Combining multiomics to analyze the molecular mechanism of hair follicle cycle change in cashmere goats from Inner Mongolia.

Sheep body size can directly reflect the growth rates and fattening rates of sheep and is also an important index for measuring the growth performance of meat sheep.Inner Mongolia Cashmere Goat is a local excellent breed of cashmere and meat dual-purpose, which is a typical heterogeneous indumentum. The hair follicles cycle through periods of vigorous growth (anagen), a regression caused by apoptosis (catagen), and relative rest (telogen). At present, it is not clear which genes affect the cycle transformation of hair follicles and unclear how proteins impact the creation and expansion of hair follicles.we using multi-omics joint analysis methodologies to investigated the possible pathways of transformation and apoptosis in goat hair follicles. The results showed that 917,1,187, and 716 proteins were specifically expressed in anagen, catagen andtelogen. The result of gene ontology (GO) annotation showed that differentially expressed proteins (DEPs) are in different growth cycle periods, and enriched GO items are mostly related to the transformation of cells and proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment result indicated that the apoptosis process has a great impact on hair follicle's growth cycle. The results of the protein interaction network of differential proteins showed that the ribosomal protein family (RPL4, RPL8, RPS16, RPS18, RPS2, RPS27A, RPS3) was the core protein in the network. The results of combined transcriptome and proteomics analysis showed that there were 16,34, and 26 overlapped DEGs and DEPs in the comparison of anagen VS catagen, catagen VS telogen and anagen VS telogen, of which API5 plays an important role in regulating protein and gene expression levels. We focused on API5 and Ribosomal protein and found that API5 affected the apoptosis process of hair follicles, and ribosomal protein was highly expressed in the resting stage of hair follicles. They are both useful as molecular marker candidate genes to study hair follicle growth and apoptosis,and they both have an essential function in the cycle transition process of hair follicles. The results of this study may provide a theoretical basis for further research on the growth and development of hair follicles in Inner Mongolian Cashmere goats.

Can the natural resource balance sheet system promote ecological civilization? --Empirical evidence from panel data of prefecture-level cities in China.

As a crucial carrier of natural resource and environmental information, the natural resources balance sheet is important in enhancing ecological governance capabilities and advancing ecological civilization construction. Utilizing panel data from Chinese prefecture cities spanning 2012 to 2018, we employ a Difference-in-Differences (DID) model to examine the policy effects of the natural resources balance sheet system. The findings indicate that compiling the natural resources balance sheet significantly promotes local ecological civilization construction, and local government environmental governance efficiency partially mediates this relationship. Further analysis indicates that the outgoing audit of natural resources and public environmental concern positively moderates the relationship between the two. Drawing on the principal-agent theory, we provide in-depth analysis and elucidation of the mechanisms through which the natural resources balance sheet promotes ecological civilization construction, offering theoretical guidance and empirical data support for strengthening the compilation and application of the natural resources balance sheet.

Recent advances in microfluidic-based spectroscopic approaches for pathogen detection.

Rapid identification of pathogens with higher sensitivity and specificity plays a significant role in maintaining public health, environmental monitoring, controlling food quality, and clinical diagnostics. Different methods have been widely used in food testing laboratories, quality control departments in food companies, hospitals, and clinical settings to identify pathogens. Some limitations in current pathogens detection methods are time-consuming, expensive, and laborious sample preparation, making it unsuitable for rapid detection. Microfluidics has emerged as a promising technology for biosensing applications due to its ability to precisely manipulate small volumes of fluids. Microfluidics platforms combined with spectroscopic techniques are capable of developing miniaturized devices that can detect and quantify pathogenic samples. The review focuses on the advancements in microfluidic devices integrated with spectroscopic methods for detecting bacterial microbes over the past five years. The review is based on several spectroscopic techniques, including fluorescence detection, surface-enhanced Raman scattering, and dynamic light scattering methods coupled with microfluidic platforms. The key detection principles of different approaches were discussed and summarized. Finally, the future possible directions and challenges in microfluidic-based spectroscopy for isolating and detecting pathogens using the latest innovations were also discussed.

Epigenetic-related gene-based prognostic model construction and validation in prostate adenocarcinoma.

Prostate adenocarcinoma (PRAD), driven by both genetic and epigenetic factors, is a common malignancy that affects men worldwide. We aimed to identify and characterize differentially expressed epigenetic-related genes (ERGs) in PRAD and investigate their potential roles in disease progression and prognosis. We used PRAD samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to identify prognosis-associated ERGs. Thirteen ERGs with two distinct expression profiles were identified through consensus clustering. Gene set variation analysis highlighted differences in pathway activities, particularly in the Hedgehog and Notch pathways. Higher epigenetic scores correlated with favorable prognosis and improved immunotherapeutic response. Experimental validation underscored the importance of CBX3 and KAT2A, suggesting their pivotal roles in PRAD. This study provides crucial insights into the epigenetic scoring approach and presents a promising prognostic tool, with CBX3 and KAT2A as key players. These findings pave the way for targeted and personalized interventions for the treatment of PRAD.

Effects of nonsynonymous single nucleotide polymorphisms of the KIAA1217, SNTA1 and LTBP1 genes on the growth traits of Ujumqin sheep.

Sheep body size can directly reflect the growth rates and fattening rates of sheep and is also an important index for measuring the growth performance of meat sheep. In this study, high-resolution resequencing data from four sheep breeds (Dorper sheep, Suffolk sheep, Ouessant sheep, and Shetland sheep) were analyzed. The nonsynonymous single nucleotide polymorphisms of three candidate genes (KIAA1217, SNTA1, and LTBP1) were also genotyped in 642 healthy Ujumqin sheep using MALDI-TOFMS and the genotyping results were associated with growth traits. The results showed that different genotypes of the KIAA1217 g.24429511T>C locus had significant effects on the chest circumferences of Ujumqin sheep. The SNTA1 g.62222626C>A locus had different effects on the chest depths, shoulder widths and rump widths of Ujumqin sheep. This study showed that these two sites can be used for marker-assisted selection, which will be beneficial for future precision molecular breeding.

Synthesis of Mono-, Di-, Tri-, and Tetra-cationic Pyridinium and Vinylpyridinium Modified [2.2]Paracyclophanes: Modular Receptors for Supramolecular Systems.

In this report, a new series of mono-, di-, tri-, and tetra-cationic pyridinium and vinyl pyridinium-modified [2.2]paracyclophanes as useful molecular tectons for supramolecular systems are described. Regioselective functionalization at specific positions, followed by resolution step and successive transformations through Pd-catalyzed Suzuki-Miyaura and Mizoroki-Heck cross-coupling chemistry furnish a series of modular PCP scaffolds. In our proof-of-concept study, on N-methylation, the PCPs bearing (cationic) pyridyl functionalities were demonstrated as useful molecular receptors in host-guest supramolecular assays. The PCPs on grafting with light-responsive azobenzene (-N=N-) functional core as side-groups impart photosensitivity that can be remotely transformed on irradiation, offering photo-controlled smart molecular functions. Furthermore, the symmetrical PCPs bearing bi-, and tetra-pyridyl functionalities at the peripheries have enormous potential to serve as ditopic and tetratopic 3D molecular tectons for engineering non-covalent supramolecular assemblies with new structural and functional attributes.

Justice at the Forefront: Cultivating felt accountability towards Artificial Intelligence among healthcare professionals.

The advent of AI has ushered in a new era of patient care, but with it emerges a contentious debate surrounding accountability for algorithmic medical decisions. Within this discourse, a spectrum of views prevails, ranging from placing accountability on AI solution providers to laying it squarely on the shoulders of healthcare professionals. In response to this debate, this study, grounded in the mutualistic partner choice (MPC) model of the evolution of morality, seeks to establish a configurational framework for cultivating felt accountability towards AI among healthcare professionals. This framework underscores two pivotal conditions: AI ethics enactment and trusting belief in AI and considers the influence of organizational complexity in the implementation of this framework. Drawing on Fuzzy-set Qualitative Comparative Analysis (fsQCA) of a sample of 401 healthcare professionals, this study reveals that a) focusing justice and autonomy in AI ethics enactment along with building trusting belief in AI reliability and functionality reinforces healthcare professionals' sense of felt accountability towards AI, b) fostering felt accountability towards AI necessitates ensuring the establishment of trust in its functionality for high complexity hospitals, and c) prioritizing justice in AI ethics enactment and trust in AI reliability is essential for low complexity hospitals.

Multisequence MRI-based radiomics signature as potential biomarkers for differentiating KRAS mutations in non-small cell lung cancer with brain metastases.

Background: Kirsten rat sarcoma virus (KRAS) has evolved from a genotype with predictive value to a therapeutic target recently. The study aimed to establish non-invasive radiomics models based on MRI to discriminate KRAS from epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations in lung cancer patients with brain metastases (BM), then further explore the optimal sequence for prediction. Methods: This retrospective study involved 317 patients (218 patients in training cohort and 99 patients in testing cohort) who had confirmed of KRAS, EGFR or ALK mutations. Radiomics features were separately extracted from T2WI, T2 fluid-attenuated inversion recovery (T2-FLAIR), diffusion weighted imaging (DWI) and contrast-enhanced T1-weighted imaging (T1-CE) sequences. The maximal information coefficient and recursive feature elimination method were used to select informative features. Then we built four radiomics models for differentiating KRAS from EGFR or ALK using random forest classifier. ROC curves were used to validate the capability of the models. Results: The four radiomics models for discriminating KRAS from EGFR all worked well, especially DWI and T2WI models (AUCs: 0.942, 0.942 in training cohort, 0.949, 0.954 in testing cohort). When KRAS compared to ALK, DWI and T2-FLAIR models showed excellent performance in two cohorts (AUCs: 0.947, 0.917 in training cohort, 0.850, 0.824 in testing cohort). Conclusions: Radiomics classifiers integrating MRI have potential to discriminate KRAS from EGFR or ALK, which are helpful to guide treatment and facilitate the discovery of new approaches capable of achieving this long-sought goal of cure in lung cancer patients with KRAS.

The human microbiome and benign prostatic hyperplasia: Current understandings and clinical implications.

The research of the human microbiome in the preceding decade has yielded novel perspectives on human health and diseases. Benign prostatic hyperplasia (BPH) is a common disease in middle-aged and elderly males, which negatively affects the life quality. Existing evidence has indicated that the human microbiome, including urinary, intra-prostate, gut, oral and blood microbiome may exert a significant impact on the natural progression of BPH. The dysbiosis of the microbiome may induce inflammation at either a local or systemic level, thereby affecting the BPH. Moreover, metabolic syndrome (MetS) caused by the microbiome can also be involved in the development of BPH. Additionally, alterations in the microbiome composition during the senility process may serve as another cause of the BPH. Here, we summarize the influence of human microbiome on BPH and explore how the microbiome is linked to BPH through inflammation, MetS, and senility. In addition, we propose promising areas of investigation and discuss the implications for advancing therapeutic approaches.

Modulating Aryl Azide Photolysis: Synthesis of a Room-Temperature Phosphorescent Carboline in Cucurbit[7]uril Host.

Cucurbit[7]uril (CB7), a supramolecular host, is employed to control the pathway of photolysis of an aryl azide in an aqueous medium. Normally, photolysis of aryl azides in bulk water culminates predominantly in the formation of azepine derivatives via intramolecular rearrangement. Remarkably, however, when this process unfolds within the protective confinement of the CB7 cavity, it results in a carboline derivative, as a consequence of a C─H amination reaction. The resulting carboline caged by CB7 reveals long-lived room temperature phosphorescence (RTP) in the solid state, with lifetimes extending up to 2.1 s. These findings underscore the potential of supramolecular hosts to modulate the photolysis of aryl azides and to facilitate novel phosphorescent materials.

Cathepsin V is correlated with the prognosis and tumor microenvironment in liver cancer.

Recent studies have shown that high cell cycle activity negatively correlates with antitumor immunity in certain cancer types. However, a similar correlation has not been proven in liver cancer. We downloaded transcriptomic profiles of the cancer genome atlas-liver hepatocellular carcinoma (TCGA-LIHC) and assessed the cell cycle distribution of samples using single sample gene set enrichment analysis (ssGSEA), termed the cell cycle score (CCS). We obtained cell cycle-related differentially expressed prognostic genes and identified CENPA, CDC20, and CTSV using LASSO regression. We studied the effect of CTSV on clinical features and immune alterations in liver cancer based on TCGA-LIHC data. In vitro and in vivo experiments were performed to validate the role of CTSV in liver cancer using liver cancer cell lines and tissues. We found that the CCS closely correlated with the clinical features and prognosis of patients in TCGA-LIHC. Analysis of differentially expressed genes (DEGs), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression identified cathepsin V (CTSV) with prognostic significance in LIHC. Importantly, single-gene survival analysis of CTSV using microarray and sequencing data indicated that high levels of CTSV expression correlated with an unfavorable prognosis in various cancers. Gene set enrichment analysis revealed that high CTSV expression closely correlated with decreased expression of metabolic genes and increased expression of cell cycle genes. Furthermore, difference and correlation analyses of the relationship between CTSV expression and immune infiltrates, determined using CIBERSORT and TIMER algorithms, revealed that CTSV expression correlated with macrophages and CD4+ T cells. In vitro and in vivo experiments revealed that knockdown of CTSV inhibited liver cancer cells proliferation. Immunohistochemical staining showed that high CTSV expression correlated with macrophage infiltration in liver cancer tissues, predicted a poor prognosis, and is associated with the effectiveness of hepatocellular carcinoma treatment. In couclusion, CTSV is a novel cell cycle-associated gene with clinical significance in HCC.

Gender differences and risk factors for acute kidney injury following cardiac surgery: A single center retrospective cohort study.

Background: We studied AKI incidence and prognosis in cardiac surgery patients under and over 60 years old. Methods: We studied AKI in patients who underwent cardiac surgery at the First Affiliated Hospital of Wenzhou Medical University between Jan 2020 and Dec 2021, using improved global prognostic criteria for diagnosis. Results: After analyzing 781 patients (402 males, 379 females), AKI incidence after surgery was 30.22 %. Adjusting for propensity scores revealed no significant difference in AKI incidence between young males (24.1 %) and females (19.3 %). However, young females had higher AKI stages. Among older patients, AKI incidence was comparable between males (43.4 %) and females (42.2 %), but females had longer intubation times. Independent risk factors for AKI included age, male gender, and BMI, while intraoperative hemoglobin level was protective. Conclusions: No gender gap in AKI frequency for <60 years old and ≥60 years old post-cardiac surgery, yet women display increased AKI severity and extended intubation duration.

Multisequence MRI-based radiomics analysis for early prediction of the risk of T790M resistance in new brain metastases.

Background: Predicting whether T790M emerges early is crucial to the adjustment of targeted drugs for non-small cell lung cancer (NSCLC) patients. This study aimed to evaluate the risk of T790M resistance in progressive new brain metastases (BMs) based on multisequence magnetic resonance imaging (MRI) radiomics. Methods: This retrospective study included 405 consecutive patients (training cohort: 294 patients; testing cohort: 111 patients) with proven NSCLC with disease progression of new BM. The radiomics features were separately extracted from T2-weighted imaging (T2WI), T2 fluid-attenuated inversion recovery (T2-FLAIR), diffusion-weighted imaging (DWI), and contrast-enhanced T1-weighted imaging (T1-CE) sequence of baseline MRI. Then, we calculated radiomics scores (rad-score) of the 4 sequences respectively and established predictive models (lesion- or patient-level) to evaluate T790M resistance within up to 14 months using random forest classifier. Receiver operating characteristic (ROC) curves and F1 scores were used to validate the performance of two models in both the training and testing cohort. Results: There were significant differences in rad-scores of the four sequences between T790M-positive and negative groups whether in the training or testing cohort (P<0.05). The lesion-level model consisting of rad-scores showed excellent discrimination, with an area under the curve (AUC) and F1-score of 0.879 and 0.798 in the training cohort, and 0.834 and 0.742 in the testing cohort, respectively. The patient-level model also showed a favorable discriminatory ability with an AUC and F1 score of 0.851 and 0.837, which was confirmed with an AUC and F1 score of 0.734 and 0.716 in the testing cohort. Conclusions: The MRI-based radiomics signatures may be new markers to identify patients at high risk of developing resistance in the early period.

CT-based nomogram for early identification of T790M resistance in metastatic non-small cell lung cancer before first-line epidermal growth factor receptor-tyrosine kinase inhibitors therapy.

BACKGROUND: To evaluate the value of computed tomography (CT) radiomics in predicting the risk of developing epidermal growth factor receptor (EGFR) T790M resistance mutation for metastatic non-small lung cancer (NSCLC) patients before first-line EGFR-tyrosine kinase inhibitors (EGFR-TKIs) therapy. METHODS: A total of 162 metastatic NSCLC patients were recruited and split into training and testing cohort. Radiomics features were extracted from tumor lesions on nonenhanced CT (NECT) and contrast-enhanced CT (CECT). Radiomics score (rad-score) of two CT scans was calculated respectively. A nomogram combining two CT scans was developed to evaluate T790M resistance within up to 14 months. Patients were followed up to calculate the time of T790M occurrence. Models were evaluated by area under the curve at receiver operating characteristic analysis (ROC-AUC), calibration curve, and decision curve analysis (DCA). The association of the nomogram with the time of T790M occurrence was evaluated by Kaplan-Meier survival analysis. RESULTS: The nomogram constructed with the rad-score of NECT and CECT for predicting T790M resistance within 14 months achieved the highest ROC-AUCs of 0.828 and 0.853 in training and testing cohorts, respectively. The DCA showed that the nomogram was clinically useful. The Kaplan-Meier analysis showed that the occurrence time of T790M difference between the high- and low-risk groups distinguished by the rad-score was significant (p < 0.001). CONCLUSIONS: The CT-based radiomics signature may provide prognostic information and improve pretreatment risk stratification in EGFR NSCLC patients before EGFR-TKIs therapy. The multimodal radiomics nomogram further improved the capability. RELEVANCE STATEMENT: Radiomics based on NECT and CECT images can effectively identify and stratify the risk of T790M resistance before the first-line TKIs treatment in metastatic non-small cell lung cancer patients. KEY POINTS: • Early identification of the risk of T790M resistance before TKIs treatment is clinically relevant. • Multimodel radiomics nomogram holds potential to be a diagnostic tool. • It provided an imaging surrogate for identifying the pretreatment risk of T790M.

Base editing of the HBG promoter induces potent fetal hemoglobin expression with no detectable off-target mutations in human HSCs.

Reactivating silenced γ-globin expression through the disruption of repressive regulatory domains offers a therapeutic strategy for treating ß-hemoglobinopathies. Here, we used transformer base editor (tBE), a recently developed cytosine base editor with no detectable off-target mutations, to disrupt transcription-factor-binding motifs in hematopoietic stem cells. By performing functional screening of six motifs with tBE, we found that directly disrupting the BCL11A-binding motif in HBG1/2 promoters triggered the highest γ-globin expression. Via a side-by-side comparison with other clinical and preclinical strategies using Cas9 nuclease or conventional BEs (ABE8e and hA3A-BE3), we found that tBE-mediated disruption of the BCL11A-binding motif at the HBG1/2 promoters triggered the highest fetal hemoglobin in healthy and ß-thalassemia patient hematopoietic stem/progenitor cells while exhibiting no detectable DNA or RNA off-target mutations. Durable therapeutic editing by tBE persisted in repopulating hematopoietic stem cells, demonstrating that tBE-mediated editing in HBG1/2 promoters is a safe and effective strategy for treating ß-hemoglobinopathies.

Research on the Security of IPv6 Communication Based on Petri Net under IoT.

The distribution of wireless network systems challenges the communication security of Internet of Things (IoT), and the IPv6 protocol is gradually becoming the main communication protocol under the IoT. The Neighbor Discovery Protocol (NDP), as the base protocol of IPv6, includes address resolution, DAD, route redirection and other functions. The NDP protocol faces many attacks, such as DDoS attacks, MITM attacks, etc. In this paper, we focus on the communication-addressing problem between nodes in the Internet of Things (IoT). We propose a Petri-Net-based NS flooding attack model for the flooding attack problem of address resolution protocols under the NDP protocol. Through a fine-grained analysis of the Petri Net model and attacking techniques, we propose another Petri-Net-based defense model under the SDN architecture, achieving security for communications. We further simulate the normal communication between nodes in the EVE-NG simulation environment. We implement a DDoS attack on the communication protocol by an attacker who obtains the attack data through the THC-IPv6 tool. In this paper, the SVM algorithm, random forest algorithm (RF) and Bayesian algorithm (NBC) are used to process the attack data. The NBC algorithm is proven to exhibit high accuracy in classifying and identifying data through experiments. Further, the abnormal data are discarded through the abnormal data processing rules issued by the controller in the SDN architecture, to ensure the security of communications between nodes.

Exploring the Darkverse: A Multi-Perspective Analysis of the Negative Societal Impacts of the Metaverse.

The Metaverse has the potential to form the next pervasive computing archetype that can transform many aspects of work and life at a societal level. Despite the many forecasted benefits from the metaverse, its negative outcomes have remained relatively unexplored with the majority of views grounded on logical thoughts derived from prior data points linked with similar technologies, somewhat lacking academic and expert perspective. This study responds to the dark side perspectives through informed and multifaceted narratives provided by invited leading academics and experts from diverse disciplinary backgrounds. The metaverse dark side perspectives covered include: technological and consumer vulnerability, privacy, and diminished reality, human-computer interface, identity theft, invasive advertising, misinformation, propaganda, phishing, financial crimes, terrorist activities, abuse, pornography, social inclusion, mental health, sexual harassment and metaverse-triggered unintended consequences. The paper concludes with a synthesis of common themes, formulating propositions, and presenting implications for practice and policy.

Identification and validation of a cellular senescence-related lncRNA signature for prognostic prediction in patients with multiple myeloma.

Multiple myeloma (MM) is the second most common hematologic malignancy, which primarily occurs in the elderly. Cellular senescence is considered to be closely associated with the occurrence and progression of malignant tumors including MM, and lncRNA can mediate the process of cellular senescence by regulating key signaling pathways such as p53/p21 and p16/RB. However, the role of cellular senescence related lncRNAs (CSRLs) in MM development has never been reported. Herein, we identified 11 CSRLs (AC004918.5, AC103858.1, AC245100.4, ACBD3-AS1, AL441992.2, ATP2A1-AS1, CCDC18-AS1, LINC00996, TMEM161B-AS1, RP11-706O15.1, and SMURF2P1) to build the CSRLs risk model, which was confirmed to be highly associated with overall survival (OS) of MM patients. We further demonstrated the strong prognostic value of the risk model in MM patients receiving different regimens, especially for those with three-drug combination of bortezomib, lenalidomide, and dexamethasone (VRd) as first-line therapy. Not only that, our risk model also excels in predicting the OS of MM patients at 1, 2, and 3 years. In order to verify the function of these CSRLs in MM, we selected the lncRNA ATP2A1-AS1 which presented the largest expression difference between high-risk groups and low-risk groups for subsequent analysis and validation. Finally, we found that down-regulation of ATP2A1-AS1 can promote cellular senescence in MM cell lines. In conclusion, the CSRLs risk model established in present study provides a novel and more accurate method for predicting MM patients' prognosis and identifies a new target for MM therapeutic intervention.

Correction: Yu et al. Comparison of Physical and Biochemical Characterizations of SARS-CoV-2 Inactivated by Different Treatments. Viruses 2022, 14, 1938.

In the original publication [...].