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Abstract The early diagnosis of liver cancer is crucial for the treatment and depends on the coordinated use of several test procedures. Early diagnosis is crucial for precision therapy in the treatment of the hepatocellular carcinoma (HCC). Therefore, in this study, the NK cell-related gene prediction model was used to provide the basis for precision therapy at the gene level and a novel basis for the treatment of patients with liver cancer. Natural killer (NK) cells have innate abilities to recognize and destroy tumor cells and thus play a crucial function as the “innate counterpart” of cytotoxic T cells. The natural killer (NK) cells is well recognized as a prospective approach for tumor immunotherapy in treating patients with HCC. In this research, we used publicly available databases to collect bioinformatics data of scRNA-seq and RNA-seq from HCC patients. To determine the NK cell-related genes (NKRGs)-based risk profile for HCC, we isolated T and natural killer (NK) cells and subjected them to analysis. Uniform Manifold Approximation and Projection plots were created to show the degree of expression of each marker gene and the distribution of distinct clusters. The connection between the immunotherapy response and the NKRGs-based signature was further analyzed, and the NKRGs-based signature was established. Eventually, a nomogram was developed using the model and clinical features to precisely predict the likelihood of survival. The prognosis of HCC can be accurately predicted using the NKRGs-based prognostic signature, and thorough characterization of the NKRGs signature of HCC may help to interpret the response of HCC to immunotherapy and propose a novel tumor treatment perspective.

Abstract Fleas are the most important insect vectors that parasitize warm-blooded animals and are known vectors of zoonotic pathogens. A recent study showed that Stenoponia polyspina parasitizing Eospalax baileyi in Zoige County have carried Bartonella spp. and Spotted fever group Rickettsia (SFGR). Accurate identification and differentiation of fleas are essential for prevention and control of zoonotic pathogens. To understand phylogenetic relationship of the subfamily Stenoponiinae, we described morphological characteristics of S. polyspina and sequenced its mitogenome with 14,933 bp in size and high A + T content (~ 79%). The S. polyspina mitogenome retained the ancestral pattern of mitochondrial gene arrangement of arthropods without rearrangement. The start codons of 13 protein-coding genes (PCGs) are traditional ATN and the stop codons are TAA or TAG. Anticodon loops of all tRNA genes were 7 bp except for trnL 2 and trnD had anticodon loops with 9 bp and the abnormal anticodon loops may be associated with frameshifting mutation. Genetic distance and Ka/Ks ratios indicated that all 13 PCGs of S. polyspina were subjected to purifying selection, with cox1 at the slowest rate and atp8 at the fastest rate. The mitogenomes of 24 species representing 7 families in the order Siphonaptera were selected to reconstruct phylogenetic tree based on concatenated nucleotide sequences of two datasets (PCGRNA matrix and PCG12RNA matrix) using Bayesian inference (BI) and Maximum likelihood (ML) methods. Phylogenetic tree supported that the superfamilies Ceratophylloidea, Vermipsylloidea, Pulicoidea were monophyletic and the superfamily Hystrichopsylloidea was paraphyletic. The family Ctenophthalmidae was monophyletic in PCGRNA-ML (codon partition) and paraphyletic in the remain trees. S. polyspina belongs to the subfamily Stenoponiinae was closely more related to the subfamily Rhadinopsyllinae. This paper explored phylogenetic position of diverse clades within the order Siphonaptera based on morphological and mitogenome data of S. polyspina. Our research enriched NCBI database of the order Siphonaptera.

Abstract Background A large number of psychological consequences including sleep health emerged during the 2019 Coronavirus disease (COVID-19) pandemic. Sleep patterns in toddlers are vulnerable to negative environmental exposures, however, very few studies on this topic have been published so far. Objectives In this paper, we aimed to investigate the sleep patterns and associated factors in toddlers from China confined at home in the context of COVID-19 pandemic. Methods From April to November 2021, a convenience sample of 493 parents of young children aged (12–35 months) were surveyed from Fuzhou, Sanming, Quanzhou, Nanping, and Longyan cities in the Fujian Province, China. A cross-sectional survey was conducted via Electronic questionnaires to collect parent and child social-demographic characteristics. The Brief Infant Sleep Questionnaire (BISQ) was used to collect data on sleep practices, sleep duration and patterns, as well as the number of nocturnal awaking . Results The mean age of toddlers was 2.11 years old, and 52.54% (259/493) were males. Among the 493 toddlers’ sleep patterns, 331(67.1%) initiated sleep accompanied by parents, 67(13.6%) slept independently, 59 (12.0%) were breast fed/bottle fed to initiate sleep, 27 (5.5%) were held and 9 (1.8%) rocked. The clear longitudinal association between the duration of night-time sleep, the frequency of nighttime awakenings, and various sleep patterns remains clear (p

2′-fucosyllactose (2′-FL) is one of the most prevalent milk oligosaccharides. In this study, the anti-obesity effect of 2′-FL was explored in high-fat diet (HFD)-fed mice. Results showed that 2′-FL alleviated body weight gain, improved serum lipid profiles and increased energy expenditure. Under cold exposure, 2′-FL group showed higher body and rectal temperature, improving adaptive thermogenesis. 2′-FL alleviated lipid accumulation, increased mitochondrial DNA content, as well as upregulated the protein expression of thermogenic markers including UCP1, PRDM16, PGC-1α and the phosphorylation of AMPK in both white and brown adipose tissue. 2′-FL also increased the diversity of gut microbiota in HFD mice. The Bacteroides/Firmicutes ratio, and the Bifidobacterium abundance were increased, while Lachnospiraceae abundance was decreased after 2′-FL treatment. Moreover, 2′-FL to HFD mice altered the bile acid profiles at levels comparable to normal diet group. These results indicates that 2′-FL promotes thermogenesis and modulates gut microbiota to alleviate obesity.

Abstract Introduction Imiquimod plays an important role in the management of condyloma and premalignant lesions. Successively, an increase of hypopigmented lesions following imiquimod application has been reported. However, the mechanisms of imiquimod on melanocytes remain unclear. This study was designed to assess the effect of Imiquimod on the functions of melanocytes in vitro. Methods Primary cultured melanocytes were isolated from normal control skin tissue. After incubation with imiquimod for 48 h in vitro, cell viability was analyzed by cell counting kit‐8 assay. Apoptosis was detected using the Annexin V‐fluorescein‐5‐isothiocyanate flow cytometry assay. Melanin content and tyrosinase activity in melanocytes were measured by colorimetric method and the modified dopachrome method. The production of inflammatory cytokine interleukin 8 (IL‐8), IL‐6, and soluble ICAM‐1 (soluble Intercellular Adhesion Molecule‐1[sICAM‐1]) in melanocytes were measured by enzyme‐linked immunosorbent assay (ELISA). Toll‐like receptor 7 (TLR7), toll‐like receptor 9 (TLR9) protein, and autophagy‐related proteins microtubule‐associated protein 1A/1B‐light chain 3 (LC3‐II), p62, mechanistic target of rapamycin (mTOR), and Atg5 were assessed using western blot analysis. Results Imiquimod significantly inhibited the activity of tyrosinase activity and decreased melanin content in melanocytes and significantly increased apoptosis and IL‐6, IL‐8, and sICAM‐1 production in melanocytes. Moreover, the expression of TLR7 and TLR9 proteins were significantly increased, and the expression of mTOR, p62 protein were markedly decreased, but the expression of LC3II/I and Atg5 protein were significantly increased in melanocytes after incubating with imiquimod. Conclusions This study shows that imiquimod directly inhibits melanogenesis and increases melanocyte apoptosis rates. These effects combined with the upregulation of TLR7 and TLR9 together with increased autophagy activity and inflammatory cytokines production, might be the main reasons leading to hypopigmented lesions after imiquimod application.

ObjectiveThis work is to investigate the alterations of the central 5-hydroxytryptamine (5-HT) system in spontaneously hypertensive rats (SHR) and the correlation with the behaviors of SHR, and to explore the effects of glucocorticoid intervention on the central 5-HT system and SHR behaviors.Materials and methodsThree weeks old SHR were chosen as the attention-deficit hyperactivity disorder (ADHD) model and treated with glucocorticoid receptor (GR) agonist or inhibitor, whereas Wista Kyoto rats (WKY) were chosen as the normal control group. Open-field test and Làt maze test were used to evaluate the spontaneous activities and non-selective attention. The levels of 5-HT in the extracellular fluid specimens of the prefrontal cortex of rats were analyzed by high-performance liquid chromatography. The expressions of GR, 5-HT1A receptor (5-HT1AR), and 5-HT2A receptor (5-HT2AR) in the prefrontal cortex were analyzed through immunohistochemistry.ResultsOur study demonstrated that the 5-HT level was lower in the prefrontal cortex of SHR compared to that of WKY. The Open-field test and Làt maze test showed that GR agonist (dexamethasone, DEX) intervention ameliorated attention deficit and hyperactive behavior, whereas GR inhibitor (RU486) aggravated the disorders. With DEX, the expression levels of 5-HT and 5-HT2AR in the prefrontal cortex of SHR were significantly higher than those in the control group, whereas the expression level of 5-HT1AR was lower. However, the expression levels of 5-HT and 5-HT2AR were significantly decreased after the intervention with RU486, while the expression level of 5-HT1AR increased. Results showed that glucocorticoid was negatively correlated with 5-HT1AR and positively correlated with 5-HT2AR.ConclusionIn the prefrontal cortex of ADHD rats, the down-regulation of 5-HT and 5-HT2AR expressions and the up-regulation of 5-HT1AR, compared with WYK rats, suggested a dysfunctional central 5-HT system in ADHD rats. The GR agonist can upregulate the expression of 5-HT and 5-HT2AR and downregulate the expression of 5-HT1AR in the prefrontal cortex of SHR as well as reduce the hyperactivity and attention deficit behavior in SHR, while the opposite was true for the GR inhibitor. It is suggested that the dysfunction of the 5-HT system in ADHD rats is closely related to glucocorticoid receptor activity.

The sleep disturbance scale for children (SDSC) has been validated in the population of Chinese children (aged 5–16 years) and has good psychometric properties. However, valid assessment tools for sleep problems in the population of infants and young children from mainland China are relatively scarce, and rates of screening and management for pediatric sleep problems are low.ObjectiveThis study is to evaluate the reliability and validity of SDSC among infants (aged 6–36 months), and to provide a reference for expanding the application of the SDSC for Chinese infants (SDSC-I).Materials and methodsFrom April to November 2021, parents of infants from Fuzhou, Quanzhou, Longyan, Sanming, and Nanping cities in Fujian Province, China completed the SDSC-I. Several factor analyses were performed to evaluate the reliability and validity of the scale.ResultsOf note, 432 out of 469 samples were valid. After item selections and exploratory factor analyses, the SDSC-I concluded six dimensions (disorders of initiating sleep, disorders of maintaining sleep, sleep hyperhidrosis, sleep breathing disorders, parasomnias, and non-restorative sleep and excessive somnolence) with 23 items. The Cronbach’s α coefficient of the scale was 0.863, and those for the six dimensions were within 0.576–0.835. The values of parameters for content validity of the scale were: IR = 0.87, I-CVI > 0.78, Kappa value > 0.74, S-CVI/UA = 0.87, S-CVI/Ave = 0.98. Principal component analysis revealed that the Kaiser-Meyer-Olkin (KMO) value was 0.84, and the factor loading of items ranged from 0.328 to 0.849, with six factors of eigenvalue more than one, which could explain 58.274% of the total variance. The confirmatory factor analysis results showed that χ2/DF was 3.556, root-mean-square error of approximation (RMSEA) was 0.077, comparative fit index (CFI) was 0.809, and standardized RMR (SRMR) was 0.070.ConclusionOur study provides evidence that the SDSC-I is reliable and valid, and it is effective for the screening and management of sleep disturbances among infants (aged 6–36 months). Compared with other questionnaires such as the Brief Infant Sleep Questionnaire (BISQ), it is worthy of popularization and application in pediatric primary care.

Drug addiction is a serious problem globally, recently exacerbated by the COVID-19 pandemic. Glial cell-derived neurotrophic factor (GDNF) is considered a potentially effective strategy for the treatment of addiction. Previous animal experiments have proven that GDNF has a good therapeutic effect on drug addiction, but its clinical application is limited due to its poor blood-brain barrier (BBB) permeability. Low-frequency focused ultrasound, combined with microbubbles, is a non-invasive and reversible technique for locally-targeted BBB opening. In the present study, magnetic resonance imaging-guided low-frequency focused ultrasound, combined with GDNF microbubbles, was used to target BBB opening in the ventral tegmental area (VTA) region. The effects of GDNF on morphine-induced conditioned place preference (CPP) and acute withdrawal symptoms in rats after a partially opened BBB were evaluated by behavioral observation. Western blot was used to detect changes in tyrosine hydroxylase (TH) expression levels in the VTA region after different treatments, and high performance liquid chromatography was used to detect the changes in monoamine neurotransmitter content. The results showed that ultrasound combined with GDNF microbubbles targeted and opened the BBB in the VTA region, and significantly increased GDNF content, destroyed morphine-induced CPP, and reduced the withdrawal symptoms of morphine addiction in rats. Furthermore, the up-regulation of TH expression and the increase of norepinephrine and dopamine content induced by morphine were significantly reversed, and the increase of 5-hydroxytryptamine content was partially reversed. Therefore, ultrasound combined with GDNF microbubbles to target and open the BBB can effectively increase the content of central GDNF, thus playing a therapeutic role in morphine addiction. Our study provides a new approach to locally open the BBB and target delivery of neurotrophic factors, such as GDNF, to treat brain diseases like addiction.

Aerial vehicle detection has significant applications in aerial surveillance and traffic control. The pictures captured by the UAV are characterized by many tiny objects and vehicles obscuring each other, significantly increasing the detection challenge. In the research of detecting vehicles in aerial images, there is a widespread problem of missed and false detections. Therefore, we customize a model based on YOLOv5 to be more suitable for detecting vehicles in aerial images. Firstly, we add one additional prediction head to detect smaller-scale objects. Furthermore, to keep the original features involved in the training process of the model, we introduce a Bidirectional Feature Pyramid Network (BiFPN) to fuse the feature information from various scales. Lastly, Soft-NMS (soft non-maximum suppression) is employed as a prediction frame filtering method, alleviating the missed detection due to the close alignment of vehicles. The experimental findings on the self-made dataset in this research indicate that compared with YOLOv5s, the mAP@0.5 and mAP@0.5:0.95 of YOLOv5-VTO increase by 3.7% and 4.7%, respectively, and the two indexes of accuracy and recall are also improved.

Sugars and phytohormones co-regulate various common responses and development processes in plants. The previous studies reveal that the cross-talk between sugar and phytohormone signaling affects cellular elongation in root and hypocotyl. The elongation of hypocotyl is vital for the initial growth and development of seedlings during the transit from skotomorphogenesis to photomorphogenesis. Here, we found that LecRK-Ⅷ.2 gene regulated hypocotyl elongation involving in cross-talk between sugar and BR signaling. The results showed that sugar treatment could partly recover the defect of brassinosteroid (BR) response in bak1 mutant. LecRK-Ⅷ.2 gene regualted hypocotyl elongation by integrating the signaling cross-talk among BR, sucrose, glucose and fructose. Expression analysis of BR signaling related genes in response to exogenous sugar and BR suggested that LecRK-Ⅷ.2 may play essential roles in regulating hypocotyl growth. We also studied the roles of sugar transporter genes (STP1 and STP13) during hypocotyl elongation in the lecrk-Ⅷ.2 mutants in response to sugar/BR. The results showed that STP1 and STP13 expression in lecrk-Ⅷ.2-1 mutants were higher than that of Col-0 plant under sugar-free conditions. The expressions of STP1 in lecrk-Ⅷ.2 mutants were down-regulated compared to Col-0 under glucose treatments. The expressions of STP13 in lecrk-Ⅷ mutants were up-regulated compared to Col-0 under sucrose treatments. Altogether, our work indicated that LecRK-Ⅷ.2 regulated hypocotyl elongation by mediating the signaling cross-talk among sucose, glucose and BR.

Background: Autophagy plays an important role in maintaining intracellular homeostasis and is essential for cell survival and cell death. Dysfunction of autophagy has been described in many autoimmune diseases but data on vitiligo are scarce. Aims: The aim of this pilot study was to investigate the expression of autophagy-related proteins in patients with vitiligo. Methods: Western blotting was used to analyze the expression of microtubule-associated protein light chain 3 (LC3II/I), autophagy-related gene 5 (Agt5), mammalian target of rapamycin (mTOR) and p62 in lesional and perilesional vitiligo skin from seven patients with active generalized vitiligo and nine patients with stable generalized vitiligo compared to control skin from six healthy subjects. Results: Our data showed increased expression of the autophagy marker LC3II/I and decreased p62 protein expression in lesional skin of active and stable vitiligo compared to control skin (P < 0.01). No significant difference in the expression of LC3II/I and p62 was found in perilesional skin of active vitiligo patients (P > 0.05) compared to control skin. Expression of LC3II/I in stable vitiligo lesional skin was higher and p62 expression was lower compared to active vitiligo lesional skin (P < 0.01). Decreased p62 expression was shown in perilesional skin of stable vitiligo patients (P < 0.05). Agt5 protein in lesional and perilesional skin of both active and stable vitiligo patients were increased (P < 0.01 and P< 0.05) compared to control skin. The expression of mTOR protein in lesional and perilesional skin of active and stable vitiligo patients was significantly lower than in control skin (P < 0.01). Conclusions: The present study indicates increased autophagy in lesional skin in vitiligo patients. Stable vitiligo lesional skin showed increased autophagy compared to active vitiligo lesional skin. Missing activation of autophagy in active vitiligo perilesional skin suggests disturbed autophagy to be associated with vitiligo.

Abstract DNA barcoding is currently an effective and widely used tool that enables rapid and accurate identification of plant species. The Orchidaceae is the second largest family of flowering plants, with more than 700 genera and 20,000 species distributed nearly worldwide. The accurate identification of Orchids not only contributes to the safe utilization of these plants, but also it is essential to the protection and utilization of germplasm resources. In this study, the DNA barcoding of 4 chloroplast genes (matK, rbcL, ndhF and ycf1) were used to provide theoretical basis for species identification, germplasm conservation and innovative utilization of orchids. By comparing the nucleotide replacement saturation of the single or combined sequences among the 4 genes, we found that these sequences reached a saturation state and were suitable for phylogenetic relationship analysis. The phylogenetic analyses based on genetic distance indicated that ndhF and ycf1 sequences were competent to identification at genus and species level of orchids in a single gene. In the combined sequences, matK + ycf1 and ndhF + ycf1 were qualified for identification at the genera and species levels, suggesting the potential roles of ndhF, ycf1, matK + ycf1 and ndhF + ycf1 as candidate barcodes for orchids. Based on the SNP sites, candidate genes were used to obtain the specific barcode of orchid plant species and generated the corresponding DNA QR code ID card that could be immediately recognized by electronic devices. This study provides innovative research methods for efficient species identification of orchids. The standardized and accurate barcode information of Orchids is provided for researchers. It lays the foundation for the conservation, evaluation, innovative utilization and protection of Orchidaceae germplasm resources.

Traditional hydrogel has usually had restricted application in the biomedical field due to lack of a control unit. Herein, Azobenzene (AZO), as a typical kind of photo-response molecule, was introduced into hydrogel by polymerization to provide a control unit for hydrogel. Simultaneously, the immobilization of AZO end group would solve the problems of uncontrollable recovery and light fatigue for AZO small molecules according to previous research. In the research, two kinds of crosslinkable AZO molecules, namely AZO crosslinker and AZO monomer, were synthesized as functional monomers or crosslinkers. Further, AZO copolymerized hydrogel and AZO crosslinked hydrogel were obtained. In order to estimate fundamental properties for contact lenses, gelation time and swelling ratio of hydrogels as a function of AZO concentration as well as crosslinking type were investigated. Moreover, synthesized hydrogels exhibited typical porous morphology, but their size and homogeneity were dependent on the type of hydrogel. In order to evaluate photo-responsive performance, detailed photo induced isomerization of both AZO copolymerized hydrogel and crosslinked hydrogel were tracked by UV spectra. The results confirmed the reversible, stable, and controllable photo responsive process. In vitro evaluation was used to investigate drug release behavior using orfloxacin and puerarin as model drugs. It was found that AZO addition as well as hydrogel type would influence puerarin release, but would have little effect on the orfloxacin release behavior in hydrogels. Furthermore, the isomer type in the hydrogel would have some effects on drug release behavior including orfloxacin and puerarin.

We demonstrate a broadband and polarization selective terahertz modulator with ultrafast modulation speed, based on the Si grating metasurface on the Sapphire substrate. The Si layer is implanted with B+ and subsequently annealed, which significantly reduces the lifetime of carriers and increases the carrier density, and thus realizes ultrafast and efficient modulation. Our modulator achieves modulation depth up to 60% for the x-polarized THz wave and less than 1% for the y-polarized THz wave in the frequency ranging from 0.5 to 2.5 THz, with switch-on and switch-off time of modulation in 20 ps and around 300 ps, respectively. The carrier dynamics of the fabricated Si grating is also studied to illustrate the ultrafast modulated mechanism. Our results pave the way for ultrafast manipulation of terahertz spectrum and shows great potential in terahertz communication.

A novel fusion-based ship detection method from polarimetric Synthetic Aperture Radar (Pol-SAR) images is proposed in this paper. After feature extraction and constant false alarm rate (CFAR) detection, the detection results of HH channel, diplane scattering by Pauli decomposition and helical factor by Barnes decomposition are fused together. The confirmed targets and potential target pixels can be obtained after the fusion process. Using the difference degree of the target, potential target pixels can be classified. The fusion-based ship detection method works accurately by utilizing three different features comprehensively. The result of applying the technique to measured Airborne Synthetic Radar (AIRSAR) data shows that the novel detection method can achieve better performance in both ship’s detection and ship’s shape preservation compared to the result of K-means clustering method and the Notch Filter method.

Abnormal expression of long non-coding RNA often contributes to unrestricted growth of cancer cells. Long non-coding RNA XIST expression is upregulated in several cancers; however, its modulatory mechanisms have not been reported in hepatocellular carcinoma. In this study, we found that XIST expression was significantly increased in hepatocellular carcinoma tissues and cell lines. XIST promoted cell cycle progression from the G1 phase to the S phase and protected cells from apoptosis, which contributed to hepatocellular carcinoma cell growth. In addition, we revealed that there was reciprocal repression between XIST and miR-139-5p. PDK1 was identified as a direct target of miR-139-5p. We proposed that XIST was responsible for hepatocellular carcinoma cell proliferation, and XIST exerted its function through the miR-139-5p/PDK1 axis.