Serum metabolic profile evidence for relationship between schizophrenia and depression: An untargeted metabolomics.

Given the genetic and clinical overlap observed between schizophrenia and depression, the present study was to identify the similarities and differences in serum metabolic profiles between patients with schizophrenia and depression. Global metabolomics research methods based on UHPLC-QTOF-MS/MS were performed. A total of 113 and 118 differential metabolites were screened and identified in depression and schizophrenia groups, respectively, as compared to health control; among those, 94 differential metabolites were shared by both. Pathway analysis indicated arginine and proline metabolism, alanine, aspartate, and glutamate metabolism were two significant metabolic pathways both in depression and schizophrenia groups as compared with health control groups, respectively. Similarly, 77 differential metabolites were identified between depression and schizophrenia groups, in which, serum N-acetylglutamine and isovalerylglycine levels showed significant differences between patients with depression and schizophrenia with p values less than 0.001 and without significant outliers. Sphingolipid metabolism was identified as a significant metabolic pathway distinguishing between depression and schizophrenia groups based on pathway analysis. Conclusively, common alterations in arginine and proline metabolism, alanine, aspartate, and glutamate metabolism were observed in patients with schizophrenia and depression; whereas differences in serum N-acetylglutamine and isovalerylglycine levels as well as sphingolipid metabolism were discovered between the two categories of patients.

Development of a pre-column derivatization ultra-high-performance liquid chromatography method for polysaccharide and monosaccharide quantification in Lycium barbarum.

Given the limited specificity and accuracy observed in the current official colorimetric quantification of polysaccharide in Lycium barbarum, our study aims to establish a novel, specific, accurate, and economic pre-column derivatization ultra-high-performance liquid chromatography (UHPLC) method for determining the monosaccharide and polysaccharide content in L. barbarum. The optimization of extraction, hydrolysis, and derivatization (using 1-phenyl-3-methyl-5-pyrazolone) processes for polysaccharide from L. barbarum was conducted initially, followed by separation of nine monosaccharides within 20 min using UHPLC with a C18 column. Subsequently, a novel method known as quantitative analysis of multiple components by single marker was developed, utilizing either additive 2-deoxy-D-ribose or any monosaccharide present in the sample as a single reference standard to simultaneously detect the contents of polysaccharide and nine monosaccharides in L. barbarum. To validate the accuracy of the established method, the quantitative results of our approach were compared to both external and internal standard method methods. The minimal relative errors in the quantitative determination of monosaccharides among the three methods confirmed the dependability of the method. By analyzing 20 batches of L. barbarum samples, D-galacturonic acid exhibited the highest content and the polysaccharide levels ranged from 3.02 to 13.04 mg/g. All data implied the specificity and accuracy of the method.

Integrating untargeted and targeted LC-MS-based metabolomics to identify the serum metabolite biomarkers for tuberculosis.

Given the limitations of untargeted metabolomics in precise metabolite quantification, our current research employed a novel approach by integrating untargeted and targeted metabolomics utilizing ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) to analyze the metabolic profile and potential biomarkers for tuberculosis (TB). A cohort of 36 TB patients and 36 healthy controls (HC) was enlisted to obtain serum samples. Multivariate pattern recognition and univariate statistical analysis were employed to screen and elucidate the differential metabolites, whereas dot plots and receiver operating characteristic (ROC) curves were established for the identification of potential biomarkers of TB. The results indicated a distinct differentiation between the two groups, identifying 99 metabolites associated with five primary metabolic pathways in relation to TB. Of these, 19 metabolites exhibited high levels of sensitivity and specificity, as evidenced by the area under curve values approaching 1. Following targeted quantitative analysis, three potential metabolites, namely, L-asparagine, L-glutamic acid, and arachidonic acid, were demonstrated excellent discriminatory ability as evidenced by the results of the ROC curve, dot plots, and random forest model. Particularly noteworthy was the enhanced diagnostic efficacy of the combination of these three metabolites compared to singular biomarkers, suggesting their potential utility as serum biomarkers for TB diagnosis.

Harmonic phase-sensitive detection for quartz-enhanced photoacoustic-thermoelastic spectroscopy.

Quartz tuning fork (QTF)-based techniques of photoacoustic spectroscopy and thermoelastic spectroscopy play a significant role in trace gas sensing due to unique high sensitivity and compactness. However, the stability of both techniques remains plagued by the inevitable and unpredictable laser power variation and demodulation phase variation. Herein, we investigate the phase change of a QTF when integrating both techniques for enhanced gas sensing. By demonstrating harmonic phase-sensitive methane detection as an example, we achieve stable gas measurement at varying laser power (2.4-9.4 mW) and varying demodulation phase (-90-90°). Besides, this method shows more tolerance to resonant frequency drift, contributing to a small signal fluctuation of ≤ 6.4 % over a wide modulation range (>10 times of the QTF bandwidth). The realization of harmonic-phase detection allows strengthening the stability of QTF-based sensors in a simple manner, especially when stable parameters, such as laser power, demodulation phase, even resonant frequency, cannot always be maintained.

L-shaped association between serum chloride levels with 90-day and 365-day all-cause mortality in critically ill patients with COPD: a retrospective cohort study.

This study aimed to investigate the association between serum chloride levels and all-cause mortality in critically ill patients with chronic obstructive pulmonary disease (COPD). Data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were extracted for analysis. Demographic information, laboratory results, medical histories, vital signs, and prognosis-related data were collected. Cox proportional hazard models were used to assess the relationship between serum chloride levels and 90-day and 365-day mortality. Subgroup analyses were conducted to explore potential interactions between serum chloride levels and various factors. The study included patients with a median age of 72.00 years, of whom 52.39% were male. Higher quartiles of serum chloride levels were associated with significantly lower levels of weight, RBC, platelet, hemoglobin, and other variables (P < 0.05), accompanied by lower 90-day and 365-day mortality (P < 0.05). Cox proportional hazard model indicated that the risk of death was significantly lower in the fourth quartile of serum chloride levels compared with the first quartile after adjusting for confounders (90-day HR = 0.54, 365-day HR = 0.52, both P < 0.05). An L-shape relationship was observed, with risks of death decreasing as serum chloride levels increased, although the magnitude decreased when levels reached 102 mmol/L. This study demonstrated an independent L-shaped association between serum chloride levels and all-cause mortality in critically ill patients with COPD. This finding helps us to understand the prognostic value of serum chloride levels in critically ill patients with COPD.

Serum metabolomics reveals the metabolic profile and potential biomarkers of ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease that significantly impairs physical function in young individuals. However, the identification of radiographic changes in AS is frequently delayed, and the diagnostic efficacy of biomarkers like HLA-B27 remains moderately effective, with unsatisfactory sensitivity and specificity. In contrast to existing literature, our current experiment utilized a larger sample size and employed both untargeted and targeted UHPLC-QTOF-MS/MS based metabolomics to identify the metabolite profile and potential biomarkers of AS. The results indicated a notable divergence between the two groups, and a total of 170 different metabolites were identified, which were associated with the 6 primary metabolic pathways exhibiting a correlation with AS. Among these, 26 metabolites exhibited high sensitivity and specificity with area under curve (AUC) values greater than 0.8. Subsequent targeted quantitative analysis discovered 3 metabolites, namely 3-amino-2-piperidone, hypoxanthine and octadecylamine, exhibiting excellent distinguishing ability based on the results of the ROC curve and the Random Forest model, thus qualifying as potential biomarkers for AS. Summarily, our untargeted and targeted metabolomics investigation offers novel and precise insights into potential biomarkers for AS, potentially enhancing diagnostic capabilities and furthering the comprehension of the condition's pathophysiology.

A comparative UHPLC-QTOF-MS/MS-based metabolomics approach reveals the metabolite profiling of wolfberry sourced from different geographical origins.

Wolfberry, known as Goji berry, is the fruit of Lycium barbarum L. (LB). As a famous functional food and TCM, the cost and efficacy of LB are closely linked to its geographical origin. The present study aimed to establish an effective method for distinguishing LB from different geographical origins. By employing UHPLC-QTOF-MS/MS combined with multivariate analysis, the metabolite profiling of LB (199 batches) obtained from Ningxia, Gansu, Qinghai, and Xinjiang, was evaluated. The results demonstrated that the method effectively distinguished LB from the four regions, with a total of 148 different metabolites being detected. Subsequent assessment using heat maps, Venn analysis, receiver operating characteristics curves and dot plots revealed 21 of these metabolites exhibited exceptional sensitivity and specificity, with under-curve values approaching 1, thus indicating their potential as biomarkers for LB. These findings strongly support the suitability of UHPLC-QTOF-MS/MS-based metabolomics as an effective approach to identify the source of LB.

Pharmacokinetic, Tissue Distribution, Metabolite, and Toxicity Evaluation of the Matrine Derivative, (6aS, 10S, 11aR, 11bR, 11cS)-10-Methylaminododecahydro-3a, 7a-Diaza-benzo (de) Anthracene-8-thione.

MASM, a structurally modified derivative of matrine, exhibits superior efficacy in reducing inflammation and liver injury in rats when compared to matrine. This study aims to investigate the pharmacokinetic profile and acute toxicity of MASM. Pharmacokinetic results revealed that MASM exhibited rapid absorption, with a Tmax ranging from 0.21 ± 0.04 h to 1.31 ± 0.53 h, and was eliminated slowly, with a t1/2 of approximately 10 h regardless of the route of administration (intravenous, intraperitoneal, or intragastric). The absolute intragastric bioavailability of MASM in rats was determined to be 44.50%, which was significantly higher than that of matrine (18.5%). MASM was detected in all rat tissues including the brain, and through the utilization of stable isotope-labeled compounds and standard references, ten metabolites of MASM, namely sophocarpine, oxysophocarpine, and oxymatrine, were tentatively identified. The LD50 of MASM in mice was determined to be 94.25 mg/kg, surpassing that of matrine (83.21 mg/kg) based on acute toxicity results. Histopathological and biochemical analysis indicated no significant alterations in the primary organs of the low- to medium-dosage groups of MASM. These findings provide valuable insights into the efficacy and toxicity profile of MASM.

Analysis of size-dependent optoelectronic properties of red AlGaInP micro-LEDs.

We have theoretically investigated the size-dependent optoelectronic properties of InGaP/AlGaInP-based red micro-LEDs through an electro-optical-thermal coupling model. The model considers thermal effects due to current crowding near the electrodes, non-thermal efficiency droop due to electron leakage, and etch defects on the LED sidewall. Sidewall defects reduce the carrier concentration at the light-emitting surface's edge and exacerbate the current crowding effect. In addition, p-side electron leakage at high current densities is the leading cause of the efficiency droop of AlGaInP LEDs. In contrast, the effect of temperature on the overall efficiency degradation of LEDs is even more significant.

Exploring the therapeutic potential of natural compounds modulating the endocannabinoid system in various diseases and disorders: review.

Cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes involved in the biosynthesis and degradation of the endocannabinoids make up the endocannabinoid system (ECS). The components of the ECS are proven to modulate a vast bulk of various physiological and pathological processes due to their abundance throughout the human body. Such discoveries have attracted the researchers' attention and emerged as a potential therapeutical target for the treatment of various diseases. In the present article, we reviewed the discoveries of natural compounds, herbs, herbs formula, and their therapeutic properties in various diseases and disorders by modulating the ECS. We also summarize the molecular mechanisms through which these compounds elicit their properties by interacting with the ECS based on the existing findings. Our study provides the insight into the use of natural compounds that modulate ECS in various diseases and disorders, which in turn may facilitate future studies exploiting natural lead compounds as novel frameworks for designing more effective and safer therapeutics.

SAW Filters on LiNbO3/SiC Heterostructure for 5G n77 and n78 Band Applications.

The 5G communication system has experienced a substantial expansion of the spectrum, which poses higher requirements to radio frequency (RF) filters in enhancing their operating frequencies and bandwidths. To this end, this work focused on solving the filtering scheme for challenging 5G n77 and n78 bands and successfully implemented the corresponding spurious-free surface acoustic wave (SAW) filters exploiting large-coupling shear horizontal (SH) modes based on X-cut LiNbO3 (LN)/silicon carbide (SiC) heterostructure. Here, we initially investigated the suppression methods for spurious modes theoretically and experimentally and summarized an effective normalized LN thickness ( [Formula: see text] range of 0.15-0.30 for mitigating Rayleigh modes and higher order modes, as well as tilted interdigital transducers (IDT) by about 24° for eliminating transverse modes. Resonators with wavelengths ( λ) from 0.95 to [Formula: see text] were also fabricated, showing a scalable resonance from 2.48 to 4.21 GHz without any in-band ripple. Two filters completely meeting 5G n77 and n78 full bands were finally constructed, showing center frequencies ( fc) of 3763 and 3560 MHz, 3-dB fractional bandwidths (FBW) of 24.8% and 15.6%, and out-of-band (OoB) rejections of 18.7 and 28.1 dB, respectively. This work reveals that X-LN/SiC heterostructure is a promising underpinning material for SAW filters in 5G commercial applications.

Microfluidic static droplet generated quantum dot arrays as color conversion layers for full-color micro-LED displays.

This paper presents an easy and intact process based on microfluidics static droplet array (SDA) technology to fabricate quantum dot (QD) arrays for full-color micro-LED displays. A minimal sub-pixel size of 20 µm was achieved, and the fluorescence-converted red and green arrays provide good light uniformity of 98.58% and 98.72%, respectively.

Dual-Passband SAW Filter Based on a 32°YX-LN/SiO2/SiC Multilayered Substrate.

To meet the demands of highly integrated and miniaturized radio frequency front-end (RFFE) modules, multi-passband filters which support multi-channel compounding come to the foreground. In this work, we proposed a new design of a dual-passband surface acoustic wave (SAW) filter based on a 32°YX-LiNbO3 (LN)/SiO2/SiC multilayered structure. The filter is of a standalone ladder topology and comprises dual-mode resonators, in which the shear horizontal (SH) mode and high-order SH mode are simultaneously excited through electrode thickness modulation. The impact of electrode thickness on the performance of the dual-mode resonator was systematically investigated by the finite element method (FEM), and resonators were prepared and verified the simulation results. The electromechanical coupling coefficients (K2) of the SH modes are 15.1% and 17.0%, while the maximum Bode-Q (Qmax) values are 150 and 247, respectively, for the fabricated resonators with wavelengths of 1 µm and 1.1 µm. In terms of the high-order SH modes in these resonators, the K2 values are 9.8% and 8.4%, and Qmax values are 190 and 262, respectively. The fabricated dual-band filter shows the center frequencies (fc) of 3065 MHz and 4808 MHz as two bands, with 3-dB fractional bandwidths (FBW) of 5.1% and 5.9%, respectively. Such a dual-band SAW filter based on a conventional ladder topology is meaningful in terms of its compact layout and diminished area occupancy. This work provides a promising avenue to constitute a high-performance dual-passband SAW filter for sub-6 GHz RF application.

Micro-nano fiber-assisted active photoacoustic spectroscopy for gas sensing.

We report on the development of all-fiber active photoacoustic spectroscopy, where active photoacoustic effect is generated by embedding a micro-nano fiber inside a fiber laser resonator to exploit the evanescent field of the high intracavity power. Acetylene detection at 1530.37 nm was selected for gas sensing demonstration. With a small diameter of 1.1 µm, the tapped fiber exploited ∼20% intracavity power for the evanescent-wave photoacoustic excitation, while only introduced a low intrinsic cavity loss of 0.08 dB. Our sensor achieved a minimum detection limit of 1 ppm at an integration time of 10 s, which can be improved to 73 ppb at 1000 s benefited from the high system stability. The sensing dynamic range was determined to be more than five orders. This spectroscopic technique combines fiber laser, photoacoustic spectroscopy, and fiber evanescent-wave absorption to achieve gas sensing with high flexibility, low optical noise, and easy optical alignment. Current limitations were discussed in detail to explore feasible ways to improve the performance in response time, dynamic range and sensitivity.

Serum and brain metabolomic study reveals the protective effects of Bai-Mi-Decoction on rats with ischemic stroke.

Bai-Mi-Decoction (BMD), which is composed of Eugenia caryophyllata, Myristica fragrans, Moschus berezovskii, and Crocus sativu, is a characteristic TCM multi-herb formula for brain disease. However, the mechanism of protective effects of BMD on ischemic stroke (IS) still has not been clarified. Our study is designed to elucidate the protective effects and underlying mechanisms of BMD on IS by employing pharmacodynamic and serum and brain metabolomic methods. In this experiment, 90 adult male Sprague-Dawley rats were randomly divided into the sham operation group (SHAM, vehicle), middle cerebral artery occlusion-reperfusion injury model group (MCAO/R, vehicle), positive control group (NMDP, 36 mg/kg/day nimodipine), and low (BMDL, 0.805 g/kg/day), moderate (BMDM, 1.61 g/kg/day), and high (BMDH, 3.22 g/kg/day) dosage of BMD prophylactic administration groups. The drugs were dissolved in 0.5% CMC-Na and orally administered to rats with equal volumes (100 g/ml body weight) once a day for 14 consecutive days. Neurological deficit score, cerebral infarct volume, change in body weight, and serum NO, SOD, MDA, GSH, and GSSG levels were determined. Pathological abnormalities using hematoxylin and eosin staining and the expression of VEGF, caspase-3, and NF-κB were analyzed. Furthermore, serum and brain metabolic profiles were explored to reveal the underlying mechanism using UHPLC-QTOF-MS/MS technology. BMD exhibited significant neuroprotective effects on MCAO/R rats. As compared to the MCAO/R model group, it could reduce the neurological deficit score and cerebral infarct volume, increase body weight, enhance GSH, SOD, and GSSG activities, and decrease NO and MDA contents of MCAO/R rats. Meanwhile, BMD could ameliorate pathological abnormalities of MCAO/R rats through reducing neuronal loss, vacuolated spaces, shrunken neurons, and destructed neuron structure, as well as regulating the expression of VEGF, caspase-3, and NF-κB. UHPLC-QTOF-MS/MS-based serum and brain metabolomics analysis found a total of 53 differential metabolites between MCAO/R and SHAM groups, of which 30 were significantly regulated by BMD intervention, and further metabolic pathway analysis implied that the protective effects were mainly associated with amino acid and glycerophospholipid metabolisms. Our pharmacodynamic and metabolomic results revealed the neuroprotective effects of BMD on MCAO/R rats, and the underlying mechanisms were probably related to amino acid and glycerophospholipid metabolisms.

The Combination of Individual Herb of Mi-Jian-Chang-Pu Formula Exerts a Synergistic Effect in the Treatment of Ischemic Stroke in Rats.

Mi-Jian-Chang-Pu formula (MJCPF), composed of Crocus sativus L. and Acorus tatarinowii Schott, is a well-known TCM for treatment of hemiplegia, facial paralysis as well as language dysfunction caused by stroke both in ancient and modern times. By using pharmacodynamics, pharmacokinetics, and metabolomics, our present study discusses whether the combination of individual herbs or major active components of MJCPF possess synergistic neuroprotective effects against ischemic stroke (IS). 108 adult male Sprague-Dawley rats were randomly and equally divided into 9 groups, including sham group (N, vehicle), middle cerebral artery occlusion (MCAO) model group (M, vehicle), positive group (P, 36 mg/kg/day nimodipine), crocin I (A1, 40 mg/kg/day), ß-asarone (B1, 15 mg/kg/day), crocin I + ß-asarone (A1B1, 55 mg/kg/day), C. sativus (A, 580 mg/kg/day), A. tatarinowii (B, 480 mg/kg/day), and C. sativus + A. tatarinowii, also named MJCPF (AB, 1060 mg/kg/day) groups. All drugs were orally administered to rats once a day for 14 consecutive days. Neurological deficit score, cerebral infarct volume, body weight change, TTC, HE and IHC staining, behavioral evaluation, metabolic profiles, and pharmacokinetic parameters were determined. MCAO led to severe brain damage including large infarct volume, more severe brain tissue injury, and worse neurological function as compared to the sham rats. All treatment groups showed a significant neuroprotective effect on MCAO rats. Furthermore, the pharmacodynamics' results demonstrated that MJCPF had a synergistic effect evidenced by small infarct volume, more regular arrangement of neuronal cells, and more improved neural function, and the levels of inflammatory factors were closer to normality. A total of 53 differential metabolites between MCAO and sham groups were screened by integration of serum and brain metabolisms, all of which were restored at varying degrees in treatment. PCA and PLS-DA analysis showed that the levels of differential metabolites treated with MJCPF were closer to the sham group than the individual herb and single compound alone or A1B1 combination. The pharmacokinetic parameters further verified the above results that MJCPF could synergistically promote drug absorption greater than others. Our integrated pharmacodynamics, metabolomics, and pharmacokinetic approach reveals the synergistic effect of MJCPF on treatment of IS, which powerfully contribute to the understanding of scientific connotation of TMC formula.

A General FEM Model for Analysis of Third-Order Nonlinearity in RF Surface Acoustic Wave Devices Based on Perturbation Theory.

This article presents a general-purpose model that enables efficient and accurate calculation of third-order nonlinear signals in surface acoustic wave (SAW) devices. This model is based on piezoelectric constitutive equations combined with perturbation theory, which can be analyzed by full finite element method (FEM). For validation, third-order harmonic (H3) responses and intermodulation distortions (IMD3) in SAW resonators are simulated, and their calculation results fit well to experimental data in the literature. Then, the generation mechanisms of the third-order nonlinearity in SAW resonators are discussed. The dominant generation mechanisms for different nonlinear signals and the relation between electrode materials and H3 peak magnitude are revealed, which provides an important guideline for further nonlinear suppression.

Micropore filling fabrication of high resolution patterned PQDs with a pixel size less than 5 µm.

PQDs are promising color converters for micro-LED applications. Here we report the micropore filling fabrication of high resolution patterned PQDs with a pixel size of 2 µm using a template with SU8 micropores.

Fractional Bandwidth up to 24% and Spurious Free SAW Filters on Bulk 15°YX-LiNbO3 Substrates Using Thickness-Modulated IDT Structures.

To cope with ubiquitous wireless connectivity and the increased and faster data delivery in 5G communication, surface acoustic wave (SAW) filters are progressively requiring wider bandwidths. Conventional bulk 15°YX-LiNbO3 substrates with a large coupling coefficient (K2) are attractive for the low-cost mass production of wideband SAW filters, but these generally suffer from spurious responses, limiting their practical application. In this work, a novel and simple SAW configuration is proposed that uses thickness-modulated interdigital transducer (IDT) structures to overcome the limitations set by spurious responses. Different from the conventional design where the thicknesses of the IDT electrodes in the series and parallel resonators generally kept the same, the proposed configuration adopts IDT electrodes of different thicknesses in the series and shunt resonators to suppress or remove unwanted spurious Rayleigh modes from the filter passband. Two different ultra-wideband SAW filter designs employing thickness-modulated IDTs were designed and fabricated to validate the effective suppression of spurious modes. The SAW filters experimentally featured spurious-free responses in the passband as well as a large 3 dB fractional bandwidth (FBW) in the 18.0% and 24.1% ranges and low insertion losses below 1 dB. This work can significantly broaden the range of applications for SAW devices and can open a pathway to commercialize ultra-wideband SAW filters in 5G communication systems.

Flexible Quantum-Dot Color-Conversion Layer Based on Microfluidics for Full-Color Micro-LEDs.

In this article, red and green perovskite quantum dots are incorporated into the pixels of a flexible color-conversion layer assembly using microfluidics. The flexible color-conversion layer is then integrated with a blue micro-LED to realize a full-color display with a pixel pitch of 200 µm. Perovskite quantum dots feature a high quantum yield, a tunable wavelength, and high stability. The flexible color-conversion layer using perovskite quantum dots shows good luminous and display performance under different bending conditions; is easy to manufacture, economical, and applicable; and has important potential applications in the development of flexible micro-displays.