Cross-Platform Comparison of Highly Sensitive Immunoassays for Inflammatory Markers in a COVID-19 Cohort.

A variety of commercial platforms are available for the simultaneous detection of multiple cytokines and associated proteins, often employing Ab pairs to capture and detect target proteins. In this study, we comprehensively evaluated the performance of three distinct platforms: the fluorescent bead-based Luminex assay, the proximity extension-based Olink assay, and a novel proximity ligation assay platform known as Alamar NULISAseq. These assessments were conducted on human serum samples from the National Institutes of Health IMPACC study, with a focus on three essential performance metrics: detectability, correlation, and differential expression. Our results reveal several key findings. First, the Alamar platform demonstrated the highest overall detectability, followed by Olink and then Luminex. Second, the correlation of protein measurements between the Alamar and Olink platforms tended to be stronger than the correlation of either of these platforms with Luminex. Third, we observed that detectability differences across the platforms often translated to differences in differential expression findings, although high detectability did not guarantee the ability to identify meaningful biological differences. Our study provides valuable insights into the comparative performance of these assays, enhancing our understanding of their strengths and limitations when assessing complex biological samples, as exemplified by the sera from this COVID-19 cohort.

Modulating PCGF4/BMI1 Stability Is an Efficient Metastasis-Regulatory Strategy Used by Distinct Subtypes of Cancer-Associated Fibroblasts in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm prone to metastasis. Whether cancer-associated fibroblasts (CAFs) affect the metastasis of ICC is unclear. Herein, ICC patient-derived CAF lines and related cancerous cell lines were established and the effects of CAFs on the tumor progressive properties of the ICC cancerous cells were analyzed. CAFs could be classified into cancer-restraining or cancer-promoting categories based on distinct tumorigenic effects. The RNA-sequencing analyses of ICC cancerous cell lines identified polycomb group ring finger 4 (PCGF4; alias BMI1) as a potential metastasis regulator. The changes of PCGF4 levels in ICC cells mirrored the restraining or promoting effects of CAFs on ICC migration. Immunohistochemical analyses on the ICC tissue microarrays indicated that PCGF4 was negatively correlated with overall survival of ICC. The promoting effects of PCGF4 on cell migration, drug resistance activity, and stemness properties were confirmed. Mechanistically, cancer-restraining CAFs triggered the proteasome-dependent degradation of PCGF4, whereas cancer-promoting CAFs enhanced the stability of PCGF4 via activating the IL-6/phosphorylated STAT3 pathway. In summary, the current data identified the role of CAFs in ICC metastasis and revealed a new mechanism of the CAFs on ICC progression in which PCGF4 acted as the key effector by both categories of CAFs. These findings shed light on developing comprehensive therapeutic strategies for ICC.

Canagliflozin regulates metabolic reprogramming in diabetic kidney disease by inducing fasting-like and aestivation-like metabolic patterns.

AIMS/HYPOTHESIS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) are antihyperglycaemic drugs that protect the kidneys of individuals with type 2 diabetes mellitus. However, the underlying mechanisms mediating the renal benefits of SGLT2i are not fully understood. Considering the fuel switches that occur during therapeutic SGLT2 inhibition, we hypothesised that SGLT2i induce fasting-like and aestivation-like metabolic patterns, both of which contribute to the regulation of metabolic reprogramming in diabetic kidney disease (DKD). METHODS: Untargeted and targeted metabolomics assays were performed on plasma samples from participants with type 2 diabetes and kidney disease (n=35, 11 women) receiving canagliflozin (CANA) 100 mg/day at baseline and 12 week follow-up. Next, a systematic snapshot of the effect of CANA on key metabolites and pathways in the kidney was obtained using db/db mice. Moreover, the effects of glycine supplementation in db/db mice and human proximal tubular epithelial cells (human kidney-2 [HK-2]) cells were studied. RESULTS: Treatment of DKD patients with CANA for 12 weeks significantly reduced HbA1c from a median (interquartile range 25-75%) of 49.0 (44.0-57.0) mmol/mol (7.9%, [7.10-9.20%]) to 42.2 (39.7-47.7) mmol/mol (6.8%, [6.40-7.70%]), and reduced urinary albumin/creatinine ratio from 67.8 (45.9-159.0) mg/mmol to 47.0 (26.0-93.6) mg/mmol. The untargeted metabolomics assay showed downregulated glycolysis and upregulated fatty acid oxidation. The targeted metabolomics assay revealed significant upregulation of glycine. The kidneys of db/db mice undergo significant metabolic reprogramming, with changes in sugar, lipid and amino acid metabolism; CANA regulated the metabolic reprogramming in the kidneys of db/db mice. In particular, the pathways for glycine, serine and threonine metabolism, as well as the metabolite of glycine, were significantly upregulated in CANA-treated kidneys. Glycine supplementation ameliorated renal lesions in db/db mice by inhibiting food intake, improving insulin sensitivity and reducing blood glucose levels. Glycine supplementation improved apoptosis of human proximal tubule cells via the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. CONCLUSIONS/INTERPRETATION: In conclusion, our study shows that CANA ameliorates DKD by inducing fasting-like and aestivation-like metabolic patterns. Furthermore, DKD was ameliorated by glycine supplementation, and the beneficial effects of glycine were probably due to the activation of the AMPK/mTOR pathway.

The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, emerging as a significant health issue on a global scale. Berberine exhibits potential for treating NAFLD, but clinical evidence remains inconclusive. This meta-analysis was conducted to assess the efficacy and safety of berberine for treating NAFLD. METHODS: This study was registered with PROSPERO (No. CRD42023462338). Identification of randomized controlled trials (RCTs) involved searching 6 databases covering the period from their initiation to 9 September 2023. The primary outcomes comprised liver function markers such as glutamyl transpeptidase (GGT), alanine transaminase (ALT), aspartate transaminase (AST), lipid indices including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment for insulin resistance (HOMA-IR) and body mass index (BMI). Review Manager 5.4 and STATA 17.0 were applied for analysis. RESULTS: Among 10 RCTs involving 811 patients, berberine demonstrated significant reductions in various parameters: ALT (standardized mean difference (SMD) = - 0.72), 95% confidence interval (Cl) [- 1.01, - 0.44], P < 0.00001), AST (SMD = - 0.79, 95% CI [- 1.17, - 0.40], P < 0.0001), GGT (SMD = - 0.62, 95% CI [- 0.95, - 0.29], P = 0.0002), TG (SMD = - 0.59, 95% CI [- 0.86, - 0.31], P < 0.0001), TC(SMD = - 0.74, 95% CI [- 1.00, - 0.49], P < 0.00001), LDL-C (SMD = - 0.53, 95% CI [- 0.88, - 0.18], P = 0.003), HDL-C (SMD = - 0.51, 95% CI [- 0.12, 1.15], P = 0.11), HOMA-IR (SMD = - 1.56, 95% CI [- 2.54, - 0.58], P = 0.002), and BMI (SMD = - 0.58, 95% CI [- 0.77, - 0.38], P < 0.00001). Importantly, Berberine exhibited a favorable safety profile, with only mild gastrointestinal adverse events reported. CONCLUSION: This meta-analysis demonstrates berberine's efficacy in improving liver enzymes, lipid profile, and insulin sensitivity in NAFLD patients. These results indicate that berberine shows promise as an adjunct therapy for NAFLD. Trial registration The protocol was registered with PROSPERO (No. CRD42023462338). Registered on September 27, 2023.

Losses of low-germinating, slow-growing species prevent grassland composition recovery from nutrient amendment.

Nutrient enrichment often alters the biomass and species composition of plant communities, but the extent to which these changes are reversible after the cessation of nutrient addition is not well-understood. Our 22-year experiment (15 years for nutrient addition and 7 years for recovery), conducted in an alpine meadow, showed that soil nitrogen concentration and pH recovered rapidly after cessation of nutrient addition. However, this was not accompanied by a full recovery of plant community composition. An incomplete recovery in plant diversity and a directional shift in species composition from grass dominance to forb dominance were observed 7 years after the nutrient addition ended. Strikingy, the historically dominant sedges with low germination rate and slow growth rate and nitrogen-fixing legumes with low germination rate were unable to re-establish after nutrient addition ceased. By contrast, rapid recovery of aboveground biomass was observed after nutrient cessation as the increase in forb biomass only partially compensated for the decline in grass biomass. These results indicate that anthropogenic nutrient input can have long-lasting effects on the structure, but not the soil chemistry and plant biomass, of grassland communities, and that the recovery of soil chemical properties and plant biomass does not necessarily guarantee the restoration of plant community structure. These findings have important implications for the management and recovery of grassland communities, many of which are experiencing alterations in resource input.

Digital cholangioscopy-assisted, direct visualization-guided, radiation-free, endoscopic retrograde intervention for cholelithiasis: technical feasibility, efficacy, and safety.

BACKGROUND: Nonradiation, digital cholangioscope (DCS)-assisted endoscopic intervention for cholelithiasis has not been widely performed. For this study, we aimed to report the feasibility, efficacy, and safety of an established DCS-guided lithotomy procedure. METHODS: Data relating to biliary exploration, stone clearance, adverse events, and follow-up were obtained from 289 patients. The choledocholithiasis-related outcomes via the DCS-guided procedure were subsequently compared to those via conventional endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Biliary access was achieved in 285 patients. The technical success rate for the exploration of the common bile duct, the cystic stump, the hilar ducts, and secondary radicals was 100%. Moreover, the success rates were 98.4%, 61.7%, and 20.7%, for the exploration of the cystic duct, complete cystic duct, and gallbladder, respectively. Suspicious or confirmed suppurative cholecystitis, cholesterol polyps, and hyperplastic polyps were detected in 42, 23, and 5 patients, respectively. Stone clearance was achieved in one session in 285 (100%), 11 (100%), 13 (100%), 7 (100%), 6 (100%), and 3 (14.3%) patients with choledocholithiasis and hepatolithiasis, cystic duct stump stones, nondiffuse located intrahepatic lithiasis, a single cystic duct stone, a single gallbladder stone, and diffuse located intrahepatic lithiasis, respectively. Complete stone clearance for diffuse intrahepatic lithiasis was achieved in 19 (90.5%) patients, and fractioned re-lithotomy was performed in 16 (76.2%) patients. One patient developed mild acute cholangitis, and 12 developed mild pancreatitis. Stones recurred in one patient. Compared with conventional ERCP, DCS-guided lithotomy has the advantages of clearing difficult-to-treat choledocholithiasis and revealing concomitant biliary lesions, and this technique has fewer complications and a decreased risk of stone recurrence. CONCLUSIONS: The technical profile, efficacy, and safety of nonradiation-guided and DCS-guided lithotomy are shown in this study. We provide a feasible modality for the endoscopic removal of cholelithiasis.

Interpretable deep learning for chromatin-informed inference of transcriptional programs driven by somatic alterations across cancers.

Cancer is a disease of gene dysregulation, where cells acquire somatic and epigenetic alterations that drive aberrant cellular signaling. These alterations adversely impact transcriptional programs and cause profound changes in gene expression. Interpreting somatic alterations within context-specific transcriptional programs will facilitate personalized therapeutic decisions but is a monumental task. Toward this goal, we develop a partially interpretable neural network model called Chromatin-informed Inference of Transcriptional Regulators Using Self-attention mechanism (CITRUS). CITRUS models the impact of somatic alterations on transcription factors and downstream transcriptional programs. Our approach employs a self-attention mechanism to model the contextual impact of somatic alterations. Furthermore, CITRUS uses a layer of hidden nodes to explicitly represent the state of transcription factors (TFs) to learn the relationships between TFs and their target genes based on TF binding motifs in the open chromatin regions of tumor samples. We apply CITRUS to genomic, transcriptomic, and epigenomic data from 17 cancer types profiled by The Cancer Genome Atlas. CITRUS predicts patient-specific TF activities and reveals transcriptional program variations between and within tumor types. We show that CITRUS yields biological insights into delineating TFs associated with somatic alterations in individual tumors. Thus, CITRUS is a promising tool for precision oncology.

COVID-19db linkage maps of cell surface proteins and transcription factors in immune cells.

The highly contagious SARS-CoV-2 and its associated disease (COVID-19) are a threat to global public health and economies. To develop effective treatments for COVID-19, we must understand the host cell types, cell states and regulators associated with infection and pathogenesis such as dysregulated transcription factors (TFs) and surface proteins, including signaling receptors. To link cell surface proteins with TFs, we recently developed SPaRTAN (Single-cell Proteomic and RNA-based Transcription factor Activity Network) by integrating parallel single-cell proteomic and transcriptomic data based on Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) and gene cis-regulatory information. We apply SPaRTAN to CITE-seq data sets from patients with varying degrees of COVID-19 severity and healthy controls to identify the associations between surface proteins and TFs in host immune cells. Here, we present COVID-19db of Immune Cell States (https://covid19db.streamlit.app/), a web server containing cell surface protein expression, SPaRTAN-inferred TF activities, and their associations with major host immune cell types. The data include four high-quality COVID-19 CITE-seq data sets with a toolset for user-friendly data analysis and visualization. We provide interactive surface protein and TF visualizations across major immune cell types for each data set, allowing comparison between various patient severity groups for the discovery of potential therapeutic targets and diagnostic biomarkers.

Discrepant modulating effects of dietary docosahexaenoic acid on cerebral lipids, fatty acid transporter expression and soluble beta-amyloid levels in ApoE-/- and C57BL/6J mice.

AIMS: The study was designed to explore the role of apolipoprotein E (ApoE) deficiency concomitant with dietary docosahexaenoic acid (DHA) treatment on brain ß-amyloid (Aß) and lipid levels. METHOD: A 5-month dietary DHA intervention was conducted in ApoE-deficient (ApoE-/- ) mice and wild-type C57BL/6J (C57 wt) mice. The Morris water maze test was performed to assess the behaviour of the animals. The cortical contents of soluble Aß1-40 and Aß1-42 were detected by enzyme-linked immunosorbent assay (ELISA). Cortical fatty acid levels were detected by gas chromatography. Gene and protein expression of molecules associated with cerebral Aß and lipid metabolism were measured using real-time polymerase chain reaction (PCR), Western blot and histological methods. RESULTS: DHA treatment increased the content of cortical DHA and n-3 polyunsaturated fatty acids (n-3 PUFAs) but decreased the ratio of n-6/n-3 PUFAs in ApoE-/- mice; whereas the content of cortical DHA and n-3 PUFAs in C57 wt mice remained unchanged after DHA treatment. Cerebral Fabp5 and Cd36 gene expression were significantly downregulated in DHA-fed C57 wt mice; cerebral Cd36 and Scarb1 gene expression were significantly upregulated, whereas Fabp5 gene expression was downregulated in DHA-fed ApoE-/- mice. In comparison with C57 wt mice, the content of cortical soluble Aß1-42 , total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) increased, whereas the level of high-density lipoprotein cholesterol (HDL-C) decreased in ApoE-/- mice. Interestingly, these differences were significantly reversed by DHA dietary treatment. CONCLUSION: DHA intervention has discrepant impacts on cerebral lipids, fatty acid transporter expression and soluble Aß levels in ApoE-/- and C57 wt mice, suggesting the modifying role of ApoE status on the responses of cerebral lipids and Aß metabolism to DHA treatment.

Taxonomic and functional biogeographies of soil bacterial communities across the Tibet plateau are better explained by abiotic conditions than distance and plant community composition.

The processes governing soil bacteria biogeography are still not fully understood. It remains unknown how the importance of environmental filtering and dispersal differs between bacterial taxonomic and functional biogeography, and whether their importance is scale-dependent. We sampled soils across the Tibet plateau, with distances among plots ranging from 20 m to 1550 km. Taxonomic composition of bacterial community was characterized by 16S amplicon sequencing and functional community composition by qPCR targeting 9 functional groups involved in N dynamics. Factors representing climate, soil and plant community were measured to assess different facets of environmental dissimilarity. Both bacterial taxonomic and functional dissimilarities were more related to abiotic dissimilarity than biotic (vegetation) dissimilarity or distance. Taxonomic dissimilarity was mostly explained by differences in soil pH and mean annual temperature (MAT), while functional dissimilarity was linked to differences in soil N and P availabilities and N:P ratio. Soil pH and MAT remained the main determinants of taxonomic dissimilarity across spatial scales. In contrast, the explanatory variables of N-related functional dissimilarity varied across the scales, with soil moisture and organic matter having the highest role across short distances (<~330 km), and available P, N:P ratio and distance being important over long distances (>~660 km). Our results demonstrate how biodiversity dimension (taxonomic versus functional aspects) and spatial scale influence the factors driving soil bacterial biogeography.

Investigation on hybrid laser ablation and its application in fused silica damage mitigation.

We present and investigate a hybrid laser-based method of surface shaping for damage mitigation on fused silica surfaces. Damage sites were removed and precisely shaped into an optically-benign cone by a procedure of femtosecond laser ablation with a subsequent CO2 laser polishing process. The morphology of the cone rim was quantitatively predicted by a numerical model. Since the heat-affected zone (HAZ) of the laser polishing process was effectively confined by the optimization of ablation parameters, the dimensions of the raised rim were reduced by an order of magnitude. The intensity of the on-axis hotspot was positively related to the dimensions of the raised rim, and thus an inapparent downstream intensification was achieved by the rim reduction. Laser-induced damage threshold (LIDT) of the cone was tested to be ∼14 J/cm2 on the input surface. Therefore, the presented method is appropriate to mitigate damage and also provides a promising approach to manufacturing functional microstructures for high-power applications.

NiS Nanosheets Decorated on Hollow Carbon Spheres from Liquefied Wood for Supercapacitors.

Carbon-based supercapacitors with high performance have a wide foreground among various energy storage devices. In this work, wood-based hollow carbon spheres (WHCS) were prepared from liquefied wood through the processes of emulsification, curing, carbonization, and activation. Then, the hydrodeposition method was used to introduce nickel sulfide (NiS) to the surface of the microspheres, obtaining NiS/WHCS as the supercapacitor electrode. The results show that NiS/WHCS microspheres exhibited a core-shell structure and flower-like morphology with a specific surface (307.55 m2 g-1) and a large total pore volume (0.14 cm3 g-1). Also, the capacitance could be up to 1533.6 F g-1 at a current density of 1 A g-1. In addition, after 1000 charge/discharge cycles, the specific capacitance remained at 72.8% at the initial current density of 5 A g-1. Hence, NiS/WHCS with excellent durability and high specific capacitance is a potential candidate for electrode materials.

Vacancy-Modified Porous g-C3N4 Nanosheets Controlled by Physical Activation for Highly Efficient Visible-Light-Driven Hydrogen Evolution and Organics Degradation.

As a promising photocatalyst material, g-C3N4 has great application potential in energy production and environmental improvement. In this work, surface-modified g-C3N4 nanosheets with excellent stability and high photocatalytic activity were successfully synthesized by physical steam activation. The charge transfer rate of carbon nitride was improved due to the synergistic effect of nitrogen defect and oxygen doping caused by steam activation. Meanwhile, the specific surface area and pore volume of the optimized sample reached 124.3 m2 g-1 and 0.42 cm3 g-1, respectively, which increased the exposed reaction sites of reactants, enhancing the photocatalytic activity of g-C3N4. In addition, this novel g-C3N4 displayed a great H2 evolution rate of 5889.39 µmol h-1 g-1 with a methylene blue degradation rate up to 6.52 × 10-3 min-1, which was 3.7 and 2.1 times of original g-C3N4, respectively. This study provided a simple and economical method to develop a highly efficient g-C3N4 photocatalyst for solar energy conversion.

Titanium Carbide MXene Quantum Dots-Modified Hydroxyapatite Hollow Microspheres as pH/Near-Infrared Dual-Response Drug Carriers.

Titanium carbide MXene quantum dots (MQDs) possess intrinsic regulatory properties and selective toxicity to cancer cells. Here, MDQs were selected for the modification of hydroxyapatite (HA) microspheres, and MXene quantum dots-modified hydroxyapatite (MQDs-HA) hollow microspheres with controllable shapes and sizes were prepared as bone drug carriers. The results show that the prepared MQDs-HA hollow microspheres had a large BET surface area (231.2 m2/g), good fluorescence, and low toxicity. In addition, MQDs-HA showed a mild storage-release behavior and good responsiveness of pH and near-infrared (NIR). Thus, the MQDs-HA hollow microspheres have broad application prospects in the field of drug delivery and photothermal therapy.

Advances in DNA methylation and demethylation in medicinal plants: a review.

DNA methylation and demethylation are widely acknowledged epigenetic phenomena which can cause heritable and phenotypic changes in functional genes without changing the DNA sequence. They can thus affect phenotype formation in medicinal plants. However, a comprehensive review of the literature summarizing current research trends in this field is lacking. Thus, this review aims to provide an up-to-date summary of current methods for the detection of 5-mC DNA methylation, identification and analysis of DNA methyltransferases and demethyltransferases, and regulation of DNA methylation in medicinal plants. The data showed that polyploidy and environmental changes can affect DNA methylation levels in medicinal plants. Changes in DNA methylation can thus regulate plant morphogenesis, growth and development, and formation of secondary metabolites. Future research is required to explore the mechanisms by which DNA methylation regulates the accumulation of secondary metabolites in medicinal plants.

Clinical and Laboratory Characteristics of IgM Primary Plasma Cell Leukemia.

BACKGROUND: The aim of the study was to investigate the clinical and laboratory characteristics of IgM primary plasma cell leukemia. METHODS: We retrospectively analyzed a case of clinical and laboratory characteristics of IgM primary plasma cell leukemia and review related literature of patient with primary plasma cell leukemia. RESULTS: Laboratory tests: Alanine aminotransferase 128 U/L, Aspartate aminotransferase 245 U/L, Globulin 47.8 g/L, Lactate dehydrogenase 1,114 U/L, Creatinine 111.7 mol/L, Serum calcium 2.47 mmol/L, ß2 microglobulin 8.52 µg/mL, Immunoglobulin G 31.41 g/L, D-dimer 2.34 mg/L, Prothrombin time 13.6 seconds Fibrinogen 2 g/L, White blood cell 7.38 x 109/L, Red blood cell 3.46 x 1012/L, Hemoglobin 115 g/L, Platelet 7 x 109/L, and 12% Primitive naive cells can be seen in peripheral blood smear. Bone marrow smear: Accounted for 52% of original cells, the cell size, shape is irregular, the edge is not neat, the cell quality is rich, stained gray blue, cytoplasmic staining uneven, some devouring blood cells can be seen in the cytoplasm or unknown substance, the nucleus shape is irregular, visible distortion and fold, is visible on the part of the nuclei cavitation sample inclusions, chromatin is meticulous, partly visible large nucleoli. Flow cytometry results showed abnormal cell group held 23.85% of nuclear cells, expression of CD38, CD138, CD117, cKappa, partly CD20, weak expressing CD45, not express CD27, CD19, CD56, CD200, CD81, cLambda. It was a monoclonal plasma cell with an abnormal phenotype, consistent with a plasma cell tumor. Immunofixation electrophoresis results showed that the serum M protein was 22.80 g/L, which was IgG-κ type, the serum free KAP light chain was 232.69 mg/L, the serum free LAM light chain was 5.37 mg/L, and the rFLC (κ-FLC: λFLC) was 43.33. The diagnosis was primary plasmacytic leukemia of light chain type. CONCLUSIONS: Primary plasma cell leukemia (pPCL) is a rare and highly aggressive plasma cell malignancy. Laboratory staff should pay more attention to and recognize the pleomorphic morphology of neoplastic plasma cells, which can enable timely clinical development of bone marrow smear, biopsy, flow cytometry, and cytogenetic tests providing help in early diagnosis and treatment.

SPaRTAN, a computational framework for linking cell-surface receptors to transcriptional regulators.

The identity and functions of specialized cell types are dependent on the complex interplay between signaling and transcriptional networks. Recently single-cell technologies have been developed that enable simultaneous quantitative analysis of cell-surface receptor expression with transcriptional states. To date, these datasets have not been used to systematically develop cell-context-specific maps of the interface between signaling and transcriptional regulators orchestrating cellular identity and function. We present SPaRTAN (Single-cell Proteomic and RNA based Transcription factor Activity Network), a computational method to link cell-surface receptors to transcription factors (TFs) by exploiting cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) datasets with cis-regulatory information. SPaRTAN is applied to immune cell types in the blood to predict the coupling of signaling receptors with cell context-specific TFs. Selected predictions are validated by prior knowledge and flow cytometry analyses. SPaRTAN is then used to predict the signaling coupled TF states of tumor infiltrating CD8+ T cells in malignant peritoneal and pleural mesotheliomas. SPaRTAN enhances the utility of CITE-seq datasets to uncover TF and cell-surface receptor relationships in diverse cellular states.

Efficacy of continuous positive airway pressure on NT-pro-BNP in obstructive sleep apnea patients: a meta-analysis.

BACKGROUND: N-terminal probrain natriuretic peptide (NT-pro-BNP) and BNP are well-known markers for the diagnosis and prognostic of heart failure. Until now, it was not clear whether BNP levels are influenced by events occurring within Obstructive sleep apnea-hypopnea syndrome (OSAHS) with continuous positive airway pressure (CPAP). METHODS: A thorough search in PubMed, EMBASE, Google Scholar, and Web of Science databases up to October 24, 2022, and a meta-analysis aimed to explore further accurate estimates of the effects of BNP on OSAHS after CPAP treatment to assess the strength of the evidence. RESULTS: The forest plot outcome indicated that CPAP therapy did not change the BNP level in patients with OSAHS, with a weighted mean difference (WMD) of -0.47 (95% CI: -1.67 to 2.62; P = 0.53] based on the random effect model because of high significant heterogeneity (I2 = 80%) among the studies. Subgroup analysis also explored the changes in BNP levels in patients with OSAHS. Begg's test (P = 0.835) and Egger's test (P = 0.245) suggested significant negative publication bias. CONCLUSION: Our meta-analysis suggests that CPAP therapy does not change the BNP level in patients with OSAHS; therefore, it is not accurate to use BNP level as an index to evaluate heart function in patients with OSAHS, but more related research should be conducted.

Can natural environments enhance acute effects of rehabilitation exercise for older adults? A pilot randomized controlled trial.

The added value of natural environments in rehabilitation exercise is unclear. This study aimed to investigate whether there are more acute health benefits for older adults after a single rehabilitation exercise session performed in an outdoor natural environment compared with an indoor environment. Twenty-two nursing home residents were randomly assigned to the outdoor (n = 11, 79.5 ± 2.1 years) or indoor group (n = 11, 78.8 ± 5.2 years). Performance test outcomes were measured pre- and post-training session. The indoor group had a significantly higher blood pressure, greater increase in heart rate, higher perceived exercise intensity and physiological fatigue than the outdoor group. The combination of rehabilitation exercise with an outdoor natural environment may reduce exercise fatigue and improve cardiovascular health in older adults, with greater acute health benefits compared with an indoor environment. Rehabilitation exercise in the natural environments may be a highly valued environmental intervention for physiotherapy in older adults.

Synthesis of Crocin I and Crocin II by Multigene Stacking in Nicotiana benthamiana.

Crocins are a group of highly valuable water-soluble carotenoids that are reported to have many pharmacological activities, such as anticancer properties, and the potential for treating neurodegenerative diseases including Alzheimer's disease. Crocins are mainly biosynthesized in the stigmas of food-medicine herbs Crocus sativus L. and Gardenia jasminoides fruits. The distribution is narrow in nature and deficient in resources, which are scarce and expensive. Recently, the synthesis of metabolites in the heterologous host has opened up the potential for large-scale and sustainable production of crocins, especially for the main active compounds crocin I and crocin II. In this study, GjCCD4a, GjALDH2C3, GjUGT74F8, and GjUGT94E13 from G. jasminoides fruits were expressed in Nicotiana benthamiana. The highest total content of crocins in T1 generation tobacco can reach 78,362 ng/g FW (fresh weight) and the dry weight is expected to reach 1,058,945 ng/g DW (dry weight). Surprisingly, the primary effective constituents crocin I and crocin II can account for 99% of the total crocins in transgenic plants. The strategy mentioned here provides an alternative platform for the scale-up production of crocin I and crocin II in tobacco.