A Synthetic Steroid 5α-Androst-3ß, 5, 6ß-triol Alleviates Radiation-Induced Brain Injury in Mice via Inhibiting GBP5/NF-κB/NLRP3 Signal Axis.

Radiotherapy for head and neck tumors can lead to a severe complication known as radiation-induced brain injury (RIBI). However, the underlying mechanism of RIBI development remains unclear, and limited prevention and treatment options are available. Neuroactive steroids have shown potential in treating neurological disorders. 5α-Androst-3ß, 5, 6ß-triol (TRIOL), a synthetic neuroprotective steroid, holds promise as a treatment candidate for RIBI patients. However, the neuroprotective effects and underlying mechanism of TRIOL on RIBI treatment are yet to be elucidated. In the present study, our findings demonstrate TRIOL's potential as a neuroprotective agent against RIBI. In gamma knife irradiation mouse model, TRIOL treatment significantly reduced brain necrosis volume, microglial activation, and neuronal loss. RNA-sequencing, immunofluorescence, real-time quantitative polymerase chain reaction, siRNA transfection, and western blotting techniques revealed that TRIOL effectively decreased microglial activation, proinflammatory cytokine release, neuron loss, and guanylate-binding protein 5 (GBP5) expression, along with its downstream signaling pathways NF-κB and NLRP3 activation in vitro. In summary, TRIOL effectively alleviate RIBI by inhibiting the GBP5/NF-κB/NLRP3 signal axis, reducing microglia activation and pro-inflammation cytokines release, rescuing neuron loss. This study highlights the potential of TRIOL as a novel and promising therapy drug for RIBI treatment.

Effects of ultrasound monitoring of gastric residual volume on feeding complications, caloric intake and prognosis of patients with severe mechanical ventilation.

BACKGROUND: Monitoring of gastric residual is an important approach for assessing gastric emptying in patients with mechanical ventilation. By monitoring gastric contents, the enteral nutrition scheme can be adjusted in time to ensure feeding safety. AIM: To investigate the effects of ultrasound monitoring on the incidence of feeding complications, daily caloric intake and prognosis of patients with severe mechanical ventilation. To analyze the clinical significance of ultrasound monitoring of gastric residual volume (GRV) up to 250 mL to provide a theoretical basis for clinical practice. METHODS: Patients admitted to the department of emergency medicine of the Affiliated Hospital of Nantong University from January 2018 to June 2022 who received invasive mechanical ventilation and continuous enteral nutrition support within 24-48 h after admission were enrolled in this study. Medical records for patients within 7 d of hospitalization were retrospectively analyzed to compare the incidence of feeding complications, daily caloric intake and clinical prognosis between patients with gastric residual ≥ 250 mL and < 250 mL, as monitored by ultrasound on the third day. RESULTS: A total of 513 patients were enrolled in this study. Incidences of abdominal distension, diarrhea, and vomiting in the < 250 mL and ≥ 250 mL groups were: 18.4% vs 21.0%, 23.9% vs 32.3% and 4.0% vs 6.5%, respectively; mortality rates were 20.8% vs 22.65%; mechanical ventilation durations were 18.30 d vs 17.56 d while lengths of stay in the intensive care units (ICU) were 19.87 d vs 19.19 ± 5.19 d. Differences in the above factors between groups were not significant. Gastric residual ≥ 250 mL was not an independent risk factor for death and prolonged ICU stay. However, target feeding time of patients in the ≥ 250 mL group was longer than that of patients in the ≥ 250 mL group, and caloric intake (22.0, 23.6, 24.8, 25.3 kcal/kg/d) for patients in the ≥ 250 mL group from the 4th day to the 7th day of hospitalization was lower than that of patients in the ≥ 250 mL group (23.2, 24.8, 25.7, 25.8 kcal/kg/d). On the 4th day (Z = 4.324, P = 0.013), on the 5th day (Z = 3.376, P = 0.033), while on the 6th day (Z = 3.098, P = 0.04), the differences were statistically significant. CONCLUSION: The use of ultrasound to monitor GRV and undertaking clinical interventions when the monitoring value is ≥ 250 mL has no significant effects on incidences of feeding complications and clinical prognostic outcomes, however, it significantly prolongs the time to reach target feeding, reduces the daily intake of calories during ICU hospitalization, and increases the risk of insufficient nutrition of patients. The accuracy and necessity of monitoring gastric remnants and monitoring frequencies should be investigated further.

A facile synthesis of a copper(I) thiourea sulphate complex and its application for highly efficient chalcopyrite solar cells.

The precursor compound plays a crucial role in the development of low-cost chalcogenide thin-film solar cells via a solution approach. In this work, we report on the synthesis of a new complex [Cu((NH2)2CS)3]2SO4·H2O through a simple redox reaction between inexpensive Cu(CH3COO)2·H2O and thiourea (TU) in water. Using this complex as a copper source, a stable dimethylformamide solution was made and copper indium sulfoselenide CuIn(S,Se)2 thin film solar cells with a high efficiency of 12.2% have been demonstrated.

A retrospective three-dimensional study of the mandibular growth during preoperative orthodontics in late adolescent patients with skeletal Class III malocclusion.

INTRODUCTION: The mandible's ongoing development presents a contraindication for combined orthodontic-orthognathic treatment. The aim of this study was to evaluate the mandibular stability before and after preoperative orthodontic treatment in late adolescent patients with skeletal Class III malocclusion and to investigate the most appropriate time to start preoperative orthodontic treatment. MATERIAL AND METHODS: The study population consisted of 58 adolescents, aged between 15 and 21 years, with skeletal Class III malocclusion; the adolescents underwent CT scans at the beginning (T1) and the end (T2) of preoperative orthodontic treatment. The CT data were analyzed using ITK-SNAP and 3D Slicer software, and the effects of age and gender on mandibular development were investigated. RESULTS: In these 58 patients, there were no significant local bone alterations in the condyle and anterior chin point between T1 and T2 and no significant changes in the mandibular branch height, mandibular body length, condylar distance, and mandibular angle distance (p>0.05). The mandibular growth at the angel of mandible was statistically significant (p<0.05), but it was not clinically significant because the mean value of the growth was small (right: 0.416±0.986 mm, left: 0.328±0.886 mm). No effect of age and gender on mandibular development was observed. CONCLUSION: The mandibular morphology was stable during preoperative orthodontic treatment in patients at the late adolescent stage. This study provides evidence for the possibility of early implementation of preoperative orthodontics.

Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr.

Pseudomonas aeruginosa is a leading cause of hospital-acquired infections. Treatment of P. aeruginosa infections is difficult given its multiple virulence mechanisms, intrinsic antibiotic resistance mechanisms, and biofilm-forming ability. Auranofin, an approved oral gold compound for rheumatoid arthritis treatment, was recently reported to inhibit the growth of multiple bacterial species. Here, we identify P. aeruginosa's global virulence factor regulator Vfr as one target of auranofin. We report the mechanistic insights into the inhibitory mechanism of auranofin and gold(I) analogues to Vfr through structural, biophysical, and phenotypic inhibition studies. This work suggests that auranofin and gold(I) analogues have potential to be developed as anti-virulence drugs against P. aeruginosa.

Blocking vicious cycle of cardiac dysfunction by external cardiopulmonary resuscitation is the key to rescue acute aluminium phosphide poisoning.

Aluminium phosphide (ALP) and aluminium zinc phosphide (ZnP), the two main ingredients of fumigation drugs, are commonly used to kill insects or rodents in grain. When exposed to water, highly toxic phosphine gas is released and absorbed through the respiratory or digestive tract. Phosphine gas could non-selectively block cytochrome oxidase, inhibit electron transfer and suppress oxidative phosphorylation, leading to cellular hypoxia and organ dysfunction. The characteristic clinical manifestations are refractory shock and metabolic acidosis with high mortality. However, patients with ALP poisoning have a chance to be cured. Here, we report a case of oral ALP poisoning that was successfully treated by extracorporeal membrane oxygenation (ECMO) combined with continuous renal replacement therapy (CRRT) during frequent ventricular fibrillation and cardiac dysfunction.

Change Rule of Diatom in Zhangweixin River in Dezhou.

OBJECTIVES: To study the annual variation of diatoms in Zhangweixin River, to provide theoretical support by using diatom examination to estimate the time and place of the corpse entering water, and to establish a diatom database. METHODS: Samples were taken from 4 sampling sites in Decheng section of Zhangweixin River for 12 consecutive months. Non-metric multi-dimensional scaling (NMDS) analysis was performed on the species and content of diatom samples. Based on the sampling site of Tianqu Road, Sprensen similarity coefficient analysis was conducted with the data of other 3 sites in Decheng section and Leling section of Zhangweixin River and Ningjin section in previous studies. RESULTS: The number of diatom species was positively correlated with diatom content. The average diatom content in different months ranged from 1 054 to 13 041/10 mL, and the species composition ranged from 8 to 16, with differences in dominant species. The similarity coefficient of diatom species within 2 km were all higher than 0.956 52, which could not be distinguished effectively. The similarity coefficients of Leling section and Ningjin section were 0.736 84 and 0.588 24 respectively, which could be effectively distinguished. CONCLUSIONS: The species and content of diatom vary in different months in Zhangweixin River, and the composition of diatom species is different in different basins, which can provide reference for estimating the time and place of the corpse entering water in the river.

Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents.

Antibiotic resistance threatens effective treatment of microbial infections globally. This situation has spurred the hunt for new antimicrobial compounds in both academia and the pharmaceutical industry. Here, we report how the widely used antitumor drug cisplatin may be repurposed as an effective antimicrobial against the nosocomial pathogen Pseudomonas aeruginosa. Cisplatin was found to effectively kill strains of P. aeruginosa. In such experiments, transcriptomic profiling showed upregulation of the recA gene, which is known to be important for DNA repair, implicating that cisplatin could interfere with DNA replication in P. aeruginosa. Cisplatin treatment significantly repressed the type III secretion system (T3SS), which is important for the secretion of exotoxins. Furthermore, cisplatin was also demonstrated to eradicate in vitro biofilms and in vivo biofilms in a murine keratitis model. This showed that cisplatin could be effectively used to eradicate biofilm infections which were otherwise difficult to be treated by conventional antibiotics. Although cisplatin is highly toxic for humans upon systemic exposure, a low toxicity was demonstrated with topical treatment. This indicated that higher-than-minimal inhibitory concentration (MIC) doses of cisplatin could be topically applied to treat persistent and recalcitrant P. aeruginosa infections.

Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa.

Since its discovery 22 years ago, the bacterial cell-to-cell communication system, termed quorum sensing (QS), has shown potential as antipathogenic target. Previous studies reported that ajoene from garlic inhibits QS in opportunistic human pathogen Pseudomonas aeruginosa. In this study, screening of an in-house compound library revealed two sulfur-containing compounds which possess structural resemblance with ajoene and inhibit QS in bioreporter assay. Following a quantitative structure-activity relationship (SAR) study, 25 disulfide bond-containing analogues were synthesized and tested for QS inhibition activities. SAR study indicated that the allyl group could be replaced with other substituents, with the most active being benzothiazole derivative (IC50 = 0.56 µM). The compounds were able to reduce QS-regulated virulence factors (elastase, rhamnolipid, and pyocyanin) and successfully inhibit P. aeruginosa infection in murine model of implant-associated infection. Altogether, the QS inhibition activity of the synthesized compounds is encouraging for further exploration of novel analogues in antimicrobial drug development.

[Development of An Implantable Optrode for Optogenetic Stimulation].

In this study,an implantable optrode was developed for optogenetics stimulation of neural population in nuclei or multi-sites in neural circuits.The optrode was composed of base layer,micro-light emitting diode(LED)and coating layer.The base layer was a 150µm thick polyimide substrate on which copper wires and contacts were fabricated by flexible printed circuit board processes.The micro-LED was soldered on the contacts using SnBi.ParyleneC was deposited over the optrode as the coating layer using a vacuum vapor deposition system.The optical output power was tested by optical power meter and the insulating property was tested using saline in the experiment.The stimulation function of the optrode was demonstrated through animal experiment.The width of the optrode was500µm and the maximum thickness of the optrode was 310µm at the LED position.The thickness of the parylene coating layer was about 1µm.The maximum optical output power of optrode was 9.31 mW and the effective illumination area was a 3.03mm2 spherical cap at 650µm deep in brain tissue.The optrode was still functional after 14 days in physiological saline.Conventional copper electrodes were used to verify the efficacy of the optrode for stimulation and robust spiking activities of the expressing Channelrhodopsin-2neurons in the entire cortex of a mouce were recorded.Obvious behavior change happened when light stimulation was applied to the expressing Channelrhodopsin-2neurons in the secondary motor cortex of the mice.The optrode has the characteristics of large effective illumination range,flexible in implantation and long-term implantable,which provide neural population in nuclei research a new tool.

In vitro and in vivo generation and characterization of Pseudomonas aeruginosa biofilm-dispersed cells via c-di-GMP manipulation.

Bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is a global secondary bacterial messenger that controls the formation of drug-resistant multicellular biofilms. Lowering the intracellular c-di-GMP content can disperse biofilms, and it is proposed as a biofilm eradication strategy. However, freshly dispersed biofilm cells exhibit a physiology distinct from biofilm and planktonic cells, and they might have a clinically relevant role in infections. Here we present in vitro and in vivo protocols for the generation and characterization of dispersed cells from Pseudomonas aeruginosa biofilms by reducing the intracellular c-di-GMP content through modulation of phosphodiesterases (PDEs). Unlike conventional protocols that demonstrate biofilm dispersal by biomass quantification, our protocols enable physiological characterization of the dispersed cells. Biomarkers of dispersed cells are identified and quantified, serving as potential targets for treating the dispersed cells. The in vitro protocol can be completed within 4 d, whereas the in vivo protocol requires 7 d.

C-di-GMP regulates Pseudomonas aeruginosa stress response to tellurite during both planktonic and biofilm modes of growth.

Stress response plays an important role on microbial adaptation under hostile environmental conditions. It is generally unclear how the signaling transduction pathway mediates a stress response in planktonic and biofilm modes of microbial communities simultaneously. Here, we showed that metalloid tellurite (TeO3(2-)) exposure induced the intracellular content of the secondary messenger cyclic di-GMP (c-di-GMP) of Pseudomonas aeruginosa. Two diguanylate cyclases (DGCs), SadC and SiaD, were responsible for the increased intracellular content of c-di-GMP. Enhanced c-di-GMP levels by TeO3(2-) further increased P. aeruginosa biofilm formation and resistance to TeO3(2-). P. aeruginosa ΔsadCΔsiaD and PAO1/p(lac)-yhjH mutants with low intracellular c-di-GMP content were more sensitive to TeO3(2-) exposure and had low relative fitness compared to the wild-type PAO1 planktonic and biofilm cultures exposed to TeO3(2-). Our study provided evidence that c-di-GMP level can play an important role in mediating stress response in microbial communities during both planktonic and biofilm modes of growth.

Multiple diguanylate cyclase-coordinated regulation of pyoverdine synthesis in Pseudomonas aeruginosa.

The nucleotide signalling molecule bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) plays an essential role in regulating microbial virulence and biofilm formation. C-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and degraded by phosphodiesterase (PDE) enzymes. One intrinsic feature of c-di-GMP signalling is the abundance of DGCs and PDEs encoded by many bacterial species. It is unclear whether the different DGCs or PDEs coordinately establish the c-di-GMP regulation or function independently of each other. Here, we provide evidence that multiple DGCs are involved in regulation of c-di-GMP on synthesis of the major iron siderophore pyoverdine in Pseudomonas aeruginosa. Constitutive expression of the WspG or YedQ DGC in P. aeruginosa is able to induce its pyoverdine synthesis. Induction of pyoverdine synthesis by high intracellular c-di-GMP depends on the synthesis of exopolysaccharides and another two DGCs, SiaD and SadC. SiaD was found to boost the c-di-GMP synthesis together with constitutively expressing YedQ. The exopolysaccharides and the SiaD DGC were found to modulate the expression of the RsmY/RsmZ ncRNAs. Induction of the RsmY/RsmZ ncRNAs might enhance the pyoverdine synthesis through SadC. Our study sheds light on a novel multiple DGC-coordinated c-di-GMP regulatory mechanism of bacteria.

Visualization of an adsorption model for surfactant transport from micelle solutions to a clean air/water interface using fluorescence microscopy.

This work pertains to visualizing a transport model for adsorption of surfactants from micelle solutions onto a clean air/water interface. Under the condition of surfactant adsorption from very dilute solutions, the time scale for diffusion of a surfactant monomer is much slower than the time scale for kinetic breakdown of the aggregates. A theoretical model predicts two regimes for the adsorption dynamics. We visualize these two regimes under the mechanism of solubilization using fluorescence microscopy, in which an insoluble fluorescent probe, NBD-HAD (4-(hexadecylamino)-7-nitrobenz-2-oxa-1,3-diazole), is used to illuminate the micelles. The dye fluoresces in the microenvironment of micelles but is quenched in the aqueous solution on laser excitation. The region containing micelles is illuminated, but the region which does not contain micelles appears dark. For surfactant solution of C(14)E(6) at concentration just above the critical micelle concentration (C(CMC)), C(CMC)=4.4 mg/L, a dark region between the bright image of the air/water interface and the micelle-containing zone is observed. This dark region becomes smaller with time and finally disappears once equilibrium is reached. For a surfactant solution of C(14)E(6) at the concentration of 4.74C(CMC), which is higher than a critical total surfactant concentration (C(T)(c)) of 4.25C(CMC), we observe bright images through surfactant solutions during the adsorption process. Fluorescence images validate the theoretical model.

Asymmetric synthesis of functionalized 1,3-diphosphines via chiral palladium complex promoted hydrophosphination of activated olefins.

Aldehyde, ester- and keto-functionalized monophosphine palladium complexes containing the ortho-metalated (R)-(1-(dimethylamino)ethyl)naphthalene as the chiral auxiliary and reaction promoter were synthesized via hydrophosphination of acrolein and the subsequent Wittig reactions in a one-pot process. Under very mild conditions, the second-stage hydrophosphination of the monophosphine substrates gave the corresponding ester-, keto-, and hydroxyl-functionalized chiral 1,3-bis(diphenylphosphino)propane palladium complexes with good yields and stereoselectivities. The coordination properties and absolute configurations of the novel 1,3-diphosphine complexes were established by single crystal X-ray crystallography. The enantiomerically pure functionalized diphosphine ligands with ester and keto functionalities could be subsequently liberated stereospecifically by treatment of the corresponding dichloro palladium complexes with aqueous potassium cyanide in high yields.

Controllable synthesis of P-chiral 1,2- and 1,3-diphosphines via asymmetric Diels-Alder reactions involving functionalized allylic phosphines as dienophiles.

Optically pure P-chiral 1,2- and 1,3-diphosphines were synthesized chemoselectively and stereoselectively from the chiral organopalladium complex promoted asymmetric Diels-Alder reaction between 3,4-dimethyl-1-phenylphosphole (DMPP) and cis- and trans-ester substituted allylic phosphines.