The Burkholderia pseudomallei KHW quorum-sensing systems produced N-octanoyl-homoserine lactone, N-decanoyl-homoserine lactone, N-(3-hydroxy)-octanoyl-homoserine lactone, N-(3-hydroxy)-decanoyl-homoserine lactone, N-(3-oxo)-decanoyl-homoserine lactone, and N-(3-oxo)-tetradecanoyl-homoserine lactone. The extracellular secretion of these acyl-homoserine lactones is dependent absolutely on the function of the B. pseudomallei BpeAB-OprB efflux pump.Burkholderia pseudomallei, a gram-negative soil bacillus, is the causative agent of melioidosis, a severe and potentially fatal emerging tropical infectious disease. Its intrinsic resistance to many antibiotics is attributed mostly to multiple multidrug efflux pumps, such as AmrAB-OprA, BpeAB-OprB, and BpeEF-OprC, which efflux aminoglycosides, macrolides, chloramphenicol, and trimethoprim (4,12,14). We hypothesized that these pumps also efflux physiological compounds that could compromise the fitness of the bacterium when accumulated to high intracellular concentrations and propose that this exerts a positive selection pressure for persistence even in the absence of antimicrobials (11).B. pseudomallei is reported to produce up to six different types of acyl-homoserine lactones (acyl-HSLs), the composition of which may differ slightly from strain to strain. For instance, strain PP844 secreted N-octanoyl-homoserine lac-, and N-(3-hydroxy)-dodecanoyl-homoserine lactone (3-hydroxy-C12HSL), while strain DD503, an amrAB-oprA efflux pump operon deletion mutant derived from 1026b, secreted only C8HSL, 3-hydroxy-C8HSL, and C10HSL (13,(17)(18)(19). It is unclear how acyl-HSLs move across the B. pseudomallei cell membranes and into the extracellular compartment, although in Pseudomonas aeruginosa, the shorter-chain acylHSLs appear to do so by diffusion while the longer-chain acyl-HSLs are secreted by multidrug efflux pumps (1, 15). In B. pseudomallei KHW, the expression of bpeAB-lacZ was induced by acyl-HSLs, and the bpeAB mutant failed to secrete any extracellular acyl-HSLs when it was cross-streaked against the JB525 reporter strain (3).Extracellular secretion of acyl-HSLs is dependent on BpeAB-OprB. In order to ascertain whether a blockage in the efflux mechanism, an inhibition of acyl-HSL synthesis, or both had contributed to the absence of extracellular acyl-HSLs in the bpeAB mutant, we compared the acyl-HSLs produced in cell supernatants of B. pseudomallei before and after the bacterial cells were permeabilized by a freeze-thaw procedure. Wild-type B. pseudomallei KHW, KHW carrying a plasmid overexpressing the BpeR repressor, the bpeAB null mutant, and a complemented bpeAB mutant were used in the comparison (Table 1), and a modified cross-streak bioassay was used for detection of acyl-HSLs (2). The culture supernatants of unpermeabilized wild-type KHW and the complemented bpeAB mutant contained acyl-HSLs but not those of the bpeAB mutant and the bpeR-overexpressing strain, both of which had impaired BpeAB-OprB function (Fig. 1, lanes U). Acyl-HSLs were detected in the cell sup...

To evaluate the application of multiple b values diffusion-weighted imaging based on biexponential signal decay model to predict the response to concurrent chemoradiotherapy in cervical cancer patients. This prospective study enrolled 28 patients (mean age: 50.89 ± 10.70 years) with cervical cancer confirmed by biopsy who received concurrent chemoradiotherapy. Pelvic magnetic resonance scans were performed 2 weeks before, 7 days and 21 days after the initiation of therapy, and 1 month after the end of the treatment. Diffusion-weighted imaging with b values of 0, 50, 450, and 850 s/mm2 were performed, and tumor volume, means of tumor apparent diffusion coefficient (ADC)min, ADCmean, ADCslow, ADCfast, and Ffast were measured. Pretreatment ADCmin and ADCslow of good outcome group were significantly higher than those of poor outcome group (P < .05). At the 7th day of the treatment, Ffast and its change rate of good outcome group were significantly higher than those of poor outcome group (P < .05). At the 7th day and 21st day of the treatment, Ffast showed a slowly increasing tendency with no significant difference compared with pretreatment value in poor outcome group (P < .05). One month post-treatment, only ADCslow change rate was significantly higher in good outcome group than that in poor outcome group. Intravoxel incoherent motion-related ADC values could be utilized to better predict the outcome of cervical cancer chemoradiotherapy.

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We present here the three-dimensional (3D) visualization fused with ultrasound and to evaluate its clinical application effect preliminarily. One hundred and eighteen patients with renal calculi in our hospital from September 2017 to December 2019 were prospectively randomized into two groups. The experimental group was treated with percutaneous renal puncture guided by the 3D visualization fused with ultrasound. The control group was treated with percutaneous renal puncture guided by B-ultrasonography (B-US). The puncture time in the experimental versus control group was 4.36 ± 1.28 min versus 10.72 ± 2.94 min (P = 0.000), operation time was 65.85 ± 10.63 min versus 81.34 ± 12.52 min (P = 0.000), and the loss of hemoglobin was 8.55 ± 3.76 g/L min versus 13.33 ± 5.81 g/L(P = 0.000), and the success rate of establishing the channel at one time was 98.41% versus 81.82% (P = 0.002), and the coincidence rate between the channel and the longitudinal axis of the target renal calyx was 88.89% versus 60.00% (P = 0.000). The 3D visualization fused with ultrasound could guide precise puncture to target calyces, reduce operation time, bleeding, and difficulty of puncture.

Mutations in the gene brain-derived neurotrophic factor (BDNF) cause obesity in humans. BDNF signaling and its expressing neurons in the hypothalamus help control feeding, energy expenditure (EE), and physical activity. However, whether the BDNF neurons interact with another EE-regulating system, the thermoregulation circuitry, remains unclear. Here, we show that BDNF neurons in the dorsomedial hypothalamus (DMH) are activated by environmental cooling and sufficient to induce body temperature increases and brown adipose tissue (BAT) thermogenesis. Conversely, blocking these neurons impairs BAT thermogenesis and cold defense, causing body weight gain and glucose intolerance. DMH BDNF neurons are therefore an important type of thermoregulatory neuron, integrating thermal afferent signals to control EE during cold defense. This reveals a critical intersection between the BDNF circuitry and the thermoregulatory system.