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The metagenome embedded in urban sewage is an attractive new data source to understand urban ecology and assess human health status at scales beyond a single host. Analyzing the viral fraction of wastewater in the ongoing COVID-19 pandemic has shown the potential of wastewater as aggregated samples for early detection, prevalence monitoring, and variant identification of human diseases in large populations. However, using census-based population size instead of real-time population estimates can mislead the interpretation of data acquired from sewage, hindering assessment of representativeness, inference of prevalence, or comparisons of taxa across sites. Here, we show that taxon abundance and sub-species diversisty in gut-associated microbiomes are new feature space to utilize for human population estimation. Using a population-scale human gut microbiome sample of over 1,100 people, we found that taxon-abundance distributions of gut-associated multi-person microbiomes exhibited generalizable relationships with respect to human population size. Here and throughout this paper, the human population size is essentially the sample size from the wastewater sample. We present a new algorithm, MicrobiomeCensus, for estimating human population size from sewage samples. MicrobiomeCensus harnesses the inter-individual variability in human gut microbiomes and performs maximum likelihood estimation based on simultaneous deviation of multiple taxa's relative abundances from their population means. MicrobiomeCensus outperformed generic algorithms in data-driven simulation benchmarks and detected population size differences in field data. New theorems are provided to justify our approach. This research provides a mathematical framework for inferring population sizes in real time from sewage samples, paving the way for more accurate ecological and public health studies utilizing the sewage metagenome. Author summary: Wastewater-based epidemiology (WBE) is an emerging field that employs sewage as aggregated samples of human populations. This approach is particularly promising for tracking diseases that can spread asymptomatically in large populations, such as the COVID-19. As a new type of biological data, sewage has its own unique challenges to utilize. While wastewater samples are usually assumed to represent large populations, it is not guaranteed, because of stochasticity in toilet flushes; unlike epidemiological experiments collecting data from individuals, sample size, i.e., the human population size represented by a wastewater sample, is a fundamental yet difficult-to-characterize parameter for sewage samples. Researchers would need to aggregate data from large areas and week-long collection to stabilize data, during which, important spikes in small areas or short time scales may be lost. It also remains challenging to turn viral titers into case prevalences, evaluating representativeness, or comparing measurements across sites/studies. This study provides a framework to estimate human population size from sewage utilizing human gut-associated microorganisms. Through analysis, we demonstrate that variance of taxon abundances and single-nucleotide polymorphism as two variables that change with population size. We provide a new tool MicrobiomeCensus that performs population size estimation from microbial taxon abundances. MicrobiomeCensus outperforms generic algorithms in terms of computational efficiency while at comparable or better accuracy. Using MicrobiomeCensus, we detected population size differences in sewage samples taken in Cambridge, MA, under two sampling approaches, i.e., "grab" or "composite" sampling. This study provides a framework to utilize individual-level microbiomes to learn from sewage, paving the way to prevalence estimation and improved spatio-temporal resolutions in WBE. [ABSTRACT FROM AUTHOR]

• A temperature-sensitive block copolymer with azlactone moieties was synthesized. • Different L -proline derivatives bearing primary amino groups were synthesized. • Immobilization of the organocatalysts on the polymer via azlactone click chemistry. • Catalyst efficiency and reusability were proven in an asymmetric aldol reaction. Nucleophilic ring-opening reaction of azlactone moieties was used for the immobilization of organocatalysts on smart block copolymers. Copolymerization of N -isopropylacrylamide with 2-vinyl-4,4-dimethylazlactone using a PEG-based macro-RAFT agent afforded temperature-sensitive block copolymers bearing azlactone side groups. Three different organocatalysts possessing primary amino groups were synthesized on the basis of L -proline and L -prolineamide using standard peptide coupling procedures. Organocatalyst immobilization was achieved using a post-polymerization reaction of the primary amino group with the azlactone moiety. The organocatalyst-functionalized block copolymers exhibited a temperature induced self-aggregation upon exceeding a critical phase transition temperature. The block copolymer aggregates with the immobilized organocatalyst in the core were subjected to the aldol reaction of cyclohexanone and p -nitrobenzaldehyde in water. Good diastereo- and enantioselectivities were observed, particularly for the immobilized prolineamides. Organocatalyst separation and reusability was demonstrated for five reaction cycles with no loss in catalyst reactivity. Finally, the applicability of the immobilized organocatalyst to the aldol reaction of cyclohexanone with differently substituted benzaldehydes in water was shown. [ABSTRACT FROM AUTHOR]

Studies on the end group stability of poly(N-isopropylacrylamide) during the atom transfer radical polymerization (ATRP) process are presented. Polymerization of N-isopropylacrylamide was conducted in different solvents using a copper(I) chloride/Me6Tren catalyst complex. The influence of the ATRP solvent as well as the polymer purification process on the end group stability was investigated. For the first time, mass spectrometry results clearly underline the loss of ω end groups via an intramolecular cyclization reaction. Furthermore, an ATRP system based on a copper(I) bromide/Me6Tren catalyst complex was introduced, that showed not only good control over the polymerization process, but also provided the opportunity of block copolymerization of N-isopropylacrylamide with acrylates and other N-substituted acrylamides. The polymers were characterized using 1H-NMR spectroscopy and size exclusion chromatography. Polymer end groups were determined via ESI-TOF mass spectrometry enhanced by ion mobility separation (IMS). [ABSTRACT FROM AUTHOR]

A 3D hydrogel layer is probed by combining surface plasmon resonance with optical waveguide spectroscopy to detect biomolecules. A template terpolymer P(DMAAm‐co‐DMIAAm‐co‐VDMA) is synthesized via reversible addition‐fragmentation chain‐transfer polymerization. The terpolymer is then modified with an amino group bearing biotin to enable biomolecular recognition for streptavidin. A hydrogel thin layer is prepared onto a gold surface after spin‐coating and photo‐crosslinking of the modified polymer. Finally, the hydrogel is utilized to quantitatively detect streptavidin by using surface plasmon resonance–optical waveguide spectroscopy measurements. An azlactone‐supported terpolymer is synthesized via reversible addition‐fragmentation chain‐transfer polymerization and then modified with a primary amine group bearing biotin to obtain a functional terpolymer. A hydrogel film constructed by the terpolymer is able to form a sensor chip to quantitatively detect streptavidin by using surface plasmon resonance–optical waveguide spectroscopy. [ABSTRACT FROM AUTHOR]

Desmoid fibromatosis (DF) is a clonal proliferative disorder of myofibroblasts, which arises, with a low incidence, in soft tissue, including within the abdomen. The incidence of DF is associated with familial adenomatous polyposis (FAP), and is more common following FAP surgery. It is rare for a patient to make his/her first visit to hospital due to DF symptoms associated with FAP. In the present report, a case of mesenteric DF associated with FAP is described. This case also had incomplete intestinal obstruction due to DF. By summarizing previous studies examining DF and FAP treatment, combined with the disease characteristics of this patient, the clinical treatment strategy for DF associated with FAP was explored. [ABSTRACT FROM AUTHOR]

Introduction: Repetitive negative thinking (RNT) is a cognitive process focusing on self-relevant and negative experiences, leading to a poor prognosis of major depressive disorder (MDD). We previously identified that connectivity between the precuneus/posterior cingulate cortex (PCC) and right temporoparietal junction (rTPJ) was positively correlated with levels of RNT. Objective: In this double-blind, randomized, sham-controlled, proof-of-concept trial, we employed real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) to delineate the neural processes that may be causally linked to RNT and could potentially become treatment targets for MDD. Methods: MDD-affected individuals were assigned to either active (n = 20) or sham feedback group (n = 19). RNT was measured by the Ruminative Response Scale-brooding subscale (RRS-B) before and 1 week after the intervention. Results: Individuals in the active but not in the sham group showed a significant reduction in the RRS-B; however, a greater reduction in the PCC-rTPJ connectivity was unrelated to a greater reduction in the RRS-B. Exploratory analyses revealed that a greater reduction in the retrosplenial cortex (RSC)-rTPJ connectivity yielded a more pronounced reduction in the RRS-B in the active but not in the sham group. Conclusions: RtfMRI-nf was effective in reducing RNT. Considering the underlying mechanism of rtfMIR-nf, the RSC and rTPJ could be part of a network (i.e., default mode network) that might collectively affect the intensity of RNT. Understanding the relationship between the functional organization of targeted neural changes and clinical metrics, such as RNT, has the potential to guide the development of mechanism-based treatment of MDD. [ABSTRACT FROM AUTHOR]

Crop rhizospheres are the foundational support for multiple ecosystem services, ranging from food production to carbon sequestration and soil fertility. Land use intensification is known to impact these fundamental ecosystem services. However, little is known about how root traits regulate the responses of rhizosphere ecosystem services to land use intensification. Here, we conducted a field experiment to explore the responses of rhizosphere ecosystem services to phosphorus (P) fertilization and maize-alfalfa intercropping, and specifically evaluated how root traits drive these responses. Results showed that unfertilized intercropping treatments produced the highest values of rhizosphere ecosystem services, including enhanced plant-soil mutualism, and the greatest abundance of soil decomposers. Unfertilized intercropped alfalfa increased nutrient cycling, soil carbon storage, and soil microbial diversity. Crop-specific root traits such as exudation and morphology are critical in explaining the responses of the rhizosphere. The exudation traits of alfalfa, and morphological traits of maize in unfertilized intercropping treatments were most important for the increases in ecosystem services. Our results highlight the importance of root traits in promoting rhizosphere ecosystem services under land use intensification. Intercropping supported rhizosphere multiservices under the more sustainable low-input system through plant-specific root trait complementarity. This is critical for developing management policies to promote the far-reaching development of agroecosystems. • Unfertilized intercropping supported a larger range of rhizosphere multiservices. • Crops optimized P capture in unfertilized soil through root traits complementarity. • Root traits regulate the response of multiservice to intercropping and fertilization. • Maize increased soil microbial diversity, nutrient cycling by morphological traits. • Alfalfa promoted soil carbon storage and microbial biomass carbon by exudate traits. [ABSTRACT FROM AUTHOR]

• PRD1-BF-1-RIZ1 homology (PR) domain containing protein-16 (PRDM16) regulates energy homeostasis and glucose and lipid metabolism, which are implicated in the etiology of type 2 diabetes (T2D). • The promoter variant rs2297828 of PRDM16 is associated with T2D susceptibility and dyslipidemia. • rs2297828 is a functional variant influencing PRDM16 promoter activity. Transcriptional regulator PRD1-BF-1-RIZ1 homology (PR) domain containing protein-16 (PRDM16) has a fundamental function in maintaining energy homeostasis and regulating glucose and lipid metabolism, which are responsible for the development of type 2 diabetes (T2D). However, the impact of genetic variation of PRDM16 gene on T2D risk remains to be investigated. Thus, we evaluated the possible association between genetic variants within PRDM16 region and T2D development in Chinese individuals. A total of 427 T2D patients and 408 healthy controls were enrolled. Ten single-nucleotide variants across PRDM16 gene were screened with the SNaPshot assay. The effect of genotypes and alleles of different variant on the T2D risk was examined under diverse genetic models. The impact of genetic variant on promoter activity was determined using an in vitro luciferase reporter gene assay. Genotypic frequency of rs2297828 in the PRDM16 promoter region was significantly different between patients with T2D and controls (P = 0.004). The minor allele A of rs2297828 was potentially associated with a higher T2D susceptibility in a dominant model (AG + AA vs GG: OR = 1.54, 95 % CI: 1.12–1.12; P = 0.007), and the subjects with either an AA homozygote or an AG heterozygote displayed increased fasting blood levels of glucose and lipids. Reporter gene assays demonstrated that rs2297828 can influence the activity of the PRDM16 promoter. We firstly observed that PRDM16 variation might influence T2D occurrence, and rs2297828 might be a functional variant that can influence the expression of PRDM16. [ABSTRACT FROM AUTHOR]

Artificial multiferroic heterostructures have recently attracted much interests due to the demonstrated magnetoelectric coupling (MEC) and unique functionalities, promising a tantalizing perspective of novel applications in next-generation electronic, memory, sensor, and energy harvesting technologies. Herein, we report a two-step magnetization reversal in PbZr 0.52 Ti 0.48 O 3 /La 0.67 Sr 0.33 MnO 3 (PZT/LSMO) superlattices, which originates from the strongly entangled strain-, ferroelectric (FE)-polarization-, and exchange-dependent effects. Specifically, the preferential occupancy of the in-plane Mn d x 2 − y 2 orbitals is triggered via the collective effects of the large tensile strain and FE polarization, giving rise to an interfacial antiferromagnetic (AFM) layer with strong AFM anisotropy. The strong spin exchange coupling between the AFM layer and the adjacent ferromagnetic (FM) layer facilitates the magnetic stratification of the FM layer, leading to two coercivities, i.e., two-step magnetization reversal. Meanwhile, a sizeable exchange bias (EB) field is induced. The emerged two-step magnetization reversal concomitant with the pronounced EB phenomenon should be a signature of an enhanced MEC in PZT/LSMO superlattices. Our results will stimulate further interests in multiferroic superlattices in applications of multiferroic-based devices. • A large orbital polarization of Mn is induced in PZT/LSMO superlattices. • A two-step magnetization reversal emerges from the PZT/LSMO superlattices. • The PZT/LSMO superlattices demonstrate a profound exchange bias effect. • Strong magnetoelectric coupling is achieved in the PZT/LSMO superlattices. [ABSTRACT FROM AUTHOR]

Propofol inhibits myocardial contraction in a dose dependent manner. The present study is designed to examine the effect of propofol on PKA mediated myocardial contraction in the absence of adrenoreceptor agonist. The contraction of isolated rat heart was measured in the presence or absence of PKA inhibitor H89 or propofol, using a pressure transducer. The levels of cAMP and PKA kinase activity were detected by ELISA. The mRNA and total protein or phosphorylation level of PKA and downstream proteins were tested in the presence or absence of PKA inhibitor H89 or propofol, using RT-PCR, QPCR and western blotting. The phosphorylation level of PKA was examined thoroughly using immunofluorescence and PKA activity non-radioactive detection kit. Propofol induced a dose-dependent negative contractile response on the rat heart. The inhibitory effect of high concentration propofol (50 μM) with 45% decease of control could be partly reversed by the PKA inhibitor H89 (10 μM) and the depressant effect of propofol decreased from 45% to 10%. PKA kinase activity was inhibited by propofol in a dose-dependent manner. Propofol also induced a decrease in phosphorylation of PKA, which was also inhibited by H89, but did not alter the production of cAMP and the mRNA levels of PKA. The downstream proteins of PKA, PLN and RyR2 were phosphorylated to a lesser extent with propofol or H89 than control. These results demonstrated that propofol induced a negative myocardial contractile response partly by mediating the PKA phosphorylation pathway. [ABSTRACT FROM AUTHOR]

Tumor microenvironments (TME) play critical roles in the growth and metastasis of tumor tissue, which provide a promising way to treat malignant tumor via manipulation of TME. However, developing proper strategy to effectively control TME is still a challenge. Herein, a Ce6@AT-PEG-MSN-Pt (CAPMP) nanomotor is fabricated to spontaneously move in tumor tissue and concurrently perform the enhanced manipulation of various tumor microenvironments including copper levels, hypoxia, local temperature and reactive oxygen species (ROS) for effective tumor therapy. The CAPMP nanomotor consists of a janus platinum-mesoporous silica core with acyl thioureas groups (copper chelator) conjugated polyethylene glycol on the surface and chlorin e6 (photosensitizer) in the pores. During therapy, the acyl thioureas groups on CAPMP would capture the over-expressed copper in tumor tissue and tumor cells to cause dramatic copper-deficiency of tumor. The chlorin e6 is in charge of the ROS (1O 2) generation in tumor via photodynamic process, which would be triggered by 660 nm irradiation. The platinum layer of CAPMP served as both photothermal agent and O 2 producer. It rapidly raised the local temperature under 808 nm irradiation, meanwhile converted the over-expressed H 2 O 2 in tumor tissue to O 2 via catalytic reaction. The O 2 production not only drove the CAPMP for sustained movement to promote its efficiency of copper capture, but reversed the hypoxic environment of tumor tissue in large and deep area, which further promoted the 1O 2 generation property of CAPMP. Both in vitro and in vivo experiments demonstrate that the raise of local temperature and enhanced 1O 2 concentration performed significant damage of tumor tissue for primary tumor elimination, while the copper deficiency and hypoxia reversion further hindered the migration of tumor cells for metastasis inhibition, resulting in an effective strategy to treat malignant tumor. [ABSTRACT FROM AUTHOR]

Objective. To summarize the experience of minimally invasive treatment in 520 patients with intracranial aneurisms on a retrospective study. Methods. The measures used in the treatment of 520 patients were reviewed in terms of timing of surgery, induced-hypotensive anesthesia, brain protection combined with temporal occlusion of the feeding artery, external drainage of CSF, dynamic monitoring of intracranial pressure, blood flow velocity, serum osmolality and CT scanning, anti-vasospasm therapy as well as selected interventional endovascular embelization of aneurysms. Results. Of the 520 patients, 485 were treated with either direct clipping or endovascular embolization and 35 patients were treated non-surgically. In 449 patients undergoing direct clipping and 36 undergoing endovascular embolization, intraoporative rupture of aneurysm occurred in 27 (6.0%) and 0%, respectively. Death occurred in 13 (2. 6%), hemiplegia in 8 (1.6%), and vegetative state in 2 (0. 4%). The operative mortality of direct clipping was 3.8% in 210 patients before 1990 and 1.8% in 275 patients after 1990 (36 patients undergoing endovascular embelization, the operative mortality was 0%). Conclusion. The outcome of patients with intracranial aneurysms can be markedly improved and the operafive mortality can be lowered by minimally invasive treatment. [ABSTRACT FROM AUTHOR]

Chemotherapy is one of the most commonly utilized approaches to treat malignant tumor. However, the well-controlled chemotherapy able to accurately manipulate local drugs for on-demand tumor treatment is still a challenge. Herein, a magnet and light dual-responsive hydrogel combining thermosensitive poly(N-acryloyl glycinamide) (PNAGA), doxorubicin (DOX) loaded and polyester (PE) capped mesoporous silica nanocarriers (MSNs) as well as Fe 3 O 4 nanoparticles (Fe 3 O 4 NPs) grafted graphene oxide (GO) was fabricated to address above issue. The Fe 3 O 4 NPs and GO respectively serve as magnetothermal agent and photothermal agent to perform hyperthermia, meanwhile to generate chain motion of PNAGA with varying degrees under different conditions of magnetic field and/or NIR irradiation. This strategy not only allowed the gel-sol transition of the hydrogel by prior heating for tumor injection, but performed controllable release routes of DOX-MSNs-PE (DMP for short) nanocarriers to meet various requirements from different patients and the changing states of tumor. Furthermore, these escaped DMP nanocarriers could be taken by surrounding tumor cells, and then deliver their drug to these cells after rapid hydrolysis of the PE cap triggered by esterase, resulting in accurate chemotherapy. Both in vitro and in vivo results indicated that the PNAGA-DMP-Fe 3 O 4 @GO hydrogel combining well-controllable chemotherapy and hyperthermia can eliminate more than 90% tumor cells and effectively inhibit the tumor growth in mice model, demonstrating the great candidate of our hydrogel for accurate tumor therapy. [ABSTRACT FROM AUTHOR]

Background: Mindfulness training has been shown to promote positive mental health outcomes and related changes in neural networks such as the default mode network, which has a central node in the posterior cingulate cortex (PCC). Previous work from our group reported on the impact of a novel, neurofeedback augmented mindfulness training (NAMT) task on regulation of PCC hemodynamic activity in typically developing adolescents. The present pilot study aimed to expand on this finding by examining the pre-post changes of the NAMT task on resting-state functional connectivity of the PCC., Methods: Thirty-one typically developing adolescents (14.77 ± 1.23 years; 45% female) underwent a resting-state functional magnetic resonance imaging scan both before and after completing the NAMT task. A linear mixed effects model was used to assess for changes in functional connectivity of the PCC across the two resting-state runs., Results: Data did not support the hypothesized decrease in connectivity between the PCC seed and other DMN regions from pre- to post-NAMT task. However, we observed a significant increase in functional connectivity between the PCC and a cluster encompassing the left hippocampus and amygdala following completion of the NAMT task (run 1 Fisher's Z  = 0.16; run 2 Fisher's Z  = 0.26)., Conclusion: Although preliminary, this finding suggests NAMT has the potential to strengthen connectivity between default mode and salience regions. We speculate that such changed connectivity may facilitate enhanced self-referential and emotional processing in adolescents., Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT04053582., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer BA-P declared a shared affiliation with the author MKS to the handling editor at the time of review. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cosgrove, Tsuchiyagaito, Cohen, Cochran, Yu, Misaki, Aupperle, Singh, Paulus and Kirlic.)

Although tailed bacteriophages (phages) of the class Caudoviricetes are thought to constitute the most abundant and ecologically relevant group of phages that can integrate their genome into the host chromosome, it is becoming increasingly clear that other prophages are widespread. Here, we show that prophages derived from filamentous and tailless phages with genome sizes below 16 kb make up the majority of prophages in marine bacteria of the genus Vibrio. To estimate prophage prevalence unaffected by database biases, we combined comparative genomics and chemical induction of 58 diverse Vibrio cyclitrophicus isolates, resulting in 107 well-curated prophages. Complemented with computationally predicted prophages, we obtained 1,158 prophages from 931 naturally co-existing strains of the family Vibrionaceae. Prophages resembling tailless and filamentous phages predominated, accounting for 80% of all prophages in V. cyclitrophicus and 60% across the Vibrionaceae. In our experimental model, prophages of all three viral realms actively replicated upon induction indicating their ability to transfer to new hosts. Indeed, prophages were rapidly gained and lost, as suggested by variable prophage content between closely related V. cyclitrophicus. Prophages related to filamentous and tailless phages were integrated into only three genomic locations and restored the function of their integration site. Despite their small size, they contained highly diverse accessory genes that may contribute to host fitness, such as phage defense systems. We propose that, like their well-studied tailed equivalent, tailless and filamentous temperate phages are active and highly abundant drivers of host ecology and evolution in marine Vibrio, which have been largely overlooked., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Mindfulness is increasingly recognized as an effective strategy for managing chronic illnesses and improving mental well-being in cancer patients. This study sought to adapt and validate a Persian version of Relaxation, Meditation, and Mindfulness Experiences Tracker Questionnaire trait month 3.1″ (P-RMMtm 3.1) for use with Iranian cancer patients. This cross-sectional study was conducted in several hospitals affiliated with Kerman University of Medical Sciences in southeastern Iran. Validity and reliability tests were administered between March and December 2023. Results showed strong psychometric properties, with a six-factor solution explaining 72.387% of the variance. The identified factors were mindful transcendence, mindful relaxation, mindful emotion, mindful focus/awareness, mindful quiet, and mindful action. Confirmatory factor analysis indices were generally satisfactory (χ2/d.f. = 2.253, RMSEA = 0.079, GFI = 0.833, CFI = 0.923, and IFI = 0.924). Cronbach's alpha values for the RMMtm 3.1 factors ranged from 0.802 to 0.89. In conclusion, the Persian version of RMMtm 3.1 is a reliable instrument for assessing relaxation, meditation, and mindfulness experiences in Iranian cancer patients. Its concise format makes it suitable for future research with this population., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

High-frequency oscillatory activity in cognition-related neural circuits during wakefulness consistently induces the growth of dendritic spines and axonal terminals. Although these structural changes are essential for cognitive functions, it is hypothesized that if these newly expanded structures fail to establish functional connections, they may become superfluous. Sleep is believed to facilitate the reduction of such redundant structures to maintain neural homeostasis. However, the mechanisms underlying this pruning process during sleep remain poorly understood. In this study, that melatonin type 3 receptors (MT 3 Rs) are selectively expressed in the stellate neurons of the medial entorhinal cortex (MEC) is demonstrated, an area where high melatonin levels are detected during sleep. Activation of MT 3 Rs during sleep initiates the shrinkage of dendritic spines in stellate neurons by downregulating neural network activity and dephosphorylating synaptic proteins in the MEC. This process is disrupted when MT 3 R expression is knocked down or when MT 3 Rs are blocked during sleep. Notably, interference with MT 3 Rs in the MEC during sleep impairs the acquisition of spatial memory but does not affect object memory acquisition following sleep. These findings reveal novel molecular mechanisms involving melatonin and MT 3 Rs in the regulation of dendritic spine shrinkage during sleep, which is crucial for the acquisition and consolidation of spatial memory., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Hepatic steatosis, the first step in the development of nonalcoholic fatty liver disease (NAFLD), is frequently observed in the aging population. However, the underlying molecular mechanism remains largely unknown. In this study, we first employed GSEA enrichment analysis to identify short-chain acyl-CoA dehydrogenase (SCAD), which participates in the mitochondrial β-oxidation of fatty acids and may be associated with hepatic steatosis in elderly individuals. Subsequently, we examined SCAD expression and hepatic triglyceride content in various aged humans and mice and found that triglycerides were markedly increased and that SCAD was upregulated in aged livers. Our further evidence in SCAD-ablated mice suggested that SCAD deletion was able to slow liver aging and ameliorate aging-associated fatty liver. Examination of the molecular pathways by which the deletion of SCAD attenuates steatosis revealed that the autophagic degradation of lipid droplets, which was not detected in elderly wild-type mice, was maintained in SCAD-deficient old mice. This was due to the decrease in the production of acetyl-coenzyme A (acetyl-CoA), which is abundant in the livers of old wild-type mice. In conclusion, our findings demonstrate that the suppression of SCAD may prevent age-associated hepatic steatosis by promoting lipophagy and that SCAD could be a promising therapeutic target for liver aging and associated steatosis., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Platelets are a significant component of the cell population in the tumour microenvironment (TME). Platelets influence other immune cells and perform cross-talk with tumour cells, playing an important role in tumour development. Extracellular vesicles (EVs) are small membrane vesicles released from the cells into the TME. They can transfer biological information, including proteins, nucleic acids, and metabolites, from secretory cells to target receptor cells. This process affects the progression of various human diseases, particularly cancer. In recent years, several studies have demonstrated that platelet-derived extracellular vesicles (PEVs) can help regulate the malignant biological behaviours of tumours, including malignant proliferation, resistance to cell death, invasion and metastasis, metabolic reprogramming, immunity, and angiogenesis. Consequently, PEVs have been identified as key regulators of tumour progression. Therefore, targeting PEVs is a potential strategy for tumour treatment. Furthermore, the extensive use of nanomaterials in medical research has indicated that engineered PEVs are ideal delivery systems for therapeutic drugs. Recent studies have demonstrated that PEV engineering technologies play a pivotal role in the treatment of tumours by combining photothermal therapy, immunotherapy, and chemotherapy. In addition, aberrant changes in PEVs are closely associated with the clinicopathological features of patients with tumours, which may serve as liquid biopsy markers for early diagnosis, monitoring disease progression, and the prognostic assessment of patients with tumours. A comprehensive investigation into the role and potential mechanisms of PEVs in tumourigenesis may provide novel diagnostic biomarkers and potential therapeutic strategies for treating human tumours., (© 2024. The Author(s).)

Background: This study delves into the intricacies of resistant hypertension (RH), a prevalent yet enigmatic chronic cardiovascular ailment that is linked to a myriad of complications. Although its full pathogenesis is still shrouded in mystery, the field of proteomics offers a beacon of hope, with its potential to shed light on the proteins that orchestrate the tapestry of life. Harnessing the power of proteomics is essential for demystifying the pathogenesis of RH, enabling more precise diagnostics and treatments, and ultimately improving prognostic outcomes., Methods: Our approach was to employ rigorous statistical analyses to home in on proteins with significant expression variances between our two cohorts. We complemented this with bioinformatics tools to unravel the intricate functions and pathways of these proteins. By synthesizing these insights with the clinical profiles of our patients, we were able to distill a set of definitive biomarkers with diagnostic potential. In our quest for clarity, we also embarked on a retrospective journey, amassing and scrutinizing clinical data from both RH and hypertension (HTN) patients. We crafted and rigorously assessed risk factor models to evaluate their diagnostic prowess., Results: Our exploration spanned across 30 blood samples from RH patients and 20 from those grappling with HTN. Our inquiry yielded some compelling revelations: (1) RH patients showcased 29 unique proteins, in contrast to the 59 unique proteins found in HTN patients. A deeper dive into the proteomic data unveiled molecular functions predominantly tied to lipid metabolism, protein networking, and oxidative stress, with a spotlight on pathways such as cholesterol metabolism, coagulation, and the complement cascade. (2) By charting receiver operating characteristic curves and rigorously analyzing the proteomic data, we surfaced 11 proteins with notable diagnostic potential, tightly interwoven with clinical metrics., Conclusion: Our research has pinpointed 11 proteins that stand as promising serum biomarkers, endowed with significant diagnostic value. This discovery marks a stride towards a more nuanced understanding and management of resistant hypertension., Competing Interests: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. The authors declare no competing interests., (© 2024 Published by Elsevier Ltd.)

Resistant hypertension (RH) poses a significant health challenge, yet its underlying pathogenesis remains unclear. This study employs untargeted proteomic techniques to analyze the plasma of patients with RH and controlled hypertension (CH), identifying 157 differentially expressed proteins, with TGFB1 emerging as a key candidate. Through gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, Protein-Protein Interaction Networks (PPI) topological analysis, TGFB1's differential regulation in RH is established. ELISA verification solidifies TGFB1's role, marking it as a potential biological target for early RH diagnosis and treatment. The study underscores the importance of proteomic approaches in enhancing our understanding of RH and improving therapeutic strategies. These findings carry implications for advancing RH diagnostics and treatment modalities, addressing a critical gap in current knowledge., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Periodontitis is one of the most common chronic oral inflammatory diseases. Over the past decade, herpes viruses, particularly Epstein-Barr virus (EBV), have been considered promising pathogenic candidates for periodontitis. However, the specific mechanism by which EBV contributes to the development of periodontitis is still unknown. This study aimed to explore the mechanism of EBV underlying the inflammatory response in human gingival fibroblasts (HGFs)., Materials and Methods: HGFs were stimulated with different concentrations of EBV (10 4 , 10 5 , 10 6 , 10 7 , and 10 8 DNA copies/mL) for 0, 8, 24, or 48 hours. The mRNA levels of interleukin (IL)-1β, tumour necrosis factor-α (TNF-α), IL-8, monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor 9 (TLR9) were measured using quantitative real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assays (ELISAs) were performed for determining the mRNA and protein levels of IL-1β, TNF-α, IL-8, and MCP-1. Real-time PCR and ELISA were performed to determine the protein levels of IL-1β, TNF-α, IL-8, and MCP-1. Activation of the TLR9/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) pathway was evaluated using western blotting., Results: The expressions of IL-1β, TNF-α, IL-8, and MCP-1 were significantly upregulated in HGFs under EBV stimulation in a concentration- and time-dependent manner. EBV promoted TLR9 and MyD88 expression and induced NF-κB transcription. On the contrary, the upregulation of these factors and the activation of NF-κB pathway were drastically inhibited by TLR9 antagonists., Conclusions: Our findings demonstrate that EBV promotes the production of inflammatory cytokines IL-1β and TNF-α and chemokines IL-8 and MCP-1 in HGFs through the TLR9/MyD88/NF-κB pathway., Competing Interests: Conflict of interest None disclosed., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

A subcortical pathway is thought to have evolved to facilitate fear information transmission, but direct evidence for its existence in humans is lacking. In recent years, rapid, preattentive, and preconscious fear processing has been demonstrated, providing indirect support for the existence of the subcortical pathway by challenging the necessity of canonical cortical pathways in fear processing. However, direct support also requires evidence for the involvement of subcortical regions in fear processing. To address this issue, here we investigate whether fear processing reflects the characteristics of the subcortical structures in the hypothesized subcortical pathway. Using a monocular/dichoptic paradigm, Experiment 1 demonstrated a same-eye advantage for fearful but not neutral face processing, suggesting that fear processing relied on monocular neurons existing mainly in the subcortex. Experiments 2 and 3 further showed insensitivity to short-wavelength stimuli and a nasal-temporal hemifield asymmetry in fear processing, both of which were functional characteristics of the superior colliculus, a key hub of the subcortical pathway. Furthermore, all three experiments revealed a low spatial frequency selectivity of fear processing, consistent with magnocellular input via subcortical neurons. These results suggest a selective involvement of subcortical structures in fear processing, which, together with the indirect evidence for automatic fear processing, provides a more complete picture of the existence of a subcortical pathway for fear processing in humans. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Never in mitosis gene A-related kinase (NEK) is an 11-membered family of serine/threonine kinases (NEK1-NEK11), which are known to play important roles in the formation and development of cancer. However, few studies have examined the roles of these kinases in the development of stomach adenocarcinoma (STAD). In this study, we conducted a comprehensive analysis of the relationships between the NEKs family members and STAD. The differential expression of the NEK genes in STAD was validated using The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER) databases, and their prognostic and diagnostic values of NEKs in STAD were assessed using the Kaplan-Meier plotter and TCGA data. The effect of NEK expression on immune cell infiltration in STAD was analysed using the TIMER and TISIDB databases. The expression levels of the majority of the NEK family members were consistently upregulated in STAD, whereas that of NEK10 was downregulated. The upregulation of NEK2/3/4/5/6/8 was closely associated with clinicopathological parameters of patients, and the overexpressed levels of these proteins had good diagnostic value for the disease. NEK1/8/9/10/11 expression correlated with poor overall survival and post-progressive survival, whereas a higher NEK1/6/9/11 level implied worse first progressive survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the NEKs may be related to immunological responses. Additionally, our study confirmed that these kinases correlated with immune cell infiltration and different immune infiltration subtypes in STAD. Our results suggest that NEK9 in particular has the potential to be used as a diagnostic and prognostic biomarker of STAD development and progression and an immune target for treatment of the disease. These findings expand our understanding of the biological functions of the NEK family members in STAD., Competing Interests: Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The author(s).)

Abstract: Pancreatic β-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes (T2D). Reserving insulin-producing β-cells and hence restoring insulin production are gaining attention in translational diabetes research, and β-cell replenishment has been the main focus for diabetes treatment. Significant findings in β-cell proliferation, transdifferentiation, pluripotent stem cell differentiation, and associated small molecules have served as promising strategies to regenerate β-cells. In this review, we summarize current knowledge on the mechanisms implicated in β-cell dynamic processes under physiological and diabetic conditions, in which genetic factors, age-related alterations, metabolic stresses, and compromised identity are critical factors contributing to β-cell failure in T2D. The article also focuses on recent advances in therapeutic strategies for diabetes treatment by promoting β-cell proliferation, inducing non-β-cell transdifferentiation, and reprograming stem cell differentiation. Although a significant challenge remains for each of these strategies, the recognition of the mechanisms responsible for β-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenous β-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

This study investigates the expression and significance of urinary protein and coagulation-fibrinolysis indicators in preeclampsia, categorized into mild preeclampsia (109 cases) and severe preeclampsia (97 cases) based on disease severity. Additionally, 110 patients with gestational hypertension (gestational hypertension group) were included for comparative analysis. General information, laboratory indicators, urinary protein, and coagulation-fibrinolysis indicator levels were collected for each group. Significant differences were observed in blood pressure among groups (P < .05), while uric acid, serum creatinine, aspartate transaminase, alanine transaminase, and triglycerides showed no significant differences (P > .05). Total cholesterol, triglycerides, and low-density Lipoprotein levels in severe preeclampsia were higher than those in mild preeclampsia and gestational hypertension groups, whereas high-density lipoprotein, albumin, and platelet levels were lower in severe preeclampsia. No significant differences were observed in prothrombin time or D-dimer levels among groups (P > .05). Urinary protein, urinary protein quantification, activated partial thromboplastin time, thrombin time, and fibrinogen were identified as influencing factors for adverse maternal and infant outcomes in severe preeclampsia patients. The study concludes that urinary protein and coagulation-fibrinolysis indicators are elevated in preeclampsia, particularly in severe preeclampsia cases, suggesting their potential use as diagnostic influencing factors for severe preeclampsia., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Colorectal cancer (CRC) is a type of gastrointestinal cancer with high morbidity and mortality rates, and is often accompanied by distant metastases. Metastasis is a major cause of shortened survival time and poor treatment outcomes for patients with CRC. However, the molecular mechanisms underlying the metastasis of CRC remain unclear. Exosomes are a class of small extracellular vesicles that originate from almost all human cells and can transmit biological information (e.g., nucleic acids, lipids, proteins, and metabolites) from secretory cells to target recipient cells. Recent studies have revealed that non-coding RNAs (ncRNAs) can be released by exosomes into the tumour microenvironment or specific tissues, and play a pivotal role in tumorigenesis by regulating a series of key molecules or signalling pathways, particularly those involved in tumour metastasis. Exosomal ncRNAs have potential as novel therapeutic targets for CRC metastasis, and can also be used as liquid biopsy biomarkers because of their specificity and sensitivity. Therefore, further investigations into the biological function and clinical value of exosomal ncRNAs will be of great value for the prevention, early diagnosis, and treatment of CRC metastasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Head and neck squamous cell carcinoma (HNSCC) ranks as the eighth most prevalent malignancy globally and has the eighth greatest fatality rate when compared to all other forms of cancer. The inhibitor of apoptosis protein (IAP) family comprises a collection of apoptosis-negative modulators characterized by at least one single baculovirus IAP repeat (BIR) domain in its N-terminal region. While the involvement of the IAP family is associated with the initiation and progression of numerous tumours, its specific role in HNSCC remains poorly understood. Thus, this study aimed to comprehensively examine changes in gene expression, immunomodulatory effects, prognosis, and functional enrichment of HNSCC utilising bioinformatics analysis. Elevated levels of distinct IAP family members were observed to varying degrees in HNSCC, with high BIRC2 expression indicating a worse prognosis. Additionally, Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to probe the enrichment of gene expression and biological processes related to the IAP family in HNSCC. The infiltration levels of immune cells were shown to be strongly associated with the IAP gene expression, as determined by subsequent analysis. Hence, BIRC2 could be an effective immunotherapy target for HNSCC. Collectively, novel knowledge of the biological roles and prognostic implications of IAP family members in HNSCC is presented in this study.

Members of microbial communities can substantially overlap in substrate use. However, what enables functionally redundant microorganisms to coassemble or even stably coexist remains poorly understood. Here, we show that during unstable successional dynamics on complex, natural organic matter, functionally redundant bacteria can coexist by partitioning low-concentration substrates even though they compete for one simple, dominant substrate. We allowed ocean microbial communities to self-assemble on leachates of the brown seaweed Fucus vesiculosus and then analyzed the competition among 10 taxonomically diverse isolates representing two distinct stages of the succession. All, but two isolates, exhibited an average of 90% ± 6% pairwise overlap in resource use, and functional redundancy of isolates from the same assembly stage was higher than that from between assembly stages, leading us to construct a simpler four-isolate community with two isolates from each of the early and late stages. We found that, although the short-term dynamics of the four-isolate communities in F. vesiculosus leachate was dependent on initial isolate ratios, in the long term, the four isolates stably coexist in F. vesiculosus leachate, albeit with some strains at low abundance. We therefore explored the potential for nonredundant substrate use by genomic content analysis and RNA expression patterns. This analysis revealed that the four isolates mainly differed in peripheral metabolic pathways, such as the ability to degrade pyrimidine, leucine, and tyrosine, as well as aromatic substrates. These results highlight the importance of fine-scale differences in metabolic strategies for supporting the frequently observed coexistence of large numbers of rare organisms in natural microbiomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Background: Cutaneous melanoma (CM) is the most common malignant tumor of the skin. Our study aimed to investigate the prognostic value of pathomics signatures for CM by combining pathomics and genomics., Purpose: The purpose of this study was to explore the potential application value of pathomics signatures., Methods: Pathology full scans, clinical information, and genomics data for CM patients were downloaded from The Cancer Genome Atlas (TCGA) database. Exploratory data analysis (EDA) was used to visualize patient characteristics. Genes related to a poorer prognosis were screened through differential analysis. Survival analysis was performed to assess the prognostic value of gene and pathomics signatures. Artificial neural network (ANN) models predicted prognosis using signatures and genes. Correlation analysis was used to explore signature-gene links., Results: The clinical traits for 468 CM samples and the genomic data and pathology images for 471 CM samples were obtained from the TCGA database. The EDA results combined with multiple machine learning (ML) models suggested that the top 5 clinical traits in terms of importance were age, biopsy site, T stage, N stage and overall disease stage, and the eight ML models had a precision lower than 0.56. A total of 60 differentially expressed genes were obtained by comparing sequencing data. A total of 413 available quantitative signatures of each pathomics image were obtained with CellProfile software. The precision of the binary classification model based on pathomics signatures was 0.99, with a loss value of 1.7119e-04. The precision of the binary classification model based on differentially expressed genes was 0.98, with a loss value of 0.1101. The precision of the binary classification model based on pathomics signatures and differentially expressed genes was 0.97, with a loss value of 0.2088. The survival analyses showed that the survival rate of the high-risk group based on gene expression and pathomics signatures was significantly lower than that of the low-risk group. A total of 222 pathomics signatures and 51 differentially expressed genes were analyzed for survival with p-values of less than 0.05. There was a certain correlation between some pathomics signatures and differential gene expression involving ANO2, LINC00158, NDNF, ADAMTS15, and ADGRB3, etc. CONCLUSION: This study evaluated the prognostic significance of pathomics signatures and differentially expressed genes in CM patients. Three ANN models were developed, and all achieved accuracy rates higher than 97%. Specifically, the pathomics signature-based ANN model maintained a remarkable accuracy of 99%. These findings highlight the CellProfile + ANN model as an excellent choice for prognostic prediction in CM patients. Furthermore, our correlation analysis experimentally demonstrated a preliminary link between disease quantification and qualitative changes. Among various features, including M stage and treatments received, special attention should be given to age, biopsy site, T stage, N stage, and overall disease stage in CM patients., (© 2023 American Association of Physicists in Medicine.)

Background: Regulatory B cells (Bregs) have been reported to suppress immune responses and alveolar bone loss in murine periodontitis models. These cells could be induced by interleukin (IL)-35 which is increased upon periodontal inflammation. Thus, this study aimed to explore the role of Bregs induced by IL-35 in periodontitis., Methods: Experimental periodontitis was induced in mice by ligature. Two weeks after ligation, the test group was systemically treated with IL-35 for 1 week. Four weeks after ligation, all mice were euthanized, and alveolar bone loss was evaluated by microcomputed tomography. Cytokines associated with periodontitis were analyzed using reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Bregs in spleens, cervical lymph nodes, and periodontal tissues were detected by flow cytometry and immunofluorescence staining., Results: In the mouse model of periodontitis, IL-35 induced the expansion of CD1d hi CD5 + B10 cells with increased interleukin-10 (IL-10) and IL-35 production. IL-35 administration also attenuated alveolar bone loss and reduced the levels of proinflammatory cytokines in situ., Conclusions: Following ligature-induced periodontitis in mice, IL-35 inhibited periodontal inflammation and alveolar bone resorption at least partially through the induction of B10 cells and IL-35 + Bregs., (© 2023 American Academy of Periodontology.)

Colon adenocarcinoma (COAD) is among the most prevalent cancers worldwide, ranking as the third most prevalent malignancy in incidence and mortality. The somatostatin receptor (SSTR) family comprises G-protein-coupled receptors (GPCRs), which couple to inhibitory G proteins (Gi and Go) upon binding to somatostatin (SST) analogs. GPCRs are involved in hormone release, neurotransmission, cell growth inhibition, and cancer suppression. However, their roles in COAD remain unclear. This study used bioinformatics to investigate the expression, prognosis, gene alterations, functional enrichment, and immunoregulatory effects of the SSTR family members in COAD. SSTR1-4 are differentially downregulated in COAD, and low SSTR2 expression indicates poor survival. Biological processes and gene expression enrichment of the SSTR family in COAD were further analyzed using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology. A strong correlation was observed between SSTR expression and immune cell infiltration. We also quantified SSTR2 expression in 25 COAD samples and adjacent normal tissues using quantitative real-time polymerase chain reaction. We analyzed its correlation with the dendritic cell-integrin subunit alpha X marker gene. The biomarker exploration of the solid tumors portal was used to confirm the correlation between SSTR2 with immunomodulators and immunotherapy responses. Our results identify SSTR2 as a promising target for COAD immunotherapy. Our findings provide new insights into the biological functions of the SSTR family and their implications for the prognosis of COAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Yang, Nie, Jiang, He and Ou.)

Background/purpose: The ligature-induced periodontitis model is an effective approach to induce inflammation and bone loss similar to that of human periodontitis. Previous clinical and in vitro studies have shown the involvement of lymphocytes in periodontitis, while, the local and systemic profile of immune cells associated with periodontitis in the ligature-induced periodontitis model in mice remains unclear., Materials and Methods: Experimental periodontitis was constructed in mice by ligating around the maxillary second molars for 14 and 28 days, respectively. Alveolar bone loss was assessed by micro-computed tomography (micro-CT). Hematoxylin and eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining were used to evaluate the histological changes in the periodontal tissues. B and T cells in the cervical lymph nodes, spleen, and peripheral blood were analyzed by flow cytometry., Results: The 14-day ligation effectively induced significant periodontal inflammation and alveolar bone loss in C57BL/6J mice, which were progressive and maintained for a relatively long-term period until day 28. In addition, CD3 + T cells and CD19 + B cells were the dominant population in both health and disease, and the B cell population within the cervical lymph nodes (LN) increased significantly under periodontitis condition, while, no significant differences of the T and B cell population among the spleen and peripheral blood were observed., Conclusion: The ligature-induced periodontitis mice model was established to perform a longitudinal assessment of changes in periodontal tissues morphologically and histologically, meanwhile, explore the local and systemic changes of the predominant immune-associated cells., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Liraglutide, an analog of human glucagon-like peptide-1 (GLP-1), has been found to improve hepatic steatosis in clinical practice. However, the underlying mechanism remains to be fully defined. Increasing evidence suggests that retinoic acid receptor-related orphan receptor α (RORα) is involved in hepatic lipid accumulation. In the current study, we investigated whether the ameliorating impact of liraglutide on lipid-induced hepatic steatosis is dependent on RORα activity and examined the underlying mechanisms. Cre-loxP-mediated, liver-specific Rorα knockout (Rora LKO) mice, and littermate controls with a Rora loxp/loxp genotype were established. The effects of liraglutide on lipid accumulation were evaluated in mice challenged with a high-fat diet (HFD) for 12 weeks. Moreover, mouse AML12 hepatocytes expressing small interfering RNA (siRNA) of Rora were exposed to palmitic acid to explore the pharmacological mechanism of liraglutide. The results showed that liraglutide treatment significantly alleviated HFD-induced liver steatosis, marked by reduced liver weight and triglyceride accumulation, improved glucose tolerance and serum levels of lipid profiles and aminotransferase. Consistently, liraglutide also ameliorated lipid deposits in a steatotic hepatocyte model in vitro. In addition, liraglutide treatment reversed the HFD-induced downregulation of Rora expression and autophagic activity in mouse liver tissues. However, the beneficial effect of liraglutide on hepatic steatosis was not observed in Rora LKO mice. Mechanistically, the ablation of Rorα in hepatocytes diminished liraglutide-induced autophagosome formation and the fusion of autophagosomes and lysosomes, resulting in weakened autophagic flux activation. Thus, our findings suggest that RORα is essential for the beneficial impact of liraglutide on lipid deposition in hepatocytes and regulates autophagic activity in the underlying mechanism., (© 2023 International Union of Biochemistry and Molecular Biology.)

Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality rates. The inhibitors of apoptosis (IAP) family act as oncogenes in various tumor types; however, their functions in HCC remain unclear. Here, we used integrated bioinformatics analysis and experimental verification to assess the expression and the prognostic and clinical value of the IAP family in HCC. Using the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) and the Tumor Immune Estimation Resource (TIMER), we analyzed the expression profiles of IAP family members in HCC tissue, normal tissues, and in patients with different stages and grades of HCC. We further verified the expression level of BIRC2 in 25 HCC samples and matched adjacent normal tissues using quantitative real-time PCR (qRT-PCR), and analyzed its correlation with the marker gene of T-helper type 1 cells (Th1)-STAT1. Meanwhile, the association between BIRC2 and the immunotherapeutic response or immunomodulators was confirmed using the Biomarker Exploration of Solid Tumors (BEST) database. The results showed that NAIP, BIRC2, BIRC3, XIAP, BIRC5, and BIRC6 mRNAs were overexpressed in HCC. The clinical stages, pathological grades, and other clinicopathological features of HCC were closely related to the expression levels of the IAP family members, especially the BIRC2 and BIRC5, which were found to be potential prognostic biomarkers for HCC. Expression of the IAPs was strongly associated with immune cell infiltration. Based on the infiltrative status of various immune cells, HCC patients with high BIRC2 and BIRC5 expression demonstrated poor overall survival (OS) rates. In patients with HCC, BIRC2 expression was noticeably elevated. Concurrently, the expression levels of BIRC2 and STAT1 showed a favorable correlation. BEST database analysis revealed that BIRC2 was a negative predictor of responsiveness to anti-programmed cell death ligand 1 (PD-L1)/cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitor treatment in HCC, and BIRC2 mRNA expression levels were positively correlated with the expression levels of the immune checkpoint genes programmed cell death protein 1 (PD-1), PD-L1, and CTLA-4 in HCC. Consequently, the IAP family may play a role in carcinogenesis and cancer-immune system interactions in HCC. Our results demonstrate that IAP family members may be viable predictive biomarkers and therapeutic targets for HCC., Competing Interests: Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The author(s).)

Pancreatic adenocarcinoma (PAAD) is a malignant tumor with high morbidity and mortality rates. The NT5DC family is an evolutionarily-conserved family of 5'-nucleosidases that catalyze the intracellular hydrolysis of nucleotides. Although the NT5DC family has been linked to the initiation and growth of several cancers, its function in PAAD remains unclear. A series of bioinformatic analyses was used to ascertain the expression, prognosis, gene changes, functional enrichment, and immune regulatory functions of the NT5DC family in PAAD. NT5C2 and NT5DC1/2 mRNA and protein levels are increased in PAAD. Furthermore, the high mRNA expressions of NT5C2, NT5DC2, and NT5DC4 indicate a poor prognosis in patients with PAAD. The enrichment of biological processes and gene expression in the NT5DC family in PAAD were investigated using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses. Further investigations into immune infiltration revealed a close relationship between NT5DC gene expression and immune cell infiltration. These findings provide new insights into the biological function and prognostic value of the NT5DC gene family in PAAD., Competing Interests: Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The author(s).)

Most patients with hypertension are complicated with insulin resistance (IR), which is one of the risk factors of hypertension and can increase the level of serum homocysteine (Hcy) by affecting Hcy's metabolic enzyme and insulin level. Investigations in recent years have shown that Hcy is an independent risk factor for cardiovascular diseases. At present, folic acid is the prominent medicine used to reduce Hcy, but its effection for Hcy has an obvious individual difference, which is closely related to individual genes. Moreover, folic acid is chiefly used in patients with Hcy ≥15 μmol/L, but Hcy ≥10 μmol/L has had an adverse effect on the cardiovascular system. Randomized clinical trials have shown that dapagliflozin can improve IR. Therefore, whether it can reduce Hcy has become a new direction. This study was a retrospective case-control study. Patients with high serum Hcy and hypertension complicated with IR were divided into two groups: the dapagliflozin group (n = 166) and the control group (n = 198). Before and after 12 weeks of treatment, the changes in serum Hcy and IR index were measured and compared. We found that dapagliflozin could reduce the serum Hcy level of patients with hypertension and IR to a certain extent. Dapagliflozin could be a viable option for hypertension complicated with IR and hyperhomocysteinemia. However, these findings need to be further confirmed in future randomized clinical trials with a large number of samples., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Optically pumped magnetometers (OPMs) can capture brain activity but are susceptible to magnetic noise. The objective of this study was to evaluate a novel methodology used to reduce magnetic noise in OPM measurements. A portable magnetoencephalography (MEG) prototype was developed with OPMs. The OPMs were divided into primary sensors and reference sensors. For each primary sensor, a synthetic gradiometer (SG) was constructed by computing a secondary sensor that simulated noise with signals from the reference sensors. MEG data from a phantom with known source signals and six human participants were used to assess the efficacy of the SGs. Magnetic noise in the OPM data appeared predominantly in a low frequency range (<4 Hz) and varied among OPMs. The SGs significantly reduced magnetic noise ( p < 0.01), enhanced the signal-to-noise ratio (SNR) ( p < 0.001) and improved the accuracy of source localization ( p < 0.02). The SGs precisely revealed movement-evoked magnetic fields in MEG data recorded from human participants. SGs provided an effective method to enhance SNR and improve the accuracy of source localization by suppressing noise. Software-simulated SGs may provide new opportunities regarding the use of OPM measurements in various clinical and research applications, especially those in which movement is relevant.

The fertilization process is a critical step in plant reproduction. However, the mechanism of action and mode of regulation of the fertilization process in gymnosperms remain unclear. In this study, we investigated the molecular regulatory networks involved in the fertilization process in Korean pine ovules through anatomical observation, physiological and biochemical assays, and transcriptome sequencing technology. The morphological and physiological results indicated that fertilization proceeds through the demise of the proteinaceous vacuole, egg cell division, and pollen tube elongation. Auxin, cytokinin, soluble sugar, and soluble starch contents begin to decline upon fertilization. Transcriptomic data analysis revealed a large number of differentially expressed genes at different times before and after fertilization. These genes were primarily involved in pathways associated with plant hormone signal transduction, protein processing in the endoplasmic reticulum, fructose metabolism, and mannose metabolism. The expression levels of several key genes were further confirmed by qRT-PCR. These findings represent an important step towards understanding the mechanisms underlying morphological changes in the Korean pine ovule during fertilization, and the physiological and transcriptional analyses lay a foundation for in-depth studies of the molecular regulatory network of the Korean pine fertilization process.

Introduction: Preeclampsia (PE), at early onset, is likely to be diagnosed as gestational hypertension (GH). Some cases of GH rapidly progress to PE within a short period of time, increasing the mortality rate of pregnant women and adverse events in neonates during the peripartum period. Oxidative stress participates in the occurrence and progression of PE. However, it is unknown whether the progression of GH to PE can be predicted., Methods: A total of 1548 patients diagnosed with PE (649 cases) or GH (899 cases) from January 2016 to June 2022 were selected as the study subjects. The 1548 patients were randomly divided into the training set (1083 cases) and the validation set (465 cases) in a 7:3 ratio. General and clinical data were collected to construct a risk factor prediction model for PE., Results: We found that (1) Systolic blood pressure (SBP), and uric acid (UA)/ superoxide dismutase (SOD) were the risk factors for the progression of GH to PE; (2) A nomogram was constructed from the prediction model, and the area under the curve (AUC) was 0.95, with a sensitivity of 87.4%, a specificity of 92.8%; (3) Build a model simplified scoring system. PE was most strongly predicted by UA/SOD (100 points), SBP (29 points), and serum potassium (19 points). The AUC was 0.92, with a sensitivity of 91.0%, a specificity of 81.7%. The clinical decision analysis curve shows that the model exhibits positive benefits when the threshold probability is at 0.01-0.91., Conclusion: These findings show that UA/SOD can predict progression of GH to PE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Yun, Yu and Xu.)

The activities of different microbes in the cow rumen have been shown to modulate the host's ability to utilize plant biomass, while the host-rumen interface has received little attention. As datasets collected worldwide have pointed to Campylobacteraceae as particularly abundant members of the rumen epithelial microbiome, we targeted this group in a subset of seven cows with meta- and isolate genome analysis. We show that the dominant Campylobacteraceae lineage has recently speciated into two populations that were structured by genome-wide selective sweeps followed by population-specific gene import and recombination. These processes led to differences in gene expression and enzyme domain composition that correspond to the ability to utilize acetate, the main carbon source for the host, at the cost of inhibition by propionate. This trade-off in competitive ability further manifests itself in differential dynamics of the two populations in vivo. By exploring population-level adaptations that otherwise remain cryptic in culture-independent analyses, our results highlight how recent evolutionary dynamics can shape key functional roles in the rumen microbiome., (© 2023. The Author(s).)