Probiotics Influence Gut Microbiota and Tumor Immune Microenvironment to Enhance Anti-Tumor Efficacy of Doxorubicin.

Probiotics have been reported to influence the gut microbiota and immune system in various diseases. Now, the potential impacts of probiotics on tumor treatment still need to be investigated. In this study, three strains of probiotics, Bifidobacterium breve BBr60 (BBr60), Pediococcus pentosaceus PP06 (PP06), and Bifidobacterium longum subsp. longum BL21 (BL21) were investigated for their combination with chemotherapeutic drugs doxorubicin (DOX). Our study showed that PP06 and BL21 have good performance in gastric acid, bile salt, and intestinal fluid tolerance, antimicrobial activity to pathogenic Staphylococcus aureus, and adhesion to Caco-2 cells. Besides, the probiotics all exhibited antioxidant effect, especially BL21. In vitro cytotoxicity and in vivo animal studies revealed that probiotics used alone could not directly induce anti-tumor effects, but the combination of PP06/BL21 and DOX exhibits a higher inhibition rate than DOX alone, via recruitment and infiltration of immune cells in the tumor region. After 16S rRNA analysis of fecal samples from animal models, it was found that BL21 could increase the abundance of Akkermansia, which may also play a role in regulating the tumor microenvironment to improve immune response. In conclusion, BL21 and PP06 in this study could enhance the anti-tumor efficacy by influencing the gut microbiota and tumor immune microenvironment.

Lactobacillus gasseri LG08 and Leuconostoc mesenteroides LM58 exert preventive effect on the development of hyperuricemia by repairing antioxidant system and intestinal flora balance.

Introduction: Currently, hyperuricemia has shown a surprisingly rising trend, which attracts widespread attention due to potentially major health risks. Considering the inevitable side effects of long-term medicine, probiotics are emerging as potential therapeutics due to their ability to improve uric acid metabolism and superior safety. Methods: In our study, two strains of probiotics, Lactobacillus gasseri LG08 (LG08) and Leuconostoc mesenteroides LM58 (LM58) isolated from kimchi were evaluated for the prebiotic properties in vitro and uric-lowering effects in vivo. Here, hyperuricemia animal model and 16S rRNA gene amplicons analysis were further studied to investigate whether these probiotics exert different effects in prevention and treatment. Results: In vivo indicators and intestinal flora immunity revealed that both LG08 and LM58 significantly prevent the development and progression of hyperuricemia, repair the antioxidant system and maintain intestinal flora balance in healthy rats, especially LM58. After hyperuricemia was formed, although the effect of LG08 and LM58 could decrease the level of uric acid, the effect to reverse and repair antioxidant levels in the body was limited. Discussion: In our study, these findings have important implications for hyperuricemia prevention and therapy, and provided more mechanistic insights into the effect of probiotics in hyperuricemia.

Optical filter-fiber combination based infrared measurement device for surface temperature measurement.

Neutral Beam Injection (NBI) is one of the four efficient ways of assistant heating on the Experimental Advanced Superconducting Tokamak (EAST) device. Measures have been taken to ensure more reliable monitoring of NBI components' thermal data. Infrared thermometers, unlike surface-mounted thermocouples, have the advantage of non-contact and thus will not cause interference and get far less chance of malfunctioning [Childs et al., Rev Sci. Instruments 71, 2959-2978 (2000)]. In this paper, the remote infrared temperature measurement with optical fiber is reported to meet the requirement of the EAST-NBI diagnostic system. Some tests have been conducted on the remote infrared temperature measurement under the working condition, and an atmospheric propagation simulation was performed to estimate the atmosphere absorption. The results indicate that the detector's response is in line with the theory, and the atmosphere absorption within a certain wavelength should not be ignored. Temperature measurement error is within one percent at temperatures above 200 °C. So, for the temperature range of 200-600 °C, the remote infrared temperature measurement by the optical fiber can fully meet its expectation.

Boron Neutron Capture Therapy: Clinical Application and Research Progress.

Boron neutron capture therapy (BNCT) is a binary modality that is used to treat a variety of malignancies, using neutrons to irradiate boron-10 (10B) nuclei that have entered tumor cells to produce highly linear energy transfer (LET) alpha particles and recoil 7Li nuclei (10B [n, α] 7Li). Therefore, the most important part in BNCT is to selectively deliver a large number of 10B to tumor cells and only a small amount to normal tissue. So far, BNCT has been used in more than 2000 cases worldwide, and the efficacy of BNCT in the treatment of head and neck cancer, malignant meningioma, melanoma and hepatocellular carcinoma has been confirmed. We collected and collated clinical studies of second-generation boron delivery agents. The combination of different drugs, the mode of administration, and the combination of multiple treatments have an important impact on patient survival. We summarized the critical issues that must be addressed, with the hope that the next generation of boron delivery agents will overcome these challenges.

A dataset of mentorship in bioscience with semantic and demographic estimations.

Mentorship in science is crucial for topic choice, career decisions, and the success of mentees and mentors. Typically, researchers who study mentorship use article co-authorship and doctoral dissertation datasets. However, available datasets of this type focus on narrow selections of fields and miss out on early career and non-publication-related interactions. Here, we describe Mentorship, a crowdsourced dataset of 743176 mentorship relationships among 738989 scientists primarily in biosciences that avoids these shortcomings. Our dataset enriches the Academic Family Tree project by adding publication data from the Microsoft Academic Graph and "semantic" representations of research using deep learning content analysis. Because gender and race have become critical dimensions when analyzing mentorship and disparities in science, we also provide estimations of these factors. We perform extensive validations of the profile-publication matching, semantic content, and demographic inferences, which mostly cover neuroscience and biomedical sciences. We anticipate this dataset will spur the study of mentorship in science and deepen our understanding of its role in scientists' career outcomes.

Nanotechnology-Employed Bacteria-Based Delivery Strategy for Enhanced Anticancer Therapy.

Bacteria and their derivatives (membrane vesicles, MVs) exhibit great advantages for targeting hypoxic tumor cores, strong penetration ability and activating immune responses, holding great potential as auspicious candidates for therapeutic and drug-delivery applications. However, the safety issues and low therapeutic efficiency by single administration still need to be solved. To further optimize their performance and to utilize their natural abilities, scientists have strived to modify bacteria with new moieties on their surface while preserving their advantages. The aim of this review is to give a comprehensive overview of a non-genetic engineering modification strategy that can be used to optimize the bacteria with nanomaterials and the design strategy that can be used to optimize MVs for better targeted therapy. Here, the advantages and disadvantages of these processes and their applicability for the development of bacteria-related delivery system as antitumor therapeutic agents are discussed. The prospect and the challenges of the above targeted delivery system are also proposed.

Effect of dialectical behavior group therapy on the anxiety and depression of medical students under the normalization of epidemic prevention and control for the COVID-19 epidemic: a randomized study.

BACKGROUND: During the epidemic, the mental health of college students was generally poor, especially anxiety and depression, which should be treated using counseling and intervention. This study aimed to observe the influence of dialectical behavior therapy on the anxiety and depression of medical students during the normalization of the prevention and control of the COVID-19 epidemic. METHODS: A total of 26 medical students (experimental group) were treated with dialectical behavior therapy intervention for 4 weeks. Changes in depression, anxiety, and stress levels were assessed by the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder (GAD-7) scale, the Somatic Self-rating Scale (SSS), and the Perceived Stress Scale (PSS-10). This group was compared with 26 medical students (control group) without intervention. RESULTS: The value-added scores of the PHQ-9 (t=2.543, P=0.014) and GAD-7 scales (t=3.790, P=0.000) in the experimental group were significantly higher than those in the control group, while in the SSS scale, the value-added score of the depressive symptoms subscale (t=2.234, P=0.030) in the experimental group was significantly higher than that of the control group. For the total score of the PSS-10 scale (t=2.435, P=0.018), the value-added score of the experimental group was significantly higher than that of the control group. CONCLUSIONS: The intervention of dialectical behavior therapy can effectively alleviate the depression and anxiety of medical students during the normalization of epidemic prevention and control. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100048784.

Design of infrared radiation diagnostic calorimeter for the prototype radio frequency driven negative ion source for neutral beam injection.

In order to study the generation and extraction of negative ions for neutral beam injection application, a prototype radio frequency driven negative ion source and the corresponding test bench are under construction at the Institute of Plasma Physics, Chinese Academy of Sciences. A new design of infrared radiation diagnostic calorimeter for testing beam characteristics is put forward. Compared with the conventional calorimeter, the calorimeter adopts the block structure (8 × 28 tungsten hexahedron blocks) and modularization design (4 modules), so it has higher precision and good scalability. The thermal performance of the calorimeter is assessed using a finite element method. Simulation results show that the design can be achieved to operate in the stable-state mode at the maximum thermal flux 6.45 MW/m2 and meet the full requirement of beam diagnosis.

Physics and engineering design of 400 keV H- accelerator for negative ion based neutral beam injection system in China.

A research project of the China Fusion Engineering Test Reactor (CFETR) Negative ion-based Neutral Beam Injection (NNBI) prototype has been started in China. The objectives of the CFETR NNBI prototype are to produce a negative hydrogen ion beam of >20 A up to 400 keV for 3600 s and to attain a neutralization efficiency of >50%. In order to identify and optimize the design of the negative ion accelerator, a self-consistent model has been developed to consider all key physics and engineering issues (electric and magnetic fields, background gas flow, beam optics, beam-gas interaction, secondary particle trajectories, power deposition on grids, heat removal design, and mounting pattern). This paper presents the primary results by applying the self-consistent model to the current design of the 400 keV H- accelerator of the CFETR NNBI prototype.

Structure design and analysis of RF ion source for negative ion source test facility.

A negative ion source acts as a critical part in a neutral beam injector (NBI). A high current ion source is required for the high-power NBI. In this paper, a prototype radio frequency (RF) ion source and its test facility are developed in the Institute of Plasma Physics, Chinese Academy of Sciences, to demonstrate the key technology of the high power negative ion source. The structure design of the RF negative ion source is presented, involving the designs of the ion source plasma generator and accelerator. The detailed structure design and analysis of the key parts of the ion source are also presented, such as the Faraday shield (FS) and accelerator grids. The fluid-thermal-structural coupling characteristics of the FS and grid are explored with different mechanisms of fluid pressure, RF power, and the structure type on the thermal stress. Then, the processing and manufacturing scheme of the FS and grids are also given. Finally, the results were presented with a manufactured three cooling channel FS. The experimental results prove that the developed structure design of the RF ion source is effective and reliable, and the correctness of finite element analysis is also verified by experimental data comparison.

Optimization design of magnetic filter for the prototype RF negative ion source at ASIPP.

For a prestudy of the key science and technology of the RF negative ion source for fusion application, a negative RF ion source test facility was developed at the Institute of Plasma Physics, Chinese Academy of Science (ASIPP). The magnetic filter field in front of the extraction system plays an important role in reducing the loss of negative hydrogen ions and inhibiting coextraction of electrons. The existing filter field of the prototype ion source is generated by permanent magnets arranged on both sides of the expansion chamber; the gradient and the uniformity of the field are poor, resulting in a large plasma distribution unevenness in the experiment. In order to reduce the B→×∇B drift and the beam deflection, the plasma nonuniformity, and the beam alignment, its gradient should be as low as possible, especially near the Plasma Grid (PG), while its strength should be as low as possible inside both the driver and the extraction region. Hence, the magnetic filter field generated by the permanent magnet and the PG current with return wires is proposed. A finite element analysis method is used to calculate the distribution of the magnetic field throughout the ion source, especially the filter profile along the centerline perpendicular to the PG and the section parallel to the PG. Several cases were compared and the final design provides a more uniform magnetic field in the region within 70 mm above the plasma grid, while the field strength is around 5 mT and the integral BdL quantity is greater than 1.2 mTm.

Research and development progress of radio frequency ion source for neutral beam injector at ASIPP.

Neutral beam injection (NBI) is one of the most effective tools of four auxiliary plasma heating methods for fusion plasma heating and current drive. Now, a next generation fusion device, China Fusion Engineering Test Reactor, is under design, and a large negative NBI is foreseen. In order to demonstrate the key technology and performance of a negative ion source, a negative radio frequency (RF) ion source test facility has been developed since 2017 in the Institute of Plasma Physics, Chinese Academy of Science. A prototype RF ion source with double drivers (having the same structure with an inner diameter of 200 mm) was developed and tested on the test facility to preresearch the key technology of the RF plasma generator. The driver is equipped with a water-cooled Faraday shield to protect the alumina cylinder from the plasma, and the plasma expands into the rectangular expansion chamber. The RF power of 100 kW with a frequency of 1 MHz is transferred to the RF driver by a matching unit. The characteristics of plasma discharge were studied with classical diagnostic tools, such as the Langmuir probe and water flow calorimeter. Based on the plasma performance tests, a high power of 82 kW plasma discharge for a long pulse of 1000 s was achieved. In this paper, the details of the ion source design, characteristics of plasma, and future research plan will be presented.

Preliminary design of diagnostic system for negative neutral beam injector at ASIPP.

According to the latest physics design of the China Fusion Engineering Test Reactor (CFETR), two neutral beam injectors (NBIs), which deliver a total of 40 MW in not less than 3600 s with 1 MeV D0, are demanded to support current drive and plasma rotation. To minimize the risks and time to provide the CFETR with reliable NBIs, a negative NBI test facility will be developed at the Institute of Plasma Physics, Chinese Academy of Science. Its mission is to understand the characteristics of the RF driven ion source and negative ion generation and extraction and to improve RF efficiency and beam quality. In order to achieve this goal, a set of diagnostic tools will be used in this test facility. For source diagnostics, optical emission spectroscopy, cavity ring-down spectroscopy, laser absorption spectroscopy, and electrostatic probes are planned to be used. Beam emission spectroscopy, W-wire calorimeters, 1D carbon fiber composite diagnostic calorimeters, beam dump with thermocouples, and water-flow calorimetry are used to assess the beam properties. The design of the diagnostic system is presented.

Preliminary result of cavity ring-down spectroscopy system for radio frequency negative ion source test facility.

Negative ion source is a core part of the neutral beam injection system for magnetic confinement fusion devices. The density of produced hydrogen negative ions is a critical parameter of the negative ion source. Cavity ring-down spectroscopy (CRDS) is an ultrasensitive absorption diagnostic technique for density measurement. Based on the photodetachment process, CRDS can measure the integrated line-of-sight hydrogen negative ion density in a high power ion source. The CRDS diagnostic system has been applied to Hefei utility negative ion test equipment with the radio frequency (RF) source, which is now one of the references for the China Fusion Engineering Test Reactor neutral beam injection system. Typical ring-down signals are obtained to calculate the density of hydrogen negative ions. The time evolution of hydrogen negative ion density is successfully measured. Preliminary experiments show the accurate relationship between RF power and measured hydrogen negative ion density.

MicRNA-320 facilitates the brain parenchyma injury via regulating IGF-1 during cerebral I/R injury in mice.

PURPOSE: To investigate the protective effects of miR-320 on cerebral ischemia/reperfusion (I/R) injury in mice and PC12 cells. METHODS: miR-320 normal control (NC), inhibitor fragment and overexpression fragments were injected into mice lateral ventricles. Thereafter, the middle cerebral artery occlusion (MCAO) for left cerebrum method was employed in order to establish a cerebral I/R injury mice model. Apoptosis in the peripheral region of cerebral infarction and the volume of cerebral infarction and brain edema were tested as well. For simulating MCAO in vitro, the PC12 cells were subjected to oxygen-glucose deprivation. The lentivirus transfection technique was used to overexpress or inhibit miR-320. Furthermore, the effects of miR-320 on the survival and apoptosis of PC12 were monitored by MTT and TUNEL detection. RESULTS: A cerebral I/R injury mice model was successfully established. MiR-320 enhanced cell apoptosis of the injury side cortical infarcted peripheral zone and increased brain infarction volume and edema volume in MCAO/R mice. In addition, Insulin growth factor-1 (IGF-1) mRNA and protein expressions in MCAO/R mice were inhibited by miR-320 as well. Moreover, the results of cell studies were consist with the animal studies. CONCLUSIONS: miR-320 may be involved in the regulation of cerebral I/R for brain parenchyma injury by inhibition of IGF-1 pathway.

Distribution and Risk Assessment of Antibiotics in a Typical River in North China Plain.

We evaluated the occurrence and distribution of 12 antibiotics from the sulfonamide (SAs), fluoroquinolone (FQs) and tetracycline (TCs) groups in the Weihe River, North China. The total antibiotic concentrations in surface water, pore water, and sediment samples ranged from 11.1 to 173.1 ng/L, 5.8 to 103.9 ng/L, and 9.5 to 153.4 µg/kg, respectively. The values of the sediment-water partitioning coefficient in the Weihe River varied widely, from not detected to 943, 2213, and 2405 L/kg for SAs, FQs, and TCs, respectively. The values of the partitioning coefficients between sediment and surface water were generally lower than those between sediment and pore water, which indicated ongoing inputs to the water. The risk assessment showed that there were relatively high ecological risks to aquatic algae in this area from sulfamethoxazole, norfloxacin, tetracycline, ofloxacin, and ciprofloxacin.

Glutamatergic and central cholinergic dysfunction in the CA1, CA2 and CA3 fields on spatial learning and memory in chronic cerebral ischemia-Induced vascular dementia of rats.

Chronic cerebral ischemia (CCI) is associated with cognitive decline in aging, vascular dementia and Alzheimer's disease. Substantial evidence has shown that chronic cerebral ischemia may cause cognitive impairment, but the underlying neurobiological mechanism is poorly understood so far. In the present study, we used a rat model of chronic cerebral ischemia by permanent bilateral common carotid artery occlusion (BCCAO) to investigate the alterations of glutamatergic and central cholinergic dysfunction, and their causal relationship with the cognitive deficits induced by chronic cerebral ischemia. We found that BCCAO rats exhibited spatial learning and memory impairments dysfunction 3 month after BCCAO. Meanwhile, vGluT levels as well as glutamatergic and central cholinergic positive neurons in the hippocampus CA1-3 field significantly decreased. The protection of glutamergic and cholinergic neurons or regulating glutamate and central cholinergic levels in hippocampal subregion may have beneficial effects on cognitive impairments associated with the possible mechanism in CCI-induced vascular dementia.

The effect of Scutellaria baicalensis stem-leaf flavonoids on spatial learning and memory in chronic cerebral ischemia-induced vascular dementia of rats.

Flavonoids have been shown to improve cognitive function and delay the dementia progression. However, the underlying mechanisms remain elusive. In the present study, we examined the effect of Scutellaria baicalensis stem-leaf total flavonoids (SSTFs) extracted from S. baicalensis Georgi on spatial learning and memory in a vascular dementia (VaD) rat model and explored its molecular mechanisms. The VaD rats were developed by permanent bilateral occlusion of the common carotid artery. Seven days after recovery, the VaD rats were treated with either 50 or 100 mg/kg of SSTF for 60 days. The spatial learning and memory was evaluated in the Morris water maze (MWM) test. The tau hyperphosphorylation and the levels of the related protein kinases or phosphatases were examined by western blot analysis. In VaD rats, SSTF treatment at 100 mg/kg significantly reduced the escape latency in training trial in MWM test. In the probe trial, SSTF treatment increased the searching time and travel distance in the target quadrant. SSTF treatment inhibited the tau phosphorylation in both cortex and hippocampus in VaD rats. Meanwhile, SSTF reduced the activity of glycogen synthase kinase 3ß and cyclin-dependent kinase 5 in VaD rats. In contrast, SSTF treatment increased the level of the protein phosphatase 2A subunit B in VaD rats. SSTF treatment significantly improved the spatial cognition in VaD rats. Our results suggest that SSTF may alleviate tau-hyperphosphorylation-induced neurotoxicity through coordinating the activity of kinases and phosphatase after a stroke. SSTF may be developed into promising novel therapeutics for VaD.

Performance of positive ion based high power ion source of EAST neutral beam injector.

The positive ion based source with a hot cathode based arc chamber and a tetrode accelerator was employed for a neutral beam injector on the experimental advanced superconducting tokamak (EAST). Four ion sources were developed and each ion source has produced 4 MW @ 80 keV hydrogen beam on the test bed. 100 s long pulse operation with modulated beam has also been tested on the test bed. The accelerator was upgraded from circular shaped to diamond shaped in the latest two ion sources. In the latest campaign of EAST experiment, four ion sources injected more than 4 MW deuterium beam with beam energy of 60 keV into EAST.

Development of a core snubber for the neutral beam injector on EAST.

A 4-MW ion source was developed for the neutral beam injector (NBI) on Experimental Advanced Superconducting Tokamak (EAST). Breakdown nevertheless can happen during ion source conditioning and routine operations and is deleterious to the high-power ion source. To protect this ion source, a core snubber was designed to absorb the breakdown energy of the EAST-NBI ion source. A prototype core snubber was developed and tested using the ion-source test bed. The results show that with a core snubber, short-circuit currents at different high-power voltages were about one-tenth of the current without the snubber. The residual energy of the distributed capacitors had been absorbed successfully and the core snubber does protect the source from damage during breakdown. The results verified the successful development of a core snubber for the EAST-NBI.