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Abstract Background Autism spectrum disorder (ASD) is heritable neurodevelopmental disorders (NDDs), but environmental risk factors have also been suggested to a play a role in its development. Prenatal, perinatal and parental factors have been associated with an increased risk of ASD in children. The aim of the present study was to explore the prenatal, perinatal, and parenting risk factors in children with autism spectrum disorder (ASD) from Beijing, China by comparing them with typically developing (TD) children. Methods A sample of 151 ASD children’s parents who from rehabilitation institutions in Beijing were enrolled in this study, and an additional 151 children from kindergartens in Beijing were recruited as a control group (child age: mean = 4.4 years). TD children were matched according to age, sex and maternal education. We explored the maternal AQ (Autism Spectrum Quotient) scores (mean:19.40-19.71, no significant difference between two groups) to referring the genetic baseline. This study evaluated 17 factors with unadjusted and adjusted analyses. Results Birth asphyxia was associated with a more than a thirteen-fold higher risk of ASD (adjusted odds ratio (AOR) = 13.42). Breastfeeding difficulties were associated with a higher risk of ASD(AOR = 3.46). Parenting influenced the risk of ASD, with low responding (LR) and harsh or neglectful parenting associated with a higher risk of ASD in offspring (AOR = 2.37 for LR, AOR = 3.42 for harsh parenting and AOR = 3.01 for neglectful parenting). Maternal fever during pregnancy was associated with a higher risk of ASD in offspring (AOR = 3.81). Conclusions Many factors were associated with ASD in offspring. Further assessment is needed to elucidate the role of modifiable environmental factors to inform prevention strategies.

The multi-physics coupled methodologies that have been widely used to analyze the complex process occurring in nuclear reactors have also been used to the R&D of numerical reactors. The advancement in the field of computer technology has helped in the development of these methodologies. Herein, we report the integration of ADPRES code and RELAP5 code into the SALOME-ICoCo framework to form a multi-physics coupling platform. The platform exploits the supervisor architecture, serial mode, mesh one-to-one correspondence and explicit coupling methods during analysis, and the uncertainty analysis tool URANIE was used. The correctness of the platform was verified through the NEACRP-L-335 benchmark. The results obtained were in accordance with the reference values. The platform could be used to accurately determine the power peak. In addition, design margins could be gained post uncertainty analysis. The initial power, inlet coolant temperature and the mass flow of assembly property significantly influence reactor safety during the rod ejections accident (REA).

Summary: Background: MRI is the routine examination to surveil the recurrence of nasopharyngeal carcinoma, but it has relatively lower sensitivity than PET/CT. We aimed to find if artificial intelligence (AI) could be competent pre-inspector for MRI radiologists and whether AI-aided MRI could perform better or even equal to PET/CT. Methods: This multicenter study enrolled 6916 patients from five hospitals between September 2009 and October 2020. A 2.5D convolutional neural network diagnostic model and a nnU-Net contouring model were developed in the training and test cohorts and used to independently predict and visualize the recurrence of patients in the internal and external validation cohorts. We evaluated the area under the ROC curve (AUC) of AI and compared AI with MRI and PET/CT in sensitivity and specificity using the McNemar test. The prospective cohort was randomized into the AI and non-AI groups, and their sensitivity and specificity were compared using the Chi-square test. Findings: The AI model achieved AUCs of 0.92 and 0.88 in the internal and external validation cohorts, corresponding to the sensitivity of 79.5% and 74.3% and specificity of 91.0% and 92.8%. It had comparable sensitivity to MRI (e.g., 74.3% vs. 74.7%, P = 0.89) but lower sensitivity than PET/CT (77.9% vs. 92.0%, P

The neural circuits regulating REM sleep are poorly understood. The authors reveal that GABAergic neurons in the rostromedial tegmental nucleus suppress the onset and maintenance of REM sleep, and that projections of these neurons to the LDT and LH mediate distinct REM sleep transitions.

Abstract Physiological rapid eye movement (REM) sleep termination is vital for initiating non-REM (NREM) sleep or arousal, whereas the suppression of excessive REM sleep is promising in treating narcolepsy. However, the neuronal mechanisms controlling REM sleep termination and keeping sleep continuation remain largely unknown. Here, we reveal a key brainstem region of GABAergic neurons in the control of both physiological REM sleep and cataplexy. Using fiber photometry and optic tetrode recording, we characterized the dorsal part of the deep mesencephalic nucleus (dDpMe) GABAergic neurons as REM relatively inactive and two different firing patterns under spontaneous sleep–wake cycles. Next, we investigated the roles of dDpMe GABAergic neuronal circuits in brain state regulation using optogenetics, RNA interference technology, and celltype-specific lesion. Physiologically, dDpMe GABAergic neurons causally suppressed REM sleep and promoted NREM sleep through the sublaterodorsal nucleus and lateral hypothalamus. In-depth studies of neural circuits revealed that sublaterodorsal nucleus glutamatergic neurons were essential for REM sleep termination by dDpMe GABAergic neurons. In addition, dDpMe GABAergic neurons efficiently suppressed cataplexy in a rodent model. Our results demonstrated that dDpMe GABAergic neurons controlled REM sleep termination along with REM/NREM transitions and represented a novel potential target to treat narcolepsy.

Summary: Background: Radiotherapy is the mainstay of treatment for nasopharyngeal carcinoma. Radiation-induced temporal lobe injury (TLI) can regress or resolve in the early phase, but it is irreversible at a later stage. However, no study has proposed a risk-based follow-up schedule for its early detection. Planning evaluation is difficult when dose-volume histogram (DVH) parameters are similar and optimization is terminated. Methods: This multicenter retrospective study included 6065 patients between 2014 and 2018. A 3D ResNet-based deep learning model was developed in training and validation cohorts and independently tested using concordance index in internal and external test cohorts. Accordingly, the patients were stratified into risk groups, and the model-predicted risks were used to develop risk-based follow-up schedules. The schedule was compared with the Radiation Therapy Oncology Group (RTOG) recommendation (every 3 months during the first 2 years and every 6 months in 3–5 years). Additionally, the model was used to evaluate plans with similar DVH parameters. Findings: Our model achieved concordance indexes of 0.831, 0.818, and 0.804, respectively, which outperformed conventional prediction models (all P

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique. Several studies have reported the effectiveness of taVNS in patients with disorders of consciousness (DOC); however, differences in the modulation paradigm have led to inconsistent treatment outcomes.Methods/designThis prospective exploratory trial will include 15 patients with a minimally conscious state (MCS) recruited according to the coma recovery scale-revised (CRS-R). Each patient will receive 5 different frequencies of taVNS (1, 10, 25, 50, and 100 Hz); sham stimulation will be used as a blank control. The order of stimulation will be randomized, and the patients’ CRS-R scores and resting electroencephalography (EEG) before and after stimulation will be recorded.DiscussionThe overall study of taVNS used in treating patients with DOC is still in the preliminary stage of exploration. Through this experiment, we aim to explore the optimal stimulation frequency parameters of taVNS for the treatment of DOC patients. Furthermore, we expect to achieve a stable improvement of consciousness in DOC patients by continuously optimizing the neuromodulation paradigm of taVNS for the treatment of DOC patients.Clinical trial registrationhttps://www.chictr.org.cn/index.aspx, identifier ChiCTR 2200063828.

Abstract Introduction The incidence of insomnia is getting higher and higher. Long-term insomnia seriously affects people’s health. Drug use is usually accompanied with adverse events. Both acupuncture and cognitive behavioral therapy for insomnia (CBT-I) have been proven to be safe and effective non-pharmacological treatments for insomnia. As the insomniacs’ bad sleep behavior and wrong cognition have not been effectively corrected, acupuncture has a quick effect, high patient compliance but unstable long-term efficacy, while CBT-I is complex, time-consuming, and expensive; additionally, patient compliance is low, and the number of trained therapists is limited, making it difficult to carry out. Therefore, this study aims to use the insomnia TCM system to construct a convenient and feasible traditional Chinese medicine e-aid cognitive behavioral therapy for insomnia (TCM-eCBT-I) for Chinese people, and combine the advantages of acupuncture and TCM-eCBT-I for maintaining long-term efficacy, and three treatments will be evaluated to provide clinicians with a more effective clinical protocol Methods and analysis This study is a single-center, open-label, randomized controlled trial. Ninety subjects will be recruited and randomly assigned to three groups: the acupuncture group, the TCM-eCBT-I group, and the acupuncture combined with TCM-eCBT-I group, in a ratio of 1:1:1. We will evaluate the Pittsburgh Sleep Quality Index (PSQI) and Dysfunctional Beliefs and Attitudes About Sleep Scale (DBAS), Insomnia Severity Index (ISI), sleep diary, Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Fatigue Scale-14 Scale (FS-14) scales. All adverse reactions will be assessed through the ADVERSE event table. All outcomes will be evaluated online at 0 weeks, 4 weeks, 8 weeks, 16 weeks, and 28weeks. Ethics and dissemination This study has been approved by the Institutional Review Board of the Affiliated Hospital of Nanjing University of Chinese Medicine (2020 NL-018-02). Informed consent will be obtained from all the subjects. The results will be shared with sleep researchers, public, and relevant academic institutions through high-impact peer-reviewed publications. Trial registration Chinese Clinical Trial Registry ChiCTR2000032960. Registered on 17 May 2020

Flowering at an appropriate time is crucial for plant development and reproduction. In Arabidopsis, the flowering process is managed by a regulatory network composed of at least 6 independent pathways. As a core protein in flowering regulation, FLOWERING LOCUS T (FT) participates in almost all these pathways. ANKYRIN REPEAT-CONTAINING PROTEIN 2A (AKR2A) was initially discovered as a 14-3-3-interacting protein. It was then found to be involved in the transportation of chloroplast outer membrane proteins and the resistance to low-temperature stress. Here, we identified an akr2a null mutant with a delayed flowering phenotype. Through the quantitative real-time PCR (qRT-PCR) and bimolecular fluorescence complementation (BiFC) assays, we demonstrated that AKR2A modulates the flowering process through its interaction with FT.

Pro-inflammatory factors may be associated with abnormalities in functional brain networks, which may be a mechanism in the pathogenesis of major depressive disorder (MDD). Electroencephalogram (EEG) microstates reflect the functioning of brain networks. However, the relationship between pro-inflammatory factors and the microstate abnormalities in patients with MDD is poorly understood. 24 MDD patients and 24 age-and sex-matched healthy controls (HC) were recruited. Montgomery-Asberg Depression Rating Scale(MADRS) were assessed. Serum (interleukin- 2(IL- 2), tumor necrosis factor-α (TNF-α) and hs-C-reactive protein (CRP)and EEG data were collected. K-means clustering was performed to characterize different microstates. For each microstate, duration, occurrence and coverage were estimated. Four microstates (e.g. A, B, C, D) were characterized, MDD group showed lower duration, occurrence and coverage of microstate B and microstate D, while higher duration of microstate A and microstate C and levels of IL-2, TNF-α, hs-CRP than HC group. The duration, occurrence and coverage of microstate D were negatively correlated with levels of pro-inflammatory factors (IL-2, TNF- α and hs- CRP) (all P

BackgroundAcupuncture is widely used as adjuvant therapy for major depressive disorder (MDD). There is robust evidence that inflammation is closely associated with MDD. To date, only a few numbers of studies have investigated the potential relationship between acupuncture and the change of inflammatory biomarkers in patients with MDD. Additionally, the results are inconsistent among studies. The current study aims to provide a comprehensive, systematic review of the association between acupuncture and changes in peripheral inflammation of patients with MDD, and clarify the alterations of inflammatory cytokines before and after acupuncture treatment by meta-analysis.Methods and analysisThis study will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible randomized controlled trials (RCTs) reporting acupuncture, with inflammatory cytokines as the outcome measured before and after intervention in patients with MDD, were searched in electronic databases, such as PubMed, Embase, Cochrane, SINOMED, Wanfang, China national knowledge infrastructure (CNKI), and Chongqing VIP (CQVIP). Primary outcomes of interest will be validated to measure the levels of inflammatory cytokines before and after acupuncture treatment in patients with MDD.DiscussionAcupuncture can drive anti-inflammatory effects, as well as symptom changes in MDD, which may represent a viable, multi-faceted treatment approach in MDD.Systematic review registration[PROSPERO], identifier [CRD42021289207 on 04 December 2021].

BackgroundSince 2011, three large-scale genome-wide association studies (GWAS) have confirmed that the CD2AP rs9349407 polymorphism is significantly connected with Alzheimer’s disease (AD) in individuals of European descent. Subsequently, this association has been replicated in European populations, but is unclear whether it can be replicated in Chinese. Recently, the correlation between rs9349407 and AD in the Chinese population has become a research hotspot.ObjectiveTo explore the association between rs9349407 polymorphism and AD in the Chinese population.Materials and methodsFirstly, based on the exclusion and inclusion criteria, we selected 11 independent studies from 8 articles exploring the correlation between rs9349407 variation and AD in Chinese. Secondly, we conducted a meta-analysis based on fixed and random effect models and conducted a heterogeneity test. Thirdly, we used the additive model, dominant model, and recessive model for subgroup analysis.ResultsWe demonstrated that the CD2AP rs9349407 polymorphism increases AD susceptibility in Chinese populations (OR = 1.33, 95% CI = 1.08–1.64, P = 7.45E-03), which is consistent with the effect observed in Caucasian populations. Additionally, subgroup analysis showed that rs9349407 under the additive model (GG + CC vs. GC, OR = 0.76, 95% CI = 0.61–0.97, P = 2.04E-02) and dominant model (GG + GC vs. CC, OR = 0.49, 95% CI = 0.32–0.74, P = 8.51E-04) were also significantly correlated with AD susceptibility, but not under the recessive model (GG vs. GC + CC, OR = 0.77, 95% CI = 0.58–1.03, P = 7.44E-02).ConclusionThese existing data suggest that rs9349307 is significantly correlated with the susceptibility to AD in the Chinese population, but future studies with large samples are needed to confirm our findings.

BackgroundCOVID-19 was first reported in 2019, and the Chinese government immediately carried out stringent and effective control measures in response to the epidemic. ObjectiveNonpharmaceutical interventions (NPIs) may have impacted incidences of other infectious diseases as well. Potential explanations underlying this reduction, however, are not clear. Hence, in this study, we aim to study the influence of the COVID-19 prevention policies on other infectious diseases (mainly class B infectious diseases) in China. MethodsTime series data sets between 2017 and 2021 for 23 notifiable infectious diseases were extracted from public data sets from the National Health Commission of the People’s Republic of China. Several indices (peak and trough amplitudes, infection selectivity, preferred time to outbreak, oscillatory strength) of each infectious disease were calculated before and after the COVID-19 outbreak. ResultsWe found that the prevention and control policies for COVID-19 had a strong, significant reduction effect on outbreaks of other infectious diseases. A clear event-related trough (ERT) was observed after the outbreak of COVID-19 under the strict control policies, and its decreasing amplitude is related to the infection selectivity and preferred outbreak time of the disease before COVID-19. We also calculated the oscillatory strength before and after the COVID-19 outbreak and found that it was significantly stronger before the COVID-19 outbreak and does not correlate with the trough amplitude. ConclusionsOur results directly demonstrate that prevention policies for COVID-19 have immediate additional benefits for controlling most class B infectious diseases, and several factors (infection selectivity, preferred outbreak time) may have contributed to the reduction in outbreaks. This study may guide the implementation of nonpharmaceutical interventions to control a wider range of infectious diseases.

Increasing evidence has revealed that the rostromedial tegmental area (RMTg) mediates many behaviors, including sleep and addiction. However, presynaptic patterns governing the activity of γ-aminobutyric acid-releasing (GABAergic) neurons, the main neuronal type in the RMTg, have not been defined. Here, we used cell-type-specific retrograde trans-synaptic rabies viruses to map and quantify the monosynaptic afferents to RMTg GABAergic neurons in mouse whole brains. We identified 71 ascending projection brain regions. Sixty-eight percent of the input neurons arise from the ipsilateral and 32% from the contralateral areas of the brain. The first three strongest projection regions were the ipsilateral lateral hypothalamus, zone incerta, and contralateral pontine reticular nucleus. Immunohistochemistry imaging showed that the input neurons in the dorsal raphe, laterodorsal tegmentum, and dorsal part of zone incerta were colocalized with serotoninergic, cholinergic, and neuronal nitric oxide synthetase-expressing neurons, respectively. However, in the lateral hypothalamus, a few input neurons innervating RMTg GABAergic neurons colocalized orexinergic neurons but lacked colocalization of melanin-concentrating hormone neurons. Our findings provide anatomical evidence to understand how RMTg GABAergic neurons integrate diverse information to exert varied functions.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective for treating major depressive disorder (MDD). We aimed to explore the modulating effect of prolonged longitudinal taVNS on the striatal subregions’ functional connectivity (FC) in MDD patients. Methods: Sixteen MDD patients were enrolled and treated with taVNS for 8 weeks. Sixteen healthy control subjects (HCs) were recruited without intervention. The resting-state FC (rsFC) based on striatal subregion seed points and the Hamilton Depression Scale (HAMD) were evaluated in the MDD patients and HCs at baseline and after 8 weeks. A two-way ANCOVA test was performed on each rsFC metric to obtain the (group-by-time) interactions. Results: The rsFC values between the left ventral caudate (vCa) and right ventral prefrontal cortex (vPFC), and between the right nucleus accumbens (NAc) and right dorsal medial prefrontal cortex (dmPFC) and ventrolateral prefrontal cortex (vlPFC) are lower in the MDD patients compared to the HCs at baseline, and increase following taVNS; the rsFC values between the left vCa and right, superior occipital gyrus (SOG), and between the left dorsal caudate (dCa) and right cuneus are higher in MDD patients and decrease following taVNS. Conclusions: Prolonged longitudinal taVNS can modulate the striatum rsFC with the prefrontal cortex, occipital cortex, temporal cortex, and intra-striatum, and these changes partly underlie any symptomatic improvements. The results indicate that prolonged longitudinal taVNS may produce beneficial treatment effects by modulating the cortical striatum circuitry in patients with MDD.

China’s desert steppe is the transition zone between the grasslands in central China and the arid desert. Ecological security in this region has long been a subject of debate, both in the local and academic communities. Heavy metals and other pollutants are readily released during industrial production, combustion, and transportation, aggravating the vulnerability of the desert steppes. To understand the impact of industrial activiteis on the heavy metal content of dust fall in the desert steppe, a total of 37 dust fall samples were collected over 90 days. An inductively-coupled plasma mass spectrometer (NexION 350X) was used to measure the concentration of heavy metals Cu, Cd, Cr, Pb, Mn, Co, and Zn in the dust. Using comprehensive pollution index and multivariate statistical analysis methods, we explored the characteristics and sources of heavy metal pollution. We also quantitatively assessed the carcinogenic risks of heavy metals resulting from dust reduction with the help of health risk assessment models. The heavy metals’ comprehensive pollution index values in the study area’s dust fall were ranked as follows: Zn > Cd > Pb > Mn > Cu > Co > Cr. Among these, Zn, Cd, and Pb were significant pollution factors in the study area, and were affected by industrial production and transportation. The high pollution index was concentrated in the north of the research industrial park and on both sides of a highway. The seven heavy metals’ total non-carcinogenic risk index (HI) values were ranked as follows: Mn > Co > Pb > Zn > Cr > Cu > Cd (only the HI of Mn was greater than one). Excluding Mn, the non-carcinogenic and carcinogenic risk index values of the other six heavy metals were within acceptable ranges. Previous studies have also shown that industrial transportation and production have had a significant impact on the heavy metal content of dust fall in the desert steppe.

Background: The role of soluble interleukin-1 receptor type 2 (sIL-1R2) in acute myocardial infarction (AMI) remains undocumented. In the present study, we aimed to evaluate the possible associations of sIL-1R2 with left ventricular (LV) function, remodeling and future clinical events in the setting of AMI. Methods: Circulating sIL-1R2 levels were quantified after percutaneous coronary intervention (PCI) on day 1 of hospital admission for 204 AMI patients, and upon enrollment of 204 healthy controls. Echocardiography was conducted in the acute phase and at 12-month follow-up. Adverse clinical events were registered after 12 months. Results: Circulating sIL-1R2 levels were significantly higher in AMI patients than in healthy controls (medians respectively 6652.81 pg/mL, 3799.13 pg/mL, p < 0.0001). AMI patients with sIL-1R2 levels less than the median had a larger proportion of worsened LV ejection fraction [a decrease in LV ejection fraction (LVEF) of more than 10% units] and reduced LVEF (a final LVEF

Abstract. Objective:. This study was performed to elucidate the clinical and epidemiological characteristics of vitiligo patients of different ages in Northwest China. Methods:. We retrospectively reviewed the case records and questionnaires of all patients diagnosed with vitiligo, who visited People's Hospital of Xinjiang Uygur Autonomous Region from May 2016 to December 2017. The clinical and epidemiological characteristics of these patients were analyzed by Pearson's χ2 test and Fisher's exact test. Results:. In total, we collected data of 571 vitiligo patients with age of 32.9 ± 16.4 years. The prevalence of segmental vitiligo in children and adolescents ≤19 years old (24/175[13.7%]) was higher than that in adults aged from 20-59 years (23/370[6.2%]) and advanced patients aged ≥60 years (1/26[3.8%]) (P = 0.020). The prevalence of progressive vitiligo was higher in children and adolescents ≤19 years (72/175[41.1%]) and adults from 20–59 years (141/370[38.1%) than in patients ≥60 years (5/26[19.2%]) (P = 0.063). Children and adolescents ≤19 years with vitiligo had a higher rate of a family history of vitiligo (20/175[11.4%]) than adults (20/370[5.4%]) and advanced age (1/26[3.8%]) (P = 0.031). Conclusions:. This study provides clinical evidence that vitiligo at different ages has different characteristics, mainly regarding an increased incidence of segmental vitiligo, a higher prevalence of atopic dermatitis and halo nevus, and a more common positive family history among children and adolescent patients.

An in-depth study of the phylogeny and taxonomy of the corticioid genus Phlebiopsis (Phanerochaetaceae) was conducted. Phylogenetic analyses of the ITS1-5.8S-ITS2 and nrLSU sequences demonstrated that Phlebiopsis is a strongly supported clade which is distinct from its sister clades of Phaeophlebiopsis, Hapalopilus, and Rhizochaete. Two genera, Australohydnum and Hjortstamia, are reduced to synonyms under Phlebiopsis as generic type species A. griseofuscescens and H. friesii, respectively, are embedded in the Phlebiopsis clade. Twenty-four lineages are resolved in the ITS phylogenetic tree of Phlebiopsis, including six new taxa, viz. P. albescens, P. brunnea, P. cylindrospora, P. magnicystidiata, P. membranacea and P. sinensis, from Sri Lanka and China. Five new combinations, viz. Phaeophlebiopsis mussooriensis, Phlebiopsis bambusicola, P. dregeana, P. griseofuscescens and P. novae-granatae, are proposed. Phlebiopsis crassa is a morphological species complex with three distinct lineages. Phlebiopsis lamprocystidiata is determined to be a later synonym of P. darjeelingensis. The new taxa are described, illustrated, and compared and contrasted to morphologically similar species. An emended description of Phlebiopsis is provided along with an identification key to 27 accepted species.

Abstract Peptides have great potential as therapeutic agents, however, their clinic applications are severely hampered by their instability and short circulation half-life. Zero-order release carriers could not only extend the circulation lifetime of peptides, but also maintain the plasma drug level constant, and thus maximize their therapeutic efficacy and minimize their toxic effect. Here using PEGylated salmon calcitonin (PEG-sCT)/tannic acid (TA) film as an example, we demonstrated that hydrogen-bonded layer-by-layer films of a PEGylated peptide and a polyphenol could be a platform for zero-order peptide release. The films were fabricated under mild conditions. The second component, TA, is a natural product and presents potential therapeutic activities itself. Unlike common carriers, the new carrier releases the peptide via gradual disintegration of the film because of its dynamic nature. The release of PEG-sCT follows a perfect zero-order kinetics without initial burst release. In addition the release rate could be tuned via external stimuli, such as pH and temperature. When implanted in rats, the films could remain the plasma level of PEG-sCT constant over an extended period. Accordingly, the serum calcium level was reduced and maintained constant over the same period, suggesting an improved therapeutic efficacy of the released drug.

Environmental stresses are major constraints that limit the leaf productivity and quality of mulberry. LncRNAs have emerged as important regulators in response to biotic and abiotic stresses in plants. However, the functions and mechanisms of most lncRNAs remain largely unknown. A novel lncRNA designated as MuLnc1 was found to be cleaved by mul-miR3954 and produce secondary siRNAs in a 21 nt phase in mulberry. It was demonstrated that one of the siRNAs produced, si161579, can silence the expression of the calmodulin-like protein gene CML27 of mulberry (MuCML27). When MuCML27 was heterologously expressed in Arabidopsis, the transgenic plants exhibited enhanced resistance to Botrytis cinerea and Pseudomonas syringae pv tomato DC3000. In addition, the transgenic MuCML27-overexpressing Arabidopsis plants are more tolerant to salt and drought stresses. Furthermore, the network of mul-miR3954-MuLnc1-siRNAs-mRNAs was modeled to elucidate the interaction between lncRNAs and sRNAs with mRNAs. All of these, taken together, suggest that MuLnc1 was associated with environmental stress in mulberry and may be considered as a potential genetic improvement target gene of mulberry. The information provided may shed light on the complicated gene expression regulatory mechanisms in mulberry stress responses.

The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the ventral tegmental area, projects to the midbrain dopaminergic system, dorsal raphe nucleus, locus coeruleus, and other regions. Whether the RMTg is involved in sleep-wake regulation is unknown. In the present study, pharmacogenetic activation of rat RMTg neurons promoted non-rapid eye movement (NREM) sleep with increased slow-wave activity (SWA). Conversely, rats after neurotoxic lesions of 8 or 16 days showed decreased NREM sleep with reduced SWA at lights on. The reduced SWA persisted at least 25 days after lesions. Similarly, pharmacological and pharmacogenetic inactivation of rat RMTg neurons decreased NREM sleep. Electrophysiological experiments combined with optogenetics showed a direct inhibitory connection between the terminals of RMTg neurons and midbrain dopaminergic neurons. The bidirectional effects of the RMTg on the sleep-wake cycle were mimicked by the modulation of ventral tegmental area (VTA)/substantia nigra compacta (SNc) dopaminergic neuronal activity using a pharmacogenetic approach. Furthermore, during the 2-hour recovery period following 6-hour sleep deprivation, the amount of NREM sleep in both the lesion and control rats was significantly increased compared with baseline levels; however, only the control rats showed a significant increase in SWA compared with baseline levels. Collectively, our findings reveal an essential role of the RMTg in the promotion of NREM sleep and homeostatic regulation.

Biotic stresses are major constraints limiting the leaf quality and productivity of mulberry. MLX56 is a unique chitin-binding protein isolated from Shin-Ichinose (Morus alba) latex that displays toxicity against lepidopteran caterpillars. In this study, the full-length cDNA encoding MLX56 was isolated from Husang 32 (M. multicaulis) and designated HMLX56. Amino acid sequence analysis and protein modeling of three MLX56 proteins showed that they were highly conserved among Morus species. Tissue expression pattern analysis showed that the HMLX56 gene was strongly expressed in mulberry bark and leaves but only slightly expressed in fruits. In addition, analysis of GUS expression indicated that the promoter of HMLX56 showed higher transcriptional activity along the vascular strands, and its activity can be regulated by various environmental factors. Like the MLX56 protein from M. alba, the HMLX56 protein showed toxicity to Plutella xylostella. Moreover, when the HMLX56 gene was ectopically expressed in Arabidopsis, the transgenic plants showed enhanced resistance to aphids, the fungal pathogen Botrytis cinerea and the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Our data suggest that the HMLX56 protein has a lectin-like molecular structure consisting of two hevein-like chitin-binding domains which provide not only chitin-binding activities but also other mechanisms of defense. The information provided here improves our understanding of the potential functions and defense mechanisms of MLX56 proteins, enabling in-depth functional analysis of latex exudates and perhaps facilitating mulberry genetic improvement in the future.

A series of 1H-2,3-dihydroperimidine derivatives was designed, synthesized, and evaluated as a new class of inhibitors of protein tyrosine phosphatase 1B (PTP1B) with IC50 values in the micromolar range. Compounds 46 and 49 showed submicromolar inhibitory activity against PTP1B, and good selectivity (3.48-fold and 2.10-fold respectively) over T-cell protein tyrosine phosphatases (TCPTP). These results have provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.

This paper aims to clarify the effect of steel fiber on the flexural toughness of the high performance concrete containing fly ash and nano-SiO2. The flexural toughness was evaluated by two methods, which are based on ASTM C1018 and DBV-1998, respectively. By means of three-point bending method, the flexural toughness indices, variation coefficients of bearing capacity, deformation energy, and equivalent flexural strength of the specimen were measured, respectively, and the relational curves between the vertical load and the midspan deflection (PV-δ) were obtained. The results indicate that steel fiber has great effect on the flexural toughness parameters and relational curves (PV-δ) of the three-point bending beam specimen. When the content of steel fiber increases from 0.5% to 2%, the flexural toughness parameters increase gradually and the curves are becoming plumper and plumper with the increase of steel fiber content, respectively. However these flexural toughness parameters begin to decrease and the curves become thinner and thinner after the steel fiber content exceeds 2%. It seems that the contribution of steel fiber to the improvement of flexural toughness of the high performance concrete containing fly ash and nano-SiO2 is well performed only when the steel fiber content is less than 2%.

A novel electrochemical method is described for the direct oxidative C--N coupling of tetrahydroquinolines and azoles, enabling the synthesis of dihydroquinoline derivatives under mild reaction conditions. In this approach, 2,2,6,6-tetramethylpiperidinooxy (TEMPO) serves as a redox mediator, and NaI not only acts as an electrolyte but also functions as an iodine mediator. The reaction exhibits good functional group tolerance and high atomic economy, resulting in moderate to excellent yields of the desired dihydroquinoline derivatives. Furthermore, by adjusting the reaction conditions, the corresponding quinoline derivatives can also be selectively obtained. [ABSTRACT FROM AUTHOR]