Search

The emergence of 5G represents a pivotal step in merging mobile communication networks with the Industrial Internet of Things. Despite the numerous advantages of 5G, the presence of unknown obstacles can adversely affect user signals. Although mitigating signal pressures can be achieved by increasing base station density, it often involves bulky equipment and high costs. To address this, we propose a deep learning-based method for controlling tunable transmissive metasurfaces and validate their scattering control capabilities in the presence of obstacles. By constructing a network model to analyze the mapping relationship between metasurface arrays and far-field scattering, rapid control of scattering characteristics is achieved. AI-driven high-performance tunable metasurfaces exhibit vast potential applications in intelligent communication, offering a universal solution for intelligent control in complex signal environments.

Abstract Microplastics (MPs) are contaminants ubiquitously found in the global biosphere that enter the body through inhalation or ingestion, posing significant risks to human health. Recent studies emerge that MPs are present in the bone marrow and damage the hematopoietic system. However, it remains largely elusive about the specific mechanisms by which MPs affect hematopoietic stem cells (HSCs) and their clinical relevance in HSC transplantation (HSCT). Here, we established a long-term MPs intake mouse model and found that MPs caused severe damage to the hematopoietic system. Oral gavage administration of MPs or fecal transplantation of microbiota from MPs-treated mice markedly undermined the self-renewal and reconstitution capacities of HSCs. Mechanistically, MPs did not directly kill HSCs but disrupted gut structure and permeability, which eventually ameliorated the abundance of Rikenellaceae and hypoxanthine in the intestine and inactivated the HPRT-Wnt signaling in bone marrow HSCs. Furthermore, administration of Rikenellaceae or hypoxanthine in mice as well as treatment of WNT10A in the culture system substantially rescued the MPs-induced HSC defects. Finally, we validated in a cohort of human patients receiving allogenic HSCT from healthy donors, and revealed that the survival time of patients was negatively correlated with levels of MPs, while positively with the abundance of Rikenellaceae, and hypoxanthine in the HSC donors’ feces and blood. Overall, our study unleashes the detrimental roles and mechanisms of MPs in HSCs, which provides potential strategies to prevent hematopoietic damage from MPs and serves as a fundamental critique for selecting suitable donors for HSCT in clinical practice.

Abstract Background Acute myocardial infarction (AMI) is characterized by inflammation, oxidative stress, and atherosclerosis, contributing to increased mortality risk. High-density lipoprotein (HDL) takes a crucial part in mitigating atherosclerosis and inflammation through its diverse functionalities. Conversely, fibrinogen is implicated in the development of atherosclerotic plaques. However, the mortality risk predictive capacity of fibrinogen to HDL-cholesterol ratio (FHR) in AMI patients remains unexplored. This research aimed to evaluate the effectiveness of FHR for mortality risk prediction in relation to AMI. Methods A retrospective study involving 13,221 AMI patients from the Cardiorenal ImprovemeNt II cohort (NCT05050877) was conducted. Baseline FHR levels were used to categorize patients into quartiles. The assessment of survival disparities among various groups was conducted by employing Kaplan‒Meier diagram. Cox regression was performed for investigating the correlation between FHR and adverse clinical outcomes, while the Fine-Gray model was applied to evaluate the subdistribution hazard ratios for cardiovascular death. Results Over a median follow-up of 4.66 years, 2309 patients experienced all-cause death, with 1007 deaths attributed to cardiovascular disease (CVD). The hazard ratio (HR) and its 95% confidence interval (CI) for cardiac and all-cause death among individuals in the top quartile of FHR were 2.70 (1.99–3.65) and 1.48 (1.26–1.75), respectively, in comparison to ones in the first quartile, after covariate adjustment. Restricted cubic spline analysis revealed that FHR was linearly correlated with all-cause mortality, irrespective of whether models were adjusted or unadjusted (all P for nonlinearity > 0.05). Conclusion AMI patients with increased baseline FHR values had higher all-cause and cardiovascular mortality, regardless of established CVD risk factors. FHR holds promise as a valuable tool for evaluating mortality risk in AMI patients. Trial registration The Cardiorenal ImprovemeNt II registry NCT05050877.

Recurrent opportunistic infections (OIs) in patients with severely immunosuppressed AIDS remain an unresolved medical challenge despite advancements in antiretroviral therapy (ART). To address this gap, we developed an HLA-mismatched allogeneic adoptive immune therapy (AAIT) specifically targeting this patient population. The safety and efficacy of this novel therapeutic approach were preliminarily confirmed in our phase 1 trial. Subsequently, a multicenter, open-label, controlled, phase 2a trial was conducted to evaluate the efficacy of AAIT in combination with ART compared with the conventional ART-only regimen. No difference in the incidence of adverse events (AEs) was observed between the two groups at the 96-week follow-up. AAIT treatment improved CD4+ T cell recovery at weeks 72 (P = 0.048) and 96 (P = 0.024) compared to the Control Group. Additionally, stratified analysis of patients in the AAIT Group showed that donor/recipient sex mismatch was significantly associated with the likelihood of patients achieving an immunological response (OR = 8.667; 95% CI, 2.010–37.377; P = 0.004). These findings suggest that AAIT serves as a promising adjunct therapy for improving the outcomes of patients with severely immunosuppressed AIDS. Further studies are needed to elucidate the immunological mechanisms underlying AAIT and identify the subpopulations that respond optimally to this therapeutic approach. This trial is registered at www.clinicaltrials.gov (NCT04098770).Trial registration: ClinicalTrials.gov identifier: NCT04098770.Trial registration: ClinicalTrials.gov identifier: NCT02651376.

Background Homemade peanut oil is widely consumed in rural areas of Southwestern China, which is easily contaminated by aflatoxins (AFs) and associated with adverse birth outcomes. Objective To identify the effect of exposure to homemade peanut oil consumption on low birth weight (LBW), preterm birth (PB) and other associated factors. Methods A prospective cohort study was conducted among pregnant women in Guangxi province, Southwestern China. Information of all eligible women on homemade peanut oil consumption and potential factors associated with LBW and PB was collected, and all were followed up until delivery. The effect of homemade peanut oil exposure was analyzed using multiple logistic regression models using the directed acyclic graph (DAG) approach. Results Of 1611 pregnant women, 1316 (81.7%) had consumed homemade peanut oil, and the rates of LBW and PB were 9.7% and 10.0%, respectively. Increased risks of LBW and PB in women with homemade peanut oil consumption were found with aORs of 1.9 (95% CI 1.1–3.2) and 1.8 (95% CI 1.1–3.0), respectively. Women with a history of PB or LBW were 3–5 times more likely to have higher rates of LBW or PB compared with those without this type of history. The odds of PB were approximately double in those taking medicine during pregnancy. Advanced maternal age, lack of physical exercise during pregnancy, passive smoking, or pregnancy complications were also more likely to have a higher risk of LBW. Conclusions Homemade peanut oil consumption was a potential risk factor for both LBW and PB, of which health authorities who are responsible for food safety of the country should pay more attention to providing recommendation for oil consumption during pregnancy.

Since its first discovery in 2017, evaporation-induced electricity has attracted extensive attention and shown significant advantages in green energy conversion. While the streaming potential-related electrokinetic effect has been intensively explored and widely recognized as the underlying mechanism, the role of coupling between water molecules and charge carriers in the material remains elusive. Here we show through carefully designed experiments that the streaming potential effect indeed plays a role but can only contribute about half to the total water-evaporation-induced voltage occurring within the partially-wetted region of the carbon black film where the solid-liquid-gas three-phase interface exists. It is also shown that water evaporation from carboxyl and amino-functionalized carbon black films produces opposite voltage signals. Detailed first-principles calculations unveil that the adsorption of water molecules can lead to reversed charge transfer in the carboxyl and amino-functionalized carbon substrates. Finally, an evaporation-driven charge transport mechanism is proposed for the induced electricity mediated by the coupling between water molecules and charge carriers in the material. The results reveal the important role of direct interaction between water molecules and materials, deepening our understanding of the mechanism for evaporation-induced hydrovoltaic effect beyond streaming potential.

Summary: Epigenetic modification shapes differentiation trajectory and regulates the exhaustion state of chimeric antigen receptor T (CAR-T) cells. Limited efficacy induced by terminal exhaustion closely ties with intrinsic transcriptional regulation. However, the comprehensive regulatory mechanisms remain largely elusive. Here, we identify class I histone deacetylase inhibitors (HDACi) as boosters of CAR-T cell function by high-throughput screening of chromatin-modifying drugs, in which M344 and chidamide enhance memory maintenance and resistance to exhaustion of CAR-T cells that induce sustained antitumor efficacy both in vitro and in vivo. Mechanistically, HDACi decrease HDAC1 expression and enhance H3K27ac activity. Multi-omics analyses from RNA-seq, ATAC-seq, and H3K27ac CUT&Tag-seq show that HDACi upregulate expression of TCF4, LEF1, and CTNNB1, which subsequently activate the canonical Wnt/β-catenin pathway. Collectively, our findings elucidate the functional roles of class I HDACi in enhancing CAR-T cell function, which provides the basis and therapeutic targets for synergic combination of CAR-T cell therapy and HDACi treatment.

Abstract With the large-scale vaccination of lipid nanoparticles (LNP)-based COVID-19 mRNA vaccines, elucidating the potential polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant LNP has become imminent. However, inconsistent findings were observed across very limited population-based studies. Herein we initiated a study using LNP carrier of Comirnaty® as a representative, and simulated real-world clinical practice covering a series of time points and various doses correlated with approved LNP-delivered drugs in a rat model. We demonstrated the time- and dose-dependency of LNP-induced anti-PEG antibodies in rats. As a thymus-independent antigen, LNP unexpectedly induced isotype switch and immune memory, leading to rapid enhancement and longer lasting time of anti-PEG IgM and IgG upon re-injection in rats. Importantly, initial LNP injection accelerated the blood clearance of subsequent dosing in rats. These findings refine our understandings on LNP and possibly other PEG derivatives, and may promote optimization of related premarket guidelines and clinical protocols.

Abstract Understanding the impact of smartphone‐based multimodal information (SMMI) on travellers' P&R (park‐and‐ride) choice behaviour is very limited so far. The purpose of this study is to better understand how SMMI, social network information, and individual characteristics influence travellers' mode choices. A stated preference experiment consisting of one P&R option and two auto‐driving routes was conducted to collect car commuters’ P&R choice data in Shanghai, China. The panel mixed logit model was utilized to determine the influencing factors. It was found that the panel mixed logit model, accounting for correlations among repeated observations of the same respondent and random taste, significantly outperforms the cross‐sectional multinomial logit model in terms of goodness‐of‐fit. Specifically, travellers are highly sensitive to the information offered by SMMI on travel time, parking fare, and crowding level in subway cars, and heterogeneities do exist in travellers' preferences for these factors. In terms of social network information, the positive propensity of online reviews and information about P&R play a positive role in P&R promotion. In addition, individual characteristics including gender, age, occupation, years of driving, and P&R experience all contribute to explaining the choice of P&R. Finally, the elasticity analysis reveals that commuters are more satisfied with P&R time than with car time, and the cross elasticity of P&R time demonstrates a limited substitution effect of P&R on private cars.

Plant flowering time is affected by endogenous and exogenous factors, but its variation patterns among different populations of a species has not been fully established. In this study, 27 Arabidopsis thaliana accessions were used to investigate the relationship between autonomous pathway gene methylation, gene expression and flowering time variation. DNA methylation analysis, RT-qPCR and transgenic verification showed that variation in the flowering time among the Arabidopsis populations ranged from 19 to 55 days and was significantly correlated with methylation of the coding regions of six upstream genes in the autonomous pathway, FLOWERING LOCUS VE (FVE), FLOWERING LOCUS Y (FY), FLOWERING LOCUS D (FLD), PEPPER (PEP), HISTONE DEACETYLASE 5 (HAD5) and Pre-mRNA Processing Protein 39-1 (PRP39-1), as well as their relative expression levels. The expression of FVE and FVE(CS) was modified separately through degenerate codon substitution of cytosine and led to earlier flowering of transgenic plants by 8 days and 25 days, respectively. An accurate determination of methylated sites in FVE and FVE(CS) among those transgenic plants and the recipient Col-0 verified the close relationship between the number of methylation sites, expression and flowering time. Our findings suggest that the methylation variation of these six key upstream transcription factors was associated with the gene expression level of the autonomous pathway and flowering time in Arabidopsis. The FVE(CS) and FVE genes in transgenic plants tended to be hypermethylated, which could be a protective mechanism for plants. However, modification of gene sequences through degenerate codon substitution to reduce cytosine can avoid hypermethylated transferred genes in transgenic plants. It may be possible to partially regulate the flowering of plants by modified trans-epigenetic technology.

To excite surface plasmon polaritons (SPPs) in an ultrathin way, metasurface‐based SPP couplers are widely used for converting propagating waves into driven waves bounded on their surfaces. Among them, the Pancharatnam–Berry (PB) metasurface coupler has a strong ability to control spin‐polarized waves, but is still limited by its coupling efficiency. Herein, a PB metasurface‐based SPP coupler that can support efficient circular‐polarization conversion with both the transverse magnetic and transverse electric modes of the SPP is proposed. The coupler is composed of an upper transmissive PB gradient metasurface and a lower eigenmode board to transform a circularly polarized plane wave into left‐handed circularly polarized and right‐handed circularly polarized surface waves that propagate in opposite directions. In the experimental results, it is indicated that the directionality factor of the tested SPP coupler is 28.6. The proposed PB metasurface coupler may pave the way for future integrated optical devices with high efficiency and excellent polarization‐split properties.

Premature ovarian insufficiency (POI) may lead to early menopause, fertility loss and birth defects without effective treatment. Here, we explored the efficacy and safety of gene therapy to rescue ovarian function in both natural ovarian aging and doxorubicin (Dox) induced POI mice. Sirt1 and Tgfbr2 were screened out and identified as key genes in both murine and human ovarian tissues. Then, adenovirus (AdV) was selected as a suited carrier for ovarian infection after comparison of multiple viral vectors. In both two models, murine fertility was significantly improved after AdV-Sirt1 and AdV-Tgfbr2 invention individually or in combination, without obvious side effects to themselves and their offspring. Compared with the control group, the successful pregnancy rate in the 9-month-old-AdV-Sirt1 group increased by 60 % (67 % vs 42 %). Meanwhile, the pregnancy rate in the AdV-Tgfbr2 + Dox group increased by 85 % (55.6 % vs 20 %). The biological process of ovarian follicle development and fibrosis was rescued. Our work demonstrated that AdV-Sirt1 and AdV-Tgfbr2 therapy alleviates natural ovarian aging and Dox-associated POI, which may be potentially applicable for female fertility protection.

Pleurotus citrinopileatus Singer (PCS) has attracted increasing attention as a raw material for medicine and food. Its quality is greatly affected by the accumulation of metabolites, which varies with the applied drying methods. In this study, we utilize an approach based on ultra-high-performance liquid chromatography/Q Exactive mass spectrometry (UHPLC-QE-MS) to reveal the metabolic profiles of PCS from three different drying methods (natural air-drying, NAD; hot-air-drying, HAD; vacuum freeze-drying, VFD). The results showed that lipids, amino acids and their derivatives were all important secondary metabolites produced during NAD, HAD and VFD treatments, with the key differential metabolites of PCS during drying including fifteen lipids and seven amino acids. Meanwhile, VFD was the best way for long-term preservation of dried PCS. Hot-drying methods, especially HAD, can improve the medicinal component of PCS. Furthermore, KEGG enrichment analysis highlighted 16 pathways and indicated that amino acid metabolism might be the key metabolite pathway for the PCS drying process. Our study elucidates the relationship between drying methods and metabolites or metabolic pathways of PCS to determine the mechanisms affecting the quality of PCS, and finally provides reference values for further development and application in functional food and medications.

Abstract The human eye, which relies on a flexible and controllable lens to focus light onto the retina, has inspired many scientific researchers to understand better and imitate the biological vision system. However, real-time environmental adaptability presents an enormous challenge for artificial eye-like focusing systems. Inspired by the mechanism of eye accommodation, we propose a supervised-evolving learning algorithm and design a neuro-metasurface focusing system. Driven by on-site learning, the system exhibits a rapid response to ever-changing incident waves and surrounding environments without any human intervention. Adaptive focusing is achieved in several scenarios with multiple incident wave sources and scattering obstacles. Our work demonstrates the unprecedented potential for real-time, fast, and complex electromagnetic (EM) wave manipulation for various purposes, such as achromatic, beam shaping, 6 G communication, and intelligent imaging.

ABSTRACTBackground: Changes in oral and hand hygiene behaviors have been reported during the COVID-19 pandemic in 2020 which may be associated with the incidence of the norovirus infection, a common cause of gastroenteritis.Objective: To estimate the trends of detection rates of norovirus gastroenteritis and associated factors before COVID-19 in 2015–2019 and during the COVID-19 in 2020 in Guangxi, China.Methods: A secondary analysis of Guangxi surveillance data of gastroenteritis patients was conducted. The detection rate in 2020 was predicted using an autoregressive integrated moving average modeland associated factors were analyzed using multiple logistic regression adjusted for interaction effects.Results: Of 7,903 gastroenteritis patients, the overall detection rate of norovirus gastroenteritis was 12.8%, (14.3% before and 6.1% during COVID-19). Detection rates gradually decreased from 2015 to 2020, of which the slope of predicted line was slightly flatter than the actual line. The odds ratios of detection were double to triple increase during COVID-19 in the younger age group and having food intake outside their homes. Tourist city, season, and types of food were independent associated factors.Conclusion: The detection rates were higher during the COVID-19 year among the population aged 45 years or less and those who consumed food outside their home.

Electromagnetic cloak or illusion, which can interfere with device detection and provide superior self-protection capabilities for animals or humans, has received much attention. The proposal of transformation optics provides a generalized strategy for realizing electromagnetic illusion. However, the complex parameter composition causes a substantial computational cost, which is not conducive to practical applications. To overcome these challenges, we report an intelligent illusory metasurface optimized by a genetic algorithm, which not only presents predefined illusory effects but also reduces the parameter space in physics. By designing a high-performance tunable metasurface, a high-fidelity inverse design is performed in simulation. Near-field and far field results show that the metasurface can generate virtual targets in different scenarios and realize electromagnetic illusion. This work is helpful in facilitating the practical application of electromagnetic illusion strategies.

Abstract Background The transversus abdominis plane (TAP) block in conjunction with intrathecal morphine has been demonstrated to provide more superior postcesarean analgesia to intrathecal morphine alone. However, the analgesia efficacy of their conjunction has not been demonstrated in patients with severe pre-eclampsia. The study aimed to compare the postcesarean analgesia of TAP block in conjunction with intrathecal morphine versus intrathecal morphine alone in women with severe pre-eclampsia. Methods Pregnant women with severe pre-eclampsia undergoing planned cesarean section were randomly allocated into 2 groups to receive TAP block with 20 ml of 0.35% Ropivacaine (TAP group) or with the same volume of 0.9% saline (Sham group) after undergoing elective cesarean section under spinal anaesthesia with 15 mg of 0.5% Ropivacaine plus 0.1 mg of morphine. The outcomes for this analysis include the visual analog scale (VAS) pain score at rest and with movement at 4,8,12,24 h after TAP block was performed, times of use of intravenous patient-controlled analgesia (PCA) within 12 h after anesthesia, the occurrence of maternal side effects, maternal satisfaction, and Apgar score at 1 and 5 min of newborns. Results 119 subjects receive TAP block with 0.35% Ropivacaine (n = 59)or 0.9% saline (n = 60). At 4,8, 12 h after TAP block, the TAP group reported lower VAS score at rest [at 4 h: 1(0,1) vs. 1(1,2), P

Rice, the main food crop in China, has been sporadically reported to suffer from weedy rice infestation. However, the overall occurrence and distribution pattern of Chinese weedy rice remains unclear because a systematic survey has not been conducted. In order to reveal the infestation of Chinese weedy rice, a field survey was conducted in 999 sampling sites all over the rice-growing regions in China from 2009 to 2016 using seven-scale visual scoring of the level of weed infestation. Weedy rice was found 39% occurrence incidence in a total of 387 sites. The sampling sites with 50% or higher overall weedy rice infestation index mainly radiated from Jiangsu, Heilongjiang, Ningxia and Guangdong to the whole East China, Northeast China, Northwest China and South China. A total of 45 morphological characters from 287 populations (collected simultaneously with the field survey) out of those occurred sites were observed and analyzed using multivariate analysis in common gardens with the same cultivation conditions in 2017 and 2019. Canonical correlation analysis showed that 45 morphological characters were significantly related to the latitude, mean temperature, minimum temperature, precipitation and mean diurnal range factors. The 287 weedy rice populations were divided into three morphological groups with climate-dependent geographical differentiation: strong tiller type only in Jiangsu, large leaf type in South China and Central China and large grain type mainly in North China. Weedy rice seriously infested rice fields and had a geography, climate and cultivated rice type-dependent morphological and biotype differentiation in China. It is suggested to pay attention to the harmfulness of weedy rice and adopt comprehensive control strategies.

Flammulina filiformis (F. filiformis) is called the ‘benefiting intelligence’ mushroom. There is a notable difference between a yellow cultivar (with a robust aroma) and a white mutant cultivar (with a high yield) of F. filiformis. A thorough analysis of aroma differences is essential to improve the aroma of high-yield strains. This study employed a combination of gas chromatography–mass spectrometry–olfactometry (GC-MS-O) and aroma extract dilution analysis (AEDA) to analyze the variations in aroma compounds. Then, the contribution of the odorants was determined using flavor dilution (FD) factors and odor activity values (OAVs). Aroma omission and recombination experiments were used to identify the key odorants. A total of 16 key aroma compounds were characterized in F. filiformis, along with four eight-carbon volatiles (3-octanone, 3-octanol, octanal, and 1-octen-3-ol). Finally, the dominant aroma characteristic was “sweet” for the yellow strain, while it was “green” for the white strain. More research is required to investigate the enzymes and corresponding genes that regulate the synthesis of aroma compounds in F. filiformis for future breeding programs.

Flammulina filiformis (F. filiformis) is one of the four major edible types of fungus in the world and has been cultivated in China since 800 CE (Anno Domini). Some of the most essential criteria for evaluating the quality of F. filiformis are the types and contents of volatile components present. A focused study on screened the terpene synthase genes involved in the aroma of offspring and compared key terpenoids between parents and offspring, which is helpful for the development and application of F. filiformis. Firstly, the volatile aroma components of parent and offspring F. filiformis were extracted using two pretreatment procedures, and then were semi-quantified by an internal standard. Forty-eight, fifty-eight, and forty-eight volatile compounds were identified in parents and offspring of three different strains, and 15, 22, and 12 aroma compounds (OAVs ≥ 1) were further screened out via calculating their odor activity values (OAVs). Terpenoids, in particular linalool and eucalyptol, which contribute more to the aroma, result in the unique green and grassy aroma of the offspring. At last, the F. filiformis genome was resequenced and the coordinates of genes related to terpenoid synthase were determined. The results showed that Scaffolds, including scaffold3.t874 and scaffold9.t157 were connected to terpenoid synthesis of offspring (No. 61523). The variant genes g269 and g61 were related to terpenoid synthase sequences. This study provides a theoretical foundation for the cultivation of more diverse and unique varieties of F. filiformis.

Abstract Summary Gamification is a new theme that has been applied in different fields and has contributed to different types of behavioural change. This paper aims to describe how gamification is adopted in the context of transportation. Methods We performed a systematic mapping of the scientific literature of Web of Science and retrieved 211 studies. After the inclusion and exclusion criteria were applied, 66 studies were selected. After the full texts were read, 30 studies remained to be analysed. Findings The results show that the most commonly used gamification elements are goals/challenges and points. Gamification provides support for outcomes such as changing travel behaviour, improving driving behaviour and encouraging bicycle commuting. The use of gamification has changed the behavior of travelers, promoted sustainable travel modes, encouraged safe driving, reduced carbon dioxide emissions and reduced energy consumption. Although gamification has achieved many positive results related to transportation, there are still many difficulties and challenges.

DNA methyltransferase 3A, a mutated gene associated with hematologic malignancies in age-related clonal haematopoiesis lacks targeted therapies. Here, the authors screen carbon nanomaterials and find graphdiyne oxide binds to mutant cells and disrupts cellular processes with a therapeutic effect in vitro and in vivo.

SARS-CoV-2 breakthrough infections in vaccinated individuals are a public health concern. Here, the authors analyse the clinical characteristics and profile immune alterations among vaccinated and non-vaccinated residents with Delta SARS-CoV-2 infection in Guangzhou.

Abstract Background The fecundity of sows is a trait of major economic in pig industry. The molecular regulation of estrus cycles can affect the fecundity of female animals. Compared with the other pig breeds, Xiang pig exhibits the special estrus behaviors. CircRNAs are thought to involve in regulation of multiple biological processes. However, the potential roles of circRNAs in ovary regulation on Xiang pig estrus are largely unknown. Results 8,937 circRNAs were identified from eight libraries constructed from the ovarian samples of Xiang pig at estrus and diestrus stages by RNA sequencing method. Of which, 1,995 were high confidence circRNAs detected at least two junction reads in each ovary sample and seven circRNAs were validated by RT-PCR method. Furthermore, we identified 290 upregulated and 15 downregulated circRNAs in estrus ovaries. These differentially expressed circRNAs (DECs) derived from 273 host genes. And 207 miRNAs were identified to be targets sponged by 156 DECs with 432 binding sites, containing more than one miRNA binding site in each circRNA. Function enrichment analysis revealed that the host genes and the targets of miRNAs sponged by DECs were enriched in several reproduction-related signaling pathways, such as ovarian steroidogenesis, oocyte maturation, circadian rhythm, estrogen signaling pathway, GnRH signaling pathway, circadian entrainment, and oocyte meiosis. The circRNA-miRNA-mRNA networks revealed that 153 miRNAs interacting with 122 DECs and 86 miRNAs interacting with 84 DECs were involved in ovarian functions and ovarian circadian entrainment and circadian rhythm respectively. The DEC-miRNA-DEG (differentially expressed gene, DEG) networks associated with reproduction-related signaling pathways contained 22 DECs,18 miRNAs and 7 DEGs. 22 DECs were recognized as hub circRNAs during the estrus phase of Xiang pigs. Conclusions The circRNAs that function as miRNA sponges could play a key role in post-transcriptional regulation of gene expression during Xiang pig’s estrus cycle.

Based on the perspective of ecology and innovation management, this paper selects seven elements from two aspects, innovation subject and innovation environment, to construct the evaluation index system for the health of pharmaceutical innovation ecological rainforest in Zhejiang from 2011 to 2019, together with the entropy weighted TOPSIS method and the obstacle factor diagnosis model. We find that the health of the pharmaceutical industry in Zhejiang can be measured as three stages: stagnation period, recovery period and development period. There is a relative balance between the development of innovation subject and innovation environment. The resilience of innovation subjects, followed by economic and cultural environment, is the key factor hindering the innovation of pharmaceutical industry in Zhejiang. Finally, we propose four countermeasures, including "deploying high-level service chains, broadening investment and financing channels for enterprises, building a reservoir of global talents, and creating an inclusive and open soft environment".

Shepherd’s-purse (Capsella bursa-pastoris), a globally distributed noxious weed species often found in wheat, has evolved resistance to ALS-inhibiting herbicides mainly due to single mutations in the ALS gene. In the present study, dose–response bioassays showed that a shepherd’s-purse population (R), collected from Xinghua, Jiangsu Province, China, had high level of resistance to the ALS-inhibiting herbicide, mesosulfuron-methyl (800-fold), and even much higher resistance levels to other reported ALS-inhibiting herbicides, tribenuron-methyl (1313-fold), bensulfuron-methyl (969-fold) and penoxsulam (613-fold). Sequencing of the open reading frame of the ALS gene revealed a double ALS gene mutation (Pro197-Ser plus Trp574-Leu) conferring the high resistance in the R plants. Docking analysis of the ALS protein and mesosulfuron-methyl predicts that the two amino acid substitutions in the R samples reduces the binding energy to the herbicide by decreasing the hydrogen bonds (H-bonds) and other interactions, thus endowing resistance to ALS-inhibiting herbicides. These results demonstrate that the double ALS mutation confers high resistance levels to ALS-inhibiting herbicides. To our knowledge, this is the first evidence of the double ALS mutation in shepherd’s-purse endowing ALS-inhibiting herbicide resistance.

Dictyophora rubrovolvata is a highly valuable and economically important edible fungus whose nutrition and flavor components may vary based on drying methods. Herein, an untargeted ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomics method combined with multivariate analysis was first performed to characterize the metabolomics profiles of D. rubrovolvata upon different drying treatments, viz., coal burning drying (CD), electrothermal hot air drying (ED), and freeze drying (FD). The results indicated that 69 differential metabolites were identified, vastly involving lipids, amino acids, nucleotides, organic acids, carbohydrates, and their derivatives, of which 13 compounds were confirmed as biomarkers in response to diverse drying treatments. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis illustrated that differential metabolites were significantly assigned to 59, 55, and 60 pathways of CD vs. ED, CD vs. FD, and FD vs. ED groups, respectively, with 9 of the top 20 KEGG pathways shared. Specifically, most of lipids, such as fatty acyls, glycerophospholipids and sphingolipids, achieved the highest levels in D. rubrovolvata after the CD treatment. ED method substantially enhanced the contents of sterol lipids, nucleotides, organic acids and carbohydrates, while the levels of amino acids, prenol lipids and glycerolipids were elevated dramatically against the FD treatment. Collectively, this study shed light on metabolomic profiles and proposed biomarkers of D. rubrovolvata subjected to multiple drying techniques, which may contribute to quality control and drying efficiency in edible fungi production.

Abstract Background The ability of a preventive nutritional intervention to reduce the morbidity of gestational diabetes mellitus (GDM) remains controversial. We aim to assess whether GDM can be prevented by an individualised nutritional intervention in pregnant women who are at high risk for the disease based on a prediction model. Methods/design A multicentre randomised controlled trial was designed to assess the efficacy of an individualised nutritional intervention for the prevention of GDM in a high-risk population screened by a novel prediction model in the first trimester. Pregnant women evaluated to be at high risk for GDM by the prediction model at less than 14 gestational weeks will be included. Women with pre-existing chronic diseases, including pregestational diabetes, or who are currently prescribed medicines that affect glucose values will be excluded. Allocation to intervention/control at a ratio of 1:1 will be conducted by a computerized randomisation system. The intervention group will complete 3-day food records and receive 3 individualised nutritional consultations with professional dieticians before the oral glucose tolerance test. The primary intention of the intervention is to promote a long-term healthy dietary pattern and prevent excessive gestational weight gain throughout pregnancy. The control group will complete 3-day food records at designated gestational weeks and receive standard antenatal care according to local health care provisions. The primary outcome is the incidence of GDM according to the criteria of the International Association of Diabetes and Pregnancy Study Group (IADPSG). A sample of 464 participants will provide 80% power to detect a 30% reduction in GDM incidence (α = 0.05 two tailed, 10% dropout). A total of 500 participants will be recruited. Discussion To date, this is the first randomised controlled trial aimed to evaluate the protective effect of an individualised nutritional intervention against GDM based on a logistic regression prediction model. Eligibility is not limited to obese women or singleton pregnancies, as in previous studies. This pragmatic trial is expected to provide valuable information on early screening and effective GDM prevention methods. Trial registration number ChiCTR, ChiCTR1900026963 . Registered 27 October 2019.

Programmable metasurfaces have attracted significant attention in various applications such as radar and 6G communications, owing to their ability freely shape the far-field pattern. However, complex calculations and simulations are always required when designing specific far-field patterns, especially when irregular obstacles are outside the metasurface. In this article, we propose a method using a four-layer artificial neural network to realize the far-field radar cross section (RCS) prediction of programmable metasurfaces in an environment with obstacles, and the prediction value agreed with the simulation data reasonably well. Results show that the proposed prediction model is characterized by better learning and generalization capacity. Our work has broad application prospects and value in complex environment signal transmission, metasurface inverse design, etc.

Flammulina Velutipes (F. velutipes) is widely planted all over the world and is rich in nutrients, which is of great benefit to the human body. However, the research on the aroma of F. velutipes is relatively rare, which limits the application of F. velutipes in deep processing, resulting in a single product and edible method of F. velutipes. The purpose of this study was to find out the aroma compounds contributing to the sensory properties of F. velutipes to promote the application of different varieties of F. velutipes in deep processing. Aromas of 7 species of F. velutipes were described and evaluated by sensory evaluation experiment. The volatile compounds in seven kinds of F. velutipes were detected by headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (GC-MS). A total of 74 volatile compounds were found, including 23 alcohols, 5 aldehydes, 2 phenols, 1 acid, 16 esters, 7 ketones, 1 ether, 13 hydrocarbons, 1 sulfide, 1 acyl compound, and 4 heterocyclic compounds. It was also found that the sensory evaluation results of sample F, C, and E had a high correlation with the content of compound, and the correlation between sample B and sample A was also high. A lexicon for describing aroma attributes of F. velutipes was developed and they could be grouped into categories, such as fruity (apple-like, banana-like, cucumber-like, citrus-like and berry-like), alcoholic (whisky-like, fermented fruit-like), milky (creamy-like), floral (hyacinth-like, phoenix-like, iris-like and mint-like), sulfurous (onion-like), and musty (mud-like). This research will provide a theoretical basis for the future study of F. velutipes aroma and the development and application of F. velutipes products.

The morel mushroom (Morchella sp.) is reputed as one of the most highly-prized edible fungi with mounting cultivated area as well as commercial popularity in China. To date, optimized methods specific for quality evaluation and constituent analysis of Morchella sp. are still non-available, impeding the healthy and sustainable development of this industry. Herein, an untargeted UPLC-Q-TOF-MS-based metabolomics approach was performed to characterize the metabolite profiles of morel samples from four distinct geographical origins of China, viz. Gansu, Guizhou, Liaoning, and Henan province. A total of 32 significantly different metabolites assigned to lipids (19), organic acids (9), amino acids (3), and ketones (1) were identified to distinguish the geographic-segregation samples amenable to multivariate analysis. These metabolites may serve as molecular markers indicative of specific regions. More importantly, the lipid, protein and amino acid metabolism were responsible for geographic differences as revealed by KEGG pathway enrichment analysis. Collectively, this study not only pioneered high-throughput methodology to evaluate quality of Morchella sp. and distinguish geographical origins in a sensitive, rapid and efficient manner, but also shed light on the potential link between physiochemical variation and geological origins from a metabolic perspective, which may be conducive to the advancement of edible fungi industry and establishment of food traceability system.

Abstract Background Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. Methods The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. Results Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. Conclusion Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro.

Azobenzene derivatives are a unique class of photo-switch molecules with promising potential for nanoscale optical applications. We have studied the self-assembly and photo-induced mechanical switching of azobenzene derivatives on Au(111) at the single-molecule level by using scanning tunneling microscope (STM). 4,4′-Dibromo-azobenzene (Br-AB) molecules are assembled into two types of well-ordered structures on Au(111) surfaces in the trans-isomer configuration. Br-AB molecules experienced configurational changes from trans-to-cis photo-isomerization upon the exposure to the UV light. This photo-isomerization of Br-AB molecules was observed to occur at random sites of ordered structure, evidenced by the appearance of bright protrusions with the height increment. Our results may open up new routes to engineer nanoscale photo-switch molecular devices.

Curvularia trifolii is an important pathogenic fungus that causes leaf spot disease in strawberry and other crops. Increased resistance in pathogenic fungi against chemical fungicides necessitates the search for biological alternatives to control plant fungal diseases. The present study aimed to perform transcriptome and metabolome analysis of C. trifolii fungi. We evaluated the potential of an alkaloid, namely alpha (α)-solanine, to inhibit the growth of Curvularia under in vitro conditions. Furthermore, transcriptomic and metabolomic analysis of treated C. trifolii was performed to identify the differential genes and metabolites. Results revealed that treatment with α-solanine resulted in the poor growth and development of fungal spores. The transcriptome analysis revealed that 1413 genes were differentially expressed (DEGs), among which 340 unigenes were up-regulated, 100 unigenes were down-regulated, and the rest were unaffected in treated samples. Gene ontology analysis revealed that the majority of the genes were related to oxidative stress in the fungus. Additionally, using ultra-high performance liquid chromatography-tandem mass spectrometry, we identified 455 metabolites, among which the majority of metabolites were related to lipid biosynthesis. The high number of genes related to lipid biosynthesis and reactive oxygen species revealed that α-solanine causes oxidative stress in Curvularia, leading to growth inhibition, and can be potentially used as an alternative to chemical fungicides.

Electromagnetic (EM) waves that bypass obstacles to achieve focus at arbitrary positions are of immense significance to communication and radar technologies. Small-sized and low-cost metasurfaces enable the accomplishment of this function. However, the magnitude-phase characteristics are challenging to analyze when there are obstacles between the metasurface and the EM wave. In this study, we creatively combined the deep reinforcement learning algorithm soft actor–critic (SAC) with a reconfigurable metasurface to construct an SAC-driven metasurface architecture that realizes focusing at any position under obstacles using real-time simulation data. The agent learns the optimal policy to achieve focus while interacting with a complex environment, and the framework proves to be effective even in complex scenes with multiple objects. Driven by real-time reinforcement learning, the knowledge learned from one environment can be flexibly transferred to another environment to maximize information utilization and save considerable iteration time. In the context of future 6G communications development, the proposed method may significantly reduce the path loss of users in an occluded state, thereby solving the open challenge of poor signal penetration. Our study may also inspire the implementation of other intelligent devices.

The spatiotemporal patterns of urban expansion have attracted worldwide attention and have been generalized into several prevalent hypotheses, such as the diffusion–coalescence hypothesis and the three-growth-type hypothesis. Although many studies have examined the applicability of these hypotheses, long-term research and evidence are still lacking. This study incorporated a compiled dataset of multisource remote sensing images and historical maps covering nine snapshots of the urban built-up area from 1914 to 2018 to monitor the urban expansion process in Hangzhou, China. A fractal analysis of the area–radius relationship was employed for areal demarcation to explore the heterogenous patterns across different intra-city spatial extents. The results show that (1) Hangzhou has experienced a turbulent period of primitive urbanization in the pre-reform era and a consecutive period of market-oriented urbanization after the economic reform; (2) the urban expansion pattern characterized by landscape metrics demonstrates the existence of multiple alternations between diffusion and coalescence phases with peculiarities across different intra-city spatial extents; (3) the analysis of urban growth types documents a consistent predominance of edge-expansion with wax and wane between infilling and leapfrogging; and (4) institutional reform, industrial development, and administrative division adjustment are the main drivers of urban expansion in Hangzhou. Our findings suggest that effective planning policies need to be raised to curb urban sprawl. Differentiated planning strategies should be proposed to accommodate unique conditions in different urban subregions. The integrated-analysis approach based on multisource remote sensing images and historical maps establishes a feasible pathway for long-term urban research.

Background Since December 2019, COVID-19 began to spread throughout the world for nearly two years. During the epidemic, the travel intensity of most urban residents has dropped significantly, and they can only complete inflexible travel such as "home to designated hospital" and "home to supermarket" and some special commuting trips. While ensuring basic travel of residents under major public health emergency, there is also a problem of high risk of infection caused by exposure of the population to the public transport network. For the discipline of urban transport, how to use planning methods to promote public health and reduce the potential spread of diseases has become a common problem faced by the government, academia and industry. Method Based on the mobility perspective of travel agents, the spatial analysis methods such as topological model of bus network structure, centrality model of public transport network and nuclear density analysis are used to obtain the exposure risk and spatial distribution characteristics of public transport from two aspects of bus stops and epidemic sites. Results The overall spatial exposure risk of Wuhan city presents an obvious "multi center circle" structure at the level of bus stops. The high and relatively high risk stops are mainly transport hubs, shopping malls and other sites, accounting for 35.63%. The medium and low-risk stops are mainly the villages and communities outside the core areas of each administrative region, accounting for 64.37%. On the other hand, at the scale of epidemic sites, the coverage covers 4018 bus stops in Wuhan, accounting for 36.5% of all bus stops, and 169 bus lines, accounting for 39.9% of all routes. High risk epidemic sites are mainly concentrated in the core areas within the jurisdiction of Wuhan City, and in the direction of urban outer circle diffusion, they are mainly distributed in the low and medium risk epidemic sites. According to the difference of the risk level of public transport exposure, the hierarchical public transport control measures are formulated. Discussion This paper proposes differentiated prevention and control countermeasures according to the difference of risk levels, and provides theoretical basis and decision-making reference for urban traffic management departments in emergency management and formulation of prevention and control countermeasures.

Tumor staging of upper tract urothelial carcinomas (UTUCs) is relatively difficult to assert accurately before surgery. Here, we used copy number (CN) signatures as a tool to explore their clinical significance of molecular stratification in UTUC. CN signatures were extracted by non-negative matrix factorization from the whole-genome sequencing (WGS) data of 90 Chinese UTUC primary tumor samples. A validation UTUC cohort (n = 56) and a cohort from urinary cell-free DNA (cfDNA) of urothelial cancer patients (n = 94) and matched primary tumors were also examined. Survival analyses were measured using the Kaplan–Meier, and Cox regression was used for multivariate analysis. Here, we identified six CN signatures (Sig1–6). Patients with a high contribution of Sig6 (Sig6high) were associated with higher microsatellite instability level and papillary architecture and had a favorable outcome. Patients with a low weighted genome integrity index were associated with positive lymph node and showed the worst outcome. Sig6high was identified to be an independently prognostic factor. The predictive significance of CN signature was identified by a validation UTUC cohort. CN signatures retained great concordance between primary tumor and urinary cfDNA. In conclusion, our results reveal that CN signature assessment for risk stratification is feasible and provides a basis for clinical studies that evaluate therapeutic interventions and prognosis.

CRISPR/Cas9 systems were established in some edible fungi based on in vivo expressed Cas9 and guide RNA. Compared with those systems, the in vitro assembled Cas9 and sgRNA ribonucleoprotein complexes (RNPs) have more advantages, but only a few examples were reported, and the editing efficiency is relatively low. In this study, we developed and optimized a CRISPR/Cas9 genome-editing method based on in vitro assembled ribonucleoprotein complexes in the mushroom Flammulina filiformis. The surfactant Triton X-100 played a critical role in the optimal method, and the targeting efficiency of the genomic editing reached 100% on a selective medium containing 5-FOA. This study is the first to use an RNP complex delivery to establish a CRISPR/Cas9 genome-editing system in F. filiformis. Moreover, compared with other methods, this method avoids the use of any foreign DNA, thus saving time and labor when it comes to plasmid construction.

Image data play an important role in our daily lives, and scholars have recently leveraged deep learning to design steganography networks to conceal and protect image data. However, the complexity of computation and the running speed have been neglected in their model designs, and steganography security still has much room for improvement. For this purpose, this paper proposes an RDA-based network, which can achieve higher security with lower computation complexity and faster running speed. To improve the hidden image’s quality and ensure that the hidden image and cover image are as similar as possible, a residual dense attention (RDA) module was designed to extract significant information from the cover image, thus assisting in reconstructing the salient target of the hidden image. In addition, we propose an activation removal strategy (ARS) to avoid undermining the fidelity of low-level features and to preserve more of the raw information from the input cover image and the secret image, which significantly boosts the concealing and revealing performance. Furthermore, to enable comprehensive supervision for the concealing and revealing processes, a mixed loss function was designed, which effectively improved the hidden image’s visual quality and enhanced the imperceptibility of secret content. Extensive experiments were conducted to verify the effectiveness and superiority of the proposed approach.

In recent years, the amount of data has increased explosively, which has spawned the large-scale development of cloud storage. Increasingly, individuals and enterprises store images in cloud space. The storage security of the cloud is generally guaranteed by encryption, but this can no longer meet the needs of image management and protection. In order to realize the management and loss tolerance of images, this paper proposes a thumbnail secret image sharing method. The proposed scheme combines the advantages of thumbnail-preserving encryption (TPE) and secret image sharing (SIS) with different meaningful shadows. Thumbnails can realize the visual management of stored images, and secret image sharing can realize the perfect security of stored images. The proposed scheme realizes the confidentiality, integrity, and availability of images, which are three elements of information security. Compared with TPE, our scheme not only realizes the visual management of images but also achieves loss tolerance and perfect security. Compared with SIS with different meaningful shadows, our scheme will greatly improve the sharing efficiency and reduce the consumption of computing resources. In this paper, the theoretical analysis and security proof of the proposed scheme are presented. In addition, we also conduct sufficient experiments and comparative explanations.

Background: Endometrial cancer is one of the most common gynecological malignancies and has exhibited an increasing incidence rate in recent years. Cancer stem cells (CSCs), which are responsible for tumor growth and chemoresistance, have been confirmed in endometrial cancer. However, it is still challenging to identify endometrial cancer stem cells to then target for therapy. Methods: Flow cytometry was used to identify the endometrial cancer stem cells. Sphere formation assay, western blotting, qRT-PCR assay, cell viability assay, xenograft assay and immunohistochemistry staining analysis were utilized to evaluate the effect of SPARC-related modular calcium binding 2 (SMOC-2) on the cells proliferation and drug resistance. Cell viability assay, qRT-PCR assay, immunofluorescence staining, Co-IP assay and luciferase reporter gene assay were performed to explore the possible molecular mechanism by which SMOC-2 activates WNT/β-catenin pathway. Findings: We found the expression of SPARC-related modular calcium binding 2 (SMOC-2), a member of SPARC family, was higher in endometrial CSCs than that in non-CSCs. SMOC-2 was also more highly expressed in spheres than in monolayer cultures. The silencing of SMOC-2 suppressed cell sphere ability; reduced the expression of the stemness-associated genes SOX2, OCT4 and NANOG; and enhanced chemosensitivity in endometrial cancer cells. By co-culture IP assay, we demonstrated that SMOC-2 directly interacted with WNT receptors (Fzd6 and LRP6), enhanced ligand-receptor interaction with canonical WNT ligands (Wnt3a and Wnt10b), and finally, activated the WNT/β-catenin pathway in endometrial cancer. SMOC-2 expression was closely correlated with CSC markers CD133 and CD44 expression in endometrial cancer tissue. Interpretation: Taken together, we conclude that SMOC-2 might be a novel endometrial cancer stem cell signature gene and therapeutic target for endometrial cancer. Fund: National Natural Science Foundation of China, Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission, Scientific and Technological Innovation Act Program of Fengxian Science and Technology Commission, Natural Science Foundation of Shanghai. Keywords: SMOC-2, Endometrial carcinoma, Cancer stem cells, Chemoresistance, WNT/β-catenin pathway

Abstract Background 5-Hydroxymethylcytosine (5hmC) is an oxidation product of 5-methylcytosine (5mC), and adjacent CpG sites in mammalian genome can be co-methylated and co-hydroxymethylated due to the processivity of DNMT and TET enzymes. Results We applied TAB-seq and oxBS-seq to selectively detect 5hmC and 5mC at base resolution in the mouse cortex, olfactory bulb and cerebellum tissues. We found that majority of the called 5hmC CpG sites frequently have 5mC modification simultaneously and are enriched in gene body regions of neuron development-related genes in brain tissues. Strikingly, by a systematic search of regions that show highly coordinated methylation and hydroxymethylation (MHBs and hMHBs), we found that MHBs significantly overlapped with hMHBs in gene body regions. Moreover, using a metric called methylation haplotype load, we defined a subset of 1361 tissue-specific MHBs and 3818 shared MHBs. Shared MHBs with low MHL correspond with developmental enhancers, and tissue-specific MHBs resemble the regulatory elements for tissue identity. Conclusions Our results provide new insights into the role of coordinately oxidized 5mC to 5hmC as distal regulatory elements may involve in regulating tissue identity.

Tuberculosis (TB) is the world's most prevalently infectious disease. Molecular mechanisms behind tuberculosis remain unknown. microRNA (miRNA) is involved in a wide variety of diseases. To validate the significant genes and miRNAs in the current sample, two messenger RNA (mRNA) expression profile datasets and three miRNA expression profile datasets were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed (DE) genes (DEGs) and miRNAs (DE miRNAs) between healthy and TB patients were filtered out. Enrichment analysis was executed, and a protein-protein interaction (PPI) network was developed to understand the enrich pathways and hub genes of TB. Additionally, the target genes of miRNA were predicted and overlapping target genes were identified. We studied a total of 181 DEGs (135 downregulated and 46 upregulated genes) and two DE miRNAs (2 downregulated miRNAs) from two gene profile datasets and three miRNA profile datasets, respectively. 10 hub genes were defined based on high degree of connectivity. A PPI network's top module was constructed. The 23 DEGs identified have a significant relationship with miRNAs. 25 critically significant Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were discovered. The detailed study revealed that, in tuberculosis, the DE miRNA and DEGs form an interaction network. The identification of novel target genes and main pathways would aid with our understanding of miRNA's function in tuberculosis progression.

Ovarian aging leads to reproductive and endocrine dysfunction, causing the disorder of multiple organs in the body and even declined quality of offspring’s health. However, few studies have investigated the changes in gene expression profile in the ovarian aging process. Here, we applied integrated bioinformatics to screen, identify, and validate the critical pathogenic genes involved in ovarian aging and uncover potential molecular mechanisms. The expression profiles of GSE84078 were downloaded from the Gene Expression Omnibus (GEO) database, which included the data from ovarian samples of 10 normal C57BL/6 mice, including old (21–22 months old, ovarian failure period) and young (5–6 months old, reproductive bloom period) ovaries. First, we filtered 931 differentially expressed genes (DEGs), including 876 upregulated and 55 downregulated genes through comparison between ovarian expression data from old and young mice. Functional enrichment analysis showed that biological functions of DEGs were primarily immune response regulation, cell–cell adhesion, and phagosome pathway. The most closely related genes among DEGs (Tyrobp, Rac2, Cd14, Zap70, Lcp2, Itgb2, H2-Ab1, and Fcer1g) were identified by constructing a protein–protein interaction (PPI) network and consequently verified using mRNA and protein quantitative detection. Finally, the immune cell infiltration in the ovarian aging process was also evaluated by applying CIBERSORT, and a correlation analysis between hub genes and immune cell type was also performed. The results suggested that plasma cells and naïve CD4+ T cells may participate in ovarian aging. The hub genes were positively correlated with memory B cells, plasma cells, M1 macrophages, Th17 cells, and immature dendritic cells. In conclusion, this study indicates that screening for DEGs and pathways in ovarian aging using bioinformatic analysis could provide potential clues for researchers to unveil the molecular mechanism underlying ovarian aging. These results could be of clinical significance and provide effective molecular targets for the treatment of ovarian aging.

Hydroxylation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes presents a particular regulatory mechanism in the mammalian brain. However, although methylation and hydroxymethylation of cytosines in non-CpG contexts have been reported, these mechanisms remain poorly understood. Here, we applied TAB-seq and oxBS-seq selectively to detect 5hmC and 5mC at base resolution in olfactory bulb derived from female mice. We found that active turnover of 5mC to 5hmC occurred in both CpG and non-CpG contexts. Strikingly, we identified a different sequence preference for 5mC and 5hmC in a CH context, in which H = A, C, or T, TNCA/TC for 5mC and NNCA/T/CN for 5hmC. More importantly, we found that genes showing 5mC to 5hmC turnover showed only limited overlap in CpG and CH contexts, and that olfactory receptor genes were marked with higher turnover of 5mC to 5hmC in non-CpG context. Collectively, we identified an unexpected sequence preference for non-CpG hydroxymethylation and distinct target genes regulated by the turnover of 5mC to 5hmC in CpG and CH contexts.

Love at first sight is a well-known and interesting phenomenon, and denotes the strong attraction to a person of the opposite sex when first meeting. As far as we know, there are no studies on the changes in physiological signals between the opposite sexes when this phenomenon occurs. Although privacy is involved, knowing how attractive a partner is may be beneficial to building a future relationship in an open society where both men and women accept each other. Therefore, this study adopts the photoplethysmography (PPG) signal acquisition method (already applied in wearable devices) to collect signals that are beneficial for utilizing the results of the analysis. In particular, this study proposes a love pulse signal recognition algorithm based on a PPG signal. First, given the high correlation between the impulse signals of love at first sight and those for physical attractiveness, photos of people with different levels of attractiveness are used to induce real emotions. Then, the PPG signal is analyzed in the time, frequency, and nonlinear domains, respectively, in order to extract its physiological characteristics. Finally, we propose the use of a variety of machine learning techniques (support vector machine (SVM), random forest (RF), linear discriminant analysis (LDA), and extreme gradient enhancement (XGBoost)) for identifying the impulsive states of love, with or without feature selection. The results show that the XGBoost classifier has the highest classification accuracy (71.09%) when using the feature selection.

A simple and high throughput method was developed and validated for simultaneous determination of valproic acid and its two toxicant ene-metabolites, 2-enevalproic acid and 4-enevalproic acid in epilepsy patient plasma using liquid chromatography–tandem mass spectrometry. Probenecid was used as internal standard and solid-phase extraction was selected for sample preparation. A chromatographic separation was performed on an Agilent Poroshell SB-C18 column (50 mm×4.6 mm i.d., 2.7 μm) by an optimized gradient elution at a flow rate of 0.9 mL/min. The total run time was 7 min. Electrospray ionization was used in negative ion mode by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 143.0→143.0 for valproic acid, m/z 140.9→140.9 for 2-enevalproic acid and 4-enevalproic acid for their poor fragments, and m/z 283.9→239.9 for probenecid. The results showed good linearity of valproic acid, 2-enevalproic acid and 4-enevalproic acid in their respective linear ranges. The correlation coefficients were more than 0.998. The intra- and inter-day precision of the assay was less than 11.0% and the accuracy ranged from 2% to 12%. This analytical method was successfully applied to assay plasma concentrations of valproic acid and its two ene-metabolites in epilepsy patient plasma and used for therapeutic drug monitoring.