Pectin supplementation accelerates post-antibiotic gut microbiome reconstitution orchestrated with reduced gut redox potential.

Antibiotic-induced gut dysbiosis (AID) is a big challenge for host health, and the recovery from this dysbiosis is often slow and incomplete. AID is typically featured by elevation in redox potential, Enterobacteriaceae load, and aerobic metabolism. In our previous study, pectin-enriched diet could decrease fecal redox potential and modulate gut microbiome. Therefore, we propose that pectin supplementation may modulate gut redox potential and favor post-antibiotic gut microbiome reconstitution from dysbiosis. In the present study, AID rats were applied to investigate the effects of pectin supplementation on post-antibiotic gut microbiome reconstitution from dysbiosis. The results showed that pectin supplementation accelerated post-antibiotic reconstitution of gut microbiome composition and function, and led to enhancement of anabolic reductive metabolism and weakening of catabolic oxidative pathways. These results were corroborated by the measurement of redox potential suggesting that pectin favors post-antibiotic recovery from dysbiosis. Transplantation of the pectin-modulated fecal microbiota (P-FMT) accelerated the decrease in antibiotics-elevated redox potential and Enterobacteriaceae load similarly to pectin supplementation. Moreover, both pectin supplementation and P-FMT enriched anaerobic members primarily from Lachnospiraceae orchestrating with enhancement on microbial reductive metabolism in post-antibiotic rats. The findings suggested that pectin supplementation accelerated post-antibiotic gut microbiome reconstitution orchestrated with reduced gut redox potential, and the effect of pectin on redox potential was mediated by intestinal microbiota remodeling.

Genomics-based analysis of four porcine-derived lactic acid bacteria strains and their evaluation as potential probiotics.

The search for probiotics and exploration of their functions are crucial for livestock farming. Recently, porcine-derived lactic acid bacteria (LAB) have shown great potential as probiotics. However, research on the evaluation of porcine-derived LAB as potential probiotics through genomics-based analysis is relatively limited. The present study analyzed four porcine-derived LAB strains (Lactobacillus johnsonii L16, Latilactobacillus curvatus ZHA1, Ligilactobacillus salivarius ZSA5 and Ligilactobacillus animalis ZSB1) using genomic techniques and combined with in vitro tests to evaluate their potential as probiotics. The genome sizes of the four strains ranged from 1,897,301 bp to 2,318,470 bp with the GC contents from 33.03 to 41.97%. Pan-genomic analysis and collinearity analysis indicated differences among the genomes of four strains. Carbohydrate active enzymes analysis revealed that L. johnsonii L16 encoded more carbohydrate active enzymes than other strains. KEGG pathway analysis and in vitro tests confirmed that L. johnsonii L16 could utilize a wide range of carbohydrates and had good utilization capacity for each carbohydrate. The four strains had genes related to acid tolerance and were tolerant to low pH, with L. johnsonii L16 showing the greatest tolerance. The four strains contained genes related to bile salt tolerance and were able to tolerate 0.1% bile salt. Four strains had antioxidant related genes and exhibited antioxidant activity in in vitro tests. They contained the genes linked with organic acid biosynthesis and exhibited antibacterial activity against enterotoxigenic Escherichia coli K88 (ETEC K88) and Salmonella 6,7:c:1,5, wherein, L. johnsonii L16 and L. salivarius ZSA5 had gene clusters encoding bacteriocin. Results suggest that genome analysis combined with in vitro tests is an effective approach for evaluating different strains as probiotics. The findings of this study indicate that L. johnsonii L16 has the potential as a probiotic strain among the four strains and provide theoretical basis for the development of probiotics in swine production.

Research on the characteristics and influencing factors of the spatial correlation network of cultivated land utilization ecological efficiency in the upper reaches of the Yangtze River, China.

Researching the structural characteristics of the spatial correlation network of cultivated land utilization ecological efficiency is of great significance to China's food security and agricultural green and low-carbon development. Taking 47 cities (autonomous prefectures) in the upper reaches of the Yangtze River as the research object, the ecological efficiency of cultivated land utilization from 2010 to 2020 was measured based on the unexpected output model (Super SBM), and the spatial correlation matrix was constructed using the revised gravity model. The structural characteristics of the spatial correlation network were analyzed using the social network model (SNA), and finally, the factors affecting the spatial correlation network of cultivated land utilization ecological efficiency in the upper reaches of the Yangtze River were analyzed through the quadratic assignment procedure (QAP) model. The results show that: (1) the ecological efficiency of cultivated land utilization in the upper reaches of the Yangtze River has been increasing year by year, but the overall level is low, and there is a large gap among provinces. Sichuan Province has the highest average value of 0.605, and Yunnan Province has the lowest average value of 0.359. (2) The ecological efficiency of cultivated land utilization in the upper reaches of the Yangtze River has broken through the provincial boundaries and has formed an obvious spatial correlation network, but the overall density is low, and the network is still relatively loose, needing further development and improvement. Chengdu, Yibin, Luzhou, and other cities are located in the center of the network and have formed four cohesive subgroups. (3)The differences in the level of agricultural economic development, the rural per capita disposable income, the differences in agricultural mechanization intensity, the regional population differences, and spatial adjacency have an impact on the spatial network of ecological efficiency of cultivated land utilization in the upper reaches of the Yangtze River. The difference in the level of agricultural economic development, the rural per capita disposable income, and the differences in agricultural mechanization intensity are negatively correlated, while the regional population differences are positively correlated with spatial adjacency.

Neural control of fluid homeostasis is engaged below 10°C in hibernation.

Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) hibernate for several months each winter without access to water,1 but the mechanisms that maintain fluid homeostasis during hibernation are poorly understood. In torpor, when body temperature (TB) reaches 4°C, squirrels decrease metabolism, slow heart rate, and reduce plasma levels of the antidiuretic hormones arginine vasopressin (AVP) and oxytocin (OXT).1 Squirrels spontaneously undergo interbout arousal (IBA) every 2 weeks, temporarily recovering an active-like metabolism and a TB of 37°C for up to 48 h.1,2 Despite the low levels of AVP and OXT during torpor, profound increases in blood pressure and heart rate during the torpor-IBA transition are not associated with massive fluid loss, suggesting the existence of a mechanism that protects against diuresis at a low TB. Here, we demonstrate that the antidiuretic hormone release pathway is activated by hypothalamic supraoptic nucleus (SON) neurons early in the torpor-arousal transition. SON neuron activity, dense-core vesicle release from the posterior pituitary, and plasma hormone levels all begin to increase before TB reaches 10°C. In vivo fiber photometry of SON neurons from hibernating squirrels, together with RNA sequencing and c-FOS immunohistochemistry, confirms that SON is electrically, transcriptionally, and translationally active to monitor blood osmolality throughout the dynamic torpor-arousal transition. Our work emphasizes the importance of the antidiuretic pathway during the torpor-arousal transition and reveals that the neurophysiological mechanism that coordinates the hormonal response to retain fluid is active at an extremely low TB, which is prohibitive for these processes in non-hibernators.

The Fecal Redox Potential in Healthy and Diarrheal Pigs and Their Correlation with Microbiota.

The redox potential plays a critical role in sustaining the stability of gut microbiota. This study measured the fecal redox potential in healthy and diarrheal pigs using direct and dilution methods and investigated their correlation with microbiota. The results showed that the fluctuations in the redox potential of healthy pig feces were consistent using two different methods and the two methods are equivalent based on an equivalence test. The redox potential was positively correlated with the number of fungi and negatively related to the total bacteria. The relative or absolute abundances of many bacteria at the phyla and genus levels were associated with redox potential. In diarrheal pigs, the potentiometric trends of the two methods demonstrated an opposing pattern and the correlation with total bacteria was reversed. Precipitously elevated redox potential was detected post-diarrhea using dilution methods. The absolute abundance of Escherichia-Shigella and Fuurnierella was positively correlated with redox potential, while both relative and absolute abundances of Limosilactobacillus were positively correlated. These results suggest that both methods are suitable for detecting gut redox potential in healthy pigs, while the dilution method is more suitable for diarrheal pigs. The findings on the correlation of Limosilactobacillus, Prevotella, and Escherichia-Shigella with redox potential offer novel insights for targeted modulation of intestinal health.

Electrochemically and Thermally Stable Inorganics-Rich Solid Electrolyte Interphase for Robust Lithium Metal Batteries.

Severe dendrite growth and high-level activity of the lithium metal anode lead to a short life span and poor safety, seriously hindering the practical applications of lithium metal batteries. With a trisalt electrolyte design, an F-/N-containing inorganics-rich solid electrolyte interphase on a lithium anode is constructed, which is electrochemically and thermally stable over long-term cycles and safety abuse conditions. As a result, its Coulombic efficiency can be maintained over 98.98% for 400 cycles. An 85.0% capacity can be retained for coin-type full cells with a 3.14 mAh cm-2 LiNi0.5 Co0.2 Mn0.3 O2 cathode after 200 cycles and 1.0 Ah pouch-type full cells with a 4.0 mAh cm-2 cathode after 72 cycles. During the thermal runaway tests of a cycled 1.0 Ah pouch cell, the onset and triggering temperatures were increased from 70.8 °C and 117.4 °C to 100.6 °C and 153.1 °C, respectively, indicating a greatly enhanced safety performance. This work gives novel insights into electrolyte and interface design, potentially paving the way for high-energy-density, long-life-span, and thermally safe lithium metal batteries.

Short-Term Supplementation of Pectin Alters Substrate Dynamics and Modulates Microbial Carbohydrate Metabolism in the Gut of a Pig Model.

The interaction of pectin and gut microbiota plays an important role in maintaining animal and human health, but this interaction is not fully understood. Here, the impact of pectin supplementation on substrate dynamics and gut microbiota (in the terminal ileum and feces) was integrally investigated in a fistula pig model. Our results showed that a pectin-supplemented diet (PEC) decreased the concentrations of starch, cellulose, and butyrate in feces but not in the terminal ileum. Metagenomic sequencing revealed that PEC had a low impact on the ileal microbiota but significantly increased plant polysaccharide-degrading genera (e.g., Bacteroides, Alistipes, and Treponema) in feces. Additionally, CAZyme profiling indicated that PEC reduced GH68 and GH8 for oligosaccharide degradation in the ileal microbiome, while it enriched GH5, GH57, and GH106 for degradation of carbohydrate substrates in feces. Metabolomic analysis confirmed that PEC increased metabolites involved in carbohydrate metabolism including glucuronate and aconitate. Collectively, pectin could promote complex carbohydrate substrate degradation in the hindgut via modulating the gut microbiota.

Supplementation of Schisandrin B in Semen Extender Improves Quality and Oxidation Resistance of Boar Spermatozoa Stored at 4 °C.

During cold storage, boar spermatozoa undergo oxidative stress, which can impair sperm function and fertilizing capacity. The objective of the present study was to assess the effects of Schisandrin B (Sch B) in semen extenders on the quality of boar semen stored at hypothermia. Semen was collected from twelve Duroc boars and diluted in extenders supplemented with different concentrations of Sch B (0 µmol/L, 2.5 µmol/L, 5 µmol/L, 10 µmol/L, 20 µmol/L, and 40 µmol/L). Here, we demonstrated that 10 µmol/L Sch B provided the best effects on motility, plasma membrane integrity, acrosome integrity, sperm normality rate, average movement velocity, wobbility, mitochondrial membrane potential (MMP), and DNA integrity of sperm. The results of Sch B effects on antioxidant factors in boar sperm showed that Sch B significantly elevated the total antioxidant capacity (T-AOC) and markedly decreased the reactive oxygen species (ROS) and malondialdehyde (MDA) content of sperm. The expression of catalase (CAT) and superoxide dismutase (SOD) mRNA was increased, while the expression of glutathione peroxidase (GPx) mRNA demonstrated no change compared to non-treated boar sperm. Compared to the non-treated group, Sch B triggered a decrease in Ca2+/protein kinase A (PKA) and lactic acid content in boar sperm. Similarly, Sch B led to a statistically higher quantitative expression of AWN mRNA and a lower quantitative expression of porcine seminal protein I (PSP-I) and porcine seminal protein II (PSP-II) mRNA. In a further reverse validation test, no significant difference was observed in any of the parameters, including adhesion protein mRNA, calcium content, lactic acid content, PKA, and protein kinase G (PKG) activity after sperm capacitation. In conclusion, the current study indicates the efficient use of Sch B with a 10 µmol/L concentration in the treatment of boar sperm through its anti-apoptosis, antioxidative, and decapacitative mechanisms, suggesting that Sch B is a novel candidate for improving antioxidation and decapacitation factors in sperm in liquid at 4 °C.

Thermoresponsive Electrolytes for Safe Lithium-Metal Batteries.

Exploring advanced strategies in alleviating the thermal runaway of lithium-metal batteries (LMBs) is critically essential. Herein, a novel electrolyte system with thermoresponsive characteristics is designed to largely enhance the thermal safety of 1.0 Ah LMBs. Specifically, vinyl carbonate (VC) with azodiisobutyronitrile is introduced as a thermoresponsive solvent to boost the thermal stability of both the solid electrolyte interphase (SEI) and electrolyte. First, abundant poly(VC) is formed in SEI with thermoresponsive electrolyte, which is more thermally stable against lithium hexafluorophosphate compared to the inorganic components widely acquired in routine electrolyte. This increases the critical temperature for thermal safety (the beginning temperature of obvious self-heating) from 71.5 to 137.4 °C. The remained VC solvents can be polymerized into poly(VC) as the battery temperature abnormally increases. The poly(VC) can not only afford as a barrier to prevent the direct contact between electrodes, but also immobilize the free liquid solvents, thereby reducing the exothermic reactions between electrodes and electrolytes. Consequently, the internal-short-circuit temperature and "ignition point" temperature (the starting temperature of thermal runaway) of LMBs are largely increased from 126.3 and 100.3 °C to 176.5 and 203.6 °C. This work provides novel insights for pursuing thermally stable LMBs with the addition of various thermoresponsive solvents in commercial electrolytes.

Puerol and pueroside derivatives from Pueraria lobata and their anti-inflammatory activity.

Five undescribed puerols and puerosides and three known analogues were obtained from the roots of Pueraria lobata. Their structures were determined by comprehensive analysis of spectroscopic data and chemical methods. Since puerol D and puerol C were racemic compounds, resolved into their enantiomers, and their absolute configurations were determined by experimental and calculated ECD spectra. Six of the isolates were evaluated for their inhibitory activities on NO generation and the expression of inflammatory factors in the LPS-stimulated RAW 264.7 macrophage cells. The results showed that (S)-puerol C, (R)-puerol C, isokuzubutenolide A and kuzubutenolide A significantly decreased the NO production (IC50 values in the range of 16.87-39.95 µM). Meanwhile, (S)-puerol C, isokuzubutenolide A and kuzubutenolide A also reduced the mRNA expression of inflammatory factors (TNF-α, IL-1ß and IL-6).

Thermally Stable Polymer-Rich Solid Electrolyte Interphase for Safe Lithium Metal Pouch Cells.

Serious safety risks caused by the high reactivity of lithium metal against electrolytes severely hamper the practicability of lithium metal batteries. By introducing unique polymerization site and more fluoride substitution, we built an in situ formed polymer-rich solid electrolyte interphase upon lithium anode to improve battery safety. The fluorine-rich and hydrogen-free polymer exhibits high thermal stability, which effectively reduces the continuous exothermic reaction between electrolyte and anode/cathode. As a result, the critical temperature for thermal safety of 1.0 Ah lithium-LiNi0.5 Co0.2 Mn0.3 O2 pouch cell can be increased from 143.2 °C to 174.2 °C. The more dangerous "ignition" point of lithium metal batteries, the starting temperature of battery thermal runaway, has been dramatically raised from 240.0 °C to 338.0 °C. This work affords novel strategies upon electrolyte design, aiming to pave the way for high-energy-density and thermally safe lithium metal batteries.

To hum or not to hum: Neural transcriptome signature of male courtship vocalization in a teleost fish.

For many animal species, vocal communication is a critical social behavior and often a necessary component of reproductive success. Additionally, vocalizations are often demanding motor acts. Wanting to know whether a specific molecular toolkit might be required for vocalization, we used RNA-sequencing to investigate neural gene expression underlying the performance of an extreme vocal behavior, the courtship hum of the plainfin midshipman fish (Porichthys notatus). Single hums can last up to 2 h and may be repeated throughout an evening of courtship activity. We asked whether vocal behavioral states are associated with specific gene expression signatures in key brain regions that regulate vocalization by comparing transcript expression levels in humming versus non-humming males. We find that the circadian-related genes period3 and Clock are significantly upregulated in the vocal motor nucleus and preoptic area-anterior hypothalamus, respectively, in humming compared with non-humming males, indicating that internal circadian clocks may differ between these divergent behavioral states. In addition, we identify suites of differentially expressed genes related to synaptic transmission, ion channels and transport, neuropeptide and hormone signaling, and metabolism and antioxidant activity that together may support the neural and energetic demands of humming behavior. Comparisons of transcript expression across regions stress regional differences in brain gene expression, while also showing coordinated gene regulation in the vocal motor circuit in preparation for courtship behavior. These results underscore the role of differential gene expression in shifts between behavioral states, in this case neuroendocrine, motor and circadian control of courtship vocalization.

Impact of Laparoscopic Converted to Open Gastrectomy on Short- and Long-Term Outcomes of Patients with Locally Advanced Gastric Cancer: A Propensity Score-Matched Analysis.

BACKGROUND: It remains unclear whether laparoscopic conversation to open gastrectomy causes higher morbidity and has an adverse effect on the long-term survival outcomes of patients with gastric cancer. This study was designed to evaluate the impact of the conversion on short and long-term outcomes of patients with locally advanced gastric cancer (AGC). METHODS: We retrospectively investigated 871 patients who initially underwent laparoscopic gastrectomy (LG) for pathologically confirmed diagnosis of AGC between February 2009 and April 2018. The patients were grouped as the conversion (CONV) group and completed laparoscopic (LAP) group. The 1:2 propensity score matching was performed to reduce the effect of bias due to the imbalanced baseline features between the two groups. Multivariate analyses were performed to identify risk factors for conversion and poor survival. RESULTS: After propensity-score matching, 168 patients (56 in the CONV group and 112 in the LAP group) were studied. The CONV group was associated with significantly longer operation time (252.4 vs. 216.7 min, P < 0.001) and greater estimated blood loss (234.8 vs. 171.2 ml, P < 0.001) as compared with the LAP group. The time to first flatus (3.8 vs. 3.3 days, P = 0.043), time to start a liquid diet (4.1 vs. 3.5 days, P = 0.021), and postoperative hospital stay (8.7 vs. 7.6 days, P = 0.020) were significantly longer in the CONV group than that in the LAP group. The overall complication rate did not differ significantly between the CONV group and the LAP group (16.1% vs. 12.5%, P = 0.692). Both 5-year overall survival (OS) and 5-year disease-free survival (DFS) did not differ significantly between the CONV group and the LAP group (P = 0.805, P = 0.945, respectively). Multivariate analysis showed that lymphovascular invasion and stage III were independent prognostic factors for poor OS and DFS, whereas conversion was not. CONCLUSIONS: The conversion from laparoscopic to open gastrectomy had no negative impact on morbidity and long-term survival outcomes for patients with locally AGC.

Transwell isolation and difference analysis of capacitated boar sperm proteins based on the iTRAQ technique.

During capacitation, proteins in boar sperm are released to maintain the stability of their own state and membrane structure. No studies have analyzed the differences between retained proteins and released proteins during sperm capacitation. In the present study, a Transwell chamber and polycarbonate membrane were used to separate the proteins of boar sperm and their released proteins. Isotopically labeled relative and absolute quantification (iTRAQ) was used to analyze each compartment protein. A total of 108 differential proteins were identified in the upper and lower chambers of the Transwell, among which 27 were significantly upregulated (p-value≤0.05 and |log2 (fold change)|≥1) and 81 were significantly downregulated (p-value≤0.05 and |log2 (fold change)|≤1). These differential proteins were mainly involved in biological processes (e.g., the regulation of cysteine peptidase activity, transmembrane transportation, ion transportation and ATP synthesis) and major signaling pathways (e.g., glutathione/galactose metabolism, cellular adhesion and PI3K-Akt), and most of them interacted with each other to some extent. In conclusion, retained proteins and released proteins of capacitated sperm were effectively separated using a Transwell chamber, and differential proteins were successfully identified from among the proteins. Bioinformatics analysis suggested that these differential proteins affect sperm capacitation mainly by adjusting sperm energy metabolism, motion characteristics and acrosome membrane status.

In vivo study of liposome-modified polyetheretherketone implant on bacteriostasis and osseointegration / 北京大学学报(医学版)

OBJECTIVE@#To develop dexamethasone plus minocycline-loaded liposomes (Dex/Mino liposomes) and apply them to improve bioinert polyetheretherketone (PEEK) surface, which could prevent post-operative bacterial contamination, enhance ossification for physiologic osseointegration, and finally reduce implant failure rates.@*METHODS@#Dex/Mino liposomes were covalently grafted onto the PEEK surface using polydopamine (pDA) coating as a medium. Confocal laser scanning microscopy was used to confirm the binding of fluorescently labeled liposomes onto the PEEK substrate, and a microplate reader was used to semiquantitatively measure the average fluorescence intensity of fluorescently labeled liposome-decorated PEEK surfaces. Moreover, the mouse subcutaneous infection model and the beagle femur implantation model were respectively conducted to verify the bioactivity of Dex/Mino liposome-modified PEEK in vivo, by means of micro computed tomography (micro-CT) and hematoxylin and eosin (HE) staining analysis.@*RESULTS@#The qualitative and quantitative results of fluorescently labeled liposomes showed that, the red fluorescence intensity of the PEEK-pDA-lipo group was stronger than that of the PEEK-NF-lipo group (P < 0.05); the liposomes were successfully and uniformly decorated on the PEEK surfaces due to the pDA coating. After mouse subcutaneous implantation of PEEKs for 24 hours, HE staining results showed that the number of inflammatory cells in the PEEK-Dex/Mino lipo group were lower than that in the inert PEEK group (P < 0.05), indicating a lower degree of infection in the test group. These results suggested that the Mino released from the liposome-functionalized surface provided an effective bacteriostasis in vivo. After beagle femoral implantation of PEEK for 8 weeks, micro-CT results showed that the PEEK-Dex/Mino lipo group newly formed more continuous bone when compared with the inert PEEK group; HE staining results showed that more new bones were formed in the PEEK-Dex/Mino lipo group than in the inert PEEK group, which were firmly bonded to the functionalized PEEK surface and extended along the PEEK interface. These results suggested that the Dex released from the liposome-functionalized surface induced effective bone regeneration in vivo.@*CONCLUSION@#Dex/Mino liposome modification enhanced the bioactivity of inert PEEK, the functionalized PEEK with enhanced antibacterial and osseointegrative capacity has great potential as an orthopedic/dental implant material for clinical application.

Clinical Characteristics of Acute Myeloid Leukemia Patients with RUNX1 Gene Mutation / 中国实验血液学杂志

OBJECTIVE@#To investigate the incidence of Runt-related transcription factor 1 (RUNX1) gene and its associated gene mutations in patients with acute myeloid leukemia (AML), and analyze its clinical characteristics and prognosis.@*METHODS@#The genomic DNA-PCR method was used to detect the exon of RUNX1 gene, and the gene mutations were analyzed by genetic sequencing. NPM1, DNMT3A, FLT3-ITD, IDH1/2, K/N-RAS, CEPBA, TET2, and WT1 co-mutations were also detected. Patients were followed up to determine efficacy and prognosis.@*RESULTS@#Among 171 patients, the RUNX1 gene mutation was detected in 17 cases, and the mutation rate was 9.9%. The type of RUNX1 gene mutation was 9 missense mutations, 4 frameshift mutations, and 4 nonsense mutations. The peripheral blood leukocyte count of the patients in mutation group was 3 (1-101) ×10@*CONCLUSION@#AML patients with RUNX1 gene mutation shows unique clinical and biological characteristics, RUNX1 mutation can be regarded as a molecular marker of poor prognosis in AML patients.

Correlation of the Expression Alteration of Tim-3 with the T Cell and B Cell Dysfunction in Peripheral Blood of Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To study the correlation of the expression alteration of Tim-3 with the T cell and B cell dysfunction in peripheral blood of multiple myeloma (MM) patients.@*METHODS@#30 patients diagnosed as MM from October 2016 to October 2018 were selected and enrolled in MM group, and 30 healthy persons whose sex and age was matched with the MM patients were selected and enrolled in healthy control group (HC). The blood samples from MM patients and HC were collected, and the peripheral blood mononuclear cells (PBMNC) were separated by density gradient centrifugation, then the serum was kept for further study. The ratios of CD3CD4Tim-3T cells, CD3CD8Tim-3T cells and the CD19+CD20-CD38+B cells were analysed by flow cytometry (FCM)，and the concentration of T cell-related cytokines IFN-γ, TNF-αand B cell-related antibodies IgA, IgM and IgG were measured by ELISA. At the same time, the differences of the ratios of CCD3CD4Tim-3T, CD3CD8Tim-3T cells and plasmablast and the concentration of IFN-γ, TNF-α, IgA, IgM and IgG between the MM patient and HC were estimated, and the correlation of the ratio of CD3CD4Tim-3T, CD3CD8Tim-3T cells with the ratio of plasmablast and the concentration of IFN-γ, TNF-α, IgA, IgM and IgG in MM patients were analyzed.@*RESULTS@#The ratio of CD3CD4Tim-3T, CD3CD8Tim-3T cells increased in MM patients, while the ratio of CD19+CD20- CD38+B cells and the concentration of IFN-γ, TNF-α, IgA, IgM and IgG decreased in MM patients. And there was a negative correlation of the ratio of CD3CD4Tim-3T cells with CD19+CD20-CD38+B cells and the concentration of IFN-γ, IgA, IgM and IgG in MM patients, while the ratio of CD3CD8Tim-3T cells just negatively correlated with the concentration of TNF-α.@*CONCLUSION@#Expression of Tim-3 on CD4 and CD8 cells elevates in the peripheral blood of MM patients, which also correlates with the function suppression of T and B cells.

Synthesis，Characterization and Anti-tumor Effect Evaluation of Novel Ampelopsin Derivative Poly （γ-glutamic Acid）-ampelopsin Conjugate / 中国药房

OBJECTIVE：To desig n and sy nthesize poly （γ-glutamic acid ）-ampelopsin（γ-PGA-AMP），and to characterize it and evaluate its anti-tumor activity in vitro . METHODS ：Synthetic product was produced through an esterification reaction between γ-PGA and ampelopsin. The structure of synthetic product was characterized by the UV spectrophotometry ，Fourier transform infrared（FT-IR）spectroscopy，1H-NMR spectra and the quantitative elemental analysis. The content of ampelopsin in synthetic product was determined by UV absorption spectrometry at 292 nm. Using 5-FU as positive control ，MTT assay was used to determine inhibitory effects of γ-PGA-AMP and ampelopsin on human breast cancer cell MCF- 7，human liver cancer cell HepG 2 and human lung cancer cell A 549. The IC 50 was calculated. RESULTS ：The results showed that the free 7-hydroxyl group of ampelopsin and the a-carboxyl group of γ-polyglutamic acid had been esterified to obtain γ-PGA-AMP；the yield of γ-PGA-AMP was 55.7％，and the content of ampelopsin was 32.3％. The inhibitory effect of γ-PGA-AMP and ampelopsin on MCF- 7，HepG2 and A 549 cells was obvious. IC 50 of γ-PGA-AMP（to 3 above tumor cells ）were 40.19，28.29 and 55.23 μg/mL，those of ampelopsin were 105.30，81.23，130.10 μg/mL，those of 5-FU were 24.72，87.98，30.99 μg/mL，respectively. CONCLUSIONS ：γ-PGA-AMP with anti-tumor effect in vitro is synthesized successfully ，and its anti-tumor effect is stronger than that of ampelopsin.

Retrospective high-resolution CT analysis of allergic bronchopulmonary aspergillosis / 中国医师进修杂志

Objective To investigate the high-resolution CT (HRCT) imaging characteristics of allergic bronchopulmonary aspergillosis (ABPA) to improve the diagnostic accuracy.Methods The clinical data of 21 patients with ABPA diagnosed in Dalian Second People's Hospital and Nanjing Lishui District Hospital of Traditional Chinese Medicine from January 2010 to June 2018 were retrospectively analyzed,and their clinical manifestations and HRCT examinations were statistically analyzed to summarize the HRCT imaging manifestations.Results Among the 21 patients,cough,expectoration and wheezing were the main clinical symptoms,followed by fever and hemoptysis;5 patients had a history of drug or food allergy.ABPA showed 18 cases of central bronchiectasis on HRCT,including 10 cases of simple bronchiectasis,9 cases with low-attenuation mucus,and 6 cases with high-attenuation mucus;patchy consolidation infiltration were seen in 11 cases;masses were seen in 2 cases;central nodules and tree buds were seen in 3 cases;mediastinal lymph nodes were enlarged in 6 cases.Conclusions HRCT imaging of ABPA is difficult to diagnose,and central bronchiectasis with high-attenuation mucus is characteristic.It can be used as a reliable basis for the diagnosis of ABPA imaging.Combined with clinical and laboratory examinations,it can generally be diagnosed clearly.

Osmolyte Depletion and Thirst Suppression Allow Hibernators to Survive for Months without Water.

Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) are obligatory hibernators who can survive over 6 months of the year in underground burrows or laboratory hibernaculum without access to food or water [1]. Hibernation consists of prolonged periods of torpor, lasting up to 18 days, which are characterized by low body temperature and suppressed metabolism. This torpidity is interspersed with short periods of interbout arousal, lasting up to 48 h, during which squirrels temporarily return to an active-like state and lose small amounts of water to urination and evaporation [2]. Water is also lost during torpor due to a positive vapor pressure difference created by the slightly higher temperature of the body compared to its surroundings [2, 3]. Here, we investigate the physiological mechanism of survival during prolonged water loss and deprivation throughout hibernation. By measuring hydration status during hibernation, we show that squirrels remain hydrated during torpor by depleting osmolytes from the extracellular fluid. During brief periods of arousal, serum osmolality and antidiuretic hormone levels are restored, but thirst remains suppressed. This decoupling of thirst and diuresis enables water retention by the kidney while suppressing the drive to leave the safety of the underground burrow in search of water. An acute increase in serum osmolality reinstates water-seeking behavior, demonstrating preservation of the physiological thirst circuit during hibernation. Better mechanistic understanding of internal osmolyte regulation and thirst suppression could translate to advancements in human medicine and long-term manned spaceflight. VIDEO ABSTRACT.