Ultrasensitive detection of SARS-CoV-2 S protein with aptamers biosensor based on surface-enhanced Raman scattering.

A rapid and accurate diagnostic modality is essential to prevent the spread of SARS-CoV-2. In this study, we proposed a SARS-CoV-2 detection sensor based on surface-enhanced Raman scattering (SERS) to achieve rapid and ultrasensitive detection. The sensor utilized spike protein deoxyribonucleic acid aptamers with strong affinity as the recognition entity to achieve high specificity. The spherical cocktail aptamers-gold nanoparticles (SCAP) SERS substrate was used as the base and Au nanoparticles modified with the Raman reporter molecule that resonates with the excitation light and spike protein aptamers were used as the SERS nanoprobe. The SCAP substrate and SERS nanoprobes were used to target and capture the SARS-CoV-2 S protein to form a sandwich structure on the Au film substrate, which can generate ultra-strong "hot spots" to achieve ultrasensitive detection. Analysis of SARS-CoV-2 S protein was performed by monitoring changes in SERS peak intensity on a SCAP SERS substrate-based detection platform. This assay detects S protein with a LOD of less than 0.7 fg mL-1 and pseudovirus as low as 0.8 TU mL-1 in about 12 min. The results of the simulated oropharyngeal swab system in this study indicated the possibility of it being used for clinical detection, providing a potential option for rapid and accurate diagnosis and more effective control of SARS-CoV-2 transmission.

Raman spectroscopic investigation on TiO2-N719 dye interfaces using Ag@TiO2 nanoparticles and potential correlation strategies.

Herein, we employ Ag@TiO2 core-shell nanoparticles for surface-enhanced Raman scattering (SERS) investigations of TiO2-N719 dye interfaces. In situ electrochemical SERS investigations of the Ag@TiO2-N719 interaction are systematically carried out under a series of electrode-potential controls. By comparing the potential dependence of resonant and pre-resonant SERS spectra recorded with different laser excitations, bidentate carboxylate linkage is considered to be involved in N719 adsorption on TiO2. Meanwhile, SCN ligand shows obvious interactions with TiO2, and their role in the adsorption and orientation of N719 on TiO2 should not be underestimated. The in situ SERS spectra of Ag@TiO2 show a clear bell-shaped intensity-potential relation for the major bands of N719. A molecule-to-TiO2 charge-transfer resonance is tentatively attributed to account for such a phenomenon. Under the influence of such a charge-transfer resonance, valuable information about the N719-TiO2 interaction as well as the intramolecular deformation of N719 is obtained.

A Silver Lining of Neuropathic Pain: Predicting Favorable Functional Outcome in Spinal Cord Injury.

Background: Neuropathic pain (NP) is a common and severe problem following spinal cord injury (SCI). However, its relationship with functional outcome remains unclear. Methods: A retrospective explorative analysis was performed on SCI patients admitted to a tertiary academic medical center between January 2018 and June 2022. The candidate predictor variables, including demographics, clinical characteristics and complications, were analyzed with logistic and linear regression. Spinal Cord Independence Measure (SCIM) scores at discharge and mean relative functional gain (mRFG) of SCIM were as outcome parameters. Results: A total of 140 SCI patients included for the final analysis. Among them, 44 (31.43%) patients were tetraplegics, and 96 (68.57%) patients were paraplegics; 68 (48.57%) patients developed NP, and 72 (51.43%) patients did not. Logistic and linear regression analyses of SCIM at discharge both showed that NP [OR=3.10, 95% CI (1.29,7.45), P=0.01; unstandardized ß=11.47, 95% CI (4.95,17.99), P<0.01; respectively] was significantly independent predictors for a favorable outcome (SCIM at discharge ≥ 50, logistic regression results) and higher SCIM total score at discharge (linear regression results). Besides, NP [unstandardized ß=15.67, 95% CI (8.94,22.41), P<0.01] was also independently associated with higher mRFG of SCIM scores. Furthermore, the NP group had significantly higher mRFG, SCIM total scores and subscales (self-care, respiration and sphincter management, and mobility) at discharge compared to the non-NP group. However, there were no significant differences in mRFG, SCIM total score or subscales at discharge among the NP subgroups in terms of locations (at level pain, below level pain, and both) or timing of occurrence (within and after one month after SCI). This study also showed that incomplete injury, lumbar-sacral injury level and non-anemia were significantly independent predictors for a favorable outcome, and higher mRFG of SCIM scores (except for non-anemia). Conclusion: NP appears independently associated with better functional recovery in SCI patients, suggesting the bright side of this undesirable complication. These findings may help to alleviate the psychological burden of NP patients and ultimately restore their confidence in rehabilitation.

Primary motor hand area corticospinal excitability indicates overall functional recovery after spinal cord injury.

Background: After spinal cord injury (SCI), the excitability of the primary motor cortex (M1) lower extremity area decreases or disappears. A recent study reported that the M1 hand area of the SCI patient encodes the activity information of both the upper and lower extremities. However, the characteristics of the M1 hand area corticospinal excitability (CSE) changes after SCI and its correlation with extremities motor function are still unknown. Methods: A retrospective study was conducted on the data of 347 SCI patients and 80 healthy controls on motor evoked potentials (MEP, reflection of CSE), extremity motor function, and activities of daily living (ADL) ability. Correlation analysis and multiple linear regression analysis were conducted to analyze the relationship between the degree of MEP hemispheric conversion and extremity motor function/ADL ability. Results: The CSE of the dominant hemisphere M1 hand area decreased in SCI patients. In 0-6 m, AIS A grade, or non-cervical injury SCI patients, the degree of M1 hand area MEP hemispheric conversion was positively correlated with total motor score, lower extremity motor score (LEMS), and ADL ability. Multiple linear regression analysis further confirmed the contribution of MEP hemispheric conversion degree in ADL changes as an independent factor. Conclusion: The closer the degree of M1 hand area MEP hemispheric conversion is to that of healthy controls, the better the extremity motor function/ADL ability patients achieve. Based on the law of this phenomenon, targeted intervention to regulate the excitability of bilateral M1 hand areas might be a novel strategy for SCI overall functional recovery.

Synthesis, characterization, and 3D-FDTD simulation of Ag@SiO2 nanoparticles for shell-isolated nanoparticle-enhanced Raman spectroscopy.

Au-seed Ag-growth nanoparticles of controllable diameter (50-100 nm), and having an ultrathin SiO(2) shell of controllable thickness (2-3 nm), were prepared for shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS). Their morphological, optical, and material properties were characterized; and their potential for use as a versatile Raman signal amplifier was investigated experimentally using pyridine as a probe molecule and theoretically by the three-dimensional finite-difference time-domain (3D-FDTD) method. We show that a SiO(2) shell as thin as 2 nm can be synthesized pinhole-free on the Ag surface of a nanoparticle, which then becomes the core. The dielectric SiO(2) shell serves to isolate the Raman-signal enhancing core and prevent it from interfering with the system under study. The SiO(2) shell also hinders oxidation of the Ag surface and nanoparticle aggregation. It significantly improves the stability and reproducibility of surface-enhanced Raman scattering (SERS) signal intensity, which is essential for SERS applications. Our 3D-FDTD simulations show that Ag-core SHINERS nanoparticles yield at least 2 orders of magnitude greater enhancement than Au-core ones when excited with green light on a smooth Ag surface, and thus add to the versatility of our SHINERS method.

Chaos synchronization in mutually coupled semiconductor lasers with asymmetrical bias currents.

We experimentally and numerically investigated the chaos synchronization characteristics of mutually coupled semiconductor lasers (MCSLs) with asymmetrical bias currents. Experimental results show that, asymmetrical bias current level of two MCSLs has obvious influence on chaos synchronization between them, and stable leader-laggard chaos synchronization can be realized under relatively large asymmetrical bias current levels. Moreover, the influences of frequency detuning and mutually coupling strength between the two lasers on chaos synchronization performance have also been discussed. Theoretical simulations basically conform to our experimental observations.

Bidirectional chaos communication between two outer semiconductor lasers coupled mutually with a central semiconductor laser.

Based on a linear chain composed of a central semiconductor laser and two outer semiconductor lasers, chaos synchronization and bidirectional communication between two outer lasers have been investigated under the case that the central laser and the two outer lasers are coupled mutually, whereas there exists no coupling between the two outer lasers. The simulation results show that high-quality and stable isochronal synchronization between the two outer lasers can be achieved, while the cross-correlation coefficients between the two outer lasers and the central laser are very low under proper operation condition. Based on the high performance chaos synchronization between the two outer lasers, message bidirectional transmissions of bit rates up to 20 Gbit/s can be realized through adopting a novel decoding scheme which is different from that based on chaos pass filtering effect. Furthermore, the security of bidirectional communication is also analyzed.

[Impact of unilateral acute testicular ischemia on the contralateral testis of rabbits in anesthetic and conscious states].

OBJECTIVE: To compare the impact of unilateral acute testicular ischemia on the hemodynamics and histology of the contralateral testis of the rabbits under consistent anesthesia with that of the rabbits in the conscious state. METHODS: Forty-two healthy male white rabbits were randomly divided into an anesthetic group (Group A) to receive injection of sodium pentobarbital (PS) and a non-anesthetic group (Group B), each including a control group of 5 animals (A0 and B0), an incomplete testicular ischemia group of 8 (A1 and B1), and a complete testicular ischemia group of 8 (A2 and B2). Testicular ischemia models were constructed by color Doppler ultrasonography. Contrast-enhanced ultrasound (CEUS) was used to observe the perfusion of the contralateral testes before and after ligating and loosening the unilateral spermatic cord in each experimental group. The control animals also underwent CEUS and measurement of the heart rate (HR) and blood pressure (BP) at the corresponding time. Histological structure changes in the contralateral testes of the rabbits were observed in both anesthetic and conscious states. RESULTS: PS anesthesia markedly suppressed the HR and BP of the rabbits. The parameters in Groups of A0, A1 and A2 showed no statistically significant changes after unilateral ligation of the spermatic cord, while Groups B1 and B2 displayed significantly decreased peak-base difference (PBD) and prolonged arrival time (AT) and half time of descending peak intensity (HT). Groups A1, B1 and B2 showed significantly increased PBD and prolonged HT shortly after loosening the spermatic cord. Focal pathological and ultrastructural changes were observed in the contralateral testes of the ischemic rabbits, but no significant difference was found in Johnson's score in comparison with the controls. The apoptotic cells were remarkably increased in Groups A1, B1 and B2. CONCLUSION: Acute testicular ischemia may induce injury to the contralateral testis to some degree, and a reflexive sympathetic response may cause hemodynamic changes in the non-anesthetic state. And the neural and vascular inhibitory effects of anesthesia could make insignificant changes of blood perfusion in the contralateral testis.

A carbon-based material with a hierarchical structure and intrinsic heteroatom sites for sodium-ion storage with ultrahigh rate and capacity.

The storage of sodium ions with carbon materials has huge potential for large-scale application due to its resource-rich and environmental advantages. However, how to realize high power density, high energy density and long cycle life are the bottlenecks restricting its development. Herein, by using a facile synthesis strategy, a carbon-based framework with a hierarchical structure and intrinsic heteroatom sites which are the characteristics contributing to ultrahigh rate and capacity has been achieved. As a result, the hierarchical carbon-based material exhibits excellent performance when used as both the anode and cathode for sodium-ion capacitors (SICs), which can deliver a high energy density of 224 W h kg-1 (at 180 W kg-1), an ultrahigh power density of 17 160 W kg-1 (at 128 W h kg-1) and ultralong cycle life (91% capacity retention after 10 000 cycles at 2 A g-1), outperforming most of the previously reported SICs with other configurations.

A Carbon Foam with Sodiophilic Surface for Highly Reversible, Ultra-Long Cycle Sodium Metal Anode.

Sodium metal anodes combine low redox potential (-2.71 V versus SHE) and high theoretical capacity (1165 mAh g-1), becoming a promising anode material for sodium-ion batteries. Due to the infinite volume change, unstable SEI films, and Na dendrite growth, it is arduous to achieve a long lifespan. Herein, an oxygen-doped carbon foam (OCF) derived from starch is reported. Heteroatom doping can significantly reduce the nucleation resistance of sodium metal; combined with its rich pore structure and large specific surface area, OCF provides abundant nucleation sites to effectively guide the nucleation and subsequent growth of sodium metal, and the nature of this foam can accommodate the deposited sodium. Furthermore, a more uniform, robust, and stable SEI layer is observed on the surface of OCF electrode, so it can maintain ultra-high reversibility and excellent integrity for a long time without dendritic growth. As a result, when the current density is 10 mA cm-2, the electrode can maintain stable 2000 cycles and the coulombic efficiency can reach to 99.83%. Na@OCF||Na3V2(PO4)3 full cell also has extremely high capacity retention of about 97.53% over 150 cycles. These results provide a simple but effective method for achieving the safety and commercialization of sodium metal anode.

Time delay signature concealment of optical feedback induced chaos in an external cavity semiconductor laser.

The time delay (TD) signature concealment of optical feedback induced chaos in an external cavity semiconductor laser is experimentally demonstrated. Both the evolution curve and the distribution map of TD signature are obtained in the parameter space of external feedback strength and injection current. The optimum parameter scope of the TD signature concealment is also specified. Furthermore, the approximately periodic evolution relation between TD signature and external cavity length is observed and indicates that the intrinsic relaxation oscillation of semiconductor laser may play an important role during the process of TD signature suppression.

Development and Validation of UHPLC-MS/MS Assay for Therapeutic Drug Monitoring of High-dose Methotrexate in Children with Acute Lymphoblastic Leukemia.

PURPOSE: Precise and timely detection of methotrexate (MTX) concentration played a key role in high-dose MTX individualization therapy in acute lymphoblastic leukemia (ALL) children to avoid serious adverse effects or nonresponse. This report described a sensibility and validation of ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for therapeutic drug monitoring (TDM) of methotrexate concentration in children's plasma. METHODS: One-step protein precipitation of samples was accomplished by adding 200 µL of acetonitrile to 100 µL of plasma sample. The separation of plasma samples was carried out on a ZORBAX Eclipse Plus C18 Rapid Resolution HD column with gradient elution using a mobile phase constituted of acetonitrile and 1% formic acid. The detection was executed by electrospray ionization (ESI) of triple quadrupole tandem mass spectrometer (TQMS) in the multiple reaction monitoring (MRM) mode with the transitions m/z 455.2 → 307.9 for methotrexate and m/z 458.2 → 311.2 for IS, separately. Linear concentration range of the calibration curve was 44-11,000 nmol/L and 44 nmol/L was the lower limit of quantification. RESULTS: The methotrexate elution time was at 1.577 min, and the overall running time was only 3.3 min. The intra- and interday precision for all the analysis results was within 11.24%, and mean recoveries rate of methotrexate exceeded 87.98%. CONCLUSION: The described and fully validated UHPLC-MS/MS method was successfully applied in clinical TDM after infusion of high-dose methotrexate 1-5 g/m2 to 41 childpatients.

[Effects of intratumoral injection of microspheres containing cobra venom cytotoxin on transplanted human hepatoma in nude mice].

OBJECTIVE: To evaluate the safety and efficacy of intratumoral injection of polylactic-co-glycolic acid (PLGA) microspheres containing cobra venom cytotoxin in nude mice with transplanted human hepatoma. METHODS: Cytotoxic activity of cytotoxin from cobra venom was determined by using methyl thiazolyl tetrazolium method in vitro. Microspheres containing cobra venom cytotoxin were prepared with a double emulsion-solvent evaporation method. Forty BALB/c nude mice were inoculated subcutaneously in right flank with hepatoma BEL-7404 cells. Thirty-two mice whose tumor size reached about 1.0 cm in diameter, were randomly assigned into normal saline group, blank microsphers group, cytotoxin group and cytotoxin-PLGA group. Nude mice were intratumorally injected with normal saline, blank microspheres, cytotoxin or cytotoxin-PLGA microspheres respectively. Internal echo characteristics and blood flow of tumors were observed by high-frequency ultrasound every week after treatment. Twenty-six days after treatment, the tumors were removed to calculate the inhibition rate of tumor growth. The tumor, heart, liver and kidney tissues were obtained for histopathological examination. RESULTS: The cytotoxin separated and purified from crude cobra venom caused intense cytotoxic effects to the BEL-7404 cells in vitro. The diameter of PLGA microspheres containing cobra venom cytotoxin was about (34.45+/-9.85)microm. Encapsulation rate was up to (78.13+/-8.92)%, and cumulative amount of cobra venom cytotoxin released from the PLGA microspheres in vitro during 30 days was up to 84.3%. After intratumoral injection, tumor volumes and weights in the cytotoxin-PLGA group were lower than those in the normal saline group, with a tumor growth inhibition rate of 52.36%. Observed under a light microscope, most tumor tissues were necrotic. No obvious morphological change could be seen on the liver, kidney and heart tissues. CONCLUSION: The above findings indicate that intratumoral injection of cytotoxin-PLGA microspheres has strong antitumor effect and can obviously lessen systemic toxicity, which may provide an effective and feasible method for hepatocellular carcinoma treatment.

[Relationship between ultrasonographic grading of varicocele and changes of seminal parameters after varicocelectomy].

OBJECTIVE: To discuss the correlation of ultrasonographic grading of varicocele (VC) with the changes of seminal parameters after varicocelectomy. METHODS: A total of 129 cases of VC were diagnosed by scrotal color Doppler ultrasonography (CDU) and graded into 3 groups: VC I, VC II and VC III, according to three different grading indexes: the regurgitant volume of pampiniform plexus veins (PPV), the maximum diameter of PPV and the combination of the regurgitant volume and the maximum diameter of PPV. All the patients underwent high ligation of the spermatic vein and semen analysis was performed before and after varicocelectomy according to the WHO guidelines. RESULTS: With the maximum diameter of PPV as the grading index, there were statistically significant differences in the seminal parameters of VC III (P < 0.05) but not in those of VC I and VC II (P > 0.05) before and after varicocelectomy, while based on the regurgitant volume of PPV or the combination of the regurgitant volume and the maximum diameter of PPV, the differences were insignificant in VC I (P > 0.05), significant in VC II (P < 0.05) and extremely significant in VC III (P < 0.01). No significant differences were found in the rate of sperm abnormality among the 3 groups after varicocelectomy (P > 0.05). CONCLUSION: Different grading indexes influence the changes of seminal parameters after varicocelectomy. The regurgitant volume of PPV and the combination of the regurgitant volume and the maximum diameter of PPV are more reasonable and reliable as the grading indexes of VC. Different grades of VC respond differently to varicocelectomy. Whether VC I necessitates varicocelectomy needs to be further investigated.

Effects of Risperidone and Paliperidone on Brain-Derived Neurotrophic Factor and N400 in First-Episode Schizophrenia.

BACKGROUND: Risperidone and paliperidone have been the mainstay treatment for schizophrenia and their potential role in neuroprotection could be associated with brain-derived neurotrophic factor (BDNF) and N400 (an event-related brain potential component). So far, different effects on both BDNF and N400 were reported in relation to various antipsychotic treatments. However, few studies have been conducted on the mechanism of risperidone and paliperidone on BDNF and N400. This study aimed to compare the effects of risperidone and paliperidone on BDNF and the N400 component of the event-related brain potential in patients with first-episode schizophrenia. METHODS: Ninety-eight patients with first-episode schizophrenia were randomly divided into the risperidone and paliperidone groups and treated with risperidone and paliperidone, respectively, for 12 weeks. Serum BDNF level, the latency, and amplitude of the N400 event-related potential before and after the treatment and Positive and Negative Syndrome Scale (PANSS) scores were compared between the two groups. RESULTS: A total of 94 patients were included in the final analysis (47 patients in each group). After the treatment, the serum BDNF levels in both groups increased (all P < 0.01), while no significant difference in serum BDNF level was found between the groups before and after the treatment (all P > 0.05). After the treatment, N400 amplitudes were increased (from 4.73 ± 2.86 µv and 4.51 ± 4.63 µv to 5.35 ± 4.18 µv and 5.52 ± 3.08 µv, respectively) under congruent condition in both risperidone and paliperidone groups (all P < 0.01). Under incongruent conditions, the N400 latencies were shortened in the paliperidone group (from 424.13 ± 110.42 ms to 4.7.41 ± 154.59 ms, P < 0.05), and the N400 amplitudes were increased in the risperidone group (from 5.80 ± 3.50 µv to 7.17 ± 5.51 µv, P < 0.01). After treatment, the total PANSS score in both groups decreased significantly (all P < 0.01), but the difference between the groups was not significant (P > 0.05). A negative correlation between the reduction rate of the PANSS score and the increase in serum BDNF level after the treatment was found in the paliperidone group but not in the risperidone group. CONCLUSIONS: Both risperidone and paliperidone could increase the serum BDNF levels in patients with first-episode schizophrenia and improve their cognitive function (N400 latency and amplitude), but their antipsychotic mechanisms might differ.

Effects of Repetitive Transcranial Magnetic Stimulation Treatment on Event-Related Potentials in Schizophrenia.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) and event-related potentials (ERPs) are a noninvasive technique that widely used in neurophysiological field. Although rTMS has shown clinical utility for a number of neurological conditions, Recently,there was little understanding of the the efficacy of rTMS on Schizophrenia(SZ) and the change of ERP between before and after rTMS treatment. The objective of this study was to investigate the characteristics of N400, mismatch negativity (MMN), and P300 before and after treatment with rTMS in SZ. METHODS: One hundred and twenty-seven SZ patients hospitalized in Shanghai Mental Health Center from March 2015 to July 2017, divided into two groups (85 patients were recruited as rTMS group and 42 were recruited as sham rTMS [ShrTMS] group) and 76 normal controls (NCs) who were the staff and refresher staff in our hospital were recruited at the same time. A Chinese-made rTMS and a Runjie WJ-1 ERPs instrument were used in the present experiment. N400 was elicited by congruent and noncongruent Chinese idioms. After rTMS treatment, N400, P300, and MMN characteristics were compared with those before treatment and NC group. RESULTS: Compared with NC, the SZ patients exhibited delays in N400, P300, and MMN latency and decreased N400, P300, and MMN amplitudes in their frontal area (P < 0.05). After 25 rTMS treatments, N400 amplitudes in the frontal area (elicited by idioms with same phonic and different shape and meaning and with different phonic, shape, and meaning) were increased in the SZ patients (P < 0.05). However, there was no significant change in N400 before and after treatment with ShrTMS in SZ patients (P > 0.05). Amplitudes for MMN and target P300 also increased in SZ patients after rTMS treatment (P < 0.05). CONCLUSIONS: Based on our preliminary findings, we believe that the combined usage of N400, MMN, and P300 could be a valuable index and an electrophysiological reference in evaluating the effects of rTMS treatment in SZ patients.

Metabolic changes in the midgut of Eri silkworm after Oral administration of 1-deoxynojirimycin: A 1H-NMR-based metabonomic study.

1-deoxynojirimycin (DNJ) is a natural D-glucose analogue and has a strong physiological activity in inhibiting α-glucosidase in vivo. The antidiabetic effects of DNJ in mice or other mammals were extensively explored, but the physiological and toxic roles of DNJ in insects was seldom reported. In this study, the biological effects of DNJ were examined in midgut extracts of fourth-instar larvae of Eri silkworm (Samia cynthia ricini, Saturniidae). Based on nuclear magnetic resonance (NMR) metabonomics technology, we analyzed the alterations of glycometabolism, lipids, and energy metabolism pathways in the midgut of S. cynthia ricini caused by DNJ. Pattern recognition analysis (partial least square-discriminant analysis, PLS-DA) showed that four groups of latex, 0.25% DNJ, 0.5% DNJ and the mixture of 0.5% DNJ and latex (1:1) were distinctly different from the control group. Moreover, several metabolic pathways of DNJ-mediated modulation in the midgut were identified. Compared with the control group, alanine, succinate, glutamate, and fumarate concentrations decreased in three groups of 0.5% DNJ, latex, and the mixture, choline levels increased in two DNJ groups, and trehalose levels increased in all experimental groups. Therefore, these results suggest that DNJ modulated lipid metabolism by limiting the hydrolysis pathways of phospholipids metabolism. Additionally, DNJ has a potent negative effect on energy metabolism by inhibiting the hydrolysis of trehalose, glycolysis and the tricarboxylic acid (TCA) cycle. Overall, DNJ, as a single-ingredient, is an efficient substance for modulating lipid metabolism and inhibiting energy metabolism.

Mitochondria-Associated Apoptosis in Human Melanoma Cells Induced by Cardanol Monoene from Cashew Nut Shell Liquid.

Cardanol monoene (CM) is the major phenolic component extracted from cashew nut shell liquid (CNSL), which has been relevant to wide range of biological effects. In this study, we found that CM could inhibit the M14 human melanoma cells proliferation in a dose dependent and time dependent manner, and the IC50 values were determined to be 23.15 ± 2.42 µM and 12.30 ± 1.67 µM after 24 and 48 h treatment, respectively. The flow cytometric analysis demonstrated that CM induced M14 cell cycle arrest at the S phase, along with the collapse of mitochondrial membrane potential (ΔΨm) and the accumulation of reactive oxygen species (ROS) level in cells, but the apoptotic cells reduced when treated with Z-VAD-FMK (pan-caspase inhibitor). Western blotting showed that the expressions of p53, cytosol cytochrome C, cleaved-caspase-3, and cleaved-PARP were up-regulated, and the expression level of Bax/Bcl-2 ratio increased significantly. The 2527 significant differentially expressed genes were obtained by RNA-seq, which were assigned to 270 KEGG pathways. These results indicated that CM induced M14 cells apoptosis via the ROS triggered mitochondrial-associated pathways, which supports the potential application of CM for the therapy of melanoma cancer.

Local injection therapy for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and ranks the third most common cause of cancer-related death. Surgical resection, liver transplantation and percutaneous ablation are generally considered the only curative treatment for early stage HCC. Besides the limitations of insufficient organ donors and a long waiting time for liver transplantation, however, resection is applied only to patients with good hepatic reserve and localized tumors, with a resectability of 30%. DATA SOURCES: Local ablation therapy, which is minimally invasive but contributes to the significant improvement of survival in patients with unresectable tumor, has been widely used in treating small HCC. Among the techniques of local therapy, percutaneous ethanol injection (PEI) with a complete response in 80% of HCCs less than 3 cm has been accepted as an alternative to surgery in patients with small HCC. Moreover, percutaneous hepatic quantified ethanol injection (PHQEI) or PEI according to the standard criteria has been confirmed to benefit patients with HCC, especially when quantified ethanol is given at a short interval (QESI, the interval was 2-3 days). RESULT: Several limitations related to local percutaneous methods may result in incomplete therapeutic effect in case of larger HCC nodules (>3 cm). CONCLUSION: The combined use of different methods according to the clinical status of patients or tumors may be essential to the effective treatment of HCC.

An Evaluation of 1-Deoxynojirimycin Oral Administration in Eri Silkworm through Fat Body Metabolomics Based on (1) H Nuclear Magnetic Resonance.

1-Deoxynojirimycin (DNJ), the main hypoglycemic constituent in mulberry (Morus alba) latex, has been extensively researched. Although there is considerable interest in the biological effects of DNJ, the roles of 1-deoxynojirimycin (DNJ) in glycometabolism and energy metabolism in insects have received little attention. In this paper, (1)H nuclear magnetic resonance ((1)H NMR) based metabonomic was performed to study the effects of the oral supplementation of 0.25% DNJ, 0.5% DNJ, latex, and the mixture of 0.5% DNJ and latex (1 : 1) on the fat body glycometabolism and energy metabolism of the fourth-instar larvae of Eri silkworms, Samia cynthia ricini. Metabolic pattern recognition analysis (partial least square-discriminant analysis, PLS-DA) of fat body extracts indicated that the groups of 0.25% DNJ, 0.5% DNJ, latex, and the mixture of 0.5% DNJ and latex (1 : 1) were significantly different from the control group. Further, compared to the control group, the metabolites levels of lactate, trehalose, succinate, malate, and fumarate were remarkably changed in experimental groups, which were involved in glycolysis, hydrolysis of trehalose, and tricarboxylic acid (TCA) cycle. Our results indicate that DNJ has a positive impact on the reverse energy metabolism of Eri silkworms and metabonomic analysis based on NMR can be used as a tool to identify potential biomarkers.