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Summary: Reducing the rate of translation promotes longevity in multiple organisms, representing a conserved mechanism for lifespan extension. Aminoacyl-tRNA synthetases (ARSs) catalyze the loading of amino acids to their cognate tRNAs, thereby playing an essential role in translation. Mutations in ARS genes are associated with various human diseases. However, little is known about the role of ARSs in aging, particularly whether and how these genes regulate lifespan. Here, using Caenorhabditis elegans as a model, we systematically characterized the role of all three types of ARS genes in lifespan regulation, including mitochondrial, cytoplasmic, and cyto-mito bifunctional ARS genes. We found that, as expected, RNAi knockdown of mitochondrial ARS genes extended lifespan. Surprisingly, knocking down cytoplasmic or cyto-mito bifunctional ARS genes shortened lifespan, though such treatment reduced the rate of translation. These results reveal opposing roles of mitochondrial and cytoplasmic ARSs in lifespan regulation, demonstrating that inhibiting translation may not always extend lifespan.

Recent evidence suggests that lung microbiota can be recognized as one of the ecological determinants of various respiratory diseases. However, alterations in the lung microbiota and associated lung immunity in these respiratory diseases remain unclear. To compare the lung microbiota and lung immune profiles in common respiratory diseases, a total of 78 patients were enrolled in the present study, including 21 patients with primary pulmonary tuberculosis (PTB), eight patients with newly diagnosed lung cancer (LC), and 49 patients with community-acquired pneumonia (CAP). Bronchoalveolar lavage fluid (BALF) was collected for microbiota and cytokine analyses. With MiSeq sequencing system, increased bacterial alpha-diversity and richness were observed in patients with LC than in those with PTB and CAP. Linear discriminant analysis effect size revealed that CAP-associated pulmonary microbiota were significantly different between the PTB and LC groups. More key functionally different genera were found in the PTB and LC groups than in the CAP group. The interaction network revealed stronger positive and negative correlations among these genera in the LC group than in the other two groups. However, increased BALF cytokine profiles were observed in the PTB group than in the other two groups, while BALF cytokines were correlated with key functional bacteria. This comparative study provides evidence for the associations among altered lung microbiota, BALF inflammation, and different respiratory disorders, which provides insight into the possible roles and mechanisms of pulmonary microbiota in the progression of respiratory disorders.

Soybean Sclerotinia stem rot caused by Sclerotinia sclerotiorum is a common disease in soybean, and effective biological control is urgently needed. We have previously confirmed that Bacillus amyloliquefaciens can effectively antagonize S. sclerotiorum in a plate competition experiment and a soybean seedling inoculation experiment. In this study, the mechanisms underlying plant death caused by S. sclerotiorum and soybean resistance to S. sclerotiorum induced by B. amyloliquefaciens were evaluated. The stems of potted soybean seedlings were inoculated with S. sclerotiorum (Gm-Ss), B. amyloliquefaciens (Gm-Ba), and their combination (Gm-Ba-Ss), using scratch treatments as a control, followed by dual RNA sequencing and bioinformatics analyses. Global gene expression levels in the Gm-Ss treatment were much lower than those in the Gm-Ba, Gm-Ba-Ss, and Gm groups, suggesting that S. sclerotiorum strongly inhibited global gene expression in soybean. In a pairwise comparison of Gm-Ss vs. Gm, 19983 differentially expressed genes (DEGs) were identified. Down-regulated DEGs were involved in various KEGG pathways, including ko01110 (biosynthesis of secondary metabolites), ko01100 (metabolic pathways), ko01120 (microbial metabolism in diverse environments), ko00500 (starch and sucrose metabolism), and ko04075 (plant hormone signal transmission), suggesting that S. sclerotiorum inoculation had a serious negative effect on soybean metabolism. In Gm-Ba vs. Gm, 13091 DEGs were identified, and these DEGs were significantly enriched in ko03010 (ribosome) and ko03008 (ribosome biogenesis in eucaryotes). Our results suggest that B. amyloliquefaciens increases the expression of genes encoding the ribosomal subunit, promotes cell wall biogenesis, and induces systemic resistance. S. sclerotiorum strongly inhibited metabolism in soybean, inhibited the synthesis of the cytoskeleton, and induced the up-regulation of programmed death and senescence-related genes via an ethylene signal transduction pathway. These results improve our understanding of S. sclerotiorum-induced plant death and soybean resistance to S. sclerotiorum induced by B. amyloliquefaciens and may contribute to the improvement of strategies to avoid yield losses.

Bark is an important protective tissue and vegetative organ of woody plants. Variations in bark thickness have a direct effect on plant growth and development, forest community structure, and terrestrial ecosystem function. However, the characteristics of these variations in tree bark thickness (BT) and adaptation to environmental factors remain unclear. In this study, we established comprehensive BT traits and environmental factor dataset for 75 major woody plant species in China and analyzed the spatial pattern and factors driving BT traits in the major woody plants of China. As results, the BT of major woody plants in China varied significantly with spatial location (latitude and longitude) (P

Abstract Increasing bacterial drug resistance to antibiotics has posed a major threat to contemporary public health, which resulted in a large number of people suffering from serious infections and ending up dying without any effective therapies every year. Here, a dynamic covalent polymeric antimicrobial, based on phenylboronic acid (PBA)‐installed micellar nanocarriers incorporating clinical vancomycin and curcumin, is developed to overcome drug‐resistant bacterial infections. The formation of this antimicrobial is facilitated by reversible dynamic covalent interactions between PBA moieties in polymeric micelles and diols in vancomycin, which impart favorable stability in blood circulation and excellent acid‐responsiveness in the infection microenvironment. Moreover, the structurally similar aromatic vancomycin and curcumin molecules can afford π–π stacking interaction to realize simultaneous delivery and release of payloads. In comparison with monotherapy, this dynamic covalent polymeric antimicrobial demonstrated more significant eradication of drug‐resistant bacteria in vitro and in vivo due to the synergism of the two drugs. Furthermore, the achieved combination therapy shows satisfied biocompatibility without unwanted toxicity. Considering various antibiotics contain diol and aromatic structures, this simple and robust strategy can become a universal platform to combat the ever‐threatening drug‐resistant infectious diseases.

Abstract Background Although lots of quantitative trait loci (QTLs) and genes present roles in litter size of some breeds, the information might not make it clear for the huge diversity of reproductive capability in pig breeds. To elucidate the inherent mechanisms of heterogeneity of reproductive capability in litter size of Xiang pig, we performed transcriptome analysis for the expression profile in ovaries using RNA-seq method. Results We identified 1,419 up-regulated and 1,376 down-regulated genes in Xiang pigs with large litter size. Among them, 1,010 differentially expressed genes (DEGs) were differently spliced between two groups with large or small litter sizes. Based on GO and KEGG analysis, numerous members of genes were gathered in ovarian steroidogenesis, steroid biosynthesis, oocyte maturation and reproduction processes. Conclusions Combined with gene biological function, twelve genes were found out that might be related with the reproductive capability of Xiang pig, of which, eleven genes were recognized as hub genes. These genes may play a role in promoting litter size by elevating steroid and peptide hormones supply through the ovary and facilitating the processes of ovulation and in vivo fertilization.

Abstract Deep learning technology provides novel solutions for increasingly complex target tracking requirements. For traditional target tracking models, the movement of the target need to be simulated by a predefined mathematical model. However, it is extremely difficult to obtain sufficient information in advance, which makes it challenging to track changeable and noisy trajectories in a timely and precise manner. A deep learning framework is constructed for automatic trajectory tracking based on learning the dynamic laws of motion, called DeepGTT. Specifically, a trajectory generator and a trajectory mapper were designed to standardise trajectory data and construct trajectory mapping, which enable the long short‐term memory–based tracking network to learn general dynamic laws. Then, to discuss the interpretability of the model, the mechanism of the deep learning framework is considered and a memory factor matrix is defined. Finally, extensive experiments are conducted on various weak manoeuvring and manoeuvring scenarios to evaluate the algorithm. Experimental results demonstrate that the DeepGTT algorithm remarkably improves accuracy and efficiency compared with most conventional algorithms and state‐of‐the‐art methods. In addition, interpretability experiments qualitatively prove that the tracking network can perceive dynamic laws when estimating the target state.

Abstract Estimation of leaf nutrient composition of dominant plant species from contrasting habitats (i.e., karst and nonkarst forests) provides an opportunity to understand how plants are adapted to karst habitats from the perspective of leaf traits. Here, we measured leaf traits—specific leaf area (SLA), concentrations of total carbon ([TC]), nitrogen ([TN]), phosphorus ([TP]), calcium ([Ca]), magnesium ([Mg]), manganese ([Mn]), minerals ([Min]), soluble sugars, soluble phenolics, lipids, and organic acids ([OA])—and calculated water‐use efficiency (WUE), construction costs (CC), and N/P ratios, and searched for correlations between these traits of 18 abundant plant species in karst and nonkarst forests in southwestern China. Variation in leaf traits within and across the abundant species was both divergent and convergent. Leaf [TC], [Ca], [Min], [OA], and CC were habitat‐dependent, while the others were not habitat‐ but species‐specific. The correlations among [TN], [TP], SLA, [TC], CC, [Min], WUE, [OA], and CC were habitat‐independent, and inherently associated with plant growth and carbon allocation; those between [CC] and [Lip], between [Ca] and [Mg], and between [Mg] and [WUE] were habitat‐dependent. Habitat significantly affected leaf [Ca] and thus indirectly affected leaf [OA], [Min], and CC. Our results indicate that plants may regulate leaf [Ca] to moderate levels via adjusting leaf [OA] under both high and low soil Ca availability, and offer new insights into the abundance of common plant species in contrasting habitats.

Abstract Background The niche of tissue development in vivo involves the growth matrix, biophysical cues and cell-cell interactions. Although natural extracellular matrixes may provide good supporting for seeding cells in vitro, it is evitable to destroy biophysical cues during decellularization. Reconstructing the bioactivities of extracellular matrix-based scaffolds is essential for their usage in tissue repair. Results In the study, a hybrid hydrogel was developed by incorporating single-wall carbon nanotubes (SWCNTs) into heart-derived extracellular matrixes. Interestingly, insoluble SWCNTs were well dispersed in hybrid hydrogel solution via the interaction with extracellular matrix proteins. Importantly, an augmented integrin-dependent niche was reconstructed in the hybrid hydrogel, which could work like biophysical cues to activate integrin-related pathway of seeding cells. As supporting scaffolds in vitro, the hybrid hydrogels were observed to significantly promote seeding cell adhesion, differentiation, as well as structural and functional development towards mature cardiac tissues. As injectable carrier scaffolds in vivo, the hybrid hydrogels were then used to delivery stem cells for myocardial repair in rats. Similarly, significantly enhanced cardiac differentiation and maturation(12.5 ± 2.3% VS 32.8 ± 5%) of stem cells were detected in vivo, resulting in improved myocardial regeneration and repair. Conclusions The study represented a simple and powerful approach for exploring bioactive scaffold to promote stem cell-based tissue repair. Graphic abstract

With the increase in energy demand, energy engineering has gradually developed to go deeper, accompanied by a complex geological environment, such as the coupling of stress and seepage. Limestone is widely found in underground rock engineering, and its stress–seepage coupling characteristics have a great influence on the safety and stability of related engineering projects. In order to study the permeability characteristics and damage evolution of limestone during the deformation and failure process under stress–seepage coupling conditions, permeability and acoustic emission tests on limestone were performed in this paper. The results showed that: the stress–strain curve demonstrated periodicity, as did the permeability change. The change in permeability in different deformation stages of axial strain and lateral strain was similar, but it was more appropriate to reflect the permeability evolution in terms of lateral strain. The permeability of the limestone slightly decreased in the volumetric compression stage, and tended to saturate after a sudden increase in the expansion stage. The presence of the confining pressure reduced the permeability of the rock. In the process of limestone deformation and failure, the level of acoustic emission activity can reflect the degree of fracture development. The permeability characteristics and acoustic emission characteristics had a good corresponding relationship. The greater the confining pressure, the higher the acoustic emission activity. The deformation and damage process of limestone experienced three stages: damage stable growth, damage acceleration development, and damage saturation.

Abstract The high locoregional recurrence rate and potential wound infection in breast cancer after surgery pose enormous risks to patient survival. In this study, a polyethylene glycol acrylate (PEGDA)‐alginate double‐network nanocomposite hydrogel (GPA) embedded with 125I‐labeled RGDY peptide‐modified gold nanorods (125I‐GNR‐RGDY) is fabricated. The double‐network hydrogel is formed by injection of GPA precursor solutions into the cavity of resected cancerous breasts of mice where gelation occurred rapidly. The enhanced temperature‐induced PEGDA polymerization driven by near‐infrared light irradiation, and then, the second polymer network is crosslinked between alginate and endogenous Ca2+ around the tumor. The double‐network hydrogel possesses a dense polymer network and tightly fixes 125I‐GNR‐RGDY, which exhibit superior persistent photothermal and radioactive effects. Hyperthermia induced by photothermal therapy can inhibit self‐repair of damaged DNA and promote blood circulation to improve the hypoxic microenvironment, which can synergistically enhance the therapeutic efficacy of brachytherapy and simultaneously eliminate pathogenic bacteria. Notably, this nanocomposite hydrogel facilitates antibacterial activity to prevent potential wound infection and is tracked by single‐photon emission computerized tomography imaging owing to isotope labeling of loaded 125I‐GNR‐RGDY. The combination of photothermal therapy and brachytherapy has enabled the possibility of proposing a novel postoperative adjuvant strategy for preventing tumor recurrence and wound infection.

Background Panax notoginseng is an important herbal medicine in China, where this crop is cultivated by replanting of seedlings. Root rot disease threatens the sustainability of P. notoginseng cultivation. Water flooding (WF) is widely used to control numerous soilborne diseases, and biogas slurry shows positive effects on the soil physiochemical properties and microbial community structure and has the potential to suppress soilborne pathogens. Hence, biogas slurry flooding (BSF) may be an effective approach for alleviating root rot disease of P. notoginseng; however, the underlying mechanism needs to be elucidated. Methods In this study, we conducted a microcosm experiment to determine if BSF can reduce the abundance of pathogens in soil and, alleviate root rot of P. notoginseng. Microcosms, containing soil collected from a patch of P. notoginseng showing symptoms of root rot disease, were subjected to WF or BSF at two concentrations for two durations (15 and 30 days), after which the changes in their physicochemical properties were investigated. Culturable microorganisms and the root rot ratio were also estimated. We next compared changes in the microbial community structure of soils under BSF with changes in WF and untreated soils through high-throughput sequencing of bacterial 16S rRNA (16S) and fungal internal transcribed spacer (ITS) genes amplicon. Results WF treatment did not obviously change the soil microbiota. In contrast, BSF treatment significantly altered the physicochemical properties and reshaped the bacterial and fungal communities, reduced the relative abundance of potential fungal pathogens (Fusarium, Cylindrocarpon, Alternaria, and Phoma), and suppressed culturable fungi and Fusarium. The changes in the microbial community structure corresponded to decreased root rot ratios. The mechanisms of fungal pathogen suppression by BSF involved several factors, including inducing anaerobic/conductive conditions, altering the soil physicochemical properties, enriching the anaerobic and culturable bacteria, and increasing the phylogenetic relatedness of the bacterial community. Conclusions BSF application can reshape the soil microbial community, reduce the abundance of potential pathogens, and alleviate root rot in P. notoginseng. Thus, it is a promising practice for controlling root rot disease in P. notoginseng.

The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity. For the first time, we used the in situ enzyme-instructed self-assembly (EISA) of a peptide derivative (Nap-GDFDFpYSV) to selectively enhance the sensitivity of cancer cells with high alkaline phosphatase (ALP) expression to ionizing radiation (IR). Compared with the in vitro pre-assembled control formed by the same molecule, assemblies formed by in situ EISA in cells greatly sensitized the ALP-high-expressing cancer cells to γ-rays, with a remarkable sensitizer enhancement ratio. Our results indicated that the enhancement was a result of fixing DNA damage, arresting cell cycles and inducing cell apoptosis. Interestingly, in vitro pre-formed assemblies mainly localized in the lysosomes after incubating with cells, while the assemblies formed via in situ EISA scattered in the cell cytosol. The accumulation of these molecules in cells could not be inhibited by endocytosis inhibitors. We believed that this molecule entered cancer cells by diffusion and then in situ self-assembled to form nanofibers under the catalysis of endogenous ALP. This study provides a successful example to utilize intracellular in situ EISA of small molecules to develop selective tumor radiosensitizers.

Abstract Background Porcine epidemic diarrhea virus (PEDV) is a causative agent of serious viral enteric disease in suckling pigs. Such diseases cause considerable economic losses in the global swine industry. Enhancing our knowledge of PEDV-induced transcriptomic responses in host cells is imperative to understanding the molecular mechanisms involved in the immune response. Here, we analyzed the transcriptomic profile of intestinal porcine epithelial cell line J2 (IPEC-J2) after infection with a classical strain of PEDV to explore the host response. Results In total, 854 genes were significantly differentially expressed after PEDV infection, including 716 upregulated and 138 downregulated genes. Functional annotation analysis revealed that the differentially expressed genes were mainly enriched in the influenza A, TNF signaling, inflammatory response, cytokine receptor interaction, and other immune-related pathways. Next, the putative promoter regions of the 854 differentially expressed genes were examined for the presence of transcription factor binding sites using the MEME tool. As a result, 504 sequences (59.02%) were identified as possessing at least one binding site of signal transducer and activator of transcription (STAT), and five STAT transcription factors were significantly induced by PEDV infection. Furthermore, we revealed the regulatory network induced by STAT members in the process of PEDV infection. Conclusion Our transcriptomic analysis described the host genetic response to PEDV infection in detail in IPEC-J2 cells, and suggested that STAT transcription factors may serve as key regulators in the response to PEDV infection. These results further our understanding of the pathogenesis of PEDV.

Abstract Backgrounds Stroke is a sudden disorder of cerebral blood circulation. Many studies have illustrated that dyslipidemia, hypertension, diabetes, smoking and excessive drinking are the traditional risk factors for stroke. This study aimed to observe the relationship between CYP1A1 and CYP1A2 variants and stroke risk in the Chinese population. Methods Agena MassARRAY Assay was used to genotype four single nucleotide polymorphisms (SNPs) in 477 cases and 480 controls. The chi-square test and logistic-regression analysis were used to explore the relationship between CYP1A1 and CYP1A2 variants and stroke risk. Results Individuals with CYP1A2 rs762551 C was associated with a lower risk of stroke than that of allele A. Age stratification analysis showed that rs762551 was only observed to be associated with a lower risk of stroke in ≤64ys age group. After gender stratification analysis, a significant association between rs762551 and stroke risk was found in males, but not in females. The four SNPs were found to be correlated with stroke risk in patients with hypertension, coronary heart disease, cerebral infarction and lacunar infarction. Conclusion In this study, the results first showed that CYP1A1 and CYP1A2 variants were associated with stroke risk. Larger and well-designed studies are needed to confirm the results.

Consecutive monocropping with sanqi (Panax notoginseng (Burkill) F.H. Chen) can increase the abundances of pathogens in soil, resulting in soil sickness. Crop rotation is one way to alleviate this problem. In the present study, there were no differences in microbial structure or bacterial alpha diversity among one-year monocropping soil, one-year rotation soil, and ten-year rotation soil. However, monocropping practices decreased fungal alpha diversity. The relative abundance of copiotrophic bacteria decreased after sanqi monocropping, while that of oligotrophic bacteria increased. Ten-year rotation significantly increased the abundance of potential beneficial bacterial genera. Moreover, the potential beneficial fungal genera were also enriched by rotation for ten years. Furthermore, the relative abundance of Cylindrocarpon spp. decreased dramatically after a ten-year rotation. The results of pot experiments showed that disease incidences after ten-year rotation were significantly decreased among the three treatments. Hence, we suggested that pausing sanqi cultivation for a long time can increase the abundance of potentially beneficial soil bacteria and fungi that are helpful for overcoming soil sickness in sanqi cultivation.

The significance of protein nanoclustering in cell polarization is unclear. Here Pan et al. show that auxin-induced TMK1/sterol nanoclustering as well as microtubule-based positive feedback regulation of the TMK1/sterol nanoclusters is critical for cell polarity formation in Arabidopsis.

Abstract Background Reproductive performance of livestock is an economically important aspect of global food production. The Chinese Meishan pig is a prolific breed, with an average of three to five more piglets per litter than European breeds; however, the genetic basis for this difference is not well understood. Results In this study, we investigated copy number variations (CNVs) of 32 Meishan pigs and 29 Duroc pigs by next-generation sequencing. A genome-wide analysis of 61 pigs revealed 12,668 copy number variable regions (CNVRs) that were further divided into three categories based on copy number (CN) of the whole population, i.e., gain (n = 7,638), and loss (n = 5,030) CNVRs. We then compared Meishan and Duroc pigs and identified 17.17 Mb of 6,387 CNVRs that only existing in Meishan pigs CNVRs that overlapped the reproduction-related gene encoding the aryl hydrocarbon receptor (AHR) gene. We found that normal AHR CN was more frequent than CN loss in four different pig breeds. An association analysis showed that AHR CN had a positive effect on litter size (P

Gaomiaozi (GMZ) bentonite is a potential buffer/backfill material for a deep geological disposal of high-level radioactive waste. It has a wide pore size distribution (PSD) with sizes ranging from several nanometers to more than one hundred microns. Thus, properly characterizing the pore structures of GMZ bentonite is a challenging issue. In this study, pressure-controlled porosimetry (PCP), rate-controlled porosimetry (RCP), and scanning electron microscopy (SEM) were used to investigate the PSD of GMZ bentonite. The results indicate that each method has its limitation, and a combined use of PCP and RCP is suitable to obtain the full-scale PSD of GMZ bentonite. Moreover, we also compared the full-scale PSD with nuclear magnetic resonance (NMR) result. It is found that there is no significant difference in the range of PSD characterization between NMR and mercury intrusion method (PCP and RCP). However, in a certain range, the detection accuracy of NMR is higher than that of mercury injection method. Finally, permeability prediction based on PCP and SEM data was conducted, and both of the two methods were found to be able to predict the permeability. The combined method is effective to obtain the full-scale PSD of GMZ bentonite, which is the key to estimation of the sealing ability of bentonite buffer. Keywords: Gaomiaozi (GMZ) bentonite, Pore size distribution (PSD), Pressure-controlled porosimetry (PCP), Rate-controlled porosimetry (RCP), Permeability, High-level radioactive waste

Soybean Sclerotinia stem rot is caused by Sclerotinia sclerotiorum infection, which causes extensive and severe damage to soybean production. Here, we isolated and patented a Bacillus amyloliquefaciens strain, and used it to verify the antagonistic effect of B. amyloliquefaciens on S. sclerotiorum and to explore the possible underlying mechanism. First, we conducted a plate confrontation experiment using the two microbes. Then, inoculation of soybean (Glycine max) seedlings with S. sclerotiorum (Gm-Ss), B. amyloliquefaciens (Gm-Ba), and their combination (Gm-Ba-Ss) was performed, followed by dual RNA sequencing analysis. Plate confrontation and inoculation experiments showed that B. amyloliquefaciens significantly antagonized S. sclerotiorum growth. The average number of fragments per kilobase of transcript per million fragments mapped of S. sclerotiorum transcripts in Gm-Ss and Gm-Ba-Ss inoculation treatments were 117.82 and 50.79, respectively, indicating that B. amyloliquefaciens strongly inhibited gene expression of S. sclerotiorum. In contrast, the average number of fragments per kilobase of transcript per million fragments mapped of B. amyloliquefaciens transcripts in Gm-Ba and Gm-Ba-Ss inoculation treatments were 479.56 and 579.66, respectively, indicating that S. sclerotiorum promoted overall gene expression in B. amyloliquefaciens. For S. sclerotiorum, 507 upregulated and 4,950 downregulated genes were identified among 8,975 genes in the paired comparison Gm-Ba-Ss vs. Gm-Ss. These differentially expressed genes (DEGs) were significantly enriched in the ribosome (ko03010) KEGG pathway. Additionally, for B. amyloliquefaciens, 294 upregulated and 178 downregulated genes were identified among all 3,154 genes in the paired comparison Gm-Ba-Ss vs. Gm-Ba, and these DEGs were mainly and significantly enriched in metabolism-related KEGG pathways, including the citrate cycle (ko00020) and carbon metabolism (ko01200). We concluded that B. amyloliquefaciens inhibits the expression of genes encoding the ribosomal subunit of S. sclerotiorum, resulting in protein synthesis inhibition in S. sclerotiorum, and thus had a strong antagonistic effect on the fungus. This study provides a scientific basis for the biological control of S. sclerotiorum by B. amyloliquefaciens.

The stress system in the brain plays a pivotal role in keeping humans and animals from harmful stimuli. However, excessive stress will cause maladaptive changes to the stress system and lead to depression. Despite the high prevalence of depression, the treatment remains limited. PKMζ, an atypical PKC isoform, has been demonstrated to play a crucial role in maintaining long-term potentiation and memory. Recent evidence shows that PKMζ is also involved in stress response and depressive-like behavior. In particular, it was demonstrated that stress that resulted in depressive-like behavior could decrease the expression of PKMζ in the prefrontal cortex, which could be reversed by antidepressants. Importantly, modulation of PKMζ expression could regulate depressive-like behaviors and the actions of antidepressants. These data suggested that PKMζ could be a molecular target for developing novel antidepressants. Here, I review the advance on the role of PKMζ in mediating stress response and its involvement in the development of depression.

BackgroundMandibular sagittal split ramus osteotomy (SSRO) is a routine surgery to correct mandibular deformities, such as mandibular retrusion, protrusion, deficiency, and asymmetry. However, nonunion/malunion of the fragments and relapse caused by fixation failure after SSRO are major concerns. Rigid fixation to maintain postosteotomy segmental stabilization is critical for success. Additionally, understanding the biomechanical characteristics of different fixation methods in SSRO with large advancements is extremely important for clinical guidance. Therefore, the aim of the present study was to evaluate the biomechanical characteristics of different SSRO methods by finite element analysis.MethodsSSRO finite element models with 5-, 10-, 15-, and 20-mm advancements were developed. Seven fixation methods, namely, two types of bicortical screws, single miniplate, dual miniplates, grid plate, dual L-shaped plates, and hybrid fixation, were positioned into the SSRO models. Molar and incisal biomechanical loads were applied to all models to simulate bite forces. We then investigated the immediate postoperative stability from four aspects, namely, the stability of the distal osteotomy segment, osteotomy regional stability, stress distribution on the mandible, and implant stress performance.ResultsThe stability of the distal osteotomy segment and osteotomy region decreased when the advancement increased. All seven fixation methods displayed favorable biomechanical stability under minor advancement (5 mm). With large advancements, bicortical screws, dual miniplates, and grid plates provided better stability. The von Mises stress was concentrated around the screws close to the osteotomy region for the proximal segment for all fixation methods, and the von Mises stress on implants increased with larger advancements. With small advancements, five fixation methods endured tolerable maximum stresses of

BackgroundThe endoscopic modified Lothrop procedure (EMLP) is an important procedure used to address frontal and anterior skull-base lesions. Two techniques were established, namely, the inside-out approach and the outside-in approach. The former technique take the frontal recess and the first olfactory filament (FOF) as key landmarks while the latter use the FOF as posterior boundary. In some cases, however, these two landmarks are not available. Therefore, we supplement the outside-in approach and named it trans-nasion-complex approach (TNCA) for EMLP that can be performed without locating these two landmarks.MethodsTwo dry human skulls were used to observe the bony nasion complex. Then, five colored silicon-injected human head specimens were dissected via TNCA for EMLP. Finally, the outcomes of patients who underwent TNCA were reviewed.ResultsThe nasion complex is an osseous complex that consists of the nasion and its adjacent structures, including the bilateral root of nasal bones, nasal process of frontal bones, anterior portion of the perpendicular plate of the ethmoid bone that connects with the inferior aspect of the nasal bones, and portions of the bilateral frontal process of the maxillary bones. Surgical landmarks for TNCA include the anterior superior portion of the nasal septum, anterior margin and axilla of the middle turbinate, frontal process of the maxilla bone, nasal process of the frontal bone and upper part of the nasal bone. These structures form a “mushroom sign” during cadaveric dissection and surgery. Twenty-one patients underwent TNCA, of whom 9 had tumors and 12 had chronic rhinosinusitis with nasal polyps (CRSwNP). None of them had major complications.ConclusionTNCA is expected to be a safe, and direct route for EMLP. Adequate understanding of the nasion complex and “mushroom sign” will be helpful to complete TNCA.

The Longmaxi Formation in the southern Sichuan Basin is an important target for shale gas exploration and development. The characteristics and stages of structural development significantly impact shale gas preservation and enrichment. Taking the Longmaxi Formation in the Yanjin–Junlian area of the southern Sichuan Basin as an example and based on the results of surface and underground structural analysis, fluid inclusion tests, apatite fission track experiments, and burial-thermal evolution history analysis, a comprehensive study of the development characteristics and structural stages of the Longmaxi Formation was carried out, and an evolution model was developed. (1) The Longmaxi Formation of the Yanjin–Junlian area has been affected by multistage structural movements and exhibits structural compounding and superposition corresponding to different stages. The formation of surface tracks of the folds and faults has been affected by multidirectional extrusion stresses of the near SN, NE, and near EW. There are three stages of underground faults in the Longmaxi Formation, and the strikes are nearly EW, NE, and nearly SN. (2) Three distribution intervals for the homogenization temperature ranges of fracture fillings are 161–195°C, 121–143°C, and 74–105°C. The apatite thermal history simulation reveals that the Longmaxi Formation experienced three stages of tectonic movement after its formation. (3) There were clearly three stages in the structural development of the Longmaxi Formation in this area: the late Jurassic–Palaeocene (55 ± 5–38 ± 2 Ma), Eocene–early Miocene (38 ± 2–15.5 ± 3.5 Ma), and late Miocene-present (15.5 ± 3.5 Ma–present). Thus, a compound fracture system with superimposed structural deformations in different directions and at different stages formed in the study area. (4) A model for the stages and development of structural tracks in the Longmaxi Formation was established in conjunction with structural analysis and geomechanical theory. The results have guiding significance for the evaluation of shale gas preservation conditions and accumulation in the study area.

With the continuous expansion of the UHV AC/DC interconnection scale, online, high-precision, and fast transient stability assessment (TSA) is very important for the safe operation of power grids. In this study, a transient stability assessment method based on the gating spatiotemporal graph neural network (GSTGNN) is proposed. A time-adaptive method is used to improve the accuracy and speed of transient stability assessment. First, in order to reduce the impact of dynamic topology on TSA after fault removal, GSTGNN is used to extract and fuse the key features of topology and attribute information of adjacent nodes to learn the spatial data correlation and improve the evaluation accuracy. Then, the extracted features are input into the gated recurrent unit (GRU) to learn the correlation of data at each time. Fast and accurate evaluation results are output from the stability threshold. At the same time, in order to avoid the influence of the quality of training samples, an improved weighted cross entropy loss function with the K-nearest neighbor (KNN) idea is used to deal with the unbalanced training samples. Through the analysis of an example, it is proved from the data visualization that the TSA method can effectively improve the assessment accuracy and shorten the assessment time.

Soybean (Glycine max L.) is the most important crop plant in the world. Soil saline-alkali seriously inhibits soybean yield and quality. This study aims to investigate the impact of graphene oxide (GO) and Rhizobium (Rh) on the expression of soybean-related genes as well as the growth and yield under saline-alkali stress. The results show that GO + Rh-treated increased the number of root nodules by 5.43 times compared with the control (Ctrl), the total nitrogen content and root system parameters of plants were also significantly improved. GO + Rh-treated reduced the Na+/K+ ratio and the osmotic substances, while the activities of antioxidant enzymes SOD, POD, CAT and APX in GO + Rh-treated soybean plants increased significantly by 69.18%, 69%, 75.64% and 48.38% compared with the control plants. The REC, MDA and H2O2 content decreased significantly by 46.73%, 42.80% and 43.53%. In addition, GA3 content, among all related saline-alkali hormones, was increased by 100.20% compared with the Ctrl. The expression level of GmGBP1, a key gene for GA3 synthesis, at most increased 6.42 times compared to the Ctrl. The results further reveal that GO + Rh-treated obviously improves the yield traits of soybean plants, which confirms that GO + Rh-treated could be effective in enhancing soybean tolerance to saline-alkali stress. Our findings provide a new strategy for improving the saline-alkali tolerance of soybean, as well as a new perspective for exploiting and utilizing large-area saline-alkali soil.

Melatonin is a tryptophan derivative synthesized in plants and animals. In humans, melatonin acts on melatonin MT1 and MT2 receptors belonging to the G protein-coupled receptor (GPCR) family. Synthetic melatonin receptor agonists are prescribed for insomnia and depressive and circadian-related disorders. Here, we tested 25 commercial plant extracts, reported to have beneficial properties in sleep disorders and anxiety, using cellular assays (2─[125I]iodomelatonin binding, cAMP inhibition, ERK1/2 activation and β-arrestin2 recruitment) in mock-transfected and HEK293 cells expressing MT1 or MT2. Various melatonin receptor-dependent and -independent effects were observed. Extract 18 (Ex18) from Pistacia vera dried fruits stood out with very potent effects in melatonin receptor expressing cells. The high content of endogenous melatonin in Ex18 (5.28 ± 0.46 mg/g extract) is consistent with this observation. Ex18 contains an additional active principle that potentiates the effect of melatonin on Gi protein-dependent pathways but not on β-arrestin2 recruitment. Further active principles potentiating exogenous melatonin were detected in several extracts. In conclusion, we identified plant extracts with various effects in GPCR-based binding and signalling assays and identified high melatonin levels and a melatonin-potentiating activity in Pistacia vera dried fruit extracts that might be of therapeutic potential.

The effects of tree age on the growth of cutting seedlings propagated from ancient trees have been an important issue in plant breeding and cultivation. In order to understand seedling growth and stress resistance stability, phenotypic measurements, physiological assays, and high-throughput transcriptome sequencing were performed on sown seedlings propagated from 5-year-old donors and cutting seedlings propagated from 5-, 300-, and 700-year-old Platycladus orientalis donors. In this study, the growth of cutting seedlings propagated from ancient trees was significantly slower; the soluble sugar and chlorophyll contents gradually decreased with the increase in the age of donors, and the flavonoid and total phenolic contents of sown seedlings were higher than those of cutting seedlings. Enrichment analysis of differential genes showed that plant hormone signal transduction, the plant–pathogen interaction, and the flavone and flavonol biosynthesis pathways were significantly up-regulated with the increasing age of cutting seedlings propagated from 300- and 700-year-old donors. A total of 104,764 differentially expressed genes were calculated using weighted gene co-expression network analysis, and 8 gene modules were obtained. Further, 10 hub genes in the blue module were identified, which revealed that the expression levels of JAZ, FLS, RPM1/RPS3, CML, and RPS2 increased with the increase in tree age. The results demonstrated that the age of the donors seriously affected the growth of P. orientalis cutting seedlings and that cutting propagation can preserve the resistance of ancient trees. The results of this study provide important insights into the effects of age on asexually propagated seedlings, reveal potential molecular mechanisms, and contribute to an improvement in the level of breeding and conservation of ancient germplasm resources of P. orientalis trees.

Beijing Black pig is an excellent cultivated black pig breed in China, with desirable body shape, tender meat quality and robust disease resistance. To explore the level of admixture and selection signatures of Beijing Black pigs, a total number of 90 individuals covering nine pig breeds were used in our study, including Beijing Black pig, Large White, Landrace, Duroc, Lantang pig, Luchuan pig, Mashen pig, Huainan pig and Min pig. These animals were resequenced with 18.19 folds mapped read depth on average. Generally, we found that Beijing Black pig was genetically closer to commercial pig breeds by population genetic structure and genetic diversity analysis, and was also affected by Chinese domestic breeds Huainan pig and Min pig. These results are consistent with the cross-breeding history of Beijing Black pig. Selection signal detections were performed on three pig breeds, Beijing Black pig, Duroc and Large White, using three complementary methods (FST, θπ, and XP-EHH). In total, 1,167 significant selected regions and 392 candidate genes were identified. Functional annotations were enriched to pathways related to immune processes and meat and lipid metabolism. Finally, potential candidate genes, influencing meat quality (GPHA2, EHD1, HNF1A, C12orf43, GLTP, TRPV4, MVK, and MMAB), reproduction (PPP2R5B and MAP9), and disease resistance (OASL, ANKRD13A, and GIT2), were further detected by gene annotation analysis. Our results advanced the understanding of the genetic mechanism behind artificial selection of Beijing Black pigs, and provided theoretical basis for the subsequent breeding and genetic research of this breed.

Drought is one of the most severe environmental stressors that place major constraints on the growth of soybeans (Glycine max L.). Graphene oxide (GO) is a nanomaterial that can promote plant growth without toxic effects. In this study, the physiological and molecular responses to drought stress with GO treatment were examined. We discovered that the relative water content (RWC) of stems and leaves treated with GO was 127 and 128% higher than that of the WT plants, respectively. The root parameters in GO-treated soybeans were increased by 33, 38, 34, and 35% than WT plants in total root length, root surface area, root diameter, and root volume, respectively. The activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) were also increased by 29, 57, 28, and 66%, respectively. However, the relative conductivity (REC), malondialdehyde (MDA), and hydrogen peroxide (H2O2) accumulation were remarkably decreased. Furthermore, the content of drought-related hormones JA, SA, and ABA in GO-treated soybeans increased by 32, 34, and 67% than WT plants, respectively. At the molecular level, the effects of GO treatment were manifested by relatively higher expression of four drought-related genes: GmP5CS, GmGOLS, GmDREB1, and GmNCED1. Taken together, our findings revealed that GO could directly increase plant defense enzymes, hormone content, and the expression of drought-related genes, thereby improving the soybean’s ability to resist drought. These findings could provide new opportunities for improving drought tolerance in soybeans through effective soil water retention agents.

Abstract Radiotherapy (RT) has been viewed as one of the most effective and extensively applied curatives in clinical cancer therapy. However, the radioresistance of tumor severely discounts the radiotherapy outcomes. Here, an innovative supramolecular radiotherapy strategy, based on the complexation of a hypoxia‐responsive macrocycle with small‐molecule radiosensitizer, is reported. To exemplify this tactic, a carboxylated azocalix[4]arene (CAC4A) is devised as molecular container to quantitatively package tumor sensitizer banoxantrone dihydrochloride (AQ4N) through reversible host–guest interaction. Benefited from the selective reduction of azo functional groups under hypoxic microenvironment, the supramolecular prodrug CAC4A•AQ4N exhibits high tumor accumulation and efficient cellular internalization, thereby significantly amplifying radiation‐mediated tumor destruction without appreciable systemic toxicity. More importantly, this supramolecular radiotherapy strategy achieves an ultrahigh sensitizer enhancement ratio (SER) value of 2.349, which is the supreme among currently reported noncovalent‐based radiosensitization approach. Further development by applying different radiosensitizing drugs can make this supramolecular strategy become a general platform for boosting therapeutic effect in cancer radiotherapies, tremendously promising for clinical translation.

Residual feed intake (RFI) is considered as a measurement of feed efficiency, which is greatly related to the growth performance in pigs. Daily feeding records can be obtained from automatic feeders. In general, RFI is usually calculated from the total measurement records during the whole test period. This measurement cannot reflect genetic changes in different growth periods during the test. A random regression model (RRM) provides a method to model such type of longitudinal data. To improve the accuracy of genetic prediction for RFI, the RRM and regular animal models were applied in this study, and their prediction performances were compared. Both traditional pedigree-based relationship matrix (A matrix) and pedigree and genomic information-based relationship matrix (H matrix) were applied for these two models. The results showed that, the prediction accuracy of the RRM was higher than that of the animal model, increasing 24.2% with A matrix and 40.9% with H matrix. Furthermore, genomic information constantly improved the accuracy of evaluation under each evaluation model. In conclusion, longitudinal traits such as RFI can describe feed efficiency better, and the RRM with both pedigree and genetic information was superior to the animal model. These results provide a feasible method of genomic prediction using longitudinal data in animal breeding.

ObjectivesTraumatic orbital apex syndrome (TOAS) is an uncommon but severe ocular complication of craniomaxillofacial fracture. The optimal surgical strategy for TOAS has not been determined. To investigate the endoscopic anatomy of the orbital apex region, propose a protocol for simultaneous endoscopic endonasal decompression of the optic canal, superior orbital fissure, and proper orbital apex (EEDCFA) for TOAS and report its use in two patients.MethodsAn endoscopic endonasal approach was utilized to dissect the orbital apex region in two silicon-injected adult cadaveric heads. The details of the procedure used for decompression of the orbital apex were determined. The effects of this procedure were determined in two patients with TOAS who underwent simultaneous decompression of the optic canal, superior orbital fissure, and proper orbital apex.ResultsThe orbital apex consisted of three portions, the contents of the optic canal superomedially; the contents of the superior orbital fissure inferolaterally; and the converging portion, or proper orbital apex, anteriorly. From an endoscopic endonasal approach, the optic nerve, superior orbital fissure, and orbital apex convergence prominences were found to form a π-shaped configuration. This π-shaped configuration was indicative of the orbital apex and was an important landmark for decompression of the orbital apex. Endonasal decompression of the orbital apex in the two patients resulted in the satisfactory recovery of extraocular mobility, with no surgical complications.ConclusionsEEDCFA is feasible, effective, and safe for patients with TOAS caused by direct compression of displaced fracture segments. The π-shaped configuration is a valuable landmark for EEDCFA.

Members of the phylum Acidobacteria are ubiquitous in various environments. Soil acidobacteria have been reported to present a variety of strategies for their success in terrestrial environments. However, owing to lack of pure culture, information on animal-associated acidobacteria are limited, except for those obtained from 16S rRNA genes. To date, only two acidobacteria have been isolated from animals, namely strain M133T obtained from coral Porites lutea and Acanthopleuribacter pedis KCTC 12899T isolated from chiton. Genomics and physiological characteristics of strain M133T and A. pedis KCTC 12899T were compared with 19 other isolates (one strain from each genus) in the phylum Acidobacteria. The results revealed that strain M133T represents a new species in a new genus in the family Acanthopleuribacteraceae. To date, these two Acanthopleuribacteraceae isolates have the largest genomes (10.85–11.79 Mb) in the phylum Acidobacteria. Horizontal gene transfer and gene duplication influenced the structure and plasticity of these large genomes. Dissimilatory nitrate reduction and abundant secondary metabolite biosynthetic gene clusters (including eicosapentaenoic acid de novo biosynthesis) are two distinct features of the Acanthopleuribacteraceae bacteria in the phylum Acidobacteria. The absence of glycoside hydrolases involved in plant polysaccharide degradation and presence of animal disease-related peptidases indicate that these bacteria have evolved to adapt to the animal hosts. In addition to low- and high-affinity respiratory oxygen reductases, enzymes for nitrate to nitrogen, and sulfhydrogenase were also detected in strain M133T, suggesting the capacity and flexibility to grow in aerobic and anaerobic environments. This study highlighted the differences in genome structure, carbohydrate and protein utilization, respiration, and secondary metabolism between animal-associated acidobacteria and other acidobacteria, especially the soil acidobacteria, displaying flexibility and versatility of the animal-associated acidobacteria in environmental adaption.

Anaerobic digestion is widely used to simultaneously generate biogas while treating different organic wastes. It is difficult to determine the source of CH4 from the complex microbial community structure using traditional microbiological pure culture techniques. Therefore, this study aimed to elucidate the microbial source of CH4 in low-temperature anaerobic digestion systems using the recently developed high-throughput sequencing technology. Herein, anaerobic digestion microbes were domesticated at 15°C and then inoculated into pig manure-containing raw materials in a batch anaerobic digester to form a low-temperature anaerobic digestion system with fermentation controlled at 15°C. Several analytical approaches including abiotic factor analysis and biotic factor analysis (high-throughput sequencing) were applied to investigate the abiotic factors, bacterial communities, and archaeal communities in the low-temperature anaerobic digestion system. The results showed that: 1) The anaerobic digestion lasted for 120 days, with 68.65 L total gas production and 31.19 L CH4 production. 2) The relative abundances of the primary and secondary dominant bacterial operational taxonomic units ranged from 8.02 to 22.84% and 5.62–17.09%, respectively, with 99% similarities to Clostridium cellulovorans (a typical cellulose- and hemicellulose-degrading bacterium) and Terrisporobacter petrolearius (a representative fermentation bacterium), respectively. Moreover, the relative abundance of the primary dominant methanogenic archaeal operational taxonomic unit ranged from 1.03 to 16.85%, with 98% similarity to Methanobacterium beijingense, which is a typical hydrogenotropic methanogen. Based on the low-temperature CH4-producing metabolic pathways of bacterial and methanogenic operational taxonomic units, Methanobacterium beijingense was found to be the primary functional microbe for CH4 production in the 15°C anaerobic digestion system.

Design of low-density SNP chips provides an opportunity for wide application of genomic selection at lower cost. A novel strategy referred to as the “block-free” method is proposed in this study to select a subset of SNPs from a high-density chip to form a low-density panel. In this method, Feature Selection using a Feature Similarity (FSFS) algorithm was first performed to remove highly correlated SNPs, and then a Multiple-Objective, Local-Optimization (MOLO) algorithm was used to pick SNPs for the low-density panel. Two other commonly used methods called the “uniform” method and the “block-based” method were also implemented for comparison purposes. A real pig dataset with 7967 individuals from three breeds containing 43,832 SNPs was used for comparison of the methods. In terms of genotype imputation accuracy and genomic prediction accuracy, our strategy was superior in most cases when the densities were lower than 1K. The genotype imputation accuracy from the low-density chip compared to the original high-density chip was higher than 90% in all pig breeds as the density increased to 1K. In addition, the accuracies of predicted genomic breeding values (GEBV) calculated using the imputed panel were nearly 90% of estimates from the original chip for all traits and breeds. Our strategy is effective to design low-density chips by making full use of information of close relationships for genomic selection in animals and plants.

Intramuscular fat content and marbling affecting meat quality are important economic traits in beef cattle. CDC10 (cell division cycle 10 or Septin 7), a member of the septin family involved in cellular proliferation, was considered as a functional and positional candidate gene for beef marbling. In a previous study, we revealed that the expression levels of CDC10 were also positively correlated with marbling scores in Japanese Black cattle. However, the regulatory mechanism of the CDC10 gene on IMF deposition in cattle remains unclear. In the present study, flow cytometry, EdU proliferation assays, and Oil Red O staining results showed that overexpression of CDC10 could promote the differentiation of bovine intramuscular preadipocyte (BIMP) and 3T3-L1 cells, whereas knockdown of CDC10 resulted in the opposite consequences. Furthermore, quantitative PCR and Western blotting results showed that overexpression of CDC10 could promote the expression levels of adipogenic marker genes PPARγ and C/EBPα at both mRNA and protein levels in BIMP and 3T3-L1 cells, whereas knockdown of CDC10 resulted in the opposite consequences. Our results provide new insights into the regulatory roles of CDC10 in adipocytes in animals.

Bentysrepinine (Y101) is a novel phenylalanine dipeptide for the treatment of hepatitis B virus. Renal excretion played an important role in the elimination of Y101 and its metabolites, M8 and M9, in healthy Chinese subjects, although the molecular mechanisms of renal excretion and potential drug–drug interactions (DDIs) remain unclear. The present study aimed to determine the organic anion transporters (OATs) involved in the renal disposition of Y101 and to predict the potential DDI between Y101 and entecavir, the first-line agent against HBV and a substrate of OAT1/3. Pharmacokinetic studies and uptake assays using rat kidney slices, as well as hOAT1/3-HEK293 cells, were performed to evaluate potential DDI. The co-administration of probenecid (an inhibitor of OATs) significantly increased the plasma concentrations and area under the plasma concentration–time curves of M8 and M9 but not Y101, while reduced renal clearance and the cumulative urinary excretion of M8 were observed in rats. The time course of Y101 and M8 uptake via rat kidney slices was temperature-dependent. Moreover, the uptake of M8 was inhibited significantly by probenecid and benzylpenicillin, but not by p-aminohippurate or tetraethyl ammonium. M8 was found to be a substrate of hOAT3, but Y101 is not a substrate of either hOAT1 or hOAT3. Additionally, the entecavir inhibited the uptake of M8 in the hOAT3-transfected cells and rat kidney slices in vitro. Interestingly, no significant changes were observed in the pharmacokinetic parameters of Y101, M8 or entecavir, regardless of intravenous or oral co-administration of Y101 and entecavir in rats. In conclusion, M8 is a substrate of OAT3 in rats and humans. Furthermore, M8 also mediates the DDI between Y101 and entecavir in vitro, mediated by OAT3. We speculate that it would be safe to use Y101 with entecavir in clinical practice. Our results provide useful information with which to predict the DDIs between Y101 and other drugs that act as substrates of OAT3.

Tibetan sheep are one of the three major coarse sheep breeds in China, and they possess a long history of formation. However, few studies have been conducted on the identification of Tibetan sheep breeds at the molecular level. In this study, a total of 448 individuals from 24 Tibetan sheep populations in the 5 regions of Tibet, Qinghai, Gansu, Yunnan, and Sichuan were analyzed using the Affymetrix Ovine SNP 600K high-density chip to construct specific single-nucleoside polymorphism (SNP) genetic marker sets of Tibetan sheep breeds. Firstly, the genetic structure analysis showed that Yunnan–Tibetan sheep (NL, Ninglang; JC, Jianchuan), Zuogong (ZG), Heizang (HZ), Gongga (GG,) and Tao sheep (TS) can be clearly distinguished from other Tibetan sheep populations. Next, based on the population differentiation index FST, the PCA and NJ tree results showed that only 60 specific SNPs can successfully separate Tibetan sheep in the Yunnan region from Tibetan sheep in other regions, and the distinguishing effect on Yunnan–Tibetan sheep reached 100%. Using the same method, we found that 4 Tibetan sheep breeds, including Zuogong (ZG, 20 SNPs), Heizang (HZ, 60 SNPs), Gongga (GG, 60 SNPs), and Tao sheep (TS, 30 SNPs), can also be distinguished from other Tibetan sheep populations with only a few SNP loci (20–60), and the distinguishing effect reached 100%. Overall, we successfully obtained a Yunnan region-specific (60 SNPs) genetic marker set and 4 breed-specific SNP genetic marker sets (20–60 SNPs) for the first time for the identification of Tibetan sheep breeds at the molecular level. These made up for the lack of genetic marker sets for the identification of Tibetan sheep breeds, and provided a genomic basis for the scientific classification and accurate identification of livestock and poultry genetic resources on the Qinghai–Tibet Plateau.

Background: The mandibular sagittal split ramus osteotomy (SSRO) is a routine operation performed to correct mandibular deformity including mandibular retrusion, protrusion, deficiency, and asymmetry. The SSRO remains a challenging procedure for junior surgeons due to a lack of adequate morphological knowledge necessary for success in clinical practice. Virtual reality (VR) and three-dimensional printed (3DP) models have been widely applied in anatomy education. The present randomized, controlled study was performed to evaluate the effect of traditional educational instruments, VR models, and 3DP models on junior surgeons learning the morphological information required to perform SSRO.Methods: Eighty-one participants were randomly assigned to three learning groups: Control, VR, and 3DP. Objective and subjective tests were used to evaluate the learning effectiveness of each learning instrument. In the objective test, participants were asked to identify 10 anatomical landmarks on normal and deformed models, draw the osteotomy line, and determine the description of SSRO. In the subjective test, participants were asked to provide feedback regarding their subjective feelings about the learning instrument used in their group.Results: The objective test results showed that the VR and 3DP groups achieved better accuracy in drawing the osteotomy line (p = 0.027) and determining the description of SSRO (p = 0.023) than the Control group. However, there was no significant difference among the three groups regarding the identification of anatomical landmarks. The VR and 3DP groups gave satisfactory subjective feedback about the usefulness in learning, good presentation, and enjoyment. The Control and 3DP groups reported positive feelings about ease of use.Conclusion: The current findings suggest that VR and 3DP models were effective instruments that assisted in the morphological understanding of SSRO-related anatomical structures. Furthermore, 3DP models may be a promising supplementary instrument to bridge the gap between conventional learning and clinical practice.

Corylus heterophylla (2n = 22) is the most widely distributed, unique, and economically important nut species in China. Chromosome-level genomes of C. avellana, C. heterophylla, and C. mandshurica have been published in 2021, but a satisfactory hazelnut genome database is absent. Northeast China is the main distribution and cultivation area of C. heterophylla, and the mechanism underlying the adaptation of C. heterophylla to extremely low temperature in this area remains unclear. Using single-molecule real-time sequencing and the chromosomal conformational capture (Hi-C) assisted genome assembly strategy, we obtained a high-quality chromosome-scale genome sequence of C. heterophylla, with a total length of 343 Mb and scaffold N50 of 32.88 Mb. A total of 94.72% of the test genes from the assembled genome could be aligned to the Embryophyta_odb9 database. In total, 22,319 protein-coding genes were predicted, and 21,056 (94.34%) were annotated in the assembled genome. A HazelOmics online database (HOD) containing the assembled genome, gene-coding sequences, protein sequences, and various types of annotation information was constructed. This database has a user-friendly and straightforward interface. In total, 439 contracted genes and 3,810 expanded genes were identified through genome evolution analysis, and 17 expanded genes were significantly enriched in the unsaturated fatty acid biosynthesis pathway (ko01040). Transcriptome analysis results showed that FAD (Cor0058010.1), SAD (Cor0141290.1), and KAT (Cor0122500.1) with high expression abundance were upregulated at the ovule maturity stage. We deduced that the expansion of these genes may promote high unsaturated fatty acid content in the kernels and improve the adaptability of C. heterophylla to the cold climate of Northeast China. The reference genome and database will be beneficial for future molecular breeding and gene function studies in this nut species, as well as for evolutionary research on species of the order Fagales.

G protein-coupled receptors (GPCRs) are among the most promising drug targets. They often form homo- and heterodimers with allosteric cross-talk between receptor entities, which contributes to fine-tuning of transmembrane signaling. Specifically controlling the activity of GPCR dimers with ligands is a good approach to clarify their physiological roles and validate them as drug targets. Here, we examined the mode of action of positive allosteric modulators (PAMs) that bind at the interface of the transmembrane domains of the heterodimeric GABAB receptor. Our site-directed mutagenesis results show that mutations of this interface impact the function of the three PAMs tested. The data support the inference that they act at the active interface between both transmembrane domains, the binding site involving residues of the TM6s of the GABAB1 and the GABAB2 subunit. Importantly, the agonist activity of these PAMs involves a key region in the central core of the GABAB2 transmembrane domain, which also controls the constitutive activity of the GABAB receptor. This region corresponds to the sodium ion binding site in class A GPCRs that controls the basal state of the receptors. Overall, these data reveal the possibility of developing allosteric compounds able to specifically modulate the activity of GPCR homo- and heterodimers by acting at their transmembrane interface.

Summary: Neurotransmitter receptors are involved in cancer progression. Among them, the heterodimeric GABAB receptor, activated by the main inhibitory neurotransmitter GABA, is composed of the transmembrane GABAB1 and GABAB2 subunits. The oncogenic role of the isoform GABAB1e (GB1e) containing only the extracellular domain of GABAB1 remains unclear. We revealed that GB1e is largely expressed in human breast cancer (BrCa) cell lines as well as in BrCa tissues where it is upregulated. Moreover, GB1e promoted the malignancy of BrCa cells both in vitro and in vivo. We propose that GB1e favors EGFR signaling by interacting with PTPN12 to disrupt the interaction between EGFR and PTPN12, and phosphorylation of Y230 and Y404 on GB1e is required in this process. Our data highlight that the GABBR1 gene through the expression of the GB1e isoform might play an important oncogenic role in BrCa and that GB1e is of interest for the treatment of some cancers.

Objective: To investigate the clinical utility of ultrasound-guided balloon occlusion in cesarean section in patients with sinister placenta previa. Methods: The Interventional and Ultrasound Departments of the authors’ center assisted obstetrics to complete cesarean section in cases of sinister placenta previa. A total of 130 patients with implanted sinister placenta previa were diagnosed using obstetrical ultrasound and magnetic resonance imaging (MRI). Before cesarean section, the balloon was positioned in the bilateral radial or abdominal aorta. Immediately after delivery of the fetus, the balloon was temporarily filled to transiently seal the target vessel. According to the obstetrician’s assessment of hemostasis, the balloon was withdrawn at the appropriate time. Among the 130 patients, there was one case of abdominal aortic occlusion, with 129 cases blocked by the bilateral common iliac artery. Results: All 130 cases were successfully blocked, with an average blocking time of

Abstract Background Triatomines are natural vectors of Chagas disease and are mainly prevalent in the Americas. In China, previous data from decades ago showed that there were two species of triatomine bugs, Triatoma rubrofasciata and T. sinica. However, the distribution, genetic characteristics and public health implications of triatomines in China are still relatively unknown. In order to gain knowledge on the distribution, genetic characteristics and public health implications of the triatomines in Guangxi, China, an entomological-epidemiological study and genetic research was conducted. Methods Different methods were used to elucidate the distribution of triatomines in Guangxi including consultations with county-level Center for Disease Prevention and Control staff and village doctors, the distribution of educational material on triatomines though the internet and social media apps such as Wechat and QQ, and conducting manual inspections and light trapping to collect triatomines. The morphological characteristics of the collected triatomines were identified under light microscopy. The mitochondrial 16S rRNA, cytochrome b (cytb) genes and nuclear 28S rRNA gene were amplified, sequenced and used in phylogenetic analyses. Results A total of 305 triatomines were captured from 54 different sites in 13 cities in Guangxi. All collected bugs were identified as T. rubrofasciata based on morphology. Most triatomine collection sites were around or inside houses. Four triatomines bite cases were observed during the investigation indicating that triatomine bites are common, the bites can cause serious anaphylaxis and skin papules and urticaria, suggesting a systemic skin response. The 16S rRNA, 28S rRNA and cytb sequence analyses of T. rubrofasciata from Guangxi and other countries showed that T. rubrofasciata sequences from different regions exhibit a high similarity, with no geographical differences. The phylogenetic tree based on the 16S rRNA and cytb genes showed that T. rubrofasciata sequences from different regions and continents were in the same cluster, indicating no differentiation among different geographical populations. Conclusions Our study showed that T. rubrofasciata is widely distributed in Guangxi and that people are commonly bitten by this insect in some regions. This highlights the need to enhance surveillance for and control of T. rubrofasciata and to strengthen the monitoring of imported Trypanosoma cruzi in China. The 16S rRNA, 28S rRNA and cytb sequence analyses of T. rubrofasciata from different regions and continents suggested that T. rubrofasciata populations exhibit high similarity, and the clustering in the phylogenetic analyses indicates that T. rubrofasciata has a close ancestor originating in the Americas.

In this article, a dielectric resonator (DR) excited wideband metasurface (MTS) antenna with differential feeding is proposed, which uses two modes of the MTS and the fundamental mode of the DR to achieve multimode operation and obtain wide bandwidth. Initially, based on the characteristic mode theory, relevant modes of the MTS are analyzed. Then, a DR operating at the fundamental mode (TEδ11x) is introduced as the magnetic current source to feed the MTS, exciting the dominant mode and high order mode (HOM) of the MTS simultaneously. However, this HOM has a weak gain at the broadside direction and large side lobes. According to the superposition principle of radiation patterns, the maximum at the broadside generated by the DR is utilized to enhance the boresight gain of the HOM, thus transforming the top-weak radiation pattern of this HOM into a broadside one and improving the gain flatness. Additionally, the differential feeding technique is introduced to improve the asymmetry of radiation pattern. Furthermore, by analyzing the out-of-phase currents and the periodicity of the MTS patches, three measures -loading transverse open-ended slots, shortening periodicity and loading longitudinal slots- are introduced to reduce the high side lobe level of the HOM while preserving radiation patterns undistorted and improving the gain stability. As a result, this HOM and the dominant mode of the MTS are combined with the fundamental mode of the DR, achieving multimode operation. Finally, the proposed antenna was fabricated and measured. The measured results agree well with the simulated ones, indicating an impedance bandwidth of 51.4% (4.38-7.41 GHz), a 5-9 dBi in-band gain and a 15 dB front-to-back ratio (FBR) within the operating band.

Abstract Background Intestinal helminth infections are a serious public health problem in developing countries. Jiangsu, an eastern coastal province of China, has an environment conducive to the transmission of intestinal parasites, and suffered human infection rates of 71.75% in 1990. Due to comprehensive anti-transmission measures undertaken throughout the province in the 1990s, the prevalence had decreased to 9.28% in 2002. In order to assess the current epidemic situation for intestinal parasitic infections in Jiangsu province, a province-wide cross-sectional survey was carried out in 2015. Methods Surveys were conducted in two main settings; rural (for soil-transmitted parasites) and urban (for Clonorchis sinensis), selected through stratified random sampling. Human infection rates were evaluated through the detection of helminth eggs or cysts (oocysts or trophozoites) of intestinal protozoa in fecal samples by microscopy. Secondary intermediate and reservoir hosts were surveyed for C. sinensis infection. Questionnaires were completed by each participant to evaluate knowledge, attitude and practice of soil-transmitted parasite and C. sinensis avoidance. Results 115 out of 30153 participants (0.38%) had intestinal helminths or protozoa. There were eight species of helminth detected and the most common parasite was the hookworm Ancylostoma duodenale. In rural settings, there were significant differences in infection rates between participants of differing economic status. In urban settings, only four cases of C. sinensis infection were detected. However, secondary intermediate and reservoir hosts were found to harbor parasites. The questionnaire survey revealed that 38.42% participants were not aware of how humans become infected by hookworms. Knowledge and awareness of C. sinensis was similarly low, with 53.22% participants combining the use of chopping boards for raw and cooked food items when preparing meals. Conclusions The prevalence of intestinal parasitic infections in Jiangsu Province in eastern China has decreased from 71.57% in 1990 to 0.38% in 2015. Control measures should now focus on parasitic infections in the elderly and in children, health promotion and the development of alternative detection methods.

G protein-coupled receptors (GPCRs), such as GABAB, can integrate extracellular signals via allosteric interactions within dimers and oligomers. Here authors use crosslinking and identify two transmembrane interfaces in GABAB which undergo a concerted rearrangement upon agonist activation.