Comparative metabolomics combined with genome sequencing provides insights into novel wolfberry-specific metabolites and their formation mechanisms.

Wolfberry (Lycium, of the family Solanaceae) has special nutritional benefits due to its valuable metabolites. Here, 16 wolfberry-specific metabolites were identified by comparing the metabolome of wolfberry with those of six species, including maize, rice, wheat, soybean, tomato and grape. The copy numbers of the riboflavin and phenyllactate degradation genes riboflavin kinase (RFK) and phenyllactate UDP-glycosyltransferase (UGT1) were lower in wolfberry than in other species, while the copy number of the phenyllactate synthesis gene hydroxyphenyl-pyruvate reductase (HPPR) was higher in wolfberry, suggesting that the copy number variation of these genes among species may be the main reason for the specific accumulation of riboflavin and phenyllactate in wolfberry. Moreover, the metabolome-based neighbor-joining tree revealed distinct clustering of monocots and dicots, suggesting that metabolites could reflect the evolutionary relationship among those species. Taken together, we identified 16 specific metabolites in wolfberry and provided new insight into the accumulation mechanism of species-specific metabolites at the genomic level.

Unveiling the hidden role of extracellular vesicles in brain metastases: a comprehensive review.

Background: Extracellular vesicles (EVs) are small, transparent vesicles that can be found in various biological fluids and are derived from the amplification of cell membranes. Recent studies have increasingly demonstrated that EVs play a crucial regulatory role in tumorigenesis and development, including the progression of metastatic tumors in distant organs. Brain metastases (BMs) are highly prevalent in patients with lung cancer, breast cancer, and melanoma, and patients often experience serious complications and are often associated with a poor prognosis. The immune microenvironment of brain metastases was different from that of the primary tumor. Nevertheless, the existing review on the role and therapeutic potential of EVs in immune microenvironment of BMs is relatively limited. Main body: This review provides a comprehensive analysis of the published research literature, summarizing the vital role of EVs in BMs. Studies have demonstrated that EVs participate in the regulation of the BMs immune microenvironment, exemplified by their ability to modify the permeability of the blood-brain barrier, change immune cell infiltration, and activate associated cells for promoting tumor cell survival and proliferation. Furthermore, EVs have the potential to serve as biomarkers for disease surveillance and prediction of BMs. Conclusion: Overall, EVs play a key role in the regulation of the immune microenvironment of brain metastasis and are expected to make advances in immunotherapy and disease diagnosis. Future studies will help reveal the specific mechanisms of EVs in brain metastases and use them as new therapeutic strategies.

Tripartite interactions of an endophytic entomopathogenic fungus, Asian corn borer, and host maize under elevated carbon dioxide.

BACKGROUND: Biological control of insect pests is encountering an unprecedented challenge in agricultural systems due to the ongoing rise in carbon dioxide (CO2) level. The use of entomopathogenic fungi (EPF) in these systems is gaining increased attention, and EPF as crop endophytes hold the potential for combining insect pest control and yield enhancement of crops, but the effects of increased CO2 concentration on this interaction are poorly understood. Here, the introduction of endophytic EPF was explored as an alternative sustainable management strategy benefiting crops under elevated CO2, using maize (Zea mays), Asian corn borer (Ostrinia furnacalis), and EPF (Beauveria bassiana) to test changes in damage to maize plants from O. furnacalis, and the nutritional status (content of carbon, nitrogen, phosphorus, potassium), biomass, and yield of maize. RESULTS: The results showed that endophytic B. bassiana could alleviate the damage caused by O. furnacalis larvae for maize plants under ambient CO2 concentration, and this effect was enhanced under higher CO2 concentration. Inoculation with B. bassiana effectively counteracted the adverse impact of elevated CO2 on maize plants by preserving the nitrogen content at its baseline level (comparable with ambient CO2 conditions without B. bassiana). Both simultaneous effects could explain the improvement of biomass and yield of maize under B. bassiana inoculation and elevated CO2. CONCLUSION: This finding provides key information about the multifaceted benefits of B. bassiana as a maize endophyte. Our results highlight the promising potential of incorporating EPF as endophytes into integrated pest management strategies, particularly under elevated CO2 concentrations. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Stereoscopic imaging of volatile organic compounds distribution in the region and tracing emission sources of volatile organic compounds using a novel movable single-photon ionization time-of-flight mass spectrometer.

This paper presents a newly developed high-performance mobile single-photon ionization time-of-flight mass spectrometry (M-SPI-TOFMS) system for on-line analysis and stereoscopic monitoring of complex gas mixtures. The system is designed for stereoscopic imaging to map the distribution of volatile organic compounds (VOCs) and trace their emission sources in urban areas and industrial parks. It mainly consists of a SPI-TOFMS instrument, a customized commercial vehicle, a meteorological five-parameter monitor with GPS, a high-power generator, and an uninterruptible power supply. The SPI technique, using a 118 nm VUV lamp, can ionize compounds with an ionization potential below 10.78 eV. Mass spectra obtained using this technique show the profiles of various VOCs and some inorganic compounds. The VOCs composition information and mobile location data are simultaneously sent to the GIS software. In GIS software, this data is used for real-time stereoscopic imaging of VOC distribution and precise tracking of VOC movement. The system can achieve a spatial data resolution of 0.69 mm at 25 km/h due to the microsecond detection speed of the M-SPI-TOFMS instrument. The laboratory test provides a rapid overview characterization of benzene, toluene, and xylene. The M-SPI-TOFMS has limits of detection and mass resolution of 33.7 pptv and 1060, respectively. Several field applications were carried out using M-SPI-TOFMS at various locations to identify VOC sources near different factories. The M-SPI-TOFMS system has a navigation monitoring speed of 25 km/h with a time resolution of 1 s. The widespread use of this system will provide accurate data to support environmental management departments in formulating VOCs pollution control policies and improving control efficiency.

Corrigendum: Association between napping and type 2 diabetes mellitus.

[This corrects the article DOI: 10.3389/fendo.2024.1294638.].

Using case-based learning supported by role-playing situational teaching method in endocrine physiology education.

Embedding clinically relevant learning experience to basic science subjects is desired for the preclinical phase of the undergraduate medical education. The present study aims to modify case-based learning (CBL) with role-playing situational teaching method and assess the student feedback and learning effect. 176 sophomore students majoring in clinical medicine from Harbin Medical University were randomly divided into two groups: the control group (n=90) who received the traditional hybrid teaching, and the experimental group (n=86), who received the role-playing situational teaching. Students in the experimental group were given a one-week pre-class preparation to dramatize a hyperthyroidism scenario through online autonomous learning of thyroid physiology, and performed the patient's consultation process in class, followed by a student presentation about key points of lecture content and a question-driven discussion. A posttest and questionnaire survey were conducted after class. The test scores of the two groups had no statistical differences, whereas the rate of excellence (high scores) of the experimental group was significantly higher than that of the control group. Furthermore, the record of online self-directed learning engagements was significantly improved in the experimental group. In the questionnaire, more than 70% of the students showed positive attitudes towards the role-playing situational teaching method and were willing to participate in other chapters of the physiology course. Such results show that CBL supported by role-playing situational teaching method encourages active learning and improves the application of basic knowledge of physiology, which can be incorporated in the preclinical curriculums to bridge the gap between theory and practice.

Case report: Light-chain amyloidosis responsive to selinexor in combination with daratumumab and dexamethasone (SDd) therapy.

The outcome of AL amyloidosis remains poor, particularly in patients with advanced organ involvement which takes long time to recovery. We conducted an observational study of two patients with AL amyloidosis treated with SDd regimen. Both patients successfully achieved significant hematological and organ responses without severe adverse events, and the time to organ response was remarkably shorter than previously reported. Notably, an over 15% reduction in interventricular septal thickness (IVST) was observed in patient#2 within 6 months. Up to now, SDd therapy has not been previously reported in AL amyloidosis and may be a promising option for these patients.

Wuliangye strong aroma baijiu promotes intestinal homeostasis by improving gut microbiota and regulating intestinal stem cell proliferation and differentiation.

BACKGROUND: Wuliangye strong aroma baijiu (hereafter, Wuliangye baijiu) is a traditional Chinese grain liquor containing short-chain fatty acids, ethyl caproate, ethyl lactate, other trace components, and a large proportion of ethanol. The effects of Wuliangye baijiu on intestinal stem cells and intestinal epithelial development have not been elucidated. Here, the role of Wuliangye baijiu in intestinal epithelial regeneration and gut microbiota modulation was investigated by administering a Lieber-DeCarli chronic ethanol liquid diet in a mouse model to mimic long-term (8 weeks') light/moderate alcohol consumption (1.6 g kg-1 day-1) in healthy human adults. RESULTS: Wuliangye baijiu promoted colonic crypt proliferation in mice. According to immunofluorescence and reverse transcription-quantitative polymerase chain reaction analyses, compared with the ethanol-only treatment, Wuliangye baijiu increased the number of intestinal stem cells and goblet cells and the expression of enteroendocrine cell differentiation markers in the mouse colon. Furthermore, gut microbiota analysis showed an increase in the relative abundance of microbiota related to intestinal homeostasis following Wuliangye baijiu administration. Notably, increased abundance of Bacteroidota, Faecalibaculum, Lachnospiraceae, and Blautia may play an essential role in promoting stem-cell-mediated intestinal epithelial development and maintaining intestinal homeostasis. CONCLUSIONS: In summary, these findings suggest that Wuliangye baijiu can be used to regulate intestinal stem cell proliferation and differentiation in mice and to alter gut microbiota distributions, thereby promoting intestinal homeostasis. This research elucidates the mechanism by which Wuliangye baijiu promotes intestinal health. © 2024 Society of Chemical Industry.

Modeling blood-brain barrier formation and cerebral cavernous malformations in human PSC-derived organoids.

The human blood-brain barrier (hBBB) is a highly specialized structure that regulates passage across blood and central nervous system (CNS) compartments. Despite its critical physiological role, there are no reliable in vitro models that can mimic hBBB development and function. Here, we constructed hBBB assembloids from brain and blood vessel organoids derived from human pluripotent stem cells. We validated the acquisition of blood-brain barrier (BBB)-specific molecular, cellular, transcriptomic, and functional characteristics and uncovered an extensive neuro-vascular crosstalk with a spatial pattern within hBBB assembloids. When we used patient-derived hBBB assembloids to model cerebral cavernous malformations (CCMs), we found that these assembloids recapitulated the cavernoma anatomy and BBB breakdown observed in patients. Upon comparison of phenotypes and transcriptome between patient-derived hBBB assembloids and primary human cavernoma tissues, we uncovered CCM-related molecular and cellular alterations. Taken together, we report hBBB assembloids that mimic the core properties of the hBBB and identify a potentially underlying cause of CCMs.

Zwitterionic Hydrogel Coating with Antisediment Properties for Marine Antifouling Applications.

Biofouling is a serious issue affecting the marine industry because the attached micro- and macrocontaminants can increase fuel consumption and damage ship hulls. A hydrophilic hydrogel-based coating is considered a promising antifouling material because it is environmentally friendly and the dense hydration layer can protect the substrate from microbial attachment. However, sediment adsorption can be an issue for hydrogel-based coatings. Their natural soft and porous structures can trap sediment from the marine environment and weaken the antifouling capability. There is still little research on the antisediment properties of hydrogels, and none of them deal with this problem. Here, we report on optimizing zwitterionic hydrogel-based coatings to improve their antisediment properties and achieve comparable performance to commercial biocidal coatings, which are the gold standard in the antifouling coating area. After 1 week of sediment contamination and 2 weeks of diatom coculturing, this optimized zwitterionic hydrogel coating maintained its antifouling properties with a few diatoms on the surface. Its large-scale samples also achieved antifouling performance similar to that of biocidal coatings in the Atlantic Ocean for 1.5 months. More importantly, our research provides a universal strategy to improve the antisediment properties of soft hydrogel-based coatings. For the first time, we report that the introduction of interfacial electrostatic interactions enhanced the antisediment properties of hydrogels.

The effects of acteoside on locomotor recovery after spinal cord injury - The role of autophagy and apoptosis signaling pathway.

In the current study, we investigated the effects of acteoside as a phenylpropanoid glycoside on interaction with neurons to assesses locomotor recovery after spinal cord injury (SCI) in rats by focusing on evaluating the factors involved in autophagy, apoptosis, inflammation and oxidative stress processes. 49 Spargue-Dawley rats were prepared and divided into seven healthy and SCI groups receiving different concentrations of acteoside. After 28 days of disease induction and treatment with acteoside, a BBB score test was used to evaluate locomotor activity. Then, by preparing spinal cord cell homogenates, the expression levels of MAP1LC3A, MAP-2, glial fibrillary acidic protein (GFAP), Nrf2, Keap-1, Caspase 3 (Casp3), Bax, Bcl-2, TNF-a, IL-1B, reactive oxygen species (ROS), and malondialdehyde (MDA) were measured. Improvement of locomotor activity in SCI rats receiving acteoside was observed two weeks after the beginning of the experiment and continued until the fourth week. Both MAP1LC3A and MAP-2 were significantly up-regulated in SCI rats treated with acteoside compared to untreated SCI rats, and GFAP levels were significantly decreased in these animals. Pro-apoptotic proteins Bax and Casp3 and anti-apoptotic protein Bcl-2 were down-regulated and up-regulated, respectively, in SCI rats receiving acteoside. In addition, a significant downregulation of iNOS, TNF-α, and IL-1ß and a decrease in contents of both ROS and MDA as well as increases in Nrf2 and Keap-1 were seen in rats receiving acteoside. Furthermore, acteoside strongly interacted with MAP1LC3A, TNF-α, and Casp3 targets with binding affinities of -8.3 kcal/mol, -8.3 kcal/mol, and -8.5 kcal/mol, respectively, determined by molecular docking studies. In general, it can be concluded that acteoside has protective effects in SCI and can be considered as an adjuvant therapy in the treatment of this disease. However, more studies, especially clinical studies, are needed in this field.

Prenatal exposure to fenvalerate causes depressive-like behavior in adulthood by inhibiting brain-derived 5-HT synthesis.

The developmental toxicity of fenvalerate, a representative pyrethroid insecticide, is well documented. The present study aimed to explore whether prenatal exposure to fenvalerate causes depression-like behavior in adulthood. Pregnant mice were orally administrated with either corn oil or fenvalerate (2 or 20 mg/kg) during pregnancy. Depressive-like behaviors were assessed by tail suspension test (TST), forced swim test (FST) and sucrose preference test (SPT). Immobility times in TST and FST were increased in offspring whose mothers were exposed to fenvalerate throughout pregnancy. By contrast, sugar preference index, as determined by SPT, was decreased in fenvalerate-exposed offspring. Prefrontal PSD95, a postsynaptic membrane marker, was downregulated in fenvalerate-exposed adulthood offspring. Fenvalerate-induced reduction of prefrontal PSD95 began at GD18 fetal period. Accordingly, prefrontal 5-HT, a neurotransmitter for synaptogenesis, was also reduced in fenvalerate-exposed GD18 fetuses. Tryptophan hydroxylase 2 (TPH2), a key enzyme for 5-HT synthesis, was downregulated in the midbrain of fenvalerate-exposed GD18 fetuses. Additional experiment showed that GRP78 and p-eIF2α, two endoplasmic reticulum stress-related proteins, were increased in the midbrain of fenvalerate-exposed fetal mice. The present results suggest that prenatal exposure to fenvalerate causes depressive-like behavior in adulthood, partially by inhibiting brain-derived 5-HT synthesis.

Histoplasmosis: An epidemiological and clinical update in China, review and a case report.

Histoplasmosis is a systemic mycosis caused by the dimorphic fungus in the genus Histoplasma. Histoplasmosis is overlooked in China. This study aims to provide an epidemiological and clinical update on histoplasmosis in China by literature review. We reviewed cases of histoplasmosis reported in recent 11 years and described a case of histoplasmosis-triggered hemophagocytic lymphohistiocytosis (HLH) in an immunocompetent patient. A total of 225 cases of histoplasmosis diagnosed in China between 2012 and 2022 were involved in this study, compared with 300 cases reviewed from 1990 to 2011, an increasing number of cases of histoplasmosis have been diagnosed in the last 11 years. The majority of cases of histoplasmosis were autochthonous cases, mainly from provinces Sichuan (56/225, 24.9%), Hunan (50/225, 22.2%), Guangdong (31/225, 13.8%), and Yunnan (24/225, 10.7%). Higher incidence (52.5%, 53/99) of histoplasmosis occurred in immunocompetent patients which is similar to those from the previous 21 years, and the prevalence of the disease did not vary highly over time. Of note, the number of histoplasmosis cases is increasing, and the geographic distribution is shifting southwards over time. Improved awareness is critically important for informing clinical practice in China.

Immunotherapy combined with cranial radiotherapy for driver-negative non-small-cell lung cancer brain metastases: a retrospective study.

Background: This study assesses immune checkpoint inhibitors' efficacy for non-small-cell lung cancer (NSCLC) with brain metastases (BM) and explores the role of cranial radiation therapy (CRT) in the immunotherapy era. Methods: The retrospective analysis screened NSCLC patients with BMs from July 2018 to December 2021. Treatment involved chemotherapy combined with immune checkpoint inhibitors as the first-line, with patients divided into CRT and non-CRT groups. Overall survival (OS), progression-free survival and intracranial progression-free survival were calculated and compared. Results: Among 113 patients, 74 who received CRT had significantly better median OS (not reached vs 15.31 months), particularly among those with one to three BMs. Factors correlating with better OS included CRT, PD-L1 expression and diagnosis-specific graded prognostic assessment scores. Conclusion: Integrating CRT with anti-PD-1 therapy notably enhanced long-term survival in NSCLC patients with BMs.

Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury: a randomized controlled study.

JOURNAL/nrgr/04.03/01300535-202412000-00032/figure1/v/2024-04-08T165401Z/r/image-tiff For patients with chronic spinal cord injury, the conventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection, pressure sores, osteoporosis, and deep vein thrombosis. Surgery is rarely performed on spinal cord injury in the chronic phase, and few treatments have been proven effective in chronic spinal cord injury patients. Development of effective therapies for chronic spinal cord injury patients is needed. We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal cord injury to compare intensive rehabilitation (weight-bearing walking training) alone with surgical intervention plus intensive rehabilitation. This clinical trial was registered at ClinicalTrials.gov (NCT02663310). The goal of surgical intervention was spinal cord detethering, restoration of cerebrospinal fluid flow, and elimination of residual spinal cord compression. We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement, reduced spasticity, and more rapid bowel and bladder functional recovery than weight-bearing walking training alone. Overall, the surgical procedures and intensive rehabilitation were safe. American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries. Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

Seismic response analysis of subway station under obliquely incident SV waves.

This paper aims to investigate the dynamic response characteristics of subway station under earthquakes. To this end, seismic waves are transformed into equivalent nodal loads on viscoelastic artificial boundaries using theories and methods of wave motion. The calculation formulas for equivalent nodal loads of SV waves incident at any angle are established, and ANSYS' APDL program compiles to automatically generate the viscoelastic artificial boundary and input the seismic loads. A finite element model of soil-subway station interaction was established, and the seismic response characteristics of a two-story three-span subway station under different incidence angles of SV waves were investigated using the above seismic input method. The results indicate that the incidence angle of seismic waves has a significant impact on the seismic response of subway station. Inclined incidence of seismic waves causes non-uniform loading and deformation of the subway station. Specifically, a small angle leads to predominantly transverse shear deformation, while a large angle causes mainly vertical shear deformation. The inclined incidence of seismic waves significantly increases the vertical acceleration of the subway station, with the effect becoming more pronounced as the angle increases. Additionally, special attention should be given to the joints between the structural slab and the side wall, slab and center column, as well as the two ends of the center column as they are vulnerable areas during earthquakes and require careful consideration in seismic design.

Greenhouse gases emissions and carbon budget estimation in horizontal subsurface flow constructed wetlands with different plant species.

Constructed wetlands (CWs) are pivotal for wastewater treatment due to their high efficiency and numerous advantages. The impact of plant species and diversity on greenhouse gas (GHG) emissions from CWs requires a more comprehensive evaluation. Moreover, controversial perspectives persist about whether CWs function as carbon sinks or sources. In this study, horizontal subsurface flow (HSSF) CWs vegetated with Cyperus alternifolius, Typhae latifolia, Acorus calamus, and the mixture of these three species were constructed to evaluate pollutant removal efficiencies and GHG emissions, and estimate carbon budgets. Polyculture CWs can stably remove COD (86.79 %), NH4+-N (97.41 %), NO3--N (98.55 %), and TP (98.48 %). They also mitigated global warming potential (GWP) by suppressing N2O emissions compared with monoculture CWs. The highest abundance of the Pseudogulbenkiania genus, crucial for denitrification, was observed in polyculture CWs, indicating that denitrification dominated in nitrogen removal. While the highest nosZ copy numbers were observed in CWs vegetated with Cyperus alternifolius, suggesting its facilitation of denitrification-related microbes. Selecting Cyperus alternifolius to increase species diversity is proposed for simultaneously maintaining the water purification capacity and reducing GHG emissions. Carbon budget estimations revealed that all four types of HSSF CWs were carbon sinks after six months of operation, with carbon accumulation capacity of 4.90 ± 1.50 (Cyperus alternifolius), 3.31 ± 2.01 (Typhae latifola), 1.78 ± 1.30 (Acorus calamus), and 2.12 ± 0.88 (polyculture) kg C/m2/yr. This study implies that under these operation conditions, CWs function as carbon sinks rather than sources, aligning with carbon peak and neutrality objectives and presenting significant potential for carbon reduction efforts.

Chromosome-level genome assembly and characterization of the Calophaca sinica genome.

Calophaca sinica is a rare plant endemic to northern China which belongs to the Fabaceae family and possesses rich nutritional value. To support the preservation of the genetic resources of this plant, we have successfully generated a high-quality genome of C. sinica (1.06 Gb). Notably, transposable elements (TEs) constituted ~73% of the genome, with long terminal repeat retrotransposons (LTR-RTs) dominating this group of elements (~54% of the genome). The average intron length of the C. sinica genome was noticeably longer than what has been observed for closely related species. The expansion of LTR-RTs and elongated introns emerged had the largest influence on the enlarged genome size of C. sinica in comparison to other Fabaceae species. The proliferation of TEs could be explained by certain modes of gene duplication, namely, whole genome duplication (WGD) and dispersed duplication (DSD). Gene family expansion, which was found to enhance genes associated with metabolism, genetic maintenance, and environmental stress resistance, was a result of transposed duplicated genes (TRD) and WGD. The presented genomic analysis sheds light on the genetic architecture of C. sinica, as well as provides a starting point for future evolutionary biology, ecology, and functional genomics studies centred around C. sinica and closely related species.

Synthesis of Asp-based lactam cyclic peptides using an amide-bonded diaminodiacid to prevent aspartimide formation.

Asp-based lactam cyclic peptides are considered promising drug candidates. However, using Fmoc solid-phase peptide synthesis (Fmoc-SPPS) for these peptides also causes aspartimide formation, resulting in low yields or even failure to obtain the target peptides. Here, we developed a diaminodiacid containing an amide bond as a ß-carboxyl-protecting group for Asp to avoid aspartimide formation. The practicality of this diaminodiacid has been illustrated by the synthesis of lactam cyclic peptide cyclo[Lys9,Asp13] KIIIA7-14 and 1Y.