Identification of receptors and factors associated with human coronaviruses in the oral cavity using single-cell RNA sequencing.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) ravaged the world, and Coronavirus Disease 2019 (COVID-19) exhibited highly prevalent oral symptoms that had significantly impacted the lives of affected patients. However, the involvement of four human coronavirus (HCoVs), namely SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-229E, in oral cavity infections remained poorly understood. We integrated single-cell RNA sequencing (scRNA-seq) data of seven human oral tissues through consistent normalization procedure, including minor salivary gland (MSG), parotid gland (PG), tongue, gingiva, buccal, periodontium and pulp. The Seurat, scDblFinder, Harmony, SingleR, Ucell and scCancer packages were comprehensively used for analysis. We identified specific cell clusters and generated expression profiles of SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) in seven oral regions, providing direction for predicting the tropism of four HCoVs for oral tissues, as well as for dental clinical treatment. Based on our analysis, it appears that various SCARFs, including ACE2, ASGR1, KREMEN1, DPP4, ANPEP, CD209, CLEC4G/M, TMPRSS family proteins (including TMPRSS2, TMPRSS4, and TMPRSS11A), and FURIN, are expressed at low levels in the oral cavity. Conversely, BSG, CTSB, and CTSL exhibit enrichment in oral tissues. Our study also demonstrates widespread expression of restriction factors, particularly IFITM1-3 and LY6E, in oral cells. Additionally, some replication, assembly, and trafficking factors appear to exhibit broad oral tissues expression patterns. Overall, the oral cavity could potentially serve as a high-risk site for SARS-CoV-2 infection, while displaying a comparatively lower degree of susceptibility towards other HCoVs (including SARS-CoV, MERS-CoV and HCoV-229E). Specifically, MSG, tongue, and gingiva represent potential sites of vulnerability for four HCoVs infection, with the MSG exhibiting a particularly high susceptibility. However, the expression patterns of SCARFs in other oral sites demonstrate relatively intricate and may only be specifically associated with SARS-CoV-2 infection. Our study sheds light on the mechanisms of HCoVs infection in the oral cavity as well as gains insight into the characteristics and distribution of possible HCoVs target cells in oral tissues, providing potential therapeutic targets for HCoVs infection in the oral cavity.

Carbohydrate restriction during lactation: A systematic review.

The quality of a mother's diet is important to ensure child growth and development and keep women healthy. This systematic review aimed to identify the outcomes of a carbohydrate-restricted diet during lactation. PubMed, EMBASE, Scopus, Web of Science, and LILACS were searched for studies published between 2012 and 2023; 16 studies were selected, all of them case reports or care series. The carbohydrate restriction described in the papers mainly was ketogenic, low-carb, low-carbohydrate and high-fat, and modified ketogenic diets. The main goal of women undertaking these diets was weight loss, with therapeutic purposes (monitored and supervised by health professionals) in only 2 cases: (1) ketogenic diet therapy for treatment of seizures in the infant and (2) to reduce symptoms of mother's gastroesophageal reflux. Most articles reported that lactating women were hospitalized, experiencing symptoms such as vomiting, muscle weakness, nausea, abdominal pain, general malaise, and fatigue. However, articles did not mention poor outcomes for the infants. Most of the studies in this review were published in the past 3 years, indicating a possible increase in cases of women practicing carbohydrate restriction during lactation for weight loss caused by body dissatisfaction. In conclusion, carbohydrate restriction during lactation may be harmful to the lactating woman and contribute to the state of lactational ketoacidosis, but infant outcomes are mainly a change in feeding patterns. Thus, education on food and nutrition is necessary for this population.

PDCD4 restricts PRRSV replication in an eIF4A-dependent manner and is antagonized by the viral nonstructural protein 9.

As obligate parasites, viruses have evolved multiple strategies to evade the host immune defense. Manipulation of the host proteasome system to degrade specific detrimental factors is a common viral countermeasure. To identify host proteins targeted for proteasomal degradation by porcine reproductive and respiratory syndrome virus (PRRSV), we conducted a quantitative proteomics screen of PRRSV-infected Marc-145 cells under the treatment with proteasome inhibitor MG132. The data revealed that the expression levels of programmed cell death 4 (PDCD4) were strongly downregulated by PRRSV and significantly rescued by MG132. Further investigation confirmed that PRRSV infection induced the translocation of PDCD4 from the nucleus to the cytoplasm, and the viral nonstructural protein 9 (Nsp9) promoted PDCD4 proteasomal degradation in the cytoplasm by activating the Akt-mTOR-S6K1 pathway. The C-terminal domain of Nsp9 was responsible for PDCD4 degradation. As for the role of PDCD4 during PRRSV infection, we demonstrated that PDCD4 knockdown favored viral replication, while its overexpression significantly attenuated replication, suggesting that PDCD4 acts as a restriction factor for PRRSV. Mechanistically, we discovered eukaryotic translation initiation factor 4A (eIF4A) was required for PRRSV. PDCD4 interacted with eIF4A through four sites (E249, D253, D414, and D418) within its two MA3 domains, disrupting eIF4A-mediated translation initiation in the 5'-untranslated region of PRRSV, thereby inhibiting PRRSV infection. Together, our study reveals the antiviral function of PDCD4 and the viral strategy to antagonize PDCD4. These results will contribute to our understanding of the immune evasion strategies employed by PRRSV and offer valuable insights for developing new antiviral targets.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) infection results in major economic losses in the global swine industry and is difficult to control effectively. Here, using a quantitative proteomics screen, we identified programmed cell death 4 (PDCD4) as a host protein targeted for proteasomal degradation by PRRSV. We demonstrated that PDCD4 restricts PRRSV replication by interacting with eukaryotic translation initiation factor 4A, which is required for translation initiation in the viral 5'-untranslated region. Additionally, four sites within two MA3 domains of PDCD4 are identified to be responsible for its antiviral function. Conversely, PRRSV nonstructural protein 9 promotes PDCD4 proteasomal degradation in the cytoplasm by activating the Akt-mTOR-S6K1 pathway, thus weakening the anti-PRRSV function. Our work unveils PDCD4 as a previously unrecognized host restriction factor for PRRSV and reveals that PRRSV develops countermeasures to overcome PDCD4. This will provide new insights into virus-host interactions and the development of new antiviral targets.

Dietary restriction plus exercise change gene expression of Cxcl12 abundant reticular cells in female mice.

INTRODUCTION: Low energy availability due to excessive exercise lowers bone mass and impairs various physiological functions, including immunity and hematopoiesis. We focused on Cxcl12 abundant reticular (CAR) cells, which are bone marrow mesenchymal stem cells and are essential for the maintenance of hematopoietic and immune cells in bone marrow. We examine the functional changes in CAR cells resulting from dietary restriction combined with exercise. MATERIALS AND METHODS: Five-week-old wild-type female mice were divided into an ad libitum group (CON), a 60% dietary restriction group (DR), an ad libitum with exercise group (CON + ex), and a 60% dietary restriction with exercise group (DR + ex). Blood parameters, bone structure parameters, and bone marrow fat volume were evaluated after 5 weeks. In addition, bone marrow CAR cells were isolated by cell sorting and analyzed for gene expression by RT-qPCR. RESULTS: Bone mineral density (BMD) was significantly decreased in DR and DR + ex compared to CON and CON + ex. Especially, cortical bone mass and thickness were significantly decreased in DR and DR + ex groups, whereas trabecular bone mass was significantly increased. Bone marrow fat volume was significantly increased in DR and DR + ex groups compared to CON and CON + ex. The number of leukocytes in the blood was significantly decreased in the DR + ex group compared to the other three groups. RT-qPCR showed a significant decrease in gene expression of both Foxc1 and Runx2 in CAR cells of the DR + ex group compared to CON. CONCLUSION: Dietary restriction combined with exercise promotes CAR cell differentiation into bone marrow adipocyte and suppresses osteoblast differentiation.

Ratiometric CRISPR/Cas12a-Triggered CHA System Coupling with the MSRE to Detect Site-Specific DNA Methylation.

The precise determination of DNA methylation at specific sites is critical for the timely detection of cancer, as DNA methylation is closely associated with the initiation and progression of cancer. Herein, a novel ratiometric fluorescence method based on the methylation-sensitive restriction enzyme (MSRE), CRISPR/Cas12a, and catalytic hairpin assembly (CHA) amplification were developed to detect site-specific methylation with high sensitivity and specificity. In detail, AciI, one of the commonly used MSREs, was employed to distinguish the methylated target from nonmethylated targets. The CRISPR/Cas12a system was utilized to recognize the site-specific target. In this process, the protospacer adjacent motif and crRNA-dependent identification, the single-base resolution of Cas12a, can effectively ensure detection specificity. The trans-cleavage ability of Cas12a can convert one target into abundant activators and can then trigger the CHA reaction, leading to the accomplishment of cascaded signal amplification. Moreover, with the structural change of the hairpin probe during CHA, two labeled dyes can be spatially separated, generating a change of the Förster resonance energy transfer signal. In general, the proposed strategy of tandem CHA after the CRISPR/Cas12a reaction not only avoids the generation of false-positive signals caused by the target-similar nucleic acid but can also improve the sensitivity. The use of ratiometric fluorescence can eradicate environmental effects by self-calibration. Consequently, the proposed approach had a detection limit of 2.02 fM. This approach could distinguish between colorectal cancer and precancerous tissue, as well as between colorectal patients and healthy people. Therefore, the developed method can serve as an excellent site-specific methylation detection tool, which is promising for biological and disease studies.

Acute hypoalgesic, neurophysiological and perceptual responses to low-load blood flow restriction exercise and high-load resistance exercise.

This study compared the acute hypoalgesic and neurophysiological responses to low-load resistance exercise with and without blood flow restriction (BFR), and free-flow, high-load exercise. Participants performed four experimental conditions where they completed baseline measures of pain pressure threshold (PPT), maximum voluntary force (MVF) with peripheral nerve stimulation to determine central and peripheral fatigue. Corticospinal excitability (CSE), corticospinal inhibition and short interval intracortical inhibition (SICI) were estimated with transcranial magnetic stimulation. Participants then performed low-load leg press exercise at 30% of one-repetition maximum (LL); low-load leg press with BFR at 40% (BFR40) or 80% (BFR80) of limb occlusion pressure; or high-load leg press of four sets of 10 repetitions at 70% one-repetition maximum (HL). Measurements were repeated at 5, 45 min and 24 h post-exercise. There were no differences in CSE or SICI between conditions (all P > 0.05); however, corticospinal inhibition was reduced to a greater extent (11%-14%) in all low-load conditions compared to HL (P < 0.005). PPTs were 12%-16% greater at 5 min post-exercise in BFR40, BFR80 and HL compared to LL (P ≤ 0.016). Neuromuscular fatigue displayed no clear difference in the magnitude or time course between conditions (all P > 0.05). In summary, low-load BFR resistance exercise does not induce different acute neurophysiological responses to low-load, free-flow exercise but it does promote a greater degree of hypoalgesia and reduces corticospinal inhibition more than high-load exercise, making it a useful rehabilitation tool. The changes in neurophysiology following exercise were not related to changes in PPT.

The dynamic responses of mood and sleep physiology to chronic sleep restriction and subsequent recovery sleep.

Healthy sleep of sufficient duration preserves mood and disturbed sleep is a risk factor for a range of psychiatric disorders. As adults commonly experience chronic sleep restriction (SR), an enhanced understanding of the dynamic relationship between sleep and mood is needed, including whether susceptibility to SR-induced mood disturbance differs between sexes. To address these gaps, data from N=221 healthy adults who completed one of two multi-day laboratory studies with identical 9-day SR protocols were analyzed. Participants randomized to the SR (n=205) condition underwent 5 nights of SR to 4 h time-in-bed and were then randomized to one of seven sleep doses that ranged from 0 h to 12 h in 2 h increments; participants randomized to the control (n=16) condition received 10 h time-in-bed on all study nights. The Profile of Mood States (POMS) was used to assess mood every 2 h during wakefulness and markers of sleep homeostasis (EEG slow-wave activity) were derived via polysomnography. Mood progressively deteriorated across SR with marked disturbances in somatic mood components. Altered sleep physiology contributed to mood disturbance whereby increased EEG slow-wave activity was associated with increased POMS Total Mood Disturbance scores, a finding specific to males. Mood was restored in a dose-response fashion where improvements were greater with longer sleep doses. These findings suggest that when lifestyle and environmental factors are inhibited in the laboratory, the affective consequences of chronic sleep loss are primarily somatic mood disturbances. Altered sleep homeostasis may contribute to mood disturbance, yet sleep-dependent mechanisms may be sex-specific.

Comparison of Blood Flow Restriction Interventions to Standard Rehabilitation After an Anterior Cruciate Ligament Injury: A Systematic Review.

BACKGROUND: Blood flow restriction training (BFR-t) data are heterogeneous. It is unclear whether rehabilitation with BFR-t after an anterior cruciate ligament (ACL) injury is more effective in improving muscle strength and muscle size than standard rehabilitation. PURPOSE: To review outcomes after an ACL injury and subsequent reconstruction in studies comparing rehabilitation with and without BFR-t. STUDY DESIGN: Systematic review. Level of evidence, 3. METHODS: A search of English-language human clinical studies published in the past 20 years (2002-2022) was carried out in 5 health sciences databases, involving participants aged 18-65 undergoing rehabilitation for an ACL injury. Outcomes associated with muscle strength, muscle size, and knee-specific patient-reported outcome measures (PROMs) were extracted from studies meeting inclusion criteria and compared. RESULTS: The literature search identified 279 studies, of which 5 met the selection criteria. Two studies suggested that BFR-t rehabilitation after an ACL injury improved knee or thigh muscle strength and muscle size compared with rehabilitation consisting of comparable and higher load resistance training, with two studies suggesting the opposite. The single study measuring PROMs showed improvement compared to traditional rehabilitation, with no difference in muscle strength or size. CONCLUSION: BFR-t after an ACL injury seems to benefit muscle strength, muscle size, and PROM scores compared with standard rehabilitation alone. However, only 1 large study included all these outcomes, which has yet to be replicated in other settings. Further studies utilizing similar methods with a common set of outcome measures are required to confirm the effects of BFR-t on ACL rehabilitation.

CircTHBS1 promotes trophoblast cell migration and invasion and inhibits trophoblast apoptosis by regulating miR-136-3p/IGF2R axis.

The precise molecular mechanism behind fetal growth restriction (FGR) is still unclear, although there is a strong connection between placental dysfunction, inadequate trophoblast invasion, and its etiology and pathogenesis. As a new type of non-coding RNA, circRNA has been shown to play a crucial role in the development of FGR. This investigation identified the downregulation of hsa_circ_0034533 (circTHBS1) in FGR placentas through high-sequencing analysis and confirmed this finding in 25 clinical placenta samples using qRT-PCR. Subsequent in vitro functional assays demonstrated that silencing circTHBS1 inhibited trophoblast proliferation, migration, invasion, and epithelial mesenchymal transition (EMT) progression and promoted apoptosis. Furthermore, when circTHBS1 was overexpressed, cell function experiments showed the opposite result. Analysis using fluorescence in situ hybridization revealed that circTHBS1 was primarily found in the cytoplasmic region. Through bioinformatics analysis, we anticipated the involvement of miR-136-3p and IGF2R in downstream processes, which was subsequently validated through qRT-PCR and dual-luciferase assays. Moreover, the inhibition of miR-136-3p or the overexpression of IGF2R partially reinstated proliferation, migration, and invasion abilities following the silencing of circTHBS1. In summary, the circTHBS1/miR-136-3p/IGF2R axis plays a crucial role in the progression and development of FGR, offering potential avenues for the exploration of biological indicators and treatment targets.

Hypertensive disorders of pregnancy and long-term maternal cardiovascular risk: Bridging epidemiological knowledge into personalized postpartum care and follow-up.

Cardiovascular disease (CVD) is globally the leading cause of death and disability. Sex-specific causes of female CVD are under-investigated. Pregnancy remains an underinvestigated sex-specific stress test for future CVD and a hitherto missed opportunity to initiate prevention of CVD at a young age. Population-based studies show a strong association between female CVD and hypertensive disorders of pregnancy. This association is also present after other pregnancy complications that are associated with placental dysfunction, including fetal growth restriction, preterm delivery and gestational diabetes mellitus. Few women are, however, offered systematic cardio-preventive follow-up after such pregnancy complications. These women typically seek help from the health system at first clinical symptom of CVD, which may be decades later. By this time, morbidity is established and years of preventive opportunities have been missed out. Early identification of modifiable risk factors starting postpartum followed by systematic preventive measures could improve maternal cardiovascular health trajectories, promoting healthier societies. In this non-systematic review we briefly summarize the epidemiological associations and pathophysiological hypotheses for the associations. We summarize current clinical follow-up strategies, including some proposed by international and national guidelines as well as user support groups. We address modifiable factors that may be underexploited in the postpartum period, including breastfeeding and blood pressure management. We suggest a way forward and discuss the remaining knowledge gaps and barriers for securing the best evidence-based follow-up, relative to available resources after a hypertensive pregnancy complication in order to prevent or delay onset of premature CVD.

Calorie restriction anti-hypertrophic effects are associated with improved mitochondrial content, blockage of Ca2+-induced mitochondrial damage, and lower reverse electron transport-mediated oxidative stress.

Calorie restriction is a nutritional intervention that reproducibly protects against the maladaptive consequences of cardiovascular diseases. Pathological cardiac hypertrophy leads to cellular growth, dysfunction (with mitochondrial dysregulation), and oxidative stress. The mechanisms behind the cardiovascular protective effects of calorie restriction are still under investigation. In this study, we show that this dietetic intervention prevents cardiac protein elevation, avoids fetal gene reprogramming (atrial natriuretic peptide), and blocks the increase in heart weight per tibia length index (HW/TL) seen in isoproterenol-induced cardiac hypertrophy. Our findings suggest that calorie restriction inhibits cardiac pathological growth while also lowering mitochondrial reverse electron transport-induced hydrogen peroxide formation and improving mitochondrial content. Calorie restriction also attenuated the opening of the Ca2+-induced mitochondrial permeability transition pore. We also found that calorie restriction blocked the negative correlation of antioxidant enzymes (superoxide dimutase and glutatione peroxidase activity) and HW/TL, leading to the maintenance of protein sulphydryls and glutathione levels. Given the nature of isoproterenol-induced cardiac hypertrophy, we investigated whether calorie restriction could alter cardiac beta-adrenergic sensitivity. Using isolated rat hearts in a Langendorff system, we found that calorie restricted hearts have preserved beta-adrenergic signaling. In contrast, hypertrophic hearts (treated for seven days with isoproterenol) were insensitive to beta-adrenergic activation using isoproterenol (50 nM). Despite protecting against cardiac hypertrophy, calorie restriction did not alter the lack of responsiveness to isoproterenol in isolated hearts harvested from isoproterenol-treated rats. These results suggest (through a series of mitochondrial, oxidative stress, and cardiac hemodynamic studies) that calorie restriction possesses beneficial effects against hypertrophic cardiomyopathy.

Near Infrared Light-Emitting Diodes Based on Colloidal InAs/ZnSe Core/Thick-Shell Quantum Dots.

Heavy-metal-free III-V colloidal quantum dots (QDs) exhibit promising attributes for application in optoelectronics. Among them, InAs QDs are demonstrating excellent optical performance with respect to absorption and emission in the near-infrared spectral domain. Recently, InAs QDs attained a substantial improvement in photoluminescence quantum yield, achieving 70% at a wavelength of 900 nm through the strategic overgrowth of a thick ZnSe shell atop the InAs core. In the present study, light-emitting diodes (LEDs) based on this type of InAs/ZnSe QDs are fabricated, reaching an external quantum efficiency (EQE) of 13.3%, a turn-on voltage of 1.5V, and a maximum radiance of 12 Wsr-1m-2. Importantly, the LEDs exhibit an extensive emission dynamic range, characterized by a nearly linear correlation between emission intensity and current density, which can be attributed to the efficient passivation provided by the thick ZnSe shell. The obtained results are comparable to state-of-the-art PbS QD LEDs. Furthermore, it should be stressed not only that the fabricated LEDs are fully RoHS-compliant but also that the emitting InAs QDs are prepared via a synthetic route based on a non-pyrophoric, cheap, and commercially available as precursor, namely tris(dimethylamino)-arsine.

[Functional MRI assessment of microstructural and perfusion changes in the kidneys of rats with intrauterine growth restriction]. / åŠŸèƒ½ç£å ±æŒ¯è¯„ä¼°å®«å† å‘è‚²è¿Ÿç¼“ä»”é¼ è‚¾è„å¾®è§‚ç»“æž„åŠçŒæ³¨æ”¹å˜.

OBJECTIVES: To explore the value of functional magnetic resonance imaging (MRI) techniques, including intravoxel incoherent motion (IVIM), T1 mapping, and T2 mapping, in assessing the microstructural and perfusion changes in the kidneys of rats with intrauterine growth restriction (IUGR). METHODS: An IUGR rat model was established through a low-protein diet during pregnancy. Offspring from pregnant rats on a low-protein diet were randomly divided into an IUGR 8-week group and an IUGR 12-week group, while offspring from pregnant rats on a normal diet were divided into a normal 8-week group and a normal 12-week group (n=8 for each group). The apparent diffusion coefficient (ADC), true diffusion coefficient (Dt), pseudo-diffusion coefficient (D*), perfusion fraction (f), T1 value, and T2 value of the renal cortex and medulla were compared, along with serum creatinine and blood urea nitrogen levels among the groups. RESULTS: The Dt value in the renal medulla was higher in the IUGR 12-week group than in the IUGR 8-week group, and the D* value in the renal medulla was lower in the IUGR 12-week group than in both the normal 12-week group and the IUGR 8-week group (P<0.05). The T1 value in the renal medulla was higher than in the cortex in the IUGR 8-week group, and the T1 value in the renal medulla was higher in the IUGR 12-week group than in both the IUGR 8-week group and the normal 12-week group, with the cortical T1 value in the IUGR 12-week group also being higher than that in the normal 12-week group (P<0.05). The T2 values in the renal medulla were higher than those in the cortex across all groups (P<0.05). There were no significant differences in the T2 values of either the cortex or medulla among the groups (P>0.05). There were no significant differences in serum creatinine and blood urea nitrogen levels among the groups (P>0.05). Glomerular hyperplasia and hypertrophy without significant fibrotic changes were observed in the IUGR 8-week group, whereas glomerular atrophy, cystic stenosis, and interstitial inflammatory infiltration and fibrosis were seen in the IUGR 12-week group. CONCLUSIONS: IVIM MRI can be used to assess and dynamically observe the microstructural and perfusion damage in the kidneys of IUGR rats. MRI T1 mapping can be used to evaluate kidney damage in IUGR rats, and the combination of MRI T1 mapping and T2 mapping can further differentiate renal fibrosis in IUGR rats.

Four modeling approaches to study restrictions on everyday life and social activities due to chronic diseases with consequences of suicidal behavior.

The purpose of this study was to discover the association between disability in everyday life and social activities due to chronic diseases and suicidal ideation (SI), suicidal plan (SP), and suicidal attempt (SA) from the Korea National Health and Nutrition Examination Survey (KNHANES), considering the cross-sectional design of this study, 2016-2018 dataset. Variables for finding the associated factors of SI, SP, and SA were confirmed through random forest (RF), decision tree, generalized linear model (GLM), and support vector machine (SVM), and the performance of each model is listed. A total of 17,323 (males: 7,530, females: 9793) responders from the KNHANES from 2016 to 2018 were employed for the study. The relationship between restrictions on daily life, social activities, and three stages of suicidal behaviors due to diseases were analyzed using the R function (R version 4.2.0), randomForest, ctree, glm, and ksvm. The F1-score is a measure used to evaluate the accuracy of the performance of a model, in the binary classification. The score of 1 indicates good performance, whereas a score of 0 signifies poor performance. Due to chronic diseases, disability in everyday life and social activities lead to suicide behaviors. In our study, we examined the impact of limitations in daily living and social activities on suicidal behaviors among participants. Our findings revealed that for those experiencing such limitations, the odds ratios (ORs) for SIs were 6.10 (95% CI: 3.99-9.34) for males and 2.61 (1.79-3.81) for females. SPs were 3.69 (2.36-5.78) for males and 3.94 (2.70-5.75) for females. Similarly, the odds ratios for SAs were 5.04 (2.51-10.13) for males and 2.71 (1.48-4.98) for females, indicating a significant association between these limitations and increased suicidal behaviors, with variances observed between genders. These results underscore the necessity of addressing daily living and social activity restrictions when considering mental health interventions and suicide prevention strategies. In RF, GLM, and SVM, F1-score were 0.8192, 0.6887, and 0.9687 in SA, respectively. Among the patients with chronic disease, those with sequelae, low incomes, and low levels of education had limitations in daily activities and social activities, which increased the likelihood of suicidal thoughts, planning, and attempts.

[Identification of Cervi Cornu (Cervus elaphus) and its formula granules based on PCR-RFLP].

Cervi Cornu is the ossified antler, or the base antler that falls off in the spring of the following year after the pilose antler is sawn off from Cervus elaphus or C. nippon, as a precious traditional Chinese medicine, has been recognized for its medicinal value and widely used in clinical practice. However, the origins of Cervi Cornu are miscellaneous, and Cervi Cornu is even mixed with adulterants in the market. Currently, there is a shortage of ways to identify Cervi Cornu and no standard to control the quality of Cervi Cornu. So it is valuable to develop a way to effectively identify Cervi Cornu from the adulterants. In this study, the differences in the mitochondrial barcode cytochrome b(Cytb) gene sequences of C. elaphus, C. nippon and their related species were compared and the specific single nucleotide polymorphism(SNP) sites on the Cytb sequences of Cervi Cornu were screened out. According to the screened SNPs, Cervi Cornu-specific primers dishmy-F and dishmy-R were designed. The PCR system was established and optimized, and the tolerance and feasibility of Taq polymerases and PCR systems affecting the repeatability of the PCR method were investigated. The amplification products of C. elaphus and C. nippon were digested using the restriction enzyme MseⅠ. The results showed that after electrophoresis of the product from PCR with the annealing temperature of 56 ℃ and 35 cycles, a single specific band at about 100 bp was observed for C. elaphus samples, and the product of C. elaphus samples was 60 bp shorter than that of C. nippon samples. There was no band for adulterants from other similar species such as Alces alces, Rangifer tarandus, Odocoileus virginianus, O. hemionus, Cap-reolus pygargus, Przewalskium albirostis and negative controls. The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method established in this study can quickly and accurately identify Cervi Cornu originated from C. elaphus in crude drugs, standard decoctions, and formula granules, and distinguish the origins of Cervi Cornu products, i.e., C. nippon and similar species. This study can be a reference for other studies on the quality standard of other formula granules of traditional Chinese medicines.

Thrombopoietin exerts a neuroprotective effect by inhibiting the suppression of neuronal proliferation and axonal outgrowth in intrauterine growth restriction rats.

Chronic hypoxia in utero causes intrauterine growth restriction (IUGR) of the fetus. IUGR infants are known to be at higher risk for neurodevelopmental disorders, but the mechanism is unclear. In this study, we analyzed the structure of the cerebral cortex using IUGR model rats generated through a reduced uterine perfusion pressure operation. IUGR rats exhibited thinner cerebral white matter and enlarged lateral ventricles compared with control rats. Expression of neuron cell markers, Satb2, microtubule-associated protein (MAP)-2, α-tubulin, and nestin was reduced in IUGR rats, indicating that neurons were diminished at various developmental stages in IUGR rats, from neural stem cells to mature neurons. However, there was no increase in apoptosis in IUGR rats. Cells positive for Ki67, a marker of cell proliferation, were reduced in neurons and all glial cells of IUGR rats. In primary neuron cultures, axonal elongation was impaired under hypoxic culture conditions mimicking the intrauterine environment of IUGR infants. Thus, in IUGR rats, chronic hypoxia in utero suppresses the proliferation of neurons and glial cells as well as axonal elongation, resulting in cortical thinning and enlarged lateral ventricles. Thrombopoietin (TPO), a platelet growth factor, inhibited the decrease in neuron number and promoted axon elongation in primary neurons under hypoxic conditions. Intraperitoneal administration of TPO to IUGR rats resulted in increases in the number of NeuN-positive cells and the area coverage of Satb2. In conclusion, suppression of neuronal proliferation and axonal outgrowth in IUGR rats resulted in cortical thinning and enlargement of lateral ventricles. TPO administration might be a novel therapeutic strategy for treating brain dysmaturation in IUGR infants.

Insight from Wild Yeast Isolates into the Molecular Mechanisms of Lifespan Variation Mediated by Caloric Restriction.

Caloric restriction (CR) is known to extend lifespan across different species and holds great promise for preventing human age-onset pathologies. However, two major challenges exist. First, despite extensive research, the mechanisms of lifespan extension in response to CR remain elusive. Second, genetic differences causing variations in response to CR and genetic factors contributing to variability of CR response on lifespan are largely unknown. Here, we took advantage of natural genetic variation across 46 diploid wild yeast isolates of Saccharomyces species and the lifespan variation under CR conditions to uncover the molecular factors associated with CR response types. We identified genes and metabolic pathways differentially regulated in CR-responsive versus non-responsive strains. Our analysis revealed that altered mitochondrial function and activation of GCN4-mediated environmental stress response are inevitably linked to lifespan variation in response to CR and a unique mitochondrial metabolite might be utilized as a predictive marker for CR response rate. In sum, our data suggests that the effects of CR on longevity may not be universal, even among closely related species or strains of a single species. Since mitochondrial mediated signaling pathways are evolutionarily conserved, the dissection of related genetic pathways will be relevant to understanding the mechanism by which CR elicits its longevity effect.

Association Between EEG Microarousal During Nocturnal Sleep and Next-Day Selective Attention in Mild Sleep-Restricted Healthy Undergraduates.

Purpose: To explore whether sleep electroencephalogram (EEG) microarousals of different standard durations predict daytime mood and attention performance in healthy individuals after mild sleep restriction. Participants and Methods: Sixteen (nine female) healthy college students were recruited to examine the correlations between nocturnal EEG microarousals of different standard durations (≥3 s, ≥5 s, ≥7 s, ≥9 s) under mild sleep restriction (1.5 h) and the following morning's subjective alertness, mood, sustained attention, and selective attention task performance. Results: Results revealed that mild sleep restriction significantly reduced subjective alertness and positive mood, while having no significant effect on negative mood, sustained attention and selective attention performance. The number of microarousals (≥5 s) was negatively associated with positive mood at 6:30. The number of microarousals was significantly and positively correlated with the response time difference value of disengagement component of the selective attention task at around 7:30 (≥5 s and ≥7 s) and 9:00 (≥5 s). The number of microarousals (≥7 s) was significantly and positively correlated with the inaccuracy difference value of orientation component of the selective attention task at around 9:00. Conclusion: The number of EEG microarousals during sleep in healthy adults with mild sleep restriction was significantly and negatively related to their daytime positive affect while positively associated with the deterioration of disengagement and orientation of selective attention performance, but this link is dependent on the standard duration of microarousals, test time and the type of task.

A senescence restriction point acting on chromatin integrates oncogenic signals.

We identify a senescence restriction point (SeRP) as a critical event for cells to commit to senescence. The SeRP integrates the intensity and duration of oncogenic stress, keeps a memory of previous stresses, and combines oncogenic signals acting on different pathways by modulating chromatin accessibility. Chromatin regions opened upon commitment to senescence are enriched in nucleolar-associated domains, which are gene-poor regions enriched in repeated sequences. Once committed to senescence, cells no longer depend on the initial stress signal and exhibit a characteristic transcriptome regulated by a transcription factor network that includes ETV4, RUNX1, OCT1, and MAFB. Consistent with a tumor suppressor role for this network, the levels of ETV4 and RUNX1 are very high in benign lesions of the pancreas but decrease dramatically in pancreatic ductal adenocarcinomas. The discovery of senescence commitment and its chromatin-linked regulation suggests potential strategies for reinstating tumor suppression in human cancers.

Continuous glucose monitoring as an objective measure of meal consumption in individuals with binge-spectrum eating disorders: A proof-of-concept study.

OBJECTIVE: Going extended periods of time without eating increases risk for binge eating and is a primary target of leading interventions for binge-spectrum eating disorders (B-EDs). However, existing treatments for B-EDs yield insufficient improvements in regular eating and subsequently, binge eating. These unsatisfactory clinical outcomes may result from limitations in assessment and promotion of regular eating in therapy. Detecting the absence of eating using passive sensing may improve clinical outcomes by facilitating more accurate monitoring of eating behaviours and powering just-in-time adaptive interventions. We developed an algorithm for detecting meal consumption (and extended periods without eating) using continuous glucose monitor (CGM) data and machine learning. METHOD: Adults with B-EDs (N = 22) wore CGMs and reported eating episodes on self-monitoring surveys for 2 weeks. Random forest models were run on CGM data to distinguish between eating and non-eating episodes. RESULTS: The optimal model distinguished eating and non-eating episodes with high accuracy (0.82), sensitivity (0.71), and specificity (0.94). CONCLUSIONS: These findings suggest that meal consumption and extended periods without eating can be detected from CGM data with high accuracy among individuals with B-EDs, which may improve clinical efforts to target dietary restriction and improve the field's understanding of its antecedents and consequences.