Electron Aggregation and Oxygen Fixation Reinforced Microwave Dynamic and Thermal Therapy for Effective Treatment of MRSA-Induced Osteomyelitis.

Antibiotics are frequently used to clinically treat osteomyelitis caused by bacterial infections. However, extended antibiotic use may result in drug resistance, which can be life threatening. Here, a heterojunction comprising Fe2 O3 /Fe3 S4 magnetic composite is constructed to achieve short-term and efficient treat osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). The Fe2 O3 /Fe3 S4 composite exhibits powerful microwave (MW) absorption properties, thereby effectively converting incident electromagnetic energy into thermal energy. Density functional theory calculations demonstrate that Fe2 O3 /Fe3 S4 possesses significant charge accumulation and oxygen-fixing capacity at the heterogeneous interface, which provides more active sites and oxygen sources for trapping electromagnetic hotspots. The finite element analysis indicates that Fe2 O3 /Fe3 S4 displays a larger electromagnetism field enhancement parameter than Fe2 O3 owing to a significant increase in electromagnetic hotspots. These hotspots contribute to charge differential accumulation and depletion motions at the interface, thereby augmenting the release of free electrons that subsequently combine with the oxygen adsorbed by Fe2 O3 /Fe3 S4 to generate reactive oxygen species (ROS) and heat. This research, which achieves extraordinary bacterial eradication through the synergistic effect of microwave thermal therapy (MWTT) and microwave dynamic therapy (MDT), presents a novel strategy for treating deep-tissue bacterial infections.

Severe Infection Mimicking AML due to Bone Marrow Suppression: a Diagnostic Challenge.

BACKGROUND: Infection may lead to agranulocytosis due to bone marrow suppression. However, a rare case with infection presented with morphological features of acute myeloid leukemia (AML). METHODS: We report a case of extreme agranulocytosis due to severe infection mimicking acute myeloid leukemia. The case was definitively diagnosed by subsequent morphology, flow cytometry, and bone marrow biopsy, and subsequent successful anti-infective treatment confirmed the diagnosis. CONCLUSIONS: To date, no case of a patient diagnosed with severe infection mimicking AML has been reported. The case emphasizes the importance of an integrated diagnostic work-up, especially careful clinical observation and differential diagnosis.

Channel prediction for intelligent FSO transmission system.

Free space optical (FSO) communication has attracted significant attention due to its high transmission rate and information security. Nevertheless, the FSO link is sensitive to various weather conditions which limit its application range. Thus, research on the FSO channel plays an important role for combatting channel fading. In the paper, we first establish a FSO transmission testbed to obtain received signal strength indication (RSSI) information of optical signal. Then we utilize an environmental chamber for indoor experiments to simulate weather changes in the real world. Finally, based on the true meteorological dataset from the official department and the RSSI dataset from the experiments, we employ expanded gated recurrent unit (GRU) neural networks to implement the FSO channel prediction. The results demonstrate that the proposed scheme can achieve the prediction of FSO channel fading with a high precision, where the absolute percentage error (APE) values lower than 6.9% account for up to ninety% of results.

Elevation of long non-coding RNA GAS5 and knockdown of microRNA-21 up-regulate RECK expression to enhance esophageal squamous cell carcinoma cell radio-sensitivity after radiotherapy.

OBJECTIVE: Lately, lncRNAs have been proposed to function in the radio-sensitivity of tumor cells, yet the role of lncRNA GAS5 in that of esophageal squamous cell carcinoma (ESCC) has scarcely been studied. This study aims to examine GAS5's effects on ESCC cell radio-sensitivity. METHODS: GAS5, miR-21 and RECK expression in radiation-sensitive and radiation-resistant ESCC tissues, and TE-1 and TE-1-R cells was determined. TE-1 and TE-1-R cells were treated with pcDNA-GAS5 or miR-21 inhibitors to figure out their roles in ESCC cell proliferation, radio-sensitivity, and apoptosis via gain- and loss-of-function experiments. RESULTS: We found underexpressed GAS5 and RECK, and overexpressed miR-21 in ESCC. GAS5 elevation and miR-21 inhibition reduced viability and the colony formation ability, and enhanced the apoptosis of ESCC cells under radiation. CONCLUSION: Our study reveals that GAS5 elevation up-regulates RECK expression by down-regulating miR-21 to increase ESCC cell apoptosis after radiation therapy, thus enhancing cell radio-sensitivity.

Tunable all-optical microwave filter with high tuning efficiency.

We propose and experimentally demonstrate a continuously tunable all-optical microwave filter based on a photonic crystal (PC) L3 cavity. Due to the small cavity mode volume and prominent optical properties, the required power to arouse the cavity nonlinear effects is low as microwatt level. Moreover, the cavity resonance could be continuously shifted by finely adjusting the input powers. Therefore, under optical single sideband modulation, the frequency interval between the optical carrier and cavity resonance could be controllable. In this case, the central frequency of the microwave photonic filter (MPF) could be continuously tuned with low power consumption. To the best of our knowledge, the experimental tuning efficiency of 101.45 GHz/mW is a record for on-chip tunable all-optical microwave filters. With dominant features of all-optical control, ultra-high tuning efficiency (101.45 GHz/mW), large rejection ratios (48 dB) and compact footprint (100 µm2), the proposed silicon nanocavity is competent to process microwave signals, which has many useful applications in on-chip energy-efficient microwave photonic systems.

Plasma lipidomic signatures of spontaneous obese rhesus monkeys.

BACKGROUND: Obesity plays crucial roles in the pathogenesis of metabolic diseases such as hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes (T2D). The underlying mechanisms linking obesity to metabolic diseases are still less understandable. METHODS: Previously, we screened a group of spontaneously obese rhesus monkeys. Here, we performed a plasma lipidomic analysis of normal and obese monkeys using gas chromatography/mass spectroscopy (GC/MS) and ultra-high performance liquid chromatography/mass spectroscopy (UPLC/MS). RESULTS: In total, 143 lipid species were identified, quantified, and classified into free fatty acids (FFA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylglycerol (PG), lysophosphatidylcholine (LPC), lysophosphatidic acid (LPA), and sphingomyelin (SM). Data analysis showed that the obese monkeys had increased levels of fatty acids palmitoleic acid (C16:1) and arachidonic acid (C20:4), FFA especially palmitic acid (C16:0), as well as certain PC species and SM species. Surprisingly, the plasma level of LPA-C16:0 was approximately four-fold greater in the obese monkeys. Conversely, the levels of most PE species were obviously reduced in the obese monkeys. CONCLUSION: Collectively, our work suggests that lipids such as FFA C16:0 and 16:0-LPA may be potential candidates for the diagnosis and study of obesity-related diseases.

SILAC-based quantitative proteomic analysis of the livers of spontaneous obese and diabetic rhesus monkeys.

Type 2 diabetes mellitus (T2DM) is a severe metabolic disorder that affects more than 10% of the population worldwide. Obesity is a major cause of insulin resistance and contributes to the development of T2DM. Liver is an essential metabolic organ that plays crucial roles in the pathogenesis of obesity and diabetes. However, the underlying mechanisms of liver in the transition of obesity to diabetes are not fully understood. The nonhuman primate rhesus monkey is an appropriate animal for research of human diseases. Here, we first screened and selected three individuals of spontaneously diabetic rhesus monkeys. Interestingly, the diabetic monkeys were obese with a high body mass index at the beginning, but gradually lost their body weight during one year of observation. Furthermore, we performed stable isotope labeling with amino acids in cell culture-based quantitative proteomics to identify proteins and signaling pathways with altered expression in the liver of obese and diabetic monkeys. In total, 3,509 proteins were identified and quantified, of which 185 proteins displayed an altered expression level. Gene ontology analysis revealed that the expression of proteins involved in fatty acids ß-oxidation and galactose metabolism was increased in obese monkeys; while proteins involved in oxidative phosphorylation and branched chain amino acid (BCAA) degradation were upregulated in diabetic monkeys. In addition, we observed mild apoptosis in the liver of diabetic monkeys, suggesting liver injury at the late onset of diabetes. Taken together, our liver proteomics may reveal a distinct metabolic transition from fatty acids ß-oxidation in obese monkey to BCAA degradation in diabetic monkeys.

Photonic arbitrary waveform generator based on Taylor synthesis method.

Arbitrary waveform generation has been widely used in optical communication, radar system and many other applications. We propose and experimentally demonstrate a silicon-on-insulator (SOI) on chip optical arbitrary waveform generator, which is based on Taylor synthesis method. In our scheme, a Gaussian pulse is launched to some cascaded microrings to obtain first-, second- and third-order differentiations. By controlling amplitude and phase of the initial pulse and successive differentiations, we can realize an arbitrary waveform generator according to Taylor expansion. We obtain several typical waveforms such as square waveform, triangular waveform, flat-top waveform, sawtooth waveform, Gaussian waveform and so on. Unlike other schemes based on Fourier synthesis or frequency-to-time mapping, our scheme is based on Taylor synthesis method. Our scheme does not require any spectral disperser or large dispersion, which are difficult to fabricate on chip. Our scheme is compact and capable for integration with electronics.

Dose regimens for Chinese adult liver transplant recipients according to the genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in recipients and donors.

OBJECTIVE: Genetic polymorphisms of the P450 2C9 enzyme (CYP2C9), CYP2C19 and CYP3A5 gene are known to affect the metabolism of many drugs applied in liver transplant recipients, such as warfarin, voriconazole, and tacrolimus. The aim of this study was to recommend dose regimens for the liver recipients based on CYP2C9, CYP2C19, and CYP3A5 genotypic combinations of liver transplant recipients and their donors. METHODS: 91 adult Han Chinese liver transplant recipients who underwent orthotopic liver transplantation at Tianjin First Central Hospital, China, between 2013 and 2014 were included in this study. CYP2C9*2, CYP2C9*3, CYP2C19* 2, CYP2C19*3 and CYP3A5*3, in both liver recipients and their grafted liver were tested by polymerase chain reaction-restriction fragment length polymorphism. The dose regimens for the liver recipients were recommended based on CYP genotypic combinations of the recipients and their donors. RESULTS: In the liver transplant recipients, the frequencies of CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, and CYP3A5*3 were found to be 2.75%, 4.40%, 0%, 24.18%, and 75.27%, respectively. Allele frequencies were significantly different for CYP2C9*2, CYP2C19*2, and CYP2C19* 3 (p < 0.001) when comparing the recipients with Chinese, Eastern Asians and Caucasians populations. Most dose regimens of drugs, especially of immunosuppressive drugs, should be adjusted according to the variant metabolism activity affected by the genetic polymorphisms in both recipients and their grafted liver. CONCLUSION: The dose regimens would present considerable intraand inter-patient variability in liver transplant recipients since the genetic polymorphisms of P450 enzyme in their grafted liver might complicate the metabolism of drugs in liver transplant recipients. Giving careful consideration to the CYP genotypic combinations of transplant recipients and donors in clinical dose regimens could optimize outcomes.

Operation bandwidth optimization of photonic differentiators.

We theoretically investigate the operation bandwidth limitation of the photonic differentiator including the upper limitation, which is restrained by the device operation bandwidth and the lower limitation, which is restrained by the energy efficiency (EE) and detecting noise level. Taking the silicon photonic crystal L3 nano-cavity (PCN) as an example, for the first time, we experimentally demonstrate that the lower limitation of the operation bandwidth does exist and differentiators with different bandwidths have significantly different acceptable pulse width range of input signals, which are consistent to the theoretical prediction. Furthermore, we put forward a novel photonic differentiator scheme employing cascaded PCNs with different Q factors, which is likely to expand the operation bandwidth range of photonic differentiator dramatically.

Arbitrary waveform generator and differentiator employing an integrated optical pulse shaper.

We propose and demonstrate an optical arbitrary waveform generator and high-order photonic differentiator based on a four-tap finite impulse response (FIR) silicon-on-insulator (SOI) on-chip circuit. Based on amplitude and phase modulation of each tap controlled by thermal heaters, we obtain several typical waveforms such as triangular waveform, sawtooth waveform, square waveform and Gaussian waveform, etc., assisted by an optical frequency comb injection. Unlike other proposed schemes, our scheme does not require a spectral disperser which is difficult to fabricate on chip with high resolution. In addition, we demonstrate first-, second- and third-order differentiators based on the optical pulse shaper. Our scheme can switch the differentiator patterns from first- to third-order freely. In addition, our scheme has distinct advantages of compactness, capability for integration with electronics.

Posterior reversible encephalopathy syndrome and graft-versus-host disease after liver transplantation: a case report and review of the literature.

Case (description): A 52-year-old male patient presented with seizures on the 16th day post liver transplantation suggesting tacrolimus-associated posterior reversible encephalopathy syndrome (PRES). On the 18th day, the patient was diagnosed with graft-versus-host disease (GVHD). Calcineurin inhibitor (CNI) was stopped and the patient received 1 g methylprednisolone and 25 g immunoglobulin. However, on the 21st day, the patient's clinical condition progressively worsened and he died of multi-organ failure. GVHD could have occurred with PRES because the CNI dose was reduced. The best treatment for patients with PRES and GVHD is using immunosuppressants other than CNI. Antibody preparations and steroids could be a standard treatment.

Population pharmacokinetic analysis of tacrolimus early after Chinese pediatric liver transplantation.

OBJECTIVE: The purpose of this study was to describe the population pharmacokinetics (PK) of tacrolimus (TAC) in 52 Chinese pediatric patients early after liver transplantation. METHODS: Details of drug dose, sampling times and concentrations were collected retrospectively from routine therapeutic drug monitoring data from the first day after surgery. A total of 488 concentration data were obtained and analyzed by a nonlinear mixed-effect modeling (NONMEM) method. A number of demographic and clinical variables were tested for their influence on TAC PK parameters. RESULTS: The PK of TAC were best described by a one-compartment model with first-order absorption and elimination. Apparent clearance (CL/F) and apparent volumes of distribution (V/F) in final population model were 5.72 L/h and 131 L, respectively. The absorption rate constant (Ka) was fixed in 4.48 h-1. The inter-individual variabilities in CL/F and V/F were 13.5% and 78.1%. In the final analysis performed in all 52 patients, the post-operation day (POD) and alanine aminotransferase (ALT) influenced TAC CL/F and V/F, and total protein (TP) was the only covariate retained on V/F. CONCLUSION: A population PK model of TAC was developed in Chinese pediatric patients early after liver transplantation. It identified significant relationships between the PK of TAC and the characteristics of the patients. POD, ALT, and TP were identified as the main factors influencing the PK of TAC. The developed model could be useful to optimize individual pediatric TAC dosing regimen in routine clinical practice.

A pharmacokinetic/pharmacodynamic analysis of a standard voriconazole regimen in different CYP2C19 genotypes by Monte Carlo simulation.

OBJECTIVES: The objective of this study was to evaluate the standard voriconazole dosage regimen (maintenance dose was 200 mg bid orally) against Aspergillus infections in different CYP2C19 genotypes from a pharmacokinetic/pharmacodynamic (PK/PD) perspective. METHOD: Monte Carlo simulation (MCS) was applied to simulate 5,000 patients by integrating published pharmacokinetic (PK) parameters, variability of PK parameters on CYP2C19 genotypes and microbiological data. RESULTS: The standard dosage regimen for poor metabolizers (PM) with Aspergillus infections was effective except A. versicolor, for heterozygous extensive metabolizers (HEM), Aspergillus fumigatus, A. terreus and A. nidulans infections could be treated effectively with the standard dosage regimen; for extensive metabolizers (EM), the standard voriconazole dosage regimen failed to achieve the best outcome for the six Aspergillus spp. Increasing dose (e.g. 300 mg bid) or even changing the antifungal drug was needed for EM and most HEM patients with Aspergillus infection. CONCLUSION: Instead of using a standard dosage regimen for all patients, the voriconazole dosage regimen needs to be optimized for patients with different CYP2C19 genotypes.

Route-asymmetrical optical transmission and logic gate based on optical gradient force.

We put forward a route-asymmetrical optical transmission scheme employing optical gradient force, which means that forward and backward propagation of an optical device have different transmittance provided they are not present simultaneously. The device is based on optical gradient force between two single-mode waveguides followed by a Mach-Zehnder interferometer. Our numerical investigation shows that the forward transmittance is about -6 dB while the backward transmittance is suppressed below -20.5 dB in C + L bands. The proposed device is passive, wideband, and compatible with complementary metal-oxide semiconductor (CMOS) process. Furthermore, we demonstrate the applications of route-asymmetrical transmission such as an all-optical switch and all-optical AND gate for all-optical information processing.

Integrated programmable photonic filter on the silicon-on-insulator platform.

We propose and demonstrate a silicon-on-insulator (SOI) on-chip programmable filter based on a four-tap finite impulse response structure. The photonic filter is programmable thanks to amplitude and phase modulation of each tap controlled by thermal heaters. We further demonstrate the tunability of the filter central wavelength, bandwidth and variable passband shape. The tuning range of the central wavelength is at least 42% of the free spectral range. The bandwidth tuning range is at least half of the free spectral range. Our scheme has distinct advantages of compactness, capability for integrating with electronics.

Prognostic model of ER-positive, HER2-negative breast cancer predicted by clinically relevant indicators.

PURPOSE: To study the clinicopathological variables connected with disease-free survival (DFS) as well as overall survival (OS) in patients who are ER-positive or HER2-negative and to propose nomograms for predicting individual risk. METHODS: In this investigation, we examined 585 (development cohort) and 291 (external validation) ER-positive, HER2-negative breast cancer patients from January 2010 to January 2014. From January 2010 to December 2014, we retrospectively reviewed and analyzed 291 (external validation) and 585 (development cohort) HER2-negative, ER-positive breast cancer patients. Cox regression analysis, both multivariate and univariate, confirmed the independence indicators for OS and DFS. RESULTS: Using cox regression analysis, both multivariate and univariate, the following variables were combined to predict the DFS of development cohort: pathological stage (HR = 1.391; 95% CI = 1.043-1.855; P value = 0.025), luminal parting (HR = 1.836; 95% CI = 1.142-2.952; P value = .012), and clinical stage (HR = 1.879; 95% CI = 1.102-3.203; P value = 0.021). Endocrine therapy (HR = 3.655; 95% CI = 1.084-12.324; P value = 0.037) and clinical stage (HR = 6.792; 95% CI = 1.672-28.345; P value = 0.009) were chosen as predictors of OS. Furthermore, we generated RS-OS and RS-DFS. According to the findings of Kaplan-Meier curves, patients who are classified as having a low risk have considerably longer DFS and OS durations than patients who are classified as having a high risk. CONCLUSION: To generate nomograms that predicted DFS and OS, independent predictors of DFS in ER-positive/HER2-negative breast cancer patients were chosen. The nomograms successfully stratified patients into prognostic categories and worked well in both internal validation and external validation.

Comparison analysis of optical frequency comb generation with nonlinear effects in highly nonlinear fibers.

We compare several schemes for broadband optical frequency comb (OFC) generation based on several nonlinear effects in highly nonlinear fiber (HNLF). Cascaded four wave mixing (CFWM) and self-phase modulation (SPM) processes in HNLF are proved to be effective ways for spectrum broadening. We investigate some parameters affecting the performance of the output OFC in detail. When only CFWM occurs in the HNLF, broadband OFC can be generated with poor power flatness. When only SPM occurs in the HNLF, we obtain a 10 GHz OFC of 103 comb lines within 5-dB power deviation. When both CFWM and SPM simultaneously occur in the HNLF, we obtain a 10 GHz OFC of 143 comb lines within 4.5-dB power deviation. All the OFC generation schemes have the advantages of tunability of central wavelength and repetition frequency.

High-order photonic differentiator employing on-chip cascaded microring resonators.

We propose and experimentally demonstrate a high-order photonic differentiator using on-chip complementary metal oxide semiconductor-compatible cascaded microring resonators, including first-, second-, and third-order differentiators. All the microring resonator units have a radius of 150 µm and a free spectral range of 80 GHz. The microring resonator can implement the first-order derivative of the optical field near its critical coupling region. Hence higher-order differentiation can be obtained by cascading more microring units on a single chip. For the periodical Gaussian optical pulse injection, the average deviations of all differentiators are less than 6.2%. The differentiation of pseudo-random bit sequence signals at 5 Gbit/s is also demonstrated. Our scheme is a compact and low-power-consumption solution since the cascaded microring units are fabricated with compact size on the silicon-on-insulator substrate.

Temperature determines the shift of thermal neutral zone and influences thermogenic capacity in striped hamsters.

The thermoneutral zone (TNZ) reflects the adaptation of mammals to their natural habitat. However, it remains unclear how TNZ shifts in response to variations in ambient temperature. To test the hypothesis that ambient temperature plays a key role in determining TNZ variations between seasons, we measured metabolic rate, body temperature, and cytochrome c oxidase (COX) activity of several visceral organs in striped hamsters (Cricetulus barabensis) either acclimated to semi-natural conditions over a year, or subjected to a gradual decrease in mean temperature from 30 ± 1°C to -15 ± 1°C. The TNZ range in striped hamsters differed seasonally, with a wider TNZ and a lower lower-critical temperature in winter compared to summer. The hamsters showed a considerable leftward shift of lower-critical temperature from 30°C to 20°C after the ambient temperature of acclimation from 30°C down to -15°C, whereas the upper-critical temperature of TNZ remained fixed at 32.5°C. The resting metabolic rate in thermoneutral zone (RMRt), nonshivering thermogenesis (NST), and COX activity of brown adipose tissue, liver, skeletal muscle, brain, and kidneys, increased significantly in hamsters acclimated at lower ambient temperatures. Following acute exposure to 5°C and -15°C, hamsters acclimated to 32.5°C had significantly lower maximal NST and lower serum thyroid tri-iodothyronine (T3 ) levels compared to those kept at 23°C. These findings suggest that acclimation to the upper-critical temperature of TNZ impairs the hamsters' thermogenic capacity to cope with extreme cold temperature. Reduced ambient temperature was mainly responsible for the leftward shift of TNZ in striped hamsters, which reflects the adaptation to cold environments.