Advances in gut-brain organ chips.

The brain and gut are sensory organs responsible for sensing, transmitting, integrating, and responding to signals from the internal and external environment. In-depth analysis of brain-gut axis interactions is important for human health and disease prevention. Current research on the brain-gut axis primarily relies on animal models. However, animal models make it difficult to study disease mechanisms due to inherent species differences, and the reproducibility of experiments is poor because of individual animal variations, which leads to a significant limitation of real-time sensory responses. Organ-on-a-chip platforms provide an innovative approach for disease treatment and personalized research by replicating brain and gut ecosystems in vitro. This enables a precise understanding of their biological functions and physiological responses. In this article, we examine the history and most current developments in brain, gut, and gut-brain chips. The importance of these systems for understanding pathophysiology and developing new drugs is emphasized throughout the review. This article also addresses future directions and present issues with the advancement and application of gut-brain-on-a-chip technologies.

Guidance of development, validation, and evaluation of algorithms for populating health status in observational studies of routinely collected data (DEVELOP-RCD).

BACKGROUND: In recent years, there has been a growing trend in the utilization of observational studies that make use of routinely collected healthcare data (RCD). These studies rely on algorithms to identify specific health conditions (e.g. diabetes or sepsis) for statistical analyses. However, there has been substantial variation in the algorithm development and validation, leading to frequently suboptimal performance and posing a significant threat to the validity of study findings. Unfortunately, these issues are often overlooked. METHODS: We systematically developed guidance for the development, validation, and evaluation of algorithms designed to identify health status (DEVELOP-RCD). Our initial efforts involved conducting both a narrative review and a systematic review of published studies on the concepts and methodological issues related to algorithm development, validation, and evaluation. Subsequently, we conducted an empirical study on an algorithm for identifying sepsis. Based on these findings, we formulated specific workflow and recommendations for algorithm development, validation, and evaluation within the guidance. Finally, the guidance underwent independent review by a panel of 20 external experts who then convened a consensus meeting to finalize it. RESULTS: A standardized workflow for algorithm development, validation, and evaluation was established. Guided by specific health status considerations, the workflow comprises four integrated steps: assessing an existing algorithm's suitability for the target health status; developing a new algorithm using recommended methods; validating the algorithm using prescribed performance measures; and evaluating the impact of the algorithm on study results. Additionally, 13 good practice recommendations were formulated with detailed explanations. Furthermore, a practical study on sepsis identification was included to demonstrate the application of this guidance. CONCLUSIONS: The establishment of guidance is intended to aid researchers and clinicians in the appropriate and accurate development and application of algorithms for identifying health status from RCD. This guidance has the potential to enhance the credibility of findings from observational studies involving RCD.

Establishment of a nomogram model for predicting therapy complications in patients with polycythemia and deep venous thrombosis.

BACKGROUND: Patients with deep venous thrombosis (DVT) residing at high altitudes can only rely on anticoagulation therapy, missing the optimal window for surgery or thrombolysis. Concurrently, under these conditions, patient outcomes can be easily complicated by high-altitude polycythemia (HAPC), which increases the difficulty of treatment and the risk of recurrent thrombosis. To prevent reaching this point, effective screening and targeted interventions are crucial. Thus, this study analyzes and provides a reference for the clinical prediction of thrombosis recurrence in patients with lower-extremity DVT combined with HAPC. AIM: To apply the nomogram model in the evaluation of complications in patients with HAPC and DVT who underwent anticoagulation therapy. METHODS: A total of 123 patients with HAPC complicated by lower-extremity DVT were followed up for 6-12 months and divided into recurrence and non-recurrence groups according to whether they experienced recurrence of lower-extremity DVT. Clinical data and laboratory indices were compared between the groups to determine the influencing factors of thrombosis recurrence in patients with lower-extremity DVT and HAPC. This study aimed to establish and verify the value of a nomogram model for predicting the risk of thrombus recurrence. RESULTS: Logistic regression analysis showed that age, immobilization during follow-up, medication compliance, compliance with wearing elastic stockings, and peripheral blood D-dimer and fibrin degradation product levels were indepen-dent risk factors for thrombosis recurrence in patients with HAPC complicated by DVT. A Hosmer-Lemeshow goodness-of-fit test demonstrated that the nomogram model established based on the results of multivariate logistic regression analysis was effective in predicting the risk of thrombosis recurrence in patients with lower-extremity DVT complicated by HAPC (χ 2 = 0.873; P > 0.05). The consistency index of the model was 0.802 (95%CI: 0.799-0.997), indicating its good accuracy and discrimination. CONCLUSION: The column chart model for the personalized prediction of thrombotic recurrence risk has good application value in predicting thrombotic recurrence in patients with lower-limb DVT combined with HAPC after discharge.

Dynamic development of microglia and macrophages after spinal cord injury.

Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response, with resident microglia and infiltrating macrophages playing pivotal roles. While previous studies have grouped these two cell types together based on similarities in structure and function, an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes. In this study, we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury. Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury, gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed. Regarding macrophages, our findings highlighted abundant communication with other cells, including fibroblasts and neurons. Both pro-inflammatory and neuroprotective effects of macrophages were also identified; the pro-inflammatory effect may be related to integrin ß2 (Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway. These findings were validated by in vivo experiments. This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury, and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.

Mycenabrunnescens (Basidiomycota, Mycenaceae), a new species of Mycena sect. Pterigenae from China.

Background: Mycena (Pers.) Roussel (1806) is a large genus of Mycenaceae known for having small to medium-sized basidiomata. It is typified by the species Mycenagalericulata (Scop.) Gray. For years, many mycologists have made important contributions to understanding Mycena and several monographs have been published. Three specimens were collected from China that belonged to the genus Mycena. On the basis of morphological analysis and phylogenetic analyses employing DNA sequences, a new species is described. New information: Mycenabrunnescens sp. nov. is described as a new species from subtropical areas of China. It is characterised by its brown pileus, whitish lamellae that turns brown when bruised, orange to brown lamellae edges, the absence of pleurocystidia and cheilocystidia with simple or branched excrescences at the apex containing yellowish-brown contents. We performed phylogenetic analyses on a concatenated dataset comprising the internal transcribed spacer and large subunit regions of nuclear ribosomal RNA using Bayesian Inference and Maximum Likelihood methods. The result showed that the new taxon clustered in an independent group and is closely related to M.albiceps and M.flosoides.

[Research status and reflection of the mechanism of TCM manipulation in the treatment of cervical spondylosis under the background of multi-disciplinary intersection].

The study of TCM manipulation's mechanism is the key scientific issue in the current manipulation research. It is the key and difficult point on the road of modernization and internationalization of Chinese orthopedics and traumatology. Meanwhile, it is also an important way to clarify systematically the scientific connotation of TCM manipulation. At present, our country is in an important period when multi-disciplinary intersection lead knowledge production, scientific innovation, and discipline development. The trend of cross-innovation between Chinese orthopedics and traumatology and other disciplines provides the carrier and method for the study of TCM manipulation's mechanism. Cervical spondylosis is the traditional dominant disease of Chinese orthopedics and traumatology. In recent years, many scholars have applied multi-disciplinary techniques and theories to explore the mechanism of TCM manipulation by focusing on the four dimensions of muscle, bone, blood vessel and nerve. The article takes the treatment of cervical spondylosis by TCM manipulation as the research entry point, and integrates the application status and implementation strategies of various techniques and theories under the background of multi-disciplinary intersection, which is conducive to the better combination, innovation and transformation of Chinese orthopedics and traumatology with other disciplines, and provides ideas and references for systematically clarifying the scientific connotation of TCM manipulation.

Comparative analysis of the color change in blue-green inclusions within neutrophils between two patients with different clinical outcomes.

Blue-green neutrophilic inclusions (BGNI), also known as "death bodies," are bright green structures observed in the cytoplasm of neutrophils or monocytes and are closely associated with acute liver failure, lactic acidosis, and other serious diseases. Some studies suggested a potential association with phagocytic lipofuscin released by damaged liver cells. The presence of BGNI typically indicated a poor prognosis. We presented two cases. Case 1 was diagnosed with novel bunyavirus infection and exhibited severe hepatic impairment and coagulation dysfunction along with the presence of BGNI in neutrophils. Despite receiving comprehensive symptomatic treatment, the patient's condition rapidly deteriorated leading to eventual demise. Case 2 had severe liver injury caused by wasp stings, and BGNI was observed. Following active treatment measures, the patient eventually achieved recovery. Throughout the disease course of case 1, there was a progressive deepening in color and increase in quantity of BGNI. Conversely, case 2 demonstrated an opposite trend. Based on the comparison of clinical outcomes and variations in color and quantity of BGNI between these two patients, it was found that an increase in the number and deepening of BGNI color corresponded to worsening condition. Conversely, a decrease in quantity and lightening of color indicated improvement. Hence, these findings suggest a possible association between changes in BGNI characteristics and prognosis.

The feasibility of targeted axillary dissection for breast cancer axillary surgery de-escalation after neoadjuvant therapy: A prospective cohort study.

PURPOSE: Targeted axillary dissection (TAD) after neoadjuvant therapy (NAT) includes removing of marked and sentinel lymph nodes (SLNs). The aim was to investigate the optimization of TAD localization techniques after NAT among breast cancer patients. METHODS: From November 2020 to 2022, we prospectively enrolled 107 lymph node-positive breast cancer patients in XX Hospital and received complete cycles of NAT. Patients were randomly divided into the following 3 groups before treatment: group A, marked node with clip (n=34); group B, marked node with 125I seed (n=32); and group C, marked node with clip and 125I seed (n=41). Dual tracers were used to search for SLNs after NAT. The main endpoint was the detection rate of marked nodes and false-negative rate (FNR). RESULTS: The detection rates using the TAD localization technique were 82.6% (28/34), 100% (32/32), and 100% (41/41) for groups A, B, and C, respectively (P>0.05). The FNR rates were 15.8%, 5.9%, and 5.6% among group A, B, and C, respectively (P>0.05). The FNR rates in cN1 patients were 5.1%, 2.7%, and 2.6%, among these three groups, respectively (P>0.05). The change in distance between 125I seeds and clips in axillary lymph nodes was <3 mm. The FNR rates of TAD guided by dye tracer, radiolabeled tracer, and dual tracers were 5.4%, 5.2%, and 3.4%, respectively (P>0.05). The negative predictive values were 93.0%, 93.0%, and 95.2%, respectively (P>0.05). CONCLUSION: Considering inexpensive and detect rate of 125I seeds, it is recommended that placement of 125I seeds to localize metastatic nodes in neoadjuvant setting. The TAD guided by dye tracer is also feasible for axillary de-escalation surgery after NAT in countries or regions without radiolabeled colloid.

A bibliometric analysis on laparoscopic pelvic floor surgery from 1996-2022.

INTRODUCTION: Pelvic organ prolapse is a common condition in middle-aged and older women. Laparoscopic pelvic floor surgery is frequently researched as a treatment for this issue. However, the effectiveness of this procedure has only been the subject of a few studies. METHODS: To quantitatively evaluate and display the relevant literature from the Web of Science database, we set the publication period of the literature from 1996 to 2022 and used VOSviewer and CiteSpace for visual analysis. RESULTS: Laparoscopic pelvic floor surgery research has increased year-on-year, with 1003 publications identified from 63 countries and published in 210 journals. In the global ranking of studies, the United States was the leader (n = 306; 30.5 %), with the most published authors being Campagna, Giuseppe (n = 17) and Scambia, Giovanni (n = 17). The International urogynecology journal included the most significant articles (n = 173; 17.2 %). Keyword analysis suggests that complications, rectal prolapse, native tissue repair, and warranty may have become hotspots in recent years. CONCLUSIONS: This bibliometric study shows that the depth and breadth of research on pelvic floor laparoscopic surgery have expanded rapidly over the last twenty-five years and that laparoscopic surgery has been recognized by different scholars or countries as an essential modality for the treatment of pelvic floor organ prolapse.

Discovering New Metallo-Deubiquitinase CSN5 Inhibitors by a Non-Catalytic Activity Assay Platform.

COP9 signalosome catalytic subunit CSN5 plays a key role in tumorigenesis and tumor immunity, showing potential as an anticancer target. Currently, only a few CSN5 inhibitors have been reported, at least partially, due to the challenges in establishing assays for CSN5 deubiquitinase activity. Here, we present the establishment and validation of a simple and reliable non-catalytic activity assay platform for identifying CSN5 inhibitors utilizing a new fluorescent probe, CFP-1, that exhibits enhanced fluorescence and fluorescence polarization features upon binding to CSN5. By using this platform, we identified 2-aminothiazole-4-carboxylic acids as new CSN5 inhibitors, which inhibited CSN5 but slightly downregulated PD-L1 in cancer cells. Furthermore, through the integration of deep learning-enabled virtual screening, we discovered that shikonins are nanomolar CSN5 inhibitors, which can upregulate PD-L1 in HCT116 cells. The binding modes of these structurally distinct inhibitors with CSN5 were explored by using microsecond-scale molecular dynamics simulations and tryptophan quenching assays.

Application effectiveness of "Youxin-1" in genetic diversity and structure analysis of local chickens.

China's local chicken breeds are rich in resources, and have formed different germplasm characteristics in the process of long-term selection and evolution. Scientific assessment of population genetic diversity and identification of inter-breed genetic structure are of great value to the protection and innovative utilization of local chicken breed resource. In order to evaluate the application effectiveness of 23K SNP chip "Youxin-1" in the analysis of genetic diversity and genetic structure of local chickens, we used RADseq to identify genomic genetic variation of 21 local chicken breeds and developed 23K chip "Youxin-1". The genetic statistics of each variety were calculated based on two sets of SNP data, and correlation, fitting and phylogenetic analysis were carried out to evaluate the application effectiveness of the chip. The results showed that the observed heterozygosity (Ho), polymorphism information content (PIC), inbred coefficient (FROH) and genetic differentiation coefficient (Fst) calculated based on the two SNP data sets were basically consistent in the 21 local chicken breeds. The genetic diversity of Langya chicken (LA), Piao chicken (PJ) and Wenchang chicken (WC) was relatively rich. The genetic diversity of Bian chickens (BJ), Langshan chickens (LS), Gushi chickens (GS), Dongxiang blue-eggshell chickens (DX) and Beijing fatty chickens (BY) was relatively poor, and the correlation coefficients of Ho, PIC, FROH and average Fst in the two groups were 0.794, 0.901, 0.926 and 0.984, respectively, all reaching extremely significant levels (P<0.01) with a high degree of fit (P<0.001) and R2 were 0.644, 0.827, 0.916 and 0.927. For the two sets of SNP data, the evolutionary tree constructed by neighbor-joining (NJ) method and maximum likelihood (ML) method was reasonable, and the 21 local chicken breeds were generally divided into six categories, which was consistent with the formation history and geographical distribution of the varieties. The 23K chip also realized reasonable clustering of the five new varieties without individual deviation. There are some differences in the estimation of genetic statistics using SNP with different densities, and data standardization is needed. 23K chip has good efficacy in the analysis of genetic diversity and structure of local chickens.

Research progress on plant-derived cardenolides(2010-2023).

Cardenolides are a class of steroidal glycoside compounds that are mainly distributed in plants, have significant physiological activity in the heart, and have been used clinically for over 200 years. To provide a reference for further research and development of these compounds, the phytochemical and biological properties of natural cardenolides (295 compounds in total) isolated between 2010 and 2023 from 17 families and hundreds of species belonging to 70-80 genera were reviewed. In vitro and in vivo studies have indicated that antitumor, antibacterial, and antiviral activities are the most commonly reported pharmacological properties of cardenolides. Antitumor activities have been thoroughly studied to understand their structure-activity relationships, revealing numerous potential anticancer molecules that lay the theoretical foundation for further development of traditional Chinese medicinal herbs and the creation of new drugs.

Friend or foe? Using eye-tracking technology to investigate the visual discrimination ability of giant pandas.

The role that visual discriminative ability plays among giant pandas in social communication and individual discrimination has received less attention than olfactory and auditory modalities. Here, we used an eye-tracker technology to investigate pupil fixation patterns for 8 captive male giant pandas Ailuropoda melanoleuca. We paired images (N = 26) of conspecifics against: 1) sympatric predators (gray wolves and tigers), and non-threatening sympatric species (golden pheasant, golden snub-nosed monkey, takin, and red panda), 2) conspecifics with atypical fur coloration (albino and brown), and 3) zookeepers/non-zookeepers wearing either work uniform or plain clothing. For each session, we tracked the panda's pupil movements and measured pupil first fixation point (FFP), fixation latency, total fixation count (TFC), and duration (TFD) of attention to each image. Overall, pandas exhibited similar attention (FFPs and TFCs) to images of predators and non-threatening sympatric species. Images of golden pheasant, snub-nosed monkey, and tiger received less attention (TFD) than images of conspecifics, whereas images of takin and red panda received more attention, suggesting a greater alertness to habitat or food competitors than to potential predators. Pandas' TFCs were greater for images of black-white conspecifics than for albino or brown phenotypes, implying that familiar color elicited more interest. Pandas reacted differently to images of men versus women. For images of women only, pandas gave more attention (TFC) to familiar combinations (uniformed zookeepers and plain-clothed non-zookeepers), consistent with the familiarity hypothesis. That pandas can use visual perception to discriminate intra-specifically and inter-specifically, including details of human appearance, has applications for panda conservation and captive husbandry.

Veillonella parvula promotes root caries development through interactions with Streptococcus mutans and Candida albicans.

Root caries is a subtype of dental caries that predominantly impacts older adults. The occurrence and progression of root caries are associated with the homeostasis of dental plaque biofilm, and microbial synergistic and antagonistic interactions in the biofilm play a significant role in maintaining the oral microecological balance. The objective of the current study was to investigate the role of Veillonella parvula in the microbial interactions and the pathogenesis of root caries. The analysis of clinical samples from patients with/without root caries revealed that Veillonella and V. parvula were abundant in the saliva of patients with root caries. More importantly, a significantly increased colonization of V. parvula was observed in root carious lesions. Further in vitro biofilm and animal study showed that V. parvula colonization increased the abundance and virulence of Streptococcus mutans and Candida albicans, leading to the formation of a polymicrobial biofilm with enhanced anti-stress capacity and cariogenicity, consequently exacerbating the severity of carious lesions. Our results indicate the critical role of V. parvula infection in the occurrence of root caries, providing a new insight for the etiological investigation and prevention of root caries.

Rnai-based functional analysis of bursicon genes related to cuticle pigmentation in a ladybird beetle.

In arthropods, the binding of a bursicon (encoded by burs and pburs) heterodimer or homodimer to a leucine-rich repeat-containing G protein coupled receptor LGR2 (encoded by rk) can activate many physiological processes, especially cuticle pigmentation during insect ecdysis. In the current paper, we intended to ascertain whether bursicon signaling mediates body coloration in the 28-spotted larger potato ladybird, Henosepilachna vigintioctomaculata, and if so, by which way bursicon signal governs the pigmentation. The high expression of Hvburs, Hvpburs and Hvrk occurred in the young larvae, pupae and adults, especially in the head and ventral nerve cord. RNA interference (RNAi) aided knockdown of Hvburs, Hvpburs or Hvrk in the prepupae caused similar phenotypic defects. The pigmentation of the resultant adults was affected, with significantly reduced dark areas on the sternums. Moreover, the accumulated mRNA levels of two sclerotin biosynthesis genes, aspartate 1-decarboxylase gene Hvadc and N-ß-alanyldopamine synthase gene Hvebony, were significantly increased in the Hvburs, Hvpburs or Hvrk RNAi beetles. Furthermore, depletion of either Hvadc or Hvebony could completely rescue the impaired coloration on the sternums of Hvpburs RNAi adult. Our results supported that bursicon heterodimer-mediated signal regulate cuticle pigmentation. The bursicon signaling may tune the ratio of melanins (dark/black, brown) to sclerotins (light yellow, colorless) exerting its regulative role in the pigmentation of H. vigintioctomaculata sternums.

Design, synthesis, and antifungal activity of novel pyrazole carboxamide derivatives containing benzimidazole moiety as potential SDH inhibitors.

To address the urgent need for new antifungal agents, a collection of novel pyrazole carboxamide derivatives incorporating a benzimidazole group were innovatively designed, synthesized, and evaluated for their efficacy against fungal pathogens. The bioassay results revealed that the EC50 values for the compounds A7 (3-(difluoromethyl)-1-methyl-N-(1-propyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazole-4-carboxamide) and B11 (N-(1-(4-chlorobenzyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide) against B. cinerea were notably low to 0.79 µg/mL and 0.56 µg/mL, respectively, demonstrating the potency comparable to that of the control fungicide boscalid, which has an EC50 value of 0.60 µg/mL. Noteworthy is the fact that in vivo tests demonstrated that A7 and B11 showed superior protective effects on tomatoes and strawberries against B. cinerea infection when juxtaposed with the commercial fungicide carbendazim. The examination through scanning electron microscopy revealed that B11 notably alters the morphology of the fungal mycelium, inducing shrinkage and roughening of the hyphal surfaces. To elucidate the mechanism of action, the study on molecular docking and molecular dynamics simulations was conducted, which suggested that B11 effectively interacts with crucial amino acid residues within the active site of succinate dehydrogenase (SDH). This investigation contributes a novel perspective for the structural design and diversification of potential SDH inhibitors, offering a promising avenue for the development of antifungal therapeutics.

Genetic Regulatory Perturbation of Gene Expression Impacted by Genomic Introgression in Fiber Development of Allotetraploid Cotton.

Interspecific genomic introgression is an important evolutionary process with respect to the generation of novel phenotypic diversity and adaptation. A key question is how gene flow perturbs gene expression networks and regulatory interactions. Here, an introgression population of two species of allopolyploid cotton (Gossypium) to delineate the regulatory perturbations of gene expression regarding fiber development accompanying fiber quality change is utilized. De novo assembly of the recipient parent (G. hirsutum Emian22) genome allowed the identification of genomic variation and introgression segments (ISs) in 323 introgression lines (ILs) from the donor parent (G. barbadense 3-79). It documented gene expression dynamics by sequencing 1,284 transcriptomes of developing fibers and characterized genetic regulatory perturbations mediated by genomic introgression using a multi-locus model. Introgression of individual homoeologous genes exhibiting extreme low or high expression bias can lead to a parallel expression bias in their non-introgressed duplicates, implying a shared yet divergent regulatory fate of duplicated genes following allopolyploidy. Additionally, the IL N182 with improved fiber quality is characterized, and the candidate gene GhFLAP1 related to fiber length is validated. This study outlines a framework for understanding introgression-mediated regulatory perturbations in polyploids, and provides insights for targeted breeding of superior upland cotton fiber.

Guided wave elastography of human skins with a layered model incorporating the effect of muscle state.

In vivo mechanical characterization of skin finds broad applications in understanding skin aging, diagnosis of some skin diseases and assessing the effectiveness of diverse skin care strategies. Skin has a layered structure consisting of the epidermis, dermis and subcutaneous layers. Although much effort has been made towards mechanical characterization of skin, it remains a challenging issue to measure the mechanical properties of an individual layer in vivo. To address this issue, we here report a guided wave elastography method for layered human skin which incorporates the effect of muscle states. Both finite element simulations and phantom experiments have been performed to validate the method. For skin-mimicking phantoms with different fat layer thicknesses, the errors in the identified shear modulus of the skin layers are no more than 11 %. In vivo experiments have been carried out on 6 healthy subjects to demonstrate the potential use of the method in clinics. A statistical analysis indicates the muscle contraction contributes to the stiffening of the skin (p < 0.001). Finally, a phase diagram has been constructed to reveal the extent to which muscle sates (including both passive and active states) affect the measurement of elastic modulus of a skin layer, which may guide the application of the method in practice.