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Arbutin, a natural polyphenol, inhibits OS cell viability, invasion and migration by down‐regulating MTHFD1L expression. miR‐338‐3p directly targets MTHFD1L. This regulatory action is associated with the inactivation of the AKT/mTOR signaling pathway., Arbutin, a glycoside extracted from the plant Arctostaphylos uva‐ursi, has been previously reported to possess antioxidant, anti‐inflammatory and anticancer effects. Here, we investigated whether arbutin affects the proliferation of the cells of the osteosarcoma (OS) cell lines MG‐63 and SW1353. Arbutin suppressed OS cell viability in a dose‐ and time‐dependent manner, as shown by Cell Counting Kit‐8 assay. Furthermore, arbutin exposure decreased the protein levels of MTHFD1L, CCND1 and phosphorylated‐protein kinase B (AKT)/phosphorylated‐mammalian target of rapamycin (mTOR). Potential upstream miRNAs of MTHFD1L were predicted using TargetScan, PICTAR5, miRanda and miRWalk. We performed luciferase activity assays to show that miR‐338‐3p directly targets and negatively regulates the expression of MTHFD1L. Knockdown of miR‐338‐3p promoted cell invasion, migration and proliferation in arbutin‐treated OS cells via MTHFD1L. In summary, our data suggest that arbutin inhibits OS cell proliferation, migration and invasion via miR‐338‐3p/MTHFD1L and by inactivating the AKT/mTOR pathway.

Background Radiotherapy (RT) is one of the main treatments for men with prostate cancer (PCa). Yet, to date, with numerous sophisticated nano-formulations as radiosensitizers have been synthesized with inspiring therapeutic effect both in vitro and in vivo, there still lacks the successful clinical translation of such nanosystems. Meanwhile, almost all the attention has been paid on the enhanced dose deposition effect by secondary electrons of nanomaterials with high atomic numbers (Z), despite that cell-cycle arrest, DNA damage and also reactive oxygen species (ROS) production are critical working mechanisms accounting for radiosensitization. Methods Herein, an ‘all-purpose’ nanostrategy based on dose deposition enhancement, cell cycle arrest and ROS production as prostate cancer radiosensitizer for potential clinical translation was proposed. The rather simple structure of docetaxel loaded Au nanoparticles (NPs) with prostate specific membrane antigen (PSMA) ligand conjugation have been successfully synthesized by a rather facile protocol. Results Enhanced cellular uptake achieved via selective internalization of the NPs by PCa cells with positive PSMA expression could guarantee the enhanced dose deposition. Moreover, the as-synthesized nanosystem could arrest cell cycle at G2/M phases, which would reduce the ability of DNA damage repair for more irradiation sensitive of the PCa cells. Meanwhile, G2/M phases arrest would further promote cascade retention and enrichment of the NPs within the cells. Furthermore, ROS generation and double strand breaks greatly promoted by the NPs under irradiation (IR) could also provide an underlying basis for effective radiosensitizers. Conclusions Investigations from in vitro and in vivo confirmed the as-synthesized NPs as an effective nano-radiosensitizer with ideal safety. More importantly, all the moieties within the present nanosystem have been approved by FDA for the purpose of PCa treatment, thus making the it highly attractive for clinical translation.

The aim of the present study was to investigate the role of microRNA-21 (miR-21) in regulating the classical WNT/β-catenin signaling pathway by targeting low-density lipoprotein-related receptor 6 (LRP6) in non-alcoholic fatty liver disease (NAFLD). For this purpose, we established a NAFLD model by feeding C57BL/6J mice a methionine-choline-deficient diet. Antagomir-21 was then injected via the tail vein, and the expression levels of WNT/β-catenin signaling pathway-related proteins, such as LRP6, glycogen synthase kinase-3β (GSK3β), p-β-catenin, β-catenin and the downstream protein, peroxisome proliferator-activated receptor γ (PPAR-γ), and lipid metabolism-related genes, including sterol regulatory element-binding transcription factor 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyl transferase 1α (CPT1α) and adenosine 5-monophosphate (AMP)-activated protein kinase α (AMPKα), were detected. The results revealed that in the NAFLD model, LRP6 expression was negatively associated with miR-21 expression. After antago-nizing the expression of miR-21, the protein level of LRP6 was increased. In addition, the WNT/β-catenin signaling pathway was activated, and lipid accumulation and inflammation were alleviated in the liver. However, the expression of PPAR-γ was not inhibited following the upregulation of the WNT signaling pathway. Taken together, the results of this study demonstrate that the inhibition of miR-21 expression can alleviate NAFLD by targeting LRP6 to activate the WNT/β-catenin signaling pathway.

Objective : To explore the histological feature of the cervical disc degeneration in patients with degenerative ossification (DO) and its potential mechanisms.Methods : A total of 96 surgical segments, from cervical disc degenerative disease patients with surgical treatment, were divided into ossification group (group O, n=46) and non-ossification group (group NO, n=50) based on preoperative radiological exams. Samples of disc tissues and osteophytes were harvested during the decompression operation. The hematoxylin-eosin staining, Masson trichrome staining and Safranin O-fast green staining were used to compare the histological differences between the two groups. And the distribution and content of transforming growth factor (TGF)-β1, p-Smad2 and p-Smad3 between the two groups were compared by a semi-quantitative immunohistochemistry (IHC) method.Results : For all the disc tissues, the content of disc cells and collagen fibers decreased gradually from the outer annulus fibrosus (OAF) to the central nucleus pulposus (NP). Compared with group NO, the number of disc cells in group O increased significantly. But for proteoglycan in the inner annulus fibrosus (IAF) and NP, the content in group O decreased significantly. IHC analysis showed that TGF-β1, p-Smad2, and p-Smad3 were detected in all tissues. For group O, the content of TGF-β1 in the OAF and NP was significantly higher than that in group NO. For p-Smad2 in IAF and p-Smad3 in OAF, the content in group O were significantly higher than group NO.Conclusion : Histologically, cervical disc degeneration in patients with DO is more severe than that without DO. Local higher content of TGF-β1, p-Smad2, and p-Smad3 are involved in the disc degeneration with DO. Further studies with multi-approach analyses are needed to better understand the role of TGF-β/Smads signaling pathway in the disc degeneration with DO.

The World Health Organization emphasized the importance of goggles and face shields for protection of medical personnel at the outbreak of the COVID-19 pandemic. Unsurprisingly, almost all countries suffered from a critical supply shortage of goggles and face shields, as well as many other types of personal protective equipment (PPE), for a long period, owing to the lack of key medical material supplies and the inefficiency of existing fabrication methods arising from the need to avoid crowds during the outbreak of COVID-19. In this paper, we propose a novel combined shield design for eye and face protection that can be rapidly fabricated using three-dimensional printing technology. The designed prototype eye-face shield is accessible to the general public, offering more possibilities for yield improvement in PPE during emergent infectious disease events such as COVID-19.

The World Health Organization emphasized the importance of goggles and face shields for protection of medical personnel at the outbreak of the COVID-19 pandemic. Unsurprisingly, almost all countries suffered from a critical supply shortage of goggles and face shields, as well as many other types of personal protective equipment (PPE), for a long period, owing to the lack of key medical material supplies and the inefficiency of existing fabrication methods arising from the need to avoid crowds during the outbreak of COVID-19. In this context, we propose a novel combined shield design for eye and face protection that can be rapidly fabricated using three-dimensional printing technology. The designed prototype eye–face shield is accessible to the general public , offering more possibilities for yield improvement in PPE during emergent infectious disease events such as COVID-19.

Objective: To analyze the levels of in vivo immunological indicators in patients with different types of malignanat lymphoma. Methods: A total of 69 patients with different types of malignanat lymphoma who were admitted in our hospital were included in the study, among which 31 had primary extranodular malignant lymphoma (extranodular group), and 38 had primary nodular malignant lymphoma (nodular group). Moreover, 34 patients with pure lymphnoditis were served as the control group. FCM and full-automatic speed scattering turbidimetry were used to detect T lymphocyte subsets proportion, IgG, IgA, IgM, C3, and C4 in the three groups. Results: The comparison of CD3+, CD4+, CD8+, NK cell proportion, and CD4+/CD8+ among the three groups was significantly different. When compared with the control group, CD3+, CD4+, CD8+, NK cell proportion, and CD4+/CD8+ in the extranodular group and nodular group were significantly reduced; moreover, CD3+, CD4+, CD8+, and CD4+/ CD8+ in the extranodular group were significantly lower than those in the nodular group, while NK cell in the extranodular group was significantly higher than that in the nodular group. The comparison of IgG, IgA, and C3 levels among the three groups was statistically significant. When compared with the control group, IgG and IgA levels in the extranodular group and nodular group were significantly elevated, while C3 level was significantly reduced, and the comparison between the extranodular group and nodular group between the two groups was statistically significant. IgM level in the extranodular group and nodular group was elevated, C4 level was reduced, but the comparison with the control group was not statistically significant. Spearman correlation analysis showed that CD3+ and CD4+ were significantly correlated with IgA, IgG, and C3. Conclusions: With the increasing of severity degree of lymphoma, the immunological level is reduced, while CD3+ and CD4+ are significantly correlated with IgA, IgG, and C3, indicating that detection of CD3+ and CD4+ proportion or IgA, IgG, and C3 contents in combined with pathological characteristics can evaluate the severity degree of malignant lymphoma in order to provide guidance for the clinical diagnosis and treatment.

Extensive evidence indicates that oxidative stress plays a pivotal role in the development of osteoporosis. We show that naringin, a natural antioxidant and anti-inflammatory compound, effectively protects human adipose-derived mesenchymal stem cells (hADMSCs) against hydrogen peroxide (H2O2)-induced inhibition of osteogenic differentiation. Naringin increased viability of hAMDSCs and attenuated H2O2-induced cytotoxicity. Naringin also reversed H2O2-induced oxidative stress. Oxidative stress induced by H2O2 inhibits osteogenic differentiation by decreasing alkaline phosphatase (ALP) activity, calcium content and mRNA expression levels of osteogenesis marker genes RUNX2 and OSX in hADMSCs. However, addition of naringin leads to a significant recovery, suggesting the protective effects of naringin against H2O2-induced inhibition of osteogenic differentiation. Furthermore, the H2O2-induced decrease of protein expressions of β-catenin and clyclin D1, two important transcriptional regulators of Wnt-signaling, was successfully rescued by naringin treatment. Also, in the presence of Wnt inhibitor DKK-1, naringin is no longer effective in stimulating ALP activity, increasing calcium content and mRNA expression levels of RUNX2 and OSX in H2O2-exposed hADMSCs. These data clearly demonstrates that naringin protects hADMSCs against oxidative stress-induced inhibition of osteogenic differentiation, which may involve Wnt signaling pathway. Our work suggests that naringin may be a useful addition to the treatment armamentarium for osteoporosis and activation of Wnt signaling may represent attractive therapeutic strategy for the treatment of degenerative disease of bone tissue.

At the time of implanting bone-related implants into human body, a variety of biological responses to the material surface occur with respect to surface chemistry and physical state. The commonly used biomaterials (e.g. titanium and its alloy, Co-Cr alloy, stainless steel, polyetheretherketone, ultra-high molecular weight polyethylene and various calcium phosphates) have many drawbacks such as lack of biocompatibility and improper mechanical properties. As surface modification is very promising technology to overcome such problems, a variety of surface modification techniques have been being investigated. This review paper covers recent advances in surface modification techniques of bone-related materials including physicochemical coating, radiation grafting, plasma surface engineering, ion beam processing and surface patterning techniques. The contents are organized with different types of techniques to applicable materials, and typical examples are also described.

Thirty-nine fosfomycin-resistant Escherichia coli isolates carrying fosA3 were obtained from pigs, chickens, dairy cows, and staff in four northeastern provinces of China between June 2015 and April 2016. The fosA3 gene was colocated with bla CTX-M genes on conjugative plasmids of the incompatibility groups IncN ( n = 12), IncN-F33:A − :B − ( n = 2), IncF33:A − :B − ( n = 14), IncF14:A − :B − ( n = 2), and IncI1/sequence type 136 (ST136) ( n = 9). Four different genetic contexts of fosA3 were detected among the 39 E. coli isolates. Three potential epidemic plasmids circulated among E. coli strains from this region.

Thirty-nine fosfomycin-resistant Escherichia coli isolates carrying fosA3 were obtained from pigs, chickens, dairy cows, and staff in four northeastern provinces of China between June 2015 and April 2016. The fosA3 gene was colocated with blaCTX-M genes on conjugative plasmids of the incompatibility groups IncN (n = 12), IncN-F33:A−:B−(n = 2), IncF33:A−:B−(n = 14), IncF14:A−:B−(n = 2), and IncI1/sequence type 136 (ST136) (n = 9). Four different genetic contexts of fosA3 were detected among the 39 E. coli isolates. Three potential epidemic plasmids circulated among E. coli strains from this region.

Objectives: To determine the complete nucleotide sequence of the multidrug resistance plasmid pSCEC2, isolated from a porcine Escherichia coli strain, and to analyse it with particular reference to the cfr gene region. Methods: Plasmid pSCEC2 was purified from its E. coli J53 transconjugant and then sequenced using the 454 GSFLX System. After draft assembly, predicted gaps were closed by PCR with subsequent sequencing of the amplicons. Results: Plasmid pSCEC2 is 135615 bp in size and contains 200 open reading frames for proteins of ≥100 amino acids. Analysis of the sequence of pSCEC2 revealed two resistance gene segments. The 4.4 kb cfr-containing segment is flanked by two IS256 elements in the same orientation, which are believed to be involved in the dissemination of the rRNA methylase genecfr. The other segment harbours the resistance genesfloR,tet(A)-tetR,strA/strB andsul2, which have previously been found on other IncA/C plasmids. Except for these two resistance gene regions, the pSCEC2 backbone displayed .99% nucleotide sequence identity to that of other IncA/C family plasmids isolated in France, Chile and the USA. Conclusions: The cfr gene was identified on an IncA/C plasmid, which is well known for its broad host range and transfer and maintenance properties. The location on such a plasmid will further accelerate the dissemination of cfr and co-located resistance genes among different Gram-negative bacteria. The genetic context of cfr on plasmid pSCEC2 underlines the complexity of cfr transfer events and confirms the role that insertion sequences play in the spread of cfr.

The collagenase cathepsin K has been shown important in the pathogenesis of rheumatoid arthritis (RA). Icariin is the major pharmacologically active flavonol diglycoside of Herba Epimedii, an herb used in Chinese traditional medicine to treat arthritis. We investigated whether icariin can inhibit the protease activity of cathepsin K and its effects on a murine model of collagen-induced arthritis (CIA). Six-week old female BALB/C mice were immunized with type II collagen and treated with vehicle alone icariin (25mg/kg) for 21 days; a control remained untreated. Serum concentrations of type I collagen C-terminal telopeptide (CTX-I) and cartilage oligomeric matrix protein (COMP) and urinary concentrations of deoxypyridinoline (DPD) were measured, and disease severity was assessed. Compared with immunized, untreated mice, immunized icariin-treated mice had significantly lower urinary DPD (~25%, p

More and more applications of nanomaterials have been achieved in the biomedicine field. Numerous nanomedical devices, such as bone grafts with nano-hydroxyapatite and the silver-based anti-bacteria products, have been developed and have been trying to enter into the Chinese market. The State Food and Drug Administration of China (SFDA) is facing a critical challenge of how to explore and supervise the safety assessment of the nanomedical products. This paper briefly introduces the approval status of nanomedical products and the current advances of the safety assessment of nanomaterials in China.

Escherichia coli isolates from diseased pigs were examined for antimicrobial susceptibility to 12 antimicrobials and possession of virulence genes (VGs), and then grouped according to the phylogenetic background and genetic relatedness. Associations between antimicrobial resistance (AMR) and VGs and between AMR and phylogenetic group were subsequently assessed. The results showed that most isolates (91%) were epidemiologically unrelated. Multiple antimicrobial-resistant phenotypes (or=5 antimicrobials) were observed in 89% of E. coli strains and the most frequent types of resistance were to sulfamethoxazole (95%), tetracycline (94%), chloramphenicol (89%), and streptomycin (84%). The majority of isolates belonged to phylogenetic group A (84%). The most prevalent VG was EAST1 (64%), followed by Stx2e (63%) and eae (47%). Resistance to ceftiofur was associated with the presence of certain VGs, whereas resistance to doxycycline and kanamycin was associated with the absence of certain VGs. These findings suggest that multidrug resistance phenotypes, a variety of VGs, and the clear associations between resistance and VGs are commonly present in E. coli strains from diseased pigs. These results indicate that there is a great need for surveillance programs in China to monitor AMR in pathogenic E. coli strains.

A novel nonconjugative plasmid of 28,489 bp from a porcine linezolid-resistant Enterococcus faecium isolate was completely sequenced. This plasmid harbored a novel type of multiresistance gene cluster that comprised the resistance genes lnu (B), lsa (E), spw , aadE , aphA3 , and two copies of erm (B), which account for resistance to macrolides, lincosamides, streptogramins, pleuromutilins, streptomycin, spectinomycin, and kanamycin/neomycin. Structural comparisons suggested that this plasmid might have developed from other enterococcal plasmids by insertion element (IS)-mediated interplasmid recombination processes.

Two porcine Escherichia coli isolates harbored the cfr gene on conjugative plasmids of 38,405 bp (pGXEC6) and 41,646 bp (pGXEC3). In these two plasmids, the cfr gene was located within a 4,612-bp region containing a tnpA -IS 26-cfr -IS 26 -Δ hyp element. Plasmid pGXEC3 was almost identical to pGXEC6 except for a 3,235-bp IS Ecp1-bla CTX-M-14b insertion. The colocation of the multiresistance cfr gene with an extended-spectrum-β-lactamase gene on a conjugative plasmid may support the dissemination of these genes by coselection.

Purpose: To develop a sensitive and rapid method for the simultaneous determination of curcumin and piperine in human plasma.Methods: The method was based on high-performance liquid chromatography (HPLC) with electrospray ionization tandem mass spectrometer (ESI-MS/MS) detection in positive ionization mode. The analytes and internal standard were isolated from acidified plasma using liquid–liquid extraction (LLE). The organic extracts were evaporated, reconstituted in mobile phase and injected into the HPLC-MS/MS system. The analytes were chromatographed on a XB-C8 analytical column and MS-MS detection was performed on an electrospray ionization tandem mass spectrometer operated in multiple reaction monitoring (MRM) mode. Precursor→product combinations of m/z 369.9→177.0, 286.3→201.1 and 285.6→193.1 were used to quantify curcumin, piperine and the internal standard (IS), respectively. The assay was validated in the concentration range of 1.0 – 100.0 ng/ml for curcumin and 0.5 – 800.0 ng/ml for piperine using 0.5 ml of plasma.Results: The lowest limit of quantification (LLOQ) for curcumin and piperine was 1.00 and 0.50 ng/ml, respectively. The precision of the assay (expressed as coefficient of variation, CV) was < 12.6 % at all concentrations within the standard curve range, with adequate assay accuracy. Stability data revealed that the drugs were stable in plasma under various test conditions.Conclusion: The method is highly selective and rugged for the estimation of curcumin and piperine in human plasma and would be applicable to toxicokinetic, pharmacokinetic, bioavailability, and bioequivalence studies.Keywords: Curcumin, Piperine; HPLC-MS/MS, Simultaneous determination

In this study, the prevalence of plasmid-mediated quinolone resistance (PMQR) was investigated in 495 Escherichia coli isolates from diseased food-producing animals in Guangdong province, China. The quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes were analysed for mutations in 55 isolates harbouring only oqxAB and all isolates harbouring other PMQR genes. Overall, 282 (57.0 %) E. coli isolates had at least one PMQR gene. oqxAB was detected in 215 isolates and predominated the PMQR genes, followed by qnrS (63 isolates), aac(6')-Ib-cr (56 isolates), qnrB (39 isolates) and qepA (18 isolates). qnrA, qnrC and qnrD were not found in any of the isolates. The rates of resistance to ciprofloxacin, enrofloxacin, levofloxacin and nalidixic acid were 75.2, 81.0, 70.5 and 97.4 %, respectively, among the 495 isolates. Eight types of mutation in gyrA were detected in 154 PMQR-positive isolates, and 147 isolates were found to have mutations in parC. PFGE analysis indicated that the PMQR-positive E. coli isolates were genetically diverse. This study demonstrated that the number of mutations in QRDRs of gyrA and/or parC was significantly associated with the MICs of quinolones (P

AIM: To evaluate the association and interaction of genetic polymorphisms in methylenetetrahydrofolate reductase (MTHER) and cytochrome P4502E1 (CYP4502E1), environment risk factors with esophageal cancer (EC) in Kazakh, a high EC incidence area of Xinjiang Uygur Autonomous Region, China. METHODS: A 1:2 matched case-control study was conducted with 120 cases of EC and 240 population- or hospital-based controls. The controls were matched for sex, nationality, area of residence and age within a 5-year difference. MTHER and CYP4502E1 genotypes were identified by PCR-based restriction fragment length polymorphism (RFLP). A conditional logistic regression model was established to identify risk factors. The strata method was adopted in interaction analysis. RESULTS: Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water (shallow well, or river) were found to be the risk factors for EC. Individuals with the MTHFR677 (C/T + T/T) genotype had a 2.62-fold (95% CI: 1.61-4.28) risk of developing EC compared with those who carried the C/C genotype. Individuals with the CYP4502E1C1/C1 genotype had a 3.00-fold (95% CI: 1.82-4.96) risk compared with those who carried the CYP4502E1 (C1/C2 + C2/C2) genotype. Gene-environment interaction analysis showed that MTHFR677 gene polymorphism was correlated with consumption of green vegetables and fresh fruit, while CYP4502E1 C1/C1 was correlated with alcohol drinking and unsafe drinking water. MTHFR and CYP4502E1 analysis of gene-gene interaction showed that individuals with the MTHFR677 (C/T + T/T) and CYP4502E1C1/C1 genotypes had a 7.41-fold (95% CI: 3.60-15.25) risk of developing EC compared with those who carried the MTHFR677C/C and CYP4502E1 RsaI C1/C2 + C2/C2 genes, and the interaction rate was higher than that of the two factors alone. CONCLUSION: Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water (shallow well, or river) and polymorphisms in MTHFR and CYP4502E1 genes are important risk factors for EC. There is a synergistic interaction among polymorphisms in MTHFR and CYP4502E1 genes and environment factors. MTHFR and CYP4502E1 genes can be used as biomarkers for prevention of EC in Kazakh, Xinjiang Uygur Autonomous Region, China.

AIM: To investigate the effect of shenfu injection on gastrointestinal microcirculation after myocardial ischemic-reperfusion (IR) injury in rabbits and probe into the mechanism. METHODS: Forty healthy flap-eared white rabbits were randomly divided into 4 groups: IR injury control group (group I), shenfu injection 5 mL/kg per h group (group II), shenfu injection 10 mL/kg per h group (group III) and shenfu injection 20 mL/kg per h group (group IV). The four groups were treated with Lactated Ringer’s solution, shenfu injection 5, 10, and 20 mL/ kg per h were infused intravenously 30 min before experiment respectively. The values of hemodynamics [mean arterial pressure (MAP), heart rate (HR), gastric intramucosal partial pressure of carbon dioxide (PCO2), blood gas analysis and pH] were measured and compared with those before myocardial ischemia, 60 min after myocardial ischemia and 60, 90, and 180 min after reperfusion. RESULTS: The MAP, HR and gastric intramucosal pH were (70.50 ± 4.50) kPa, (165 ± 14) beats per min, 7.032 ± 0.024 in groupI 60 min after myocardial ischemia, which were significantly decreased compared with those before myocardial ischemia (88.50 ± 9.75 kPa, 217 ± 18 beats per min, 7.112 ± 0.035, P < 0.05). The MAP, HR and gastric intramucosal pH were significantly decreased in groupI 60, 90, and 180 min after reperfusion (61.50 ± 5.25 kPa, 133 ± 31 beats per min, 6.997 ± 0.025) compared with those before reperfusion respectively (P < 0.05), whereas the values were insignificantly different in groups II, III or IV after reperfusion, compared with those before reperfusion, and there were no significant differences between groups II, III, and IV after reperfusion. CONCLUSION: Pre-infusion of shenfu injection has a protective effect on gastrointestinal microcirculation after myocardial IR injury in rabbits, in a dose independent manner.

Summary Highly susceptible inbred male C57BL/6 mice were infected intraperitoneally with 2 × 107 cfu of a virulent Salmonella typhimurium strain. Tissue sections were taken from the spleen 2 and 3 days after infection for examination by electronmicroscopy. Rapid infiltration of polymorphs and macrophages was evident at the site of infection. These inflammatory phagocytes displayed avid destructive action against ingested bacteria. Bacterial multiplication occurred primarily in extracellular locations within sinusoids or in lesions containing disintegrating host cells.