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Abstract Background Patients with advanced cancer and family caregivers often use avoidant coping strategies, such as delaying advance care planning discussions, which contribute to deterioration in their quality of life. Mindfulness-based interventions have shown promise in improving quality of life in this population but have rarely been applied to advance care planning. This pilot trial examined the preliminary efficacy of a group-based Mindfulness to Enhance Quality of Life and Support Advance Care Planning (MEANING) intervention for patient-caregiver dyads coping with advanced cancer. Primary outcomes were patient and caregiver quality of life or well-being, and secondary outcomes included patient advanced care planning engagement (self-efficacy and readiness) and other psychological and symptom outcomes. Methods In this pilot trial, dyads coping with advanced cancer were recruited from five oncology clinics in the midwestern U.S. and randomized to six weekly group sessions of a mindfulness intervention (n = 33 dyads) or usual care (n = 22 dyads). Outcomes were assessed via surveys at baseline, post-intervention, and 1 month post-intervention. All available data were included in the multilevel models assessing intervention efficacy. Results Patients in the MEANING condition experienced significant increases in existential well-being and self-efficacy for advance care planning across follow-ups, whereas usual care patients did not. Other group differences in outcomes were not statistically significant. These outcomes included other facets of patient well-being, caregiver quality of life, patient readiness for advance care planning, caregiver burden, and patient and caregiver depressive symptoms, anxiety, sleep disturbance, cognitive avoidance, and peaceful acceptance of cancer. However, only MEANING patients showed moderate increases in psychological well-being across follow-ups, and MEANING caregivers showed moderate increases in quality of life at 1-month follow-up. Certain psychological outcomes, such as caregiver burden at 1-month follow-up, also showed moderate improvement in the MEANING condition. Patients in both conditions reported small to moderate increases in readiness to engage in advance care planning. Conclusions A mindfulness-based intervention showed promise in improving quality-of-life and advance care planning outcomes in patients and caregivers coping with advanced cancer and warrants further testing. Trial Registration ClinicalTrials.gov NCT03257007. Registered 22 August 2017, https://clinicaltrials.gov/ct2/show/NCT03257007 .

Branded applications (apps) have become core touchpoints for improving consumer shopping experiences in omni-channel retailing, and many firms have developed different types of branded apps to provide additional value. Moreover, continuous usage intention is the key to improving enterprises’ gain efficiency and consumers’ brand loyalty. This study aims to reveal how branded apps achieve continuance intention from the perspective of consumer perceptions by combining the technology acceptance model and investigating the impact of differences in channel features on usage behavior between the two types of branded apps. An experiment was designed comparing transaction- and experience-oriented branded apps. A structural equation modeling technique was employed to validate the model based on the survey data of respondents from the experimental groups. The results show that the supportive role of omni-channel has a unique experience mechanism that promotes continuous usage intention. However, there are two discrepant results regarding the effect of perceived complementarity on perceived usefulness in transaction- and experience-oriented branded apps. The mediating role of perceived usefulness between perceived consistency, complementarity, ease of use and consumer satisfaction was supported in the experience-oriented apps but rejected in the transaction-oriented apps.

Triboelectrification, a process that transforms mechanical energy into electrical energy through friction, holds promise for eco-friendly wastewater treatment. This study delves into the enhancement of tribocatalytic dye degradation using SrTiO3, a material notable for its non-piezoelectric and centrosymmetric properties. The synthesis of uni- and bi-doped SrTiO3 particles, achieved through a solid-state reaction at 1000 °C, results in a high-purity cubic perovskite structure. Doping with rhodium (Rh) and carbon (C) causes crystal lattice contraction, internal stress, and significant oxygen vacancies. These changes notably improve tribocatalytic efficiency under solar irradiation, with Rh-doped SrTiO3 demonstrating an impressive degradation rate of approximately 88% for Rhodamine B (RhB), along with reaction rate constants near 0.9 h−1 at 554 nm and a noticeable blueshift. This study highlights that defects introduced by doping are integral to this process, boosting catalytic activity through energy state modification and enhancing surface redox radical production. Additionally, these defects are instrumental in generating a flexoelectric field, which markedly influences the separation of electron–hole pairs under solar irradiation. Our findings illuminate the complex interplay between material composition, defect states, and environmental conditions, paving the way for advanced strategies in environmental remediation through optimized tribocatalytic activity.

Abstract Aims of this study This study aims to investigate the potential of Huangqin Tang (HQT), a traditional Chinese medicine formulation, in the treatment of breast cancer (BC) through a comprehensive approach integrating network pharmacology, molecular docking, and experimental validation. Methods Chemical composition and target information of HQT were collected using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease-related target genes were obtained from the GeneCards database. Network pharmacological analysis, including construction of compound-disease-target networks and protein-protein interaction networks, was performed. Molecular docking simulations were conducted to evaluate the binding affinity between HQT components and key targets. Experimental validation was carried out using cell viability assays, clone formation assays, flow cytometry, Western blotting, and pathway analysis. Results A total of 210 candidate targets were identified. Network analysis revealed STAT3, AKT1, MAPK3 etc. as central targets. Enrichment analysis suggested HQT may exert anti-tumor effects through regulating lipid metabolism and inflammation related pathways. Molecular docking showed that the key compounds baicalein, wogonin, kaempferol and quercetin all bound effectively to MAPK1. The binding of baicalein to IL6 and naringenin to TNF-α was also relatively stable. The experimental results demonstrated that HQT effectively inhibited the proliferation of breast cancer cells, with IC50 values of 2.334 mg/mL and 1.749 mg/mL in MCF-7 cells at 24 h and 48 h, and IC50 values of 1.286 mg/mL and 1.496 mg/mL in MDA-MB-231 cells at 24 h and 48 h, respectively. Furthermore, HQT induced cell cycle arrest at the G2/M phase in breast cancer cells and downregulated the expression of related proteins including CDK1, Cyclin B1, CDK2, and Cyclin E. Additionally, HQT promoted apoptosis in breast cancer cells by upregulating the expression of Bak and CC-3, while downregulating the expression of Bcl-2. Notably, HQT also exhibited regulatory effects on the HIF-1 signaling pathway. Conclusions This study provides insights into the potential multi-component and multi-target mechanisms of HQT against BC, suggesting it may achieve therapeutic effects through regulating inflammatory response and cancer-related pathways via the identified active compounds and targets. The findings highlight the importance of integrating traditional medicine with modern approaches for the development of novel cancer therapies.

Introduction: Hair loss is one of the common clinical conditions in modern society. Although it is not a serious disease that threatens human life, it brings great mental stress and psychological burden to patients. This study investigated the role of dendrobium officinale polysaccharide (DOP) in hair follicle regeneration and hair growth and its related mechanisms. Methods: After in vitro culture of mouse antennal hair follicles and mouse dermal papilla cells (DPCs), and mouse vascular endothelial cells (MVECs), the effects of DOP upon hair follicles and cells were evaluated using multiple methods. DOP effects were evaluated by measuring tentacle growth, HE staining, immunofluorescence, Western blot, CCK-8, ALP staining, tube formation, scratch test, and Transwell. LDH levels, WNT signaling proteins, and therapeutic mechanisms were also analyzed. Results: DOP promoted tentacle hair follicle and DPCs growth in mice and the angiogenic, migratory and invasive capacities of MVECs. Meanwhile, DOP was also capable of enhancing angiogenesis and proliferation-related protein expression. Mechanistically, DOP activated the WNT signaling and promoted the expression level of β-catenin, a pivotal protein of the pathway, and the pathway target proteins Cyclin D1, C-Myc, and LDH activity. The promotional effects of DOP on the biological functions of DPCs and MVECs could be effectively reversed by the WNT signaling pathway inhibitor IWR-1. Conclusion: DOP advances hair follicle and hair growth via the activation of the WNT signaling. This finding provides a mechanistic reference and theoretical basis for the clinical use of DOP in treating hair loss.

Proteotoxic stress impairs cellular homeostasis and underlies the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). The proteasomal and autophagic degradation of proteins are two major pathways for protein quality control in the cell. Here, we report a genome-wide CRISPR screen uncovering a major regulator of cytotoxicity resulting from the inhibition of the proteasome. Dihydrolipoamide branched chain transacylase E2 (DBT) was found to be a robust suppressor, the loss of which protects against proteasome inhibition-associated cell death through promoting clearance of ubiquitinated proteins. Loss of DBT altered the metabolic and energetic status of the cell and resulted in activation of autophagy in an AMP-activated protein kinase (AMPK)-dependent mechanism in the presence of proteasomal inhibition. Loss of DBT protected against proteotoxicity induced by ALS-linked mutant TDP-43 in Drosophila and mammalian neurons. DBT is upregulated in the tissues of ALS patients. These results demonstrate that DBT is a master switch in the metabolic control of protein quality control with implications in neurodegenerative diseases.

Reprogramming of cancer metabolism has become increasingly concerned over the last decade, particularly the reprogramming of glucose metabolism, also known as the ''Warburg effect''. The reprogramming of glucose metabolism is considered a novel hallmark of human cancers. A growing number of studies have shown that reprogramming of glucose metabolism can regulate many biological processes of cancers, including carcinogenesis, progression, metastasis, and drug resistance. In this review, we summarize the major biological functions, clinical significance, potential targets and signaling pathways of glucose metabolic reprogramming in human cancers. Moreover, the applications of natural products and small molecule inhibitors targeting glucose metabolic reprogramming are analyzed, some clinical agents targeting glucose metabolic reprogramming and trial statuses are summarized, as well as the pros and cons of targeting glucose metabolic reprogramming for cancer therapy are analyzed. Overall, the reprogramming of glucose metabolism plays an important role in the prediction, prevention, diagnosis and treatment of human cancers. Glucose metabolic reprogramming-related targets have great potential to serve as biomarkers for improving individual outcomes and prognosis in cancer patients. The clinical innovations related to targeting the reprogramming of glucose metabolism will be a hotspot for cancer therapy research in the future. We suggest that more high-quality clinical trials with more abundant drug formulations and toxicology experiments would be beneficial for the development and clinical application of drugs targeting reprogramming of glucose metabolism.This review will provide the researchers with the broader perspective and comprehensive understanding about the important significance of glucose metabolic reprogramming in human cancers.

ABSTRACT Transposon sequencing (Tn-seq) is a powerful genome-wide technique to assess bacterial fitness under varying growth conditions. However, screening via Tn-seq in vivo is challenging. Dose limitations and host restrictions create bottlenecks that diminish the transposon mutant pool being screened. Here, we have developed a murine model with a disruption in Akr1c13 that renders the resulting RECON−/− mouse resistant to high-dose infection. We leveraged this model to perform a Tn-seq screen of the human pathogen Listeria monocytogenes in vivo. We identified 135 genes which were required for L. monocytogenes growth in mice including novel genes not previously identified for host survival. We identified organ-specific requirements for L. monocytogenes survival and investigated the role of the folate enzyme FolD in L. monocytogenes liver pathogenesis. A mutant lacking folD was impaired for growth in murine livers by 2.5-log10 compared to wild type and failed to spread cell-to-cell in fibroblasts. In contrast, a mutant in alsR, which encodes a transcription factor that represses an operon involved in D-allose catabolism, was attenuated in both livers and spleens of mice by 4-log10 and 3-log10, respectively, but showed modest phenotypes in in vitro models. We confirmed that dysregulation of the D-allose catabolism operon is responsible for the in vivo growth defect, as deletion of the operon in the ∆alsR background rescued virulence. By undertaking an unbiased, genome-wide screen in mice, we have identified novel fitness determinants for L. monocytogenes host infection, which highlights the utility of the RECON−/− mouse model for future screening efforts.IMPORTANCEListeria monocytogenes is the gram-positive bacterium responsible for the food-borne disease listeriosis. Although infections with L. monocytogenes are limiting in healthy hosts, vulnerable populations, including pregnant and elderly people, can experience high rates of mortality. Thus, understanding the breadth of genetic requirements for L. monocytogenes in vivo survival will present new opportunities for treatment and prevention of listeriosis. We developed a murine model of infection using a RECON−/− mouse that is restrictive to systemic L. monocytogenes infection. We utilized this model to screen for L. monocytogenes genes required in vivo via transposon sequencing. We identified the liver-specific gene folD and a repressor, alsR, that only exhibits an in vivo growth defect. AlsR controls the expression of the D-allose operon which is a marker in diagnostic techniques to identify pathogenic Listeria. A better understanding of the role of the D-allose operon in human disease may further inform diagnostic and prevention measures.

Abstract Patients with glycogen storage disease type Ib (GSD‐Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD‐Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo‐polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single‐cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper‐activation of the CCL4L2‐VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD‐Ib. Collectively, the microbiota‐driven pathomechanism of IBD is demonstrated in GSD‐Ib and revealed the active role of the CCL4L2‐VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2‐VISR axis may represent a potential therapy for GSD‐associated IBD.

Engagement in healthy lifestyles is pivotal for early adolescents’ growth and healthy development. Despite burgeoning research on the determinants of healthy lifestyles among adolescents, there is a dearth of research investigating the role of adolescents’ health mindsets. This study examined whether and how implicit theories of health and future self-continuity affect adolescents’ (N = 440; 49.5% girls; Mage = 10.8, SD = 0.6) engagement in healthy lifestyles. The results indicated that implicit theories of health and future self-continuity accounted for 2.5–5.8% of the variances in behaviour indicators (i.e. (un)healthy eating, physical activity, and sleep quality) and more than 20.3% of the variances in mental well-being indicators (i.e. flourishing and emotional balance) of healthy lifestyles among adolescents. Future self-continuity explained the positive effects of implicit theories of health on adolescents’ engagement in healthy lifestyles. The results have implications for tailoring effective interventions to promote healthy living among adolescents.

AbstractPouteria caimito is a commercially valuable tropical fruit tree and has medicinal effects in Brazilian folklore. In this thesis, thirteen compounds were isolated for the first time from the fruit of P. caimito by ethanol extraction and various chromatographic column chromatography methods. The thirteen compounds were identified by NMR, HR-ESI-MS and various physicochemical data to contain nine triterpenoids. The results of activity screening experiments showed that compounds 2, 3 and 5 exhibited anti-inflammatory activity, while most of the triterpenoids exhibited anti-RSV, and anti-HSV activity to varying degrees. Based on these results, the content of compound 5 was determined due to its good pharmacological activity to be 13.3250 mg/kg in the fresh fruit. This study scientifically demonstrated the health benefits of consuming P. caimito fruits and also provided new ideas for further development and utilization of P. caimito. It not only has good potential as an anti-inflammatory or antiviral functional food but also can be considered a natural source of triterpenoids.

ObjectiveTo study the effectiveness of liver transplantation (LT) in treating mitochondrial DNA depletion syndrome (MDS) caused by the MPV17 gene variant.Case presentationA boy aged 2.8 years presented with edema of the lower limbs and abdomen, which persisted for over 10 days and was of unknown origin; this was accompanied by abnormal liver function, intractable hypoglycemia, and hyperlactatemia. During the second week of onset, he developed acute-on-chronic liver failure and was diagnosed with MDS due to homozygous variant c.293C>T in the MPV17 gene. Subsequently, he underwent LT from a cadaveric donor. At follow-up after 15 months, his liver function was found to be normal, without any symptoms. Additionally, a literature review was performed that included MDS patients with the MPV17 variant who underwent LT. The results demonstrated that the survival rates for MDS patients who underwent LT were 69.5%, 38.6%, 38.6%, and 38.6% at 1-year, 5-year, 10-year, and 20-year intervals, respectively. Sub-group analyses revealed the survival rate of MDS patients with isolated liver disease (83.33%, 5/6) was higher than that of hepatocerebral MDS patients (44.44%, 8/18). Fifteen variants were identified in the MPV17 gene, and patients with the c.293C>T (p.P98l) variant exhibited the highest survival rate.ConclusionHepatocerebral MDS patients without neurological symptoms may benefit from LT.

ABSTRACT A riboswitch generally regulates the expression of its downstream genes through conformational change in its expression platform (EP) upon ligand binding. The cyclic diguanosine monophosphate (c-di-GMP) class I riboswitch Bc1 is widespread and conserved among Bacillus cereus group species. In this study, we revealed that Bc1 has a long EP with two typical ρ-independent terminator sequences 28 bp apart. The upstream terminator T1 is dominant in vitro, while downstream terminator T2 is more efficient in vivo. Through mutation analysis, we elucidated that Bc1 exerts a rare and incoherent “transcription-translation” dual regulation with T2 playing a crucial role. However, we found that Bc1 did not respond to c-di-GMP under in vitro transcription conditions, and the expressions of downstream genes did not change with fluctuation in intracellular c-di-GMP concentration. To explore this puzzle, we conducted SHAPE-MaP and confirmed the interaction of Bc1 with c-di-GMP. This shows that as c-di-GMP concentration increases, T1 unfolds but T2 remains almost intact and functional. The presence of T2 masks the effect of T1 unwinding, resulting in no response of Bc1 to c-di-GMP. The high Shannon entropy values of EP region imply the potential alternative structures of Bc1. We also found that zinc uptake regulator can specifically bind to the dual terminator coding sequence and slightly trigger the response of Bc1 to c-di-GMP. This work will shed light on the dual-regulation riboswitch and enrich our understanding of the RNA world.IMPORTANCEIn nature, riboswitches are involved in a variety of metabolic regulation, most of which preferentially regulate transcription termination or translation initiation of downstream genes in specific ways. Alternatively, the same or different riboswitches can exist in tandem to enhance regulatory effects or respond to multiple ligands. However, many putative conserved riboswitches have not yet been experimentally validated. Here, we found that the c-di-GMP riboswitch Bc1 with a long EP could form a dual terminator and exhibit non-canonical and incoherent “transcription-translation” dual regulation. Besides, zinc uptake regulator specifically bound to the coding sequence of the Bc1 EP and slightly mediated the action of Bc1. The application of SHAPE-MaP to the dual regulation mechanism of Bc1 may establish the foundation for future studies of such complex untranslated regions in other bacterial genomes.

Abstract Background Cannabis sativa, a dioecious plant that has been cultivated worldwide for thousands of years, is known for its secondary metabolites, especially cannabinoids, which possess several medicinal effects. In this study, we investigated the autopolyploidization effects on the biosynthesis and accumulation of these metabolites, transcriptomic and metabolomic analyses were performed to explore the gene expression and metabolic variations in industrial hemp autotetraploids and their diploid progenitors. Results Through these analyses, we obtained 1,663 differentially expressed metabolites and 1,103 differentially expressed genes. Integrative analysis revealed that phenylpropanoid and terpenoid biosynthesis were regulated by polyploidization. No substantial differences were found in the cannabidiol or tetrahydrocannabinol content between tetraploids and diploids. Following polyploidization, some transcription factors, including nine bHLH and eight MYB transcription factors, affected the metabolic biosynthesis as regulators. Additionally, several pivotal catalytic genes, such as flavonol synthase/flavanone 3-hydroxylase, related to the phenylpropanoid metabolic pathway, were identified as being modulated by polyploidization. Conclusions This study enhances the overall understanding of the impact of autopolyploidization in C. sativa and the findings may encourage the application of polyploid breeding for increasing the content of important secondary metabolites in industrial hemp.

For the prompt planting of subsequent crops, most of China’s corn harvest must occur before full maturity, with a grain moisture content above 25%. Harvesting moist corn presents challenges due to significant grain damage during threshing. We conducted a high-speed photography observation test of moist corn threshing. It demonstrated that corn ears, when passing through the threshing cylinder, often break into pieces. Grains on divided corncobs can be threshed more easily and earlier than those on undivided ones, suggesting that pre-dividing corn ears reduces grain damage. An experiment using the Lianchuang 825 variety examined the effect of moisture content and the divided rate of corncobs (DRC) on grain damage. The results showed that as moisture content increased from 25% to 37%, grain damage to undivided ears increased from 3.75% to 37.71%. Dividing corn ears before threshing significantly reduced damage, with an eight-piece division reducing damage by approximately 70% across all moisture levels. Verification with the Jinyu 1233 variety confirmed that a higher DRC consistently reduced damage. This study provides a new approach to reducing damage in moist corn threshing and aids in the development of low-damage threshing devices.

A van der Waals (vdW) heterostructure is formed by combining multiple materials through vdW bonds. It can combine the advantages of electronic, optical, thermal, and magnetic properties of different 2D materials and has the potential to develop into the next generation of high‐performance functional devices. Herein, the current research advances of vdW heterostructures are reviewed. First, current fabrication methods and physical structures of vdW heterostructures are summarized. The 2D/nD (n = 0,1,2,3) mixed‐dimensional heterostructures are discussed in detail. Second, a new type of vdW heterostructure is introduced based on two‐dimensional electron gas with a nanoscale junction interface. Finally, the application prospects of vdW heterostructures in photoelectric and memory devices are further outlined by combing new applications in the neural networks. This review shows that vdW heterostructures have great advantages in high integration, energy harvesting, and logical operations, and it provides directions and suggestions for the future research and application of environmentally friendly, high‐performance, and smart functional devices.

Abstract Atomically precise metal nanoclusters (NCs) have emerged as a promising frontier in the field of electrochemical CO2 reduction reactions (CO2RR) because of their distinctive catalytic properties. Although numerous metal NCs are developed for CO2RR, their use in practical applications has suffered from their low‐yield synthesis and insufficient catalytic activity. In this study, the large‐scale synthesis and electrocatalytic performance of ClAg14(C≡CtBu)12+ NCs, which exhibit remarkable efficiency in catalyzing CO2‐to‐CO electroreduction with a CO selectivity of over 99% are reported. The underlying mechanisms behind this extraordinary CO2RR activity of ClAg14(C≡CtBu)12+ NCs are investigated by a combination of electrokinetic and theoretical studies. These analyses reveal that different active sites, generated through electrochemical activation, have unique adsorption properties for the reaction intermediates, leading to enhanced CO2RR and suppressed hydrogen production. Furthermore, industrially relevant CO2‐to‐CO electroreduction using ClAg14(C≡CtBu)12+ NCs in a zero‐gap CO2 electrolyzer, achieving high energy efficiency of 51% and catalyst activity of over 1400 A g−1 at a current density of 400 mA cm−2 is demonstrated.

Abstract Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation often obtain de novo resistance or develop secondary resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), which restricts the clinical benefit for the patients. The activation of phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway is one of the most important mechanisms for the EGFR-TKIs resistance beyond T790M mutation. There are currently no drugs simultaneously targeting EGFR and PI3K signal pathways, and combination of these two pathway inhibitors may be a possible strategy to reverse theses resistances. To test whether this combinational strategy works, we investigated the therapeutic effects and mechanisms of combining BYL719, a PI3Kα inhibitor, with gefitinib, an EGFR-TKI inhibitor in EGFR-TKIs resistance NSCLC models induced by PI3K/AKT activation. Our results demonstrated that PIK3CA mutated cells showed increased growth rate and less sensitive or even resistant to gefitinib, associated with increased PI3K/AKT expression. The combination of BYL719 and gefitinib resulted in synergistic effect compared with the single agents alone in EGFR-mutated NSCLC cells with PI3K/AKT activation. The inhibition of AKT phosphorylation by BYL719 increased the antitumor efficacy of gefitinib in these cell lines. Moreover, the combined effect and mechanism of gefitinib and BYL719 were also confirmed in the NSCLC cells and patient-derived organoids under 3D culture condition, as well as in vivo. Taken together, the data indicate that PIK3CA mutation induces more aggressive growth and gefitinib resistance in NSCLC cells, and the combination treatment with gefitinib and BYL719 is a promising therapeutic approach to overcoming EGFR-TKIs resistance induced by PI3K/AKT activation.

Efficient carbon emission reduction technologies in buildings are necessary for achieving the “Dual carbon” goal in China. In this study, a comprehensive evaluation model is proposed to assess the effect of carbon emission reduction based on the analytic hierarchy process–entropy weight–coefficient of variation model which takes newly built residential buildings in Zhuzhou City as the research object. The results show that the preferred materials for the roof and exterior walls of the building’s envelope structure were flame-retardant extruded polystyrene boards, and porous shale bricks were preferred as the main materials for the exterior walls. In addition, the rooftop solar photovoltaic system and energy-saving air conditioning technology were suitable in terms of being renewable and were better utilized. In the end, carbon emissions were significantly reduced when using the building decarbonization technologies. This study provides a new reference for choosing materials and technologies for the design of residential buildings in Hunan Province and even other regions with hot summers and cold winters.

To identify program characteristics that influence the retention of women of reproductive age in the C ommunity-based A ddiction Re duction program (CARE), mixed-method analyses of CARE survey data and CARE Peer Recovery Coach (PRC) narrative entries of participant encounters were performed. About 251 women were enrolled in this prospective community-based implementation science intervention. We compared survey responses by race for treatment status, treatment motivation scales, and retention in the program at intake, 2-, 6-, 9-, and 12-month follow ups using Chi-square/ T -tests. Qualitative analysis of PRC narrative entries was conducted following thematic analysis and crystallization immersion analytic methods. White compared with Black women in CARE were significantly more likely to be in treatment at intake ( P

Wheat is the main component for producing the flavor liquor Daqu. It is essential to meet the raw material quality requirements for high-quality Daqu to breed special wheat varieties and simultaneously develop the supporting cultivation practices. From 2018 to 2020, a field experiment involving four representative wheat cultivars (Chuanmai 104, Mianmai 367, Xikemai 8, and Shumai 1671) and six nitrogen application rates (0, 45, 90, 135, 180, and 225 kg/hm2) in four different agro-ecological sites (Guanghan, Zitong, and Xichang in Sichuan Province, and Nanzhang in Hubei Province) in the upper and middle reaches of the Yangtze River basin was conducted. This study evaluated the main quality parameters of wheat raw materials and the quality of the flavor liquor Daqu. The results showed that, for most sensory and chemical parameters of Daqu, the main effects of year, location and variety, were all significant (P

Abstract Macrofossils with unambiguous biogenic origin and predating the one-billion-year-old multicellular fossils Bangiomorpha and Proterocladus interpreted as crown-group eukaryotes are quite rare. Horodyskia is one of these few macrofossils, and it extends from the early Mesoproterozoic Era to the terminal Ediacaran Period. The biological interpretation of this enigmatic fossil, however, has been a matter of controversy since its discovery in 1982, largely because there was no evidence for the preservation of organic walls. Here we report new carbonaceous compressions of Horodyskia from the Tonian successions (~950–720 Ma) in North China. The macrofossils herein with bona fide organic walls reinforce the biogenicity of Horodyskia. Aided by the new material, we reconstruct Horodyskia as a colonial organism composed of a chain of organic-walled vesicles that likely represent multinucleated (coenocytic) cells of early eukaryotes. Two species of Horodyskia are differentiated on the basis of vesicle sizes, and their co-existence in the Tonian assemblage provides a link between the Mesoproterozoic (H. moniliformis) and the Ediacaran (H. minor) species. Our study thus provides evidence that eukaryotes have acquired macroscopic size through the combination of coenocytism and colonial multicellularity at least ~1.48 Ga, and highlights an exceptionally long range and morphological stasis of this Proterozoic macrofossils.

Abstract Traumatic brain injury (TBI) is the leading cause of disability and death, and the social burden of mortality and morbidity caused by TBI is significant. Under the influence of comprehensive factors, such as social environment, lifestyle, and employment type, the incidence of TBI continues to increase annually. Current pharmacotherapy of TBI mainly focuses on symptomatic supportive treatment, aiming to reduce intracranial pressure, ease pain, alleviate irritability, and fight infection. In this study, we summarized numerous studies covering the use of neuroprotective agents in different animal models and clinical trials after TBI. However, we found that no drug has been approved as specifically effective for the treatment of TBI. Effective therapeutic strategies for TBI remain an urgent need, and attention is turning toward traditional Chinese medicine. We analyzed the reasons why existing high-profile drugs had failed to show clinical benefits and offered our views on the research of traditional herbal medicine for treating TBI.

Rapeseed blanket seedling transplanters have developed rapidly due to their high efficiency and adaptability to the soil in many areas of China. However, during the transplanter’s longitudinal seedling conveying process, seedling blanket compression leads to inaccurate conveying and thus declined seedling picking performance. In this paper, a mechanical compression test was carried out on rapeseed seedling blankets. The longitudinal compression force of the rapeseed seedling blanket on a transplanter was calculated through mechanical analysis. A compression model of the rapeseed seedling blanket was established to determine how the blanket’s mechanical characteristics and the device’s structural parameters affect blanket compression. In addition, with the index of longitudinal compression Y1, the coefficient of variation in the longitudinal seedling conveying distance Y2, and the qualified-block-cutting rate Y3, the interactive influence between the seedling tray tilt angle A, the seedling blanket moisture content B, and the seedling blanket thickness C were analyzed using response surface analysis. Aiming to reduce blanket compression and enhance the accuracy of longitudinal seedling conveying and block-cutting quality, the optimized results show that the predicted optimal parameters were a 50.14° seedling tray tilt angle, a 71.86% seedling blanket moisture content, and a 22.13 mm seedling blanket thickness. Using these optimized parameters, the transplanter achieved a blanket longitudinal compression of 18.17 mm, a coefficient of variation in the longitudinal seedling conveying distance of 1.142, and a qualified-block-cutting rate of 90%. Subsequently, a validation test was performed, revealing a high degree of conformity between the optimization model and the experimental data. Thus, the predicted optimal parameters can provide significantly reduced compression and a high seedling conveying performance. The results of this study provide theoretical and empirical support for the optimized design and operation of mechanized rapeseed blanket seedling transplanting.

(1) Background: Various types of adjuvants are added during application to enhance the spraying effect, but most adjuvant formulations are proprietary products, and their exact compositions have not been disclosed. (2) Methods: The spatial distributions of droplet sizes and velocities generated by the atomization of different polymer adjuvants were measured based on the phase Doppler interferometer (PDI) measurement method. The sub-area statistical method was used to quantitatively analyze the droplet characteristics at various points below the nozzle. (3) Results: The polymer (polyethylene oxide (PEO))/associative surfactant (sodium dodecyl sulfate (SDS)) can increase the droplet size and velocity of the solution after atomization by increasing the amount of the polymer/associative surfactant to reduce the equilibrium surface tension of the solution and increase the viscosity. Different concentrations of polymer/associative surfactant atomization produced larger droplet sizes and better uniformity than polymer/non-associative surfactant (polysorbate-20 (Tween20)). At the same position, the relationship between droplet velocities for the three adjuvant combinations was roughly as follows: PEO/SDS solution had the highest velocity, followed by PEO solution, and PEO/Tween20 solution had the lowest velocity. (4) Conclusions: The optimal of droplet size distribution can be achieved by adding appropriate amounts of associative surfactants to polymers.

To address the lack of available information on the soil physical conditions suitable for rapeseed blanket-shaped seedling transplanting, as well as the lack of protocols for the optimisation of soil tillage components in the utilisation of an integrated rapeseed blanket seedling combined transplanter, the physical parameters of different soil conditions and their impact on the growth of rapeseed after transplanting were investigated in this study. The aim was to determine the suitable soil physical parameters for rapeseed blanket-shaped seedling transplanting. First, the changes in soil firmness, soil bulk density, and soil moisture content during the installation of the rapeseed blanket seedling combined transplanter were tested and analysed, providing preliminary data for subsequent research. Using the variables of soil firmness and soil moisture content in the micro-environment around the roots and stems (30–50 mm) after rapeseed seedling transplantation and indicators such as the survival rate, root diameter, seedling height, and dry weight, an experiment on the growth of rapeseed blanket-shaped seedlings was conducted based on the furrow cutting transplanting principle. The results indicated that during the initial stage of rapeseed transplanting, the soil moisture content significantly influenced the vitality of the rapeseed plants. Under a high soil moisture content, the typically lengthy seedling period was shortened, and the effect on vitality was good, with minimal influence from the soil firmness. After seedling establishment, the rapeseed growth was significantly affected by the soil firmness. When the soil moisture content was less than 20%, increasing the soil firmness to 500 kPa was beneficial for moisture retention and rapeseed seedling growth. At a soil moisture content ranging from 20 to 25%, a soil firmness of 400 kPa was most suitable for both rapeseed vitality and late-stage growth. When the soil moisture content exceeded 25%, reducing the soil firmness to 300 kPa was beneficial for rapeseed growth, as an excessively high moisture content may lead to soil compaction, affecting seedling development. This study provides a theoretical basis for optimizing the design of soil tillage components in the application of an integrated rapeseed blanket seedling combined transplanter and for the high-yield management of rapeseed after transplanting.

ABSTRACT Folic acid and its derivatives are required for the synthesis of purines, pyrimidines, and some amino acids. Antifolate antibiotics that target the folic acid metabolism pathway are commonly used for the treatment of listeriosis caused by the intracellular pathogen Listeria monocytogenes (Lm). In recent work in mBio, Feng et al. sought to understand the role of folic acid metabolism in Lm virulence (Y. Feng, S. Chang, D. A. Portnoy, 2023, mBio https://doi.org/10.1128/mbio.01074-23). The authors discovered that N-formylmethionine, an amino acid utilized by bacteria to initiate protein synthesis, is crucial for Lm intracellular growth and pathogenesis. Surprisingly, purines and thymidine were found to be dispensable for Lm infection. Together these results demonstrate that while Lm can obtain many essential nutrients from the host cytosol, including purines and most amino acids, it requires N-formylmethionine biosynthesis to properly regulate translation initiation during infection.

Abstract Layered lithium‐rich manganese‐based oxide (LRMO) has the limitation of inevitable evolution of lattice oxygen release and layered structure transformation. Herein, a multilayer reconstruction strategy is applied to LRMO via facile pyrolysis of potassium Prussian blue. The multilayer interface is visually observed using an atomic‐resolution scanning transmission electron microscope and a high‐resolution transmission electron microscope. Combined with the electrochemical characterization, the redox of lattice oxygen is suppressed during the initial charging. In situ X‐ray diffraction and the high‐resolution transmission electron microscope demonstrate that the suppressed evolution of lattice oxygen eliminates the variation in the unit cell parameters during initial (de)lithiation, which further prevents lattice distortion during long cycling. As a result, the initial Coulombic efficiency of the modified LRMO is up to 87.31%, and the rate capacity and long‐term cycle stability also improved considerably. In this work, a facile surface reconstruction strategy is used to suppress vigorous anionic redox, which is expected to stimulate material design in high‐performance lithium ion batteries.

Background: CD200-CD200R plays a critical role in regulating the human tumor microenvironment, but its role in cervical cancer remains unclear. Methods: A total of 62 paraffin blocks of tumor tissues were collected from cervical cancer patients. Expression of CD200 and cathepsin K (CTSK) in cancer tissues and para-cancerous tissues was analyzed by immunohistochemistry. Stably transfected CD200 cells were established in HeLa and SiHa cells. Human THP-1 monocytes were induced to differentiate into M2 macrophages. HeLa and SiHa cells were cultured in conditioned medium from M2 macrophages to observe the effects of CD200-CD200R on invasion, CTSK, p65NF-κB, and cisplatin or paclitaxel sensitivity in cervical cancer cells. HeLa cells were injected to induce xenograft tumors in mice, and a CTSK inhibitor, MK-0822, was used to confirm the regulation of CTSK and paclitaxel sensitivity by CD200-CD200R in vivo. Results: A significant decrease in CD200 and CTSK expression was found in tumor cancer tissues compared with para-cancerous tissues. Only CD200 overexpression did not affect cervical cell invasion, but CD200-CD200R could enhance the cell invasion and resistance to cisplatin or paclitaxel. Meanwhile, expression of CTSK and p-p65NF-κB in cancer cells stably transfected with CD200 was obviously increased after culture in conditioned medium from M2 macrophages compared with transfection with the plasmid control. In vivo, CTSK inhibition significantly suppressed the effects of CD200-CD200R overexpression on the response to paclitaxel by suppressing the CTSK-mediated NF-κB pathway. Conclusions: CD200-CD200R regulates CTSK-mediated NF-κB pathway to affect cisplatin or paclitaxel sensitivity in cervical cancer, which provides a possible immunotherapeutic target and combination strategy for advanced cervical cancer.

ABSTRACT The Yangtze finless porpoise (YFP) (Neophocaena asiaeorientalis asiaeorientalis) is a critically endangered freshwater cetacean, with about 1,249 individuals thought to be left in the wild. However, viral entities and viral diseases of YFPs remain obscure. In this study, anal swabs for virome analysis were collected during the physical examination of YFPs in the Tian-E-Zhou Oxbow (TEO) ex situ reserve. A total of 19 eukaryotic viral species belonging to 9 families, including Papillomaviridae, Herpesviridae, Picornaviridae, Picobirnaviridae, Caliciviridae, Retroviridae, Parvoviridae, Virgaviridae, and Narnaviridae, and other unclassified viruses were identified based on metasequencing. Among these detected viruses, a novel herpesvirus (NaHV), two different kobuviruses (NaKV1-2), and six different papillomaviruses (NaPV1 to -6) were considered potential risks to YFPs and confirmed by PCR or reverse transcription-PCR (RT-PCR). Most YFPs sampled were found to harbor one or more kinds of detected viral genomes (52/58 [89.7%]). Surveillance results demonstrated that kobuvirus and herpesvirus displayed obvious age distribution and PVs showed significant gender difference in YFPs. According to species demarcation criteria in individual genera in Papillomaviridae, two novel species (referred to as Omikronpapillomavirus 2 and 3) and four novel isolates of PV were identified in YFPs. Further evolutionary analysis suggested that NaPVs would occupy the mucosal niche and that virus-host codivergence mixed with duplications and host-switching events drives the evolution of cetacean PVs. Divergence times of PVs in YFP and other cetacean reflect the incipient speciation of YFPs. In summary, our findings revealed the potential viral entities, their prevalence, and their evolutionary history in YFPs, which raises an important issue regarding effects of viral infection on the fitness of YFPs. IMPORTANCE The Yangtze finless porpoise (YFP) is the only cetacean species in freshwater following the functional extinction of the baiji (Lipotes vexillifer). Health management, disease treatment, and other special measures are important for maintaining the existing YFP populations, especially in in situ and ex situ reserves. The discovery of potential viral entities and their prevalence in YFPs raises an important issue regarding the effects of viral infection on the fitness of YFPs and may contribute to the conservation of YFPs. The evolutionary history of papillomaviruses in YFP and other cetaceans reflects the phylogeny of their hosts and supports the status of incipient species, opening a window to investigate the evolutionary adaptation of cetaceans to freshwater as well as their phylogeny to remedy the deficiency of fossil evidence.

Industry 4.0 has placed significant emphasis on interconnectivity, digitalization, and automation. Among the myriad innovative technologies that have surfaced, artificial intelligence (AI) stands out as especially instrumental in the development of fully autonomous factories. Product quality inspection is a critical component of industrial manufacturing. An accurate and reliable AI-based Anomaly Detection and Localization (ADL) system for industrial product quality inspection is essential in real-world manufacturing factories. Collecting massive anomalous products is difficult because the number of anomalous products is limited and rare in a realistic manufacturing scenario. Therefore, the paper treats the ADL problem as a cold-start challenge, training the defects inspection network only using nominal (non-defective) images. Significantly, the paper aims to bridge the gap between academic research and real-world manufacturing industry applications. The paper lists issues that current state-of-the-art academic research faces when applied in real-world manufacturing settings, then a Reliable Anomaly Detection and Localization (RADL) system is developed to solve the issues. RADL is improved in three aspects. Firstly, the common image pre-processing method is modified by considering the characteristics of real-world industrial images. Secondly, a Fake Defect Feature Augmentation (FDFA) strategy to mitigate the scarcity of real-world data. Thirdly, a Hardness-aware Cross-Entropy loss (HCELoss) is adopted to enhance the stability and reliability of the system. On the public MVTec AD benchmarks, the proposed RADL outperforms previous methods with 99.53% in I-AUROC, 97.85% in P-AUROC, and 91.60% in PRO. Furthermore, RADL is evaluated under industrial manufacturing settings in two real-world datasets collected from industrial production lines. The experimental results demonstrate the superiority of the proposed strategies in a public dataset and real-world manufacturing industrial environments.

Tuberculosis (TB) is a global health threat, killing approximately 1.5 million people each year. The eradication of Mycobacterium tuberculosis, the main causative agent of TB, is increasingly challenging due to the emergence of extensive drug-resistant strains. Vaccination is considered an effective way to protect the host from pathogens, but the only clinically approved TB vaccine, Bacillus Calmette-Guérin (BCG), has limited protection in adults. Multi-epitope vaccines have been found to enhance immunity to diseases by selectively combining epitopes from several candidate proteins. This study aimed to design a multi-epitope vaccine against TB using an immuno-informatics approach. Through functional enrichment, we identified eight proteins secreted by M. tuberculosis that are either required for pathogenesis, secreted into extracellular space, or both. We then analyzed the epitopes of these proteins and selected 16 helper T lymphocyte epitopes with interferon-γ inducing activity, 15 cytotoxic T lymphocyte epitopes, and 10 linear B-cell epitopes, and conjugated them with adjuvant and Pan HLA DR-binding epitope (PADRE) using appropriate linkers. Moreover, we predicted the tertiary structure of this vaccine, its potential interaction with Toll-Like Receptor-4 (TLR4), and the immune response it might elicit. The results showed that this vaccine had a strong affinity for TLR4, which could significantly stimulate CD4+ and CD8+ cells to secrete immune factors and B lymphocytes to secrete immunoglobulins, so as to obtain good humoral and cellular immunity. Overall, this multi-epitope protein was predicted to be stable, safe, highly antigenic, and highly immunogenic, which has the potential to serve as a global vaccine against TB.

Abstract Gastrointestinal cancers (GICs) occupy more than 30% of the cancer-related incidence and mortality around the world. Despite advances in the treatment strategies, the long-term overall survival has not been improved for patients with GICs. Recently, the novel patient-derived organoid (PDO) culture technology has become a powerful tool for GICs in a manner that recapitulates the morphology, pathology, genetic, phenotypic, and behavior traits of the original tumors. Excitingly, a number of evidences suggest that the versatile technology has great potential for personalized treatment, suppling the clinical application of molecularly guided personalized treatment. In the paper, we summarize the literature on the topics of establishing organoid biobanks of PDOs, and their application in the personalized treatment allowing for radiotherapy, chemotherapy, targeted therapy, and immunotherapy selection for GICs. Despite the limitations of current organoid models, high-throughput drug screening of GIC PDO combined with next-generation sequencing technology represents a novel and pivotal preclinical model for precision medicine of tumors and has a great value in promoting the transformation from basic cancer research to clinical application.

Abstract Although traffic deadlock at an intersection is a common phenomenon during rush hours, the deadlock formation metrics such as formation probability and duration have not been derived yet. As Petri Net (PN)‐based approach can formulate the deadlock formation in analytical form and has been applied in numerous traffic flow studies, the PN is employed to investigate the deadlock formation probability and duration. First, each of the four main components of an intersection is formulated, namely vehicle trajectory, traffic signal, vehicle arrivals, and conflict behaviour, as a Petri Net (or IntersectionPN), and name them CellularPN, TrafficLightPN, DemandPN, and ConflictPN, respectively. Together, the entire intersection becomes an IntersectionPN, on which the system's three classes of states are defined, namely the deadlock state, the trap state, and the live state. The deadlock occurrence is formulated as an integer programming problem, while the formation probability and duration are studied by constructing a reachability graph that leads to the Markov chain of the system. A case study shows that the developed model is able to reproduce an intersection deadlock, and that the focus is on two priority behaviours: “First Enter First Serve” and “Pure Stochastic”. The results show that different behaviours lead to different deadlock formation metrics and that, when the saturation flow rate degrades (due to events such as severe weather conditions), a deadlock will occur more quickly. The research results provide the analysis tool for probabilistic deadlock formation. It can also be applied to the intersection deadlock prevention and control.

The identification of tumor-related microRNAs (miRNAs) exhibits excellent promise for the early diagnosis of cancer and other bioanalytical applications. Therefore, we developed a sensitive and efficient biosensor using polyadenine (polyA)-mediated fluorescent spherical nucleic acid (FSNA) for miRNA analysis based on strand displacement reactions on gold nanoparticle (AuNP) surfaces and electrokinetic signal amplification (ESA) on a microfluidic chip. In this FSNA, polyA-DNA biosensor was anchored on AuNP surfaces via intrinsic affinity between adenine and Au. The upright conformational polyA-DNA recognition block hybridized with 6-carboxyfluorescein-labeled reporter-DNA, resulting in fluorescence quenching of FSNA probes induced by AuNP-based resonance energy transfer. Reporter DNA was replaced in the presence of target miRNA, leading to the recovery of reporter-DNA fluorescence. Subsequently, reporter-DNAs were accumulated and detected in the front of with Nafion membrane in the microchannel by ESA. Our method showed high selectivity and sensitivity with a limit of detection of 1.3 pM. This method could also be used to detect miRNA-21 in human serum and urine samples, with recoveries of 104.0%–113.3% and 104.9%–108.0%, respectively. Furthermore, we constructed a chip with three parallel channels for the simultaneous detection of multiple tumor-related miRNAs (miRNA-21, miRNA-141, and miRNA-375), which increased the detection efficiency. Our universal method can be applied to other DNA/RNA analyses by altering recognition sequences.

Testicular two-dimensional ultrasound is a testing modality that is often used to evaluate azoospermia and other related diseases. With the continuous development of deep learning in recent years, the combination of deep learning and testicular ultrasound appears unstoppable despite a lack of relevant standards. One of the major problems associated with the digitization of ultrasound images is the uneven quality of data however, and a standardized data source and acquisition process has not yet been developed. Such a standard could fill the current gap, and establish acquisition criteria for ultrasound images of testes during the male reproductive period, including grayscale ultrasound, shear wave elastography, and contrast-enhanced ultrasound. By following these guidelines the quality of testicular ultrasound images would be improved and standardized, which would lay a solid foundation for the standardization of testicular ultrasound images, and assist automated evaluation of testicular spermatogenic function of whole testis in azoospermic males.

Background: Mortality is high for severe alcohol-associated hepatitis (AH). Corticosteroids are the standard of care for patients without contraindications. Recent data showed that interleukin-1β receptor antagonist anakinra attenuated inflammation and liver damage. We designed a multicenter, double-blind, randomized controlled trial to assess the safety and efficacy of anakinra compared to prednisone. Methods: Patients meeting the clinical and biochemical criteria for severe AH with MELD scores between 20 and 35 were recruited at eight clinical sites. Eligible patients enrolled in the study were randomized to anakinra, 100 mg subcutaneous injection for 14 days, plus zinc sulfate 220 mg for 90 days, vs. prednisone 40 mg PO daily for 30 days. Matching placebos for anakinra, zinc, and prednisone were provided to mask the treatment. Participants were followed for 180 days. The primary outcome was overall survival at 90 days. An unadjusted log-rank test was used to compare the survival of the two treatments in the first 90 days. Between July 10, 2020, and March 4, 2022, we screened 1082 patients with severe AH, and 147 eligible patients were enrolled and randomized. The average baseline MELD score was 25 [range 20–35], Maddrey discriminant function (MDF) was 59.4 [range 20.2–197.5]. The mean aspartate transaminase (AST)-to-alanine transaminase (ALT) ratio was 3.5. The baseline characteristics were not statistically different between the two treatment groups. Conclusions: The study provided a direct comparison of the survival benefits and safety profiles of anakinra plus zinc vs. prednisone in patients with severe AH.

Keloids are considered the manifestation of a fibroproliferative disease characterized by chronic inflammation that is induced following skin injury. Deciphering the underlying mechanism of keloid formation is essential for improving treatment outcomes. Here, we found that more macrophages were activated toward the M2 subtype in keloid dermis when compared with normal dermis. Western blotting revealed that the level of phosphorylated STAT6 (p-STAT6), a known inducer of M2 polarization, was higher in keloid fibroblasts as opposed to fibroblasts from normal dermis. Moreover, keloid fibrosis was shown to be positively correlated with the level of p-STAT6. Further, we identified downregulation of IL-13RA2, a decoy receptor for IL-13, in keloid fibroblasts compared with fibroblasts from normal dermis. Ectopic expression of IL-13RA2 in keloid fibroblasts resulted in inhibition of STAT6 phosphorylation, cell proliferation, migration, invasion, extracellular matrix secretion, and myofibroblast marker expression, as well as an increase in apoptosis. Consistently, knockdown of IL-13RA2 in normal fibroblasts induced a keloidal status. Furthermore, both in vitro application and intratumoral injection of p-STAT6 inhibitor AS1517499 in a patient-derived xenograft keloid-implantation mouse model resulted in proliferation inhibition and tissue necrosis, apoptosis, and myofibroblast marker reduction. Collectively, this study elucidates the key role of IL-13RA2 in keloid pathology and inspires further translational research of keloid treatment concerning JAK/STAT6 inhibition.

BackgroundImmunohistochemical microvessel density (MVD) is an early indicator of angiogenesis and it could be used to evaluate the therapeutic efficacy of non-small cell lung cancer (NSCLC). We sought to identify the ability of contrast-enhanced ultrasound (CEUS) in evaluating MVD of subpleural NSCLC.MethodsWe prospectively collected CEUS data of NSCLC confirmed by ultrasound-guided transthoracic needle biopsy from October 2019 to February 2021, The MVD of NSCLC counted by CD34-positive vessels of immunohistochemical staining. Microflow enhancement (MFE) of CEUS was divided into “dead wood”, “cotton”, and “vascular” patterns. Pathology subgroup and MVD between different MFE patterns were analyzed, respectively. The arrival time, time to peak, peak intensity (PI), and area under curve (AUC) derivefrom time-intensity curve of CEUS with MVD in NSCLC and its pathological subgroups (adenocarcinoma and squamous cell carcinoma) were subjected to correlation analysis.ResultsA total of 87 patients were included in this study, consisting of 53 cases of adenocarcinoma and 34 cases of squamous cell carcinoma with a mean MVD of 27.8 ± 12.2 mm–1. There was a significant statistical difference in MFE patterns between two pathological subgroups (p < 0.05). Besides, the MVD of “cotton” and “vascular” patterns were significantly higher than that of “dead wood” pattern (both of p < 0.05), whereas there was no significant difference in MVD between “cotton” pattern and “vascular” pattern. PI and AUC of CEUS were positively correlated with the MVD of NSCLC (r = 0.497, p < 0.001, and r = 0.367, p < 0.001, respectively). Besides, PI and AUC of CEUS were positively correlated with the MVD of squamous cell carcinoma (r = 0.802, and r = 0.663, respectively; both of p < 0.001). Only the PI was positively correlated with the MVD of lung adenocarcinoma (r = 0.288, p = 0.037).ConclusionsMFE patterns and quantitative parameters of CEUS had good correlation with MVD of NSCLC, especially in squamous cell carcinoma.

Tropaeolum majus (nasturtium) is an important ornamental and medicinal plant due to its colorful flowers, shield-shaped leaves, and richness in mineral elements and bioactive compounds. However, the key genes related to these important biological traits, as well as their expression patterns and functions, remain obscure. In this study, to choose appropriate reference genes for quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis, we screened 14 candidate genes from the transcriptome of T. majus and evaluated their expression stability. Through evaluation with four commonly used algorithms (geNorm, NormFinder, BestKeeper, and RefFinder), EXP1, EXP2, and TUB6 were found to be the most stably expressed genes among different organs, while EXP1 combined with CYP2 was identified as the optimal reference gene combination for seeds at different development stages. For all the tested samples, EXP1, EXP2, CYP2, and ACT2 were the most suitable reference genes. Moreover, the target gene KCS11 involved in very-long-chain fatty acid biosynthesis was employed to confirm the most and least stable reference genes in different organs, seeds at different development stages, and all the tested samples. The expression profiles of KCS11 were similar, with minor differences based on the analysis of different stable reference genes (either alone or in combination), while the expression profiles were diverse and the relative expression level was overestimated when using the least stable ones. These results suggest that the appropriate selection of reference genes is critical for the normalization of gene expression. Furthermore, the reference genes screened in this study will greatly improve the accuracy of the qRT-PCR quantification of candidate genes involved in the many biological characteristics of nasturtium.

Non-small cell lung cancer (NSCLC) is a common clinical malignant tumor with limited therapeutic drugs. Leading by cytotoxicity against NSCLC cell lines (A549 and PC9), bioactivity-guided isolation of components from Peganum harmala seeds led to the isolation of pegaharoline A (PA). PA was elucidated as a structurally novel aniline derivative, originating from tryptamine with a pyrrole ring cleaved and the degradation of carbon. Biological studies showed that PA significantly inhibited NSCLC cell proliferation, suppressed DNA synthesis, arrested the cell cycle, suppressed colony formation and HUVEC angiogenesis, and blocked cell invasion and migration. Molecular docking and surface plasmon resonance (SPR) demonstrated PA could bind with CD133, correspondingly decreased CD133 expression to activate autophagy via inhibiting the PI3K/AKT/mTOR pathway, and increased ROS levels, Bax, and cleaved caspase-3 to promote apoptosis. PA could also decrease p-cyclinD1 and p-Erk1/2 and block the EMT pathway to inhibit NSCLC cell growth, invasion, and migration. According to these results, PA could inhibit NSCLC cell growth by blocking PI3K/AKT/mTOR and EMT pathways. This study provides evidence that PA has a promising future as a candidate for developing drugs for treating NSCLC.

Abstract Delayed luminescence (DL) is gradually used in various detection of biological systems as a rapid detection technique, however, its biological mechanism was still not clear. In this study, a new model of DL detection system for liquid biological samples is established to investigate the DL emission of Saccharomyces cerevisiae cells cultured in different glucose concentrations. We analyzed the relationship between the DL emission and cell growth, cell vitality, mitochondrial morphology, mitochondrial DNA (mtDNA) copy number, adenosine triphosphate (ATP), oxygen consumption rate (OCR), as well as mitochondria membrane potential (MMP) in S. cerevisiae cells cultured with 0.01, 0.05, 0.15, 3, 10 and 20 g/L glucose respectively. It was found that the DL emission had strong correlation with mitochondrial morphology, OCR, and MMP. The results suggested that DL is an indicator of mitochondria status under different glucose supply conditions, and may be an effective method to detect mitochondrial metabolism related disorders.

BackgroundIn the past two years, studies have found a significant increase in neutrophil extracellular traps (NETs) in patients with IgA vasculitis (IgAV), which is correlated with the severity of the disease. NETs have been reported as an intervention target in inflammatory and autoimmune diseases. This study aimed to investigate the effect of targeted degradation of NETs using DNase I in IgAV rat model.MethodsTwenty-four Sprague-Dawley rats were randomly divided into three groups: the IgAV model group, the DNase I intervention group and the normal control group, with an average of 8 rats in each group. The model group was established by using Indian ink, ovalbumin, and Freund's complete adjuvant. In the intervention group, DNase I was injected through tail vein 3 days before the end of established model. The circulating cell free-DNA (cf-DNA) and myeloperoxidase-DNA (MPO-DNA) were analyzed. The presence of NETs in the kidney, gastric antrum and descending duodenum were detected using multiple fluorescences immunohistochemistry and Western blots. Morphological changes of the tissues were observed.ResultsAfter the intervention of DNase I, there was a significant reduction in cf-DNA and MPO-DNA levels in the intervention group compared to the IgAV model group (all PConclusionThe degradation of NETs can be targeted by DNase I to mitigate tissue damage in IgAV rat models. Targeted regulation of NETs holds potential as a therapeutic approach for IgAV.

NSCLC (non-small cell lung cancer) is one of the most common and lethal malignant tumors, with low 5-year overall survival rate. Curcumol showed antitumor activity in several cancers, but evidence about its effect on NSCLC remains unclear. In the present study, we found that Curcumol markedly inhibited NSCLC cells proliferation, migration and invasion. Endothelial cells are an important part of tumor microenvironment. Tube formation assay and wound healing assay indicated that A549 derived conditioned medium affected HUVECs (human umbilical vein endothelial cells). Mechanistically, Curcumol downregulated the expression of SP1 (specificity protein 1) while upregulated miR-125b-5p, followed by decreasing VEGFA expression in NSCLC cells. Furthermore, overexpression of SP1 partially reversed the inhibitory effect of Curcumol on A549 and H1975 cell viability and VEGFA expression. Inhibition of miR-125b-5p presented similar effect. Interestingly, there was mutual modulation between SP1 and miR-125b-5p. Collectively, our study revealed that Curcumol inhibited cell growth and angiogenesis of NSCLC in vitro and in vivo, possibly through SP1/miR-125b-5p/VEGFA regulatory mechanism. These findings may provide effective therapy strategies for NSCLC treatment.

Breast cancer is a malignant tumor that has a high mortality rate and mostly occurs in women. Although significant progress has been made in the implementation of personalized treatment strategies for molecular subtypes in breast cancer, the therapeutic response is often not satisfactory. Studies have reported that long non-coding RNAs (lncRNAs) are abnormally expressed in breast cancer and closely related to the occurrence and development of breast cancer. In addition, the high tissue and cell-type specificity makes lncRNAs particularly attractive as diagnostic biomarkers, prognostic factors, and specific therapeutic targets. Therefore, an in-depth understanding of the regulatory mechanisms of lncRNAs in breast cancer is essential for developing new treatment strategies. In this review, we systematically elucidate the general characteristics, potential mechanisms, and targeted therapy of lncRNAs and discuss the emerging functions of lncRNAs in breast cancer. Additionally, we also highlight the advantages and challenges of using lncRNAs as biomarkers for diagnosis or therapeutic targets for drug resistance in breast cancer and present future perspectives in clinical practice.

BackgroundWilson’s disease (WD) is a rare cause of acute liver failure (ALF) and has a high fatality rate. Rapid and accurate diagnosis is important for ALF because of WD (ALF-WD). Our objective was to establish a simple, rapid, and accurate diagnostic test to distinguish ALF-WD from non-WD ALF (NWDALF) in children.Materials and methodsThe data from all cases with pediatric ALF were retrospectively collected and analyzed. We performed receiver operator characteristics curve (ROC) analysis and confirmed the optimum cut-off points.ResultsFifty-eight patients with pediatric ALF (12 with WD, 46 with other etiologies) were included. Older age was observed in ALF-WD compared to NWDALF (11.16 ± 2.51 years vs. 3.34 ± 3.81 years, p < 0.001). An analysis based on routine biochemical testings revealed that total bilirubin (TBil), direct bilirubin, indirect bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST:ALT ratio, alkaline phosphatase (ALP), ALP:TBil ratio, serum albumin, gamma-glutamyl transferase, cholinesterase, hemoglobin, and platelet were statistically significant between the ALF-WD and NWDALF groups. The optimum cut-off points were obtained through ROC analysis. A scoring system was formed by assigning a score of 1 or 0 to patients who met the 13 cut-off points. Using ROC analysis, we determined a cut-off point of ≥ 6.5 for ALF-WD with 91.7% sensitivity and 97.8% specificity (p < 0.0001). In addition, a best cut-off point of ≥ 1.5 based on only five variables (ALT, AST, AST:ALT ratio, ALP, and ALP:TBil ratio), had 100% sensitivity and 91.3% specificity for ALF-WD (p < 0.0001). Based on this, when age was calculated as the sixth indicator, the best cut-off value of ≥ 2.5 had 100% sensitivity and 97.8% specificity (p < 00.0001).ConclusionOur study developed a new scoring system that consists of simple laboratory tests with good sensitivity and specificity and can be used by clinicians to quickly distinguish ALF-WD from NWDALF in children.

BackgroundMalignant pleural mesothelioma (MPM) is a highly invasive malignant tumor. Ultrasound guidance has the advantages of real-time, convenience and nonradiative. We sought to identify diagnostic value and its influenced factors of ultrasound-guided percutaneous pleural needle biopsy (US-PPNB) for MPM.MethodsPatients who underwent US-PPNB between March 2014 and March 2020 and were finally diagnosed with MPM were retrospectively analyzed. We retrospectively analyzed the US-PPNBs pathological results of all patients clinically confirmed as MPM, and divided US-PPNBs into correctly and incorrectly diagnosed groups. Patient, thoracic, and biopsy variables that affected diagnostic accuracy were assessed. All variables significant on univariate analyses were subjected to multivariate logistic regression to identify significant predictors of diagnostic accuracy. We derived cutoffs for all significant continuous variables and used the Mantel–Haenszel test to determine whether the diagnostic accuracy of US-PPNB for MPM increased with pleural thickness.ResultsIn total, 49 patients with clinically confirmed MPM underwent US-PPNB; 37 diagnoses were correct and 12 were incorrect (accuracy = 75.5%). The pleura was significantly thicker in the correctly diagnosed group (p

Diarrhea predominant irritable bowel syndrome (IBS) is a highly relapsing gastrointestinal disorder decreasing the quality of life. Existing studies indicated that the therapeutic effects maintained for a period of time after the treatments were discontinued (post-treatment therapeutic effects or PTTE). In this study, we aim to assess the PTTE of tongxie. We performed a multiple center, controlled, double blind study of patients with IBS randomized to tongxie (n = 120) or placebo (n = 120) for 4 weeks and followed up for 57 weeks. The primary outcomes were abdominal pains and stool consistency. The secondary outcomes were pain frequency and stool frequency. Tertiary outcomes were adverse effects and global overall symptom. The outcome data were collected at days 1, 2, 3, weeks 1 and 4 during the treatment and at days 1, 2, 3, until week 57 during the post-treatment. Significantly more patients receiving tongxie were clinical responders to the primary and secondary endpoints from day 1 until the end of the treatment. The positive effects of tongxie were maintained until 17–25 weeks after tongxie was discontinued. The relapse-free probabilities in the tongxie group were significantly higher than those in the placebo group (P