Plasma proteome profiling reveals dynamic of cholesterol marker after dual blocker therapy.

Dual blocker therapy (DBT) has the enhanced antitumor benefits than the monotherapy. Yet, few effective biomarkers are developed to monitor the therapy response. Herein, we investigate the DBT longitudinal plasma proteome profiling including 113 longitudinal samples from 22 patients who received anti-PD1 and anti-CTLA4 DBT therapy. The results show the immune response and cholesterol metabolism are upregulated after the first DBT cycle. Notably, the cholesterol metabolism is activated in the disease non-progressive group (DNP) during the therapy. Correspondingly, the clinical indicator prealbumin (PA), free triiodothyronine (FT3) and triiodothyronine (T3) show significantly positive association with the cholesterol metabolism. Furthermore, by integrating proteome and radiology approach, we observe the high-density lipoprotein partial remodeling are activated in DNP group and identify a candidate biomarker APOC3 that can reflect DBT response. Above, we establish a machine learning model to predict the DBT response and the model performance is validated by an independent cohort with balanced accuracy is 0.96. Thus, the plasma proteome profiling strategy evaluates the alteration of cholesterol metabolism and identifies a panel of biomarkers in DBT.

Overexpression of GPX2 gene regulates the development of porcine preadipocytes and skeletal muscle cells through MAPK signaling pathway.

Glutathione peroxidase 2 (GPX2) is a selenium-dependent enzyme and protects cells against oxidative damage. Recently, GPX2 has been identified as a candidate gene for backfat and feed efficiency in pigs. However, it is unclear whether GPX2 regulates the development of porcine preadipocytes and skeletal muscle cells. In this study, adenoviral gene transfer was used to overexpress GPX2. Our findings suggest that overexpression of GPX2 gene inhibited proliferation of porcine preadipocytes. And the process is accompanied by the reduction of the p-p38. GPX2 inhibited adipogenic differentiation and promoted lipid degradation, while ERK1/2 was reduced and p-p38 was increased. Proliferation of porcine skeletal muscle cells was induced after GPX2 overexpression, was accompanied by activation in JNK, ERK1/2, and p-p38. Overexpression methods confirmed that GPX2 has a promoting function in myoblastic differentiation. ERK1/2 pathway was activated and p38 was suppressed during the process. This study lays a foundation for the functional study of GPX2 and provides theoretical support for promoting subcutaneous fat reduction and muscle growth.

Surface Reconstruction for Selective Oxidation of Tetrahydroisoquinoline.

Integration of hydrogen evolution with the oxidation of organic substances in one electrochemical system is highly desirable. However, achieving selective oxidation of organic substances in the integrated system is still highly challenging. In this study, a phosphorylated NiMoO4 nanoneedle-like array was designed as the catalytic active electrode for the integration of highly selective electrochemical dehydrogenation of tetrahydroisoquinolines (THIQs) with hydrogen production. The leaching of anions, including MoO42- and PO43-, facilitates the reconstruction of the catalyst. As a result, nickel oxyhydroxides with the doping of PO43- and richness of defects are in situ formed. In situ Raman and density functional theory calculations have shown that the high catalytic activity is attributed to the in situ formed PO43- involved NiOOH substance. In the dehydrogenation process, the involved C-H bond but not the N-H bond is first destroyed. A two-electrode system was then fabricated with the optimized electrode that shows a benchmark current density of 10 mA cm-2 at 1.783 V, providing a yield of 70% for dihydroisoquinolines. A robust stability was also shown for this integrated electrochemical system. The understanding of the reconstruction behavior and the achievement of selective dehydrogenation will provide some hints for electrochemical synthesis.

The combination of berberine and isoliquiritigenin synergistically improved adipose inflammation and obesity-induced insulin resistance.

White adipose tissue accumulation and inflammation contribute to obesity by inducing insulin resistance. Herein, we aimed to screen the synergistic components of the herbal pair Coptidis Rhizoma-Glycyrrhizae Radix et Rhizoma for the treatment of insulin resistance and explore the potential synergistic mechanisms. Enzyme-linked immunosorbent assay and quantitative PCR were used to detect expression levels of inflammatory genes in vitro and in vivo. Western blotting and immunohistochemistry were performed to detect protein levels of the insulin signaling pathway and macrophage markers. The effects on obesity-induced insulin resistance were verified using a diet-induced obesity (DIO) mouse model. Interactions between macrophage and adipocyte were assessed using a cellular supernatant transfer assay. Berberine (BBR) and isoliquiritigenin (ISL) alleviated mRNA levels and secretion of inflammatory genes in vitro and in vivo. Furthermore, BBR acted synergistically with ISL to ameliorate obesity and dyslipidemia in DIO mice. Meanwhile, the combination treatment significantly improved glucose intolerance and insulin resistance and decreased M1-macrophage accumulation and infiltration in the adipose tissue. Mechanistically, co-treatment with BBR and ISL upregulated the protein expression of the IRS1-PI3K-Akt insulin signaling pathway, enhanced glucose uptake in adipocyte, and suppressed the interaction between macrophage and adipocyte. BBR and ISL were identified as the synergistic components of the herbal pair Coptidis Rhizoma-Glycyrrhizae Radix et Rhizoma for treating insulin resistance. The synergistic combination of BBR with ISL can be a promising and effective strategy for improving obesity-induced adipose inflammation and insulin resistance.

Relationship between age and remimazolam dose required for inducing loss of consciousness in older surgical patients.

Background: Remimazolam is a new ultra-short-acting benzodiazepine for procedural sedation and general anaesthesia, characterised by rapid onset of action, quick recovery, and organ-independent metabolism. Older patients tend to sustain more treatment-emergent adverse events (TEAEs) and worse perioperative prognoses after receiving remimazolam. However, few studies have investigated the appropriate dose of remimazolam for loss of consciousness (LOC) in geriatric patients. We designed this study to provide evidence for dose references and elucidate the relationship between age and remimazolam requirement for inducing LOC during anaesthesia induction. Methods: Exactly 120 patients scheduled for general surgery under general anaesthesia were included and divided into two groups: Group A (60 patients, 18-64 years) and Group B (60 patients, ≥ 65 years). LOC, defined as a Modified Observer's Assessment of Alertness and Sedation score at 1 had been reached, emerged after all participants received a continuous infusion of remimazolam at a rate of 0.05 mg/kg/min. Results: The remimazolam required for inducing LOC was 0.26 and 0.19 mg/kg in groups A and B, respectively, and the remimazolam dose in group B decreased by 26.9% compared to group A. According to the bivariate linear correlation analysis, remimazolam requirement was negatively correlated with age. Multivariable linear regression models and further adjustments for potential impact factors indicated that age was an independent factor for the remimazolam dose required for LOC. Conclusion: This study demonstrated that age was significantly and independently correlated with the remimazolam requirement for inducing LOC. To obtain haemodynamic stability during the induction of general anaesthesia, appropriately reducing the remimazolam dose is recommended for geriatric patients.

Neural mechanism of non-adaptive cognitive emotion regulation in patients with non-suicidal self-injury.

BACKGROUND: The incidence of non-suicidal self-injury (NSSI) has been on the rise in recent years. Studies have shown that people with NSSI have difficulties in emotion regulation and cognitive control. In addition, some studies have investigated the cognitive emotion regulation of people with NSSI which found that they have difficulties in cognitive emotion regulation, but there was a lack of research on cognitive emotion regulation strategies and related neural mechanisms. METHODS: This study included 117 people with NSSI (age = 19.47 ± 5.13, male = 17) and 84 non-NSSI participants (age = 19.86 ± 4.14, male = 16). People with NSSI met the DSM-5 diagnostic criteria, and non-NSSI participants had no mental or physical disorders. The study collected all participants' data of Cognitive Emotion Regulation Questionnaire (CERQ) and functional magnetic resonance imaging (fMRI) to explore the differences in psychological performance and brain between two groups. Afterwards, Machine learning was used to select the found differential brain regions to obtain the highest correlation regions with NSSI. Then, Allen's Human Brain Atlas database was used to compare with the information on the abnormal brain regions of people with NSSI to find the genetic information related to NSSI. In addition, gene enrichment analysis was carried out to find the related pathways and specific cells that may have differences. RESULTS: The differences between NSSI participants and non-NSSI participants were as follows: positive refocusing (t = -4.74, p < 0.01); refocusing on plans (t = -4.11, p < 0.01); positive reappraisal (t = -9.22, p < 0.01); self-blame (t = 6.30, p < 0.01); rumination (t = 3.64, p < 0.01); catastrophizing (t = 9.10, p < 0.01), and blaming others (t = 2.52, p < 0.01), the precentral gyrus (t = 6.04, pFDR < 0.05) and the rolandic operculum (t = -4.57, pFDR < 0.05). Rolandic operculum activity was negatively correlated with blaming others (r = -0.20, p < 0.05). Epigenetic results showed that excitatory neurons (p < 0.01) and inhibitory neurons (p < 0.01) were significant differences in two pathways, "trans-synaptic signaling" (p < -log108) and "modulation of chemical synaptic transmission" (p < -log108) in both cells. CONCLUSIONS: People with NSSI are more inclined to adopt non-adaptive cognitive emotion regulation strategies. Rolandic operculum is also abnormally active. Abnormal changes in the rolandic operculum of them are associated with non-adaptive cognitive emotion regulation strategies. Changes in the excitatory and inhibitory neurons provide hints to explore the abnormalities of the neurological mechanisms at the cellular level of them. Trial registration number NCT04094623.

Melatonin regulates the antioxidant capacity of sheep granulosa cells through a novel uORF-Nrf2aa mediated Nrf2/KEAP1 pathway.

Ovarian dysfunction stands as a prevalent contributor to female infertility, with its etiology intertwined with genetic, autoimmune, and environmental factors. Within the ovarian follicles, granulosa cells (GCs) represent the predominant cell population. Alterations in GCs, notably oxidative stress (OS) and the consequential surge in reactive oxygen species (ROS), play pivotal roles in the orchestration of ovarian function. Nrf2aa, a newly identified upstream open reading frame (uORF), is situated within the 5' untranslated region (5'UTR) of sheep Nrf2 mRNA and is regulated by melatonin, a crucial intrafollicular antioxidant. In this study, we have noted that Nrf2aa has the capacity to encode a peptide and exerts a negative regulatory effect on the translation efficiency (TE) of the Nrf2 CDs region. Further in vitro experiments, we observed that interfering with Nrf2aa can enhance the cellular functionality of GCs under 3-np-induced oxidative stress, while overexpressing Nrf2aa has the opposite effect. Furthermore, overexpression of Nrf2aa counteracts the rescuing effect of melatonin on the cellular functions of GCs under oxidative stress conditions, including estrogen secretion, proliferation, apoptosis, and many more. Finally, we confirmed that Nrf2aa, by regulating the expression of key proteins in the Nrf2/KEAP1 signaling pathway, further modulates the antioxidant levels in GCs.

Biosynthetic pathway analysis combined with feature-based molecular networking to comprehensively characterize the chemical constituents in seeds of Sterculia lychnophora.

INTRODUCTION: The seeds of Sterculia lychnophora Hance, commonly known as Pangdahai (PDH) in Chinese, have found extensive use in both culinary and traditional medicinal practices. However, a comprehensive understanding of the chemical composition of PDH has been lacking. OBJECTIVES: This study proposes a strategy that integrates biosynthetic pathway analysis with feature-based molecular networking (FBMN), aiming for a thorough and global characterization of the chemical compositions of PDH. METHODOLOGY: The FBMN map reveals potential compounds with structural similarity, and the MS/MS fragments could be annotated based on library matches, which could predict the plausible biosynthetic pathways in PDH, accomplishing the annotation of compounds clustered in FBMN by integrating biosynthetic pathways. RESULTS: Consequently, 126 compounds were plausibly or unambiguously identified, including 37 phenolic acids and glycosides, 20 flavonoids and glycosides, 12 procyanidins, 21 alkaloids, 22 lipids, and 14 others. Leveraging the information, 40 compounds, including 1 unique isoquinoline alkaloid and 2 rare linear furocoumarins, were isolated and confirmed. CONCLUSIONS: This study not only demonstrates a highly effective approach for identifying compounds within complex herbal mixtures but also establishes a robust foundation for the further development of PDH.

Syringic acid attenuates acute lung injury by modulating macrophage polarization in LPS-induced mice.

BACKGROUND: Acute lung injury (ALI) is a continuum of lung changes caused by multiple lung injuries, characterized by a syndrome of uncontrolled systemic inflammation that often leads to significant morbidity and death. Anti-inflammatory is one of its treatment methods, but there is no safe and available drug therapy. Syringic acid (SA) is a natural organic compound commonly found in a variety of plants, especially in certain woody plants and fruits. In modern pharmacological studies, SA has anti-inflammatory effects and therefore may be a potentially safe and available compound for the treatment of acute lung injury. PURPOSE: This study attempts to reveal the protective mechanism of SA against ALI by affecting the polarization of macrophages and the activation of NF-κB signaling pathway. Trying to find a safer and more effective drug therapy for clinical use. METHODS: We constructed the ALI model using C57BL/6 mice by intratracheal instillation of LPS (10 mg/kg). Histological analysis was performed with hematoxylin and eosin (H&E). The wet-dry ratio of the whole lung was measured to evaluate pulmonary edema. The effect of SA on macrophage M1-type was detected by flow cytometry. BCA protein quantification method was used to determine the total protein concentration in bronchoalveolar lavage fluid (BALF). The levels of Interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α in BALF were determined by the ELISA kits, and RT-qPCR was used to detect the expression levels of IL-6, IL-1ß and TNF-α mRNA of lung tissue. Western blot was used to detect the expression levels of iNOS and COX-2 and the phosphorylation of p65 and IκBα in the NF-κB pathway in lung tissue. In vitro experiments were conducted with RAW267.4 cell inflammation model induced by 100 ng/ml LPS and A549 cell inflammation model induced by 10 µg/ml LPS. The effects of SA on M1-type and M2-type macrophages of RAW267.4 macrophages induced by LPS were detected by flow cytometry. The toxicity of compound SA to A549 cells was detected by MTT method which to determine the safe dose of SA. The expressions of COX-2 and the phosphorylation of p65 and IκBα protein in NF-κB pathway were detected by Western blot. RESULTS: We found that the pre-treatment of SA significantly reduced the degree of lung injury, and the infiltration of neutrophils in the lung interstitium and alveolar space of the lung. The formation of transparent membrane in lung tissue and thickening of alveolar septum were significantly reduced compared with the model group, and the wet-dry ratio of the lung was also reduced. ELISA and RT-qPCR results showed that SA could significantly inhibit the production of IL-6, IL-1ß, TNF-α. At the same time, SA could significantly inhibit the expression of iNOS and COX-2 proteins, and could inhibit the phosphorylation of p65 and IκBα proteins. in a dose-dependent manner. In vitro experiments, we found that flow cytometry showed that SA could significantly inhibit the polarization of macrophages from M0 type macrophages to M1-type macrophages, while SA could promote the polarization of M1-type macrophages to M2-type macrophages. The results of MTT assay showed that SA had no obvious cytotoxicity to A549 cells when the concentration was not higher than 80 µM, while LPS could promote the proliferation of A549 cells. In the study of anti-inflammatory effect, SA can significantly inhibit the expression of COX-2 and the phosphorylation of p65 and IκBα proteins in LPS-induced A549 cells. CONCLUSION: SA has possessed a crucial anti-ALI role in LPS-induced mice. The mechanism was elucidated, suggesting that the inhibition of macrophage polarization to M1-type and the promotion of macrophage polarization to M2-type, as well as the inhibition of NF-κB pathway by SA may be the reasons for its anti-ALI. This finding provides important molecular evidence for the further application of SA in the clinical treatment of ALI.

Mechanism of CO2 in promoting the hydrogenation of levulinic acid to γ-valerolactone catalyzed by RuCl3 in aqueous solution.

A Ru-containing complex shows good catalytic performance toward the hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL) with the assistance of organic base ligands (OBLs) and CO2. Herein, we report the competitive mechanisms for the hydrogenation of LA to GVL, 4-oxopentanal (OT), and 2-methyltetrahydro-2,5-furandiol (MFD) with HCOOH or H2 as the H source catalyzed by RuCl3 in aqueous solution at the M06/def2-TZVP, 6-311++G(d,p) theoretical level. Kinetically, the hydrodehydration of LA to GVL is predominant, with OT and MFD as side products. With HCOOH as the H source, initially, the OBL (triethylamine, pyridine, or triphenylphosphine) is responsible for capturing H+ from HCOOH, leading to HCOO- and [HL]+. Next, the Ru3+ site is in charge of sieving H- from HCOO-, yielding [RuH]2+ hydride and CO2. Alternatively, with H2 as the H source, the OBL stimulates the heterolysis of H-H bond with the aid of Ru3+ active species, producing [RuH]2+ and [HL]+. Toward the [RuH]2+ formation, H2 as the H source exhibits higher activity than HCOOH as the H source in the presence of an OBL. Thereafter, H- in [RuH]2+ gets transferred to the unsaturated C site of ketone carbonyl in LA. Afterwards, the Ru3+ active species is capable of cleaving the C-OH bond in 4-hydroxyvaleric acid, yielding [RuOH]2+ hydroxide and GVL. Subsequently, CO2 promotes Ru-OH bond cleavage in [RuOH]2+, forming HCO3- and regenerating the Ru3+-active species owing to its Lewis acidity. Lastly, between the resultant HCO3- and [HL]+, a neutralization reaction occurs, generating H2O, CO2, and OBLs. Thus, the present study provides insights into the promotive roles of additives such as CO2 and OBLs in Ru-catalyzed hydrogenation.

Reconstructing Kaolinite Compounds for Remarkably Enhanced Adsorption of Congo Red.

Organic dyes are widely used in many important areas, but they also bring many issues for water pollution. To address the above issues, a reconstructed kaolinite hybrid compound (γ-AlOOH@A-Kaol) was obtained from raw kaolinite (Kaol) in this work. The product was then characterized by X-ray diffraction (XRD), Fourier-transform infrared (ATR-FTIR), Brunauer-Emmett-Teller (BET), and scanning electron microscopy (SEM), and the absorption properties of γ-AlOOH@A-Kaol for congo red were further studied. The results demonstrated that flower-like γ-AlOOH with nanolamellae were uniformly loaded on the surface of acid-treated Kaol with a porous structure (A-Kaol). In addition, the surface area (36.5 m2/g), pore volume (0.146 cm3/g), and pore size (13.0 nm) of γ-AlOOH@A-Kaol were different from those of A-Kaol (127.4 m2/g, 0.127 cm3/g, and 4.28 nm, respectively) and γ-AlOOH (34.1 m2/g, 0.315 cm3/g, and 21.5 nm, respectively). The unique structure could significantly enhance the sorption capacity for congo red, which could exceed 1000 mg/g. The reasons may be ascribed to the abundant groups of -OH, large specific surface area, and porous structure of γ-AlOOH@A-Kaol. This work provides an efficient route for comprehensive utilization and production of Kaol-based compound materials that could be used in the field of environmental conservation.

In situ/Operando Synchrotron Radiation Analytical Techniques for CO2/CO Reduction Reaction: From Atomic Scales to Mesoscales.

Electrocatalytic carbon dioxide/carbon monoxide reduction reaction (CO(2)RR) has emerged as a prospective and appealing strategy to realize carbon neutrality for manufacturing sustainable chemical products. Developing highly active electrocatalysts and stable devices has been demonstrated as effective approach to enhance the conversion efficiency of CO(2)RR. In order to rationally design electrocatalysts and devices, a comprehensive understanding of the intrinsic structure evolution within catalysts and micro-environment change around electrode interface, particularly under operation conditions, is indispensable. Synchrotron radiation has been recognized as a versatile characterization platform, garnering widespread attention owing to its high brightness, elevated flux, excellent directivity, strong polarization and exceptional stability. This review systematically introduces the applications of synchrotron radiation technologies classified by radiation sources with varying wavelengths in CO(2)RR. By virtue of in situ/operando synchrotron radiationanalytical techniques, we also summarize relevant dynamic evolution processes from electronic structure, atomic configuration, molecular adsorption, crystal lattice and devices, spanning scales from the angstrom to the micrometer. The merits and limitations of diverse synchrotron characterization techniques are summarized, and their applicable scenarios in CO(2)RR are further presented. On the basis of the state-of-the-art fourth-generation synchrotron facilities, a perspective for further deeper understanding of the CO(2)RR process using synchrotron radiation analytical techniques is proposed.

Tracking investigation of archaeal composition and methanogenesis function from parental to offspring pigs.

Archaea play a crucial role in microbial systems, including driving biochemical reactions and affecting host health by producing methane through hydrogen. The study of swine gut archaea has a positive significance in reducing methane emissions and improving feed utilization efficiency. However, the development and functional changes of archaea in the pig intestines have been overlooked for a long time. In this study, 54 fecal samples were collected from 36 parental pigs (18 boars and 18 pregnant/lactating sows), and 108 fecal samples from 18 offspring pigs during lactation, nursery, growing, and finishing stages were tracked and collected for metagenomic sequencing. We obtained 14 archaeal non-redundant metagenome-assembled genomes (MAGs). These archaea were classified as Methanobacteriota and Thermoplasmatota at the phylum level, and Methanobrevibacter, Methanosphaera, MX-02, and UBA71 at the genus level, involving hydrogenotrophic, methylotrophic, and acetoclastic pathways. The hydrogenotrophic pathway dominated the methanogenesis function, and the vast majority of archaea participated in it. Dietary changes profoundly affected the archaeal composition and methanogenesis function in pigs. The abundance of hydrogen-producing bacteria in parental pigs fed high-fiber diets was higher than that in offspring pigs fed low-fiber diets. The methanogenesis function was positively correlated with fiber decomposition functions and negatively correlated with the starch decomposition function. Increased abundance of sulfate reductase and fumarate reductase, as well as decreased acetate/propionate ratio, indicated that the upregulation of alternative hydrogen uptake pathways competing with methanogens may be the reason for the reduced methanogenesis function. These findings contribute to providing information and direction in the pig industry for the development of strategies to reduce methane emissions, improve feed efficiency, and maintain intestinal health.

[Differences in the Elderly Care Service Demand,Preference,and Tendency Between Urban and Rural Areas in the Pearl River Delta].

Objective To understand the differences in the demand,preference,and tendency for elderly care services between urban and rural areas in the Pearl River Delta (PRD),and to provide reference for the planning and balanced allocation of elderly care resources in urban and rural areas. Methods Using the multi-stage stratified random sampling method,we selected 7 community health service centers in 2 prefecture-level cities in the PRD and conducted a questionnaire survey on the elderly care service demand,preference,and tendency among 1919 regular residents aged 60 years and above who attended the centers. Results A total of 641 urban elderly residents (33.4%) and 1278 rural elderly residents (66.6%) were surveyed in the PRD.The urban and rural elderly residents showed differences in the child number (χ2=43.379,P<0.001),willingness to purchase socialized elderly care services (χ2=104.141,P<0.001),and attitudes to the concept of raising child to avoid elderly hardship (χ2=65.632,P<0.001).The proportion (71.8%) of rural elderly residents who prefer family-based elderly care was higher than that (57.1%) of urban elderly residents (χ2=41.373,P<0.001).The proportion (62.2%) of urban elderly residents clearly expressing their willingness to choose institutions for elderly care was higher than that (44.0%) of rural elderly residents (χ2=57.007,P<0.001).Compared with family-based elderly care,the willingness to choose institutional or community-based in-house elderly care was low among the urban elderly residents with surplus monthly household income or balanced income and expenditure;urban males,those with college education background or above,and those who purchased socialized elderly care services tended to prefer community-based in-house elderly care.In rural areas,the elderly residents who had local household registry were prone to choose institutional or community-based in-house elderly care,while those who had more than one child and those who were satisfied with the current living conditions were less willing to choose community-based in-house elderly care. Conclusions It is suggested that the urban-rural differences in the elderly care service demand,preference and tendency should be fully considered in the planning and allocation of urban and rural elderly care resources.Efforts remain to be made to develop diversified social elderly care services tailored to the characteristics of urban and rural areas.

Screening performance of COPD-PS scale, COPD-SQ scale, peak expiratory flow, and their combinations for chronic obstructive pulmonary disease in the primary healthcare in Haicang District, Xiamen City.

Objectives: This study aimed to evaluate the screening performance of COPD-PS questionnaire, COPD-SQ questionnaire, peak expiratory flow (PEF), COPD-PS questionnaire combined with PEF, and COPD-SQ questionnaire combined with PEF for chronic obstructive pulmonary disease (COPD). Methods: This was a cross-sectional study. We distributed self-designed surveys and COPD screening scales (COPD-PS questionnaire and COPD-SQ questionnaire) to residents who underwent physical examination in five community health centers in Haicang District, Xiamen City, from February 2023 to May 2023, and measured their lung function and PEF with a portable device. We used logistic regression to obtain the coefficients of COPD-PS questionnaire, COPD-SQ questionnaire, and PEF, and plotted the receiver operating characteristic curves of each tool for diagnosing COPD and moderate-to-severe COPD. We evaluated and compared the optimal cut-off points and scores of sensitivity, specificity, Youden index, and area under the curve (AUC) values, and assessed the screening efficiency of different methods. Results: Of the 3,537 residents who completed the COPD-SQ questionnaire, COPD-PS questionnaire, and spirometry, 840 were diagnosed with COPD. We obtained the coefficients of COPD-PS questionnaire combined with peak expiratory flow (PEF), and COPD-SQ questionnaire combined with PEF, by logistic regression as -0.479-0.358 × PEF +0.321 × COPD-PS score and - 1.286-0.315 × PEF +0.125 × COPD-SQ score, respectively. The sensitivity of diagnosing COPD by COPD-SQ questionnaire, COPD-PS questionnaire, PEF, COPD-PS questionnaire combined with PEF, and COPD-SQ questionnaire combined with PEF were 0.439, 0.586, 0.519, 0.586, 0.612 respectively, and the specificity were 0.725, 0.621, 0.688, 0.689, 0.663 respectively, with ROC values of 0.606 (95%CI: 0.586-0.626), 0.640 (0.619-0.661), 0.641 (0.619-0.663), 0.678 (0.657-0.699), 0.685 (0.664-0.706) respectively. The sensitivity of diagnosing GOLD II and above by COPD-SQ questionnaire, COPD-PS questionnaire, PEF, COPD-PS questionnaire combined with PEF, and COPD-SQ questionnaire combined with PEF were 0.489, 0.620, 0.665, 0.630, 0.781 respectively, and the specificity were 0.714, 0.603, 0.700, 0.811, 0.629 respectively, with ROC values of 0.631 (95%CI: 0.606-0.655), 0.653 (0.626-0.679), 0.753 (0.730-0.777), 0.784 (0.762-0.806), 0.766 (0.744-0.789) respectively. Conclusion: Our study found that the accuracy of COPD screening by COPD-SQ questionnaire and COPD-PS questionnaire can be improved by combining the results of PEF. The screening performance of COPD-SQ questionnaire combined with PEF is relatively better. In future research, further studies are needed to optimize the performance of screening tools and understand whether their use will affect clinical outcomes.

Linking growth performance and carcass traits with enterotypes in Muscovy ducks.

Objective: Enterotypes (ETs) are the clustering of gut microbial community structures, which could serve as indicators of growth performance and carcass traits. However, ETs have been sparsely investigated in waterfowl. The objective of this study was to identify the ileal ETs and explore the correlation of the ETs with growth performance and carcass traits in Muscovy ducks. Methods: A total of 200 Muscovy ducks were randomly selected from a population of 5,000 ducks at 70-day old, weighed and slaughtered. The growth performance and carcass traits, including body weight, dressed weight and evidenced weight, dressed percentage, percentage of apparent yield, breast muscle weight, leg muscle weight, percentage of leg muscle and percentage of breast muscle, were determined. The contents of ileum were collected for the isolation of DNA and 16S rRNA gene sequencing. The ETs were identified based on the 16S rRNA gene sequencing data and the correlation of the ETs with growth performance and carcass traits was performed by Spearman correlation analysis. Results: Three ETs (ET1, ET2, and ET3) were observed in the ileal microbiota of Muscovy ducks with significant differences in number of features and α-diversity among these ETs (P < 0.05). Streptococcus, Candida Arthritis, and Bacteroidetes were the presentative genus in ET1 to ET3, respectively. Correlation analysis revealed that Lactococcus and Bradyrhizobium were significantly correlated with percentage of eviscerated yield and leg muscle weight (P < 0.05) while ETs were found to have a close association with percentage of eviscerated yield, leg muscle weight, and percentage of leg muscle in Muscovy ducks. However, the growth performance of ducks with different ETs did not show significant difference (P > 0.05). Lactococcus were found to be significantly correlated with leg muscle weight, dressed weight, and percentage of eviscerated yield. Conclusion: Our findings revealed a substantial variation in carcass traits associated with enterotypes in Muscovy ducks. It is implied that ETs might have the potential to serve as a valuable biomarker for assessing duck carcass traits. It would provide novel insights into the interaction of gut microbiota with growth performance and carcass traits of ducks.

Population Pharmacokinetics of Lamotrigine and Its N2-Glucuronide Metabolite in Chinese Patients with Epilepsy.

BACKGROUND: Lamotrigine is a new antiepileptic drug with substantial interindividual variability in its pharmacokinetics and therapeutic responses. This study aimed to develop population pharmacokinetic (PPK) models of lamotrigine and its N2-glucuronide metabolites for model-informed individualized therapy. METHODS: A total of 353 plasma concentrations from Chinese patients with epilepsy receiving oral lamotrigine were used to develop a population PPK model using a nonlinear mixed effects modeling method. One- and two-compartment models were applied to the nonmetabolite and metabolite model, respectively. Forward addition and backward elimination were used to establish the final model. Model validation was performed using standard goodness-of-fit, bootstrap, visual predictive checks, and normalized prediction distribution errors. Finally, simulations were performed to propose lamotrigine dosages in different situations to achieve trough concentrations within the reference interval (2.5-15 mg/L). RESULTS: For both final population PPK models, coadministration with valproic acid (VPA) or enzyme inducer, and body weight significantly affected lamotrigine clearance. The final models for lamotrigine clearance were and for nonmetabolite and metabolite models, respectively. The precision of the PPK parameters was acceptable, and the models exhibited good predictability. Monte Carlo simulations revealed that the lamotrigine dosage administered to patients combined with an enzyme inducer must be tripled that administered with VPA to reach the target trough concentration. CONCLUSIONS: Variability in the pharmacokinetics of lamotrigine is large. Coadministration of VPA or an enzyme inducer and body weight are the most important factors in lamotrigine clearance in Chinese patients with epilepsy. The developed population PPK models might support further optimization of lamotrigine dosing regimens.

PPP2R2A promotes Hu sheep pituitary cell proliferation and gonadotropin secretion associated with prolificacy.

The anterior pituitary plays a critical role in the endocrine system, contains gonadotrophs, which regulate reproductive efficiency by secreting follicle-stimulating hormone (FSH) and luteinizing hormone (LH). PPP2R2A is a serine-threonine phosphatase that regulates reproductive functions in both females and males, its function in pituitary cells remain unclear. Hu sheep is a highly prolific breed, which makes it suitable for studying reproductive mechanisms. In this study, the relative abundances of PPP2R2A mRNA expression were higher in the pituitary of high-prolificacy (HF) Hu sheep compared to those of low-prolificacy (LF) Hu sheep. Additionally, we demonstrated that PPP2R2A promotes pituitary cell proliferation and gonadotropin secretion using the EdU assay and ELISA, respectively. Moreover, it inhibits pituitary cell apoptosis using flow cytometry. Furthermore, PPP2R2A may affect pituitary cell function by regulating the AKT/mTOR signaling pathway. In summary, our findings suggest that PPP2R2A may play a role in regulating pituitary function and influencing the secretion of gonadotropins.

Preparation of spore-immobilized glutathione reductase and its application in inhibiting browning of pear wine.

BACKGROUND: Browning is the key problem hindering the industrialization of pear wine. The use of high-yield glutathione Saccharomyces cerevisiae in the fermentation of pear wine can inhibit browning. Glutathione reductase (GR) can ensure the reduction of glutathione. Spore immobilization of enzymes is a new technology. It is a new attempt to apply spore-immobilized GR in combination with high-yield glutathione S. cerevisiae to inhibit browning of pear wine. RESULTS: Saccharomyces cerevisiae spore immobilization enzyme technology was used to immobilize GR in the spores of mutant S. cerevisiae dit1∆, osw2∆ and chs3∆ and wild-type S. cerevisiae. The enzyme activity of GR immobilized by chs3∆ spores was the highest of 3.08 U mg-1 min-1. The chs3∆ spore-immobilized GR had certain resistance to ethanol, citric acid, sucrose, glucose and proteinase K. Electron microscopy analysis showed that the spore wall of chs3∆ had moderate size holes, which might be the main reason why it immobilized GR with the highest enzyme activity. And the GR was immobilized between the prespore membrane and mannoprotein layer of the spore wall. When chs3∆ spore-immobilized GR (chs3∆-GR) was added to Dangshan pear wine fermented by high-yield glutathione S. cerevisiae JN32-9, the presence of chs3∆-GR could further protect amino acids, polyphenols and glucose from oxidation, thereby reducing the browning of the pear wine during storage by 47.32%. CONCLUSION: GR immobilized by S. cerevisiae spores was effective in inhibiting the browning of pear wine. The method was simple, green and effective and did not increase the production cost of pear wine. © 2024 Society of Chemical Industry.

Total sleep deprivation alters spontaneous brain activity in medical staff during routine clinical work: a resting-state functional MR imaging study.

Objectives: To assess the effect of total sleep deprivation (TSD) on spontaneous brain activity in medical staff during routine clinical practice. Methods: A total of 36 medical staff members underwent resting-state functional MRI (rs-fMRI) scans and neuropsychological tests twice, corresponding to rested wakefulness (RW) after normal sleep and 24 h of acute TSD. The rs-fMRI features, including the mean fractional amplitude of low-frequency fluctuation (mfALFF), z-score transformed regional homogeneity (zReHo), and functional connectivity (zFC), were compared between RW and TSD. Correlation coefficients between the change in altered rs-fMRI features and the change in altered scores of neuropsychological tests after TSD were calculated. Receiver operating characteristic (ROC) and logistic regression analyses were performed to evaluate the diagnostic efficacy of significantly altered rs-fMRI features in distinguishing between RW and TSD states. Results: Brain regions, including right superior temporal gyrus, bilateral postcentral gyrus, left medial superior frontal gyrus, left middle temporal gyrus, right precentral gyrus, and left precuneus, showed significantly enhanced rs-fMRI features (mfALFF, zReHo, zFC) after TSD. Moreover, the changes in altered rs-fMRI features of the right superior temporal gyrus, bilateral postcentral gyrus, left middle temporal gyrus, and left precuneus were significantly correlated with the changes in several altered scores of neuropsychological tests. The combination of mfALFF (bilateral postcentral gyrus) and zFC (left medial superior frontal gyrus and left precuneus) showed the highest area under the curve (0.870) in distinguishing RW from TSD. Conclusion: Spontaneous brain activity alterations occurred after TSD in routine clinical practice, which might explain the reduced performances of these participants in neurocognitive tests after TSD. These alterations might be potential imaging biomarkers for assessing the impact of TSD and distinguishing between RW and TSD states.