Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury: PERK as a potential target for intervention.

JOURNAL/nrgr/04.03/01300535-202505000-00028/figure1/v/2024-07-28T173839Z/r/image-tiff Several studies have shown that activation of unfolded protein response and endoplasmic reticulum (ER) stress plays a crucial role in severe cerebral ischemia/reperfusion injury. Autophagy occurs within hours after cerebral ischemia, but the relationship between ER stress and autophagy remains unclear. In this study, we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury. We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 subunit alpha (eIF2α)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP), increased neuronal apoptosis, and induced autophagy. Furthermore, inhibition of ER stress using inhibitors or by siRNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis, indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy. Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis, indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury. Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy, and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

A quantitative LC-MS/MS method for investigation of polysubstance use involving heroin and cocaine.

Concurrent use of heroin and cocaine (known as the "speedball") prevails among substance use disorder populations, especially in opioid-dependent individuals, with severe consequences and a high fatality rate. Little is known about the patterns and correlations of the concurrent use of heroin and cocaine. It is vital to investigate such a polydrug use in both humans and animals to uncover concomitant toxicity and the cause of fatal overdose (death). In this study, we aimed to shed some light on the role of cocaine in the etiology of heroin-related deaths in the context of molecular pharmacokinetics (PK). For the purpose, a high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of heroin, cocaine, and their metabolites in whole blood was developed and fully validated in accordance with the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. Then, this method was used to analyze heroin, cocaine, and their metabolites in blood from the rats intraperitoneally administered non-lethal 10 mg/kg heroin or 20 mg/kg cocaine alone, or their combination that is lethal with a proximal mortality of 33 %. The obtained results from the rats that experienced the lethal toxicity revealed that the concurrent use of heroin and cocaine significantly increased the risk of fatality from overdose. Heroin significantly slowed down the elimination of cocaine and its main metabolites in blood, while cocaine significantly enhanced heroin metabolism from 6-monoacetylmorphine (6-MAM) to morphine. Similar elimination half-lives for other heroin metabolites were observed. These findings are reported for the first time in this study, facilitating our understanding of the polysubstance metabolism and severe consequences produced by the polydrug use.

[Efficiency of different large language models in China in response to consultations about PCa-related perioperative nursing and health education].

OBJECTIVE: To evaluate the efficiency of the four domestic language models, ERNIE Bot, ChatGLM2, Spark Desk and Qwen-14B-Chat, all with a massive user base and significant social attention, in response to consultations about PCa-related perioperative nursing and health education. METHODS: We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases, and inputted the questions into each of the four language models for simulation consultation. Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy, comprehensiveness, understandability, humanistic care, and case analysis. We evaluated and compared the performance of the four models using visualization tools and statistical analyses. RESULTS: All the models generated high-quality texts with no misleading information and exhibited satisfactory performance. Qwen-14B-Chat scored the highest in all aspects and showed relatively stable outputs in multiple tests compared with ChatGLM2. Spark Desk performed well in terms of understandability but lacked comprehensiveness and humanistic care. Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis. The overall performance of ERNIE Bot was slightly inferior. All things considered, Qwen-14B-Chat was superior to the other three models in consultations about PCa-related perioperative nursing and health education. CONCLUSION: In PCa-related perioperative nursing, large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support, so as to improve the patient compliance and the quality of clinical treatment and nursing.

Cryo-EM structure of ACE2-SIT1 in complex with Tiagabine.

The pharmacology of amino acid transporters in the SLC6 family is poorly developed compared to that of the neurotransmitter transporters. To identify new inhibitors of the proline transporter SIT1 (SLC6A20), its expression in Xenopus laevis oocytes was optimized. Trafficking of SIT1 was augmented by co-expression of angiotensin-converting enzyme 2 (ACE2) in oocytes but there was no strict requirement for co-expression of ACE2. A pharmacophore-guided screen identified tiagabine as a potent non-competitive inhibitor of SIT1. To understand its binding mode, we determined the cryo-electron microscopy (cryo-EM) structure of ACE2-SIT1 bound with tiagabine. The inhibitor binds close to the orthosteric proline binding site, but due to its size extends into the cytosolic vestibule. This causes the transporter to adopt an inward-open conformation, in which the intracellular gate is blocked. This study provides the first structural insight into inhibition of SIT1 and generates tools for a better understanding of the ACE2-SIT1 complex. These findings may have significance for SARS-CoV-2 binding to its receptor ACE2 in human lung alveolar cells where SIT1 and ACE2 are functionally expressed.

A thalamic nucleus reuniens-lateral septum-lateral hypothalamus circuit for comorbid anxiety-like behaviors in chronic itch.

Chronic itch often clinically coexists with anxiety symptoms, creating a vicious cycle of itch-anxiety comorbidities that are difficult to treat. However, the neuronal circuit mechanisms underlying the comorbidity of anxiety in chronic itch remain elusive. Here, we report anxiety-like behaviors in mouse models of chronic itch and identify γ-aminobutyric acid-releasing (GABAergic) neurons in the lateral septum (LS) as the key player in chronic itch-induced anxiety. In addition, chronic itch is accompanied with enhanced activity and synaptic plasticity of excitatory projections from the thalamic nucleus reuniens (Re) onto LS GABAergic neurons. Selective chemogenetic inhibition of the Re → LS circuit notably alleviated chronic itch-induced anxiety, with no impact on anxiety induced by restraint stress. Last, GABAergic neurons in lateral hypothalamus (LH) receive monosynaptic inhibition from LS GABAergic neurons to mediate chronic itch-induced anxiety. These findings underscore the potential significance of the Re → LS → LH pathway in regulating anxiety-like comorbid symptoms associated with chronic itch.

Centrifugated lateral flow assay strips based on dual-emission carbon dots modified with europium ions for ratiometric determination and on-site discrimination of tetracyclines in environment.

Due to the serious detrimental impact on human health, antibiotic pollution particularly tetracyclines residues has become a serious problem. Herein, a multiple response fluorescent probe consisted of dual-emission carbon dots and Eu3+ (D-CDs@Eu3+) is designed for the determination and discrimination of tetracyclines (TCs). Specifically, the carboxyl and amidogen group of dual-emission carbon dots (D-CDs) can coordinate with Eu3+ to form the D-CDs@Eu3+. Upon adding TCs, the fluorescence intensities of D-CDs at 405 nm and 495 nm are quenched due to inner filter effect (IFE) and the localization of fluorescence resonance energy transfer (L-FRET) between the D-CDs@Eu3+ and TC. Simultaneously, the D-CDs@Eu3+ may chelate with TCs to enhance the occurrence of antenna effect, while the characteristic peaks of Eu3+ at 590 nm and 615 nm are enhanced. On these bases, the TCs detection is achieved with low detection limits from 46.7 to 72.0 nM. Additionally, through the distinct efficiencies of L-FRET, the discrimination of TCs is achieved. Moreover, a novel centrifugated lateral flow assay strips (CLFASs) device is developed by integrating the D-CDs@Eu3+, lateral flow assay strips and smartphone using RGB variations for TCs detection, achieving remarkable recoveries (98.6-103.7 %) in real samples. Therefore, this CLFASs device provides a reliable approach for the TCs detection, demonstrating potential applications.

Impact of formaldehyde on ozone formation in Central China: Important role of biogenic emission in forest region.

Formaldehyde (HCHO) is an important source for driving tropospheric ozone (O3) formation. This study investigated the combined effects of anthropogenic and biogenic emission on O3 formation in the Guanzhong Basin (GZB), Central China, providing useful information into the mechanisms of O3 formation due to the interaction between anthropogenic and biogenic volatile organic compounds (VOCs). A severe O3 pollution episode in summer of 2017 was simulated using the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) to examine the impacts of ambient HCHO on ground-level O3. Results showed secondary HCHO dominated ambient levels, peaking in the afternoon (up to 86 %), while primary emissions contributed 14 % on average. This enhanced O3 production by 7.7 % during the morning rush hour and 24.3 % in the afternoon. In addition, HCHO concentration peaked before that of O3, suggesting it plays significant role in O3 formation. Biogenic emission oxidation contributed 3.1 µg m-3 (53.1 %) of HCHO and 5.2 pptv (40.1 %) of hydroperoxyl radicals (HO2) in average urban areas, where the downwind regions of the forests had high nitrogen oxides (NOx) levels and favorable conditions for O3 production (17.3 µg m-3, 20.5 %). In forested regions, sustained isoprene oxidation led to elevated oxidized VOCs including HCHO and acetaldehyde downwind, which practiced further photolysis of O3 formation with anthropogenic NOx in urban areas. Sensitivity experiments recommend controlling industrial and traffic NOx emissions, with regional joint prevention and regulation, which are essential to reduce O3 pollution.

A multi-frequency approach of the altered functional connectome for autism spectrum disorder identification.

Autism spectrum disorder stands as a multifaceted and heterogeneous neurodevelopmental condition. The utilization of functional magnetic resonance imaging to construct functional brain networks proves instrumental in comprehending the intricate interplay between brain activity and autism spectrum disorder, thereby elucidating the underlying pathogenesis at the cerebral level. Traditional functional brain networks, however, typically confine their examination to connectivity effects within a specific frequency band, disregarding potential connections among brain areas that span different frequency bands. To harness the full potential of interregional connections across diverse frequency bands within the brain, our study endeavors to develop a novel multi-frequency analysis method for constructing a comprehensive functional brain networks that incorporates multiple frequencies. Specifically, our approach involves the initial decomposition of functional magnetic resonance imaging into distinct frequency bands through wavelet transform. Subsequently, Pearson correlation is employed to generate corresponding functional brain networks and kernel for each frequency band. Finally, the classification was performed by a multi-kernel support vector machine, to preserve the connectivity effects within each band and the connectivity patterns shared among the different bands. Our proposed multi-frequency functional brain networks method yielded notable results, achieving an accuracy of 89.1%, a sensitivity of 86.67%, and an area under the curve of 0.942 in a publicly available autism spectrum disorder dataset.

Au-modified ceria nanozyme prevents and treats hypoxia-induced pulmonary hypertension with greatly improved enzymatic activity and safety.

BACKGROUND: Despite recent advances the prognosis of pulmonary hypertension remains poor and warrants novel therapeutic options. Extensive studies, including ours, have revealed that hypoxia-induced pulmonary hypertension is associated with high oxidative stress. Cerium oxide nanozyme or nanoparticles (CeNPs) have displayed catalytic activity mimicking both catalase and superoxide dismutase functions and have been widely used as an anti-oxidative stress approach. However, whether CeNPs can attenuate hypoxia-induced pulmonary vascular oxidative stress and pulmonary hypertension is unknown. RESULTS: In this study, we designed a new ceria nanozyme or nanoparticle (AuCeNPs) exhibiting enhanced enzyme activity. The AuCeNPs significantly blunted the increase of reactive oxygen species and intracellular calcium concentration while limiting proliferation of pulmonary artery smooth muscle cells and pulmonary vasoconstriction in a model of hypoxia-induced pulmonary hypertension. In addition, the inhalation of nebulized AuCeNPs, but not CeNPs, not only prevented but also blunted hypoxia-induced pulmonary hypertension in rats. The benefits of AuCeNPs were associated with limited increase of intracellular calcium concentration as well as enhancement of extracellular calcium-sensing receptor (CaSR) activity and expression in rat pulmonary artery smooth muscle cells. Nebulised AuCeNPs showed a favorable safety profile, systemic arterial pressure, liver and kidney function, plasma Ca2+ level, and blood biochemical parameters were not affected. CONCLUSION: We conclude that AuCeNPs is an improved reactive oxygen species scavenger that effectively prevents and treats hypoxia-induced pulmonary hypertension.

Maresin1 restrains chronic inflammation and Aß production to ameliorate Alzheimer's disease via modulating ADAM10/17 and its associated neuroprotective signal pathways: A pilot study.

Chronic inflammation is an important pathogenetic factor that leads to the progression of Alzheimer's disease (AD), and specialized pro-resolving lipid mediators (SPMs) play critical role in regulating inflammatory responses during AD pathogenesis. Maresin1 (MaR1) is the latest discovered SPMs, and it is found that MaR1 improves AD cognitive impairment by regulating neurotrophic pathways to protect AD synapses and reduce Aß production, which made MaR1 as candidate agent for AD treatment. Unfortunately, the underlying mechanisms are still largely known. In this study, the AD mice and cellular models were subjected to MaR1 treatment, and we found that MaR1 reduced Aß production to ameliorate AD-related symptoms and increased the expression levels of ADAM10/17, sAPPα and sAPPß to exert its anti-inflammatory role. In addition, as it was determined by Western Blot analysis, we observed that MaR1 could affected the neuroprotective signal pathways. Specifically, MaR1 downregulated p57NTR and upregulated TrkA to activate the p75NTR/TrkA signal pathway, and it could increase the expression levels of p-PI3K and p-Akt, and downregulated p-mTOR to activate the PI3K/AKT/ERK/mTOR pathway. Finally, we verified the role of ADAM10/17 in regulating AD progression, and we found that silencing of ADAM10/17 inactivated the above neuroprotective signal pathways to aggravate AD pathogenesis. In conclusion, MaR1 is verified as potential therapeutic agent for AD by eliminating Aß production, upregulating ADAM10/17, sAPPα and sAPPß, and activating the neuroprotective p75NTR/TrkA pathway and the PI3K/AKT/ERK/mTOR pathway.

Mechanism and application of fibrous proteins in diabetic wound healing: a literature review.

Diabetic wounds are more complex than normal chronic wounds because of factors such as hypoxia, reduced local angiogenesis, and prolonged inflammation phase. Fibrous proteins, including collagen, fibrin, laminin, fibronectin, elastin etc., possess excellent inherent properties that make them highly advantageous in the area of wound healing. Accumulating evidence suggests that they contribute to the healing process of diabetic wounds by facilitating the repair and remodel of extracellular matrix, stimulating the development of vascular and granulation tissue, and so on. However, there is currently a lack of a comprehensive review of the application of these proteins in diabetes wounds. An overview of fibrous protein characteristics and the alterations linked to diabetic wounds is given in this article's initial section. Next is a summary of the advanced applications of fibrous proteins in the last five years, including acellular dermal matrix, hydrogel, foam, scaffold, and electrospun nanofibrous membrane. These dressings have the ability to actively promote healing in addition to just covering wounds compared to traditional wound dressings like gauze or bandage. Research on fibrous proteins and their role in diabetic wound healing may result in novel therapeutic modalities that lower the incidence of diabetic wounds and thereby enhance the health of diabetic patients.

MTF2 facilitates the advancement of osteosarcoma through mediating EZH2/SFRP1/Wnt signaling.

BACKGROUND: Osteosarcoma is a soft tissue neoplasm with elevated recurrence risk and highly metastatic potential. Metal response element binding transcriptional factor 2 (MTF2) has been revealed to exert multiple activities in human tissues. The present research was conducted to explore the functions and related response mechanism of MTF2 in osteosarcoma which have not been introduced yet. METHODS: Bioinformatics tools identified the differential MTF2 expression in osteosarcoma tissues. MTF2 expression in osteosarcoma cells was examined with Western blot. Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-2'-deoxyuridine (EDU) staining, wound healing as well as transwell assays measured cell proliferation, migration and invasion, respectively. Flow cytometry assay detected the cellular apoptotic level. Western blot also measured the expressions of proteins associated with epithelial mesenchymal transition (EMT), apoptosis and enhancer of zeste homolog 2 (EZH2)/secreted frizzled-related protein 1 (SFRP1)/Wnt signaling. Co-immunoprecipitation (Co-IP) assay confirmed MTF2-EZH2 interaction. RESULTS: MTF2 expression was increased in osteosarcoma tissues and cells. MTF2 interference effectively inhibited the proliferation, migration and invasion of osteosarcoma cells and promoted the cellular apoptotic rate. MTF2 directly bound to EZH2 and MTF2 silence reduced EZH2 expression, activated SFRP1 expression and blocked Wnt signaling in osteosarcoma cells. EZH2 upregulation or SFRP1 antagonist WAY-316606 partly counteracted the impacts of MTF2 down-regulation on the SFRP1/Wnt signaling and the biological phenotypes of osteosarcoma cells. CONCLUSIONS: MTF2 might down-regulate SFRP1 to activate Wnt signaling and drive the progression of osteosarcoma via interaction with EZH2 protein.

Associations of BMI growth rates and body composition with cardiometabolic risks in Chinese preschool children.

OBJECTIVE: To examine the relationship between body mass index (BMI) growth rates, body composition, and cardiometabolic markers in preschool children. METHODS: Three-year-old children were recruited for this cohort study. BMI and body composition measurements were obtained at enrollment, with multiple BMI measurements spanning ages 1 month to 3 years extracted from medical records. Levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-cholesterol (non-HDL-C), remnant cholesterol (RC), uric acid (UA), and fasting plasma glucose (FPG) were measured at 3 years. Data analyses employed piecewise linear mixed models and logistic regression models. RESULTS: Out of 3822 children recruited, 3015 were included in the analysis. The accelerated zBMI growth rate between 6 and 24 months was positively correlated with high TG and LDL-C levels, with sex, birthweight, and size-for-gestational age disparities. Obesity increased the risks of high TG level and the highest RC quartile in boys. Fat mass index (FMI) and percentage of fat mass (FM%) were linked with high UA level and dyslipidemia, particularly high TG and non-HDL-C levels, in boys. Fat-free mass index (FFMI) showed negative associations with high levels of TC and non-HDL-C in boys and high LDL-C level in girls (P<0.05). CONCLUSIONS: This study underscores the significant impact of BMI growth rates and body composition on cardiometabolic markers in 3-year-old children. The effects of BMI growth rates in specific periods varied by sex, birthweight, and size-for-gestational age, and boys exhibiting a higher susceptibility to adverse outcomes.

Development and validation of a rating scale for barriers to and facilitators of nurses' participation intentions in "Internet + Nursing Service".

BACKGROUND: Given increases in China's aging population, the growing demand for public health services and the shortage of human resources among nurses have become more prominent. Under such a background, "Internet + Nursing Services" have received more attention. Thus, exploring the barriers to and facilitators of nurses' willingness to participate in "Internet + Nursing Services" and utilizing internet technology to increase the supply of nursing services has become a key issue. OBJECTIVE: This study aimed to develop a scale for assessing the barriers to and facilitators of nurses' willingness to participate in "Internet + Nursing Services" and to test the validity and reliability of the scale. METHODS: A preliminary scale was developed based on a literature review, theoretical research, semistructured qualitative interviews, and two rounds of Delphi expert inquiry. A convenient sampling method was used for the questionnaire survey. A 5-point Likert scale was used to evaluate the importance of the items. The survey data of 659 clinical nurses obtained from February to March 2023 were used for item analysis, exploratory factor analysis (EFA), and reliability and validity tests of the scale. The survey data of 538 clinical nurses obtained in April 2023 were used for confirmatory factor analysis (CFA) of the final scale. RESULTS: The final scale consists of 25 items and 4 dimensions (performance expectations, perceived risk, need for professional knowledge training, and nonprofessional knowledge training). The scale showed good structural validity and content validity: the Cronbach's α coefficient of the scale was 0.955, the split-half reliability was 0.778, the test-retest reliability was 0.944, the kaiser-meyer-olkin(KMO) value was 0.960, and the cumulative variance contribution rate of the 4 common factors was 83.147%. The scale content validity index(S-CVI) was 0.914. The confirmatory factor analysis model had favorable fit indices: χ2/df = 4.234, RMSEA = 0.078, NFI = 0.940, IFI = 0.953, TLI = 0.947, and CFI = 0.953. CONCLUSION: The scale for assessing the barriers to and facilitators of nurses' willingness to participate in "Internet + Nursing Services" has good reliability and validity, and provides a reference for evaluating nurses' willingness to participate in "Internet + Nursing Services".

Dynamic Viral Load Monitoring and Metagenomic Sequencing in Acute Retinal Necrosis Caused by Varicella-Zoster Virus.

PURPOSE: To analyze the trend of intraocular viral load after antiviral treatment in patients with varicella-zoster virus (VZV) induced acute retinal necrosis (ARN), and to explore the effect of viral genotypes on clinical manifestations. METHODS: In this case series, viral load was detected using polymerase chain reaction from aqueous humor during treatment; viral load curves were fitted, and the time required to reach the inflection point between plateau phase and logarithmic reduction phase (Tinflection) was estimated. Variations in viral genomes were detected by metagenomic sequencing. RESULTS: Twenty eyes of 20 patients were included. The median (interquartile range) initial viral load was 5.9×107 (1.1×107-1.1×108) copies/mL. The average duration of retinitis was 5±3 weeks. The average Tinflection was 4.2±1.6 days. Tinflection was correlated with the duration of retinitis (P=0.025). Patients with VZVs carrying the p.S715* variation in ribonucleotide reductase (RNR) subunit 1 gene had lower initial viral loads (median 1.3×107 copies/ml) than those without (median 1.1×108 copies/ml; adjusted P=0.030). CONCLUSIONS: The inflection of viral load curve is helpful to estimate the length of plateau phase and the duration of retinitis during antiviral treatment in ARN patients. Loss-of-function variation in RNR gene might be correlated with lower virulence of VZV.

YTHDF3 Regulates the Degradation and Stability of m6A-Enriched Transcripts to Facilitate the Progression of Castration-Resistant Prostate Cancer.

RNA N6-methyladenosine (m6A) readers mediate cancer progression. However, the functional role and potential mechanisms of the m6A readers in prostate cancer tumorigenicity remain to be elucidated. In this study, we demonstrate that YTHDF3 expression is elevated in castration-resistant prostate cancer (CRPC) and positively correlated to high grade, bone metastasis and poor survival. YTHDF3 expression promoted CRPC cell proliferation, epithelial to mesenchymal transition (EMT) and tumour progression. Mechanistically, YTHDF3 promoted the RNA degradation of SPOP and NXK3.1 but stabilized RNA expressions of TWIST1 and SNAI2 dependent on m6A to facilitate cell proliferation and EMT. Additionally, YTHDF3 expression enhanced AKT activity via degrading SPOP in an m6A-dependent manner. Importantly, we found that melatonin can compete with m6A to occupy the m6A-binding cage of YTHDF3, leading to inhibition of YTHFD3 and its target expressions as well as CRPC tumour growth. Our findings uncover an essential role of YTHDF3 in the progression of CRPC and highlight the role of melatonin in anti-CRPC activity.

Multiple Stimulus Response Material Based on Sr-tcbpe MOF for Mechanochromism, Visualization Labeling, and Etching Toward TNP.

The abuse and excessive discharge of organic pollutants such as nitroaromatic compounds (NACs) have become a hot topic of concern for all humanity and society, and the development of fast, effective, and targeted technical means for detecting NACs also faces many challenges. Here, we reported a strontium-based metal-organic framework (MOF) {[Sr2(tcbpe)(H2O)4]}n (Sr-tcbpe), in which tcbpe represents deprotonated 4',4‴,4″‴,4‴‴-(ethene-1,1,2,2-tetrayl)tetrakis(([1,1'biphenyl]-4-carboxylic acid)). In Sr-tcbpe, Sr-O polyhedron and deprotonated tcbpe4- ligand have a staggered connection to form a self-assembled three-dimensional network structure. In addition, it is found that Sr-tcbpe undergoes no luminescent color change when grinding under solvent protection, while mechanochromic fluorescence behavior is observed when grinding directly, leading to luminescent color changes from cyan to green (Sr-tcbpe-G). Additionally, Sr-tcbpe and Sr-tcbpe-G could selectively detect PNP, DNP, and TNP, and Sr-tcbpe achieves visual fluorescence sensing detection toward TNP at a limit of detection as low as 2.25 µM. Moreover, during the detection process, unexpectedly, TNP exhibits a selective etching effect on Sr-tcbpe, which could drill nano holes with different sizes on the surface area of MOF materials to a certain extent, achieving the conversion of chemical energy to mechanical energy. In addition, the successful preparation of a portable sensor Sr-tcbpe@gypsum block provides a platform for the perfect combination of mechanochromic fluorescence behavior and visualization detection toward TNP. It lays the foundation for the practical application of MOF materials in daily life.

A mini-review of isolation, purification, structural characteristics and bioactivities of polysaccharides from Aralia elata (Miq.) Seem.

In recent years, the isolation, purification, structural characterization of plant polysaccharides from natural resources have arrested widespread attention. Aralia elata (Miq.) Seem (A. elata) belongs to the Aralia genus of the Araliaceae family, which is one of the most popular edible mountain vegetables in East Asia. A. elata has been widely distributed in China, particularly in Liaoning, Jilin, and Heilongjiang provinces in northeast China, in which it has been used as a traditional herbal medicine for thousands of years to treat various diseases, such as hepatitis and rheumatoid arthritis. A. elata polysaccharides (AEPs) are one of the major active ingredients of A. elata, the monosaccharide composition of which consist primarily of Gal, Glc, Man, Ara, and Rha, with molecular weights ranging from 1.56 × 104 Da to 1.12 × 105 Da. AEPs have attracted worldwide attention owing to their various biological activities, including antioxidant activity, antitumor activity and hepatoprotection. The present review aims to comprehensively summarize the research advances on the polysaccharides isolated from A. elata, including the extraction, separation, physical-chemical properties, structural characteristics, and bioactivities over the past few decades. This review would establish a solid foundation for further development and application in the field of AEPs.

Avatrombopag as alternative therapy for severe aplastic anemia patients who are intolerant or unresponsive to eltrombopag.

Introduction: Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, EPAG contains a typical biphenyl structure, which causes liver function damage. Methods: Twenty patients with SAA who were intolerant or refractory to EPAG were enrolled in a multicenter prospective registry of the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100045895) from October 2020 to June 2023. Results: Eight patients who were ineffective to EPAG, six with kidney impairment, and nine with abnormal liver function (two with concomitant liver and kidney impairment) were converted to avatrombopag (AVA) therapy with the median duration of AVA treatment was 6 (3-24) months. 17 cases (85%) achieved trilineage hematological response (HR): complete remission (CR) in 3 cases (15%), good partial remission (GPR) in 4 cases (20%), partial remission (PR) in 10 cases (50%), and no response (NR) in 3 cases (15%). The median time to response was 1.7 (0.5-6.9) months, with 16 cases (94%) achieving response within six months and 17 cases (100%) within 12 months. 9 cases (50%) achieved transfusion independence. AVA converted treatment was associated with higher neutrophil counts (0.8×109/L vs 2.2×109/L, p=0.0003), platelet counts (11×109/L vs 39×109/L, p=0.0008), hemoglobin count (59g/L vs 98g/L, p=0.0002), red cell count (1.06×1012/L vs 2.97×1012/L, p=0.001), and absolute reticulocyte count (31.99 ×109/L vs 67.05×109/L p=0.0004) were all significantly elevated compared with the pre-treatment level. After the conversion to AVA therapy, liver and kidney function indexes were maintained within the normal range, no AVA related grade 2 or higher adverse events occurred, and no thrombotic events occurred. Conclusion: The conversion to AVA was an optimal choice for patients with SAA who were EPAG intolerant or refractory. Clinical trial registration: http://www.chictr.org.cn/showproj.html?proj=125480, identifier ChiCTR2100045895.