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The gut microbiota is a complex community of microorganisms inhabiting the intestinal tract, which plays a vital role in human health. It is intricately involved in the metabolism, and it also affects diverse physiological processes. The gut–lung axis is a bidirectional pathway between the gastrointestinal tract and the lungs. Recent research has shown that the gut microbiome plays a crucial role in immune response regulation in the lungs and the development of lung diseases. In this review, we present the interrelated factors concerning gut microbiota and the associated metabolites in pulmonary hypertension (PH), a lethal disease characterized by elevated pulmonary vascular pressure and resistance. Our research team explored the role of gut‐microbiota‐derived metabolites in cardiovascular diseases and established the correlation between metabolites such as putrescine, succinate, trimethylamine N‐oxide (TMAO), and N, N, N‐trimethyl‐5‐aminovaleric acid with the diseases. Furthermore, we found that specific metabolites, such as TMAO and betaine, have significant clinical value in PH, suggesting their potential as biomarkers in disease management. In detailing the interplay between the gut microbiota, their metabolites, and PH, we underscored the potential therapeutic approaches modulating this microbiota. Ultimately, we endeavor to alleviate the substantial socioeconomic burden associated with this disease. This review presents a unique exploratory analysis of the link between gut microbiota and PH, intending to propel further investigations in the gut–lung axis. Highlights: The significant development in gut microbiota has brought an unprecedented paradigm for pulmonary hypertension (PH) management in recent years, which has delighted researchers and clinicians in precise disease control.The gut–lung axis is the bidirectional interaction between the gut and lung, which occurs through circulation, the nervous system, and other physiological processes, ultimately affecting the health of both the gut and the lung.We provided a comprehensive landscape of gut microbiota and its associated metabolites in PH, emphasizing the interplay between microorganisms and hosts in modulating PH.With the rapid development of technologies, including metagenomic and metabolomics on gut microbiota, the association of microorganisms and the human body will be untangled eventually, which will bring the dawn for disease cure followed by prognosis improvement among patients with PH. [ABSTRACT FROM AUTHOR]

The quasi‐2D Ruddlesden–Popper layered perovskites with single‐phase multiferroicity have attracted much attention in recent magnetoelectric memory applications. We have systematically investigated the optical and magnetic properties of Ru‐doped hybrid improper perovskite Ca3Mn2O7 both experimentally and using first‐principles calculations. The Ca3RuxMn2−xO7 (x = 0, 0.02, 0.06, 0.10) powders were successfully synthesized using the sol–gel method. Ru doping enhanced the ferromagnetism of Ca3Mn2O7. The quasi‐2D antiferromagnetic (AFM) fluctuation effect was observed in Ca3Mn2O7 and in certain doped samples. We also found that the optical bandgaps of the doped samples were reduced after doping, agreeing with the results of the first‐principles calculations. Infrared absorption spectra indicated the distortion of the Mn–O bonds was possibly due to the Jahn–Teller effect. To analyze the electronic structures and to understand the detailed atomic contributions of magnetic moments, the Crystal Orbital Hamilton Population (COHP) and Integrated COHP of the (Mn,Ru)O6 octahedra were also calculated. The Ru‐doped materials with the coexistence of ferromagnetic and AFM orderings are expected to be excellent candidates for magnetoelectric devices. [ABSTRACT FROM AUTHOR]

Summary: Molecular characterization of genetically modified organisms (GMOs) yields basic information on exogenous DNA integration, including integration sites, entire inserted sequences and structures, flanking sequences and copy number, providing key data for biosafety assessment. However, there are few effective methods for deciphering transgene integration, especially for large DNA fragment integration with complex rearrangement, inversion and tandem repeats. Herein, we developed a universal Large Integrated DNA Fragments Enrichment strategy combined with PacBio Sequencing (LIFE‐Seq) for deciphering transgene integration in GMOs. Universal tilling DNA probes targeting transgenic elements and exogenous genes facilitate specific enrichment of large inserted DNA fragments associated with transgenes from plant genomes, followed by PacBio sequencing. LIFE‐Seq were evaluated using six GM events and four crop species. Target DNA fragments averaging ~6275 bp were enriched and sequenced, generating ~26 352 high fidelity reads for each sample. Transgene integration structures were determined with high repeatability and sensitivity. Compared with next‐generation whole‐genome sequencing, LIFE‐Seq achieved better data integrity and accuracy, greater universality and lower cost, especially for transgenic crops with complex inserted DNA structures. LIFE‐Seq could be applied in molecular characterization of transgenic crops and animals, and complex DNA structure analysis in genetics research. [ABSTRACT FROM AUTHOR]

Rapid progress has been made to identify and study the causative agent leading to coronavirus disease 2019 (COVID‐19) but many questions including who is most susceptible and what determines severity remain unanswered. Angiotensin‐converting enzyme 2 (ACE2) is a key factor in the infection process of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). In this study, molecularly specific positron emission tomography imaging agents for targeting ACE2 are first developed, and these novel agents are evaluated in vitro, in preclinical model systems, and in a first‐in‐human translational ACE2 imaging of healthy volunteers and a SARS‐CoV‐2 recovered patient (NCT04422457). ACE2 expression levels in different organs in live subjects are quantitatively delineated and observable differences are measured in the patient recovered from COVID‐19. Surprising sites of uptake in the breast, reproductive system and very low uptake in pulmonary tissues are reported. This novel method can add a unique tool to facilitate SARS‐CoV‐2 related research and improve understanding of this enigmatic disease. Molecular imaging provides quantitative annotation of ACE2, the SARS‐CoV‐2 entry receptor, to noninvasively monitor organs impacted by the COVID‐19. [ABSTRACT FROM AUTHOR]

Rapid progress has been made to identify and study the causative agent leading to coronavirus disease 2019 (COVID‐19) but many questions including who is most susceptible and what determines severity remain unanswered. Angiotensin‐converting enzyme 2 (ACE2) is a key factor in the infection process of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). In this study, molecularly specific positron emission tomography imaging agents for targeting ACE2 are first developed, and these novel agents are evaluated in vitro, in preclinical model systems, and in a first‐in‐human translational ACE2 imaging of healthy volunteers and a SARS‐CoV‐2 recovered patient (NCT04422457). ACE2 expression levels in different organs in live subjects are quantitatively delineated and observable differences are measured in the patient recovered from COVID‐19. Surprising sites of uptake in the breast, reproductive system and very low uptake in pulmonary tissues are reported. This novel method can add a unique tool to facilitate SARS‐CoV‐2 related research and improve understanding of this enigmatic disease. Molecular imaging provides quantitative annotation of ACE2, the SARS‐CoV‐2 entry receptor, to noninvasively monitor organs impacted by the COVID‐19. [ABSTRACT FROM AUTHOR]

Retention after treatment and effective anchorage control are two essential factors in orthodontics. Our study aimed to explore the effects of fucoidan on orthodontic tooth movement (OTM) and the involvement of macrophages. We established a murine OTM model to test the effect of fucoidan administration. We found that mice injected with fucoidan had a deceleration in OTM and a higher bone mineral density. Moreover, fucoidan increased the proportion of F4/80+CD206+ macrophages and promoted the messenger RNA expression of Arg‐1, CD206, and IL‐10 at both in vivo and in vitro levels. In addition, macrophages showed lower expression of TNF‐α, IL‐1β, and IL‐6 and a decrease in F4/80+CD11c+ cells. Mechanistically, the level of phosphorylated STAT3 was elevated in unpolarized and restorative macrophages after treatment with fucoidan. Taken together, our findings suggest that fucoidan treatment inhibits OTM and enhances the stability of teeth after movement by promoting restorative macrophages through the STAT3 pathway. [ABSTRACT FROM AUTHOR]

Background: Adverse drug reactions (ADR) are severe problems in global public health, and result in high mortality and morbidity. Various trends of ADR‐related hospitalisations have been studied in many countries, while estimates of the trends in Australia are limited. Aim: To examine trends in ADR‐related hospitalisations in New South Wales (NSW). Methods: Data were extracted from the Admitted Patient Data Collection, a census of hospital separations in NSW. We estimated age‐adjusted rates of ADR‐related hospitalisation between 1 July 2001 and 30 June 2014 and rates by patient characteristics, main therapeutic medication groups and clinical condition groups that warranted the hospitalisation. We used the percentage change annualised estimator to evaluate rates over time. Results: A total of 315 274 NSW residents admitted for urgent care of ADR was identified. The age‐adjusted rates of ADR‐related hospitalisations nearly doubled and increased by 5.8% (95% CI: 5.0–6.6%) per annum, with an in‐hospital death rate increase of 2.4% (1.6–3.3%). Agranulocytosis (2.7%), nausea and vomiting (2.4%) and heart failure (2.4%) were the most common conditions that led to ADR‐related hospitalisations over 13 years, with acute renal failure (1.4%) recently emerging as the leading adverse condition. Participants aged between 65 and 84 years accounted for nearly half of ADR hospitalisations (45.6%), with age‐adjusted rate increasing from 103.9 in 2001–2002 to 189.0 per 100 000 NSW residents in 2013–2014. Anticoagulants (13.5%) were the most common medications contributing to ADR‐related hospitalisation, followed by opioid analgesics (9.6%). Conclusion: ADR‐related hospitalisation remains a population health burden, with significant increase over time. The findings call for continuing efforts to prevent ADR, especially among high‐risk populations, such as older people. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Stigma towards people with mental illness impedes effective treatment. A recent study found that Chinese students were less socially accepting of people with mental illness than counterparts from other countries. The current study examined stigma among Chinese medical students at different levels of training. Methods: Medical students (N = 1372 from 12 Chinese schools) were surveyed with a questionnaire addressing attitudes and beliefs about people with mental illness. Analysis of variance was used to compare responses from students: (1) with no psychiatry training; (2) who had only taken a didactic course; and (3) who had completed both a course and a clinical rotation. Specific attitudes were identified through factor analysis. Interest in further training and other personal experience were also examined. Results: Factor analysis revealed attitudes favoring: (1) social acceptance of people with mental illness, (2) not believing in supernatural causes of mental illness, (3) bio‐psycho‐social causation, (4) rehabilitation, and (5) social integration. The absence of consistent trends across training levels suggested that education did not increase nonstigmatized attitudes. Areas of most stigmatization were low social acceptance and little favor for social integration. Measures most strongly correlated with nonstigmatized attitudes were as follows: interest in clinical psychiatry, belief that psychiatry should be more valued, and having friends with mental illness. Discussion: Although medical school education showed little effect on attitudes, students with more individual experiences such as planning to continue clinical psychiatric training, believing psychiatry should be more valued, and having friends with mental illness had less stigmatized attitudes than others. [ABSTRACT FROM AUTHOR]

Emerging high entropy compounds (HECs) have attracted huge attention in electrochemical energy‐related applications. The features of ultrafine size and carbon incorporation show great potential to boost the ion‐storage kinetics of HECs. However, they are rarely reported because high‐temperature calcination tends to result in larger crystallites, phase separation, and carbon reduction. Herein, using the NaCl self‐assembly template method, by introducing a high‐pressure field in the calcination process, the atom diffusion and phase separation are inhibited for the general formation of HECs, and the HEC aggregation is inhibited for obtaining ultrafine size. The general preparation of ultrafine‐sized (<10 nm) HECs (nitrides, oxides, sulfides, and phosphates) anchored on porous carbon composites is realized. They are demonstrated by combining advanced characterization technologies with theoretical computations. Ultrafine‐sized high entropy sulfides‐MnFeCoCuSnMo/porous carbon (HES‐MnFeCoCuSnMo/PC) as representative anodes exhibit excellent sodium‐ion storage kinetics and capacities (a high rating capacity of 278 mAh g−1 at 10 A g−1 for full cell and a high cycling capacity of 281 mAh g−1 at 20 A g−1 after 6000 cycles for half cell) due to the combining advantages of high entropy effect, ultrafine size, and PC incorporation. Our work provides a new opportunity for designing and fabricating ultrafine‐sized HECs. [ABSTRACT FROM AUTHOR]

Background: The GPNMB single‐nucleotide polymorphism rs199347 and GBA1 variants both associate with Lewy body disorder (LBD) risk. GPNMB encodes glycoprotein nonmetastatic melanoma protein B (GPNMB), a biomarker for GBA1‐associated Gaucher's disease. Objective: The aim of this study was to determine whether GPNMB levels (1) differ in LBD with and without GBA1 variants and (2) associate with rs199347 genotype. Methods: We quantified GPNMB levels in plasma and cerebrospinal fluid (CSF) from 124 individuals with LBD with one GBA1 variant (121 plasma, 14 CSF), 631 individuals with LBD without GBA1 variants (626 plasma, 41 CSF), 9 neurologically normal individuals with one GBA1 variant (plasma), and 2 individuals with two GBA1 variants (plasma). We tested for associations between GPNMB levels and rs199347 or GBA1 status. Results: GPNMB levels associate with rs199347 genotype in plasma (P = 0.022) and CSF (P = 0.007), but not with GBA1 status. Conclusions: rs199347 is a protein quantitative trait locus for GPNMB. GPNMB levels are unaltered in individuals carrying one GBA1 variant. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Estrogen receptor alpha (ER‐α) action is critical for hormone‐dependent breast cancer, and ER‐α dysregulation can lead to the emergence of resistance to endocrine therapy. Here, it is found that TRIM4 is downregulated in tamoxifen (TAM)‐resistant breast cancer cells, while the loss of TRIM4 is associated with an unfavorable prognosis. In vitro and in vivo experiments confirm that TRIM4 increased ER‐α expression and the sensitivity of breast cancer cells to TAM. Mechanistically, TRIM4 is found to target SET, and TRIM4‐SET interactions are mediated by the RING and B‐box domains of TRIM4 and the carboxyl terminus of SET. Moreover, it is determined that TRIM4 catalyzed the K48‐linked polyubiquitination of SET (K150 and K172), promoting its proteasomal degradation and disassociation from p53 and PP2A. Once released, p53 and PP2A are able to further promote ESR1 gene transcription and enhance mRNA stability. Moreover, univariate and multivariate Cox proportional hazards regression analyses confirm that TRIM4 expression is an independent predictor of overall survival and recurrence‐free survival outcomes in patients with ER‐α positive breast cancer. Taken together, the data highlights a previously undiscovered mechanism and suggest that TRIM4 is a valuable biomarker that can be analyzed to predict response to endocrine therapy in breast cancer patients. [ABSTRACT FROM AUTHOR]

Class A1 scavenger receptors (SR-A1) are membrane glycoproteins that can form homotrimers. This receptor was originally defined by its ability to mediate the accumulation of lipids in macrophages. Subsequent studies reveal that SR-A1 plays critical roles in innate immunity, cell apoptosis and proliferation. This review highlights recent advances in understanding the structure, receptor pathway and regulation of SR-A1. Although its role in atherosclerosis is disputable, recent discoveries suggest that SR-A1 function in anti-inflammatory responses by promoting an M2 macrophage phenotype in cardiovascular diseases. Therefore, SR-A1 may be a potential target for therapeutic intervention of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Resource‐rich FeS2 is a promising anode for potassium‐ion batteries (PIBs). However, polysulfides emerge due to FeS2 conversion during discharging, which dissolve into the ether‐based electrolyte and cause the continuous capacity degradation in PIBs. To address the polysulfides dissolution in PIBs, a graphene–shell‐encapsulated FeS2 is fabricated and embedded in N/S codoped 3D hollow carbon spheres. As a protective pocket, the graphene–shell can effectively accommodate polysulfides inside the core–shell, inhibiting the polysulfides shuttle effect to enhance cycle stability of electrode. The density functional theory (DFT) calculations demonstrate that graphene–shells have a strong adsorption capacity for polysulfides, and the interfacial interaction between KFeS2 and graphene–shell can boost the K ion mobility. As a result, the composite exhibits superior‐rate properties (524 and 224 mA h g−1 at 0.1 and 8 A g−1, respectively) and long‐term cycle stability. This work demonstrates the promotion and protective effect of the graphene–shell for the FeS2 to storage K from both experimental and computational perspectives. These research outputs can provide guidance for designing other metal‐based sulfide electrodes for PIBs. [ABSTRACT FROM AUTHOR]

Four manufacturing impurities of D&C Red No. 33 isolated by counter‐current chromatography were analyzed by NMR and ESI mass spectrometry. Three of these impurities were reported previously with minimal details of structural determination. All four are structurally related to the main component of the dye. The fourth exhibited an unusual discrepancy between the NMR structure and its chemical formula suggested by ESI‐MS results. Structural determination and assignment of the main component and four impurities are discussed as well as resolution of the discrepancy between the NMR and ESI‐MS results of the fourth impurity. [ABSTRACT FROM AUTHOR]

Multivariable stochastic degradation system (MSDS) is quite common in industries such as blast furnace ironmaking, vehicle transportation, and aerospace manufacturing. Large‐scale complex equipments may be affected by multiple factors, resulting in not just a single deteriorating performance characteristic. It is difficult to handle unknown failure structures of practical systems by using traditional univariate degradation modeling methods. A novel health index (HI) is constructed to quantitatively analyze the health state for the overall system. Considering the interaction between internal reactions and external environments, the fractional Brownian motion (FBM), a typical non‐Markovian diffusion process, is added for the purpose of reflecting stochastic uncertainties and memory effects. Based on the wavelet estimators and the maximum likelihood estimation (MLE) algorithm, multi‐sensor observations of degradation variables are analyzed simultaneously to identify model parameters. A closed‐form distribution of system‐level remaining useful life (RUL) is obtained with a mild two‐layer approximation. Relevant case studies are then handled that adequately demonstrate the effectiveness and the practical utility of the proposed method. [ABSTRACT FROM AUTHOR]

Background: The distant metastasis was the most predictive characters of poor prognosis for triple‐negative breast cancer (TNBC). We aimed to evaluate the correlation between patient characters and preferential distant metastatic sites (DMS) and its effects on prognosis. Methods: Using the 2010‐2014 Surveillance, Epidemiology, and End Results Program (SEER) data, patients with TNBC were classified into eight histologic subtypes. Patient characters were compared using a chi‐squared test. Logistic regression was used for identification of predictive factors. The log‐rank testing was utilized with disease‐specific survival (DSS) and overall survival (OS) as the primary outcomes. Results: A total of 23 270 patients with TNBC were involved, including 1544 patients with distant metastatic cancer. Bone metastasis was diagnosed in 559 cases, brain metastasis in 124 cases, liver metastasis found in 369 cases and lung metastasis in 492 cases. Histologic subtypes including metaplastic breast carcinoma and invasive lobular carcinoma showed significant differences in preferential DMS compared with invasive ductal carcinoma. Furthermore, we found different histologic subtypes with specific DMS showed various prognosis. We also evaluated different DMS of specific histologic subtypes showed different prognosis. Conclusion: Certain histologic subtypes of breast cancer are associated with preferential DMS and prognosis; this knowledge may help to further understand the mechanism of breast cancer metastasis and to monitor the prognosis of patients with TNBC. [ABSTRACT FROM AUTHOR]

Recently, long noncoding RNAs (lncRNAs) have become the key gene regulators and prognostic biomarkers in various cancers. Through microarray data, Linc00339 was identified as a candidate oncogenic lncRNA. We compared the expression levels of Linc00339 in several breast cancer cell lines and normal mammary gland epithelial cell line. The effects of Linc00339 on tumor progression were examined both in vitro and in vivo. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays were applied to evaluate the functions of Linc00339, miR‐377‐3p, and HOXC6 on cell proliferation. Flow cytometry analysis was used to detect apoptosis and cell cycle distribution. Overall survival (OS) was analyzed using data from The Cancer Genome Atlas and molecular taxonomy of breast cancer international consortium (METABRIC). Dual luciferase assay and RNA immunoprecipitation were performed to confirm the interaction between Linc003339 and miR‐377‐3p. Linc00339 was increased in breast cancer cell lines compared with the normal epithelial cell. Through in vitro and in vivo experiments, Linc00339 overexpression promoted triple‐negative breast cancer (TNBC) proliferation, inhibited cell cycle arrest, and suppressed apoptosis. Silencing of Linc00339 obtained the opposite effects. Mechanistic investigations demonstrated that Linc00339 could sponge miR‐377‐3p and regulate its expression. Higher expression of miR‐377‐3p indicated longer OS in breast cancer patients, especially in TNBC patients. Overexpression of miR‐377‐3p retarded TNBC cell growth through regulating cell cycle distribution and apoptosis. And miR‐377‐3p was involved in Linc00339‐mediated TNBC proliferation through regulating HOXC6 expression. Knockdown of HOXC6 inhibited TNBC progression. In conclusion, our results illuminated that the novel Linc00339/miR‐377‐3p/HOXC6 axis played a critical role in TNBC progression and might be a promising therapeutic target for TNBC treatment. [ABSTRACT FROM AUTHOR]

Rapid proliferation and metastasis of breast cancers resulted in poor prognosis in clinic. Recent studies have proved that long noncoding RNAs (lncRNAs) were involved in tumor progression. In this study, we aimed to determine the roles and mechanisms of lncRNA–cell division cycle 6 (CDC6) in regulating proliferation and metastasis of breast cancer. Clinically, lncRNA–CDC6 was highly expressed in tumor tissues and was positively correlated with clinical stages of breast cancers. Functionally, the ectopic expression of lncRNA–CDC6 promoted proliferation via regulation of G1 phase checkpoint, and further promoting the migration capability. Moreover, lncRNA–CDC6 could function as competitive endogenous RNA (ceRNA) via directly sponging of microRNA‐215 (miR‐215), which further regulating the expression of CDC6. Taken together, our results proved that lncRNA–CDC6 could function as ceRNA and promote the proliferation and metastasis of breast cancer cells, which provided a novel prognostic marker for breast cancers in clinic. Clinically, long noncoding RNAs (lncRNA)–cell division cycle 6 (CDC6) was highly expressed in tumor tissues and was positively correlated with clinical stages of breast cancers. Functionally, ectopic expression of lncRNA–CDC6 promoted proliferation via regulation of G1 phase checkpoint, and further promoting the migration capability. Moreover, lncRNA–CDC6 could function as competitive endogenous RNA (ceRNA) via directly sponging of microRNA‐215 (miR‐215), which further regulating the expression of CDC6. [ABSTRACT FROM AUTHOR]