A neutrophil-biomimic platform for eradicating metastatic breast cancer stem-like cells by redox microenvironment modulation and hypoxia-triggered differentiation therapy

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.

Medicine+information: Exploring patent applications in precision therapy in cardiac surgery / 中国胸心血管外科临床杂志

@#Currently, in precision cardiac surgery, there are still some pressing issues that need to be addressed. For example, cardiopulmonary bypass remains a critical factor in precise surgical treatment, and many core aspects still rely on the experience and subjective judgment of cardiopulmonary bypass specialists and surgeons, lacking precise data feedback. With the increasing elderly population and rising surgical complexity, precise feedback during cardiopulmonary bypass becomes crucial for improving surgical success rates and facilitating high-complexity procedures. Overcoming these key challenges requires not only a solid medical background but also close collaboration among multiple interdisciplinary fields. Establishing a multidisciplinary team encompassing professionals from the medical, information, software, and related industries can provide high-quality solutions to these challenges. This article shows several patents from a collaborative medical and electronic information team, illustrating how to identify unresolved technical issues and find corresponding solutions in the field of precision cardiac surgery while sharing experiences in applying for invention patents.

Areca catechu L.ameliorates chronic unpredictable mil stress-induced depression behavior in rats by the promotion of the BDNF signaling pathway / 中国药理学与毒理学杂志

OBJECTIVE To investigated the anti-de-pressant effects of the fruit Areca catechu L.(ACL)and elucidated its potential underlying mechanism using a rat model of chronic unpredictable mild stress(CUMS).METHODS CUMS was induced in rats to establish a depression animal model for 28 d.According to the baseline sucrose preference,the male rats were divided into six different groups.They were treated with parox-etine hydrochloride,ACL,and water once a day until the behavioral tests were performed.The levels of corticoste-rone(CORT),malondialdehyde(MDA),catalase(CAT),and total superoxide dismutase(T-SOD)in serum were de-tected using a commercial kit,and the concentrations of 5-hydroxytryptamine(5-HT)and dopamine(DA)mono-amine neurotransmitters in the brain tissues were detect-ed by liquid chromatography-tandem mass spectrometry.Doublecortin(DCX)expression in the hippocampal den-tate gyrus(DG)was determined by immunofluorescence,and the relative abundance of brain-derived neurotrophic factor(BDNF),TrkB,PI3K,p-Akt/Akt,PSD-95,and p-GSK-3β/GSK-3β of brain tissues were assayed by West-ern blotting.RESULTS ACL markedly increased sucrose preference,decreased the immobility time,and short-ened the feeding latency of CUMS-induced rats.CUMS induction resulted in marked changes in the contents of the monoamine neurotransmitters(5-HT and DA)in the hippocampus and cortex of brain tissues and the levels of CORT,MDA,CAT,and T-SOD in serum,whereas ACL administration alleviated these considerable changes.ACL promoted DCX expression in DG and increased the protein levels of BDNF,TrkB,PI3K,p-Akt/Akt,PSD-95,and p-GSK-3β/GSK-3β in the brains of CUMS-induced rats.CONCLUSION Our results indicated that ACL may improve depression-like behaviors in CUMS-induced rats by decreasing the hyperfunction and oxidative stress of the hypothalamic-pituitary-adrenal axis,stimulating hippo-campal neurogenesis,and activating the BDNF signaling pathway.

Protective effects of ginsenosides Rg1 and Rb1 against cognitive impairment induced by simulated microgravity in rats / 中国药理学与毒理学杂志

OBJECTIVE Microgravity exerts several negative effects on the learning and memory of astro-nauts during space flight.Rg1 and Rb1,the key steroidal components of ginseng,have shown potent neuroprotec-tive effects with a high safety profile.The object of the current study is to investigate the influence of Rg1 and Rb1 on simulated microgravity-induced memory and learning dysfunction in the hindlimb suspension(HLS)rat model.METHODS The HLS rats were orally administered Rg1(30 and 60 μmol·kg-1)or Rb1(30 and 60 μmol·kg-1)for four weeks.The Morris water maze test(MWM)and reward operating conditioning reflex test(ROCR)were conducted to evaluate spatial and associative learning and memory.After the behavior tests,the serum and the prefrontal cortex(PFC)were dissected to measure the mechanism.RESULTS Rg1 and Rb1 treatment amelio-rated the cognitive deficits of HLS-exposure rats in MWM and ROCR,reduced reactive oxygen species generation and increased antioxidant enzyme activity.Rg1 and Rb1 also assisted in the recovery of mitochondrial complex Ⅰ(NADH dehydrogenase)activities and Mfn2,and decrea-sed Drp-1 expression.Furthermore,Rg1 and Rb1 reduced the ratio of Bax/Bcl-2 and the expression of cleaved-cas-pase 3,cytochrome c,increased the levels of SYN,PSD95 and activated BDNF-TrkB/PI3K-Akt pathway in the PFC.CONCLUSION Rg1 and Rb1 treatment attenuated cog-nitive deficits induced by HLS,mitigated mitochondrial dysfunction,attenuated oxidative stress,inhibited apopto-sis,and increased the synaptic plasticity,which was partly mediated by the modulation of the BDNF-TrkB/PI3K-Akt signaling.

Did Chinese children with imaginary companions attribute more agencies to non-human items: Evidences from behavioral cues and appearance characteristics.

Previous studies have focused on the relationship between imaginary companions (ICs) and children's social developments. As far as we know, few studies have focused on the relationship between ICs and children's agency attributions. This study aimed to explore the potential differences in agency attributions between children with and without ICs, children with egalitarian IC relationships and hierarchical IC relationships. Children's agency attributions were measured by two experiments. One was based on behavioral cues (Random animations/ToM animations) and the other was based on appearance characteristics (ball/doll). The results revealed that children with ICs attributed more cognitive properties to Random and ToM animations than children without ICs. Compared with children without ICs, children with ICs attributed marginally more biological properties to a ball and more psychological properties to a ball and a doll. However, children with egalitarian and hierarchical IC relationships did not differ in their agency attributions. The results suggest that children with ICs are more likely to attribute agencies to non-human items with behavioral cues or appearance characteristics than children without ICs. Compared with child-IC relationship qualities, IC status may be more related to children's agency attributions. However, only a correlation between IC status and children's agency attributions was found in this study and it is interesting for future researchers to investigate the potential causal directions between children's IC status and their agency attributions. If one of the causal directions or both the causal directions exist, future researchers can further explore the underlying mechanism.

Research progress in the application of functional near infrared spectroscopy in children language development / 中华实用儿科临床杂志

Functional near infrared spectroscopy (fNIRS) is an emerging neuroimaging technology, which has such advantages as non-invasiveness, portability, robustness to motion and no noise over other neuroimaging tools.Therefore, it has important values in the research of children language development.fNIRS has been currently applied to the study of neonatal word recognition, infant speech perception, language functional lateralization, bilingual cognitive mechanism, language related neurodevelopmental disorders, etc.It has a bright future of applications in the field of children language development.

Clinical efficacy of Qianjin Weijing Decoction in the treatment of severe pneumonia with accumulation of phlegm and heat in the lung / 中国基层医药

Objective:To investigate the clinical efficacy of Qianjin Weijing Decoction in the treatment of severe pneumonia with the accumulation of phlegm and heat in the lung. Methods:Eighty patients with severe pneumonia with the accumulation of phlegm and heat in the lung received treatment in Wenzhou Hospital of Traditional Chinese Medicine from December 2018 to December 2020. They were randomly allocated to undergo routine treatments (control group, n = 40) or routine treatments combined with Qianjin Weijing Decoction (observation group, n = 40) for 7 days. Clinical efficacy, blood gas analysis, oxygenation index, inflammatory factors (C-reactive protein and procalcitonin), and sequential organ failure score were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [87.50% (35/40) vs. 65.00% (26/40), χ2 = 5.59, P < 0.05]. Partial pressure of carbon dioxide (PaCO 2) post-treatment was significantly lower in the observation group than that in the control group [(30.24 ± 2.68) mmHg vs. (39.95 ± 3.27) mmHg, t = 14.52, P < 0.05]. The partial pressure of blood oxygen (PaO 2) and oxygenation index (PaO 2/FiO 2) in the observation group were (76.85 ± 4.56) mmHg and (326.84 ± 8.49) mmHg, respectively, which were significantly higher than those in the control group [(68.39 ± 4.12) mmHg, (284.16 ± 15.56) mmHg, t = -8.70, -15.22, both P < 0.05). Serum levels of C-reactive protein and procalcitonin post-treatment in the observation group were (23.12 ± 6.56) mg/L and (0.31 ± 0.08) μg/L, respectively, which were significantly lower than those in the control group [(38.92 ± 5.62) mg/L, (0.78 ± 0.20) μg/L, t = 11.56, 13.80, both P < 0.05]. Sequential organ failure score was significantly lower in the observation group than in the control group [(2.31 ± 0.46) points vs. (5.12 ± 1.25) points, t = 13.34, P < 0.05)]. Conclusion:Qianjin Weijing Decoction has a good therapeutic effect on severe pneumonia with the accumulation of phlegm and heat in the lung. The treatment can improve blood gas analysis and decrease inflammatory factor levels with a good prognosis.

Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.

Efficacy of Qingfei oral liquid for idiopathic pulmonary fibrosis in rats and related network pharmacology study / 浙江大学学报·医学版

To investigate the therapeutic effect and mechanism of Qingfei oral liquid in idiopathic pulmonary fibrosis. Seventy-two male SD rats were divided into control group, model group, pirofenidone group and Qingfei group with 18 animals in each group. The idiopathic pulmonary fibrosis was induced in last three groups by intratracheal injection of bleomycin; pirofenidone group was given oral administration of pirofenidone b.i.d for 21 d, and Qingfei group was given Qingfei oral liquid 3.6 mL/kg q.d for Lung tissues were obtained for HE staining, Masson staining and transforming growth factor (TGF)-β immunohistochemical staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected in tissue homogenates. The BATMAN-TCM database was used to retrieve the chemical components and their corresponding targets of Qingfei oral solution by network pharmacology method, and then the component-target-disease network diagram was constructed. Finally, the pathway enrichment analysis was carried out to explore the molecular mechanism of Qingfei oral liquid against idiopathic fibrosis. Histopathology results showed that Qingfei oral liquid had a similar relieving effect on pulmonary fibrosis as the positive drug pirfenidone; TGF-β secretion had a significant reduction in lung tissues of Qingfei group; and Qingfei oral liquid had better regulatory effect on SOD, MDA and GSH than pirfenidone. The results of component-target-disease network and pathway enrichment analysis showed that the related molecular pathways were concentrated in inflammation, extracellular matrix and cytokines. Qingfei oral liquid has a good therapeutic effect on idiopathic pulmonary fibrosis in rats via regulation of inflammation, extracellular matrix and cytokines.

Immune response induced by 14-3-3.3 recombinant protein vaccine of Taenia solium in mice / 中华地方病学杂志

Objective:To explore the potential of Taenia solium (Ts) 14-3-3.3 protein as a candidate molecule for cysticercosis vaccine. Methods:Sixty Kunming mice with the body weight of 18 - 22 g were selected and divided into 3 groups according to their body weight via the random number table method, including normal saline control group (control group), Ts14-3-3.3 recombinant protein vaccine group (vaccine group), and Ts14-3-3.3 recombinant protein vaccine + adjuvant group (vaccine + adjuvant group), with 20 mice in each group. The multi-point subcutaneous injection method was adopted. After the first immunization at 0 week, the booster immunization was carried out twice, a total of 3 times, with an interval of 2 weeks. Four mice in the three groups were killed at 0, 2, 4, 6 and 8 weeks after the first immunization, and the blood of eyeballs and spleen were collected aseptically for serum separation and preparation of spleen lymphocytes suspension [treatment: cell suspension, antigen-stimulate and concanavalin (Con) A-stimulate], respectively. The levels of mouse serum specific immunoglobulin (Ig) G, IgG2a, IgG1 and IgE were detected by indirect enzyme-linked immunosorbent assay (ELISA). The proliferation level of mouse spleen lymphocytes was detected via the CCK-8 method. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-13 and IL-10 in culture supernatant of mouse spleen lymphocytes were determined by double-antibody sandwich ELISA.Results:The IgG, IgG2a, and IgG1 levels of the vaccine and vaccine + adjuvant groups immunized for 2 to 8 weeks were higher than those of the control group, and the above indicators of the vaccine + adjuvant group were higher than those of the vaccine group ( P < 0.05). With the same treatment between the groups, the proliferation levels of spleen lymphocytes and the levels of TNF-α, IL-12, IL-13, and IL-10 in the culture supernatant after 2 - 8 weeks of immunization were statistically significantly different ( P < 0.05); the proliferation levels of spleen lymphocytes and the levels of TNF-α, IL-12, IL-13 and IL-10 in the culture supernatant of the vaccine and vaccine + adjuvant groups immunized for 2 to 8 weeks were higher than those of the control group, and the above indicators of the vaccine + adjuvant group were higher than those of the vaccine group ( P < 0.05). When treatment was different in the group, the proliferation levels of spleen lymphocytes and the levels of TNF-α, IL-12, IL-13 and IL-10 in the culture supernatant of the antigen-stimulate and ConA-stimulate were higher than those of the cell suspension, and the above indicators of the ConA-stimulate were higher than those of the antigen-stimulate ( P < 0.05). Conclusion:The recombinant protein vaccine of Ts14-3-3.3 can induce an effective immune response in mice.

The analysis of epidemiological characteristics of COVID-19 cases in Hebei Province / 公共卫生与预防医学

Objective To analyze the epidemiological characteristics of the novel coronavirus pneumonia epidemic in Hebei Province, and to provide a scientific basis for the prevention and control of the novel coronavirus pneumonia epidemic. Methods Descriptive epidemiological methods were used to analyze the epidemiological characteristics of all COVID-19 cases reported in Hebei Province from January 22, 2020 to September 22, 2020. Results As of September 22, 2020, a total of 365 confirmed cases had been reported in Hubei Province, including 339 local confirmed cases and 26 imported cases, of which 18 were critical cases, 34 severe cases, and 6 deaths. Among the confirmed cases, 198 were males and 167 were females, with a male to female ratio of 1.19:1. The epidemic situation in Hebei Province can be divided into three stages: The first stage (January 22 to April 6) was dominated by imported cases from Hubei Province, with 318 reported cases, accounting for 87.12% of the total cases, and the mortality rate was 1.89%; The second stage (June 14 - July 25) was the spread caused by cases in Beijing Xinfadi market, with 21 cases reported, accounting for 5.75% of the total cases, and the mortality rate was 0%; The third stage (July 26 - September 22) was mainly imported cases from abroad, with 26 cases reported, accounting for 7.12% of the total cases, and the mortality rate was 0%. Conclusion The COVID-19 epidemic situation in Hebei Province has been under control. In view of the continuous spread of the epidemic situation in foreign countries, it is extremely important to strictly prevent the import of overseas epidemics and prevent the outbreak from rebounding.

Effect of acute hypervolemic hemodilution with 6% hydroxyethyl starch 130/0.4 on pharmacodynamics of propofol during successful laryngeal mask airway implantation / 中华麻醉学杂志

Objective:To investigate the effect of acute hypervolemic hemodilution (AHH) with 6% hydroxyethyl starch 130/0.4 on pharmacodynamics of propofol during successful laryngeal mask airway (LMA) implantation.Methods:American Society of Anesthesiology physical status Ⅰ or Ⅱ patients, aged 30-60 yr, with body mass index of 18.5-25.0 kg/m 2, undergoing elective extensive total hysterectomy under general anesthesia, were divided into 2 groups: AHH group (group A) and control group (group C). In group A, 6% hydroxyethyl starch 130/0.4 was infused at a rate of 20 ml/min for AHH, and the target hematocrit was 30%.In group C, lactated Ringer′s solution was infused according to the " 4-2-1" rule to supplement physiological requirements, and anesthesia induction was performed after 10 min of stabilization.Sufentanil was administered by target-controlled infusion using Bovil pharmacokinetic model with effect-site concentration (Ce) of 0.25 ng/ml, 3 min later propofol was given by target-controlled infusion using Schnider model.The Ce of propofol in the first patient was set at 5.0 μg/ml.Each time the concentration of propofol was increased/decreased by 0.5 μg/ml according to the sequential method.LMA was inserted following 1 min equilibration between plasma concentration and Ce of propofol.The trial was terminated when 8 consecutive inflection points of failed/successful LMA insertion occurred.The EC 5, EC 50, EC 95 and 95% confidence interval (95% CI) of propofol were calculated by probit regression analysis. Results:In group A, the EC 5 (95% CI), EC 50 (95% CI) and EC 95 (95% CI) of propofol when LMA was successfully placed were 4.237 (3.090-4.514) μg/ml, 4.802 (4.500-5.078) μg/ml and 5.443 (5.125-7.304) μg/ml, respectively.In group C, the EC 5 (95% CI), EC 50 (95% CI) and EC 95 (95% CI) of propofol when LMA was successfully placed were 2.408 (1.190-2.756) μg/ml, 3.120 (2.690-3.472) μg/ml and 4.042 (3.582-7.431) μg/ml, respectively.There was significant difference in EC 5, EC 50 and EC 95 between the two groups ( P<0.01). Conclusion:AHH with 6% hydroxyethyl starch 130/0.4 can decrease the efficacy of propofol when LMA is successfully implanted.

Safety analysis of endoscopic retrograde cholangiopancreatography and its associated treatments in the elderly / 中华老年医学杂志

Objective:To investigate the safety of endoscopic retrograde cholangiopancreatogra-phy(ERCP)and its associated treatments in the elderly aged 65 years and over, and analyze the related factors leading to postoperative complications.Methods:Totally 512 patients who received ERCP and its associated treatments in the Department of Gastroenterology, Peking University People's Hospital from January 2013 to January 2019 were included retrospectively.The clinical data, operative procedures and postoperative complications were collected.The differences in underlying diseases, operative procedures and postoperative complications between the elderly group(≥65 years old, n=301)and the non-elderly group(n=211)were compared, and the correlations between them were analyzed.Results:The proportion of hypertension, diabetes, heart disease and diverticulum beside the nipple was higher in the elderly group than in the non-elderly group(all P<0.01). The proportion of preoperative medication of anticoagulant and antiplatelet drugs was higher in the elderly group than in the non-elderly group(all P<0.01). There were no significant differences in cholelithiasis, history of biliary surgery, history of ERCP, immunity disease and tumor between the two groups(all P>0.05). Endoscopic sphincterotomy was the most common ERCP-associated treatments in both groups, followed by the order of endoscopic balloon dilation of the nipple, endoscopic biliary stent drainage, pancreatic duct intubation, and pancreatic duct stenting.The proportions of endoscopic papillary balloon dilation and endoscopic biliary stent drainage were 34.6%(104 cases)and 18.9%(57 cases)respectively, in the elderly group, which were statistically significantly higher than 25.6%(54 cases)and 11.4%(24 cases)in the non-elderly group(all P<0.05). The common bile duct diameter and maximum stone diameter were(1.32±0.43)cm and(1.04±0.53)cm, respectively in the elderly group, which were statistically significantly higher than those in the non-elderly group(1.16±0.40)cm and(0.81±0.03)cm respectively, ( t values were -4.23 and -4.76, respectively, all P<0.01). The proportions of endoscopic papillary balloon dilation and biliary stent drainage were statistically significantly higher in elderly patients than in non-elderly patients(all P<0.05). The incidence of intraoperative bleeding was 4.0%(12 cases)and 5.7%(12 cases)in the elderly group and non-elderly group, respectively, with no statistical significance( χ2=0.08, P>0.05). There was no significant difference in the incidence of postoperative pancreatitis, bleeding, perforation, infection and contrast agent-related complications(all P>0.05). Conclusions:Clinically widely used high-risk endoscopic papillary balloon dilation and endoscopic biliary stent drainage(ERCP-associated treatments)are frequently performed in elderly patients, and do not increase intraoperative bleeding and postoperative complications in the elderly.Therefore, ERCP-associated treatments are safe for the elderly.

Resveratrol inhibits the migration, invasion and epithelial-mesenchymal transition in liver cancer cells through up- miR-186-5p expression / 浙江大学学报·医学版

To investigate the molecular mechanism of resveratrol inhibiting the metastasis of liver cancer . HepG2 and Huh7 cells were treated with different concentrations of resveratrol, and the cell viability was determined by CCK-8 assay to determine the optimal concentration of resveratrol for subsequent experiments. The expressions of miR-186-5p in liver cancer tissues and liver cancer cells were determined by quantitative real-time RT-PCR. The migration and invasion of HepG2 and Huh7 cells were detected by wound healing assay and Transwell assay, and the expression levels of epithelial-mesenchymal transition (EMT) related proteins were determined by Western blotting. Resveratrol with concentration of had no effect on the viability of HepG2 and Huh7 cells, so the concentration of resveratrol in subsequent experiments was 6.25 μmol/L. Resveratrol inhibited the wound healing and invasion of liver cancer cells; increased the expression of E-cadherin, and decreased the expression of vimentin and Twist1. The expression of miR-186-5p was significantly down-regulated in liver cancer tissues and cells compared with the adjacent tissues and normal liver cells (both <0.05). Furthermore, resveratrol induced the expression of miR-186-5p in liver cancer cells (both <0.01). Overexpression of miR-186-5p suppressed the migration, invasion and EMT of liver cancer cells. Knockdown of miR-186-5p blocked the inhibition effects of resveratrol on the migration, invasion and EMT of liver cancer cells. Resveratrol could inhibit the metastasis of liver cancer , which might be associated with up-regulating miR-186-5p.

Natural medicinal ingredients induce tumor ferroptosis and related mechanisms / 浙江大学学报·医学版

Ferroptosis is an iron-dependent programmed cell death characterized by reactive oxygen species-induced lipid peroxide accumulation, which is different from cell apoptosis, pyroptosis, necrosis or autophagy. Ferroptosis plays an important role in the regulation of tumorigenesis and tumor development. Recent studies have shown that natural medicinal ingredients can induce ferroptosis in tumor cells through glutathione (GSH)/glutathione peroxidase 4 (GPx4) pathway, iron metabolism, lipid metabolism or other mechanisms. It has been reported that more than 30 natural medicinal ingredients can induce ferroptosis in tumor cells with multiple pathways and multiple targets. This article reviews the current research progress on the antitumor effects of natural medicinal ingredients through inducing cell ferroptosis.

The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through Potently Downregulating MHC-I

SARS-CoV-2 infection have caused global pandemic and claimed over 5,000,000 tolls1-4. Although the genetic sequences of their etiologic viruses are of high homology, the clinical and pathological characteristics of COVID-19 significantly differ from SARS5,6. Especially, it seems that SARS-CoV-2 undergoes vast replication in vivo without being effectively monitored by anti-viral immunity7. Here, we show that the viral protein encoded from open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all the viral proteins, can directly interact with MHC-I molecules and significantly down-regulates their surface expression on various cell types. In contrast, ORF8a and ORF8b of SARS-CoV do not exert this function. In the ORF8-expressing cells, MHC-I molecules are selectively target for lysosomal degradation by an autophagy-dependent mechanism. As a result, CTLs inefficiently eliminate the ORF8-expressing cells. Our results demonstrate that ORF8 protein disrupts antigen presentation and reduces the recognition and the elimination of virus-infected cells by CTLs8. Therefore, we suggest that the inhibition of ORF8 function could be a strategy to improve the special immune surveillance and accelerate the eradication of SARS-CoV-2 in vivo.

Teicoplanin potently blocks the cell entry of 2019-nCoV

Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanism and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the clinic to treat bacterial infection, significantly restrained the cell entry of Ebola virus, SARS-CoV and MERS-CoV by specifically inhibiting the activity of cathepsin L (CTSL). Here, we found that the cleavage sites of CTSL on the Spike of SARS-CoV-2 were highly conserved among all the variants. The treatment with teicoplanin suppressed the proteolytic activity of CTSL on Spike and prevented the cellular infection of different pseudotyped SARS-CoV-2 viruses. Teicoplanin potently prevented the entry of authentic SARS-CoV-2 into the cellular cytoplasm with an IC50 of 2.038 M for the Wuhan-Hu-1 reference strain and an IC50 of 2.116 M for the SARS-CoV-2 (D614G) variant. The pre-treatment of teicoplanin also prevented SARS-CoV-2 infection in hACE2 mice. In summary, our data reveal that CTSL is required for both SARS-CoV-2 and SARS-CoV infection and demonstrate the therapeutic potential of teicoplanin for universal anti-CoVs intervention. ImportanceDisease prevention and treatment are two important countermeasures to end the coronavirus disease 2019 (COVID-19). However, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, evolves all the time, resulting in the emerging of many epidemic SARS-CoV-2 mutants, which significantly impairs the effectiveness of early strain-based vaccines and antibodies. Developing universal vaccines and broad-spectrum antiviral drugs are essential to confront SARS-CoV-2 mutants including those may emerge in the future. Our study reported here showed that the cleavage sites of cellular cathepsin L (CTSL) are highly conserved among all the SARS-CoV-2 mutants and SARS-CoV. The CTSL inhibitor teicoplanin not only inhibited the cell entry of two live SARS-CoV-2 strains and various pseudotyped viruses but also prevented live virus infection in animal models. Based on our previous finding that teicoplanin also inhibited SARS-CoV and MERS-CoV infection, we believe that teicoplanin possesses the potential to become a universal anti-CoVs drug.

A systematic strategy for screening therapeutic constituents of (Turcz) Baill infiltrated blood-brain barrier oriented in lesions using ethanol and water extracts: a novel perspective for exploring chemical material basis of herb medicines

, a widely used Chinese herbal medicine, was considered as central nervous system (CNS) drug for years. Both ethanol extracts (EES) and water extracts (WES) of it were applied clinically. Unfortunately, the difference of their efficacy and even effective material foundation of remains obscure. In this study, to explore the active constituents of , we compared pharmacodynamics and chemical profiles / of EES/WES for the first time using multiple chemical analysis, pharmacological and data processing approaches. It was proved that there was no significant difference in the anti-depressive effects between WES and EES. However, the contents of most components and in plasma were higher in EES than those in WES, which was unconvincing for their similar efficacy. Therefore, we further explored components of targeted onto brain and the results showed that 5 lignans were identified with definite absorptivity respectively both in EES and WES caused by the limitation of blood-brain barrier. Moreover, bioinformatic analysis predicted their anti-depressive action. Above all, the systematic strategy screened 5 brain-targeted effective substances of and it was suggested that exploring the components into nidi would promote the studies on herbs effective material basis.

Antagonistic activity of volatile metabolites from Trichoderma asperellum / 生物工程学报

Trichoderma spp. is a kind of filamentous fungi with important biocontrol value. Twelve strains of Trichoderma spp. were isolated from the soils of different types of crops in Shaoxing, Zhejiang and Foshan, Guangdong. The antagonistic resistance to Fusarium oxysporum was compared by plate confrontation test. The further analysis of volatile secondary metabolites for two strains were carried out using HS-SPME-GC-MS analysis. The results showed that T. asperellum ZJSX5003 and GDFS1009 had fast growth ability, and the inhibition effects on F. oxysporum were 73% and 74% respectively. Six identical volatile metabolites were detected as follows 2-Methyl-1-propanol, 3-Methyl-1-butanol, 3-Methyl-3-buten-1-ol, Acetyl methyl carbinol, Butane-2,3-diol and 6-n-pentyl-2H-pyran-2-one (6-PAP). Among them, 6-PAP was validated to have a higher inhibitory effect on F. oxysporum in vitro. This study will provide basis for the development of biocontrol agents with metabolites of Trichoderma, such as 6-PAP.

A compact, high signal-to-noise ratio line-detector array Compton scatter imaging system based on silicon photomultipliers.

We develop a compact, high signal-to-noise ratio line-detector array Compton scatter imaging system based on Y2SiO5 scintillators and silicon photomultipliers. It is shown that the system's response uniformity is better than 98% for low-Zeff materials after a specific correction. Backscatter images of an "IHEP"-character model, cubes of different materials, and some other applications are presented, to show its potential for use in nondestructive testing.