. SX granules regulated the expression of HRAS, MAPK3, and STAT3 in ICH condition. In conclusion, SX granules improved behavioral dysfunction, abnormal alterations in brain tissue, and cell morphology in ICH rats, and potential molecular mechanism was linked with the expression of multiple genes.

Selective inhibition of c-Met signaling pathways with a bispecific DNA nanoconnector for the targeted therapy of cancer.

Hepatocyte growth factor receptor (c-Met) is a suitable molecular target for the targeted therapy of cancer. Novel c-Met-targeting drugs need to be developed because conventional small-molecule inhibitors and antibodies of c-Met have some limitations. To synthesize such drugs, we developed a bispecific DNA nanoconnector (STPA) to inhibit c-Met function. STPA was constructed by using DNA triangular prism as a scaffold and aptamers as binding molecules. After c-Met-specific SL1 and nucleolin-specific AS1411 aptamers were integrated with STPA, STPA could bind to c-Met and nucleolin on the cell membrane. This led to the formation of the c-Met/STPA/nucleolin complex, which in turn blocked c-Met activation. In vitro experiments showed that STPA could not only inhibit the c-Met signaling pathways but also facilitate c-Met degradation through lysosomes. STPA also inhibited c-Met-promoted cell migration, invasion, and proliferation. The results of in vivo experiments showed that STPA could specifically target to tumor site in xenograft mouse model, and inhibit tumor growth with low toxicity by downregulating c-Met pathways. This study provided a novel and simple strategy to develop c-Met-targeting drugs for the targeted therapy of cancer.