P53 and BCL-2 family proteins PUMA and NOXA define competitive fitness in pluripotent cell competition.

Cell Competition is a process by which neighboring cells compare their fitness. As a result, viable but suboptimal cells are selectively eliminated in the presence of fitter cells. In the early mammalian embryo, epiblast pluripotent cells undergo extensive Cell Competition, which prevents suboptimal cells from contributing to the newly forming organism. While competitive ability is regulated by MYC in the epiblast, the mechanisms that contribute to competitive fitness in this context are largely unknown. Here, we report that P53 and its pro-apoptotic targets PUMA and NOXA regulate apoptosis susceptibility and competitive fitness in pluripotent cells. PUMA is widely expressed specifically in pluripotent cells in vitro and in vivo. We found that P53 regulates MYC levels in pluripotent cells, which connects these two Cell Competition pathways, however, MYC and PUMA/NOXA levels are independently regulated by P53. We propose a model that integrates a bifurcated P53 pathway regulating both MYC and PUMA/NOXA levels and determines competitive fitness.

Hidden hotspots of amphibian biodiversity in China.

Identifying and protecting hotspots of endemism and species richness is crucial for mitigating the global biodiversity crisis. However, our understanding of spatial diversity patterns is far from complete, which severely limits our ability to conserve biodiversity hotspots. Here, we report a comprehensive analysis of amphibian species diversity in China, one of the most species-rich countries on Earth. Our study combines 20 y of field surveys with new molecular analyses of 521 described species and also identifies 100 potential cryptic species. We identify 10 hotspots of amphibian diversity in China, each with exceptional species richness and endemism and with exceptional phylogenetic diversity and phylogenetic endemism (based on a new time-calibrated, species-level phylogeny for Chinese amphibians). These 10 hotspots encompass 59.6% of China's described amphibian species, 49.0% of cryptic species, and 55.6% of species endemic to China. Only four of these 10 hotspots correspond to previously recognized biodiversity hotspots. The six new hotspots include the Nanling Mountains and other mountain ranges in South China. Among the 186 species in the six new hotspots, only 9.7% are well covered by protected areas and most (88.2%) are exposed to high human impacts. Five of the six new hotspots are under very high human pressure and are in urgent need of protection. We also find that patterns of richness in cryptic species are significantly related to those in described species but are not identical.

A new capacity of gut microbiota: Fermentation of engineered inorganic carbon nanomaterials into endogenous organic metabolites.

Carbon-based nanomaterials (CNMs) have recently been found in humans raising a great concern over their adverse roles in the hosts. However, our knowledge of the in vivo behavior and fate of CNMs, especially their biological processes elicited by the gut microbiota, remains poor. Here, we uncovered the integration of CNMs (single-walled carbon nanotubes and graphene oxide) into the endogenous carbon flow through degradation and fermentation, mediated by the gut microbiota of mice using isotope tracing and gene sequencing. As a newly available carbon source for the gut microbiota, microbial fermentation leads to the incorporation of inorganic carbon from the CNMs into organic butyrate through the pyruvate pathway. Furthermore, the butyrate-producing bacteria are identified to show a preference for the CNMs as their favorable source, and excessive butyrate derived from microbial CNMs fermentation further impacts on the function (proliferation and differentiation) of intestinal stem cells in mouse and intestinal organoid models. Collectively, our results unlock the unknown fermentation processes of CNMs in the gut of hosts and underscore an urgent need for assessing the transformation of CNMs and their health risk via the gut-centric physiological and anatomical pathways.

Automatic recognition of protein subcellular location patterns in single cells from immunofluorescence images based on deep learning.

With the improvement of single-cell measurement techniques, there is a growing awareness that individual differences exist among cells, and protein expression distribution can vary across cells in the same tissue or cell line. Pinpointing the protein subcellular locations in single cells is crucial for mapping functional specificity of proteins and studying related diseases. Currently, research about single-cell protein location is still in its infancy, and most studies and databases do not annotate proteins at the cell level. For example, in the human protein atlas database, an immunofluorescence image stained for a particular protein shows multiple cells, but the subcellular location annotation is for the whole image, ignoring intercellular difference. In this study, we used large-scale immunofluorescence images and image-level subcellular locations to develop a deep-learning-based pipeline that could accurately recognize protein localizations in single cells. The pipeline consisted of two deep learning models, i.e. an image-based model and a cell-based model. The former used a multi-instance learning framework to comprehensively model protein distribution in multiple cells in each image, and could give both image-level and cell-level predictions. The latter firstly used clustering and heuristics algorithms to assign pseudo-labels of subcellular locations to the segmented cell images, and then used the pseudo-labels to train a classification model. Finally, the image-based model was fused with the cell-based model at the decision level to obtain the final ensemble model for single-cell prediction. Our experimental results showed that the ensemble model could achieve higher accuracy and robustness on independent test sets than state-of-the-art methods.

[Synthesis and tissue distribution of bufadienolides in Bufo bufo gargarizans].

This study explored the biosynthesis of bufadienolides(BDs) in Bufo bufo gargarizans to solve the dilemma of the decreasing resources of B. bufo gargarizans and provide a theoretical basis for the sustainable utilization of the resources. Ultra-high performance liquid chromatography-Orbitrap-mass spectrometry(UHPLC-Orbitrap-MS) was employed to detect the synthesis sites of BDs in B. bufo gargarizans, and the results were verified by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI) and homogenate incubation experiments. BDs in B. bufo gargarizans had the highest content in the liver and the highest concentration in the gallbladder, in addition to the parotid gland and skin, which suggested that the liver could synthesize BDs. The results of DESI-MSI also showed that BDs were mainly enriched in the liver rather than the immature parotid gland. The incubation experiment of liver homogenates demonstrated the liver of B. bufo gargarizans had the ability to synthesize BDs. This study showed that the liver was a major organ for the synthesis of BDs in B. bufo gargarizans during metamorphosis, development, and growth, which provided strong theoretical support for the biosynthesis of BDs and the sustainable utilization of B. bufo gargarizans resources.

[Evaluation of efficacy of Dihuang Baoyuan Granules for diabetes mellitus and composition and in vivo distribution analysis based on UHPLC-LTQ-Orbitrap MS].

Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 µm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.

Species Persistence with Hybridization in Toad-Headed Lizards Driven by Divergent Selection and Low Recombination.

Speciation plays a central role in evolutionary studies, and particularly how reproductive isolation (RI) evolves. The origins and persistence of RI are distinct processes that require separate evaluations. Treating them separately clarifies the drivers of speciation and then it is possible to link the processes to understand large-scale patterns of diversity. Recent genomic studies have focused predominantly on how species or RI originate. However, we know little about how species persist in face of gene flow. Here, we evaluate a contact zone of two closely related toad-headed lizards (Phrynocephalus) using a chromosome-level genome assembly and population genomics. To some extent, recent asymmetric introgression from Phrynocephalus putjatai to P. vlangalii reduces their genomic differences. However, their highly divergent regions (HDRs) have heterogeneous distributions across the genomes. Functional gene annotation indicates that many genes within HDRs are involved in reproduction and RI. Compared with allopatric populations, contact areas exhibit recent divergent selection on the HDRs and a lower population recombination rate. Taken together, this implies that divergent selection and low genetic recombination help maintain RI. This study provides insights into the genomic mechanisms that drive RI and two species persistence in the face of gene flow during the late stage of speciation.

Long-Read Genome Sequencing Provides Molecular Insights into Scavenging and Societal Complexity in Spotted Hyena Crocuta crocuta.

The spotted hyena (Crocuta crocuta) is a large and unique terrestrial carnivore. It is a particularly fascinating species due to its distinct phenotypic traits, especially its complex social structure and scavenging lifestyle, with associated high dietary exposure to microbial pathogens. However, the underlying molecular mechanisms related to these phenotypes remain elusive. Here, we sequenced and assembled a high-quality long-read genome of the spotted hyena, with a contig N50 length of ∼13.75 Mb. Based on comparative genomics, immunoglobulin family members (e.g., IGKV4-1) showed significant adaptive duplications in the spotted hyena and striped hyena. Furthermore, immune-related genes (e.g., CD8A, LAG3, and TLR3) experienced species-specific positive selection in the spotted hyena lineage. These results suggest that immune tolerance between the spotted hyena and closely related striped hyena has undergone adaptive divergence to cope with prolonged dietary exposure to microbial pathogens from scavenging. Furthermore, we provided the potential genetic insights underlying social complexity, hinting at social behavior and cognition. Specifically, the RECNE-associated genes (e.g., UGP2 and ACTR2) in the spotted hyena genome are involved in regulation of social communication. Taken together, our genomic analyses provide molecular insights into the scavenging lifestyle and societal complexity of spotted hyenas.

Evidence of cure for extranodal nasal-type natural killer/T-cell lymphoma with current treatment: an analysis of the CLCG database.

Survival from extranodal nasal-type NK/T-cell lymphoma (ENKTCL) has substantially improved over the last decade. However, there is little consensus as to whether a population of patients with ENKTCL can be considered "cured" of the disease. We aimed to evaluate the statistical "cure" of ENKTCL in the modern treatment era. This retrospective multicentric study reviewed the clinical data of 1,955 patients with ENKTCL treated with non-anthracycline-based chemotherapy and/or radiotherapy in the China Lymphoma Collaborative Group multicenter database between 2008 and 2016. A non-mixture cure model with incorporation of background mortality was fitted to estimate cure fractions, median survival times and cure time points. The relative survival curves attained plateau for the entire cohort and most subsets, indicating that the notion of cure was robust. The overall cure fraction was 71.9%. The median survival was 1.1 years in uncured patients. The cure time was 4.5 years, indicating that beyond this time, mortality in ENKTCL patients was statistically equivalent to that in the general population. Cure probability was associated with B symptoms, stage, performance status, lactate dehydrogenase, primary tumor invasion, and primary upper aerodigestive tract site. Elderly patients (>60 years) had a similar cure fraction to that of younger patients. The 5-year overall survival rate correlated well with the cure fraction across risk-stratified groups. Thus, statistical cure is possible in ENKTCL patients receiving current treatment strategies. Overall probability of cure is favorable, though it is affected by the presence of risk factors. These findings have a high potential impact on clinical practice and patients' perspective.

Outcome and risk prediction of early progression in patients with extranodal natural killer/T cell lymphoma from the CLCG study.

Recently, progression-free survival at 24 months (PFS24) was defined as clinically relevant for patients with extranodal NK/T cell lymphoma. Herein, the clinical data from two independent random cohorts (696 patients each in the primary and validation datasets) were used to develop and validate a risk index for PFS24 (PFS24-RI), and evaluate its ability to predict early progression. Patients achieving PFS24 had a 5-year overall survival (OS) of 95.8%, whereas OS was only 21.2% in those failing PFS24 (P<0.001). PFS24 was an important predictor of subsequent OS, independent of risk stratification. The proportion of patients achieving PFS24 and 5-year OS rates correlated linearly among risk-stratified groups. Based on multivariate analysis of the primary dataset, the PFS24-RI included five risk factors: stage II or III/IV, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group score ≥2, primary tumor invasion, and extra-upper aerodigestive tract. PFS24-RI stratified the patients into low-risk (0), intermediate-risk (1-2), high-risk (≥3) groups with different prognoses. Harrell's C-index of PFS24-RI for PFS24 prediction was 0.667 in the validation dataset, indicating a good discriminative ability. PFS24-RI calibration indicated that the actual observed and predicted probability of failing PFS24 agreed well. PFS24-RI provided the probability of achieving PFS24 at an individual patient level.

CdSe/TiO2NTs Heterojunction-Based Nonenzymatic Photoelectrochemical Sensor for Glucose Detection.

Compared with a single semiconductor, the heterojunction formed by two different semiconductors usually has higher light utilization and better photoelectric performance. By using stable TiO2 nanotubes as the main subject, CdSe/TiO2NTs heterojunctions were synthesized by a hydrothermal method. XRD, TEM, SEM, PL, UV-vis, and EIS were used to characterize the fabricated CdSe/TiO2NTs. Under visible light irradiation, CdSe/TiO2NTs heterojunctions exhibited a higher absorption intensity and lower degree of photogenerated carrier recombination than TiO2. The electrons and holes were proven to be effectively separated in this heterojunction via theoretical calculation. Under CdSe/TiO2NTs' optimal conditions, the glucose concentrations (10-90 µM) had a linear relationship with the photocurrent value, and the detection limit was 3.1 µM. Moreover, the CdSe/TiO2NTs sensor exhibited good selectivity and stability. Based on the experimental data and theoretical calculations, its PEC sensing mechanism was also illuminated.

Bifidobacterium spp. as functional foods: A review of current status, challenges, and strategies.

Members of Bifidobacterium are among the first microbes to colonize the human intestine naturally, their abundance and diversity in the colon are closely related to host health. Recently, the gut microbiota has been gradually proven to be crucial mediators of various metabolic processes between the external environment and the host. Therefore, the health-promoting benefits of Bifidobacterium spp. and their applications in food have gradually been widely concerned. The main purpose of this review is to comprehensively introduce general features, colonization methods, and safety of Bifidobacterium spp. in the human gut, highlighting its health benefits and industrial applications. On this basis, the existing limitations and scope for future research are also discussed. Bifidobacteria have beneficial effects on the host's digestive system, immune system, and nervous system. However, the first prerequisite for functioning is to have enough live bacteria before consumption and successfully colonize the colon after ingestion. At present, strain breeding, optimization (e.g., selecting acid and bile resistant strains, adaptive evolution, high cell density culture), and external protection technology (e.g., microencapsulation and protectants) are the main strategies to address these challenges in food application.

Impacts of climate change on herpetofauna diversity in the Qinghai-Tibetan Plateau.

Although numerous studies on the impacts of climate change on biodiversity have been published, only a handful are focused on the intraspecific level or consider population-level models (separate models per population). We endeavored to fill this knowledge gap relative to the Qinghai-Tibetan plateau (QTP) by combining species distribution modeling (SDMs) with population genetics (i.e., population-level models) and phylogenetic methods (i.e., phylogenetic tree reconstruction and phylogenetic diversity analyses). We applied our models to 11 endemic and widely distributed herpetofauna species inhabiting high elevations in the QTP. We aimed to determine the influence of environmental heterogeneity on species' responses to climate change, the magnitude of climate-change impacts on intraspecific diversity, and the relationship between species range loss and intraspecific diversity losses under 2 shared socioeconomic pathways (SSP245 and SSP585) and 3 future periods (2050s, 2070s, and 2090s). The effects of global climatic change were more pronounced at the intraspecific level (22% of haplotypes lost and 36% of populations lost) than the morphospecies level in the SSP585 climate change scenario. Maintenance of genetic diversity was in general determined by a combination of factors including range changes, species genetic structure, and the part of the range predicted to be lost. This is owing to the fact that the loss and survival of populations were observed in species irrespective of the predicted range changes (contraction or expansion). In the southeast (mountainous regions), climate change had less of an effect on range size (>100% in 3 species) than in central and northern QTP plateau regions (range size <100% in all species). This may be attributed to environmental heterogeneity, which provided pockets of suitable climate in the southeast, whereas ecosystems in the north and central regions were homogeneous. Generally, our results imply that mountainous regions with high environmental heterogeneity and high genetic diversity may buffer the adverse impacts of climate change on species distribution and intraspecific diversity. Therefore, genetic structure and characteristics of the ecosystem may be crucial for conservation under climate change.

Impactos del cambio climático sobre la diversidad de herpetofauna en la meseta Qinghai-Tíbet Región Aunque se han publicado numerosos estudios sobre los impactos del cambio climática en la biodiversidad, son muy pocos los que se enfocan en el nivel intraespecífico o que consideran modelos a nivel poblacional (modelos separados por población). Intentamos cerrar este vacío de conocimiento en relación con la meseta Qinghai-Tíbet (MQT) con la combinación entre modelos de distribución de especies (MDE) y genética poblacional (modelos a nivel poblacional) y métodos filogenéticos (reconstrucción de árboles filogenéticos y análisis de diversidad filogenética). Aplicamos nuestros modelos a once especies endémicas de herpetofauna con distribución amplia en las elevaciones más altas de la MQT. Nos planteamos determinar la influencia de la heterogeneidad de las especies sobre la respuesta de las especies al cambio climático, la magnitud de los impactos del cambio climático sobre la diversidad intraespecífica y la relación entre la pérdida de distribución de la especie y las pérdidas de diversidad intraespecífica bajo dos vías socioeconómicas (SSP245 y SSP585) y tres periodos del futuro (2050s, 2070s y 2090s). Los efectos del cambio climático global fueron más pronunciados a nivel intraespecífico (22% de pérdida en los haplotipos y 36% en las poblaciones) que al nivel morfoespecie en el escenario de cambio climático SSP585. El mantenimiento de la diversidad genética casi siempre estuvo determinado por una combinación de factores que incluyen cambios en la distribución, estructura genética de las especies y la parte de la distribución que se pronosticó se perdería. Esto se debe a que observamos la pérdida y supervivencia de las poblaciones sin importar los cambios pronosticados en la distribución (contracción o expansión). En las regiones montañosas del sureste, el cambio climático tuvo un efecto menor sobre la distribución (>100% en tres especies) comparado con las regiones de la meseta central y del norte de la MQT (distribución <100% en todas las especies). Esto puede atribuirse a la heterogeneidad ambiental, la cual proporciona recovecos de clima adecuado en el sureste, mientras que los ecosistemas en las regiones central y norte fueron homogéneos. De manera general, nuestros resultados implican que las regiones montañosas con una elevada heterogeneidad ambiental y una gran diversidad genética podrían reducir los impactos adversos del cambio climático sobre la distribución de las especies y la diversidad intraespecífica. Por lo tanto, la estructura genética y las características del ecosistema pueden ser cruciales para conservar bajo el cambio climático.

The prediction of postoperative delirium with the preoperative bispectral index in older aged patients: a cohort study.

BACKGROUND: Postoperative delirium (POD) is the most common postoperative complication in elderly patients, especially in older aged patients (aged 75 years or over). The development of electroencephalography analysis could provide indicators for early detection, intervention, and evaluation. If there are pathophysiological changes in the brain, the BIS value will also change accordingly. In this study, we investigated the predictive value of the preoperative bispectral (BIS) index in POD for patients aged over 75 years. METHODS: In this prospective study, patients (≥ 75 years) undergoing elective non-neurosurgery and non-cardiac surgery under general anesthesia were included (n = 308). Informed consent was obtained from all involved patients. Before the operation and during the first 5 postoperative days, delirium was assessed with the confusion assessment method by trained researchers twice every day. Thereafter, the preoperative bedside BIS of each patient was dynamically acquired by the BIS VISTA monitoring system and the BIS monitoring of electrodes. A series of evaluation scales were assessed before and after surgery. A preoperative predictive score was generated according to the results of multivariable logistic regression. The receiver operating characteristic curves were drawn and the area under the curves was estimated to evaluate the perioperative diagnostic values of BIS and preoperative predictive score for POD. The specificity, sensitivity, positive predictive value (PPV), and negative predictive (NPV) value were calculated. RESULTS: Delirium occurred in 50 of 308 (16.2%) patients. The median BIS of delirious patients was 86.7 (interquartile range [IQR] 80.0-94.0), lower than that of the non-delirious 91.9 (IQR 89.7-95.4, P < 0.001). According to the ROC curve of the BIS index, the optimal cut-off value was 84, with a sensitivity of 48%, specificity of 87%, PPV 43%, NPV 89% for forecasting POD and the area under curves was 0.67. While integrating BIS, mini-mental state examination, anemia, activities of daily living, and blood urea nitrogen, the model had a sensitivity of 78%, specificity of 74%, PPV of 0.37%, and NPV of 95% for forecasting POD, and the area under curves was 0.83. CONCLUSIONS: Preoperative bedside BIS in delirium patients was lower than that in non-delirium patients when undergoing non-neurosurgery and non-cardiac surgery in patients aged over 75. The model of integrating BIS, mini-mental state examination, anemia, activities of daily living, and blood urea nitrogen is a promising tool for predicting postoperative delirium in patients aged over 75.

Greater habitual resveratrol intakes were associated with lower risk of hip fracture- a 1:1 matched case-control study in Chinese elderly.

The aim of the study was to testify the association of dietary resveratrol (RSV) intakes with hip fracture risk in Chinese elderly. This was a 1:1 age- and gender- matched case-control study. Eligible cases were newly diagnosed patients of hip fracture. Dietary assessment was made by a 79-item validated food frequency questionnaire. Habitual RSV intakes were estimated as the sum of trans- and cis- isomers of resveratrol and piceid according to the available database. Multivariable conditional logistic regression was applied to examine the relationship of dietary RSV and RSV-rich foods with hip fracture risk. A total of 1,070 pairs of hip fracture incident cases and controls were recruited and 1,065 were included for analysis. Compared with the lowest group, total RSV in the highest quartile group had significantly reduced hip fracture risk by 66.3% (OR: 0.337, 0.222 ~ 0.571, ptrend < 0.001). Similar findings were observed for cis- and trans-RSV, cis- and trans-Piceid, as well as RSV-rich foods (grapes, apples and nuts) respectively. Subgroup analysis suggested more evident findings among female and less obese participants. Our findings demonstrated that higher habitual RSV intakes and RSV-rich foods, even in a relatively low amount, were associated with reduced risk of hip fracture in Chinese elderly.

Glucose Biosensor Based on Glucose Oxidase Immobilized on BSA Cross-Linked Nanocomposite Modified Glassy Carbon Electrode.

Glucose sensors based blood glucose detection are of great significance for the diagnosis and treatment of diabetes because diabetes has aroused wide concern in the world. In this study, bovine serum albumin (BSA) was used to cross-link glucose oxidase (GOD) on a glassy carbon electrode (GCE) modified by a composite of hydroxy fullerene (HFs) and multi-walled carbon nanotubes (MWCNTs) and protected with a glutaraldehyde (GLA)/Nafion (NF) composite membrane to prepare a novel glucose biosensor. The modified materials were analyzed by UV-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), and cyclic voltammetry (CV). The prepared MWCNTs-HFs composite has excellent conductivity, the addition of BSA regulates MWCNTs-HFs hydrophobicity and biocompatibility, and better immobilizes GOD on MWCNTs-HFs. MWCNTs-BSA-HFs plays a synergistic role in the electrochemical response to glucose. The biosensor shows high sensitivity (167 µA·mM-1·cm-2), wide calibration range (0.01-3.5 mM), and low detection limit (17 µM). The apparent Michaelis-Menten constant Kmapp is 119 µM. Additionally, the proposed biosensor has good selectivity and excellent storage stability (120 days). The practicability of the biosensor was evaluated in real plasma samples, and the recovery rate was satisfactory.

eConnect: implementation and preliminary evaluation of a virtually delivered attachment-based parenting intervention during COVID-19.

Connect, an attachment-based and trauma-informed parenting group intervention, has been demonstrated to improve adolescent mental health, parental wellbeing, and family functioning. We report on the online adaptation and delivery of Connect (eConnect) and pre-post treatment changes in parent, family and youth functioning in a clinical sample (N= 190) of parents of youth with serious mental health challenges. Consistent with research evaluating in-person Connect, parents reported significant reductions in youth internalizing and externalizing problems, attachment anxiety and avoidance, and aggression toward parents. Parents also reported significant reductions in caregiver strain and aggression toward their child. Unlike prior research, parent depressed mood did not decline, perhaps due to pandemic stressors. Program completion was remarkably high (84.7%), and parents reported high program satisfaction. Uptake by eConnect program facilitators and host agencies was extremely positive, suggesting good potential for sustainability and broadened program accessibility. Randomized clinical trials and implementation within diverse populations are needed.

[Tissue distribution of Qingfei Paidu Decoction based on HPLC-MS/MS].

The tissue distribution of Qingfei Paidu Decoction was studied by HPLC-MS/MS in vivo. Hypersil GOLD C_(18) column(2.1 mm×50 mm, 1.9 µm) was used for gradient elution with acetonitrile as the mobile phase A and 0.1% formic acid solution as the mobile phase B. High-resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning mode and multiple response monitoring(MRM) mode was employed to analyze the behaviors of the active components of Qingfei Paidu Decoction in diffe-rent tissues. The results showed that 19, 9, 17, 14, 22, 19, 24, and 2 compounds were detected in plasma, heart, liver, spleen, lung, kidney, large intestine, and brain, respectively. The compounds belonged to 8 groups, covering 14 herbs in the prescription. After administration with Qingfei Paidu Decoction, the compounds were rapidly distributed in various tissues, especially in the lung, liver, large intestine, and kidney. The majority of the compounds displayed secondary distribution. This study comprehensively analyzed the distribution rules of the main active components in Qingfei Paidu Decoction and provided a basis for the clinical application.

[Systematic comparison of two kinds of Bufonis Venenum derived from different Bufo gargarizans subspecies based on metabolomics and antitumor activity].

This paper compared the differences between two kinds of Bufonis Venenum produced by Bufo gargarizans gargarizans and B. gararizans andrewsi, and verified the rationality of the market value orientation of Bufonis Venenum based on the zebrafish mo-del. Twenty batches of Bufonis Venenum from Jiangsu province, Hebei province, Liaoning province, Jilin province, and Liangshan, Sichuan province, including B. gargarizans gargarizans and B. gararizans andrewsi, were collected. The UHPLC-LTQ-Orbitrap-MS combined with principal component analysis was used to compare the differences between two kinds of Bufonis Venenum. According to the limiting conditions of VIP>1, FC<0.5 or FC>2.0, and peak total area ratio>1%, 9 differential markers were determined, which were cinobufagin, cinobufotalin, arenobufagin, resibufogenin, scillaredin A, resibufagin, 3-(N-suberoylargininyl)-arenobufagin, 3-(N-suberoylargininyl)-marinobufagin, and 3-(N-suberoylargininyl)-resibufogenin. The content of 20 batches of Bufonis Venenum was determined according to the Chinese Pharmacopoeia(2020 edition) by high-performance liquid chromatography, and the 2 batches of Bufonis Venenum, CS7(8.99% of total content) and CS9(5.03% of total content), with the largest difference in the total content of the three quality control indexes of the Chinese Pharmacopoeia(bufalin, cinobufagin, and resibufogenin) were selected to evaluate their anti-liver tumor activity based on the zebrafish model. The tumor inhibition rates of the 2 batches were 38.06% and 45.29%, respectively, proving that only using the quality control indexes of the Chinese Pharmacopoeia as the value orientation of Bufonis Venenum market circulation was unreasonable. This research provides data support for the effective utilization of Bufonis Venenum resources and the establishment of a rational quality evaluation system of Bufonis Venenum.

[Study on biomarkers of acteoside in treating puromycin aminonucleoside nephropathy in young rats based on non-targeted urine metabolomics technology].

This study aims to reveal the endogenous metabolic characteristics of acteoside in the young rat model of purinomycin aminonucleoside nephropathy(PAN) by non-targeted urine metabolomics and decipher the potential mechanism of action. Biochemical indicators in the urine of rats from each group were determined by an automatic biochemical analyzer. The potential biomarkers and related core metabolic pathways were identified by ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). MetaboAnalyst 5.0 was used to establish the receiver operating characteristic(ROC) curve for evaluating the clinical diagnostic performance of core metabolites. The results showed that acteoside significantly decreased urinary protein-to-creatinine ratio in PAN young rats. A total of 17 differential metabolites were screened out by non-targeted urine metabolomics in PAN young rats and they were involved in phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis. Thirtten differential metabolites were screened by acteoside intervention in PAN young rats, and they were involved in phenylalanine metabolism and arginine and proline metabolism. Among them, leucylproline and acetophenone were the differential metabolites that were significantly recovered after acteoside treatment. These pathways suggest that acteoside treats PAN in young rats by regulating amino acid metabolism. The area under the curve of two core biomarkers, leucylproline and acetophenone, were both greater than 0.9. In summary, acteoside may restore amino acid metabolism by regulating endogenous differential metabolites in PAN young rats, which will help to clarify the mechanism of acteoside in treating chronic glomerulonephritis in children. The characteristic biomarkers screened out have a high diagnostic value for evaluating the treatment of chronic glomerulonephritis in children with acteoside.