Morphological, anatomical, and transcriptomics analysis reveals the regulatory mechanisms of cassava plant height development.

BACKGROUND: Cassava is one of three major potato crops and the sixth most important food crop globally. Improving yield remains a primary aim in cassava breeding. Notably, plant height significantly impacts the yield and quality of crops; however, the mechanisms underlying cassava plant height development are yet to be elucidated. RESULTS: In this study, we investigated the mechanisms responsible for cassava plant height development using phenotypic, anatomical, and transcriptomic analyses. Phenotypic and anatomical analysis revealed that compared to the high-stem cassava cultivar, the dwarf-stem cassava cultivar exhibited a significant reduction in plant height and a notable increase in internode tissue xylem area. Meanwhile, physiological analysis demonstrated that the lignin content of dwarf cassava was significantly higher than that of high cassava. Notably, transcriptome analysis of internode tissues identified several differentially expressed genes involved in cell wall synthesis and expansion, plant hormone signal transduction, phenylpropanoid biosynthesis, and flavonoid biosynthesis between the two cassava cultivars. CONCLUSIONS: Our findings suggest that internode tissue cell division, secondary wall lignification, and hormone-related gene expression play important roles in cassava plant height development. Ultimately, this study provides new insights into the mechanisms of plant height morphogenesis in cassava and identifies candidate regulatory genes associated with plant height that can serve as valuable genetic resources for future crop dwarfing breeding.

Research progress on prediction of RNA-protein binding sites in the past five years.

Accurately predicting RNA-protein binding sites is essential to gain a deeper comprehension of the protein-RNA interactions and their regulatory mechanisms, which are fundamental in gene expression and regulation. However, conventional biological approaches to detect these sites are often costly and time-consuming. In contrast, computational methods for predicting RNA protein binding sites are both cost-effective and expeditious. This review synthesizes already existing computational methods, summarizing commonly used databases for predicting RNA protein binding sites. In addition, applications and innovations of computational methods using traditional machine learning and deep learning for RNA protein binding site prediction during 2018-2023 are presented. These methods cover a wide range of aspects such as effective database utilization, feature selection and encoding, innovative classification algorithms, and evaluation strategies. Exploring the limitations of existing computational methods, this paper delves into the potential directions for future development. DeepRKE, RDense, and DeepDW all employ convolutional neural networks and long and short-term memory networks to construct prediction models, yet their algorithm design and feature encoding differ, resulting in diverse prediction performances.

Intrinsic capacity loss rates and protective factors among individuals aged 80 years and older in Chinese nursing homes: A latent class analysis.

Prior to this cross-sectional study, the intrinsic capacity (IC) loss rates and protective factors in nursing homes for individuals aged 80 and older remained unexplored. Analysing 434 participants, this study found 86.9 % of individuals experienced the loss of at least one IC domain, with detailed losses in locomotion, vision, vitality, hearing, psychological, and cognitive capacities at rates of 83.2 %, 52.8 %, 50.9 %, 46.5 %, 44.9 %, and 44.0 %, respectively. Following latent class analysis (LCA), five distinct IC impairment patterns were noted, with locomotor impairment emerging as a central component across most classes. IC protective factors for persons aged 80 years and older included financial stability, being male or younger within the cohort, junior high school or higher education, being married, no smoking history, manageable comorbidity levels, minimal medication use, good sleep, and not using assistive devices. Based on these five classes, this study provides a potential practical framework alongside recommendations for IC care strategies in the oldest-old, emphasising the importance of locomotor function in maintaining the overall IC.

Application of MFI-5 in severe complications and unfavorable outcomes after radical resection of colorectal cancer.

BACKGROUND: Frailty is considered a characteristic manifestation of physiological decline in multiple organ systems, which significantly increases the vulnerability of elderly individuals with colorectal cancer (CRC) and is associated with a poor prognosis. While studies have demonstrated that the 11-factor Modified Frailty Index (mFI-11) can effectively predict adverse outcomes following radical resection of CRC, there is a lack of research on the applicability of the 5-factor Modified Frailty Index (mFI-5) within this patient population. METHODS: In this retrospective analysis, we examined a cohort of CRC patients aged 65 years and above who had undergone radical resection. For each patient, we calculated their mFI-5 score, considering a score of ≥ 2 as an indication of frailty. We conducted univariate and multivariate analyses to assess the association between the mFI-5 and adverse outcomes as well as postoperative complications. RESULTS: Patients with an mFI-5 score ≥ 2 exhibited a significantly higher incidence of serious postoperative complications (53% vs. 30%; P = 0.001) and experienced a longer hospital stay [19.00 (15.00-24.50) vs. 17.00 (14.00-20.00); P < 0.05]. Notably, an mFI-5 score greater than 2 emerged as an independent risk factor for severe postoperative complications (odds ratio: 2.297; 95% confidence interval: 1.216 to 4.339; P = 0.01). Furthermore, the mFI-5 score displayed predictive capabilities for severe postoperative complications with an area under the receiver operating characteristic (ROC) curve of 0.629 (95% confidence interval: 0.551 to 0.707; P < 0.05). CONCLUSION: The mFI-5 demonstrates a high level of sensitivity in predicting serious complications, prolonged hospital stays, and mortality following radical resection of colorectal carcinoma. As a practical clinical assessment tool, the mFI-5 enables the identification of high-risk patients and facilitates preoperative optimization.

Ultrafast Luminescent Light-Up Guest Detection Based on the Lock of the Host Molecular Vibration.

Light-up luminescence sensors have been employed in real-time in situ visual detection of target molecules including volatile organic compounds (VOCs). However, currently employed light-up sensors, which are generally based on the aggregation-induced emission (AIE) or solvent-induced energy transfer effect, exhibit limited sensitivity for light-up detection and poor recycling performances thereby significantly hindering their industrial applications. Inspired by the low-temperature enhanced luminescence phenomenon, we herein propose and show that a guest-lock-induced luminescence enhancement mechanism can be used to realize the ultrafast light-up detection of target VOCs. Through introduction of chlorinated hydrocarbons to lock the molecular vibrations within a designed [Cu4I4]-based metal-organic framework (MOF), luminescence intensity could be enhanced significantly at room temperature. This guest-lock-induced luminescence enhancement is brought about by weak supramolecular interactions between the host framework and the guest molecules, allowing highly sensitive and specific detection of the guest vapor with ultrafast response time (<1 s). Single-crystal X-ray diffraction (SCXRD) analysis of guest molecules-loaded MOFs and density functional theory (DFT) calculations were employed to investigate the host-guest interactions involved in this phenomenon. Moreover, the above MOF sensor successfully achieved real-time detection of a toxic chloroaromatic molecule, chlorobenzene. The guest-lock-induced light-up mechanism opens up a route to discovering high-performance ultrafast light-up luminescent sensors for real-time detection applications.

Activin a promotes myofibroblast differentiation of endometrial mesenchymal stem cells via STAT3-dependent Smad/CTGF pathway.

BACKGROUND: Endometriosis, characterized by the presence of functional endometrial tissues outside the uterus, is one of the most common gynecological disorders. Endometrial mesenchymal stem cells (MSCs) are crucial for the occurrence and development of endometriosis. Ectopic endometrial MSCs exist in the peritoneal cavity. Thus, the bioactive factors in endometriotic peritoneal fluid may regulate the biological behaviors of endometrial MSCs. METHODS: In this study, after assessing the concentration of Activin A in peritoneal fluid using ELISA, we isolated and cultured endometrial MSCs and investigated whether Activin A stimulated endometrial MSCs to differentiate into myofibroblasts and clarified the underlying mechanisms by quantitative real-time PCR, Western blot analysis, immunofluorescent staining, RNA interference and Chromatin immunoprecipitation. We also employed the inhibitors of Activin A to explore the possibility of suppressing the development of fibrosis in endometriosis using primary endometrial MSCs cultures and a mouse model of endometriosis. RESULTS: Here, we revealed that Activin A significantly elevated in endometriotic peritoneal fluid and activin receptor-like kinase (ALK4), the specific receptor for Activin A, obviously enhanced in ectopic endometrial MSCs compared with eutopic endometrial MSCs from women with or without endometriosis. Next, we found that Activin A drived myofibroblast differentiation of endometrial MSCs, with extremely enhanced expression of connective tissue growth factor (CTGF). CTGF was shown to be required for Activin A-induced expression of ACTA2, COL1A1 and FN1 in endometrial MSCs. CTGF induction by Activin A in endometrial MSCs involved the activation of Smad2/3, as evidenced by the phosphorylation and nuclear translocation of Smad2/3 as well as the binding of Smad2/3 to CTGF promoter. Furthermore, Smad/CTGF pathway in endometrial MSCs required activation of STAT3 while independent of PI3K, JNK and p-38 pathways. In addition, we also demonstrated that inhibition of Activin A pathway impeded myofibroblast differentiation of endometrial MSCs and ameliorated fibrosis in endometriosis mice. CONCLUSIONS: Activin A promotes myofibroblast differentiation of endometrial mesenchymal stem cells via STAT3-dependent Smad/CTGF pathway. The results provided the first evidence that STAT3 acted as a crucial Activin A downstream mediator to regulate CTGF production. Our data may supplement the stem cell theory of endometriosis and provide the experimental basis to treat endometriosis-associated fibrosis by manipulating Activin A signaling.

[Application Status and Development Trends of Medical Proton and Heavy Ion Accelerators].

Cancer therapy with accelerated proton or heavy ion beam is the most advanced radiotherapy technology, which is recognized by the international community at present. It is of great practical significance to study the medical proton and heavy ion accelerators and the radiotherapy technology, in order to promote the development of the advanced medical radiotherapy equipments and improve the quality of life of cancer patients in China. After a brief overview of cancer therapy with proton and heavy ion beam, this paper summarized and analyzed the application status of medical proton accelerators and medical heavy ion accelerators at home and abroad, and finally put forward the future development trends of medical proton and heavy ion accelerators and the radiotherapy technology, it can provide a reference for the progress and development strategies of the advanced radiotherapy equipments in China.

The Central Hinge Link Truncation of the Antimicrobial Peptide Fowlicidin-3 Enhances Its Cell Selectivity without Antibacterial Activity Loss.

Antimicrobial peptides (AMPs) have been paid considerable attention because of their broad-spectrum antimicrobial activity and a reduced possibility of the development of bacterial drug resistance. Fowlicidin-3 (Fow-3) is an identified type of chicken cathelicidin AMP that has exhibited considerable antimicrobial activity and cytotoxicity. To reduce cell toxicity and improve cell selectivity, several truncated peptides of fowlicidin-3, Fow-3(1-15), Fow-3(1-19), Fow-3(1-15-20-27), and Fow-3(20-27), were synthesized. Our results indicated that neither the N- nor C-terminal segment alone [Fow-3(1-15), Fow-3(1-19), Fow-3(20-27)] was sufficient to confer antibacterial activity. However, Fow-3(1-19) with the inclusion of the central hinge link (-AGIN-) retained substantial cell toxicity, which other analogs lost. Fow-3(1-15-20-27) displayed potent antimicrobial activity for a wide range of Gram-negative and Gram-positive bacteria and no obvious hemolytic activity or cytotoxicity. The central link region was shown to be critically important in the function of cell toxicity but was not relevant to antibacterial activity. Fow-3(1-15-20-27) maintained antibacterial activity in the presence of physiological concentrations of salts. The results from fluorescence spectroscopy, scanning electron microcopy, and transmission electron microcopy showed that Fow-3(1-15-20-27) as well as fowlicidin-3 killed bacterial cells by increasing membrane permeability and damaging the membrane envelope integrity. Fow-3(1-15-20-27) could be a promising antimicrobial agent for clinical application.

Synthesis, G-quadruplexes DNA binding, and photocytotoxicity of novel cationic expanded porphyrins.

Intensive reports allowed the conclusion that molecules with extended aromatic surfaces always do good jobs in the DNA interactions. Inspired by the previous successful researches, herein, we designed a series of cationic porphyrins with expanded planar substituents, and evaluated their binding behaviors to G-quadruplex DNA using the combination of surface-enhanced raman, circular dichroism, absorption spectroscopy and fluorescence resonance energy transfer melting assays. Asymmetrical tetracationic porphyrin with one phenyl-4-N-methyl-4-pyridyl group and three N-methyl-4-pyridyl groups exhibit the best G4-DNA binding affinities among all the designed compounds, suggesting that the bulk of the substituents should be matched to the width of the grooves they putatively lie in. Theoretical calculations applying the density functional theory have been carried out and explain the binding properties of these porphyrins reasonably. Meanwhile, these porphyrins were proved to be potential photochemotherapeutic agents since they have photocytotoxic activities against both myeloma cell (Ag8.653) and gliomas cell (U251) lines.

Hydrogen-rich saline attenuates neuronal ischemia--reperfusion injury by protecting mitochondrial function in rats.

BACKGROUND: Hydrogen, a popular antioxidant gas, can selectively reduce cytotoxic oxygen radicals and has been found to protect against ischemia-reperfusion (I/R) injury of multiple organs. Acute neuronal death during I/R has been attributed to loss of mitochondrial permeability transition coupled with mitochondrial dysfunction. This study was designed to investigate the potential therapeutic effect of hydrogen-rich saline on neuronal mitochondrial injury from global cerebral I/R in rats. MATERIALS AND METHODS: We used a four-vessel occlusion model of global cerebral ischemia and reperfusion, with Sprague-Dawley rats. The rats were divided randomly into six groups (n = 90): sham (group S), I/R (group I/R), normal saline (group NS), atractyloside (group A), hydrogen-rich saline (group H), and hydrogen-rich saline + atractyloside (group HA). In groups H and HA, intraperitoneal hydrogen-rich saline (5 mL/kg) was injected immediately after reperfusion, whereas the equal volume of NS was injected in the other four groups. In groups A and HA, atractyloside (15 µL) was intracerebroventricularly injected 10 min before reperfusion, whereas groups NS and H received equal NS. The mitochondrial permeability transition pore opening and mitochondrial membrane potential were measured by spectrophotometry. Cytochrome c protein expression in the mitochondria and cytoplasm was detected by western blot. The hippocampus mitochondria ultrastructure was examined with transmission electron microscope. The histologic damage in hippocampus was assessed by hematoxylin and eosin staining. RESULTS: Hydrogen-rich saline treatment significantly improved the amount of surviving cells (P < 0.05). Furthermore, hydrogen-rich saline not only reduced tissue damage, the degree of mitochondrial swelling, and the loss of mitochondrial membrane potential but also preserved the mitochondrial cytochrome c content (P < 0.05). CONCLUSIONS: Our study showed that hydrogen-rich saline was able to attenuate neuronal I/R injury, probably by protecting mitochondrial function in rats.

The potential mechanisms of Aß-receptor for advanced glycation end-products interaction disrupting tight junctions of the blood-brain barrier in Alzheimer's disease.

The receptor for advanced glycation end-products (RAGE) is a multiligand membrane receptor that has been implicated in the cytotoxicity effects of ß-amyloid protein (Aß) in AD. Positive feedback mechanism of RAGE within blood-brain barrier (BBB) and/or cells inside the brain is proposed, including interaction with Aß stimulating activation of proinflammatory cytokines, release of reactive oxygen species (ROS), which leads to neuron damage and BBB dysfunction. RAGE is the main factor mediating Aß cytotoxicity. Attenuation of RAGE activity may inhibit Aß from accumulation in the cerebral blood vessels and prevent neurotoxicity. Furthermore, RAGE may serve as a therapeutic target for Alzheimer's disease by inhibiting pathophysiological consequences of Aß-RAGE interaction. Tight junctions (TJ) are identified as the basic structure of the BBB and RAGE-mediated Aß cytotoxicity to the brain microvascular endothelial cells (BMEC), resulting in damaged BBB structural integrity. However, the potential mechanism is poorly studied.

Changes of serum CA125 and PGE2 before and after high-intensity focused ultrasound combined with GnRH-a in treatment of patients with adenomyosis.

This study aimed to investigate the changes of serum carbohydrate antigen 125 (CA125) and prostaglandin E2 (PGE2) in patients with adenomyosis before and after treatment with high-intensity focused ultrasound (HIFU) combined with gonadotropin-releasing hormone agonist (GnRH-a). One hundred and sixty-five patients with adenomyosis who received HIFU combined with GnRH-a were selected as case group. Sixty-five healthy women who underwent physical examination at the same time were taken as normal control group. At the end of follow-up 6 months after treatment, the case group were divided into effective subgroup and ineffective subgroup according to clinical efficacy. Changes of serum CA125 and PGE2 were analyzed. Serum CA125 and PGE2 levels in the case group were higher than those in the normal control group before treatment (both P < 0.001). Serum CA125 and PGE2 levels in the case group 6 months after treatment were lower than those before treatment (both P < 0.001). There was no difference in serum CA125 and PGE2 levels between effective subgroup and ineffective subgroup before treatment (P = 0.351, 0.284, respectively). Serum CA125 and PGE2 levels in the effective subgroup were lower than those in the ineffective subgroup 6 months after treatment (both P < 0.001). Serum CA125 and PGE2 may be involved in the development of adenomyosis, and their expression levels may be related to the prognosis of patients. Levels of serum CA125 and PGE2 in patients with adenomyosis decrease after treatment with HIFU combined with GnRH-a. The detection of serum CA125 and PGE2 may be used as an index to diagnose adenomyosis and evaluate the therapeutic effect of HIFU combined with GnRH-a.

Overexpression of circulating CD38+ NK cells in colorectal cancer was associated with lymph node metastasis and poor prognosis.

Introduction: Lymph node metastasis (LNM) is a critical prognostic factor for colorectal cancer (CRC). Due to the potential influence of immune system on CRC progression, investigation into lymphocyte subsets as clinical markers has gained attention. The objective of this study was to assess the capability of lymphocyte subsets in evaluating the lymph node status and prognosis of CRC. Methods: Lymphocyte subsets, including T cells (CD3+), natural killer cells (NK, CD3- CD56+), natural killer-like T cells (NK-like T, CD3+ CD56+), CD38+ NK cells (CD3- CD56+ CD38+) and CD38+ NK-like T cells (CD3+ CD56+ CD38+), were detected by flow cytometry. Univariate and multivariate analyses were used to assess the risk factors of LNM. The prognostic role of parameters was evaluated by survival analysis. Results: The proportion of CD38+ NK cells within the NK cell population was significantly higher in LNM-positive patients (p <0.0001). However, no significant differences were observed in the proportions of other lymphocyte subsets. Poorer histologic grade (odds ratio [OR] =4.76, p =0.03), lymphovascular invasion (LVI) (OR =22.38, p <0.01), and CD38+ NK cells (high) (OR =4.54, p <0.01) were identified as independent risk factors for LNM. Furthermore, high proportion of CD38+ NK cells was associated with poor prognosis of CRC patients (HR=2.37, p =0.03). Conclusions: It was demonstrated that the proportion of CD38+ NK cells was a marker overexpressed in LNM-positive patients compared with LNM-negative patients. Moreover, an elevated proportion of CD38+ NK cells is a risk factor for LNM and poor prognosis in CRC.

Simultaneous determination of unecritinib (TQ-B3101) and its active metabolite crizotinib in rat plasma by LC-MS/MS：An application to pharmacokinetic studies.

Unecritinib (TQ-B3101) is a selective tyrosine kinase receptor inhibitor. In the study, in vitro metabolic experiments revealed that the hydrolysis of TQ-B3101 was mainly catalyzed by carboxylesterase 2 (CES2), followed by CES1. Next, a sensitive and reliable LC-MS/MS method was established for the simultaneous determination of TQ-B3101 and its metabolite crizotinib in rat plasma. To prevent in vitro hydrolysis of TQ-B3101, sodium fluoride, the CESs inhibitor at a concentration of 2 M, was immediately added after whole blood collection. Plasma samples were extracted by acetonitrile-induced protein precipitation method, and chromatographically separated on a Gemini C18 column (50 mm × 2.0 mm i.d., 5 µm) using gradient elution with a mobile phase of 0.1% formic acid and 5 mmol/L ammonium acetate with 0.1% formic acid. The retention times for TQ-B3101 and crizotinib were 2.61 and 2.38 min, respectively. The analytes were detected with tandem mass spectrometer by positive electrospray ionization, using the ion transitions at m/z 492.3 → 302.3 for TQ-B3101, m/z 450.3 → 260.3 for crizotinib, and m/z 494.0 → 394.3 for imatinib (internal standard). Method validation was conducted in the linear range of 1.00-800 ng/mL for the two analytes. The precision, accuracy and stabilities all met the acceptance criteria. The pharmacokinetic study indicated that TQ-B3101 was rapidly hydrolyzed to crizotinib with the elimination half-life of 1.11 h after a single gavage administration of 27 mg/kg to Sprague-Dawley rats, and the plasma exposure of TQ-B3101 was only 2.98% of that of crizotinib.

Effects of Social Support Provided by Disabled Older Adults to Others on Their Own Depressive Symptoms: A Moderated Mediation Model.

Purpose: While previous studies have extensively examined the impact of receiving positive social support during social support interactions on depressive symptoms among older adults, adverse effects experienced, such as being rejected or ignored, are often overlooked. Moreover, there has been limited discussion on the effects of giving social support to others. Thus, this study investigates the impacts of social support given by disabled older adults to others on their own depressive symptoms, as well as the mediating role of receiving social support (both positive and negative aspects) and the moderating effect of the activity of daily living (ADL). Patients and Methods: This cross-sectional, community-based study was conducted in Wenzhou and Jiaxing City, China, from September 2021 to September 2022, with a total of 255 disabled older adults meeting the inclusion and exclusion criteria. The data were collected face-to-face using a structured questionnaire. The participants were asked to complete the Barthel Index Scale, the Chinese version of the Positive and Negative Social Exchange Scale, the Giving Social Support questionnaire, and the Short Form Chinese Geriatric Depression Scale to measure disability, receiving positive and negative social support, giving social support, and depressive symptoms, respectively. Descriptive statistical analysis, correlation analysis, mediation effect tests, and moderation effect tests were used to analyse the questionnaire data. Results: The social support provided by disabled older adults to others primarily involved companionship and care. The positive aspect of social support received was largely emotional support, while the negative aspect was mainly characterised by failure to obtain help and unsympathetic behaviour. Providing social support was found to be associated with a potential beneficial effect on depressive symptoms, linked to lower severity, with this effect fully mediated by receiving social support. Specifically, receiving emotional support accounted for 56.63% of the effect size, while failure to obtain help and unsympathetic behaviour contributed 21.55%, and rejection and neglect collectively accounted for 21.83%. Additionally, the effect was partially moderated by ADL, with older adults exhibiting lower ADL scores showing a greater benefit from both giving and receiving social support compared to those with higher ADL scores. Conclusion: It is imperative to recognise and encourage disabled older adults to provide social support to others, especially emotional support, while reducing negative feedback, such as neglect and unnecessary blame. This could alleviate their depressive symptoms and promote psycho-social well-being.

The effect of social isolation on the cognitive ability of the oldest old in Chinese nursing homes in post-COVID-19: a moderated chain mediation model.

Background: Both pre-or post-COVID-19, older adults residing in nursing homes are at significant risk for social isolation, which is negatively associated with cognitive ability. Currently, the elderly aged 80 years and older are the fastest-growing age group globally. The extent of social isolation within this group post-COVID-19 and its impact on cognitive abilities remain inadequately explored. Objective: This research aimed to evaluate the prevalence of social isolation among the oldest old in Chinese nursing homes post-COVID-19 and to investigate the mediating and moderating roles of basic activities of daily living (BADL), depression, and subjective socioeconomic status in the relationship between social isolation and cognitive ability. Methods: This cross-sectional study included 453 participants aged 80 years and older from 11 nursing homes in Ningbo, Zhejiang Province, China. Social isolation was assessed using the Lubben Social Network Scale-6 (LSNS-6), cognitive ability using the Mini-Mental State Examination (MMSE), BADL using the Barthel Index (BI), and depression using the Patient Health Questionnaire-9 items (PHQ-9). Mediation and moderation effects were statistically analyzed using SPSS 23.0 and PROCESS 3.5. Results: The mean age of the study sample was 87.1 ± 3.8 years, among whom 60.3% (n = 273) were female, and 56.1% experienced social isolation, with 41.1% and 63.1% being isolated from family and friends, respectively. Social isolation indirectly affected cognitive ability through BADL and depression, respectively, and through the chain mediation effect of BADL and depression. Subjective socioeconomic status moderated the relationships between social isolation and BADL and between social isolation and depression. However, no moderating effect of subjective socioeconomic status was found between social isolation and cognitive ability. Conclusion: This study deepens our understanding of the current state of social isolation and its mechanisms of action in the oldest old post-COVID-19 and provides a new basis for future public health policy development and related research.

Exploring the effective components of honey-processed licorice (Glycyrrhiza uralensis Fisch.) in attenuating Doxorubicin-induced myocardial cytotoxicity by combining network pharmacology and in vitro experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is widely used clinically as one of the most famous traditional Chinese herbs. Its herb roasted with honey is called honey-processed licorice (HPL). Modern studies have shown that HPL has a stronger cardioprotective ability compared to raw licorice (RL), however the material basis and mechanism of action of the potential cardioprotection have not been fully elucidated. AIM OF THE STUDY: To screen and validate the material basis of cardioprotection exerted by HPL and to preliminarily predict the potential mechanism of action. MATERIALS AND METHODS: UPLC-QTOF-MS/MS was used to analyze HPL samples with different processing levels, and differential compounds were screened out through principal component analysis. Network pharmacology and molecular docking were applied to explore the association between differential compounds and doxorubicin cardiomyopathy and their mechanisms of action were predicted. An in vitro model was established to verify the cardioprotective effects of differential compounds. RESULTS: Six differential compounds were screened as key components of HPL for potential cardioprotection. Based on network pharmacology, 113 potential important targets for the treatment of Dox-induced cardiotoxicity were screened. KEGG enrichment analysis predicted that the PI3K-Akt pathway was closely related to the mechanism of action of active ingredients. Molecular docking results showed that the six differential compounds all had good binding activity with Nrf2 protein. In addition, in vitro experiments had shown that five of the active ingredients (liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, and licochalcone A) can significantly increase Dox-induced H9c2 cell viability, SOD activity, and mitochondrial membrane potential, significantly reduces MDA levels and inhibits ROS generation. CONCLUSION: Liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin and licochalcone A are key components of HPL with potential cardioprotective capabilities. Five active ingredients can alleviate Dox-induced cardiotoxicity by inhibiting oxidative stress and mitochondrial damage.

Safety and efficacy of PD-1 and PD-L1 inhibitors in relapsed and refractory Hodgkin's lymphoma: a systematic review and meta-analysis of 20 prospective studies.

BACKGROUND: Inhibitors of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) have been used in the treatment of relapsed and refractory Hodgkin's lymphoma (R/R HL) recently. To further understand the safety and efficacy of PD-1/PD-L1 inhibitors in R/R HL, we conducted this meta-analysis. METHODS: Databases and the Clinical Registration Platforms have been systematically searched for related studies by March 2022. For safety analysis, the incidence and exhibition of any grade and grade 3 or higher adverse effects (AEs) were evaluated. Besides, severe AEs (SAEs), treatment-related deaths, and AEs leading to treatment discontinuation were summarized. The overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, progression-free survival (PFS), overall survival (OS), and duration of response (DOR) were calculated for efficacy analysis. All processes were implemented mainly through the package Meta and MetaSurv of software R 4.1.2. RESULTS: Overall 20 studies and 1440 patients were enrolled. The pooled incidence of any grade and grade 3 or higher AEs were 92% and 26%, respectively. The pooled ORR, CR rate and PR rate were 79%, 44% and 34%, respectively. The most common AEs were neuropathy (29%), nausea (27%), pyrexia (26%), and leukopenia (25%), and the most common grade 3 or higher AEs included leukopenia (10%), infusion reaction (8%), weight gain (3%), and neutropenia (2.7%). In survival analysis, pembrolizumab monotherapy appeared to perform better compared to nivolumab monotherapy. CONCLUSIONS: PD-1/PD-L1 inhibitors show promising efficacy and tolerable AEs in the treatment of R/R HL.

What happens to regulatory T cells in multiple myeloma.

Abnormal tumor microenvironment and immune escape in multiple myeloma (MM) are associated with regulatory T cells (Tregs), which play an important role in maintaining self-tolerance and regulating the overall immune response to infection or tumor cells. In patients with MM, there are abnormalities in the number, function and distribution of Tregs, and these abnormalities may be related to the disease stage, risk grade and prognosis of patients. During the treatment, Tregs have different responses to various treatment regiments, thus affecting the therapeutic effect of MM. It is also possible to predict the therapeutic response by observing the changes of Tregs. In addition to the above, we reviewed the application of Tregs in the treatment of MM. In conclusion, there is still much room for research on the mechanism and application of Tregs in MM.

A Preliminary Study of Brain Functional Magnetic Resonance Imaging in Text Reading and Comprehension.

BACKGROUND: Few studies have focused on the changes in human brain function activities caused by reading Chinese characters with different intelligibility and whether it can reflect the understanding and cognitive ability of the human brain. OBJECTIVE: Task-fMRI based on Chinese character reading tasks with different intelligibility was used to explore activated brain regions and their cognitive changes. METHODS: Volunteers were randomly recruited using advertisements. Forty volunteers were recruited based on strict inclusion and exclusion criteria, and 40 volunteers were recruited. Brain function data of 40 healthy right-handed volunteers in fuzzy/clear Chinese reading tasks were collected using a Siemens Skyra 3.0T magnetic resonance scanner. Data were preprocessed and statistically analyzed using the statistical software SPM12.0 to observe the activation of the cortex and analyze its characteristics and possible changes in cognitive function. RESULTS: Task-fMRI analysis: (1) The main brain regions activated in fuzzy/clear reading tasks were located in the occipital visual cortex (P < 0.001); (2) a paired sample t-test suggested that there was a significant difference in BOLD signals in the brain regions activated by fuzzy/clear reading tasks (P < 0.001, equiv Z = 4.25). Compared with the fuzzy reading task, the brain regions more strongly activated in the clear reading task were mainly located in the right superior frontal gyrus and the bilateral temporal lobe. Compared with the clear reading task, the brain region that was more strongly activated in the fuzzy reading task was mainly located in the right fusiform gyrus. CONCLUSION: Clear Chinese character information mainly activates the dorsal stream of the visual-spatial network. This reflects the information transmission of the brain after understanding the text content and is responsible for guiding and controlling attention. Fuzzy words that cannot provide clear text content activate the fusiform gyrus of the ventral stream of the visual-spatial network, strengthening the function of orthographic processing.