Network Pharmacology and Bioinformatics Analyses Identify the Core Genes and Pyroptosis-Related Mechanisms of Nardostachys Chinensis for Atrial Fibrillation.

BACKGROUND: Nardostachys chinensis is an herbal medicine widely used in the treatment of atrial fibrillation (AF), but the mechanism is unclear. OBJECTIVE: To explore the molecular mechanism of N. chinensis against AF. METHODS: The TCMSP was used to screen the active N. chinensis compounds and their targets. Differentially expressed genes (DEGs) for AF were identified using open-access databases. Using Venn diagrams, the cross-targets of N. chinensis, pyroptosis, and AF were obtained. The genes underwent molecular docking as well as gene set enrichment analysis (GSEA). A nomogram based on candidate genes was constructed and evaluated with the clinical impact curve. After that, the immune infiltration of the dataset was analyzed by single sample GSEA (ssGSEA). Finally, microRNAs (miRNAs) and transcription factors (TFs) were predicted based on candidate genes. RESULTS: Tumor necrosis factor (TNF) and caspase-8 (CASP8) were obtained as candidate genes by taking the intersection of DEGs, targets of N. chinensis, and pyroptosis-related genes. Tolllike receptor (TLR) and peroxisome proliferator-activated receptor (PPAR) signaling pathways were linked to candidate genes. Additionally, immune cell infiltration analysis revealed that CASP8 was associated with natural killer T cells, natural killer cells, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSC), macrophages, CD8 T cells, and CD4 T cells. Finally, miR-34a-5p and several TFs were found to regulate the expression of CASP8 and TNF. CONCLUSION: CASP8 and TNF are potential targets of N. chinensis intervention in pyroptosisrelated AF, and the TLR/NLRP3 signaling pathway may be associated with this process.

Exploring Shared Biomarkers of Myocardial Infarction and Alzheimer's Disease via Single-Cell/Nucleus Sequencing and Bioinformatics Analysis.

BACKGROUND: Patients are at increased risk of dementia, including Alzheimer's disease (AD), after myocardial infarction (MI), but the biological link between MI and AD is unclear. OBJECTIVE: To understand the association between the pathogenesis of MI and AD and identify common biomarkers of both diseases. METHODS: Using public databases, we identified common biomarkers of MI and AD. Least absolute shrinkage and selection operator (LASSO) regression and protein-protein interaction (PPI) network were performed to further screen hub biomarkers. Functional enrichment analyses were performed on the hub biomarkers. Single-cell/nucleus analysis was utilized to further analyze the hub biomarkers at the cellular level in carotid atherosclerosis and AD datasets. Motif enrichment analysis was used to screen key transcription factors. RESULTS: 26 common differentially expressed genes were screened between MI and AD. Function enrichment analyses showed that these differentially expressed genes were mainly associated with inflammatory pathways. A key gene, Regulator of G-protein Signaling 1 (RGS1), was obtained by LASSO regression and PPI network. RGS1 was confirmed to mainly express in macrophages and microglia according to single-cell/nucleus analysis. The difference in expression of RGS1 in macrophages and microglia between disease groups and controls was statistically significant (p < 0.0001). The expression of RGS1 in the disease groups was upregulated with the differentiation of macrophages and microglia. RelA was a key transcription factor regulating RGS1. CONCLUSION: Macrophages and microglia are involved in the inflammatory response of MI and AD. RGS1 may be a key biomarker in this process.

Identification of gene signatures related to hypoxia and angiogenesis in pancreatic cancer to aid immunotherapy and prognosis.

Background: One of the most diverse tumors is pancreatic cancer (PC), which makes predicting the prognosis challenging. PC development is directly related to hypoxia, angiogenesis, and immunotherapy. It is still unclear how the three features are related. Methods: The Genotype-Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA) database were employed to obtain sequencing data for healthy pancreatic tissues and PC tissues, respectively. According to the constructed hypoxic prognostic model (HPM) and angiogenic prognostic model (APM), 4 subtypes of PC were identified. Hypoxia and angiogenesis prognostic model (HAPM) was established based on differentially expressed genes (DEGs) between high-angiogenesis/high-hypoxia (HH) and low-angiogenesis/low-hypoxia (LL) subgroups. Base on the median risk score, PC patients were separated into high-risk and low-risk groups, and clinical traits, prognosis, percentage of immune cell infiltration, PD-1 expression, and the fraction of T-cell depletion were compared between the groups. Finally, the predictive accuracy of the tumor immune dysfunction and rejection (TIDE) and tumor inflammatory signature (TIS) models, as well as HAPM, was compared. Result: We analyzed the mRNA sequencing data from 178 PC tissues and 171 normal pancreatic tissues to obtain 9527 DEGs. We discovered 200 genes linked with hypoxia and 36 genes involved with angiogenesis through the literature. We found the core genes related with hypoxia and angiogenesis in PC by intersecting the DEGs of the HH and LL subgroups with those of PC via WGCNA. IL-17 signaling pathway, ECM-receptor interactions, cytokine receptor interactions, etc. were all enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) results of core genes. HAPM has good predictive efficiency, according to an evaluation of KM survival curves and ROC curves. The external dataset also validated the model's ability to anticipate outcomes. Patients in the high- and low-risk groups were compared for PD1 expression and T-cell exclusion scores, which suggested that the model might be used to forecast which PC patients might benefit from immunotherapy. Conclusions: The probable molecular processes connecting hypoxia and angiogenesis are described in this work, and a model is developed that may be utilized to forecast the prognosis for PC patients and the benefits of immunotherapy.

Microbial communities and biosynthetic pathways for the production of sulfated polysaccharides in the activated sludge system.

Sulfated polysaccharides (SP) are widely used as industrial additives and pharmaceutical intermediates. As SP can only be extracted from sea algae, making them scarce raw materials. Recently, SP have been detected and extracted from the waste activated sludge of a saline secondary wastewater treatment plant, suggesting that there are alternative primary producers and synthesis pathways of the SP within the biological activated sludge. This study aimed to identify the primary SP producers, the SP biosynthesis pathways as well as the SP production rates in different types of activated sludges cultivated anoxically and/or anaerobically, with and without the presence of sufficient sulfate. The results showed that alternating anaerobic/anoxic conditions in sludge effectively produced the SP by the ordinary heterotrophic organisms (OHOs). The synthesis pathways for the three most common bioactive SP viz. fucoidan, carrageen, and heparin, were identified and elucidated at both the substrate and enzymatic levels. The Western Blot analyses revealed key enzymes for the SP synthesis (e.g., GDP-L-fucose-synthetase, GDP-fucose-pyrophosphorylase, ß-1,4-galactosyltransferase), when sulfate was sufficient (>170 mg S/L) under an alternating anaerobic/anoxic conditions. In contrast, the absence of sulfate suppressed the SP production during the initial step of the SP generation. The synthesis of the SP in the sulfate-reducing (anaerobic) sludge was suppressed by the enzymatic inhibition, when sulfide exceeded 160 mg S/L, due to the competition for energy between the SP synthesis and sulfide detoxification. However, in the case of the sulfide-oxidizing sludge both the organic carbon and metabolism energy deficiencies inhibited the SP production. The findings of this study expand the understandings of the SP synthesis in the activated sludge under different operating conditions, including different sulfate levels.

Revealing the methanogenic pathways for anaerobic digestion of key components in food waste: Performance, microbial community, and implications.

Anaerobic digestion (AD) process is widely considered the most sustainable technology for food waste (FW) disposal due to its advantage of biomethane recovery and beneficial environmental consequences. However, the effects of key components in FW (i.e. starchy food, vegetables, fruits, and meats) on AD process and their methanogenic pathways remain unclear. In this study, the biochemical methane potential (BMP) of cooked rice, cabbage, banana peel, pork and local FW was 288, 283, 254, 630, and 476 NmL CH4/g VSadded, with t80 (time required for 80% methane produced) of 3, 9, 3, 11 and 11 days, respectively. Kinetic analysis suggested diverse hydrolysis rates (0.104-0.679 d-1) and specific methane yields (39-119 NmL CH4/g VSadded/d). The relative abundances of key methanogens in the reactors were diverse, leading to the variation in acetoclastic and hydrogenotrophic methanogenic pathways. This study provides fundamental information for the operation of AD systems with different FW compositions.

Anaerobic digestion of saline waste activated sludge and recovering raw sulfated polysaccharides.

This study investigated a new bioresource technology of recovering raw chemicals of sulfated polysaccharides (SPs) from the digested saline waste activated sludge (WASsaline) that naturally contained 3-30% (w/w) of SPs. Two bench-scale anaerobic digestion (AD) experiments were conducted under mesophilic and thermophilic conditions; the effectiveness of extracting SPs from digested WASsaline and the biochemical characteristics of SPs were examined. After 20-days of digestion, the results showed that approximately 54 - 58% of initial total SPs in WASsaline were recoverable, in which 38 - 48% in solid digestate and 10-15% in liquid supernatant). The extracted raw chemicals of SPs were proven to be of high purity (>80%) and demonstrating significant properties such as anti-inflammation, anti-oxidation, and anti-coagulation for potential pharmaceutical-like application.

Recovery of high-value and scarce resources from biological wastewater treatment: Sulfated polysaccharides.

Recovering materials with high value and increasing market demand from sewage and/or sludge is becoming more attractive than recovering traditional resources such as nutrients and biogas. Sulfated polysaccharides (SPs) are valuable and scarce raw materials that can only be produced from marine algae and a few types of animal tissues. This study evaluated if SPs are present in activated sludge obtained from saline sewage with a high level of sulfates present. The presence of SPs-containing extracellular polymeric substances (EPS) was confirmed and quantified for both sludge from lab-scale reactors and full-scale plants for the first time. SPs in the sludge of a lab-scale reactor operated under alternating aerobic/anoxic conditions with 500 mg/L sulfate in the influent (which is typical of Hong Kong saline sewage) reached 342.8 ±â€¯0.3% mg/gVSS, and sludge taken from a full-scale saline wastewater treatment plant (WWTP) contained 418.1 ±â€¯0.4% mg/gVSS of SPs. Purity of the extracted SPs was comparable to that of commercial industrial-grade products. Key bioactivities of SPs (i.e. fucoidan, carrageenan and heparin), namely anti-angiogenesis, anticoagulant and antioxidant, were confirmed after extraction and purification. Interestingly, operating conditions had a strong influence on the contents and types of SPs synthesized in sludge as well as its bioactivities. Although the detailed synthetic pathways of SPs in activated sludge remain unclear, the current study has made a first attempt to recover a high-value scarce resource from biological wastewater treatment.

The role of sulfate in aerobic granular sludge process for emerging sulfate-laden wastewater treatment.

Sulfate-rich wastewaters pose a major threat to mainstream wastewater treatment due to the unpreventable production of sulfide and associated shift in functional bacteria. Aerobic granular sludge could mitigate these challenges in view of its high tolerance and resilience against changes in various environmental conditions. This study aims to confirm the feasibility of aerobic granular sludge in the treatment of sulfate containing wastewater, investigate the impact of sulfate on nutrient removal and granulation, and reveal metabolic relationships in the above processes. Experiments were conducted using five sequencing batch reactors with different sulfate concentrations operated under alternating anoxic/aerobic condition. Results showed that effect of sulfate on chemical oxygen demand (COD) removal is negligible, while phosphate removal was enhanced from 12% to 87% with an increase in sulfate from 0 to 200 mg/L. However, a long acclimatization of the biomass (more than 70 days) is needed at a sulfate concentration of 500 mg/L and a total deterioration of phosphate removal at 1000 mg/L. Batch tests revealed that sulfide promoted volatile fatty acids (VFAs) uptake, producing more energy for phosphate uptake when sulfate concentrations were beneath 200 mg/L. However, sulfide detoxification became energy dominating, leaving insufficient energy for Polyhydroxyalkanoate (PHA) synthesis and phosphate uptake when sulfate content was further increased. Granulation accelerated with increasing sulfate levels by enhanced production of N-Acyl homoserine lactones (AHLs), a kind of quorum sensing (QS) auto-inducer, using S-Adenosyl Methionine (SAM) as primer. The current study demonstrates interactions among sulfate metabolism, nutrients removal and granulation, and confirms the feasibility of using the aerobic granular sludge process for sulfate-laden wastewaters treatment with low to medium sulfate content.

Ultrahigh-speed Si-integrated on-chip laser with tailored dynamic characteristics.

For on-chip interconnects, an ideal light source should have an ultralow energy consumption per bandwidth (operating en-ergy) as well as sufficient output power for error-free detection. Nanocavity lasers have been considered the most ideal for smaller operating energy. However, they have a challenge in obtaining a sufficient output power. Here, as an alternative, we propose an ultrahigh-speed microcavity laser structure, based on a vertical cavity with a high-contrast grating (HCG) mirror for transverse magnetic (TM) polarisation. By using the TM HCG, a very small mode volume and an un-pumped compact optical feedback structure can be realised, which together tailor the frequency response function for achieving a very high speed at low injection currents. Furthermore, light can be emitted laterally into a Si waveguide. From an 1.54-µm optically-pumped laser, a 3-dB frequency of 27 GHz was obtained at a pumping level corresponding to sub-mA. Using measured 3-dB frequen-cies and calculated equivalent currents, the modulation current efficiency factor (MCEF) is estimated to be 42.1 GHz/mA1/2, which is superior among microcavity lasers. This shows a high potential for a very high speed at low injection currents or avery small heat generation at high bitrates, which are highly desirable for both on-chip and off-chip applications.

Threshold Characteristics of Slow-Light Photonic Crystal Lasers.

The threshold properties of photonic crystal quantum dot lasers operating in the slow-light regime are investigated experimentally and theoretically. Measurements show that, in contrast to conventional lasers, the threshold gain attains a minimum value for a specific cavity length. The experimental results are explained by an analytical theory for the laser threshold that takes into account the effects of slow light and random disorder due to unavoidable fabrication imperfections. Longer lasers are found to operate deeper into the slow-light region, leading to a trade-off between slow-light induced reduction of the mirror loss and slow-light enhancement of disorder-induced losses.

Thermal analysis of line-defect photonic crystal lasers.

We report a systematic study of thermal effects in photonic crystal membrane lasers based on line-defect cavities. Two material platforms, InGaAsP and InP, are investigated experimentally and numerically. Lasers with quantum dot layers embedded in an InP membrane exhibit lasing at room temperature under CW optical pumping, whereas InGaAsP membranes only lase under pulsed conditions. By varying the duty cycle of the pump beam, we quantify the heating induced by optical pumping in the two material platforms and compare their thermal properties. Full 3D finite element simulations show the spatial temperature profile and are in good agreement with the experimental results concerning the thermal tolerance of the two platforms.

Demultiplexing of OTDM-DPSK signals based on a single semiconductor optical amplifier and optical filtering.

We propose and demonstrate the use of a single semiconductor optical amplifier (SOA) and optical filtering to time demultiplex tributaries from an optical time division multiplexing-differential phase shift keying (OTDM-DPSK) signal. The scheme takes advantage of the fact that phase variations added to the target channel by cross-phase modulation from the control signal are effectively subtracted in the differential demodulation scheme employed for DPSK signals. Demultiplexing from 80 to 40 Gbit/s is demonstrated with moderate power penalty using an SOA with recovery time twice as long as the bit period at 80 Gbit/s. Large dynamic ranges for the input power and SOA current are experimentally demonstrated. The scheme is expected to be scalable toward higher bit rates.

Simple and efficient methods for the accurate evaluation of patterning effects in ultrafast photonic switches.

Although patterning effects (PEs) are known to be a limiting factor of ultrafast photonic switches based on semiconductor optical amplifiers (SOAs), a simple approach for their evaluation in numerical simulations and experiments is missing. In this work, we experimentally investigate and verify a theoretical prediction of the pseudo random binary sequence (PRBS) length needed to capture the full impact of PEs. A wide range of SOAs and operation conditions are investigated. The very simple form of the PRBS length condition highlights the role of two parameters, i.e. the recovery time of the SOAs as well as the operation bit rate. Furthermore, a simple and effective method for probing the maximum PEs is demonstrated, which may relieve the computational effort or the experimental difficulties associated with the use of long PRBSs for the simulation or characterization of SOA-based switches. Good agrement with conventional PRBS characterization is obtained. The method is suitable for quick and systematic estimation and optimization of the switching performance.

Wideband 360 degrees microwave photonic phase shifter based on slow light in semiconductor optical amplifiers.

In this work we demonstrate for the first time, to the best of our knowledge, a continuously tunable 360 degrees microwave phase shifter spanning a microwave bandwidth of several tens of GHz (up to 40 GHz). The proposed device exploits the phenomenon of coherent population oscillations, enhanced by optical filtering, in combination with a regeneration stage realized by four-wave mixing effects. This combination provides scalability: three hybrid stages are demonstrated but the technology allows an all-integrated device. The microwave operation frequency limitations of the suggested technique, dictated by the underlying physics, are also analyzed.

Widely tunable microwave phase shifter based on silicon-on-insulator dual-microring resonator.

We propose and demonstrate tunable microwave phase shifters based on electrically tunable silicon-on-insulator microring resonators. The phase-shifting range and the RF-power variation are analyzed. A maximum phase-shifting range of 0-600 degrees is achieved by utilizing a dual-microring resonator. A quasi-linear phase shift of 360 degrees with RF-power variation lower than 2dB and a continuous 270 degrees phase shift without RF-power variation at a microwave frequency of 40GHz are also demonstrated.

Optically fed microwave true-time delay based on a compact liquid-crystal photonic-bandgap-fiber device.

An electrically tunable liquid-crystal, photonic-bandgap-fiber-device-based, optically fed microwave, true-time delay is demonstrated with the response time in the millisecond range. A maximum electrically controlled phase shift of around 70 degrees at 15 GHz and an averaged 12.9 ps true-time delay over the entire modulation frequency range of 1-15 GHz are obtained.

Photonic generation of ultrawideband monocycle and doublet pulses by using a semiconductor-optical-amplifier-based wavelength converter.

Photonic generation of ultrawideband (UWB) monocycle and doublet pulses is experimentally demonstrated using a cascaded electroabsorption modulator (EAM) and semiconductor optical amplifier by exploiting a combination of cross-absorption modulation and cross-gain modulation. The polarities and shapes of UWB monocycle and doublet pulses can be simply controlled using an optical time-delay controller and the reverse voltage applied to the EAM. The corresponding measured rf spectra meet the UWB criteria.

Microwave phase shifter with controllable power response based on slow- and fast-light effects in semiconductor optical amplifiers.

We suggest and experimentally demonstrate a method for increasing the tunable rf phase shift of semiconductor waveguides while at the same time enabling control of the rf power. This method is based on the use of slow- and fast-light effects in a cascade of semiconductor optical amplifiers combined with the use of spectral filtering to enhance the role of refractive index dynamics. A continuously tunable phase shift of approximately 240 degrees at a microwave frequency of 19 GHz is demonstrated in a cascade of two semiconductor optical amplifiers, while maintaining an rf power change of less than 1.6 dB. The technique is scalable to more amplifiers and should allow realization of an rf phase shift of 360 degrees.

The role of input chirp on phase shifters based on slow and fast light effects in semiconductor optical amplifiers.

We experimentally investigate the initial chirp dependence of slow and fast light effects in a semiconductor optical amplifier followed by an optical filter. It is shown that the enhancement of the phase shift due to optical filtering strongly depends on the chirp of the input optical signal. We demonstrate approximately 120 degrees phase delay as well as approximately 170 degrees phase advance at a microwave frequency of 19 GHz for different optimum values of the input chirp. The experimental results are shown to be in good agreement with numerical results based on a four-wave mixing model. Finally, a simple physical explanation based on an analytical perturbative approach is presented.

Enhancing light slow-down in semiconductor optical amplifiers by optical filtering.

We show that the degree of light-speed control in a semiconductor optical amplifier can be significantly extended by the introduction of optical filtering. We achieve a phase shift of approximately 150 degrees at 19 GHz modulation frequency, corresponding to a several-fold increase of the absolute phase shift as well as the achievable bandwidth. We show good quantitative agreement with numerical simulations, including the effects of population oscillations and four-wave mixing, and provide a simple physical explanation based on an analytical perturbation approach.