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Abstract Sex characteristics exhibit significant disparities in various human diseases, including prevalent cardiovascular diseases, cancers, metabolic disorders, autoimmune diseases, and neurodegenerative diseases. Risk profiles and pathological manifestations of these diseases exhibit notable variations between sexes. The underlying reasons for these sex disparities encompass multifactorial elements, such as physiology, genetics, and environment. Recent studies have shown that human body systems demonstrate sex-specific gene expression during critical developmental stages and gene editing processes. These genes, differentially expressed based on different sex, may be regulated by androgen or estrogen-responsive elements, thereby influencing the incidence and presentation of cardiovascular, oncological, metabolic, immune, and neurological diseases across sexes. However, despite the existence of sex differences in patients with human diseases, treatment guidelines predominantly rely on male data due to the underrepresentation of women in clinical trials. At present, there exists a substantial knowledge gap concerning sex-specific mechanisms and clinical treatments for diverse diseases. Therefore, this review aims to elucidate the advances of sex differences on human diseases by examining epidemiological factors, pathogenesis, and innovative progress of clinical treatments in accordance with the distinctive risk characteristics of each disease and provide a new theoretical and practical basis for further optimizing individualized treatment and improving patient prognosis.

Abstract Background M1 macrophages are closely associated with cardiac injury after myocardial infarction (MI). Increasing evidence shows that exosomes play a key role in pathophysiological regulation after MI, but the role of M1 macrophage-derived exosomes (M1-Exos) in myocardial regeneration remains unclear. In this study, we explored the impact of M1 macrophage-derived exosomes on cardiomyocytes regeneration in vitro and in vivo. Methods M0 macrophages were induced to differentiate into M1 macrophages with GM-CSF (50 ng/mL) and IFN-γ (20 ng/mL). Then M1-Exos were isolated and co-incubated with cardiomyocytes. Cardiomyocyte proliferation was detected by pH3 or ki67 staining. Quantitative real-time PCR (qPCR) was used to test the level of miR-155 in macrophages, macrophage-derived exosomes and exosome-treated cardiomyocytes. MI model was constructed and LV-miR-155 was injected around the infarct area, the proliferation of cardiomyocytes was counted by pH3 or ki67 staining. The downstream gene and pathway of miR-155 were predicted and verified by dual-luciferase reporter gene assay, qPCR and immunoblotting analysis. IL-6 (50 ng/mL) was added to cardiomyocytes transfected with miR-155 mimics, and the proliferation of cardiomyocytes was calculated by immunofluorescence. The protein expressions of IL-6R, p-JAK2 and p-STAT3 were detected by Western blot. Results The results showed that M1-Exos suppressed cardiomyocytes proliferation. Meanwhile, miR-155 was highly expressed in M1-Exos and transferred to cardiomyocytes. miR-155 inhibited the proliferation of cardiomyocytes and antagonized the pro-proliferation effect of interleukin 6 (IL-6). Furthermore, miR-155 targeted gene IL-6 receptor (IL-6R) and inhibited the Janus kinase 2(JAK)/Signal transducer and activator of transcription (STAT3) signaling pathway. Conclusion M1-Exos inhibited cardiomyocyte proliferation by delivering miR-155 and inhibiting the IL-6R/JAK/STAT3 signaling pathway. This study provided new insight and potential treatment strategy for the regulation of myocardial regeneration and cardiac repair by macrophages.

Abstract Ubiquitin-proteasome system (UPS) is involved in vascular smooth muscle cell (VSMC) proliferation. Deubiquitinating enzymes (DUBs) have an essential role in the UPS-regulated stability of the substrate; however, the function of DUBs in intimal hyperplasia remains unclear. We screened DUBs to identify a protein responsible for regulating VSMC proliferation and identified USP14 protein that mediates cancer development, inflammation, and foam cell formation. USP14 promotes human aortic smooth muscle cell and A7r5 cell growth in vitro, and its inhibition or deficiency decreases the intimal area in the mice carotid artery ligation model. In addition, USP14 stabilizes Skp2 expression by decreasing its degradation, while Skp2 overexpression rescues USP14 loss-induced issues. The current findings suggested an essential role of USP14 in the pathology of vascular remodeling, deeming it a promising target for arterial restenosis therapy.

Abstract Accurate indel calling plays an important role in precision medicine. A benchmarking indel set is essential for thoroughly evaluating the indel calling performance of bioinformatics pipelines. A reference sample with a set of known-positive variants was developed in the FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, but the known indels in the known-positive set were limited. This project sought to provide an enriched set of known indels that would be more translationally relevant by focusing on additional cancer related regions. A thorough manual review process completed by 42 reviewers, two advisors, and a judging panel of three researchers significantly enriched the known indel set by an additional 516 indels. The extended benchmarking indel set has a large range of variant allele frequencies (VAFs), with 87% of them having a VAF below 20% in reference Sample A. The reference Sample A and the indel set can be used for comprehensive benchmarking of indel calling across a wider range of VAF values in the lower range. Indel length was also variable, but the majority were under 10 base pairs (bps). Most of the indels were within coding regions, with the remainder in the gene regulatory regions. Although high confidence can be derived from the robust study design and meticulous human review, this extensive indel set has not undergone orthogonal validation. The extended benchmarking indel set, along with the indels in the previously published known-positive set, was the truth set used to benchmark indel calling pipelines in a community challenge hosted on the precisionFDA platform. This benchmarking indel set and reference samples can be utilized for a comprehensive evaluation of indel calling pipelines. Additionally, the insights and solutions obtained during the manual review process can aid in improving the performance of these pipelines.

Abstract Background Cotton accounts for 80% of the global natural fibre production. Its leaf hairiness affects insect resistance, fibre yield, and economic value. However, this phenotype is still qualitatively assessed by visually attributing a Genotype Hairiness Score (GHS) to a leaf/plant, or by using the HairNet deep-learning model which also outputs a GHS. Here, we introduce HairNet2, a quantitative deep-learning model which detects leaf hairs (trichomes) from images and outputs a segmentation mask and a Leaf Trichome Score (LTS). Results Trichomes of 1250 images were annotated (AnnCoT) and a combination of six Feature Extractor modules and five Segmentation modules were tested alongside a range of loss functions and data augmentation techniques. HairNet2 was further validated on the dataset used to build HairNet (CotLeaf-1), a similar dataset collected in two subsequent seasons (CotLeaf-2), and a dataset collected on two genetically diverse populations (CotLeaf-X). The main findings of this study are that (1) leaf number, environment and image position did not significantly affect results, (2) although GHS and LTS mostly correlated for individual GHS classes, results at the genotype level revealed a strong LTS heterogeneity within a given GHS class, (3) LTS correlated strongly with expert scoring of individual images. Conclusions HairNet2 is the first quantitative and scalable deep-learning model able to measure leaf hairiness. Results obtained with HairNet2 concur with the qualitative values used by breeders at both extremes of the scale (GHS 1-2, and 5-5+), but interestingly suggest a reordering of genotypes with intermediate values (GHS 3-4+). Finely ranking mild phenotypes is a difficult task for humans. In addition to providing assistance with this task, HairNet2 opens the door to selecting plants with specific leaf hairiness characteristics which may be associated with other beneficial traits to deliver better varieties.

Abstract Background Aberrant expression and activation of circular RNAs (circRNAs) are closely associated with various cancers. The role of circ_MAPK9 (hsa_circ_0001566) in cancer progression remains unknown. This study aims to investigate the function, mechanism and clinical significance of circ_MAPK9 in hepatocellular carcinoma (HCC). Methods Circ_MAPK9 expression on the microarray of tumor from clinical HCC patients was detected by in situ hybridization (ISH). Circ_MAPK9 knockdown was achieved with siRNAs in SMMC-7721 and SK-Hep1 HCC cell lines. The biological function of circ_MAPK9 was verified in vitro by CCK8 test, colony formation assay, transwell assay, PI-Annexin V staining, and in vivo by xenograft tumor in nude mice. Fluorescent in situ hybridization (FISH), subcellular fractionation assay, a dual-luciferase reporter assay and rescue experiments were employed for further mechanistic investigation. Results The expression of circ_MAPK9 was significantly up-regulated in HCC tissues and cells, which was found to be associated with poor prognosis. Patients with high expression of circ_MAPK9 had a shorter overall survival and disease-free survival in comparison to those with low circ_MAPK9 expression. Functional assays showed that circ_MAPK9 knockdown suppressed cellular proliferation, migration, invasion and tumor growth in vivo, and promoted apoptosis in HCC cells. Moreover, we found that circ_MAPK9 knockdown could inhibit aerobic glycolysis by decreasing the production of adenosine triphosphate (ATP) and lactic acid, which was mediated by lactate dehydrogenase (LDHA). Mechanistically, circ_MAPK9 functioned as ceRNA via sponging miR-642b-3p and alleviated the inhibitory effect of miR-642b-3p on its target signal transducer and activator of transcription 3 (STAT3) and LDHA, thereby leading to STAT3 activation and LDHA expression. Conclusions Circ_MAPK9, as an oncogene, promotes HCC growth and metastasis through miR-642b-3p/STAT3-LDHA axis. Circ_MAPK9 could serve as a potential biomarker for HCC poor prognosis and diagnosis.

Regional grouting treatment is an effective technical means to prevent mine water disasters, and the grouting effect is affected by many factors. In actual grouting engineering, the single constant-rate grouting method is often transformed into a variable-parameter grouting process. However, research on grouting rates has been insufficient. This investigation focused on the issue of “the diffusion law of variable-rate grouting slurry in regional governance”. Methods such as theoretical analysis, numerical simulation, and field verification were used to evaluate the diffusion mechanism of variable-rate fracture grouting. The results indicated that the key parameters of variable-rate grouting, such as slurry diffusion distance and grouting pressure, were affected by the grouting rate. The decrease in the grouting rate reduced the migration speed of the slurry and the grouting pressure. The time for constant-velocity grouting and variable-velocity grouting to reach the same diffusion distance was 60 s and 108 s, respectively, which can be achieved with lower grouting pressure. When the grouting rate was 7.5 L/min and 30 L/min, the maximum grout diffusion distance was 2.81 m and 5.64 m, respectively, which required greater grouting pressure. The slurry diffusion rate decreased with the reduction in the grouting rate. Under the same diffusion distance conditions, variable-rate grouting took longer than constant high-rate grouting. In variable-rate grouting, the grouting pressure decreased stepwise with the grouting rate, with a final pressure drop of 77.4%. In grouting practice, the innovative use of the rate-reducing grouting method can greatly reduce the final grouting pressure under the premise of changing the slurry diffusion distance less, which can not only ensure the stability of surrounding rock but also reduce the cost of high-pressure grouting and the risk of grouting operation. The investigation results can provide scientific guidance for ground grouting renovation projects in deep coal mine water hazard areas.

Abstract Verticillium dahliae is a soil-borne hemibiotrophic fungal pathogen that threatens cotton production worldwide. In this study, we assemble the genomes of two V. dahliae isolates: the more virulence and defoliating isolate V991 and nondefoliating isolate 1cd3-2. Transcriptome and comparative genomics analyses show that genes associated with pathogen virulence are mostly induced at the late stage of infection (Stage II), accompanied by a burst of reactive oxygen species (ROS), with upregulation of more genes involved in defense response in cotton. We identify the V991-specific virulence gene SP3 that is highly expressed during the infection Stage II. V. dahliae SP3 knock-out strain shows attenuated virulence and triggers less ROS production in cotton plants. To control the disease, we employ polyethyleneimine-coated MXene quantum dots (PEI-MQDs) that possess the ability to remove ROS. Cotton seedlings treated with PEI-MQDs are capable of maintaining ROS homeostasis with enhanced peroxidase, catalase, and glutathione peroxidase activities and exhibit improved tolerance to V. dahliae. These results suggest that V. dahliae trigger ROS production to promote infection and scavenging ROS is an effective way to manage this disease. This study reveals a virulence mechanism of V. dahliae and provides a means for V. dahliae resistance that benefits cotton production.

Abstract Background The approach of directly testing yarn quality to define fibre quality breeding objectives and progress the selection is attractive but difficult when considering the need for time and labour. The question remains whether yarn prediction tools from textile research can serve as an alternative. In this study, using a dataset from three seasons of field testing recombinant inbred line population, Cottonspec, a software developed by the Commonwealth Scientific and Industrial Research Organisation (CSIRO) for predicting ring spun yarn quality from fibre properties measured by High Volume Instrument (HVI), was used to select improved fibre quality and lint yield in the population. The population was derived from an advanced generation inter-crossing of four CSIRO conventional commercial varieties. The Cottonspec program was able to provide an integrated index of the fibre qualities affecting yarn properties. That was compared with selection based on HVI-measured fibre properties, and two composite fibre quality variables, namely, fibre quality index (FQI), and premium and discount (PD) points. The latter represents the net points of fibre length, strength, and micronaire based on the Premiums and Discounts Schedule used in the market while modified by the inclusion of elongation. Results The population had large variations for lint yield, fibre properties, predicted yarn properties, and composite fibre quality values. Lint yield with all fibre quality traits was not correlated. When the selection was conducted first to keep those with improved fibre quality, and followed for high yields, a large proportion in the resultant populations was the same between selections based on Cottonspec predicted yarn quality and HVI-measured fibre properties. They both exceeded the selection based on FQI and PD points. Conclusions The population contained elite segregants with improved yield and fibre properties, and Cottonspec predicted yarn quality is useful to effectively capture these elites. There is a need to further develop yarn quality prediction tools through collaborative efforts with textile mills, to draw better connectedness between fibre and yarn quality. This connection will support the entire cotton value chain research and evolution.

Aptamers are short, single-stranded DNA or RNA molecules that selectively bind to a target molecule. Aptamer-complement duplex (ACD) is often used to design molecular switches capable of producing a detectable signal or triggering a structural change upon aptamer binding to a target. However, such aptamer switch generally faces an increased dissociation constant (Kd) due to the energy barrier of the complementary duplex. We reported a competitive hybridization mechanism to modulate the binding affinity of an ACD to a target adenosine. Using the computation-guided design, we calculated the aptamer folding energy for the duplex length from 11-nt to 15-nt, and experimentally measured increased apparent Kd values resulted from these extended duplexes. Using a set of strands to compete with the ACD hybridization, it reduced the aptamer folding energy to facilitate aptamer switches with decreased apparent Kd values ranging from over 400 μM without a competing strand to ∼30 μM with a competing strand. This competitive aptamer switch was also found sensitive to single-nucleotide mutations of a competing strand. Our work provides an approach to modulate the binding affinity and the sensitivity of aptamer-complement duplexes, which could be useful in the nucleic acids-based sensing and nanomedicine.

The backless cable-stayed bridge has the advantages of beautiful shape and reasonable force, but due to the low overall stiffness of the bridge pylon during cantilever construction, it is susceptible to the effect of solar temperature. To reveal the temperature deformation laws and achieve accurate alignment prediction during the installation process of steel–concrete composite pylons in complex environments, a refined numerical simulation model for the 3D bridge temperature field was established based on the proposed automatic sunshine-shadow recognition method. Subsequently, the optimal time periods for construction control are provided. The results of the study show that, during the cantilever construction of the bridge pylon, one pylon column will shade the other pylon column, resulting in asynchronous deformation that can reach 7.6 mm. The effect of solar temperature on the displacement of the bridge pylon is significant, where the maximum daily change in transverse displacement in the cantilevered state of the pylon can reach 33.6 mm, and the maximum change in cable force value can reach 52 kN. In order to mitigate the effect of solar radiation, the best construction time for the bridge pylon is 19:30~9:30, while the tensioning and measurement of the cable should be avoided from 6:00~18:00. This strategy ensures that the control of the pylon top displacement is maintained within 1/4000 of the pylon height, and the error in cable force is kept within 5%.

Abstract Cereal cyst nematodes (CCNs) lead to major losses in the cereal crop industry worldwide and have been reported in many provinces of China. However, this plant nematode’s distribution and genetic differences are not fully understood. In the present study, 821 soil and host root samples were collected from 16 provinces in 2019–2022 to investigate the distribution of the CCNs. Heterodera avenae was detected in 56.39% of the total samples, primarily in Hubei, Henan, Hebei, Shandong, Shanxi, Gansu, Beijing, Tianjin, Inner Mongolia, Ningxia, Xinjiang, Qinghai, Anhui, Shaanxi, and Jiangsu. H. filipjevi was present in 21 samples, with a detection rate of 2.60%, and it was found mainly in Henan, Anhui, Jiangsu, Shandong, Shanxi, and Qinghai. A phylogenetic analysis of the internal transcribed spacer (ITS) region of the rRNA gene indicated that significant evolutionary and genetic differences existed between the Chinese populations and populations from other countries. Our results indicate that ITS1 can be used as a phylogenetic analysis and genetic target for H. avenae populations. The haplotypes of the ITS1 sequences of H. avenae populations from 14 countries were analyzed, and we speculate that H. avenae originated in a Middle East hotspot, then spread westwards to Europe and the United States and eastwards to China and Australia. Genetic differences between Asian and European populations suggest that the Himalayas and Kunlun Mountains formed a barrier that resulted in the formation of a separate evolutionary group in China. The phylogenetic and haplotype analysis results from different hosts showed significant differences among populations isolated from different hosts, and those isolated from weeds were distinct from those from other hosts, indicating that the rich genetic diversity of H. avenae populations is related to the large number of available hosts. Above all, geographic barriers, time of origin, and host adaptation might explain the current known distribution patterns of Chinese H. avenae populations.

Introduction: Plant parasitic cyst nematodes secrete a number of effectors into hosts to initiate formation of syncytia and infection causing huge yield losses. Objectives: The identified cyst nematode effectors are still limited, and the cyst nematode effectors-involved interaction mechanisms between cyst nematodes and plants remain largely unknown. Methods: The t-SNARE domain-containing effector in beet cyst nematode (BCN) was identified by In situ hybridization and immunohistochemistry analyses. The mutant of effector gene was designed by protein structure modeling analysis. The functions of effector gene and its mutant were analyzed by genetic transformation in Arabidopsis and infection by BCN. The protein–protein interaction was analyzed by yeast two hybrid, BiFC and pulldown assays. Gene expression was assayed by quantitative real-time PCR. Results: A t-SNARE domain-containing BCN HsSNARE1 was identified as an effector, and its mutant HsSNARE1-M1 carrying three mutations (E141D, A143T and −148S) that altered regional structure from random coils to α-helixes was designed and constructed. Transgenic analyses indicated that expression of HsSNARE1 significantly enhanced while expression of HsSNARE1-M1 and highly homologous HgSNARE1 remarkably suppressed BCN susceptibility of Arabidopsis. HsSNARE1 interacted with AtSNAP2 and AtPR1 via its t-SNARE domain and N-terminal, respectively, while HsSNARE1-M1/HgSNARE1 could not interact with AtPR1 but bound AtSNAP2. AtSNAP2, AtSHMT4 and AtPR1 interacted pairwise, but neither HsSNARE1 nor HsSNARE1-M1/HgSNARE1 could interact with AtSHMT4. Expression of HsSNARE1 significantly suppressed while expression of HsSNARE1-M1/HgSNARE1 considerably induced both AtSHMT4 and AtPR1 in transgenic Arabidopsis infected with BCN. Overexpression of AtPR1 significantly suppressed BCN susceptibility of Arabidopsis. Conclusions: This work identified a t-SNARE-domain containing cyst nematode effector HsSNARE1 and deciphered a molecular mode of action of the t-SNARE-domain containing cyst nematode effectors that HsSNARE1 promotes cyst nematode disease by interaction with both AtSNAP2 and AtPR1 and significant suppression of both AtSHMT4 and AtPR1, which is mediated by three structure change-causing amino acid residues.

Fusarium oxysporum f. sp. vasinfectum (Fov) is a common soilborne fungal pathogen that causes Fusarium wilt (FW) disease in cotton. Although considerable progress has been made in cotton disease-resistance breeding against FW in China, and the R gene conferring resistance to Fov race 7 (FOV) in Upland cotton (Gossypium hirsutum) has been identified, knowledge regarding the evolution of fungal pathogenicity and virulence factors in Fov remains limited. In this study, we present a reference-scale genome assembly and annotation for FOV7, created through the integration of single-molecule real-time sequencing (PacBio) and high-throughput chromosome conformation capture (Hi-C) techniques. Comparative genomics analysis revealed the presence of six supernumerary scaffolds specific to FOV7. The genes or sequences within this region can potentially serve as reliable diagnostic markers for distinguishing Fov race 7. Furthermore, we conducted an analysis of the xylem sap proteome of FOV7-infected cotton plants, leading to the identification of 19 proteins that are secreted in xylem (FovSIX). Through a pathogenicity test involving knockout mutants, we demonstrated that FovSIX16 is crucial for the full virulence of FOV7. Overall, this study sheds light on the underlying mechanisms of Fov’s pathogenicity and provides valuable insights into potential management strategies for controlling FW.

Ditylenchus destructor and D. dipsaci are important nematodes that have a significant economic impact on agronomic and horticultural plants worldwide. Microscopic observation alone may not distinguish between D. destructor and D. dipsaci. Accurate and rapid identification of these two species is essential for effective pest management. In the present study, a species-specific PCR assay was developed to detect and differentiate D. destructor and D. dipsaci based on the rDNA-ITS sequences. The primers developed in this study can specifically amplify fragments of DNA from D. destructor and D. dipsaci in the target population, without amplifying DNA from other non-target nematodes within the genus Ditylenchus. The sensitivity test revealed that this procedure has the ability to detect single second-stage juveniles (J2) of D. dipsaci at a dilution of 1/128 and D. destructor at a dilution of 1/64. Additionally, it can detect genomic DNA (gDNA) at concentrations of 10 pg/µL for D. dipsaci and 1 ng/µL for D. destructor. These results align with previously reported results obtained through RPA and LAMP methods. Furthermore, the primers developed in this study for D. destructor not only were able to amplify six different haplotypes of nematodes but also successfully detected it in infested plant roots and soil samples, thereby shortening the time and reducing the number of steps required for detection. Thus, this assay, which does not necessitate taxonomic or morphological expertise, significantly enhances the diagnosis of D. destructor and D. dipsaci in infested fields. This advancement aids in the early control of these nematodes.

Abstract To ensure the safety operation of inter-basin water transfer project, it is important to understand the seismic performance of shallow-buried large-scale segment-connected pipeline structure under earthquake and other multiple actions. In this paper, a 3D FE model is built in details for the seismic assessment of large-scale prestressed concrete inverted-siphon shallow-buried under riverbed, and a method is proposed to realize multiple interactions of the viscoelastic boundary elements to finite elements, the compressible fluid to structure and the sealed joints made of rubber belt between adjacent segments. The inverted-siphon is longitudinally composited by 58 segments in total length of 858.64 m, and transversally consisits of three rectanguler-section boxes with net dimension of each box of 6.5 m width and 6.6 m height. The main influencing factors are set as the thickness of overburden soil, the flow condition and the engineering geological condition. The time-history analysis is carried out on the 3D FE model under Elcentro seismic wave excitation. The numerical analyses figures out the main vibration modes and vibrational frequency of this inverted-siphon, reveals the regions of peak tensile stress appeared on the concrete surface and the risk sealed joints with extremum relative displacement. This provides a scientific reference to take specific prevention measures of anti-earthquake, based on a deep understanding to the seismic cracking of concrete and the tearing broken of sealed joints for this kind of segment-connected pipeline structure.

The severity of Verticillium wilt on cotton caused by defoliating strains of Verticillium dahliae has gradually increased and threatens production worldwide. Identification of the molecular components of leaf defoliation may increase cotton tolerance to V. dahliae. Ethylene, a major player in plant physiological processes, is often associated with senescence and defoliation of plants. We investigated the cotton–V. dahliae interaction with a focus on the role of ethylene in defoliation and defense against V. dahliae. Cotton plants inoculated with V. dahliae isolate V991, a defoliating strain, accumulated more ethylene and showed increased disease symptoms than those inoculated with a non-defoliating strain. In cotton with a transiently silenced ethylene synthesis gene (GhACOs) and signaling gene (GhEINs) during cotton–V. dahliae interaction, ethylene produced was derived from cotton and more ethylene increased cotton susceptibility and defoliation rate. Overexpression of AtCTR1, a negative regulator in ethylene signaling, in cotton reduced sensitivity to ethylene and increased plant resistance to V. dahliae. Collectively, the results indicated precise regulation of ethylene synthesis or signaling pathways improve cotton resistant to Verticillium wilt.

Brain cancer is the most aggressive one among various cancers. It has a drastic impact on people's lives because of the failure in treatment efficacy of the currently employed strategies. Various strategies used to relieve pain in brain cancer patients and to prolong survival time include radiotherapy, chemotherapy, and surgery. Nevertheless, several inevitable limitations are accompanied by such treatments due to unsatisfactory curative effects. Generally, the treatment of cancers is very challenging due to many reasons including drugs’ intrinsic factors and physiological barriers. Blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) are the two additional hurdles in the way of therapeutic agents to brain tumors delivery. Combinatorial and targeted therapies specifically in cancer show a very promising role where nanocarriers’ based formulations are designed primarily to achieve tumor-specific drug release. A dual-targeting strategy is a versatile way of chemotherapeutics delivery to brain tumors that gets the aid of combined ligands and mediators that cross the BBB and reaches the target site efficiently. In contrast to single targeting where one receptor or mediator is targeted, the dual-targeting strategy is expected to produce a multiple-fold increase in therapeutic efficacy for cancer therapy, especially in brain tumors. In a nutshell, a dual-targeting strategy for brain tumors enhances the delivery efficiency of chemotherapeutic agents via penetration across the blood-brain barrier and enhances the targeting of tumor cells. This review article highlights the ongoing status of the brain tumor therapy enhanced by nanoparticle based delivery with the aid of dual-targeting strategies. The future perspectives in this regard have also been highlighted.

Despite surgical and therapeutic advances, glioblastoma multiforme (GBM) is among the most fatal primary brain tumor that is aggressive in nature. Patients with GBM have a median lifespan of just 15 months when treated with the current standard of therapy, which includes surgical resection and concomitant chemo-radiotherapy. In recent years, nanotechnology has shown considerable promise in treating a variety of illnesses, and certain nanomaterials have been proven to pass the blood–brain barrier (BBB) and stay in glioblastoma tissues. Recent preclinical research suggests that the diagnosis and treatment of brain tumor is significantly explored through the intervention of nanomaterials that has showed enhanced effect. In order to elicit an antitumor response, it is necessary to retain the therapeutic candidates within glioblastoma tissues and this job is effectively carried out by nanocarrier particularly functionalized nanocarriers. In the arena of neoplastic diseases including GBM have achieved great attention in recent decades. Furthermore, interleukin-13 receptor α chain variant 2 (IL13Rα2) is a highly expressed and studied target in GBM that is lacked by the surrounding environment. The absence of IL13Rα2 in surrounding normal tissues has made it a suitable target in glioblastoma therapy. In this review article, we highlighted the role of IL13Rα2 as a potential target in GBM along with design and fabrication of efficient targeting strategies for IL13Rα2 through surface functionalized nanocarriers.

Abstract Soybean cyst nematode (SCN, Heterodera glycines) is widely considered as the model plant-parasitic nematode, which secretes effector proteins to manipulate host responses. In this study, we cloned a dorsal gland-expressed effector protein SCN-27D09 that belongs to the same family as Hg10A07 in SCN. We used the model plant pathogen rice blast fungus (Magnaporthe oryzae) to quickly predict and characterize the functions of SCN-27D09. By using M. oryzae secretion system in barley, we confirmed that the signal peptide of SCN-27D09 has secretory activity and can guide the protein into the host cells. Heterologous expression of SCN-27D09 in M. oryzae significantly enhanced the susceptibility of barley to M. oryzae. SCN-27D09 can inhibit Bax-triggered cell death when expressed in Nicotiana benthamiana. Overexpression of SCN-27D09 in soybean hairy root also increased the susceptibility of soybean plants to SCN. Moreover, yeast two-hybrid and firefly luciferase complementation imaging assays showed that SCN-27D09 interacts with a soybean plant kinase GmIPK-2. Functional characterization of GmIPK-2 revealed its positive role in soybean resistance, indicating that SCN-27D09 might compromise the function of GmIPK-2 to facilitate nematode infection. Our results not only uncover the biological role of SCN-27D09 in suppressing plant defense responses and therefore promoting nematode parasitism, but also reaffirm the potential application of the model plant pathogenic fungus M. oryzae in investigating the pathogenic roles of candidate effectors of phytonematodes.

Background and aims: Berberine is one of the most promising clinically tested natural alkaloids, and immunotherapy using natural killer (NK) cells is a potentially effective treatment for hepatocellular carcinoma (HCC). This study aims to elucidate the effect of berberine on the anti-HCC effect of NK92-MI cells. Materials and methods: Human HCC SMMC-7721 and Hep3B cells were co-incubated with NK92-MI cells, berberine (60 or 80 μmol/L), or their combination for 36 h. To evaluate the killing effect of NK92-MI cells on HCC cells, the release of lactate dehydrogenase (LDH) in HCC cells was measured. The anti-tumor effects of berberine, NK92-MI cells, and their combinations were evaluated by MTS, EdU, Tunel, and Western blot assays. A male BALB/c nude mouse subcutaneous tumor model was used to investigate the anti-HCC effect of berberine and NK92-MI cells in vivo. Results: The LDH assay showed that berberine enhanced the cytotoxicity of NK92-MI cells on HCC cells. The combination of berberine and NK92-MI cells demonstrated more obvious anti-HCC effect than did the berberine or NK92-MI single treatment in inhibiting cell proliferation and inducing apoptosis both in vitro and in vivo. Mechanistically, the expression of programmed cell death-ligand 1 (PD-L1) in HCC cells was upregulated after co-culture with NK-92MI cells. PD-L1 expression was knocked down, thereby inhibiting the proliferation and promoting apoptosis of HCC cells, and inhibited by berberine that blocked the secretion of interferon gamma (IFN-γ), thereby enhancing the anti-tumor effect of NK92-MI cells. Conclusions: Current data show that the immunomodulatory role of berberine is to enhance the cytotoxic effect of NK92-MI cells and inhibit tumor immune escape by reducing the expression of PD-L1. Our study provides a rationale for the clinical application of berberine in combination with NK cells for the treatment of HCC.

GmSNAP18 and GmSHMT08 are two major genes conferring soybean cyst nematode (SCN) resistance in soybean. Overexpression of either of these two soybean genes would enhance the susceptibility of Arabidopsis to beet cyst nematode (BCN), while overexpression of either of their corresponding orthologs in Arabidopsis, AtSNAP2 and AtSHMT4, would suppress it. However, the mechanism by which these two pairs of orthologous genes boost or inhibit BCN susceptibility of Arabidopsis still remains elusive. In this study, Arabidopsis with simultaneously overexpressed GmSNAP18 and GmSHMT0 suppressed the growth of underground as well as above-ground parts of plants. Furthermore, Arabidopsis that simultaneously overexpressed GmSNAP18 and GmSHMT08 substantially stimulated BCN susceptibility and remarkably suppressed expression of AtPR1 in the salicylic acid signaling pathway. However, simultaneous overexpression of GmSNAP18 and GmSHMT08 did not impact the expression of AtJAR1 and AtHEL1 in the jasmonic acid and ethylene signaling pathways. GmSNAP18, GmSHMT08, and a pathogenesis-related (PR) protein, GmPR08-Bet VI, in soybean, and AtSNAP2, AtSHMT4, and AtPR1 in Arabidopsis could interact pair-wisely for mediating SCN and BCN resistance in soybean and Arabidopsis, respectively. Both AtSNAP2 and AtPR1 were localized on the plasma membrane, and AtSHMT4 was localized both on the plasma membrane and in the nucleus of cells. Nevertheless, after interactions, AtSNAP2 and AtPR1 could partially translocate into the cell nucleus. GmSNAP18 interacted with AtSHMT4, and GmSHMT4 interacted with AtSNAP2. However, neither GmSNAP18 nor GmSHMT08 interacted with AtPR1. Thus, no pairwise interactions among α-SNAPs, SHMTs, and AtPR1 occurred in Arabidopsis overexpressing either GmSNAP18 or GmSHMT08, or both of them. Transgenic Arabidopsis overexpressing either GmSNAP18 or GmSHMT08 substantially suppressed AtPR1 expression, while transgenic Arabidopsis overexpressing either AtSNAP2 or AtSHMT4 remarkably enhanced it. Taken together, no pairwise interactions of GmSNAP18, GmSHMT08, and AtPR1 with suppressed expression of AtPR1 enhanced BCN susceptibility in Arabidopsis. This study may provide a clue that nematode-resistant or -susceptible functions of plant genes likely depend on both hosts and nematode species.

Abstract Myocardial ischemia/reperfusion (I/R) injury is a complex pathological process that is still not fully understood. The oxidative stress response has a critical role in the occurrence and progression of myocardial ischemia/reperfusion injury. This study investigated the specific mechanism of ubiquitin-specific protease 7 (USP7) regulation of myocardial ischemia/reperfusion injury from the perspective of proteasome degradation and its relation with the Keap1 pathway, a vital regulator of cytoprotective responses to endogenous and exogenous stress induced by reactive oxygen species (ROS) and electrophiles. Our data indicated that USP7 expression is increased during myocardial ischemia/reperfusion injury in mice, while its inhibiting suppressed the generation of oxygen free radicals and myocardial cell apoptosis, reduced myocardial tissue damage, and improved heart function. Mechanistically, USP7 stabilizes Keap1 by regulating its ubiquitination. Taken together, these findings demonstrate the potential therapeutic effect of USP7 on myocardial ischemia/reperfusion injury.

Abstract Potato rot nematode Ditylenchus destructor is one of the most damaging pests in potato-producing regions and causes severe yield losses worldwide. However, D. destructor has been rarely reported in potato crops in China. We collected 542 samples from 17 Chinese provinces during 2016–2020 for the detection of D. destructor using species-specific primers and universal primers targeting ribosomal internal transcribed spacer (ITS) or 28S ribosomal RNA (rRNA) sequences. D. destructor was detected in 14.94% of total samples, primarily in Inner Mongolia Autonomous Region (43 sites), Jilin Province (12 sites), and Shaanxi Province (9 sites). The nematode was for the first time detected in Guizhou Province and Ningxia Hui Autonomous Region. Phylogenetic analysis of 33 ITS sequences along with the prediction of the secondary structure of the helix H9 of ITS1 sequences revealed that haplotypes A, B, and C accounted for 6.06%, 9.09%, and 69.70% of our detections, respectively, while 15.15% were comprised of haplotypes H–L, and extensive genetic diversity of ITS sequences was detected in samples from Gansu Province. Using RNAfold software, we analyzed the haplotypes of 124 Chinese D. destructor populations based on their ITS sequences, and the results showed that haplotypes A, B, C, E, F, and new haplotypes M–P accounted for 49.19%, 12.10%, 15.32%, 3.23%, 1.61%, and 18.55% of the total sequences, respectively. Infection tests on the potato cultivar ‘Helan 15’ showed significant difference in infection capacity among different D. destructor populations. The information obtained in this study on spatial patterns of D. destructor haplotypes in China provides valuable insights into the development of an integrated approach for the management of this plant-parasitic nematode.

Abstract Accumulation of obsolete biomolecules can accelerate cell senescence and organism aging. The two efficient intracellular systems, namely the ubiquitin‐proteasome system and the autophagy‐lysosome system, play important roles in dealing with cellular wastes. However, how multicellular organisms orchestrate the processing of obsolete molecules and delay aging remains unclear. Herein, it is shown that prevention of exosome release by GW4869 or Rab27a−/− accelerated senescence in various cells and mice, while stimulating exosome release by nutrient restriction delays aging. Interestingly, exosomes isolate from serum‐deprived cells or diet‐restricted human plasma, enriched with garbage biomolecules, including misfolded proteins, oxidized lipids, and proteins. These cellular wastes can be englobed by macrophages, eventually, for disintegration in vivo. Inhibition of nutrient‐sensing mTORC1 signaling increases exosome release and delays senescence, while constitutive activation of mTORC1 reduces exosome secretion and exacerbates senescence in vitro and in mice. Notably, inhibition of exosome release attenuates nutrient restriction‐ or rapamycin‐delayed senescence, supporting a key role for exosome secretion in this process. This study reveals a potential mechanism by which stimulated exosome release delays aging in multicellular organisms, by orchestrating the harmful biomolecules disposal via exosomes and macrophages.

Abstract Background Leaf hairiness (pubescence) is an important plant phenotype which regulates leaf transpiration, affects sunlight penetration, and provides increased resistance or susceptibility against certain insects. Cotton accounts for 80% of global natural fibre production, and in this crop leaf hairiness also affects fibre yield and value. Currently, this key phenotype is measured visually which is slow, laborious and operator-biased. Here, we propose a simple, high-throughput and low-cost imaging method combined with a deep-learning model, HairNet, to classify leaf images with great accuracy. Results A dataset of $$\sim $$ ∼ 13,600 leaf images from 27 genotypes of Cotton was generated. Images were collected from leaves at two different positions in the canopy (leaf 3 & leaf 4), from genotypes grown in two consecutive years and in two growth environments (glasshouse & field). This dataset was used to build a 4-part deep learning model called HairNet. On the whole dataset, HairNet achieved accuracies of 89% per image and 95% per leaf. The impact of leaf selection, year and environment on HairNet accuracy was then investigated using subsets of the whole dataset. It was found that as long as examples of the year and environment tested were present in the training population, HairNet achieved very high accuracy per image (86–96%) and per leaf (90–99%). Leaf selection had no effect on HairNet accuracy, making it a robust model. Conclusions HairNet classifies images of cotton leaves according to their hairiness with very high accuracy. The simple imaging methodology presented in this study and the high accuracy on a single image per leaf achieved by HairNet demonstrates that it is implementable at scale. We propose that HairNet replaces the current visual scoring of this trait. The HairNet code and dataset can be used as a baseline to measure this trait in other species or to score other microscopic but important phenotypes.

Abstract Verticillium wilt is one of the most important diseases affecting cotton production in China. The fungus, Verticillium dahliae, has a wide host range and a high degree of genetic variability. No resistance resources have been found in the available planting resources, thus presenting difficulties and challenges for our study. The long-term production practice shows that selection of disease-resistant varieties is the most economical and effective measure to control Verticillium wilt of cotton to reduce the yield loss and quality decline of cotton. In this paper, we summarized the genetic mapping population, the analysis method of genetic localization, the discovery, mining and cloning of disease-resistant quantitative trait loci/markers, and the analysis of their genetic functions, so as to provide information for the molecular breeding approach of disease-resistant cotton.

Abstract Soybean cyst nematode (SCN), Heterodera glycines, is one of the most important pests in soybean production worldwide. In China, 11 different races of SCN, including a newly identified race ‘X12’ with super-virulence, have been surveyed and found to be distributed in 22 provinces. Among them, races 1, 3 and 4 are dominant in the two principal soybean-producing areas, Northeast China and Huanghuaihai Valley, causing over 120 million dollars of annual yield loss. Rapid and reliable PCR-based approaches have been developed for the molecular diagnosis of SCN. High-throughput methods for the identification of soybean resistance against SCN are also developed with specific single nucleotide polymorphism markers by using Kompetitive Allele Specific PCR technology. Over 10,000 soybean germplasm sources were evaluated for their SCN resistance, and 28 SCN-resistant soybean accessions were selected to construct an applied core collection, which has been used for soybean breeding in China. Recently, the genome sequences of SCN and soybean are publically available, and two major SCN-resistant genes (rhg1 and Rhg4) have been identified in soybean, which greatly facilitate the researches on SCN virulence and soybean resistance, and also soybean resistance breeding against SCN. However, the management of SCN still faces many bottlenecks, for instance, the single resistance genes in soybean cultivars can be easily overcome by new SCN races; the identified resistance genes are inadequate to meet the practical breeding needs; and our understanding of the mechanisms of SCN virulence and soybean resistance to SCN are limited. SCN is a destructive threat to soybean production throughout the world including China. In this review, the major progress on soybean SCN is summarized, mainly focusing on the recent research progress in SCN, soybean resistance to SCN and integrated management of SCN in China, and aiming at a better understanding of the current SCN research status and prospects for future work.

Abstract Background Soybean cyst nematode, Heterodera glycines, is one of the most devastating pathogens of soybean and causes severe annual yield losses worldwide. Different soybean varieties exhibit different responses to H. glycines infection at various levels, such as the genomic, transcriptional, proteomic and metabolomic levels. However, there have not yet been any reports of the differential responses of incompatible and compatible soybean varieties infected with H. glycines based on combined metabolomic and transcriptomic analyses. Results In this study, the incompatible soybean variety PI437654 and three compatible soybean varieties, Williams 82, Zhonghuang 13 and Hefeng 47, were used to clarify the differences in metabolites and transcriptomics before and after the infection with HG1.2.3.5.7. A local metabolite-calibrated database was used to identify potentially differential metabolites, and the differences in metabolites and metabolic pathways were compared between the incompatible and compatible soybean varieties after inoculation with HG1.2.3.5.7. In total, 37 differential metabolites and 20 KEGG metabolic pathways were identified, which were divided into three categories: metabolites/pathways overlapped in the incompatible and compatible soybeans, and metabolites/pathways specific to either the incompatible or compatible soybean varieties. Twelve differential metabolites were found to be involved in predicted KEGG metabolite pathways. Moreover, 14 specific differential metabolites (such as significantly up-regulated nicotine and down-regulated D-aspartic acid) and their associated KEGG pathways (such as the tropane, piperidine and pyridine alkaloid biosynthesis, alanine, aspartate and glutamate metabolism, sphingolipid metabolism and arginine biosynthesis) were significantly altered and abundantly enriched in the incompatible soybean variety PI437654, and likely played pivotal roles in defending against HG1.2.3.5.7 infection. Three key metabolites (N-acetyltranexamic acid, nicotine and D,L-tryptophan) found to be significantly up-regulated in the incompatible soybean variety PI437654 infected by HG1.2.3.5.7 were classified into two types and used for combined analyses with the transcriptomic expression profiling. Associated genes were predicted, along with the likely corresponding biological processes, cellular components, molecular functions and pathways. Conclusions Our results not only identified potential novel metabolites and associated genes involved in the incompatible response of PI437654 to soybean cyst nematode HG1.2.3.5.7, but also provided new insights into the interactions between soybeans and soybean cyst nematodes.

Abstract Background Non-alcoholic steatohepatitis (NASH) is a key stage in leading development of non-alcoholic simple fatty liver (NAFL) into cirrhosis and even liver cancer. This study aimed at exploring the lncRNAs expression profile in NASH and the biological function of a novel LncRNA-gm9795. Methods Microarray analysis was performed to compare the expression profiles of lncRNAs in the liver of NASH, NAFLD and normal mice (5 mice for each group). Methionine-choline-deficient Medium (MCD) with Lipopolysaccharide (LPS) or palmitic acid (PA)were used to built NASH cell models. The role and mechanism of LncRNA-gm9795 in NASH were explored by knocking down or over-expressing its expression. Results A total of 381 lncRNAs were found to be not only highly expressed in NAFLD, but also is going to go even higher in NASH. A novel LncRNA-gm9795 was significantly highly expressed in liver tissues of NASH animal models and NASH cell models. By staining with Nile red, we found that gm9795 did not affect the fat accumulation of NASH. However, gm9795 in NASH cell models significantly promoted the expression of TNF $$\alpha {}$$ α , IL-6, IL-1 $$\beta {}$$ β , the important inflammatory mediators in NASH. At the same time, we found that gm9795 upregulated the key molecules in endoplasmic reticulum stress (ERS), while NF- $$\kappa {}$$ κ B/JNK pathways were also activated. When ERS activator Thapsigargin (TG) was introduced in cells with Ggm9757 si-RNA, NF- $$\kappa {}$$ κ B and JNK pathways were activated. Conversely, ERS inhibitor Tauroursodeoxycholic acid (TUDCA) inhibited NF-kB and JNK pathways in cells with gm9795 overexpression plasmid. Conclusion LncRNA-gm9795 promotes inflammatory response in NASH through NF-kB and JNK pathways by ERS, which might provide theoretical basis for revealing the pathogenesis of NASH and discovering new therapeutic targets

Abstract Background Nitrogen-based nutrients are the main factors affecting rice growth and development. Root systems play an important role in helping plants to obtain nutrients from the soil. Root morphology and physiology are often closely related to above-ground plant organs performance. Therefore, it is important to understand the regulatory effects of nitrogen (N) on rice root growth to improve nitrogen use efficiency. Results In this study, changes in the rice root traits under low N (13.33 ppm), normal N (40 ppm) and high N (120 ppm) conditions were performed through root morphology analysis. These results show that, compared with normal N conditions, root growth is promoted under low N conditions, and inhibited under high N conditions. To understand the molecular mechanism underlying the rice root response to low and high N conditions, comparative proteomics analysis was performed using a tandem mass tag (TMT)-based approach, and differentially abundant proteins (DAPs) were further characterized. Compared with normal N conditions, a total of 291 and 211 DAPs were identified under low and high N conditions, respectively. The abundance of proteins involved in cell differentiation, cell wall modification, phenylpropanoid biosynthesis, and protein synthesis was differentially altered, which was an important reason for changes in root morphology. Furthermore, although both low and high N can cause nitrogen stress, rice roots revealed obvious differences in adaptation to low and high N. Conclusions These results provide insights into global changes in the response of rice roots to nitrogen availability and may facilitate the development of rice cultivars with high nitrogen use efficiency through root-based genetic improvements.

The Commonwealth Scientific and Industrial Research Organisation (CSIRO) cotton breeding program is the sole breeding effort for cotton in Australia, developing high performing cultivars for the local industry which is worth∼AU$3 billion per annum. The program is supported by Cotton Breeding Australia, a Joint Venture between CSIRO and the program’s commercial partner, Cotton Seed Distributors Ltd. (CSD). While the Australian industry is the focus, CSIRO cultivars have global impact in North America, South America, and Europe. The program is unique compared with many other public and commercial breeding programs because it focuses on diverse and integrated research with commercial outcomes. It represents the full research pipeline, supporting extensive long-term fundamental molecular research; native and genetically modified (GM) trait development; germplasm enhancement focused on yield and fiber quality improvements; integration of third-party GM traits; all culminating in the release of new commercial cultivars. This review presents evidence of past breeding successes and outlines current breeding efforts, in the areas of yield and fiber quality improvement, as well as the development of germplasm that is resistant to pests, diseases and abiotic stressors. The success of the program is based on the development of superior germplasm largely through field phenotyping, together with strong commercial partnerships with CSD and Bayer CropScience. These relationships assist in having a shared focus and ensuring commercial impact is maintained, while also providing access to markets, traits, and technology. The historical successes, current foci and future requirements of the CSIRO cotton breeding program have been used to develop a framework designed to augment our breeding system for the future. This will focus on utilizing emerging technologies from the genome to phenome, as well as a panomics approach with data management and integration to develop, test and incorporate new technologies into a breeding program. In addition to streamlining the breeding pipeline for increased genetic gain, this technology will increase the speed of trait and marker identification for use in genome editing, genomic selection and molecular assisted breeding, ultimately producing novel germplasm that will meet the coming challenges of the 21st Century.

The discovery of gas hydrates in the Muli Depression has made the South Qilian Basin (SQB) a hotspot for oil and gas exploration. Although many studies have been carried out on the gas hydrates, the geochemical characteristics have rarely been reported, which can effectively indicate the genetic type, diffusion, biodegradation, and thermal maturity of natural gas. In this contribution, the molecular composition and carbon isotopes of alkane gases were collected from gas hydrates and free gases in drilled boreholes of the Muli Depression. The results show that the majority of natural gases are oil-type gases, with a little coal-type gases. The natural gases have undergone biodegradation, leading to a decrease in the propane content and an increase in the methane content, with a heavier carbon isotope of propane and a lighter carbon isotope of methane. Some of the natural gases have experienced diffusion, resulting in a decrease in the methane content and an increasing value of Δ(δ13C1-δ13C2). Furthermore, the wet gases from natural gases were derived from the cracking of kerogen and crude oil at the thermal maturity stage. The dry gases in small quantities were produced by biodegradation of the wet gases. We propose that the potential for light oil and condensate exists in the Jurassic Yaojie Formation. Our new findings on the geochemical characteristics of natural gases provide new constraints for the study of petroleum systems and deeply buried sediments in the SQB.

Abstract Background Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4−/− mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 knockdown using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

Abstract Background There has been little published data on estimates of HBV and/or HCV coinfection in HIV-positive patients in China or an understanding of how this coinfection varies with different factors. Therefore, this study aimed to determine, through a systematic review and meta-analysis, the prevalence of HBV and/or HCV in HIV-positive patients in China and explore variations in prevalence. Methods The Medicine, Web of Science, Chinese Web of Knowledge, and Wanfang databases were searched using a search strategy combining key words and related disease-specific subject terms to identify relevant cohort or cross-sectional studies published up to April 2019. Included articles were assessed for quality. Pooled prevalence and 95% confidence intervals (CIs) were calculated according to study region and other specific characteristics. Results Our searches identified 7843 records, but only 66 studies were included in our meta-analysis. The pooled HBsAg prevalence in HIV-positive patients was 13.7% (95% CI 12.3–15.3%), with variations found in terms of age and geographic region. The meta-HCV prevalence was 24.7% (95% CI 19.3–30.5%), which varied over the study period and age. The pooled HBV-HCV coinfection prevalence was 3.5% (95% CI 2.4–4.8%), with variations found in terms of age and geographic region. Conclusion Given the high burden of HBV and HCV coinfections in HIV-positive patients, the incorporation of comprehensive screening, treatment, prevention, and vaccination programs into general HIV management in China is imperative.

The instability of scale factor and null shift are closely related to the change of the light intensity of a total reflection prism laser gyro (TRPLG). To improve the light intensity stability, the light intensity stabilization principle of TRPLG was analyzed, and a mathematical model of light intensity stabilization system was established. Aiming at the problem that original system has a long adjustment time, a series correction method of adding a proportional integral differential (PID) link in the forward channel was adopted. According to the third-order optimal design, the original I-type third-order overdamped system was optimized to the new II-type third-order underdamped system, which ultimately improved the system's dynamic and steady-state performance. Feedforward compensation was used to introduce the light intensity disturbance during the longitudinal mode hopping into the closed-loop system, which realized the full compensation of the light intensity error and improved the light intensity characteristics during the longitudinal mode hopping. Combined with the above two methods, experimental results showed that the new system with feedforward compensation improved the light intensity stability by 32% at constant temperature and by 40% at variable temperature, with the TRPLG's bias stability improved by more than 16% at constant temperature and by 22% at variable temperature.

Context Curcumin has antitumor, antioxidative, anti-inflammatory, and anti-proliferative properties. Objective To investigate the role of miR-22 during curcumin-induced changes in vascular smooth muscle cells (VSMC) and neointima formation in balloon-injured rat abdominal aorta. Materials and methods Sprague-Dawley rats were randomised to the sham-operated (n = 10), operated control (injured, n = 10), and curcumin treatment (n = 10) groups. miR-22 expression was determined by real-time PCR. SP1 was assessed by western blot and real-time PCR. Rat aortic smooth muscle A7r5 cells were used to determine VSMC proliferation and migration, which were measured by the MTS, EdU staining, Transwell, and wound healing assays. Results miR-22 levels declined following arterial balloon injury in vivo (48% at 3d, p

The Iqe coalfield is one of the most significant coal production bases in the Qaidam Basin. Over the last few decades, core explorations have targeted the Dameigou Formation for No. 7 coal seam (M7). Although many M7 coal samples have been analyzed for coal components in the laboratory, the systematic understanding of the components and changes of coal in the whole Iqe coalfield is still inadequate. In this study, we focus on building log interpretation models to accurately calculate the content of coal components of M7, including ash yield (A ad ), volatile matter (V daf ), fixed carbon (FC ad ), and moisture (M ad ). Multiple regression analysis and statistical method, combined with the rock volume model, were used to establish log interpretation models of coal components. A total of 28 coal samples from ZK1, ZK2, ZK11-5, ZK23-4, and ZK36-9 wells in the Iqe coalfield were involved in the modeling, as well as well-logs parameters, such as radioactivity (GR), compensation density (DEN), acoustic (AC), and resistivity (RLLD). According to sensitivity analysis, the fitted A ad and V daf contents of M7 increase with the increasing of DEN and GR values, whereas the FC ad content shows the opposite way. Furthermore, the positive relationship between A ad and V daf ( R 2 = 0.59) and the negative relationship between A ad and FC ad ( R 2 = 0.92) as well as V daf and FC ad ( R 2 = 0.69) indicate that A ad is a key factor in coal and should be prior determined. Finally, based on the multiple regression analysis and rock volume model, we proposed log interpretation models for M7 coal components in the Iqe coalfield, these models have been examined successfully by the case studies from the same coalfield and will provide new insights into the application of geophysical log parameters for coal quality evaluation.

Cyst nematodes are one of the most important pathogens worldwide. Most cyst nematode species have been reported recently in China. From 2016 to 2020, an extensive survey of cyst nematodes was conducted in the Bashang region of Hebei Province. A total of 158 soil samples were collected, and cyst-forming nematodes were isolated from five soil samples. Morphological and molecular characterization showed that four of the cyst-forming nematode populations were Heterodera glycines (SCN), named populations of ZM, KM, CB and FN, respectively. These SCN populations were collected from Zhangbei County, Kangbao County, Chabei Management Area of Zhangjiakou and Fengning Manchu Autonomous County of Chengde, respectively, where the corresponding cyst densities were 57, 41, 103 and 31 cysts/200 cc soil. Furthermore, the populations of ZM, KM and CB were identified as race 4, whereas the FN population was identified as race 3. The cyst-forming nematode population was collected from Zhangbei County of Zhangjiakou, which was confirmed to be Heterodera schachtii (SBCN), named population ZZ, and the cyst density was 94 cysts/200 cc soil. It is a new disease of Chinese cabbage caused by SBCN based on Koch’s postulates. Fourteen cultivars from five plant families were evaluated as hosts for SBCN. Chinese cabbage (cv. Linglonghuang012) and cabbage (cv. Chunwang) were suitable hosts, while celery (cv. Yuhuang), potato (cv. Helan 15) and eggplant (cv. Junlang) were nonhosts. The obtained results regarding the occurrence, distribution, races of SCN and hosts of SBCN in the Bashang region in this study provide a reference for SCN and SBCN management.

Regorafenib resistance is a key limiting factor in the treatment of advanced hepatocellular carcinoma (HCC). Increasing evidence has demonstrated that Berberine (BBR) can synergistically enhance the therapeutic effect of various chemotherapeutic agents. However, the contribution of BBR on regorafenib therapy remains unclear. The purpose of this study was to explore the combined treatment effect of berberine and regorafenib in HCC. We found that BBR enhanced the cytotoxicity of regorafenib in HCC cells. Compared with regorafenib alone, the combined treatment of BBR and regorafenib significantly inhibited the proliferation of HCC cells and induced cellular apoptosis. Meanwhile, the combined treatment group with BBR (10mg/kg/day) and regorafenib (5mg/kg/day) had a dramatic inhibitory effect on the growth of HCC xenograft tumors in nude mice. The increased apoptosis of xenograft tumors was seen in the combined treatment group. Moreover, a comprehensive circular RNA sequencing was performed to identify differentially expressed circRNAs in HCC cells after exposure to 100µM BBR and 5µM regorafenib. The volcano plot and scatter plot analyses revealed that there were 58 up-regulated and 19 down-regulated differentially expressed circRNAs between the combination treatment and control groups. Among them, the expression of hsa_circ_0032029 and hsa_circ_0008928 were up-regulated in HCC cells after treatment with 100µM BBR and 5µM regorafenib. Taken together, this study demonstrated that BBR enhanced the anti-HCC effect of regorafenib both in vitro and in vivo. The synergistic anti-tumor effect of BBR and regorafenib might be related to the up-regulation of hsa_circ_0032029 and hsa_circ_0008928 in HCC cells.

Abstract The Juhugeng Sag, located in northwest of the Muli Basin, Tibetan Plateau, has been investigated for coal and petroleum resources during the past several decades. There have been successful recoveries of gas hydrates during recent years from the Middle Jurassic Yaojie Formation that offer insight into the origin of the hydrocarbon gases from the complex sag feature. This study examines the organic geochemical and stable carbon isotopic characteristics of shale and coal samples from the Middle Jurassic Yaojie Formation of the Juhugeng Sag, as well as compares with carbon isotopes, gas amounts and components of hydrate-bound gas. A total of 19 samples from surface mining, including 12 samples of black shale and 7 samples of coal, were analysed using a micro-photometer, a gas chromatograph, Rock–Eval and isotope methods. All the shale samples contained 100% type I kerogen, and the random vitrinite reflectance values vary from 0.65% to 1.32% and achieve thermal pyrolysis phase. Isotope values of methane (δ 13C ranging from − 52.6‰ to − 39.5‰ and δD ranging from − 285‰ to − 227‰) in the hydrate bound gases suggest that the methane originates mainly from thermogenic contributions. It is proposed that ethane from the gas hydrate is thermogenic-produced, and this conjecture is supported by the fact that most of the gas hydrate also contains more than 30% of thermogenic C2+ hydrocarbons and is similar to structure II hydrate. Carbon isotope data from the gas hydrates show a positive carbon isotope series (δ 13C1

Abstract Background Rice tiller number (TN) is one of the most important components associated with rice grain yield. Around one hundred rice TN genes have been identified, but dissecting the genetic architecture of rice TN variations remains difficult because of its complex trait and control by both major genes and quantitative trait loci (QTLs). Results In this study, we used a subset of the rice diversity population II (S-RDP-II), genotyped with 700,000 single nucleotide polymorphisms (SNPs), to identify the loci associated with tiller number variations (LATNs) through a genome-wide association study (GWAS). The analysis revealed that 23 LATNs are significantly associated with TN variations. Among the 23 LATNs, eight are co-localized with previously cloned TN genes, and the remaining 15 LATNs are novel. DNA sequence analysis of the 15 novel LATNs led to the identification of five candidate genes using the accessions with extreme TN phenotypes. Genetic variations in two of the genes are mainly located in the promoter regions. qRT-PCR analysis showed that the expression levels of these two genes are also closely associated with TN variations. Conclusions We identified 15 novel LATNs that contribute significantly to the genetic variation of rice TN. Of these 15, the five identified TN-associated candidate genes will enhance our understanding of rice tillering and can be used as molecular markers for improving rice yield.

The heart regeneration after apical resection and myocardial infarction in neonatal mice has been studied for years. However, the response of neonatal mouse heart under pressure overload is seldom explored. This study aimed to induce pressure overload in neonatal mice through a transverse aortic constriction (TAC) with different-gauge needles so as to investigate the effect of pressure overload on cardiomyocyte proliferation and hypertrophy in these mice. Myocardial hypertrophy was evaluated by echocardiographic, pathological, and molecular analyses. Cardiomyocyte proliferation was detected by immune-staining of phospho-histone H3, Ki67, and 5-bromo-2-deoxyuridine. Mild pressure overload induced with a 30-gauge needle stimulated cardiomyocyte proliferation, adaptive hypertrophy, and angiogenesis. The heart function was not hampered even 21 days after the surgery. Moderate pressure overload induced with a 32-gauge needle led to pathological myocardial hypertrophy, fibrosis, and heart failure 7 days after the surgery. The gene and protein expression levels of markers of hypertrophy and fibrosis increased in 32-gauge TAC group compared with that in sham and 30-gauge TAC groups. The mice barely survived after severe pressure overload induced with a 34-gauge needle. The findings of this study might provide new insights into cardiomyocyte proliferation and hypertrophy in neonatal mice under pressure overload.

Excessive prostaglandin E2 (PGE2) is the key pathological basis for COVID-19 and a Celebrex treatment of hospitalized COVID-19 patients with comorbidities led to 100% discharged rate and zero death (Hong et al. 2020). It is also suggested that SARS-CoV-2 infected multiple organs and the SARS-CoV nucleocapsid (N) protein transcriptionally drives the expression of the host COX-2 gene. In order to test whether SARS-CoV-2 N protein activates COX-2 transcription in multiple human relevant cell types, an expression inducible human embryonic stem cell line was generated by piggyBac transposon system. This cell line maintained its pluripotency, differentiation potentials, normal morphology and karyotype.

Abstract Fusarium wilt (FW) disease of cotton, caused by the fungus Fusarium oxysporum f. sp. vasinfectum (Fov), causes severe losses in cotton production worldwide. Though significant advancements have been made in development of FW‐resistant Upland cotton (Gossypium hirsutum) in resistance screening programs, the precise resistance genes and the corresponding molecular mechanisms for resistance to Fov remain unclear. Herein it is reported that Fov7, a gene unlike canonical plant disease‐resistance (R) genes, putatively encoding a GLUTAMATE RECEPTOR‐LIKE (GLR) protein, confers resistance to Fov race 7 in Upland cotton. A single nucleotide polymorphism (SNP) (C/A) in GhGLR4.8, resulting in an amino acid change (L/I), is associated with Fov resistance. A PCR‐based DNA marker (GhGLR4.8SNP(A/C)) is developed and shown to cosegregate with the Fov resistance. CRISPR/Cas9‐mediated knockout of Fov7 results in cotton lines extremely susceptible to Fov race 7 with a loss of the ability to induce calcium influx in response to total secreted proteins (SEPs) of Fov. Furthermore, coinfiltration of SEPs with GhGLR4.8A results in a hypersensitive response. This first report of a GLR‐encoding gene that functions as an R gene provides a new insight into plant–pathogen interactions and a new handle to develop cotton cultivars with resistance to Fov race 7.

Allium macrostemon saponin is a traditional Chinese medicine that exhibits anti-atherosclerosis effects. However, the mechanism of its action has not been fully clarified. Platelet activation induced by CD40L plays an important role in the process of atherosis. In the present study, we demonstrate for the first time that A. macrostemon saponin inhibits platelet activation induced by CD40L. Moreover, the effects of saponin on platelet activation were achieved by activation of the classical CD40L-associated pathway, including the PI3K/Akt, MAPK and NF-κB proteins. In addition, the present study further demonstrated that saponin exhibited an effect on the TRAF2-mediated ubiquitination degradation, which contributed to the inhibition of the CD40 pathway and its downstream members. The findings determine that A. macrostemon saponin inhibits activation of platelets via activation of downstream proteins of the CD40 pathway. This in turn affected TRAF2-associated ubiquitination degradation and caused an anti-thrombotic effect.

BackgroundSeveral long non-coding RNAs (lncRNAs) have been associated with cell senescence, termed senescence-associated lncRNAs (SAL-RNAs). However, the mechanisms involved for SAL-RNAs in aging are not fully elucidated. In the present study, we investigated the effects of SAL-RNAs on aged human bone marrow-derived mesenchymal stem cells (hBM-MSCs), and the possible means to counteract such effects to improve the regenerative capacity of aged hBM-MSCs.MethodsBy comparing the lncRNAs expression of hBM-MSCs derived from young and old individuals, lnc-CYP7A1-1 was identified as being significantly increased with age. Using predictive software, the expression of Spectrin Repeat Containing Nuclear Envelope Protein 1 (SYNE1), was found to be decreased with age. Next, through lentiviral constructs, we downregulated the expression of lnc-CYP7A1-1 or SYNE1 in hBM-MSCs separately. Additionally, hBM-MSCs proliferation, survival, migration, and senescence were investigated in vitro. In vivo, lnc-CYP7A1-1 downregulated aged hBM-MSCs were implanted into infarcted mouse hearts after myocardial infarction (MI), and cardiac function was measured. Through lentivirus-mediated downregulation of lnc-CYP7A1-1 in aged hBM-MSCs, we revealed that cell senescence was decreased, whereas cell proliferation, migration, and survival were increased. On the other hand, downregulation of SYNE1, the target gene of lnc-CYP7A1-1, in young hBM-MSCs increased cell senescence, yet decreased cell proliferation, migration, and survival. Downregulation of lnc-CYP7A1-1 in aged hBM-MSCs induced cell rejuvenation, yet this effect was attenuated by repression of SYNE1. In vivo, transplantation of lnc-CYP7A1-1 downregulated old hBM-MSCs improved cardiac function after MI.ConclusionDown-regulation of lnc-CYP7A1-1 rejuvenated aged hBM-MSCs and improved cardiac function when implanted into the infarcted mouse hearts, possibly through its target gene SYNE1.

Previous studies have demonstrated that sludge hydrolysis and short-chain fatty acids (SCFAs) production were improved through NaCl assistant anaerobic fermentation. However, the effect of NaCl concentrations on hydrolase activity and microbial community structure was rarely reported. In this study, it was found that α-glucosidase activity and some carbohydrate-degrading bacteria were inhibited in NaCl tests, owing to their vulnerability to high NaCl concentration. Correspondingly, the microbial community richness and diversity were reduced compared with the control test, while the evenness was not affected by NaCl concentration. By contrast, the protease activity was increased in the presence of NaCl and reached the highest activity at the NaCl concentration of 20 g/L. The protein-degrading and SCFAs-producing bacteria (e.g., Clostridium algidicarnis and Proteiniclasticum) were enriched in the presence of NaCl, which were salt-tolerant.