Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress-induced anxiety-like behavior.

JOURNAL/nrgr/04.03/01300535-202506000-00024/figure1/v/2024-08-05T133530Z/r/image-tiff The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions. Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress-induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2 agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice. After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.

Carbapenem-resistant Klebsiella oxytoca transmission linked to preoperative shaving in emergency neurosurgery, tracked by rapid detection via chromogenic medium and whole genome sequencing.

Objectives: This study describes the detection and tracking of emergency neurosurgical cross-transmission infections with carbapenem-resistant Klebsiella oxytoca (CRKO). Methods: We conducted an epidemiological investigation and a rapid screening of 66 surveillance samples using the chromogenic selective medium. Two CRKO isolates from infected patients and three from the preoperative shaving razors had similar resistance profiles identified by the clinical laboratory. Results: The whole genome sequencing (WGS) results identified all isolates as Klebsiella michiganensis (a species in the K. oxytoca complex) with sequence type 29 (ST29) and carrying resistance genes bla KPC-2 and bla OXY-5, as well as IncF plasmids. The pairwise average nucleotide identity values of 5 isolates ranged from 99.993% to 99.999%. Moreover, these isolates displayed a maximum genetic difference of 3 among 5,229 targets in the core genome multilocus sequence typing scheme, and the razors were confirmed as the contamination source. After the implementation of controls and standardized shaving procedures, no new CRKO infections occurred. Conclusion: Contaminated razors can be sources of neurosurgical site infections with CRKO, and standard shaving procedures need to be established. Chromogenic selective medium can help rapidly identify targeted pathogens, and WGS technologies are effective mean in tracking the transmission source in an epidemic or outbreak investigation. Our findings increase the understanding of microbial transmission in surgery to improve patient care quality.

Technology acceptance of the video game-based swallowing function training system among healthcare providers and dysphagia patients: A qualitative study.

Objective: Dysphagia is highly prevalent worldwide, causing serious complications. Video-game based rehabilitation training can increase dysphagia patient motivation and adherence. However, the acceptance of video game systems by patients and healthcare providers is still not fully explored. This study aimed to explore the acceptance of the video game swallowing training system among potential users. Methods: The in-depth interviews were conducted face-to-face between July and October 2023 at a rehabilitation center in China, with a sample size based on the principle of information saturation. Interviews were audio-recorded and transcribed verbatim, and the data were analyzed using theory-driven thematic analysis methods based on the technology acceptance model. Results: A total of 19 participants participated in the interviews, which included 11 hospitalized dysphagia patients, three rehabilitation therapists, one doctor, and four nurses. Three themes and seven subthemes were identified. Sufficient training content, interesting interaction between the game and the rehabilitation training, intuitive page design, and efficient training modes were related to the usefulness of the system; user-friendly page design and simple interface could make it easier for participants to use the system. Overall, the availability of the video game system for use without geographical or time limitations led to a high level of participant intention to use the system, but it is still challenging to use it in the real world. Conclusions: The results of the study showed that participants were generally accepted and willing to use the video game system for dysphagia rehabilitation training. The video game-based swallowing function training system can be helpful in assisting with dysphagia rehabilitation.

An integrated targeted metabolome of phytohormones and transcriptomics analysis provides insight into the new generation of crops: Polygonatum kingianum var. grandifolium and Polygonatum kingianum.

Huangjing is becoming a new generation of crop. Polygonatum kingianum var. grandifolium (XHJ) is a variant of P. kingianum (DHJ), and they are treated as Huangjing. Unlike other Polygonatum species, the rhizome bud of XHJ can germinate both in spring and autumn, which contributes to its high rhizome yield. However, the molecular mechanism of the autumn shooting of XHJ was still unknown. In the present study, cellular observation, comparative targeted metabolome of phytohormones, and transcriptome analysis between XHJ and DHJ in autumn were conducted. Interestingly, 'Diterpenoid biosynthesis' (ko00904) and 'Plant hormone signal transduction' (ko04075) were commonly enriched by differentially accumulated phytohormones (DAPs) and differentially expressed genes (DEGs) in all tissues, which indicated the high auxin content, low cytokinin (CTK) content, and low abscisic acid/gibberellin (ABA/GA) ratio might contribute to the XHJ rhizome buds' differentiation and germination in autumn. Moreover, according to the weighted gene co-expression network analysis (WCGNA), transcript factors (TFs) related to auxin, CTK, GA, and jasmonic acid (JA) metabolism were screened, such as AP2/ERFs, WRKY, and NAC, which deserve further research. In conclusion, we comprehensively illustrated the mechanism of XHJ natural autumn shooting through cytological, metabolic, and transcriptomic analysis, which improves our understanding of the high yield of XHJ rhizomes and the diversity of shooting mechanisms in Polygonatum to lay the foundation for the further development of the Huangjing industry.

Bariatric surgeries and cardiac structure and function: Systematic review and network meta-analysis.

BACKGROUND: Obesity, a global health problem, is causally implicated in the development of cardiovascular disease. Bariatric surgeries are effective treatment options for obesity; however, the effectiveness of different bariatric surgeries on cardiac structure and function is not fully understood. We undertook a systematic review and network meta-analysis to comprehensively assess this effectiveness. DATA SOURCE: PubMed, Web of Science, and EMBASE were searched from their inception until November 11, 2023. Studies that compared bariatric surgeries vis-à-vis non-surgical treatment, placebo, and other bariatric surgeries, as well as reported changes in left ventricular mass or its index (LVM or LVMI) or left ventricular ejection fraction (LVEF), were summarized. RESULTS: Total 19 studies (17 cohort studies and 2 randomized controlled trials) and 2012 adults were meta-analyzed. Patients receiving gastric bypass had appreciably lowered LVM (weighted mean difference [WMD]: -43.86 g, 95% confidence interval [CI] -61.09 to -26.63, p < 0.01) and LVMI (standardized mean difference: -0.67, 95% CI -1.03 to -0.32, p < 0.01) compared with other bariatric surgeries. No significant improvement in LVEF was noted across all surgeries. The drop in body mass index was most pronounced for biliopancreatic diversion with duodenal switch (WMD -16.33 kg/m2, 95% CI -21.60 to -11.05, p < 0.01). CONCLUSIONS: Our findings of this network meta-analysis indicated that gastric bypass proved best for the improvement in cardiac structure, and there was no obvious improvement in cardiac function for all bariatric surgeries. Further studies are required to better understand the differing effectiveness of bariatric surgeries on cardiac structure and function and the underlying molecular mechanisms.

Observation of Circular Dichroism Induced by Electronic Chirality.

Chiral phases of matter, characterized by a definite handedness, abound in nature, ranging from the crystal structure of quartz to spiraling spin states in helical magnets. In 1T-TiSe_{2} a source of chirality has been proposed that stands apart from these classical examples as it arises from combined electronic charge and quantum orbital fluctuations. This may allow its chirality to be accessed and manipulated without imposing either structural or magnetic handedness. However, direct bulk evidence that broken inversion symmetry and chirality are intrinsic to TiSe_{2} remains elusive. Here, employing resonant elastic x-ray scattering technique, we reveal the presence of circular dichroism, i.e., polarization dependence of the resonant diffraction intensity, up to ∼40% at forbidden Bragg peaks that emerge at the charge and orbital ordering transition. The dichroism varies dramatically with incident energy and azimuthal angle. Comparison to calculated scattering intensities traces its origin to bulk chiral electronic order in TiSe_{2} and establishes resonant elastic x-ray scattering as a sensitive probe to electronic chirality.

Cobalt-catalyzed dithiolation of unactivated alkenes with thiols: facile access to diverse vicinal dithioethers.

Direct dithiolation of alkenes with thiols has been rarely reported. Herein, a simple cobalt-catalyzed aerobic approach has been developed to realize this transformation. With the aid of HFIP, diverse vicinal dithioethers including symmetric and unsymmetric ones could be obtained from readily available substrates. Gram-scale synthesis and late-stage modification of complex molecules highlight the practicability of this approach.

Nursing students' experiences of digital learning in Chinese higher education institutions: A descriptive qualitative study.

BACKGROUND: As digital learning is rapidly developing and being applied to almost all subjects in higher education nursing. Although digital learning has been shown to have a wide range of benefits, little is known about research into Chinese students' perceptions of digital learning, and there is a need to explore students' digital learning experiences. AIM: This study aimed to explore the digital learning experiences of undergraduate nursing students in Chinese higher education institutions, with the aim of informing future improvements in digital teaching and learning. DESIGN: A descriptive qualitative study. SETTINGS: This study was conducted at six universities in three cities in China. PARTICIPANTS: Twenty-six nursing students with at least one year's experience of digital learning. METHOD: Semi-structured online interviews were used to collect the data, and conventional content analysis was used to analyze the data. FINDINGS: Nursing students' digital learning experiences were categorized into three themes: positive digital learning experience, negative digital learning experience, and barriers to digital learning perception of students. CONCLUSIONS: With the help of advanced digital technology, students can access rich and diversified learning resources anytime and anywhere according to their personal learning pace and interests, which greatly enhances their autonomy and interest in learning. Open online courses have effectively compensated for regional differences in teachers' qualifications, enabling students in remote areas to enjoy high-quality teaching from top educational institutions and giving a solid impetus for improving nursing education in China. However, with the popularity of digital teaching, its design and innovation shortcomings have gradually emerged: students feel lonely and alienated when learning online, and long for more of the interaction and care found in traditional teaching. At the same time, the lack of regulation and assessment standards has created inequities in learning and affected student motivation.

Heterodimeric diketopiperazine alkaloids from Penicillium expansum MA147 and their cytotoxicity.

Four previously undescribed heterodimeric diketopiperazine alkaloids, expansines A-D, were identified from the solid rice medium fermented by Penicillium expansum MA147, along with one new resorcylic acid derivative and five known compounds. Their structures and relative/absolute configurations were elucidated by interpretation of their spectroscopic data, quantum chemical calculations, and chemical conversion. Some obtained compounds were evaluated for the cytotoxicity against a triple-negative breast cancer cell line MDA-MB-231, and expansine C showed an IC50 value of 3.23 µM. In further mechanistic studies, we found that it might act by increasing the expression of ATP-binding cassette transporter A1 and reducing cellular cholesterol levels, suggesting its potential as a novel anti-cancer agent.

Adverse pregnancy outcomes and multiple cancers risk in both mother and offspring: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Adverse pregnancy outcomes have reached epidemic proportions in recent years with serious health ramifications, especially for diverse cancers risk. Therefore, we carried out an umbrella review to systematically evaluate the validity and strength of the data and the extent of potential biases of the established association between adverse pregnancy outcomes and cancers risk in both mother and offspring. METHODS: PubMed, Embase, and Web of Science databases were searched from inception until 18 January 2024. Meta-analyses of observational studies investigating the relationship between adverse pregnancy outcomes and multiple cancers risk in both mother and offspring were included. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. The protocol for this umbrella review was prospectively registered in PROSPERO (CRD42023470544). RESULTS: The search identified 129 meta-analyses of observational studies and 42 types of cancer. Moderate certainty of evidence, exhibiting statistical significance, has been observed linking per kilogram increase in birth weight to a heightened risk of breast cancer (OR = 1.07, 95% CI = 1.02-1.12), prostate cancer (OR = 1.02, 95% CI = 1.00-1.05), leukemia (OR = 1.18, 95% CI = 1.13-1.23), and acute lymphoblastic leukemia in offspring (OR = 1.18, 95% CI = 1.12-1.23); rubella infection during pregnancy to an increased risk of leukemia in offspring (OR = 2.79, 95% CI = 1.16-6.71); and a linear dose-response association between an increase in the proportion of optimal birth weight and an elevated risk of acute lymphoblastic leukemia in offspring (OR = 1.16, 95% CI = 1.09-1.24), respectively. CONCLUSIONS: Although some adverse pregnancy outcomes have clinically promising associations with risk of several cancers in both mother and offspring, it is essential to conduct additional research to solidify the evidence, evaluate causality, and ascertain clinical utility.

Plasma proteomic and polygenic profiling improve risk stratification and personalized screening for colorectal cancer.

This study aims to identify colorectal cancer (CRC)-related proteomic profiles and develop a prediction model for CRC onset by integrating proteomic profiles with genetic and non-genetic factors (QCancer-15) to improve the risk stratification and estimate of personalized initial screening age. Here, using a two-stage strategy, we prioritize 15 protein biomarkers as predictors to construct a protein risk score (ProS). The risk prediction model integrating proteomic profiles with polygenic risk score (PRS) and QCancer-15 risk score (QCancer-S) shows improved performance (C-statistic: 0.79 vs. 0.71, P = 4.94E-03 in training cohort; 0.75 vs 0.69, P = 5.49E-04 in validation cohort) and net benefit than QCancer-S alone. The combined model markedly stratifies the risk of CRC onset. Participants with high ProS, PRS, or combined risk score are proposed to start screening at age 46, 41, or before 40 years old. In this work, the integration of blood proteomics with PRS and QCancer-15 demonstrates improved performance for risk stratification and clinical implication for the derivation of risk-adapted starting ages of CRC screening, which may contribute to the decision-making process for CRC screening.

Roles of oral and gut microbiota in acute myocardial infarction.

INTRODUCTION: The significance of oral/gut microbiota in acute myocardial infarction (AMI) has been increasingly appreciated. However, correlations between oral/gut microbiota and AMI parameter, as well as the key microbiota that may have a crucial function in this process, remain unclear. OBJECTIVES: To investigate the composition and structure of oral and gut microbiota associated with AMI and explore the roles of specific bacterial species in the progression of AMI. METHODS: We conducted a case-control study with 37 AMI patients and 36 controls. Oral and gut sample were collected and sequenced. Using correlation analysis, we combined bioinformatics data with AMI clinical parameters and obtained heatmaps of correlation coefficients. Additionally, we used antibiotics to eliminate the gut microbiota of C57BL/6J mice, followed by the transplantation of selected bacteria to verify the gut colonization of oral bacteria and their impact on AMI. RESULTS: The component of oral and gut microbiota of AMI group showed significant alterations when compared to the control group. 17 salivary genera, 21 subgingival genera, and 8 gut genera in AMI group substantially differed from those in control group. Additionally, 19 genera from saliva, 19 genera from subgingival plaque, and 11 genera from feces substantially correlated with AMI clinical parameters. Orally administrated S.o (Streptococcus oralis subsp. dentisani), S.p (Streptococcus parasanguinis), and S.s (Streptococcus salivarius) were able to colonize in the gut and exacerbate myocardial infarction. CONCLUSION: There is a strong correlation between oral/gut microbiota and AMI. Streptococcus spp. is capable to transmit from oral to gut and exacerbate myocardial infarction in mice. Monitoring and control of specific oral microbiota may be an effective new strategy for improving the therapy of AMI.

Disitamab vedotin combined with apatinib in gastric cancer: A case report and review of literature.

BACKGROUND: In patients with human epidermal growth factor receptor 2 (HER2)-overexpressing gastric cancer (GC), the combination of HER2 targeting and a standard first-line chemotherapy regimen has been demonstrated to significantly improve their prognosis. However, in a proportion of patients, cancer progresses within a short period of time, and there is currently no standard treatment after disease progression. CASE SUMMARY: This study presents a case of a 51-year-old male with advanced GC who underwent radical resection (Billroth type II subtotal gastrectomy and gastrojejunostomy) and resection of liver metastases. Immunohistochemical staining revealed a HER2 score of 2+, a dMMR status, and a Ki67 proliferation index of 30% to 40%. The gene test results indicated the presence of ERBB2 amplification and a PD-L1 expression level of less than 5%. Since December 2021, the patient has experienced disease progression during both first-line (two cycles of KN026 combined with KN046) and second-line (five cycles of nivolumab combined with trastuzumab and SOX chemotherapy) treatment regimens. The patient's prognosis following the first and second lines of treatment was unfavorable, with progression occurring in a relatively short time. For third-line therapy, disitamab vedotin (RC48) plus apatinib was used. At the time of this report, the patient had achieved a progression-free survival (PFS) of 25.8 months, which exceeded the median survival time for patients with advanced GC. CONCLUSION: Despite the unfavorable prognosis associated with advanced GC, the implementation of personalized treatment approaches may still prove beneficial for select patients. In patients with HER2-positive GC with extensive metastatic involvement, the use of the HER2-targeted combination with apatinib has demonstrated the potential to prolong both PFS and overall survival.

Research progress of exosomes from different sources in myocardial ischemia.

Ischemic heart disease refers to the imbalance between the supply and demand of myocardial blood; it has various causes and results in a class of clinical diseases characterized by myocardial ischemia (MI). In recent years, the incidence of cardiovascular disease has become higher and higher, and the number of patients with ischemic heart disease has also increased year by year. Traditional treatment methods include drug therapy and surgical treatment, both of which have limitations. The former maybe develop risks of drug resistance and has more significant side effects, while the latter may damage blood vessels and risk infection. At this stage, a new cell-free treatment method needs to be explored. Many research results have shown that exosomes from different cell sources can protect the ischemic myocardium via intercellular action methods, such as promoting angiogenesis, inhibiting myocardial fibrosis, apoptosis and pyroptosis, and providing a new basis for the treatment of MI. In this review, we briefly introduce the formation and consequences of myocardial ischemia and the biology of exosomes, and then focus on the role and mechanism of exosomes from different sources in MI. We also discuss the role and mechanism of exosomes pretreated with Chinese and Western medicines on myocardial ischemia. We also discuss the potential of exosomes as diagnostic markers and therapeutic drug for MI.

Gastric cancer liver metastasis will reduce the efficacy of immunotherapy.

Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells, leading to notable efficacy in patients with non-small cell lung cancer, melanoma, and other malignancies through immunotherapy utilization. However, secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression, resulting in reduced overall effectiveness of immune therapy. Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates, progression-free survival, and overall survival when secondary malignant tumors develop in the liver. Through Liu's retrospective analysis, valuable insights are provided for the future clinical management of these patients. Therefore, in patients with gastric cancer (GC), the occurrence of liver metastasis might be indicative of reduced efficacy of immunotherapy. Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.

An overview on the legacy and risks of Polychlorinated Biphenyls (PCBs) and Organochlorinated Pesticides (OCPs) in the polar regions.

Polychlorinated Biphenyls (PCBs) and Organochlorinated Pesticides (OCPs) are 'trapped' in a variety of environmental media and can therefore undergo further processing by geochemical cycles. By reviewing a wide range of research studies, we present and discuss the main progresses that affect legacy contaminants, such as migration and transformation processes, biological effects assessment across all Arctic media. PCBs and OCPs demonstrated an overall decreasing concentration trend over time in the Arctic. Ecological risk assessment was undertaken by comparison with two standards, suggesting that there was no ecological risk in either soil or sediment. The concentrations of HCB, ΣHCHs, ΣDDTs, chlordane, mirex, and ΣPCBs increased with trophic levels (TLs), showing a significant linear correlation (P < 0.001). The calculated trophic magnification factors (TMFs) values ranged from 0.0004 to 26.63, among which DDTs had the highest value. Future research need to focus on the long-term fate of PCBs and OCPs.

Microbiological mechanism of hydrogen fertilizer effect in soil.

For a long time, intercropping and rotation of leguminous with non-leguminous crops is widely used to reduce the application of nitrogen fertilizer and increase yield in agroecosystems. At present, most researchers considered that this management measure is helpful for reducing fertilizer consumption and increasing its efficiency, as it can improve nutrient supply of legumestonon-legumes, the spatial nutrient utilization efficiency by enhancing soil spatial heterogeneity, and improve soil structure and disease resistance. However, current theories cannot fully explain the positive effect of crop rotation and inter-cropping systems involving legumes. A large amount of hydrogen (H2) can be produced as an obligatory by-product of nitrogenase responsible for nitrogen (N2) fixation in the root nodules of leguminous plants. Despite of substantial amounts of H2 enriched in the rhizosphere of legumes, only a minor proportion of H2 is found to leak to soil surface. Increasing evidence showed that most H2 released in soil is immediately depleted in the surrounding of N2-fixing nodules by H2-oxidizing bacteria (HOB) thriving in soil. HOB can use H2 as an electron donor to assimilate and fix CO2 through redox reactions to synthesize cellular substances and consequently promote plant growth. To date, however, little is known about the biological mechanism and ecological process behind the "hydrogen fertilizer effect". Therefore, we review the H2-induced plant growth-promoting effects and its microbiological mechanisms. Our aims were to explore a new way for enhancing agroecosystem production, and to provide scientific basis for future utilization of H2 in agricultural production practices.

Chloroplast ATP synthase restricts photosynthesis under fluctuating light in tomato but not in maize.

Photosynthesis in fluctuating light requires coordinated adjustments of diffusion conductance and biochemical capacity, but the role of chloroplast ATP synthase activity (gH+) in dynamic photosynthesis is not well understood. In this study, we measured gas exchange, chlorophyll fluorescence and electrochromic shift signals in fluctuating light for leaves of tomato (Solanum lycopersicum) and maize (Zea mays). During the transition from sun to shade, simultaneous increases in gH+, effective quantum yield of PSII, and net CO2 assimilation rate (AN) occurred in tomato but uncoupled in maize, indicating that gH + limited AN during the sun-to-shade transition in tomato but not in maize. During the shade-to-sun transition, gH + increased simultaneously with stomatal conductance, mesophyll conductance and Rubisco carboxylation capacity in tomato, suggesting that gH+ is an overlooked factor affecting light induction of AN in tomato. By comparison, gH + maintained at high levels in maize and its AN was mainly restricted by stomatal conductance. Our results reveal that the kinetics of gH+ in fluctuating light differs between species, and chloroplast ATP synthase may be a potential target for improving dynamic photosynthesis in crops such as tomato.