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The aim of this study was to explore and analyze the main features of the top 100 most-cited original articles, systematic reviews (SRs)/meta-analyses (MAs) in the field of robotic surgery, through scientometric analysis. VOSviewer and Excel 2019 were employed to conduct this scientometric study. We found that the majority of original articles (72/100) were published during the 2000s, while the majority of the top 100 most-cited SRs/MAs (91/100) during the 2010s. The USA was the most dominant country (n = 78), Henry Ford Health System was the most productive institution (n = 10), and Menon M was the largest contributing first author (n = 5) of the top 100 most-cited original articles. The USA was the most dominant country (n = 33), University of Padua was the most productive institution (n = 9), and Ficarra V was the largest contributing first author (n = 4) of the top 100 most-cited SRs/MAs. The top 100 most-cited original articles in robotic surgery have focused on the feasibility, outcomes and learning curve of robotic surgery for various neoplasms and cancers. The top 100 most-cited SRs/MAs have focused on the differences between robotic surgery and other types of surgery, with respect to the learning curve, costs, outcomes and experience in treating neoplasms, cancer and other diseases. In the future, the formation of cross-institutional and cross-disciplinary cooperation teams should be promoted and corresponding regulations and standards for specific diseases should be developed to regulate and promote the development of robotic surgery.

Background Studies on the epidemiology and prognosis of primary breast lymphoma (PBL) are lack for low incidence. Therefore, we aimed to investigate the epidemiological characteristics of PBL and develop nomograms to predict patient survival. Methods Data of patients who were diagnosed with PBL from 1975 to 2011 and incidence rate of PBL from 1975 to 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Time-varying multivariable Cox regression analysis was performed to identify independent prognostic factors for overall survival (OS) and disease-specific survival (DSS). Nomograms were constructed based on the independent prognostic factors identified in multivariate Cox regression analysis. Results A total of 1427 patients diagnosed with PBL were identified with the average age of 67.1 years. The overall incidence of PBL is 1.35/1,000,000 (adjusted to the United States standard population in 2000) from 1975 to 2017, with a significant upward trend by an annual percentage change (APC) of 2.91 (95%CI 2.29–3.94, P, Highlights • The incident of PBL was calculated. • Nomograms were constructed to predict OS and DSS. • Patients are divided into the low-risk, medium-risk, and high-risk.

There is currently no formal consensus on the administration of adjuvant chemotherapy to stage I lung squamous cell carcinoma (LUSC) patients despite the poor prognosis. The side effects of adjuvant chemotherapy need to be balanced against the risk of tumour recurrence. Prognostic markers are thus needed to identify those at higher risks and recommend individualised treatment regimens. Clinical and sequencing data of stage I patients were retrieved from the Lung Squamous Cell Carcinoma project of the Cancer Genome Atlas (TCGA) and three tissue microarray datasets. In a novel K-resample gene selection algorithm, gene-wise Cox proportional hazard regressions were repeated for 50 iterations with random resamples from the TCGA training dataset. The top 200 genes with the best predictive power for survival were chosen to undergo an L1-penalised Cox regression for further gene selection. A total of 602 samples of LUSC were included, of which 42.2% came from female patients, 45.3% were stage IA cancer. From an initial pool of 11,212 genes in the TCGA training dataset, a final set of 12 genes were selected to construct the multivariate Cox prognostic model. Among the 12 selected genes, 5 genes, STAU1, ADGRF1, ATF7IP2, MALL and KRT23, were adverse prognostic factors for patients, while seven genes, NDUFB1, CNPY2, ZNF394, PIN4, FZD8, NBPF26 and EPYC, were positive prognostic factors. An equation for risk score was thus constructed from the final multivariate Cox model. The model performance was tested in the sequestered TCGA testing dataset and validated in external tissue microarray datasets (GSE4573, GSE31210 and GSE50081), demonstrating its efficacy in stratifying patients into high- and low-risk groups with significant survival difference both in the whole set (including stage IA and IB) and in the stage IA only subgroup of each set. The prognostic power remains significant after adjusting for standard clinical factors. When benchmarked against other prominent gene-signature based prognostic models, the model outperformed the rest in the TCGA testing dataset and in predicting long-term risk at eight years in all three validation datasets. The 12-gene prognostic model may serve as a useful complementary clinical risk-stratification tool for stage I and especially stage IA lung squamous cell carcinoma patients to guide clinical decision making.

Key points Tamoxifen-inducible skeletal muscle-specific AXIN1 knockout (AXIN1 imKO) in mouse does not affect whole-body energy substrate metabolism. AXIN1 imKO does not affect AICAR or insulin-stimulated glucose uptake in adult skeletal muscle AXIN1 imKO does not affect adult skeletal muscle AMPK or mTORC1 signaling during AICAR/insulin/amino acid incubation, contraction and exercise. During exercise, α2/β2/γ3AMPK and AMP/ATP ratio show greater increases in AXIN1 imKO than wild-type in gastrocnemius muscle. Abstract AXIN1 is a scaffold protein known to interact with >20 proteins in signal transduction pathways regulating cellular development and function. Recently, AXIN1 was proposed to assemble a protein complex essential to catabolic-anabolic transition by coordinating AMPK activation and inactivation of mTORC1 and to regulate glucose uptake-stimulation by both AMPK and insulin. To investigate whether AXIN1 is permissive for adult skeletal muscle function, a phenotypic in vivo and ex vivo characterization of tamoxifen-inducible skeletal muscle-specific AXIN1 knockout (AXIN1 imKO) mice was conducted. AXIN1 imKO did not influence AMPK/mTORC1 signaling or glucose uptake stimulation, neither at rest nor in response to different exercise/contraction protocols, pharmacological AMPK activation, insulin or amino acids stimulation. The only genotypic difference observed was in exercising gastrocnemius muscle, where AXIN1 imKO displayed elevated α2/β2/γ3 AMPK activity and AMP/ATP ratio compared to wild-type mice. Our work shows that AXIN1 imKO generally does not affect skeletal muscle AMPK/mTORC1 signaling and glucose metabolism, likely due to functional redundancy of its homolog AXIN2. This article is protected by copyright. All rights reserved.

Plant hormone abscisic acid (ABA) is essential for regulating plant growth and various stress responses. ABA-mediated signaling depends on local ABA levels rather than the overall cellular ABA concentration. While cellular concentration of ABA can be detected using Förster resonance energy transfer (FRET)-based ABA probes, direct imaging of subcellular ABA levels remains unsolved. Here, we modified the previously reported ABAleon2.1 and generated a new ABA sensor, named ABAleon2.1_Tao3. Via transient expression in tobacco (Nicotiana tabacum) protoplasts, we targeted ABAleon2.1_Tao3s to the endoplasmic reticulum (ER) membrane with the ABA sensing unit facing the cytosol and the ER, respectively, through a nanobody–epitope-mediated protein interaction. Combining FRET with fluorescence lifetime imaging microscopy, ABA-triggered-specific increases in the fluorescence lifetime of the donor mTurquoise in the ABAleon2.1_Tao3 were detected in both transient assays and stably transformed Arabidopsis plants. In tobacco protoplasts, ER membrane-targeted ABAleon2.1_Tao3s showed a generally higher basal level of ABA in the ER than that in the cytosol and ER-specific alterations in the level of ABA upon environmental cues. In ABAleon2.1_Tao3-transformed Arabidopsis roots, mannitol triggered increases in cytosolic ABA in the division zone and increases in ER ABA in the elongation and maturation zone within 1 h after treatment, both of which were abolished in the bg1-2 mutant, suggesting the requirement for BG1 in osmotic stress-triggered early ABA induction in Arabidopsis roots. These data demonstrate that ABAleon2.1_Tao3s can be used to monitor ABA levels in the cytosol and the ER, providing key information on stress-induced changes in the level of ABA in different subcellular compartments.

Although lots of tyrosinases have been isolated from bacteria, few studies are focused on tyrosinases from Bacillus sp.. In this study, a tyrosinase from B. aryabhattai TCCC 111983 (TYR) was functionally expressed, purified, and then biochemically characterized. The recombinant tyrosinase (rTYR) presented a good catalytic activity in a broad temperature and pH range, retaining over 60% of the relative activity at 30 °C–90 °C and 45% at pH 3.0 to 10.0. Especially, rTYR exhibited 20% of its maximum activity at 0 °C, and it also showed a variable stability towards different effectors. It presented high tolerance towards salinity and chloride, retaining 81% of its original activity in 2 M NaCl. Kinetic parameters indicated that rTYR displayed a relatively good affinity for both l -tyrosine and l -DOPA. Additionally, rTYR demonstrated remarkable advantages on efficient decolorizing azo and anthraquinonic food dyes (carmine and erythrosin), and more five industrial dyes with or without mediators in acidic, neutral, and alkaline conditions. As the first report on the tyrosinase from B. aryabhattai, the aforementioned results indicated that rTYR would be potential for food industrial applications.

As the main byproduct of cotton fiber, the cotton seed yields about 1.6 times that of fiber, with its oil rich in unsaturated fatty acids, mainly linoleic acid. It is desirable for breeders to increase the oil content of cottonseed without affecting the yield and quality of cotton fiber. In this study, a seed-specific promoter- (alpha-globulin gene promoter-) driven GhDGAT1 overexpression vector (PαGlob-GhDGAT1) was constructed and used to transform an upland cotton line YZ1 (Gossypium hirsutum). Overexpression of the cotton gene GhDGAT1 in cotton seeds increased its total oil content from 4.7% to 13.9% in different transgenic lines and different generations. With the increase of oil content, the composition and contents of the main fatty acids in cotton seed also changed, as reflected by the contents of the main saturated fatty acids and unsaturated oleic acid. GhDGAT1 could be used to increase oil content and improve oil composition in cottonseed.

Inland river basins include critical habitats and provide various ecosystem services in extremely arid lands. However, we know little about the distribution patterns of soil fungal communities in these river basins. We investigated the distribution patterns of soil fungal communities from the riparian oasis zone (ROZ) to the circumjacent desert zone (CDZ) at the lower reaches of the Heihe River. The results indicated that soil fungal communities were mainly dominated by the phyla Ascomycota and Basidiomycota across all samples. The dominant soil fungi taxa were significantly different between ROZ and CDZ habitats at both the phylum and genus levels. Fungal alpha diversity was mainly affected by spatial factors and plant functional traits, and Pearson correlation analysis revealed that fungal alpha diversity was more closely related to plant functional traits than soil properties. Furthermore, fungal community structure was best explained by spatial factors and plant attributes (including plant diversity and plant functional traits). Together, our findings provide new insights into the significance of spatial factors and plant attributes for predicting distributions of fungal communities in arid inland river basins, which will help us better understand the functions and services of these ecosystems.

Minimally invasive surgery includes traditional laparoscopic and robot-assisted surgery. Although many studies related to robotic surgery and laparoscopic surgery have been published, when doing our search, scientometric studies that focus on related robotic surgery versus laparoscopic surgery were limited. In this study, we aimed to analyze and review the research hots and research status of robotic surgery versus laparoscopic surgery. We searched publications that involved robotic surgery versus laparoscopic surgery in the Web of Science database from 1980 to May 23, 2020. The top 100 publications were published in 2012 with the number of 17 and citations ranged from 618 to 64. Published across 34 different journals, namely European urology (n = 17) and others, the greatest contribution among 36 institutes was made by the Cleveland Clinic (n = 11). Of the top 100 publications, a total of 429 unique words were identified and the most frequently occurring keyword was laparoscopy (n = 33). The co-occurrence of keywords in the top 100 publications indicated that the study of diseases mainly focused on prostatectomy, complications, prostate cancer, retropubic prostatectomy, nephron-sparing surgery, lymph-node dissection, total mesenteric excision, sexual function, rectal cancer, and assisted distal gastrectomy. In recent years, comparative research on robot and laparoscopic surgery has decreased and most studies focus on cancer.

Skotomorphogenesis occurs after germination and before excavation in plants. It inhibits excessive absorbed energy in cells and can prevent the lethal photooxidative damage caused by transitioning from skotomorphogenesis to photomorphogenesis for light energy utilization. To investigate the mechanisms underlying photoreactions in soybean [Glycine max (L.) Merr.], we identified and isolated soybean phytochrome-interaction factor 1 (GmPIF1). A yeast two-hybrid (Y2H) assay showed that GmPIF1 interacted with photoactive PHYTOCHROME A (PHYA) and B (PHYB) in both soybean and Arabidopsis (GmPHYA, GmPHYB, AtPHYA, and AtPHYB). To analyze its function, we ectopically over-expressed GmPIF1 in wild type and pif1 mutant Arabidopsis. In etiolated seedlings, GmPIF1 caused hypocotyl elongation, cotyledon closed, apical hooks folded, and less accumulation of protochlorophyllide. In Y2H, GmPIF1 interacted with AtHDA15 that inhibited chlorophyll synthesis under dark conditions. After transition from darkness to white light, GmPIF1 promotes the reduction of photobleaching and induced de-etiolation. Moreover, GmPIF1 inhibited PHYA- and PHYB-mediated seed germination. Our findings increase our understanding of the regulatory network of light response in soybean and provide useful gene resources for soybean breeding in programs and genetics engineering.

Taraxacum officinale (dandelion) and Radix Astragali are traditional medicinal and edible plants with high nutritional value. In this study, the synergistic hypoglycemic effect of DRE and Radix Astragali extract (RAE) was evaluated. Our results showed that water extract of dandelion (DRE‐w), mainly containing polysaccharides (63.92 ± 1.82 mg/g), total flavonoid (2.57 ± 0.06 mg/g), total phenolic compounds (8.93 ± 0.34 mg/g), and saponins (0.54 ± 0.05 mg/g), exhibited significantly inhibitory effect on α‐glucosidase and α‐amylase. DRE‐w and RAE had synergistic hypoglycemic effect; we found that DRE‐w and its combination with RAE could relieve the state of insulin resistance in IR‐HepG2 cells. The combination could more significantly increase the glucose consumption and intracellular glycogen content, and improve the activity of hexokinase and pyruvate kinase in IR‐HepG2 cells. In summary, DRE and its combination with RAE can be developed as the drugs or functional foods for diabetes prevention and treatment., In this study, the effect of dandelion root extracts (DREs) on the hypoglycemic effect and analysis of active compounds were investigated. We found that DRE and RAE had synergistic hypoglycemic effect. We believe that the results of this research are significant to the development of functional foods and healthcare drugs with hypoglycemic effects.

BACKGROUND Although Streptomyces mobaraense transglutaminase (MTG) has been extensively applied to enhance the functional characteristics of soy protein isolate (SPI) through cross-linking, various transglutaminases (TGs) in nature may provide more choice in the food industry. Previous research reported that TG derived from Bacillus subtilis (BTG) exhibited better pH stability and thermostability than MTG. RESULTS An attempt was made to study the influence of BTG induced cross-linking on the properties of SPI. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results indicated that almost all protein constituents (α', α, β, AS, and BS) in SPI could be cross-linked with BTG treatment. The BTG treatment also resulted in a significant increase (*P

The pandemic novel coronavirus disease (COVID-19) has become a global concern in which the respiratory system is not the only one involved. Previous researches have presented the common clinical manifestations including respiratory symptoms (i.e., fever and cough), fatigue and myalgia. However, there is limited evidence for neurological and psychological influences of SARS-CoV-2. In this review, we discuss the common neurological manifestations of COVID-19 including acute cerebrovascular disease (i.e., cerebral hemorrhage) and muscle ache. Possible viral transmission to the nervous system may occur via circulation, an upper nasal transcribrial route and/or conjunctival route. Moreover, we cannot ignore the psychological influence on the public, medical staff and confirmed patients. Dealing with public psychological barriers and performing psychological crisis intervention are an important part of public health interventions.

A new laccase gene from newly isolated Bacillus licheniformis TCCC 111219 was actively expressed in Escherichia coli. This recombinant laccase (rLAC) exhibited a high stability towards a wide pH range and high temperatures. 170% of the initial activity was detected at pH 10.0 after 10-d incubation, and 60% of the initial activity was even kept after 2-h incubation at 70 °C. It indicated that only single type of extreme environment, such as strong alkaline environment (300 K, pH 12) or high temperature (370 K, pH 7), did not show obvious impact on the structural stability of rLAC during molecular dynamics simulation process. But the four loop regions of rLAC where the active site is situated were seriously destroyed when strong alkaline and high temperature environment existed simultaneously (370 K, pH 12) because of the damage of hydrogen bonds and salt bridges. Moreover, this thermo- and alkaline-stable enzyme could efficiently decolorize the structurally differing azo, triphenylmethane, and anthraquinone dyes with appropriate mediator at pH 3.0, 7.0, and 9.0 at 60 °C. These rare characteristics suggested its high potential in industrial applications to decolorize textile dyeing effluent.

Objectives Mesenchymal-epithelial transition (MET) amplification is a rare gene alteration in lung cancer. The aim of this study was to investigate the clinical characteristics of MET amplification in lung cancer and the response to crizotinib by subsets of patients with MET amplification detected by next-generation sequencing (NGS). Patients and methods We collected NGS sequencing data for patients with MET amplification in our institution from January 2018 to April 2019. The efficacy of crizotinib in MET amplification was retrospectively analyzed. Results A total of 2694 patients received NGS tests, 3.27 % (82/2507) of patients had primary MET amplification, and acquired MET amplification accounted for 16.04 % (30/187) of re-biopsy patients. Only 19 patients received monotherapy with crizotinib. In survival analysis, ten patients with copy number greater than 4 (CN > 4) had longer median PFS (mPFS) (4.76 months; 95 %CI: 1.67–7.85 months) compared with other nine patients (CN ≤ 4) (2.10 months; 95 %CI: 1.53–2.68 months; P = 0.063), but failed to get a statistical significance. No significant differences were observed between median PFS (mPFS) of the patients with primary and acquired MET amplification (4.04 months vs 2.76 months; P = 0.310). Conclusions Primary and acquired MET amplification were detected in 3.27 % and 16.04 % of lung cancer patients, respectively. Patients with CN > 4 seemed to have longer PFS after crizotinib treatment. No significant differences in PFS were observed between patients with primary and acquired MET amplification.

Basic helix-loop-helix (bHLH) transcription factors (TFs) are known to play significant roles in plant growth and development, secondary metabolite synthesis, and stress responses. However, the functions of soybean [Glycine max (L.) Merr.] bHLH TFs have been less widely explored. The main purpose of this study was to explore the function of a bHLH TF subfamily gene, GmbHLH3, by overexpression in wild type Arabidopsis thaliana (L.) Heynh. GmbHLH3 is a homolog of Arabidopsis bHLH3 (AtbHLH3) that participates in the regulation of jasmonic acid (JA) signaling. Several cis-regulatory elements responding to methyl-jasmonate (MeJA), including G-Box CGTCA and TGACG motifs, were found in the promoter of GmbHLH3. GmbHLH3 is located in the nucleus. It can form dimers with AtbHLH3, AtbHLH13, and GmbHLH3a, respectively, by yeast two-hybrid and bimolecular fluorescence complementation assay. GmbHLH3 induced root growth by suppressing expression of AtPDF1.2, AtVSPP1, AtLOX2, and AtTAT1 under MeJA treatment. GmbHLH3 inhibited JA-induced leaf senescence by limiting transcription levels of the senescence-related genes AtSAG29, AtAZF2, AtWRKY22, and AtMKP2, and the chlorophyll degradation genes AtSGR, AtNYC1, AtCLH1, AtPPH, and AtPAO. Under long day conditions, in the absence of JA treatment the GmbHLH3-overexpression lines tended to have a reduced time to flowering. Moreover, GmbHLH3 transcript expression pattern analysis revealed that MeJA treatment could induce GmbHLH3 transcript in soybean. This study provides evidence that JA treatment alters the effects of GmbHLH3 on the regulation of plant growth and gene expression. It contributes to future research on the functions of bHLH TFs in soybean.

The regulatory T cells (Tregs) are a subpopulation of lymphocytes that suppress the immune responses. The prognostic value of Tregs in lymphoma patients remains controversial. Thus, we conducted this meta-analysis to clarify the role of Tregs in the prognosis of lymphoma patients. We searched PubMed, Embase, and Web of Science to obtain eligible studies that evaluated the prognostic factor of Tregs for lymphoma patients. Hazards ratios (HRs) with the matching 95% confidence intervals (95%CIs) were merged to estimate the prognostic value of Tregs. We finally retrieved 23 eligible studies, including a total of 2269 patients. The overall pooled analysis on all types of lymphomas showed that Tregs had a significantly positive association with prolonged overall survival (OS) (HR = 0.633, 95% CI 0.528–0.758) and progression-free survival (PFS) (HR = 0.451, 95% CI 0.261–0.779). Subgroup analysis indicated that high Tregs were significantly correlated with longer OS in Hodgkin lymphoma, diffuse large B cell lymphoma, and natural killer/T cell lymphoma. However, there was no significant association of Tregs with T cell lymphoma and follicular lymphoma. Increased Tregs indicates a better prognosis for patients with lymphoma. Tregs could be used as a valuable prognostic biomarker of lymphoma patients.

Key points Muscle contractions increase protein synthesis in a mechanistic target of rapamycin (mTOR)-dependent manner, yet it is unclear which/how mTOR complexes regulate muscle protein synthesis. We investigated the requirement of mTOR Complex 2 (mTORC2) in contraction-stimulated muscle protein synthesis. mTORC2 inhibition by muscle-specific Rictor knockout (Rictor mKO) did not prevent contraction-induced muscle protein synthesis. Rapamycin prevented contraction-induced muscle protein synthesis in Rictor mKO but not wild-type mice. Abstract Protein synthesis increases following muscle contractions. Previous studies have shown that inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) suppresses the early but not late muscle protein synthesis response, while inhibition of both mTORC1 and mTORC2 abolishes the two effects. Therefore, we hypothesized that mTORC2 regulates muscle protein synthesis following muscle contractions. To test this, we investigated the effect of mTORC2 inhibition by mouse muscle-specific Rictor knockout (Rictor mKO) on muscle protein synthesis 3 h after contraction. The right gastrocnemius muscles of Rictor mKO and wild-type (WT) mice were isometrically contracted using percutaneous electrical stimulation, while the left gastrocnemius muscles served as controls. Vehicle or the mTORC1 inhibitor rapamycin (1.5 mg/kg) was injected intraperitoneally 1 h before contraction. Treatment of WT mice with rapamycin and Rictor mKO lowered protein synthesis in general, but the response to contractions was intact 3 h after contractions in both conditions. Rapamycin treatment in Rictor mKO mice prevented contraction-stimulated muscle protein synthesis. Notably, signalling traditionally associated with mTORC1 was increased by muscle contractions despite rapamycin treatment. In rapamycin-treated Rictor mKO mice, the same mTORC1 signalling was blocked following contractions. Our results indicate that although neither rapamycin-sensitive mTOR/mTORC1 nor mTORC2 is necessary for contraction-induced muscle protein synthesis, combined inhibition of rapamycin-sensitive mTOR/mTORC1 and mTORC2 synergistically inhibits contraction-induced muscle protein synthesis.

Polyol and sugar osmolytes are commonly used in therapeutic protein formulations. How they may affect protein structure and function is an important question. In this work, through NMR measurements, we show that glycerol and sorbitol (polyols), as well as glucose (sugar), can shorten protein backbone hydrogen bonds. The hydrogen bond shortening is also captured by molecular dynamics simulations, which suggest a hydrogen bond competition mechanism. Specifically, osmolytes weaken hydrogen bonds between the protein and solvent to strengthen those within the protein. Although the hydrogen bond change is small, with the average experimental cross hydrogen bond 3hJNC′ coupling of two proteins GB3 and TTHA increased by ~ 0.01 Hz by the three osmolytes (160 g/L), its effect on protein function should not be overlooked. This is exemplified by the PDZ3−peptide binding where several intermolecular hydrogen bonds are formed and osmolytes shift the equilibrium towards the bound state., With NMR and MD simulations, Li, Chen et al. comprehensively probe the effects of osmolytes on hydrogen bond formation in proteins. They show that polyol and sugar osmolytes weaken hydrogen bonding between the protein and solvent while strengthening those within the protein.

Iron is essential for all bacteria. In most bacteria, intracellular iron homeostasis is tightly regulated by the ferric uptake regulator Fur. However, how Fur activates the iron-uptake system during iron deficiency is not fully elucidated. In this study, we found that YdiV, the flagella gene inhibitor, is involved in iron homeostasis in Escherichia coli. Iron deficiency triggers overexpression of YdiV. High levels of YdiV then transforms Fur into a novel form which does not bind DNA in a peptidyl-prolyl cis-trans isomerase SlyD dependent manner. Thus, the cooperation of YdiV, SlyD and Fur activates the gene expression of iron-uptake systems under conditions of iron deficiency. Bacterial invasion assays also demonstrated that both ydiV and slyD are necessary for the survival and growth of uropathogenic E. coli in bladder epithelial cells. This reveals a mechanism where YdiV not only represses flagella expression to make E. coli invisible to the host immune system, but it also promotes iron acquisition to help E. coli overcome host nutritional immunity.

Bioactive peptides are an emerging area of biomedical research in the study of numerous human diseases, including acute alcoholic liver injury (AALI). To study the role and mechanism of the milk‑derived hexapeptide Pro‑Gly‑Pro‑Ile‑Pro‑Asn (PGPIPN) in preventing and reducing AALI, the present study established a mouse model of AALI. PGPIPN was used as a therapeutic drug, and glutathione (GSH) was used as a positive control. The body and liver weights of mice were measured, and the liver indexes were calculated to observe mice health. The pathological morphology of liver tissues stained with hematoxylin and eosin were examined to analyze hepatic injury, and hepatocyte apoptosis was measured with a TUNEL assay. The concentrations or activities of alanine aminotransferase (ALT), aspartate aminotransferase, tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6, triglyceride, total cholesterol, malondialdehyde, superoxide dismutase and GSH peroxidase (GSH‑PX) were detected in serum and/or liver homogenates. The 78 kDa glucose‑regulated protein (GRP78), protein kinase R‑like (PKR) endoplasmic reticulum kinase (PERK), phosphorylated (p)‑PERK, eukaryotic initiation factor 2α (eIF‑2α), p-eIF-2α, inositol‑requiring enzyme 1α (IRE‑1α), spliced X‑box binding protein 1 (XBP‑1s), C/EBP homologous protein (CHOP), caspase‑3 and cleaved caspase‑3 proteins associated with endoplasmic reticulum stress in hepatocytes were assessed by western blotting, and RNA levels of XBP‑1s, CHOP and caspase‑3 genes were assessed by reverse transcription‑quantitative PCR. The results suggested that PGPIPN attenuated alcoholic hepatocyte damage in animal models and reduced hepatocyte oxidative stress in a dose‑dependent manner. Moreover, PGPIPN reduced endoplasmic reticulum stress by regulating the expression levels of p‑PERK, p‑eIF‑2α, XBP‑1s, CHOP, caspase‑3 and cleaved caspase‑3. Collectively, the present results indicated that PGPIPN, as a potential therapeutic drug for AALI, exerted a protective effect on the liver and could reduce liver damage.

It is generally assumed that DNA methylation changes at genomic regions targeted by the de novo RNA-directed DNA methylation (RdDM) pathway are unstable. Here, we show that RdDM targets in Arabidopsis can be classified into two groups on the basis of whether there is remethylation following the restoration of NRPD1 function in nrpd1 mutant plants—remethylable loci and non-remethylable loci. In contrast to the remethylable loci, the non-remethylable loci contain higher levels of the euchromatic marks of trimethylation at Lys 4 of histone H3 (H3K4me3), which interferes with the recruitment of the RdDM molecular machinery, and acetylation at Lys 18 of histone H3 (H3K18ac), which helps to recruit the DNA demethylase ROS1 to antagonize RdDM. Here, using targeted methylation erasure by CRISPR–dCas9–TET1, we demonstrate that methylated CG (mCG) and mCHG (where H represents A, C or T) are memory marks that are required for targeting the RdDM machinery to remethylable loci. Our results show that histone and DNA methylation marks are critical in determining the ability of RdDM target loci to form stable epialleles, and contribute to understanding the formation and transmission of epialleles. A study shows that RNA-directed DNA methylation target loci in Arabidopsis can be classified into two groups—remethylable and non-remethylable loci—characterized by different histone and DNA methylation marks that determine the ability of these loci to form stable epialleles.

Sodium dodecyl sulfate (SDS), a representative anionic surfactant, is a commonly used reagent in studies of the cell membrane and cell wall. However, the mechanisms through which SDS affects cellular functions have not yet been fully examined. Thus, to gain further insights into the cellular functions and responses to SDS, we tested a haploid library of Saccharomyces cerevisiae single-gene deletion mutants to identify genes required for tolerance to SDS. After two rounds of screening, we found 730 sensitive and 77 resistant mutants. Among the sensitive mutants, mitochondrial gene expression; the mitogen-activated protein kinase signaling pathway; the metabolic pathways involved in glycoprotein, lipid, purine metabolic process, oxidative phosphorylation, cellular amino acid biosynthesis and pentose phosphate pathway were found to be enriched. Additionally, we identified a set of transcription factors related to SDS responses. Among the resistant mutants, disruption of ribosome biogenesis and translation alleviated SDS-induced cytotoxicity. Collectively, our results provided new insights into the mechanisms through which SDS regulates the cell membrane or cell wall.

Key points AMP-activated protein kinase (AMPK)-dependent Raptor Ser792 phosphorylation does not influence mechanistic target of rapamycin complex 1 (mTORC1)-S6K1 activation by intense muscle contraction. α2 -AMPK activity-deficient mice have lower contraction-stimulated protein synthesis. Increasing glycogen activates mTORC1-S6K1. Normalizing muscle glycogen content rescues reduced protein synthesis in AMPK-deficient mice. Abstract The mechansitic target of rapamycin complex 1 (mTORC1)-S6K1 signalling pathway regulates muscle growth-related protein synthesis and is antagonized by AMP-activated protein kinase (AMPK) in multiple cell types. Resistance exercise stimulates skeletal muscle mTORC1-S6K1 and AMPK signalling and post-contraction protein synthesis. Glycogen inhibits AMPK and has been proposed as a pro-anabolic stimulus. The present study aimed to investigate how muscle mTORC1-S6K1 signalling and protein synthesis respond to resistance exercise-mimicking contraction in the absence of AMPK and with glycogen manipulation. Resistance exercise-mimicking unilateral in situ contraction of musculus quadriceps femoris in anaesthetized wild-type and dominant negative α2 AMPK kinase dead transgenic (KD-AMPK) mice, measuring muscle mTORC1 and AMPK signalling immediately (0 h) and 4 h post-contraction, and protein-synthesis at 4 h. Muscle glycogen manipulation by 5 day oral gavage of the glycogen phosphorylase inhibitor CP316819 and sucrose (80 g L-1 ) in the drinking water prior to in situ contraction. The mTORC1-S6K1 and AMPK signalling axes were coactivated immediately post-contraction, despite potent AMPK-dependent Ser792 phosphorylation on the mTORC1 subunit raptor. KD-AMPK muscles displayed normal mTORC1-S6K1 activation at 0 h and 4 h post-exercise, although there was impaired contraction-stimulated protein synthesis 4 h post-contraction. Pharmacological/dietary elevation of muscle glycogen content augmented contraction-stimulated mTORC1-S6K1-S6 signalling and rescued the reduced protein synthesis-response in KD-AMPK to wild-type levels. mTORC-S6K1 signalling is not influenced by α2 -AMPK during or after intense muscle contraction. Elevated glycogen augments mTORC1-S6K1 signalling. α2 -AMPK-deficient KD-AMPK mice display impaired contraction-induced muscle protein synthesis, which can be rescued by normalizing muscle glycogen content.

Despite the administration of new effective drugs in recent years, relapse and drug resistance are still the main obstacles in multiple myeloma (MM) treatment, making MM an incurable disease. To overcome drug resistance in MM, it is critical to understand the underlying mechanisms of malfunctioning gene expression and develop novel targeted therapies. During the past few decades, with the discovery and characterization of noncoding RNAs (ncRNAs), the landscape of dysregulated ncRNAs of cancers as well as their biological and pathobiological functions in tumorigenesis and drug resistance have been recognized. Studies about ncRNAs improved the understanding of variations of drug response among individuals at a level distinguished from genetic polymorphism, and provided with new orientations for targeted therapies. In this review, we will summarize the emerging impact and underlying molecular mechanisms of the most relevant classes of ncRNAs in drug resistance of MM, and discuss the potential as well as strategies of treating ncRNAs as therapeutic targets.

Background Pneumonia is a common acute lower respiratory infection in children and elders. Circular RNAs (circRNAs) have recently been uncovered to play important roles in pneumonia. However, the function and mechanism of circ_0038467 in pneumonia remain elusive. Methods Cell viability and apoptosis were determined using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The levels of interleukin 6 (IL-6), IL-8 and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was performed to assess the expression of related proteins. Circ_0038467 was characterized by Ribonuclease R (RNase) digestion and subcellular localization assays. The levels of circ_0038467 and miR-338-3p were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The direct interaction between circ_0038467 and miR-338-3p was validated by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Results Our data indicated that lipopolysaccharide (LPS) induced an inflammatory injury in 16HBE cells by repressing cell viability and enhancing cell apoptosis and proinflammatory cytokines production. Circ_0038467 was upregulated and miR-338-3p was downregulated in LPS-treated 16HBE cells. Circ_0038467 knockdown or miR-338-3p overexpression attenuated LPS-induced 16HBE cell inflammatory injury. Moreover, circ_0038467 acted as a sponge of miR-338-3p in 16HBE cells. MiR-338-3p mediated the alleviated effect of circ_0038467 knockdown on LPS-induced 16HBE cell inflammatory injury. Additionally, the Janus kinase/ signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway was involved in the circ_0038467/miR-338-3p axis-mediated regulation in LPS-induced 16HBE cell inflammatory injury. Conclusions The current work had led to the identification of circ_0038467 knockdown that alleviated LPS-induced inflammatory injury in 16HBE cells at least partly through sponging miR-338-3p and regulating JAK/STAT3 pathway, highlighting novel molecular targets for the treatment of pneumonia.

Soil salinity significantly reduces soybean (Glycine max L.) production worldwide. Plants resistance to stress conditions is a complex characteristic regulated by multiple signaling pathways. The v-Myb avian myeloblastosis viral oncogene homolog (MYB) transcription factor (TF) plays a crucial role in plant development, secondary metabolism, and abiotic stress responses. GmMYB68-overexpression and RNA interference (RNAi) lines were established for examining the function of G. max GmMYB68 in plant responses to abiotic stresses. The predicted amino acid sequence of GmMYB68 was similar to that of R2R3-MYB proteins. Quantitative real-time PCR analysis revealed that GmMYB68 expression varied in response to abiotic stresses. GmMYB68-overexpression lines showed enhanced resistance to salt and alkali stresses and their osmotic adjustment and photosynthetic rates were also stronger than that of GmMYB68-RNAi and wild type plants. Although wild type and transgenic plants showed no significant differences in agronomic traits under normal conditions, the overexpression of GmMYB68 increased grain number and 100-grain weights under salt stress. Our study identified a valuable TF associated with stress response in soybean, as its overexpression might help improve salt and alkali tolerance in soybean and other crops.

While recent research suggests that visual biofeedback can facilitate speech production training in clinical populations and second language (L2) learners, individual learners' responsiveness to biofeedback is highly variable. This study investigated the hypothesis that the type of biofeedback provided, visual-acoustic versus ultrasound, could interact with individuals' acuity in auditory and somatosensory domains. Specifically, it was hypothesized that learners with lower acuity in a sensory domain would show greater learning in response to biofeedback targeting that domain. Production variability and phonological awareness were also investigated as predictors. Sixty female native speakers of English received 30 min of training, randomly assigned to feature visual-acoustic or ultrasound biofeedback, for each of two Mandarin vowels. On average, participants showed a moderate magnitude of improvement (decrease in Euclidean distance from a native-speaker target) across both vowels and biofeedback conditions. The hypothesis of an interaction between sensory acuity and biofeedback type was not supported, but phonological awareness and production variability were predictive of learning gains, consistent with previous research. Specifically, high phonological awareness and low production variability post-training were associated with better outcomes, although these effects were mediated by vowel target. This line of research could have implications for personalized learning in both L2 pedagogy and clinical practice.

The plant aquaporins (AQPs) are highly conserved integral membrane proteins that participate in multiple developmental processes and responses to various stresses. In this study, a total of 35 AQP genes were identified in the watermelon genome. The phylogenetic analysis showed that these AQPs can be divided into five types, including 16 plasma membrane intrinsic proteins (PIPs), eight tonoplast intrinsic proteins (TIPs), eight nodulin 26-like intrinsic proteins (NIPs), two small basic intrinsic proteins (SIPs), and one uncategorized X intrinsic protein (XIP). A number of cis-elements related to plant responses to hormones and stresses were detected in the promoter sequences of ClAQP genes. Chromosome distribution analysis revealed that the genes are unevenly distributed on eight chromosomes, with chromosomes 1 and 4 possessing the most genes. Expression analysis at different developmental stages in flesh and rind indicated that most of ClAQPs have tissue-specific expression. Meanwhile, some other AQP genes showed differential expression in response to cold, salt, and ABA treatments, which is consistent with the organization of the stress-responsive cis-elements detected in the promoter regions. Our results lay a foundation for understanding the specific functions of ClAQP genes to help the genetic improvement of watermelon.

We screened a haploid library of Saccharomyces cerevisiae single-gene deletion mutants to identify nonessential genes associated with increased sensitivity to or resistance against the cell wall antagonist calcofluor white. Through a genome-wide screen, we isolated 537 strains that had an altered growth rate relative to wild type, of which 485 showed increased sensitivity and 52 showed increased resistance to calcofluor white. The MAPK signaling pathway, N-glycan biosynthesis, endocytosis, vacuole acidification, autophagy, and the sulfur relay system were identified as being associated with calcofluor white sensitivity. Resistance genes were mainly involved in chitin metabolism and the RIM101 pathway or encoded several components of the ESCRT complexes or related to cysteine and methionine metabolism and RNA degradation. Further investigation indicated a clear global response network that S. cerevisiae relies on in the presence of the cell wall antagonist calcofluor white, which may help us to understand fungal cell wall remodeling and the mechanisms of toxicity of calcofluor white with respect to eukaryotic cells.

Salt stress seriously restricts crop yield and quality, leading to an urgent need to understand its effects on plants and the mechanism of plant responses. Although phytohormones are crucial for plant responses to salt stress, the role of phytohormone signal transduction in the salt stress responses of stress-resistant species such as Sophora alopecuroides has not been reported. Herein, we combined transcriptome and metabolome analyses to evaluate expression changes of key genes and metabolites associated with plant hormone signal transduction in S. alopecuroides roots under salt stress for 0 h to 72 h. Auxin, cytokinin, brassinosteroid, and gibberellin signals were predominantly involved in regulating S. alopecuroides growth and recovery under salt stress. Ethylene and jasmonic acid signals may negatively regulate the response of S. alopecuroides to salt stress. Abscisic acid and salicylic acid are significantly upregulated under salt stress, and their signals may positively regulate the plant response to salt stress. Additionally, salicylic acid (SA) might regulate the balance between plant growth and resistance by preventing reduction in growth-promoting hormones and maintaining high levels of abscisic acid (ABA). This study provides insight into the mechanism of salt stress response in S. alopecuroides and the corresponding role of plant hormones, which is beneficial for crop resistance breeding.

BackgroundHeavy ion radiotherapy (HIRT) has great advantages as tumor radiotherapy.MethodsBased on 1,558 literatures from core collections of Web of Science from 1980 to 2020, this study visually analyzes the evolution of HIRT research, and sorts out the hotspots and trends of HIRT research using CiteSpace software.ResultsResearch on HIRT has received more extensive attention over the last 40 years. The development of HIRT is not only closely related to radiation and oncology, but also closely related to the development of human society. In terms of citation frequency, “International Journal of Radiation Oncology*Biology*Physics” was the top journal. In terms of influence, “Radiotherapy and Oncology” was the top journal. “Radiation therapy” and “carbon ion radiotherapy” were the two most frequently used keywords in this field.ConclusionThe evolution of the HIRT research has occurred in approximately three stages, including technological exploration, safety and effectiveness research and technological breakthroughs. Finally, some suggestions for future research are put forward.

Challenges have been recognized in healthcare of patients with Alzheimer’s disease (AD) in the COVID-19 pandemic, given a high infection and mortality rate of COVID-19 in these patients. This situation urges the identification of underlying risks and preferably biomarkers for evidence-based, more effective healthcare. Towards this goal, current literature review and network analysis synthesize available information on the AD-related gene APOE into four lines of mechanistic evidence. At a cellular level, the risk isoform APOE4 confers high infectivity by the underlying coronavirus SARS-CoV-2; at a genetic level, APOE4 is associated with severe COVID-19; at a pathway level, networking connects APOE with COVID-19 risk factors such as ACE2, TMPRSS2, NRP1, and LZTFL1; at a behavioral level, APOE4-associated dementia may increase the exposure to coronavirus infection which causes COVID-19. Thus, APOE4 could exert multiple actions for high infection and mortality rates of the patients, or generally, with COVID-19.

BACKGROUND Depression is one of the most common and specific symptoms among menopausal women, leading to significant personal, family, and economic burdens. Some studies have shown that phytoestrogens can help relieve symptoms of depression. OBJECTIVES This systematic review and meta-analysis aim to assess the efficacy and safety of phytoestrogens in treating depression among menopausal women. METHODS A comprehensive search for relevant studies published until November 25, 2020, was conducted in PubMed, the Cochrane Library, Chinese Biomedical Literature Database, Web of Science, and EMBASE. Statistical analyses were performed with R 4.0.3.and Review Manager 5.4. RESULTS 2183 studies were identified and 10 studies with 15 independent reports were included, involving 1248 participants. The quality of the four studies was assessed as high risk, six studies were assessed as unclear. The analyses conducted according random effects model indicated the significant positive effect on depressive symptoms for postmenopausal women compared with the placebo (SMD = -0.62; 95% CI = -1.13 to -0.12; Q = 45.62, df = 14, P 100 mg/d) and ultralow dose (0

The aim of this cross-sectional study was to examine the mediating effects of individual affect and relationship satisfaction on the relationship between self-esteem and Problematic Internet Use (PIU). Affect was measured using the Positive and Negative Affect Schedule (PANAS), relationship satisfaction was assessed using a positive and negative semantic dimension scale, self-esteem was measured using the Rosenberg Self-Esteem Scale, and PIU was measured using the Problematic Internet Use scale with a sample of 507 Chinese university students (Mage = 20.41 years, SD = 2.49). The relationships between the variables were tested using structural equation modelling with a multiple mediation model. The results revealed that negative affect and the negative semantic dimensions of relationship satisfaction mediated the relationship between self-esteem and PIU. The implications of the results and the study’s theoretical contributions are discussed.

Exposure to air pollution has been suggested to be associated with an increased risk of women’s health disorders. However, it remains unknown to what extent changes in ambient air pollution affect gynecological cancer. In our case–control study, the logistic regression model was combined with the restricted cubic spline to examine the association of short-term exposure to air pollution with gynecological cancer events using the clinical data of 35,989 women in Beijing from December 2008 to December 2017. We assessed the women’s exposure to air pollutants using the monitor located nearest to each woman’s residence and working places, adjusting for age, occupation, ambient temperature, and ambient humidity. The adjusted odds ratios (ORs) were examined to evaluate gynecologic cancer risk in six time windows (Phase 1–Phase 6) of women’s exposure to air pollutants (PM2.5, CO, O3, and SO2) and the highest ORs were found in Phase 4 (240 days). Then, the higher adjusted ORs were found associated with the increased concentrations of each pollutant (PM2.5, CO, O3, and SO2) in Phase 4. For instance, the adjusted OR of gynecological cancer risk for a 1.0-mg m−3 increase in CO exposures was 1.010 (95% CI: 0.881–1.139) below 0.8 mg m−3, 1.032 (95% CI: 0.871–1.194) at 0.8–1.0 mg m−3, 1.059 (95% CI: 0.973–1.145) at 1.0–1.4 mg m−3, and 1.120 (95% CI: 0.993–1.246) above 1.4 mg m−3. The ORs calculated in different air pollution levels accessed us to identify the nonlinear association between women’s exposure to air pollutants (PM2.5, CO, O3, and SO2) and the gynecological cancer risk. This study supports that the gynecologic risks associated with air pollution should be considered in improved public health preventive measures and policymaking to minimize the dangerous effects of air pollution.

We planned to dig the carcinostasis activity of physcion 8-O-β-glucopyranoside (PG) in ovarian cancer cells and explored whether long non-coding RNA NORAD was the potential cause of the carcinostasis impact of PG. The impacts of PG on the tumour cell behaviours (including cell viability, apoptosis, migration and invasion) of SKOV3 cells were grabbed. The levels of NORAD in cancer tissues and cell lines were determined; afterwards, the impacts of abnormal expression of NORAD on the tumour cell behaviours of SKOV3 cells were assessed. Moreover, we explored whether NORAD modulated the level of STAT3 by competitively sponging miR-608, thus mediating the antineoplastic effects of PG on ovarian cancer cells. PG suppressed cell viability, enhanced apoptosis and lessened migration and invasion of SKOV3 cells. NORAD was upregulated in ovarian cancer tissues and cells. Silencing of NORAD lessened cell viability, migration and invasion, but induced apoptosis of SKOV3 cells, whereas overexpression of NORAD had opposite effects. Moreover, PG decreased the expression of NORAD. Overexpression of NORAD reversed the effects of PG treatment on the cell biological performances of SKOV3 cells, which were further reversed after overexpression of miR-608 simultaneously. Furthermore, STAT3 was tested as a target gene of miR-608, and the impact of NORAD in PG-treated SKOV3 cells were through the miR-608-mediated STAT3. Our findings reveal that NORAD/miR-608/STAT3 axis is pivotal in mediating the antineoplastic impacts of PG on ovarian cancer cells, which may offer a novel explanation in the therapy of ovarian cancer.

Barrett's esophagus (BE) is an acquired condition in which normal squamous epithelium is replaced with metaplastic columnar epithelium as a consequence of gastroesophageal reflux disease. BE is known as a precursor of esophageal adenocarcinoma. Currently, the molecular mechanism underlying epithelial metaplasia in BE patients remains unknown. Therefore, we investigated the role of Krüppel-like factor 5 (KLF5) signaling in the initiation of BE-associated metaplasia. Sprague-Dawley (SD) rats were used to create a surgical model of bile reflux injury. Immunohistochemistry was performed to analyze human and mouse esophageal specimens. Human esophageal squamous epithelial (HET-1A) cells were treated with bile acid and used in transfection experiments. Quantitative real-time PCR and western blot analysis were performed to detect the expression of KLF5, CDX2, MUC2 and villin. Epithelial tissue from both the rat BE model and human BE patients strongly expressed KLF5, CDX2, MUC2, and villin. Bile acid treatment also increased the expression of KLF5, CDX2, MUC2 and villin in esophageal epithelial cells in a time-dependent manner. Moreover, siRNA-mediated knockdown of KLF5 blocked the expression of CDX2, MUC2 and villin, but transfection of a KLF5 expression vector into esophageal epithelial cells promoted their transdifferentiation into columnar-like cells, as demonstrated by increased expression of the intestinal markers CDX2, MUC2 and villin. Thus, in addition to its function as a transcription factor, KLF5 may be linked to an increased risk of BE development.

Botulinum toxin A (botox) is a toxin used for spasticity treatment and cosmetic purposes. Botox blocks the excitation of skeletal muscle fibers by preventing the release of acetylcholine from motor nerves, a process termed chemical denervation. Surgical denervation is associated with increased expression of the canonical insulin-activated kinase Akt, lower expression of glucose handling proteins GLUT4 and hexokinase II (HKII) and insulin resistant glucose uptake, but it is not known if botox has a similar effect. To test this, we performed a time-course study using supra-maximal insulin-stimulation in mouse soleus ex vivo. No effect was observed in the glucose transport responsiveness at day 1, 7 and 21 after intramuscular botox injection, despite lower expression of GLUT4, HKII and expression and phosphorylation of TBC1D4. Akt protein expression and phosphorylation of the upstream kinase Akt were increased by botox treatment at day 21. In a follow-up study, botox decreased submaximal insulin-stimulated glucose transport. The marked alterations of insulin signaling, GLUT4 and HKII and submaximal insulin-stimulated glucose transport are a potential concern with botox treatment which merit further investigation in human muscle. Furthermore, the botox-induced chemical denervation model may be a less invasive alternative to surgical denervation.

In this study, Salmonella prevalence and antimicrobial resistance were evaluated at various production stages in 2 geographically separated breeder farms (referred to as G and F). Day-old chicks for the breeder flock at farm F were purchased from farm G. A total of 219 Salmonella isolates, all identified as Salmonella enterica subsp. enterica serovar Enteritidis, were recovered from 1,430 samples (sick chicken carcasses and/or dead embryos). The isolation rates at breeder farms G and F were 10.53% (56/532) and 18.15% (163/898), respectively. Resistance to 4–6 antimicrobial agents was the most frequent phenotype during the laying stage at both farms, suggesting that chicks are exposed to higher risk of antimicrobial-resistant Salmonella infection during this stage of the breeding process. Using clustered regularly interspaced short palindromic repeat (CRISPR) typing, 5 CRISPR patterns were identified, out of which one pattern was shared by the 2 farms. In addition, pulsed-field gel electrophoresis (PFGE) typing result indicated that 2 clusters (PF-1 and PF-2) were shared among the 2 breeder farms, suggesting that strains were transmitted from breeder farm G to farm F via the trade of day-old chicks. Our findings suggested that the trade of day-old breeder chicks could be one of the potential Salmonella transmission routes, and antibiotics should be administered with caution during the laying stage.

Objective Chronic ad libitum low protein-high carbohydrate diet (LPHC) increases health- and life-span in mice. A periodized (p) LPHC regimen would be a more practical long-term human lifestyle intervention, but the metabolic benefits of pLPHC are not known. Also, the interactions between LPHC diet and exercise training have not been investigated. Presently, we aimed to provide proof-of-concept data in mice of the efficacy of pLPHC and to explore the potential interactions with concurrent exercise training. Methods A detailed phenotypic and molecular characterization of mice undergoing different durations of 14 d LPHC (5 E% protein)/14 d control diet cycles for up to 4 months with or without concurrent access to activity wheels allowing voluntary exercise training. Results pLPHC conferred metabolic benefits similar to chronic LPHC, including increased FGF21 and adaptive thermogenesis, obesity-protection despite increased total energy intake and improved insulin sensitivity. The improved insulin sensitivity showed large fluctuations between diet periods and was lost within 14 days of switching back to control diet. Parallel exercise training improved weight maintenance but impaired the FGF21 response to pLPHC whereas repeated pLPHC cycles progressively augmented this response. Both the FGF21 suppression by exercise and potentiation by repeated cycles correlated tightly with Nupr1 mRNA in liver, suggesting dependence on liver integrated stress response. Conclusion These results suggest that pLPHC may be a viable strategy to promote human health but also highlight the transient nature of the benefits and that the interaction with other lifestyle-interventions such as exercise training warrants consideration., Graphical abstract Image 1, Highlights • Periodized (p) low-protein-high-carbohydrate (LPHC) diet confers metabolic benefits. • The metabolic improvements by pLPHC diet are highly transient. • The liver FGF21 and integrated stress response to pLPHC is lowered by exercise and increased by repeated pLPHC cycles.

DNA methylation is a conserved epigenetic mark that is critical for many biological processes in plants and mammals. In Arabidopsis, the antagonistic activities of RNA-directed DNA methylation (RdDM) and ROS1-dependent active DNA demethylation are key for the dynamic regulation of locus-specific DNA methylation. However, the molecular factors that coordinate RdDM and active demethylation are largely unknown. Here we report that CLSY4 and its three paralogous SWI2/SNF2-type chromatin-remodeling proteins function in both RdDM and DNA demethylation in Arabidopsis. We initially identified CLSY4 in a genetic screen for DNA demethylation factors and subsequently demonstrated that it also is important in RdDM. Comprehensive genetic analyses using single and high order mutants of CLSY family proteins revealed their roles as double agents in the balance between methylation and demethylation reactions. The four CLSY proteins collectively are necessary for the canonical RdDM pathway; at the same time, each CLSY likely mediates DNA demethylation at specific loci where DNA methylation depends on RdDM. These results indicate that the four chromatin-remodeling proteins have dual functions in regulating genomic DNA methylation, and thus provide new insights into the dynamic regulation of DNA methylation in a model multicellular eukaryotic organism.

Highlights • Currently, chest computed tomography is recommended as the first-line imaging test for detecting COVID-19 pneumonia. • The most typical CT imaging finding of COVID-19 patients is ground-glass opacity, combined with reticular and/or interlobular septal thickening and consolidation. • CT is useful for monitoring patients with COVID-19, identifying associated vascular abnormalities and making differential diagnosis., With the rapid spread of COVID-19 worldwide, early detection and efficient isolation of suspected patients are especially important to prevent the transmission. Although nucleic acid testing of SARS-CoV-2 is still the gold standard for diagnosis, there are well-recognized early-detection problems including time-consuming in the diagnosis process, noticeable false-negative rate in the early stage and lacking nucleic acid testing kits in some areas. Therefore, effective and rational applications of imaging technologies are critical in aiding the screen and helping the diagnosis of suspected patients. Currently, chest computed tomography is recommended as the first-line imaging test for detecting COVID-19 pneumonia, which could allow not only early detection of the typical chest manifestations, but also timely estimation of the disease severity and therapeutic effects. In addition, other radiological methods including chest X-ray, magnetic resonance imaging, and positron emission computed tomography also show significant advantages in the detection of COVID-19 pneumonia. This review summarizes the applications of radiology and nuclear medicine in detecting and diagnosing COVID-19. It highlights the importance for these technologies to curb the rapid transmission during the pandemic, considering findings from special groups such as children and pregnant women.

Aims EphA4 is a member of the Eph receptor family, and expressed mainly in central nervous system (CNS), which is involved in CNS development and multiple diseases. Due to the variability in EphA4 expression, we wondered if EphA4 is expressed in other tissues, and what role does EphA4 play? Materials and methods We generated an EphA4 knockout (KO) rat line with red fluorescent marker protein encoded by the mCherry cassette inserted downstream of the EphA4 promoter as a reporter. Using this system, we observed high expression of EphA4 in the heart atria and in the brain. Key findings EphaA4 KO rats (EphA4−/−) developed obvious atrial hypertrophy with an increased atria-to-heart weight ratio and atrial cardiomyocyte cross-sectional area at six months of age. EphA4−/− rats had reduced atrial end diastolic volume (EDV), atrial ejection fraction (EF) and left ventricular EF. They also exhibited increased amplitude of QRS complexes and QT intervals, with invisible p waves. RNA sequencing revealed that EphA4 KO altered the transcription of multiple genes involved in regulation of transcription and translation, ion binding, metabolism and cell adhesion. Deletion of EphA4 reduced IGF1 mRNA and protein expression, which is involved in cardiac remodeling. Significance Our data demonstrated that EphA4 was highly expressed in the atria and its deletion caused atrial dysfunction. Our findings also suggested that the EphA4 KO rat could be a potential model for studies on atrial remodeling.

Background. Lower limb spasticity is a common complication after stroke, which seriously affects the quality of life and rehabilitation of patients. There are different treatment methods for poststroke spasticity. It has been found in clinical practice that governor vessel electroacupuncture (GV-EA) can effectively relieve poststroke upper extremity spasticity, but the efficacy of treatment of lower extremity spasticity needs to be further verified. This study aims to design a randomized controlled trial to evaluate the efficacy of GV-EA in the treatment of poststroke lower limb spasticity. Methods/Design. This is a randomized, controlled trial. Patients (N = 177) will be randomized to receive routine therapeutic drug and rehabilitation treatment plus GV-EA (experimental group) or routine therapeutic drug and rehabilitation treatment plus EA (control group 1) or routine therapeutic drug and rehabilitation treatment (control group 2). All patients will receive 20 sessions of treatment for 4 weeks. The primary outcomes are the RMS value and the Modified Ashworth Scale. Secondary outcomes include the Fugl–Meyer Assessment for Lower Extremity (FMA-LE) and the Modified Barthel Index score. All outcome measures will be evaluated at the beginning and after the intervention (4 weeks). Discussion. This trial will observe the clinical effect of GV-EA on lower extremity spasticity after stroke, especially its influence on surface electromyography characteristics, and provide high-quality experimental evidence for the clinical application of GV-EA based on surface electromyography in the treatment of poststroke lower limb spasticity. Trial Registration. China Clinical Trials Registry No. ChiCTR1900027969. Registered on 7 December 2019.

Medical staff treating Coronavirus Disease 2019 (COVID-19) patients are at high risk for exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and many have been infected, which may cause panic among medical workers, their relatives, health professionals, and government leaders. We report the epidemiologic and clinical characteristics of healthcare workers and that the majority of infected medical staff had milder symptoms/conditions with a better prognosis than admitted patients. Timely improvement to medical staff’s working conditions such as allowing adequate rest and providing sufficient medical protection is extremely important.

Tuberculosis is one of the most important infectious diseases worldwide and macrophage apoptosis is the major host defense mechanism against TB. We attempted to characterize the role of miRNA (miR)-125b-5p on mycobacterium tuberculosis (Mtb) infection and macrophages behaviors in vitro. According to fluorescence-activated cell separation (FACS), primary monocytes (CD14(+)) in TB patients were accumulated, and apoptotic monocytes were decreased. Peripheral blood mononuclear cells (PBMCs)-derived macrophages (MDMs) and monocytic cells THP-1-derived macrophage-like cells (TDMs) in vitro were used to be infected with H37Rv. After infection, colony-forming units assay revealed the increase of bacterial activity, FACS demonstrated the decrease of apoptosis rate of MDMs and TDMs, as well as promoted levels of IL-6, TNF-α, Bax, and Bim and suppressed levels of IL-10 and Bcl-2, examined by enzyme-linked immunosorbent assay (ELISA) and western blot assay. Expression of miR-125b-5p and DNA damage-regulated autophagy modulator 2 (DRAM2) was examined, and real-time PCR and western blot assay showed that miR-125b-5p was upregulated, whereas DRAM2 was downregulated in primary monocytes and H37Rv-infected macrophages (MDMs and TDMs). Moreover, blocking miR-125b-5p could attenuated H37Rv-induced bacterial activity and inflammatory response of MDMs and TDMs, accompanied with apoptosis inhibition. Whereas these effects of miR-125b-5p knockdown were abolished by downregulating DRAM2. In mechanism, DRAM2 was a downstream target of miR-125b-5p, as evidenced by dual-luciferase reporter assay. Collectively, silencing miR-125b-5p could protect human macrophages against Mtb infection through promoting apoptosis and inhibiting inflammatory response via targeting DRAM2, suggesting a novel target for Mtb eliminating. Abbreviations: TB: tuberculosis; PBMCs: peripheral blood mononuclear cells; Mtb: mycobacterium tuberculosis; AFB: acid fast bacilli; FITC: fluorescein isothiocyanate; MDMs: monocytes-derived macrophages; TDMs: THP-1-derived macrophage-like cells; ERFP: Mtb-enhanced red fluorescent protein; CFU: colony-forming units; ELISA: enzyme-linked immunosorbent assay; FACS: fluorescence-activated cell separation; PI: propidium iodide; DRAM2: DNA damage-regulated autophagy modulator 2; Real-time PCR: real-time polymerase chain reaction; in-miR-125b-5p: miR-125b-5p inhibitor; si-DRAM2: siRNA against DRAM2

In recent years, emerging evidence has suggested that noncoding RNAs (ncRNAs) participate in nearly every aspect of biological processes and play a crucial role in the genesis and progression of numerous tumors, including B-cell lymphoma. The exploration of ncRNA dysregulations and their functions in B-cell lymphoma provides new insights into lymphoma pathogenesis and is essential for indicating future clinical trials and optimizing the diagnostic and therapeutic strategies. In this review, we summarize the role of ncRNAs in B-cell lymphoma and discuss their potential in clinical applications.

Background To characterize the effects of mutation subtypes and concomitant pathogenic mutations on progression-free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations treated with chemotherapy. Methods We retrospectively found that patients who underwent genomic analysis from January 2017 to December 2019, and 101 patients with advanced EGFR ex20ins NSCLC were found. Binary logistic regression and Cox regression were used to determine how EGFR ex20ins mutation subtypes and concomitant mutations are associated with PFS and OS. Results A total of 8,348 patients were screened and 101 advanced EGFR ex20ins NSCLC patients were detected. Fifty-five patients who received chemotherapy (n=49) or TKIs (n=6) as first-line treatment were recorded for PFS and OS. PFS and OS were significantly longer in the platinum-based chemotherapy group (median PFS: 7.6 versus 5.6 months; P=0.001; median OS: 19.9 versus 7.4 months; P=0.027) than in the TKI group. Common mutations include Ala767_Val769dupAlaSerVal (A767_V769dupASV), Ser768_Asp770dupSerValAsp (S768_D770dupSVD) and Ala763_Tyr764insPheGlnGluAla (A763_Y764insFQEA). On binary logistic regression, common mutations (OR =17.04, 95% CI: 1.39-209.56; P=0.027) and number of concomitant mutations ≤1 (OR =34.67, 95% CI: 2.02-595.48; P=0.015) is significantly associated with durable clinical benefit (DCB). On multivariable analysis, common mutations (HR =0.26, 95% CI: 0.0.10-0.63; P=0.003) and the number of concomitant mutations ≤1 (HR =0.33, 95% CI: 0.15-0.73; P=0.006) were significantly associated with longer PFS. Conclusions Common mutations and the number of concomitant mutations ≤1 correlate with a biomarker that predicts benefit from chemotherapy and confers excellent prognosis for advanced patients with advanced EGFR ex20ins NSCLC. Patients with common mutations and with only one concomitant mutation had the greatest PFS and patients with uncommon mutations, and with over one concomitant mutation had the worst prognosis.

Lipoxygenases (LOXs) are non-haem iron-containing dioxygenases and play vital roles in a variety of plant biological processes. Here, we first carried out the genome-wide identification of LOX genes in watermelon. A total of 16 LOX genes were identified, which could be classified into two categories according to phylogenetic analysis: the 9-LOXs (ClLOX1&ndash, 4, 12, and 15) and 13-LOXs (ClLOX5&ndash, 11, 13, 14, and 16). Furthermore, the protein structures, intrachromosomal distributions, and gene structures were thoroughly analyzed. Cis-element analysis of the promoter regions indicated that the expression of ClLOX genes may be influenced by stress and plant hormones. Bioinformatic and expression analyses revealed that the expression of ClLOX genes is tissue-specific and hormone-responsive. The detected LOX genes exhibited distinctive expression patterns in various tissues. Different ClLOX genes showed different responses to methyl jasmonate (MeJA), salicylic acid (SA), and ethylene (ET) treatments, particularly ClLOX7, which exhibited the most active response to the above treatments. This study provides valuable information for a better understanding of the functions of LOX genes and further exploration of the LOX gene family in watermelon.