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Abstract Background Transgender and gender diverse individuals often face structural barriers to health care because of their gender minority status. The aim of this study was to examine the association between gender minority stress and access to specific health care services among transgender women and transfeminine people in China. Methods This multicenter cross-sectional study recruited participants between January 1st and June 30th 2020. Eligible participants were 18 years or older, assigned male at birth, not currently identifying as male, and living in China. Gender minority stress was measured using 45 items adapted from validated subscales. We examined access to health care services and interventions relevant to transgender and gender diverse people, including gender affirming interventions (hormones, surgeries), human immunodeficiency virus (HIV) and sexually transmitted infections (STIs) testing, pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP). Multivariable regression was used to measure correlations between gender minority stress and access to health care service. Results Three hundred and twenty-four people completed a survey and data from 277 (85.5%) people were analyzed. The mean age was 29 years old (standard deviation [SD] = 8). Participants used hormones (118/277, 42.6%), gender affirming surgery (26/277, 9.4%), HIV testing (220/277, 79.4%), STI testing (132/277, 47.7%), PrEP (24/276, 8.7%), and PEP (29/267, 10.9%). Using gender affirming hormones was associated with higher levels of discrimination (adjusted odds ratio [aOR] 1.41, 95% confidence interval [CI] 1.17–1.70) and internalized transphobia (aOR 1.06, 95%CI 1.00–1.12). STI testing was associated with lower levels of internalized transphobia (aOR 0.91, 95%CI 0.84–0.98). Conclusions Our data suggest that gender minority stress is closely related to using health services. Stigma reduction interventions and gender-affirming medical support are needed to improve transgender health.

Cathepsin B (Cat B) is a lysosomal cysteine protease that plays an essential role in cellular metabolism. Cat B is overexpressed in lung cancer cells. Fluorescence imaging techniques have been developed for measuring intracellular Cat B levels, which, however, suffers from limited penetration depth and interferences from autofluorescence background. To resolve these technical difficulties, we designed a novel Cat B biosensor detected by hyperpolarized xenon magnetic resonance imaging. It consists of a cryptophane cage as a 129Xe NMR reporter and an amide bond as a Cat B-specific cleavable group. When the biosensor interacts with Cat B, the cleavage of amide bond leads to changes in 129Xe chemical shift. Combing with hyperpolarization-chemical exchange saturation transfer (Hyper-CEST), our biosensor provides a novel method for responsive detection of Cat B.

BackgroundTourette syndrome (TS) is a developmental neuropsychiatric disorder. Behavior therapy, especially habit reversal training (HRT), has gradually become regarded as one of the core therapies for TS. Mindfulness approaches can improve psychological adjustment and reduce stress and anxiety, suggesting potential benefits when incorporated into behavior therapy. To improve the efficacy of HRT, we combined it with mindfulness, an approach named mindfulness-based habitual reversal training (MHRT). The aim of this protocol is to investigate the efficacy and neural mechanisms of MHRT for TS.Methods/designWe will perform a randomized control trial (RCT) to evaluate the efficacy and neural mechanisms of MHRT. The sample will include 160 participants (including 120 patients with TS and 40 healthy controls). The patient sample will be randomly divided into three groups exposed to three different types of training: MHRT, HRT, and psychoeducation and supportive therapy (PST). Participants will be assessed and undergo resting-state fMRI scans at baseline and at the end of the 12-week training. The Yale Global Tic Severity Scale (YGTSS) and Premonitory Urge for Tic Scale (PUTS) will be used to assess the severity of tic symptoms and premonitory urges. The primary outcomes are change scores on the YGTSS and other assessments from baseline and the end of the training. The secondary outcomes are the neural correlates of these trainings among these groups based on graph theory, which is used to characterize brain functional connectivity networks. The default mode network (DMN) and the salience network (SN) will be assessed (which have been associated with mindfulness as well as the generation of tic symptoms) by network parameters, including clustering coefficients and shortest path lengths. Changes in these network parameters will be regarded as the neural correlates of the behavioral training.DiscussionMHRT was newly developed for the treatment of TS. MHRT may lead to greater reductions in tic severity than traditional HRT. Changes in the network parameters of the DMN and SN may show associations with the efficacy of MHRT.Clinical trial registrationhttp://www.chictr.org.cn, ChiCTR2100053077, China.

ABSTRACT: The objective of this study was to compare the immunomodulatory effects of the chicken soups prepared with the native free-range chickens and the commercial caged broilers in the immunosuppressive mice. The immunosuppressive mice model was established by the intraperitoneal injection of 100 mg of cyclophosphamide (CTX) per kg body weight. The powders of Gushi Chicken Soup (GCS), Honglashan Chicken Soup (HCS), and Cobb Broiler Soup (CBS) were prepared by high-pressure stewing followed by spray drying. The chicken soups' nutrient content and the effects of three chicken soups on the body weight, organ index, blood index, and serum cytokine and immunoglobulin contents in the immunosuppressive mice were determined. The three chicken soups promoted the recovery of immunosuppressive mice, but the expression mechanisms were different. The GCS was more effective than the HCS and CBS in restoring blood index, promoting cytokine secretion, and increasing immunoglobulin content (P < 0.05). The HCS stimulated the Th1-type immune response and promoted immunoglobulin secretion (P < 0.05), while the CBS increased the production of CD4+ and promoted the T-cell functions better than other soups (P < 0.05). Although soups from the native free-range chickens and the commercial caged broilers showed distinctly different mechanisms in promoting immunity, both could be used as potential immunomodulators.

Honokiol (HKL), a biphenolic compound, is derived from the bark of Magnolia officinalis, which is used in traditional Chinese medicine for gastrointestinal complaints. HKL has diverse pharmacological activities and has protective effects in various disease models. However, the role and mechanism of HKL in treating chronic kidney disease (CKD) remain unclear. This study was designed to investigate whether HKL can alleviate CKD and the potential mechanism by which it acts. Male Sprague-Dawley rats were fed 0.75% w/w adenine feed for 3 weeks to induce CKD. HKL was administered by gavage at a dose of 5 mg/kg/day for 4 weeks. Using a special kit, serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. To assess renal pathology, periodic acid-Schiff and Masson’s trichrome staining were conducted. Renal lipid profiles were analyzed by ultra-high-performance liquid chromatography/mass spectrometry (UHPLC/MS). The results showed that the administration of HKL reduced Scr and BUN and alleviated renal tubular atrophy and tubulointerstitial fibrosis in an adenine-induced CKD rat model. By using lipidomics, we identified 113 lipids (47 lipids in negative ion mode, 66 lipids in positive ion mode) that could be significantly reversed by HKL treatment in CKD rat kidneys. Most of these lipids belonged to the phosphatidylcholine (PC), ceramide (Cer), phosphatidylethanolamine (PE), and triacylglycerol (TAG) classes. Moreover, HKL improved fatty acid oxidation in the kidneys of CKD rats. In conclusion, this study found that HKL can protect against adenine-induced CKD, possibly through the regulation of lipid metabolism.

Yellow leaf disease (YLD) has been a major limiting factor threatening areca palm commonly known as betel palm (Areca catechu L.) plantations in Hainan, China. The YLD disease is closely associated with areca palm velarivirus 1 (APV1), which belongs to the family Closteroviridae. YLD-affected betel palms show more serious yellowing symptoms in winter than in summer based on anecdotal observations. In the present work, the underlying mechanism was investigated. We first observed that the severity of YLD symptoms was closely related with the APV1 viral titer determined by qRT-PCR and ELISA under natural conditions. To further investigate whether temperature plays a key role in APV1 accumulation, the areca palm seedlings were artificially inoculated with APV1-positive mealybugs (Ferrisia virgata) and then cultivated under controlled conditions. According to our results, the YLD symptoms severity in inoculated seedlings were closely associated with temperature, e.g., severest symptoms at low temperature (16/22 ± 2°C, night/day), severer symptoms at room temperature (24/26 ± 2°C, night/day), while moderate symptoms at high temperature (27/34 ± 2°C, night/day). The qRT-PCR and ELISA results showed that APV1 titer accumulates significantly abundant at low temperature as compared to high and room temperatures. In conclusion, this is the first report about the temperature effects on the symptoms severity of YLD and APV1 titer, which may have important implications for the epidemiology of YLD.

Constructing payments for ecosystem services (PES) for inter-basin water transfer is one of the effective means to adjust the interest relationship and promote low-carbon development in the region. The inter-basin water transfer ecological compensation policy (IWTECP) in China is a PES project facing a series of problems. To this end, we applied contingent valuation method (CVM) to examine the willingness to pay (WTP) in water-receiving area and willingness to accept (WTA) in water-source area of the eastern route of South-to-North Water Transfer Project, China. The WTP and WTA values were 206.29 RMB/(person·year) (USD 32.37/(person·year)) and 443.29 RMB/(person·year) (USD 69.55/(person·year)) respectively. Bayesian network model was employed to explore the influencing factors, it was found that educational background, per capita monthly household income and the recognition of the importance of the project to the city or the country had the greater influence on WTP, while age, per capita monthly household income and the influence of project on personal life were the most influential factors on WTA. By comparing the influencing factors of WTP and WTA, the intention preference of the respondents was discussed. Then, SWOT matrix analysis method was adopted to put forward incentive mechanism from the perspectives of internal public background and external environmental policies. Our results could provide incentive policies for target groups of consumers, improve the efficiency of ecological protection, and promote the reform of the IWTECP.

Tilia endochrysea Handel-Mazzetti 1926, distributed in the southern margin of Chinese Subtropical Zone, is the only one species in genus Tilia has dehiscent fruit. The whole chloroplast genome of T. endochrysea was 162,838 bp with 36.46% GC content, including a large single-copy (LSC) region of 91,264 bp, a small single-copy (SSC) region of 20,414 bp, and a pair of inverted repeats (IRs) of 51,160 bp. The chloroplast genome encodes 130 genes, including 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic tree shows T. endochrysea was the basal taxon in Tilia and closely related to Craigia yunnanensis (Smith et Evans 1921).

The diversity of waterbirds is threatened, and haemosporidian parasite infection is considered one of the most important causative factors. However, to date, only a few studies focusing on specific parasite species have been carried out, which cannot reflect the general patterns at the community level. To test whether the reported haemosporidian diversity in waterbirds is underestimated, we estimated the prevalence and lineage diversity of avian haemosporidian parasites in 353 waterbirds from 26 species in the Tumuji National Nature Reserve, Northeast China, as well as the host-parasite associations. According to the molecular analysis of cytochrome b (cyt b) barcode sequences, 28.3% of the birds were infected by 49 distinct parasite lineages, including 11 Plasmodium, 12 Haemoproteus, and 26 Leucocytozoon lineages, of which 39 were novel. The highest prevalence was contributed by Leucocytozoon (13.31%), followed by Plasmodium (13.03%) and Haemoproteus (4.25%), which suggested that waterbirds were infected to a lesser extent by Haemoproteus than by the other two genera. Among the most sampled birds, species belonging to Anatidae appeared to be susceptible to Leucocytozoon but resistant to Plasmodium, while Rallidae presented the opposite pattern. On the phylogenetic tree, most of the Leucocytozoon lineages detected in Anatidae clustered together and formed two well-supported clades, while lineages restricted to Gruidae were distantly related to other parasites in all three genera. SW5 was the most abundant lineage and therefore might be a major threat to waterbirds; among the hosts, the common coot harboured the highest diversity of parasite lineages and thus could act as a reservoir for potential transmission. This is the first study of avian haemosporidian infections in a wild waterbird community in Asia. Our findings have doubled the number of lineages recorded in waterbirds, broadened our understanding of host-parasite associations, and addressed the importance of studying haemosporidian infections in wild waterbird conservation.

Abstract The human oral and gut commensal microbes play vital roles in the development and maintenance of immune homeostasis, while its association with susceptibility and severity of SARS-CoV-2 infection is barely understood. In this study, we investigated the dynamics of the oral and intestinal flora before and after the clearance of SARS-CoV-2 in 53 COVID-19 patients, and then examined their microbiome alterations in comparison to 76 healthy individuals. A total of 140 throat swab samples and 81 fecal samples from these COVID-19 patients during hospitalization, and 44 throat swab samples and 32 fecal samples from sex and age-matched healthy individuals were collected and then subjected to 16S rRNA sequencing and viral load inspection. We found that SARS-CoV-2 infection was associated with alterations of the microbiome community in patients as indicated by both alpha and beta diversity indexes. Several bacterial taxa were identified related to SARS-CoV-2 infection, wherein elevated Granulicatella and Rothia mucilaginosa were found in both oral and gut microbiome. The SARS-CoV-2 viral load in those samples was also calculated to identify potential dynamics between COVID-19 and the microbiome. These findings provide a meaningful baseline for microbes in the digestive tract of COVID-19 patients and will shed light on new dimensions for disease pathophysiology, potential microbial biomarkers, and treatment strategies for COVID-19.

Abstract Background Although avian Plasmodium species are widespread and common across the globe, limited data exist on how genetically variable their populations are. Here, the hypothesis that the avian blood parasite Plasmodium relictum exhibits very low genetic diversity in its Western Palearctic transmission area (from Morocco to Sweden in the north and Transcaucasia in the east) was tested. Methods The genetic diversity of Plasmodium relictum was investigated by sequencing a portion (block 14) of the fast-evolving merozoite surface protein 1 (MSP1) gene in 75 different P. relictum infections from 36 host species. Furthermore, the full-length MSP1 sequences representing the common block 14 allele was sequenced in order to investigate if additional variation could be found outside block 14. Results The majority (72 of 75) of the sequenced infections shared the same MSP1 allele. This common allele has previously been found to be the dominant allele transmitted in Europe. Conclusion The results corroborate earlier findings derived from a limited dataset that the globally transmitted malaria parasite P. relictum exhibits very low genetic diversity in its Western Palearctic transmission area. This is likely the result of a recent introduction event or a selective sweep.

Abstract Background The worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment. Results Here, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers (PLGA-LPV@M). In the study, PLGA-LPV@M could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19 patients serum could be reduced by PLGA-LPV@M as well. In a mouse model of coronavirus infection, PLGA-LPV@M exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction. Conclusion Collectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment.

In the subcooled boiling flow under low-pressure conditions, bubble characteristic diameter is of great influence on the surface heat transfer coefficient. However, large errors are still found in calculations using traditional mechanistic models or empirical correlations, especially for wide experimental condition. In this paper, we propose a widely applicable data-driven model using artificial neural networks (ANN) to predict the bubble maximum diameter and investigate the effect of experimental conditions. After a series of analyses on structural parameters and input parameters, the ANN model is established and validated based on six available experimental databases. The result shows that the relative error is around 14%. Uncertainty analysis is carried out for the four experimental conditions and two structural conditions. The results show the measuring accuracy of pressure is one of the most sensitive parameters on the prediction of bubble maximum diameter in the subcooled boiling flow under 1.0 MPa, especially for the bubble sizes larger than 0.5 mm. According to the results of uncertainty analysis, a new correlation is proposed for coefficients C and φ, which are used to express the effect of pressure and fluid dynamic. The new correlation works well for all the experimental databases, and the error for bubble datasets of large size is also modified. Furthermore, another independent validation with a low relative error to 14% is provided to prove the accuracy of the new correlation.

PurposeStomach 36 (ST36, zusanli) is one of the important acupoints in acupuncture. Despite clinical functional magnetic resonance imaging (fMRI) studies of ST36 acupuncture, the brain activities and the neural mechanism following acupuncture at ST36 remain unclear.MethodsLiterature searches were conducted on online databases, including MEDLINE, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang database, WeiPu database, and China Biology Medicine, for task-based fMRI studies of acupuncture at ST36 in healthy subjects. Brain regions activated by ST36 acupuncture were systematically evaluated and subjected to seed-based d mapping meta-analysis. Subgroup analysis was conducted on control procedures, manual acupuncture, electrical acupuncture (EA), and acupuncture-specific activations. Meta-regression analysis was performed to explore the effects of needle retention time on brain activities following ST36 acupuncture stimulation. The activated brain regions were further decoded and mapped on large-scale functional networks to further decipher the clinical relevance of acupuncturing at ST36.ResultsA total of sixteen studies, involving a total of 401 right-handed healthy participants, that satisfied the inclusion criteria were included in the present meta-analysis. Meta-analysis showed that acupuncturing on ST36 positively activates the opercular part of the right inferior frontal gyrus (IFG.R), left superior temporal gyrus (STG.L), and right median cingulate/paracingulate gyri (MCG.R) regions. Needle retention time in an acupuncture session positively correlates with the activation of the left olfactory cortex, as shown in meta-regression analysis. Subgroup analysis revealed that EA stimulation may be a source of heterogeneity in the pooled results. Functional network mappings showed that the activated areas were mapped to the auditory network and salience network. Further functional decoding analysis showed that acupuncture on ST36 was associated with pain, secondary somatosensory, sound and language processing, and mood regulation.ConclusionAcupuncture at ST36 in healthy individuals positively activates the opercular part of IFG.R, STG.L, and MCG.R. The left olfactory cortex may exhibit positive needle retention time-dependent activities. Our findings may have clinical implications for acupuncture in analgesia, language processing, and mood disorders.Systematic Review Registrationhttps://inplasy.com/inplasy-2021-12-0035.

Tilia is a complex genus in the family Malvaceae that has high ecological and economical values. Owing to the lack of sufficient distinguishable morphological and molecular characteristics, interspecific relationships in this genus are not clear. Chloroplast (cp) genomes are small, meanwhile most angiosperms usually undergo matrilineal inheritance. Consequently, they can be used in molecular systematics and phylogenetic analyses. Here, we sequenced and assembled cp genomes from T. endochrysea, T. tomentosa, T. miqueliana, T. americana and T. cordata, and compared them with those of seven previously reported Tilia species. Similar gene contents, gene orders and GC contents existed among the 12 cp genomes, which ranged from 162,564 to 162,855 bp and encoded 113 unique genes. Abundant simple sequence repeats (119–127) and dispersed repeats (97–135) were detected in Tilia cp genomes. In total, 11 hypervariable regions were identified that could be suitable for species identification and phylogenetic studies. A phylogenetic analysis of Malvaceae based on 5 hypervariable genes (matK + ndhF + rpoB + rpoC2+ycf1) revealed that all eight subfamilies were monophyletic groups. Additionally, the genus Tilia was divided into three groups on the basis of all 521 molecular variation loci. The current study provides valuable insights into the genomic evolution of the genus Tilia.

Because of their high molecular heat conductivity, low-Prandtl number liquid metal is a promising candidate coolant for various designs of advanced nuclear systems such as liquid metal–cooled fast reactors and accelerator-driven sub-critical system (ADS). With the fast-growing computational capacity, more and more attention has been paid to applying computational fluid dynamics (CFD) methods in thermal design and safety assessment of such systems for a detailed analysis of three-dimensional thermal–hydraulic behaviors. However, numerical modeling of turbulent heat transfer for low-Prandtl number liquid metal remains a challenging task. Numerical approaches such as wall-resolved large eddy simulation (LES) or direct numerical simulation (DNS), which can provide detailed insight into the physics of the liquid metal flow and the associated heat transfer, were widely applied to investigate the turbulent heat transfer phenomenon. However, these approaches suffer from the enormous computational consumption and are hence limited only to simple geometrical configurations with low to moderate Reynolds numbers. The Reynolds-averaged Navier–Stokes (RANS) approach associated with a turbulent Prandtl number Prt accounting for the turbulent heat flux based on Reynolds analogy is still, at least in the current state in most of the circumstances, the only feasible approach for practical engineering applications. However, the conventional choice of Prt in the order of 0.9∼unity in many commercial computational fluid dynamics codes is not valid for the low-Prandtl number liquid metal. In this study, LES/DNS simulation results of a simple forced turbulent channel flow up to a friction Reynolds number Reτ of 2000 at Pr of 0.01 and 0.025 were used as references, to which the Reynolds-averaged Navier–Stokes approach with varying Prt was compared. It was found that the appropriate Prt for the RANS approach decreases with bulk Peclet number Peb and approaches a constant value of 1.5 when Peb becomes larger than 2000. Based on this calibrated relation with Peb, a new model for Prt used in the RANS approach was proposed. Validation of the proposed model was carried out with available LES/DNS results on the local temperature profile in the concentric annulus and bare rod bundle, as well as with experimental correlations on the Nusselt number in a circular tube and bare rod bundle.

While SARS-CoV-2 S protein targeting monoclonal antibodies (mAbs) are well studied, little is known about N protein-targeting mAbs. Here, Kang et al. provide the crystal structure of the N protein RNA binding domain with a mAb derived from a convalescent patient and show that it compromises the N protein-induced complement hyperactivation.

Abstract Background Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). An accurate prediction tool for endometrial receptivity (ER) is extraordinarily needed to precisely guide successful embryo implantation. We aimed to establish an RNA-Seq-based endometrial receptivity test (rsERT) tool using transcriptomic biomarkers and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with RIF. Methods This was a two-phase strategy comprising tool establishment with retrospective data and benefit evaluation with a prospective, nonrandomized controlled trial. In the first phase, rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 IVF patients with normal WOI timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n = 56; control group, n = 86). pET guided by rsERT was performed in the experimental group and conventional ET in the control group. Results The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using tenfold cross-validation. The intrauterine pregnancy rate (IPR) of the experimental group (50.0%) was significantly improved compared to that (23.7%) of the control group (RR, 2.107; 95% CI 1.159 to 3.830; P = 0.017) when transferring day-3 embryos. Although not significantly different, the IPR of the experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of the control group (RR, 1.562; 95% CI 0.898 to 2.718; P = 0.111) when transferring blastocysts. Conclusions The rsERT was developed to accurately predict the WOI period and significantly improve the pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET. Trial registration Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx

Dynamic mesh atomizers have been widely used in various fields because of their compact structure, low energy consumption, and low production costs. The finite element method is an important technique to analyze the factors affecting the atomization performance of dynamic mesh atomizers. However, at present, there is a lack of decisive solutions to the basic problems of boundary setting in terms of the simulation and vibration displacement characteristics of atomizers under different vibration modes. In this paper, two errors were found in the Vibration Analysis of a Piezoelectric Ultrasonic Atomizer to Control Atomization Rate paper written by Esteban Guerra-Bravo et al. in 2021. First, in the finite element analysis, the boundary condition of the atomizing sheet was set to be fixed, which is inconsistent with the actual support situation and seriously affects the vibration of the atomizing sheet. Second, in the simulation result, from the first mode to the third mode, the growth rate of the maximum displacement at the center of the atomizing sheet was as high as 77.12%, even up to 221.05%, which is inconsistent with the existing vibration theory. In view of these errors, in this paper, the working principle of dynamic mesh atomizers is analyzed and the vibration equation of the atomizing sheet under peripheral simple support is derived. Through comparison with the literature, it was proven that the boundary setting and vibration displacement of the atomizing sheet in the original paper are unreasonable. By measuring the atomizing rate of the atomizing sheet under different boundary conditions, it was proven that the peripheral freedom of the atomizing sheet should be greater than or equal to 1, namely, peripheral freedom or peripheral simply supported. The vibration displacement theory was used for the simulation, and the relationship between the vibration displacement and resonant frequency of the atomizing sheet under peripheral simple support was measured. It was found that with the increase in the resonance frequency, the maximum displacement of vibration modes with only nodal circles was larger than that of the other vibration modes, and the maximum displacement increased slightly with the increase in the number of nodal circles by about 0.98%.

Phosvitin (PV) from egg yolk is an excellent substrate for the production of phosphopeptides, which have a strong calcium chelating capacity and promoting calcium absorption and bone mineralization. This study investigated the effect of PV hydrolysates produced using a effective preparation method (high temperature (121°C) and mild pressure (0.1 MPa), HTMP) or HTMP pretreatment and trypsin hydrolysis combination (HTMP-PV18) on the physiology of an osteoblast MC3T3-E1 cells line. The proliferation, apoptosis, and differentiation of MC3T3-E1 cells were analyzed using the CCK-8, flow cytometry, and RT-PCR reactions, respectively. Both the HTMP-PV and HTMP-PV18 increased the proliferation, and inhibited the apoptosis of MC3T3-E1 cells significantly. The HTMP-PV increased the proliferation of MC3T3-E1 cells by 147.12 ± 2.11% and the HTMP-PV18 by 136.43 ± 4.51%. In addition, the HTMP-PV and HTMP-PV18 effectively promoted the expression of genes related to the OPG/RANKL signaling channel during cell differentiation. This indicated that both the HTMP-PV and HTMP-PV18 have the potential to promote bone mineralization by improving the proliferation and differentiation of osteoblastic cells.

Mishra, Huang et al. identify 29 linear SARS-CoV-2 epitopes that are immunoreactive with the plasma from individuals who had asymptomatic, mild, or severe SARS-CoV-2 infections. This study suggests the possibility of using these peptides to discriminate the exposure to SARS-CoV-2 and other human coronaviruses.

Dual-cooled annular fuel allows a significant increase in power density while maintaining or improving safety margins. However, the dual-cooled design brings much higher Zircaloy charge in reactor core, which could cause a great threaten of hydrogen explosion during severe accidents. Hence, an innovative fuel combined dual-cooled annular geometry and SiC cladding was proposed for the first time in this study. Capabilities of fuel design and behavior simulation were developed for this new fuel by the upgrade of FROBA-ANNULAR code. Considering characteristics of both SiC cladding and dual-cooled annular geometry, the basic fuel design was proposed and preliminary proved to be feasible. After that, a design optimization study was conducted, and the optimal values of as-fabricated plenum pressure and gas gap sizes were obtained. Finally, the performance simulation of the new fuel was carried out with the full consideration of realistic operation conditions. Results indicate that in addition to possessing advantages of both dual-cooled annular fuel and accident tolerant cladding at the same time, this innovative fuel could overcome the brittle failure issue of SiC induced by pellet-cladding interaction.

Abstract Macrophages are critical mediators of tissue homeostasis, with the function of tissue development and repair, but also in defense against pathogens. Tumor-associated macrophages (TAMs) are considered as the main component in the tumor microenvironment and play an important role in tumor initiation, growth, invasion, and metastasis. Recently, metabolic studies have revealeded specific metabolic pathways in macrophages are tightly associated with their phenotype and function. Generally, pro-inflammatory macrophages (M1) rely mainly on glycolysis and exhibit impairment of the tricarboxylic acid (TCA) cycle and mitochondrial oxidative phosphorylation (OXPHOS), whereas anti-inflammatory macrophages (M2) are more dependent on mitochondrial OXPHOS. However, accumulating evidence suggests that macrophage metabolism is not as simple as previously thought. This review discusses recent advances in immunometabolism and describes how metabolism determines macrophage phenotype and function. In addition, we describe the metabolic characteristics of TAMs as well as their therapeutic implications. Finally, we discuss recent obstacles facing this area as well as promising directions for future study.

Context The uric acid metabolism pathway is more similar in primates and humans than in rodents. However, there are no reports of using primates to establish animal models of hyperuricaemia (HUA). Objectives To establish an animal model highly related to HUA in humans. Materials and methods Inosine (75, 100 and 200 mg/kg) was intraperitoneally administered to adult male rhesus monkeys (n = 5/group). Blood samples were collected over 8 h, and serum uric acid (SUA) level was determined using commercial assay kits. XO and PNP expression in the liver and URAT1, OAT4 and ABCG2 expression in the kidneys were examined by qPCR and Western blotting to assess the effects of inosine on purine and uric acid metabolism. The validity of the acute HUA model was assessed using ulodesine, allopurinol and febuxostat. Results Inosine (200 mg/kg) effectively increased the SUA level in rhesus monkeys from 51.77 ± 14.48 at 0 h to 178.32 ± 14.47 μmol/L within 30 min and to peak levels (201.41 ± 42.73 μmol/L) at 1 h. PNP mRNA level was increased, whereas XO mRNA and protein levels in the liver were decreased by the inosine group compared with those in the control group. No changes in mRNA and protein levels of the renal uric acid transporter were observed. Ulodesine, allopurinol and febuxostat eliminated the inosine-induced elevation in SUA in tested monkeys. Conclusions An acute HUA animal model with high reproducibility was induced; it can be applied to evaluate new anti-HUA drugs in vivo and explore the disease pathogenesis.

Microfluidic devices or systems to generate recirculating flow are increasingly utilized in the fields of chemistry, biomedicine, biology, with bottlenecks in integration and miniaturization needed a breakthrough. Here, a concept for a highly integrated valve-less piezoelectric micropump generating recirculating flow (VPMGRF) is proposed, simultaneously realizing innovation in theory and method. Based on fluid inertiaand energy dissipation of vortexes, a novel double-loop tube was designed to achieve fluid flow in different directions along various paths, with the flow characteristics at different cross-sectional areas explored through computational fluid dynamics (CFD). Afterwards, as valve bodies, the double-loop tubes were connected with a piezoelectric-actuated chamber to constitute the VPMGRF, which was followed by establishing a theoretical model of the vibration, fluid dynamics, and net flow rate. Eventually, experimental results showed that VPMGRFs could generate internal recirculating flow and had a pump effect. The maximum net flow rate reached 5.19 mL/min at 8 Hz, corresponding to a vibrator amplitude of 35 μm and an output pressure amplitude of 4.27 kPa. Furthermore, the larger the characteristic length of the cross section, the greater the amplitude of the vibrators, the larger the amplitude of output pressure, and the slower the flow rate.

According to the WORLD Disabled Persons federation (WPF), there are a large number of disabled people in the world, accounting for over 400 million in the Asia-Pacific region alone. This paper discusses the application of the Internet of Things technology in the rehabilitation of special populations, aiming at achieving high allocation of resources without changing personnel allocation, realizing innovation to improve economic benefits without changing personnel allocation, and rationally optimizing resource allocation to achieve maximum. Firstly, we give an overview of the Internet of Things technology and its application, and introduce the sensor, RFID, embedded system and other technologies. Then, we discuss the application of Internet of Things technology in the rehabilitation of disabled people, from the rehabilitation needs of disabled people and the application of Internet of Things technology in the field of rehabilitation. Then, from the statistical analysis of the application of Internet of Things technology in the rehabilitation field in the past 10 years, we obtained the shortcomings of the application of Internet of Things technology in the rehabilitation field and some space for further exploration. Finally, we believe that the application of Internet of Things technology to the rehabilitation management of persons with disabilities will be a breakthrough in the rehabilitation management of persons with disabilities, and have important reference value for the rehabilitation management of persons with disabilities worldwide. We also hope that understanding, respecting, caring and helping people with disabilities will increasingly become a global consensus and action.

The inhibitory performance of imidazole [1,2-a] pyrimidine derivatives, namely, 2,4-diphenylbenzo [4,5]imidazo [1,2-a]pyrimidine (DPIP) and 2-(4-octylphenyl)-4-phenylbenzo [4,5]imidazo [1,2-a]pyrimidine (OPIP), against mild steel corrosion in 1 mol L−1 HCl solution was studied by weight loss at different temperatures, potentiodynamic polarization curves (PDP), electrochemical impedance spectroscopy (EIS), and surface analysis technology. The two corrosion inhibitors showed an outstanding inhibition performance, and the inhibition efficiency achieved 91.9% for OPIP and 90.5% for DPIP at a concentration of 0.1 mmol L−1. Electrochemical methods showed that DPIP and OPIP behaved as mixed-type inhibitors. Density function theory (DFT) and molecular dynamic simulation (MD) were approached to theoretically study the relationship of the inhibitor structure and anti-corrosion performance, which were also compatible with the weight loss and electrochemical observations.

Background: The mechanism of tumorigenicity potentially evolved in mesenchymal stem cells (MSCs) remains elusive, resulting in inconsistent clinical application efficacy. We hypothesized that subclones in MSCs contribute to their tumorgenicity, and we approached MSC-subclones at the single-cell level.Methods: MSCs were cultured in an osteogenic differentiation medium and harvested on days 12, 19, and 25 for cell differentiation analysis using Alizarin Red and followed with the single-cell transcriptome.Results: Single-cell RNA-seq analysis reveals a discrete cluster of MSCs during osteogenesis, including differentiation-resistant MSCs (DR-MSCs), differentiated osteoblasts (DO), and precursor osteoblasts (PO). The DR-MSCs population resembled cancer initiation cells and were subjected to further analysis of the yes associated protein 1 (YAP1) network. Verteporfin was also used for YAP1 inhibition in cancer cell lines to confirm the role of YAP1 in MSC--involved tumorigenicity. Clinical data from various cancer types were analyzed to reveal relationships among YAP1, OCT4, and CDH6 in MSC--involved tumorigenicity. The expression of cadherin 6 (CDH6), octamer-binding transcription factor 4 (OCT4), and YAP1 expression was significantly upregulated in DR-MSCs compared to PO and DO. YAP1 inhibition by Verteporfin accelerated the differentiation of MSCs and suppressed the expression of YAP1, CDH6, and OCT4. A survey of 56 clinical cohorts revealed a high degree of co-expression among CDH6, YAP1, and OCT4 in various solid tumors. YAP1 inhibition also down-regulated HeLa cell viability and gradually inhibited YAP1 nuclear localization while reducing the transcription of CDH6 and OCT4.Conclusions: We used single-cell sequencing to analyze undifferentiated MSCs and to discover a carcinogenic pathway in single-cell MSCs of differentiated resistance subclones.

Low temperature is a key factor limiting the rubber plantation extending to high latitude area. Previous work has shown that cold-induced DNA demethylation was coordinated with the expression of cold-responsive (COR) genes in Hevea brasiliensis. In this work, reduced representation bisulphite sequencing analysis of H. brasiliensis showed that cold treatment induced global genomic DNA demethylation and altered the sequence contexts of methylated cytosines, but the levels of mCG methylation in transposable elements were slightly enhanced by cold treatment. Integrated analysis of the DNA methylome and transcriptome revealed 400 genes whose expression correlated with altered DNA methylation. DNA demethylation in the upstream region of gene seems to correlate with higher gene expression, whereas demethylation in the gene body has less association. Our results suggest that cold treatment globally change the genomic DNA methylation status of the rubber tree, which might coordinate reprogramming of the transcriptome.

Altered lipid metabolism has been associated with tumour malignancy, but underlying mechanisms are not clear. Here the authors show that proto-oncogene Src interacts and phosphorylates metabolic enzyme phosphatidic acid phosphatase LPIN1 (lipin-1) to promote growth and metastasis in breast cancer.

Abstract Background Letrozole can significantly decrease the estrogen level, and has been administrated to prevent the incidence of early ovary hyperstimulation syndrome (OHSS). However, the effect of Letrozole on prevention of OHSS reached to controversial conclusions. The present meta-analysis aim to examine whether Letrozole could reduce the incidence of early OHSS after assisted reproductive technology (ART). Methods An exhaustive electronic literature search was conducted on MEDLINE, Google Scholar, CNKI and WANFANG MED ONLINE, from inception until May 2018. We include clinical trials that examined the effect of Letrozole on the prevention of early OHSS. The main outcome measures were the incidence of total early OHSS, mild early OHSS, moderate early OHSS, and severe early OHSS. Results Eight studies included in the review. Of these, five publications evaluated the effect of Letrozolel on the prevention of total, mild, moderate, and severe OHSS, respectively. The results indicated that there was a significantly decreased incidence of total OHSS with Letrozole compared with control group, and there were no significantly differences in the incidence of mild, moderate, and severe OHSS between study group with Letrozole and control group. Eight studies reported the incidence of moderate + severe OHSS. We found a significant decrease in incidence of moderate + severe OHSS in high-risk women with Letrozole. Conclusions Letrozole has no beneficial effect on the prevention of mild, moderate, and severe OHSS, individually; Letrozole should not be considered as the first-line treatment for prevention of OHSS. Further cohort studies are required to explore the effect of Letrozole on the prevention of OHSS. Plain English Summary This study aimed to examine whether Letrozole could reduce the incidence of early OHSS after assisted reproductive technology (ART). A meta-analysis including 8 studies was conducted. There were no significantly differences in the incidence of mild, moderate, and severe OHSS between study group with Letrozole and control group. Letrozole has no beneficial effect on the prevention of mild, moderate, and severe OHSS, individually.

The mechanistic details of fatty acid uptake into cells remains poorly understood. Here, the authors identify CD36 internalization via cavaeolae and demonstrate dynamic palmitoylationof CD36 is required for endocytic uptake of fatty acids.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background Accurate quantification of infection intensity is essential to estimate infection patterns of avian haemosporidian parasites in order to understand the evolution of host-parasite associations. Traditional microscopy is cost-effective but requires high-quality blood smears and considerable experience, while the widely used semi-quantitative qPCR methods are mostly employed with ideal, laboratory-based golden samples and standard curves, which may limit the comparison of parasitemia from different laboratories. Methods Here we present a digital droplet PCR (ddPCR) protocol for absolute quantification of avian haemosporidians in raptors. Novel primers were designed that target a conserved fragment of a rRNA region of the mitochondrial genome of the parasites. Sensitivity and repeatability were evaluated compared to qPCR and other assays. Results This ddPCR assay enables accurate quantification of haemosporidian parasites belonging to Plasmodium, Haemoproteus and Leucocytozoon with minimum infection quantities of 10−5 (i.e. one parasite copy in 105 host genomes) without the use of standard curves. Quantities assessed by ddPCR were more accurate than qPCR using the same primers through reduction of non-specific amplification in low-intensity samples. The ddPCR technique was more consistent among technical duplicates and reactions, especially when infection intensities were low, and this technique demonstrated equal sensitivity with high correspondence (R 2 = 0.97) compared to the widely used qPCR assay. Both ddPCR and qPCR identified more positive samples than the standard nested PCR protocol for the cytb gene used for barcoding avian haemosporidians. Conclusions We developed a novel ddPCR assay enabling accurate quantification of avian haemosporidians without golden samples or standard curves. This assay can be used as a robust method for investigating infection patterns in different host-parasite assemblages and can facilitate the comparison of results from different laboratories.

Abstract Background To evaluate the etiology, demographic profile, clinical features, and outcomes in patients with peripapillary subretinal hemorrhage (PSH). Methods Thirty-eight eyes of 37 consecutive patients with PSH were enrolled in this prospective observational study over 4 years; all were followed for 2 years. The main outcome measures were demographic profile, possible etiology, clinical features, outcome, and prognosis. Results Sixty-eight percent (26/38) of eyes were in female patients; the mean patient age was 20 years. Only 1 patient (1/37) showed bilateral involvement. All patients experienced acute onset of PSH. All eyes were myopic and their best-corrected visual acuities ranged from 20/1000 to 20/12.5. The fundus features of affected eyes were classified into 3 groups: (1) PSH alone (4/38 eyes, 10.5%); (2) PSH with intrapapillary hemorrhage (17/38 eyes, 44.7%); (3) PSH with intrapapillary and vitreous hemorrhage (17/38 eyes, 44.7%). PSH occurred in nasal edges of optic discs with a crescent shape and dull-red color. All affected optic discs were small and crowded, exhibiting variable degrees of tilting. The cup of affected optic discs was narrower and deeper than that of normal control discs. Other ancillary tests provided no additional value. After a mean follow-up of 2.85 months, the hemorrhages resolved spontaneously without sequelae. Recurrence of disease was not observed in any patients. Conclusions PSH is common in myopic eyes with tilted optic discs. We suspect that these hemorrhages occurred as a result of abrupt movement acting on a morphologically vulnerable optic disc.

The heterointerface between complex oxides and van der Waals materials presents a versatile platform for exploring new functionalities. Here, the authors report an unconventional nonlinear optical filtering effect resulting from the interfacial polar alignment between monolayer MoS2 and a ferroelectric oxide thin film.

Hyperspectral imaging is a technique that integrates multiple spectral bands and image information. Its applications range from improving the accuracy of cancer diagnosis to testing the quality of products. Here, we introduce a double-filtering technique that provides high-resolution diagnostic histological images within minutes. The hyperspectral microscopic imaging system is built based on an acousto-optic tunable filter (AOTF). The optimized system is analyzed from the perspective of spectrum and imaging. The spectral resolution can be improved by 37.08 % to 59.95% in the visible light range. The side lobe is obviously inhibited and the purity of spectrum is improved. Furthermore, the example of hyperspectral microscopic imaging is demonstrated with unstained gastric cancer tissue sections to assess the ability of the system in terms of its spectral performances and image quality. The microscopic imaging results of single filtering optical path system and single crystal double filtering optical path system are compared. In general, the optimized double filtering system achieves excellent performance in bandwidth compression and side lobe suppression, especially the first application of hyperspectral microscopy combined with microscope in the visible light range.

Summary: During atherosclerosis plaque progression, pathological intraplaque angiogenesis leads to plaque rupture accompanied by thrombosis, which is probably the most important cause of arteries complications such as cerebral and myocardial infarction. Even though few treatments are available to mitigate plaque rupture, further investigation is required to develop a robust optimized therapeutic method. In this study using rabbit and mouse atherosclerotic models, sinoporphyrin sodium (DVDMS)-mediated sonodynamic therapy reduced abnormal angiogenesis and plaque rupture. Briefly, DVDMS is injected to animals, and then the plaque was locally exposed to pulse ultrasound for a few minutes. Furthermore, a small size clinical trial was conducted on patients with atherosclerosis. Notably, a significant reduction of arterial inflammation and angiogenesis was recorded following a short period of DVDMS-mediated sonodynamic therapy treatment. This beneficial outcome was almost equivalent to the therapeutic outcome after 3-month intensive statin treatment. Key Words: apoptosis-induced apoptosis, atherosclerotic plaque, endothelial cell, macrophage, neovascularization, sonodynamic therapy

The construction of deep foundation pits adjacent to existing subway tunnels faces enormous challenges, and once a safety accident occurs, there are often mass injuries that cause substantial economic losses. However, there are many shortcomings and defects in the traditional methods of assessing the safety of the pit itself and the existing tunnel in the construction of the deep foundation pit adjacent to existing tunnels. This study establishes an optimized complex network-based dynamic risk assessment model to dynamically assess the overall risk of deep foundation pits in adjacent existing tunnels systematically, solving the challenges of inaccurate risk assessment and inaccurate description of correlations between nonstationary time series data. In this study, we first divide the monitoring data into time windows and describe the correlation between nonstationary time-series monitoring data within each window based on the MF-DCCA method and the threshold method, and establish the adjacency matrix to prepare for the establishment of an optimized complex network model. Secondly, based on the adjacency matrix, a complex network model under different time windows is constructed, and risk assessment indexes are established through the topological parameters of the complex network model to explore the evolution of risk in time and space, so as to realize the risk distribution and quantitative evolution assessment of the system which is deep foundation pit adjacent to existing subway tunnels. Finally, the proposed method is tested by taking the Nanning underground comprehensive utilization project as an example. The results show that this method can quantify the risk of the construction of deep foundation pits adjacent to existing tunnels more effectively than the traditional method to describe the evolution law better. It has important guiding significance for strengthening the safety risk monitoring and safety management of the construction system of deep foundation pits adjacent to existing tunnels.

BackgroundWith the progressive course of diabetes and the decline in islet function, the cognitive dysfunction of patients aggravated.ObjectiveWe aimed to investigate the roles of brain-derived neurotrophic factor (BDNF) and the Val66Met polymorphism in mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 169 Chinese patients with T2DM were involved and divided into long-term (diabetes duration >10 years) and short-term (diabetes duration ≤10 years) diabetes, and in each group, the patients were separated as MCI and the control. Demographic characteristics, clinical variables, and cognitive performances were assessed. The plasma BDNF level was measured via enzyme-linked immunosorbent assay. The Val66Met polymorphisms were analyzed.ResultsLong-term T2DM have lower 2 h postprandial C-peptide (p < 0.05). The BDNF level was slightly higher in patients with MCI than in the controls in each duration group without statistical significance. The relationship of BDNF to Montreal Cognitive Assessment was not proven either. However, in the long-term diabetes group, BDNF concentration remained as an independent factor of logical memory test (β = −0.27; p < 0.05), and they were negatively correlated (r = −0.267; p = 0.022); BDNF was also negatively correlated with fasting C-peptide (r = −0.260; p = 0.022), 2 h postprandial C-peptide (r = −0.251; p = 0.028), and homeostasis model assessment of insulin resistance (r = −0.312; p = 0.006). In genotypic groups, BDNF Val/Val performed better in logical memory test than Met/Met and Val/Met.ConclusionElevated peripheral BDNF level associated with declined islet function, when combined with its Val66Met polymorphism, may forecast memory dysfunction in patients with long-term T2DM.

BackgroundMedicinal dendrobiums are used popularly in traditional Chinese medicine for the treatment of diabetes, while their active compounds and mechanism remain unclear. This review aimed to evaluate the mechanism and active compounds of medicinal dendrobiums in diabetes management through a systematic approach.MethodsA systematic approach was conducted to search for the mechanism and active phytochemicals in Dendrobium responsible for anti-diabetic actions using databases PubMed, Embase, and SciFinder.ResultsCurrent literature indicates polysaccharides, bibenzyls, phenanthrene, and alkaloids are commonly isolated in Dendrobium genusin which polysaccharides and bibenzyls are most aboundant. Many animal studies have shown that polysaccharides from the species of Dendrobium provide with antidiabetic effects by lowering glucose level and reversing chronic inflammation of T2DM taken orally at 200 mg/kg. Dendrobium polysaccharides protect pancreatic β-cell dysfunction and insulin resistance in liver. Dendrobium polysaccharides up-regulate the abundance of short-chain fatty acid to stimulate GLP-1 secretion through gut microbiota. Bibenzyls also have great potency to inhibit the progression of the chronic inflammation in cellular studies.ConclusionPolysaccharides and bibenzyls are the major active compounds in medicinal dendrobiums for diabetic management through the mechanisms of lowering glucose level and reversing chronic inflammation of T2DM by modulating pancreatic β-cell dysfunction and insulin resistance in liver as a result from gut microbita regulation.

Accidents occur frequently while constructing deep foundation pits for metro stations, thereby risking substantial economic losses and casualties. To subject the construction of such pits to scientific and rational risk assessment and overcome the limitations of existing risk evaluation models and risk fusion problems, proposed here is a risk-assessment model for such pits based on fuzzy evidential reasoning and the two-tuple linguistic analytic network process (TL-ANP). First, the risk loss indicators are optimized, the weights of different risk events and of each risk loss indicator in the metro-station deep-foundation-pit construction project are calculated using TL-ANP, and trapezoidal fuzzy numbers are used to describe the occurrence probability of each risk event and loss. Second, relying on a table of expert weight indices, the best–worst method based on generalized interval-valued trapezoidal fuzzy numbers is used to determine the weights of experts. Finally, the overall risk grade of the construction project is evaluated by aggregating the risk levels of all risk events through an evidence-reasoning algorithm. The analysis results for a deep foundation pit for a station on Line 5 of Nanning Metro show that the model provides a quantitative basis for determining expert weights and risk loss weights reasonably and improving the reliability of the evaluation system. Also, not only does applying the method show that such a construction project can be judged as having a certain risk grade, but more importantly it can identify the key factors and loss indicators affecting the overall risk grade of the pit, whereupon risk control measures can be adopted in a targeted manner. In comparison with traditional methods, the proposed method is shown to be practical and effective, providing a reference basis for analyzing the risks of similar projects in the future and guaranteeing construction safety.

Rice (Oryza sativa L.), one of the most important food crops worldwide, is a facultative short-day (SD) plant in which flowering is modulated by seasonal and temperature cues. The photoperiodic molecular network is the core network for regulating flowering in rice, and is composed of photoreceptors, a circadian clock, a photoperiodic flowering core module, and florigen genes. The Hd1-DTH8-Ghd7-PRR37 module, a photoperiodic flowering core module, improves the latitude adaptation through mediating the multiple daylength-sensing processes in rice. However, how the other photoperiod-related genes regulate daylength-sensing and latitude adaptation remains largely unknown. Here, we determined that mutations in the photoreceptor and circadian clock genes can generate different daylength-sensing processes. Furthermore, we measured the yield-related traits in various mutants, including the main panicle length, grains per panicle, seed-setting rate, hundred-grain weight, and yield per panicle. Our results showed that the prr37, elf3-1 and ehd1 mutants can change the daylength-sensing processes and exhibit longer main panicle lengths and more grains per panicle. Hence, the PRR37, ELF3-1 and Ehd1 locus has excellent potential for latitude adaptation and production improvement in rice breeding. In summary, this study systematically explored how vital elements of the photoperiod network regulate daylength sensing and yield traits, providing critical information for their breeding applications.

Hammer testing, a nondestructive testing method, has been demonstrated to provide information on structural damage. One of the biggest challenges with this testing method is the simultaneous identification of surface, internal, and composite damage (consisting of both surface and internal damage) in a complex environment, such as post-disaster. A method of identification based on variable-frequency hammering is proposed to solve this problem. The importance and feasibility of using variable-frequency impact hammers and the generated acoustic data to identify multiple types of damage in concrete structures are presented. First, a type of variable-frequency hammering acoustic feature was generated using acoustic feature extraction and selection based on the acoustic data obtained from variable-frequency hammering. Second, a damage recognition model was established using a support vector machine to identify four types of damage occurring simultaneously in the same concrete member specimens, including a type of composite damage with two types of damage occurring simultaneously within 20 mm. Finally, the feasibility of this variable-frequency hammering method was verified experimentally. This method exhibited good performance, with an accuracy of 97.8%; moreover, the method ensures that the feature dimensionality remains unchanged while increasing the effective information of the data.

The herbaceous peony (Paeonia lactiflora Pall.) has high ornamental and nutritional value, and the seeds of P. lactiflora can be used to produce high-quality edible oil. However, low seed yield limits the application of P. lactiflora. This can be mitigated by insect pollinators. Here, we evaluated the pollination services of honeybees (Apis mellifera L.) in a P. lactiflora field. We found that A. mellifera provided pollination for P. lactiflora throughout the day especially in the period from 10:00–15:00. Seed number and weight were significantly increased when P. lactiflora was pollinated by A. mellifera. Furthermore, a DNA barcode, the rbcL gene, was used to analyze pollen samples from the corbiculae (pollen baskets) of A. mellifera (bee pollen, BP) and P. lactiflora flowers (flower pollen, FP). High homology of rbcL genes in the BP and FP suggested that BP was collected from P. lactiflora. Based on our results, A. mellifera provided efficient pollination for P. lactiflora. Therefore, A. mellifera could be a good candidate pollinator for P. lactiflora and could be applied in the field.

Dengue Virus (DENV) infection can cause severe illness such as highly fatality dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Innate immune activation by Nod-like receptors (NLRs) is a critical part of host defense against viral infection. Here, we revealed a key mechanism of NLRP12-mediated regulation in DENV infection. Firstly, NLRP12 expression was inhibited in human macrophage following DENV or other flaviviruses (JEV, YFV, ZIKV) infection. Positive regulatory domain 1 (PRDM1) was induced by DENV or poly(I:C) and suppressed NLRP12 expression, which was dependent on TBK-1/IRF3 and NF-κB signaling pathways. Moreover, NLRP12 inhibited DENV and other flaviviruses (JEV, YFV, ZIKV) replication, which relied on the well-conserved nucleotide binding structures of its NACHT domain. Furthermore, NLRP12 could interact with heat shock protein 90 (HSP90) dependent on its Walker A and Walker B sites. In addition, NLRP12 enhanced the production of type I IFNs (IFN-α/β) and interferon-stimulated genes (ISGs), including IFITM3, TRAIL and Viperin. Inhibition of HSP90 with 17-DMAG impaired the upregulation of type I IFNs and ISGs induced by NLRP12. Taken together, we demonstrated a novel mechanism that NLRP12 exerted anti-viral properties in DENV and other flaviviruses (JEV, YFV, ZIKV) infection, which brings up a potential target for the treatment of DENV infection.

Subcooled boiling flow is a typical phenomenon of a high efficiency of heat transfer in the nuclear reactor. Bubble characteristic sizes are important parameters for the mechanism investigation of subcooled boiling flow. Compared to the empirical correlation and force analysis model, the heat balance model is an effective method to describe the growth of bubble and calculate the bubble maximum diameter. After a wide investigation of the law of bubble growth, some researchers concluded that the bubble diameter would increase all the time during the process. However after a detailed mathematical analysis by use of Squeeze Theorem, new model is developed for the bubble growth model according to heat balance theory in this paper. Compared to the traditional Unal's model, new model indicates the existence of local bubble maximum diameter during the bubble growth's process. In addition, a key group value is provided for the area ratios of different heat fluxes. Several databases are used for validation of the new model. The errors are around 20% which show the accuracy of the new method.

Background: We aimed to evaluate the comparative efficacy and safety of anti–vascular endothelial growth factor (anti-VEGF) monotherapy to identify its utilization and prioritization in patients with neovascular age-related macular degeneration (nAMD).Methods: Eligible studies included randomized controlled trials comparing the recommended anti-VEGF agents (ranibizumab, bevacizumab, aflibercept, brolucizumab, and conbercept) under various therapeutic regimens. Outcomes of interest included the mean change in best-corrected visual acuity (BCVA), serious adverse events, the proportion of patients who gained ≥15 letters or lost