The prognostic significance of ubiquitination-related genes in multiple myeloma by bioinformatics analysis.

BACKGROUND: Immunoregulatory drugs regulate the ubiquitin-proteasome system, which is the main treatment for multiple myeloma (MM) at present. In this study, bioinformatics analysis was used to construct the risk model and evaluate the prognostic value of ubiquitination-related genes in MM. METHODS AND RESULTS: The data on ubiquitination-related genes and MM samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The consistent cluster analysis and ESTIMATE algorithm were used to create distinct clusters. The MM prognostic risk model was constructed through single-factor and multiple-factor analysis. The ROC curve was plotted to compare the survival difference between high- and low-risk groups. The nomogram was used to validate the predictive capability of the risk model. A total of 87 ubiquitination-related genes were obtained, with 47 genes showing high expression in the MM group. According to the consistent cluster analysis, 4 clusters were determined. The immune infiltration, survival, and prognosis differed significantly among the 4 clusters. The tumor purity was higher in clusters 1 and 3 than in clusters 2 and 4, while the immune score and stromal score were lower in clusters 1 and 3. The proportion of B cells memory, plasma cells, and T cells CD4 naïve was the lowest in cluster 4. The model genes KLHL24, HERC6, USP3, TNIP1, and CISH were highly expressed in the high-risk group. AICAr and BMS.754,807 exhibited higher drug sensitivity in the low-risk group, whereas Bleomycin showed higher drug sensitivity in the high-risk group. The nomogram of the risk model demonstrated good efficacy in predicting the survival of MM patients using TCGA and GEO datasets. CONCLUSIONS: The risk model constructed by ubiquitination-related genes can be effectively used to predict the prognosis of MM patients. KLHL24, HERC6, USP3, TNIP1, and CISH genes in MM warrant further investigation as therapeutic targets and to combat drug resistance.

Pre-Clinical Assessment of SAR442257, a CD38/CD3xCD28 Trispecific T Cell Engager in Treatment of Relapsed/Refractory Multiple Myeloma.

Current treatment strategies for multiple myeloma (MM) are highly effective, but most patients develop relapsed/refractory disease (RRMM). The anti-CD38/CD3xCD28 trispecific antibody SAR442257 targets CD38 and CD28 on MM cells and co-stimulates CD3 and CD28 on T cells (TCs). We evaluated different key aspects such as MM cells and T cells avidity interaction, tumor killing, and biomarkers for drug potency in three distinct cohorts of RRMM patients. We found that a significantly higher proportion of RRMM patients (86%) exhibited aberrant co-expression of CD28 compared to newly diagnosed MM (NDMM) patients (19%). Furthermore, SAR442257 mediated significantly higher TC activation, resulting in enhanced MM killing compared to bispecific functional knockout controls for all relapse cohorts (Pearson's r = 0.7). Finally, patients refractory to anti-CD38 therapy had higher levels of TGF-ß (up to 20-fold) compared to other cohorts. This can limit the activity of SAR442257. Vactoserib, a TGF-ß inhibitor, was able to mitigate this effect and restore sensitivity to SAR442257 in these experiments. In conclusion, SAR442257 has high potential for enhancing TC cytotoxicity by co-targeting CD38 and CD28 on MM and CD3/CD28 on T cells.

Ex Vivo Efficacy of SAR442257 Anti-CD38 Trispecific T-cell Engager in Multiple Myeloma Relapsed After Daratumumab and BCMA-targeted Therapies.

T cell-engaging antibodies (TCEs) are showing promising efficacy in relapsed/refractory multiple myeloma, even in patients that relapsed after B-cell maturation antigen (BCMA)-targeted therapy. Patients with multiple myeloma may have compromised T-cell health unaccounted for by preclinical models. Here, we use Myeloma Drug Sensitivity Testing (My-DST) for ex vivo measurement of anti-multiple myeloma cytotoxicity for the trispecific CD38/CD28xCD3 TCE SAR442257 through activation of the patients' own endogenous T cells to inform clinical development of the compound in multiple myeloma. My-DST incubates primary mononuclear cells in humanized media for 48 hours followed by flow cytometry for multiple myeloma cell viability with or without drug treatment. SAR442257 was tested on 34 samples from patients with multiple myeloma across disease settings. Potential biomarkers, T-cell dependence, and degranulation were assessed. SAR442257 was effective at low dose in My-DST cultures. High ex vivo response rates were observed in primary aspirates taken from patients with multiple myeloma at diagnosis, with modestly reduced response in multiple myeloma recently treated with anti-CD38 mAbs. SAR442257 was highly effective in patients relapsing after BCMA therapy. The CD38/CD28xCD3 trispecific format was substantially more effective than a conventional bispecific CD38/CD3 antibody format and CD38 mAbs. Anti-multiple myeloma cell cytotoxicity was dependent on the presence of endogenous T cells. Surface CD38 expression was the strongest biomarker of TCE response. My-DST is capable of measuring T cell-dependent killing using the multiple myeloma patient's own bone marrow-derived T cells. SAR442257 shows promise for multiple myeloma and may be best suited for patients declared resistant to both CD38 mAbs and BCMA-targeted therapy. SIGNIFICANCE: This study introduces the use of My-DST to measure and characterize sensitivity to anti-CD38 T-cell engager SAR442257 in primary samples using matched endogenous T cells. Preclinical testing in samples from patients with diverse treatment history supports further testing in post-chimeric antigen receptor T-cell multiple myeloma.

Ame-miR-980-3p participates in autophagy-mediated midgut remodelling in Apis mellifera via targeting Atg2B.

Autophagy is a process that serves to degrade damaged proteins and organelles, thereby promoting cell homeostasis, differentiation, development and survival. Many miRNAs have been found to have regulatory roles in autophagy. In insects, it has been shown that autophagy is involved in hormone-regulated programmed cell death during metamorphic midgut remodelling. However, whether this is also true during the remodelling of the honey bee midgut is unclear. In the present study, we explored the relationship between autophagy and midgut remodelling and sought to identify miRNAs involved in this physiological process. We found that autophagy occurred during midgut remodelling and that the inhibition of autophagy resulted in midgut dysplasia in prepupae. Differentially expressed miRNAs enriched in the autophagy signalling pathway during midgut remodelling were identified by small RNA-seq. Ame-miR-980-3p, which targets the autophagy-related gene Atg2B, was screened out. Furthermore, abnormal expression of ame-miR-980-3p in the pupal stage led to the thinning of the midgut wall of newly emerged bees (NE). When ame-miR-980-3p expression was inhibited, the intestinal villi of NE bees became significantly shorter and sparse, and the lipid signal in the peritrophic matrix of Pb almost disappeared, indicating that the adult midgut was underdeveloped and the lipid absorption ability was weakened. Taken together, ame-miR-980-3p targeted Atg2B to participate in the regulation of midgut autophagy in the pupae, and the abnormal expression of ame-miR-980-3p would interfere with cell proliferation and death in the process of midgut remodelling, hinder the formation of adult midgut and eventually lead to adult midgut dysplasia and affect the lipid absorption function of the midgut in Apis mellifera.

Carcinoma with signet ring cell differentiation associated with invasive breast cancer: A case report.

Carcinoma with signet ring cell differentiation is uncommon in patients with invasive breast cancer. Clinical evidence has suggested that the prognosis of this tumor is usually poor if the stage is advanced. The case of a 40-year-old female patient with primary cancer in the right breast accompanied by bilateral neck, axillary, right subclavian and mediastinal lymph node metastases, and left breast metastasis is presented in the current study. The patient developed superior vena cava syndrome and was restricted in lifting the upper right limb when presenting at the Third Affiliated Hospital of Shenzhen University, Shenzhen. The histopathological and immunohistochemical features included ~80% of the tumor cell area having a signet ring cell pattern, exhibiting the phenotype of lobular carcinoma, and ~20% of the tumor cell area exhibiting a ductal carcinoma immunophenotype with neuroendocrine expression The patient received chemotherapy with paclitaxel liposomes and doxorubicin hydrochloride liposomes according to the general guidelines for the treatment of stage IV breast carcinoma. The patient achieved a partial response after 4 cycles of treatment, and then experienced progressive disease in the form of brain metastasis after 6 cycles. Owing to the rarity of carcinoma with signet ring cell differentiation in invasive breast carcinoma, this case report discusses the patient's clinical and histopathological characteristics, and the treatment prognosis.

AccsHSP21.7 enhances the antioxidant capacity of Apis cerana cerana.

BACKGROUND: The widespread use of glyphosate has many adverse effects on Apis cerana cerana. Due to the incomplete understanding of the molecular mechanisms of glyphosate toxicity, there are no available methods for mitigating the threat of glyphosate to Apis cerana cerana. Small heat shock proteins (sHSPs) play an important role in resisting oxidative stress, but their mechanism of action in Apis cerana cerana remains unclear. RESULTS: In this experiment, we cloned and identified AccsHSP21.7. Studies have shown that AccsHSP21.7 contains binding motifs for various transcription factors related to oxidative stress. Abiotic stresses induced the expression of AccsHSP21.7. Bacteriostatic testing of a recombinant AccsHSP21.7 protein proved that Escherichia coli overexpressing AccsHSP21.7 showed increased resistance to oxidative stress. Knocking down the AccsHSP21.7 gene caused significant damage to midgut cells, which seriously disrupted the antioxidant system in Apis cerana cerana and greatly increased mortality under glyphosate stress. CONCLUSION: This study investigated the relationship between antioxidant regulation and the AccsHSP21.7 gene at the molecular level, and the results have guiding significance for the improvement of stress resistance in Apis cerana cerana. © 2023 Society of Chemical Industry.

Role of c-Jun NH2 -terminal kinase-mediated mitogen-activated protein kinase pathway in response to pesticides in Apis cerana cerana.

The mitogen-activated protein kinase (MAPK) cascade pathway plays an important role in regulating stress responses. The function of the c-Jun NH2 -terminal kinase (JNK), a component of the MAPK cascade pathway, in Apis cerana cerana (Acc) remains unclear. Here, JNK was isolated and identified from Acc. Bioinformatics analyses revealed there is a typical serine/threonine protein kinase catalytic domain in the AccJNK protein. An expression profile analysis showed that AccJNK was significantly induced by pesticide treatments. To further explore the functional mechanisms of AccJNK, a yeast 2-hybrid screen was performed, activator protein-1 (AP-1) was screened as the interaction partner of AccJNK, and the interaction relationship was further verified by pull-down assay. Quantitative real-time polymerase chain reaction showed the expression pattern of AccAP-1 was similar to that of AccJNK. After a knockdown of AccJNK or AccAP-1 by RNA interference, the survival rate of Acc after pesticide treatments increased. Additionally, the expression levels of antioxidant-related genes and the activities of antioxidant enzymes increased, suggesting that the knockdown of AccJNK or AccAP-1 increased the antioxidant capacity of bees. Our study revealed that the JNK-mediated MAPK pathway responds to pesticide stress by altering the antioxidant capacity of Acc.

Glucose metabolism enhancement by 10-hydroxy-2-decenoic acid via the PI3K/AKT signaling pathway in high-fat-diet/streptozotocin induced type 2 diabetic mice.

10-Hydroxy-2-decenoic acid (10-HDA) is a principal active ingredients of royal jelly. Several recent studies demonstrated that 10-HDA has potential anti-type 2 diabetes mellitus (T2DM) properties. To evaluate the anti-T2DM effect of 10-HDA and explore its underlying molecular mechanisms, we used high fat diet (HFD) combined with streptozotocin (STZ) injection to establish a diabetes model. Mice were randomly divided into four groups (8 mice per group): control group, 10-HDA group, T2DM group, and T2DM + 10-HDA group. The 10-HDA and T2DM + 10-HDA groups were administered intragastric 10-HDA (100 mg per kg body weight), while the control and T2DM groups were administered a vehicle, daily for 4 weeks. Our analysis indicated that there was no significant difference in body weight between T2DM + 10-HDA and control group mice (P > 0.05). Treatment with 10-HDA reduced fasting blood glucose and increased insulin levels in diabetic mice (P < 0.05), as well as increasing the area of pancreatic islets (P < 0.05), and alleviating vacuolar degeneration in the liver. Further, 10-HDA intervention increased superoxide dismutase, catalase, and glutathione peroxidase activities in diabetic mouse liver, alleviated lipid peroxidation, inhibited liver NF-κB nuclear translocation, decreased IL-6 and TNF-α content, and increased P-PI3K, P-AKT, and P-GSK3ß protein levels (all P < 0.05). Fifteen potential biomarkers were screened by analysis of liver metabolomics data, of which hexadecanamide, stearamide, pentadecanoic acid, and fatty acid esters of hydroxy fatty acids (16:0/18:1) were highly abundant. In conclusion, 10-HDA has clear hypoglycemic effects on diabetic mice, through the PI3K/AKT/GSK3ß signaling pathway.

Baicalein Ameliorates Myocardial Ischemia Through Reduction of Oxidative Stress, Inflammation and Apoptosis via TLR4/MyD88/MAPKS/NF-κB Pathway and Regulation of Ca2+ Homeostasis by L-type Ca2+ Channels.

Background: Baicalein (Bai) is the principal ingredient of Scutellaria baicalensis Georgi. Reports concerning the therapeutic advantages in treating cardiovascular diseases have been published. However, its protective mechanism towards myocardial ischemia (MI) is undefined. Objective: The aim of this study was to investigate the protective mechanisms of Bai on mouse and rat models of MI. Methods: Mice were pre-treated with Bai (30 and 60 mg/kg/day) for 7 days followed by subcutaneous injections of isoproterenol (ISO, 85 mg/kg/day) for 2 days to establish the MI model. Electrocardiograms were recorded and serum was used to detect creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA). Cardiac tissues were used to detect Ca2+ concentration, morphological pathologies, reactive oxygen species (ROS), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, the expression levels of Bcl-2-associated X (Bax), B cell lymphoma-2 (Bcl-2), Caspase-3, Toll-like receptor-4 (TLR4), myeloid differentiation protein 88 (MyD88), nuclear factor-kappa B (NF-κB), p-p38, p-extracellular signal-regulated kinase1/2 (p-ERK1/2) and c-Jun N-terminal kinase (p-JNK) were assessed by western blots in myocardial tissues. The effects of Bai on L-type Ca2+ currents (ICa-L), contractility and Ca2+ transients in rat isolated cardiomyocytes were monitored by using patch clamp technique and IonOptix system. Moreover, ISO-induced H9c2 myocardial injury was used to detect levels of inflammation and apoptosis. Results: Bai caused an improvement in heart rate, ST-segment and heart coefficients. Moreover, Bai led to a reduction in CK, LDH and Ca2+ concentrations and improved morphological pathologies. Bai inhibited ROS generation and reinstated SOD, CAT and GSH activities in addition to inhibition of replenishing MDA content. Also, expressions of IL-6 and TNF-α in addition to Bax and Caspase-3 were suppressed, while Bcl-2 expression was upregulated. Bai inhibited protein expressions of TLR4/MyD88/MAPKS/NF-κB and significantly inhibited ICa-L, myocyte contraction and Ca2+ transients. Furthermore, Bai caused a reduction in inflammation and apoptosis in H9c2 cells. Conclusions: Bai demonstrated ameliorative actions towards MI, which might have been related to attenuation of oxidative stress, inflammation and apoptosis via suppression of TLR4/MyD88/MAPKS/NF-κB pathway and adjustment of Ca2+ homeostasis via L-type Ca2+ channels.

Characterisation of the heat shock protein Tid and its involvement in stress response regulation in Apis cerana.

Objective: The impact of various environmental stresses on native Apis cerana cerana fitness has attracted intense attention in China. However, the defence responses of A. cerana cerana to different stressors are poorly understood. Here, we aimed to elucidate the regulatory mechanism mediated by the tumorous imaginal discs (Tid) protein of A. cerana cerana (AccTid) in response to stressors. Methods: We used some bioinformatics softwares to analyse the characterisation of Tid. Then, qRT-PCR, RNA interference and heat resistance detection assays were used to explore the function of Tid in stress response in A. cerana cerana. Results: AccTid is a homologous gene of human Tid1 and Drosophila Tid56, contains a conserved J domain and belongs to the heat shock protein DnaJA subfamily. The level of AccTid induced expression was increased under temperature increases from 40°C to 43°C and 46°C, and AccTid knockdown decreased the heat resistance of A. cerana cerana, indicating that the upregulation of AccTid plays an important role when A. cerana cerana is exposed to heat stress. Interestingly, contrary to the results of heat stress treatment, the transcriptional level of AccTid was inhibited by cold, H2O2 and some agrochemical stresses and showed no significant change under ultraviolet ray and sodium arsenite stress. These results suggested that the requirement of A. cerana cerana for Tid differs markedly under different stress conditions. In addition, knockdown of AccTid increased the mRNA levels of some Hsps and antioxidant genes. The upregulation of these Hsps and antioxidant genes may be a functional complement of AccTid knockdown. Conclusion: AccTid plays a crucial role in A. cerana cerana stress responses and may mediate oxidative damage caused by various stresses. Our findings will offer fundamental knowledge for further investigations of the defence mechanism of A. cerana cerana against environmental stresses.

Regulation of a New Type of Selenium-Rich Royal Jelly on Gut Microbiota Profile in Mice.

Royal jelly (RJ) and selenium (Se)-rich foods have well-known health benefits which are attributable to a broad range of pharmacologic effects including antioxidant, bacteriostatic, anticancer, and immunoregulatory activities. However, there was no study to combine Se with RJ. Here, Se-rich RJ (SRJ) was produced by feeding sodium selenite to honeybees (Apis mellifera). To further clarify the function of SRJ, mice were then fed RJ or SRJ for 30 days, and their antioxidant capacity and gut microbiota profile were analyzed. The results showed that SRJ treatment could more effectively increase glutathione peroxidase levels in the liver and kidney, as well as total antioxidant activity in the liver and superoxide dismutase level in the kidney. Additionally, the ratio of Firmicutes/Bacteroidetes and relative abundance of the Lachnospiraceae and Prevotellaceae families were increased, whereas the abundance of Helicobacterceae was decreased in mice treated with SRJ. At the genus level, SRJ increased the relative abundance of Lachnospiraceae NK4A136 group, Prevotellaceae UCG 001, Rikenellaceae RC9 gut group, and Oscillibacter and decreased that of Alistipes. And the functional prediction of gut microbiota indicated SRJ treatment could enhance the amino acid metabolism. Correlation analysis indicated that SRJ could optimize the functional network of gut microbiota and the interactions between the gut microbiota and the host. These results suggested the SRJ had potential therapeutic applications in the improvement of overall health or treatment of diseases related to oxidative stress or dysbiosis.

Based on Activation of p62-Keap1-Nrf2 Pathway, Hesperidin Protects Arsenic-Trioxide-Induced Cardiotoxicity in Mice.

Background: Hesperidin (HES) is a flavonoid glycoside found in the tangerine peel and has antioxidant properties. Arsenic trioxide (ATO) is an anti-tumour drug; however, its serious cardiotoxicity limits its clinical application. In addition, the protection of HES against ATO-induced cardiotoxicity has not been explored. Objective: The study aims to investigate and identify the underlying effect and mechanism of HES on ATO-induced cardiotoxicity. Methods: Fifty mice were randomly assigned to five groups. Mice were orally given HES:100 or 300 mg/kg/day concurrently and given ATO intraperitoneal injections: 7.5 mg/kg/day for 1 week. Blood and heart tissues were collected for examination. Evaluated in serum was the levels of creatine kinase (CK), lactate dehydrogenase (LDH) and cardiac troponin I (cTnI). In addition, evaluated in heart tissues were the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, cleaved-Caspase-3, p62, Kelch-like ECH-associated protein 1 (Keap1), and nuclear factor erythroid 2-related factor 2 (Nrf2). The heart tissues were also examined for histopathology and mitochondrial ultrastructure. Results: Compared with the ATO group, the HES treatment groups reduced the levels of CK, LDH, cTnI, ROS, MDA, TNF-α, IL-6, Bax, Caspase-3, cleaved-Caspase-3 and Keap1 and enhanced the levels of SOD, GSH, CAT, Bcl-2, p62 and Nrf2. Conclusions: The results demonstrate that HES protects against ATO-induced cardiotoxicity, through inhibiting oxidative stress, and subsequent inflammation and apoptosis. The underlying results are closely related to the regulation of the p62-Keap1-Nrf2 signalling pathway.

Selenium-rich royal jelly inhibits hepatocellular carcinoma through PI3K/AKT and VEGF pathways in H22 tumor-bearing mice.

Royal jelly (RJ) and selenium (Se)-rich foods have well-known health benefits that are attributable to a broad range of pharmacological effects including antioxidant, anti-tumor, and immunoregulatory activities. However, the physiological effects of Se-rich RJ, which is produced by feeding Apis mellifera (Hymenoptera: Apidae) sodium selenite sucrose solution, are not well understood. The anti-hepatoma activity and mechanism of Se-rich RJ in H22 tumor-bearing mice were investigated in the current study. The findings showed that the content of organic and inorganic Se in Se-rich RJ was significantly higher than that in RJ. Furthermore, interleukin-2 (IL-2) levels and tumor necrosis factor-α (TNF-α) production in serum were increased and the malondialdehyde (MDA) content in liver was decreased in mice fed RJ and Se-rich RJ. 16SrRNA sequencing and serum untargeted metabolomics showed that RJ and Se-rich RJ could modulate the gut microbiota, and fisetin and L-glutathione oxidized were the main anti-tumor components in RJ and Se-rich RJ. Further analysis showed 11-deoxy prostaglandin F1ß was the specific anti-tumor metabolite in mice treated with Se-rich RJ compared with RJ. The results indicated that RJ and Se-rich RJ could inhibit the expression of PI3K and phosphorylation of AKT, induce cell apoptosis through the activation of caspase-9 and caspase-3, and regulate Bcl-2/Bax expression. RJ and Se-rich RJ also inhibited the expression of COX-2 and VEGF. To summarize, the findings clearly demonstrate that Se-rich RJ could inhibit tumor growth by inducing apoptosis and inhibiting angiogenesis as well as exhibit anti-tumor effects by improving immune function and antioxidant activities. The results indicated that Se-rich RJ could be a potential functional food for the management and prevention of cancer.

AccPDIA6 from Apis cerana cerana plays important roles in antioxidation.

PDIA6 is a member of the protein disulfide isomerase (PDI) family, shows disulfide isomerase activity and oxidoreductase activity, and can act as a molecular chaperone. Its biological functions include modulating apoptosis, regulating the proliferation and invasion of cancer cells, supporting thrombosis and modulating insulin secretion. However, the roles of PDIA6 in Apis cerana cerana are poorly understood. Herein, we obtained the PDIA6 gene from A. cerana cerana (AccPDIA6). We investigated the expression patterns of AccPDIA6 in response to oxidative stress induced by H2O2, UV, HgCl2, extreme temperatures (4 °C, 42 °C) and pesticides (thiamethoxam and hexythiazox) and found that AccPDIA6 was upregulated by these treatments. Western blot analysis indicated that AccPDIA6 was also upregulated by oxidative stress at the protein level. In addition, a survival test demonstrated that the survival rate of E. coli cells expressing AccPDIA6 increased under oxidative stress, suggesting a possible antioxidant function of AccPDIA6. In addition, we tested the transcripts of other antioxidant genes and found that some of them were downregulated in AccPDIA6 knockdown samples. It was also discovered that the antioxidant enzymatic activity of superoxide dismutase (SOD) decreased in AccPDIA6-silenced bees. Moreover, the survival rate of AccPDIA6 knockdown bees decreased under oxidative stress, implying that AccPDIA6 may function in the oxidative stress response by enhancing the viability of honeybees. Taken together, these results indicated that AccPDIA6 may play an essential role in counteracting oxidative stress.

Royal jelly enhanced the antioxidant activities and modulated the gut microbiota in healthy mice.

Royal jelly (RJ) is a well-known traditional health food that has a wide range of pharmacological activities. In this study, mice were fed with different doses of RJ for 30 days and their antioxidant activities and gut microbiota were measured to examine the correlation between gut microbiota and overall health. RJ did not influence the feed consumption or relative organ weight, but RJ did increase the amount of serum interleukin 10 (IL-10), as well as the levels of antioxidant activities in the liver and kidney. The middle dose of RJ (RJM) decreased the relative abundance of Proteobacteria at phylum level, increased the relative abundance of Lachnospiraceae_NK4A136_group and Bacteroides. Correlation analysis indicated that RJ could optimize the functional network of gut microbiota and the interactions between the gut microbiota and the host. In conclusion, RJ could enhance the antioxidant activities and modulate the gut microbiota. RJM treatment had a more positive effect on physical health compared with RJL and RJH treatments. PRACTICAL APPLICATIONS: Royal jelly is a healthy dietary supplement which has a wide range of functions. The research helps us know the action mechanism of RJ in healthy body and analyzed the correlation of gut microbiota and physiological state. The appropriate dose of RJ was also studied and the health functions of RJ for healthy body were proved. This research could help to increase the RJ consuming in market.

SHOULD WE BEGIN REGULATING THE RADIATION SAFETY OF CABINET X-RAY SYSTEMS?

Radiation measurements were conducted at 22 cabinet X-ray systems in Beijing, China, between 2015 and 2019. The median dose rates in the closed-drapes position were 0.11, 0.14, 0.12, 0.14, 0.34 and 0.17 µGy h-1 at the operator position and 5 cm from the surface of the left side, right side, top, entrance and exit, respectively. When a scattering object was passed through the entrance/exit (open-drapes position), the dose rates of eight systems ranged from 1.19 to 6.72 µGy h-1 (median: 3.75 µGy h-1). From 2015 to 2019, we monitored the personal dose equivalent Hp (10) 589 times. The personal dose equivalent of three workers exceeded 1 mSv year-1. However, the integrity of equipment shielding needs to be checked regularly to ensure safe operation. The regulation of radiation protection by employers, technician support institutes or government departments is thus warranted to limit the radiation exposure of workers and the public.

Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: a phase 1 study.

Ivosidenib (AG-120) and enasidenib (AG-221) are targeted oral inhibitors of the mutant isocitrate dehydrogenase (mIDH) 1 and 2 enzymes, respectively. Given their effectiveness as single agents in mIDH1/2 relapsed or refractory acute myeloid leukemia (AML), this phase 1 study evaluated the safety and efficacy of ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed mIDH1/2 AML. Ivosidenib 500 mg once daily and enasidenib 100 mg once daily were well tolerated in this setting, with safety profiles generally consistent with those of induction and consolidation chemotherapy alone. The frequency of IDH differentiation syndrome was low, as expected given the concurrent administration of cytotoxic chemotherapy. In patients receiving ivosidenib, the frequency and grades of QT interval prolongation were similar to those observed with ivosidenib monotherapy. Increases in total bilirubin were more frequently observed in patients treated with enasidenib, consistent with this inhibitor's known potential to inhibit UGT1A1, but did not appear to have significant clinical consequences. In patients receiving ivosidenib (n = 60) or enasidenib (n = 91), end-of-induction complete remission (CR) rates were 55% and 47%, respectively, and CR/CR with incomplete neutrophil or platelet recovery (CR/CRi/CRp) rates were 72% and 63%, respectively. In patients with a best overall response of CR/CRi/CRp, 16/41 (39%) receiving ivosidenib had IDH1 mutation clearance and 15/64 (23%) receiving enasidenib had IDH2 mutation clearance by digital polymerase chain reaction; furthermore, 16/20 (80%) and 10/16 (63%), respectively, became negative for measurable residual disease by multiparameter flow cytometry. This trial was registered at www.clinicaltrials.gov as #NCT02632708.