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Abstract Although epigenetic modification has long been recognized as a vital force influencing gene regulation in plants, the dynamics of chromatin structure implicated in the intertwined transcriptional regulation of duplicated genes in polyploids have yet to be understood. Here, we document the dynamic organization of chromatin structure in two subgenomes of allotetraploid cotton (Gossypium hirsutum) by generating 3D genomic, epigenomic and transcriptomic datasets from 12 major tissues/developmental stages covering the life cycle. We systematically identify a subset of genes that are closely associated with specific tissue functions. Interestingly, these genes exhibit not only higher tissue specificity but also a more pronounced homoeologous bias. We comprehensively elucidate the intricate process of subgenomic collaboration and divergence across various tissues. A comparison among subgenomes in the 12 tissues reveals widespread differences in the reorganization of 3D genome structures, with the Dt subgenome exhibiting a higher extent of dynamic chromatin status than the At subgenome. Moreover, we construct a comprehensive atlas of putative functional genome elements and discover that 37 cis-regulatory elements (CREs) have selection signals acquired during domestication and improvement. These data and analyses are publicly available to the research community through a web portal. In summary, this study provides abundant resources and depicts the regulatory architecture of the genome, which thereby facilitates the understanding of biological processes and guides cotton breeding.

Abstract Background CRISPR/Cas13 system, recognized for its compact size and specificity in targeting RNA, is currently employed for RNA degradation. However, the potential of various CRISPR/Cas13 subtypes, particularly concerning the knockdown of endogenous transcripts, remains to be comprehensively characterized in plants. Results Here we present a full spectrum of editing profiles for seven Cas13 orthologs from five distinct subtypes: VI-A (LwaCas13a), VI-B (PbuCas13b), VI-D (RfxCas13d), VI-X (Cas13x.1 and Cas13x.2), and VI-Y (Cas13y.1 and Cas13y.2). A systematic evaluation of the knockdown effects on two endogenous transcripts (GhCLA and GhPGF in cotton) as well as an RNA virus (TMV in tobacco) reveals that RfxCas13d, Cas13x.1, and Cas13x.2 exhibit enhanced stability with editing efficiencies ranging from 58 to 80%, closely followed by Cas13y.1 and Cas13y.2. Notably, both Cas13x.1 and Cas13y.1 can simultaneously degrade two endogenous transcripts through a tRNA-crRNA cassette approach, achieving editing efficiencies of up to 50%. Furthermore, different Cas13 orthologs enable varying degrees of endogenous transcript knockdown with minimal off-target effects, generating germplasms that exhibit a diverse spectrum of mutant phenotypes. Transgenic tobacco plants show significant reductions in damage, along with mild oxidative stress and minimal accumulation of viral particles after TMV infection. Conclusions In conclusion, our study presents an efficient and reliable platform for transcriptome editing that holds promise for plant functional research and future crop improvement.

Objective Retention or sacrifice of the posterior cruciate ligament (PCL) is one of the most controversial issues while performing total knee arthroplasty (TKA). This study aimed to evaluate the impact of PCL resection on flexion–extension gaps, femoral component rotation, and bone resection amounts during robot‐assisted TKA. Methods This prospective study included 40 patients with knee osteoarthritis who underwent robot‐assisted posterior‐stabilized (PS) TKA between September 2021 and February 2022. Of the patients, 75% were women (30/40) with a mean age and BMI of 72.6 years and 27.4 kg/m2, respectively. The guidance module and camera stand assembly were used to capture gaps before and after PCL resection. Measurements of femoral component rotation and bone resection amounts were made in cruciate‐retaining (CR) TKA mode and PS‐TKA mode. Results After PCL resection, the mean change in the medial and lateral compartments of flexion gaps increased by 2.0 and 0.6 mm, respectively (p

Purpose/aim: IgA nephropathy represents a prevalent form of the common kidney disease globally, accounting for the majority of cases of chronic kidney disease and renal failure. Cuscuta chinensis Lam has been shown to nourish the liver and tonify the kidney, consolidate essence, and arrest polyuria, However, whether Cuscuta chinensis Lam has the protective effects on IgA nephropathy and the underlying mechanisms remain unclear. Methods: A network pharmacology analysis was employed to examine the interactions between the active ingredients and core targets, with a view to elucidating the possible potential mechanisms in Cuscuta chinensis Lam. extract (CCLE) in the treatment of IgA nephropathy. Sprague-Dawley rats were administered with bovine serum albumin (BSA) with a dose of 800 mg/kg−1 every other day for a period of 12 weeks to obtain IgA nephropathy model. lipopolysaccharide (LPS) was injected through the tail vein at a dose of 0.05 mg at the 6th week, 8th week, and 10th week; 0.1 mL of CCl4 and 0.3 mL of castor oil were injected subcutaneously once a week for 12 weeks; the rats were gavaged with CCLE for 6 weeks from 13th week. Biochemical analysis, tGFR analysis, enzyme-linked immunosorbent assay (ELISA) analysis, periodic acid-Schiff (PAS) staining, Masson staining, and immunofluorescence staining were employed to evaluate the impact of CCLE on IgA nephropathy in rat. Western blotting was utilized to investigate the underlying mechanisms. Results: The results demonstrated that a significant decrease in the glomerular filtration rate, accompanied by a notable elevation in biochemical indexes in rats in model group, including the ratio of total protein to creatinine in urine, sCr, BUN, TG, AST, ALT, IL-1β and TNF-α; additionally, the rats in the model group exhibited substantial histopathological alterations, characterized by the presence of many IgA deposits; CCLE has been demonstrated to enhance the glomerular filtration rate, downregulate the levels of sCr, BUN, TG, AST, ALT, IL-1β and TNF-α, reduce the IgA deposition, and ameliorate the histopathological changes in IgA nephropathy rats; Western blotting demonstrated CCLE can suppress the expressions of p-PI3K, p-AKT, p-IKK, p-NF-κB, and p-IκB in IgA nephropathy rats. Conclusion: CCLE demonstrated superior protective effects on BSA + LPS + CCl4 + castor oil-induced IgA nephropathy in rats by regulating the PI3K-AKT and NF-κB signaling pathways. These findings suggest that CCLE has potential as a therapeutic agent for the treatment of IgA nephropathy.

BackgroundDepression is a major global public health concern, with research indicating a correlation between personality traits and depression. This study aimed to explore the potential mediating roles of self-efficacy and walking in the relationship between personality traits and depression among Chinese residents.MethodsA cross-sectional questionnaire survey was conducted from July 10 to September 15, 2021, involving 11,031 Chinese residents across 23 provinces, 5 autonomous regions, and 4 municipalities Participants provided data on demographics, personality traits (using the Ten-Item Personality Inventory), self-efficacy (using the New General Self-Efficacy Scale), chronic disease self-management (using the Chronic Disease Self-Management Study Measures), and depression (using the Patient Health Questionnaire-9). After screening, data from 8,499 participants were analyzed. Sequential mediation models were employed, with the Big Five personality traits as predictors, depression as the outcome, and self-efficacy and walking as the mediators.ResultsExtraversion, agreeableness, conscientiousness, and emotional stability were negatively correlated with depression, with self-efficacy and walking as positive mediators in these relationships. Conversely, openness was positively associated with depression, and the self-efficacy-walking chain did not mediate this relationship but rather masked the effect of openness on depression.ConclusionsOur findings suggest that self-efficacy and walking are significant mediators in the relationship between personality traits and depression, potentially mitigating the risk of depressive episodes.

Abstract The cotton bollworm causes severe mechanical damage to plants during feeding and leaves oral secretions (OSs) at the mechanical wounds. The role these OSs play in the invasion of plants is still largely unknown. Here, a novel H. armigera effector peptidyl prolyl trans‐isomerase 5 (PPI5) was isolated and characterized. PPI5 induces the programmed cell death (PCD) due to the unfolded protein response (UPR) in tobacco leaf. We reveal that PPI5 is important for the growth and development of cotton bollworm on plants, as it renders plants more susceptible to feeding. The GhFKBP17‐2, was identified as a host target for PPI5 with peptidyl‐prolyl isomerase (PPIase) activity. CRISPR/Cas9 knock‐out cotton mutant (CR‐GhFKBP17‐1/3), VIGS (TRV: GhFKBP17‐2) and overexpression lines (OE‐GhFKBP17‐1/3) were created and the data indicate that GhFKBP17‐2 positively regulates endoplasmic reticulum (ER) stress‐mediated plant immunity in response to cotton bollworm infestation. We further confirm that PPI5 represses JA and SA levels by downregulating the expression of JA‐ and SA‐associated genes, including JAZ3/9, MYC2/3, JAR4, PR4, LSD1, PAD4, ICS1 and PR1/5. Taken together, our results reveal that PPI5 reduces plant defense responses and makes plants more susceptible to cotton bollworm infection by targeting and suppressing GhFKBP17‐2 ‐mediated plant immunity.

Abstract The occurrence of whole-genome duplication or polyploidy may promote plant adaptability to harsh environments. Here, we clarify the evolutionary relationship of eight GhCIPK6 homologous genes in upland cotton (Gossypium hirsutum). Gene expression and interaction analyses indicate that GhCIPK6 homologous genes show significant functional changes after polyploidy. Among these, GhCIPK6D1 and GhCIPK6D3 are significantly up-regulated by drought stress. Functional studies reveal that high GhCIPK6D1 expression promotes cotton drought sensitivity, while GhCIPK6D3 expression promotes drought tolerance, indicating clear functional differentiation. Genetic and biochemical analyses confirm the synergistic negative and positive regulation of cotton drought resistance through GhCBL1A1-GhCIPK6D1 and GhCBL2A1-GhCIPK6D3, respectively, to regulate stomatal movement by controlling the directional flow of K+ in guard cells. These results reveal differentiated roles of GhCIPK6 homologous genes in response to drought stress in upland cotton following polyploidy. The work provides a different perspective for exploring the functionalization and subfunctionalization of duplicated genes in response to polyploidization.

Cotton fiber is one of the main raw materials for the textile industry. In recent years, many cotton fiber quality QTL have been identified, but few were applied in breeding. In this study, a genome wide association study (GWAS) of fiber-quality traits in 265 upland cotton breeding intermediate lines (GhBreeding), combined with genome-wide selective sweep analysis (GSSA) and genomic selection (GS), revealed 25 QTL. Most of these QTL were ignored by only using GWAS. The CRISPR/Cas9 mutants of GhMYB_D13 had shorter fiber, which indicates the credibility of QTL to a certain extent. Then these QTL were verified in other cotton natural populations, 5 stable QTL were found having broad potential for application in breeding. Additionally, among these 5 stable QTL, superior genotypes of 4 showed an enrichment in most improved new varieties widely cultivated currently. These findings provide insights for how to identify more QTL through combined multiple genomic analysis to apply in breeding.

With global warming, crop plants are challenged by heat stress during reproductive growth, leading to male sterility and yield reduction. The balance between reactive oxygen species (ROS) generation and scavenging is disrupted by stress, resulting in oxidative stress which is harmful to crop growth. However, recent advances have shown that ROS signaling via proteins that sense the redox state is positive for plant performance under stress. ROS signaling is also involved in regulating anther development, such as timely tapetum degeneration. We summarize recent progress in uncovering the mechanism of heat stress effects on ROS homeostasis and discuss the relationship between oxidative stress and metabolic disorder, which is often observed during anther development under heat stress. We propose experimental and breeding strategies to improve field crop tolerance to heat stress.

Abstract Background Cotton is a major world cash crop and an important source of natural fiber, oil, and protein. Drought stress is becoming a restrictive factor affecting cotton production. To facilitate the development of drought-tolerant cotton varieties, it is necessary to study the molecular mechanism of drought stress response by exploring key drought-resistant genes and related regulatory factors. Results In this study, two cotton varieties, ZY007 (drought-sensitive) and ZY168 (drought-tolerant), showing obvious phenotypic differences under drought stress, were selected. A total of 25,898 drought-induced genes were identified, exhibiting significant enrichment in pathways related to plant stress responses. Under drought induction, At subgenome expression bias was observed at the whole-genome level, which may be due to stronger inhibition of Dt subgenome expression. A gene co-expression module that was significantly associated with drought resistance was identified. About 90% of topologically associating domain (TAD) boundaries were stable, and 6613 TAD variation events were identified between the two varieties under drought. We identified 92 genes in ZY007 and 98 in ZY168 related to chromatin 3D structural variation and induced by drought stress. These genes are closely linked to the cotton response to drought stress through canonical hormone-responsive pathways, modulation of kinase and phosphatase activities, facilitation of calcium ion transport, and other related molecular mechanisms. Conclusions These results lay a foundation for elucidating the molecular mechanism of the cotton drought response and provide important regulatory locus and gene resources for the future molecular breeding of drought-resistant cotton varieties.

Abstract N6‐methyladenosine (m6A) is the most prevalent internal modification of mRNA and plays an important role in regulating plant growth. However, there is still a lack of effective tools to precisely modify m6A sites of individual transcripts in plants. Here, programmable m6A editing tools are developed by combining CRISPR/dCas13(Rx) with the methyltransferase GhMTA (Targeted RNA Methylation Editor, TME) or the demethyltransferase GhALKBH10 (Targeted RNA Demethylation Editor, TDE). These editors enable efficient deposition or removal of m6A modifications at targeted sites of endo‐transcripts GhECA1 and GhDi19 within a broad editing window ranging from 0 to 46 nt. TDE editor significantly decreases m6A levels by 24%–76%, while the TME editor increases m6A enrichment, ranging from 1.37‐ to 2.51‐fold. Furthermore, installation and removal of m6A modifications play opposing roles in regulating GhECA1 and GhDi19 mRNA transcripts, which may be attributed to the fact that their m6A sites are located in different regions of the genes. Most importantly, targeting the GhDi19 transcript with TME editor plants results in a significant increase in root length and enhanced drought resistance. Collectively, these m6A editors can be applied to study the function of specific m6A modifications and have the potential for future applications in crop improvement.

Abstract Interspecific genomic introgression is an important evolutionary process with respect to the generation of novel phenotypic diversity and adaptation. A key question is how gene flow perturbs gene expression networks and regulatory interactions. Here, an introgression population of two species of allopolyploid cotton (Gossypium) to delineate the regulatory perturbations of gene expression regarding fiber development accompanying fiber quality change is utilized. De novo assembly of the recipient parent (G. hirsutum Emian22) genome allowed the identification of genomic variation and introgression segments (ISs) in 323 introgression lines (ILs) from the donor parent (G. barbadense 3–79). It documented gene expression dynamics by sequencing 1,284 transcriptomes of developing fibers and characterized genetic regulatory perturbations mediated by genomic introgression using a multi‐locus model. Introgression of individual homoeologous genes exhibiting extreme low or high expression bias can lead to a parallel expression bias in their non‐introgressed duplicates, implying a shared yet divergent regulatory fate of duplicated genes following allopolyploidy. Additionally, the IL N182 with improved fiber quality is characterized, and the candidate gene GhFLAP1 related to fiber length is validated. This study outlines a framework for understanding introgression‐mediated regulatory perturbations in polyploids, and provides insights for targeted breeding of superior upland cotton fiber.

Abstract Global water scarcity and extreme weather intensify drought stress, significantly reducing cotton yield and quality worldwide. Drought treatments are conducted using a population of chromosome segment substitution lines generated from E22 (G. hirsutum) and 3–79 (G. barbadense) as parental lines either show superior yields or fiber quality under both control and drought conditions. Fourteen datasets, covering 4 yields and 4 quality traits, are compiled and assessed for drought resistance using the drought resistance coefficient (DRC) and membership function value of drought resistance (MFVD). Genome‐wide association studies, linkage analysis, and bulked segregant analysis are combined to analyze the DR‐related QTL. A total of 121 significant QTL are identified by DRC and MFVD of the 8 traits. CRISPR/Cas9 and virus‐induced gene silencing techniques verified DRR1 and DRT1 as pivotal genes in regulating drought resistant of cotton, with hap3‐79 exhibiting greater drought resistance than hapE22 concerning DRR1 and DRT1. Moreover, 14 markers with superior yield and fiber quality are selected for drought treatment. This study offers valuable insights into yield and fiber quality variations between G. hirsutum and G. barbadense amid drought, providing crucial theoretical and technological backing for developing cotton varieties resilient to drought, with high yield and superior fiber quality.

Abstract Background Transposable elements (TEs) have a profound influence on the trajectory of plant evolution, driving genome expansion and catalyzing phenotypic diversification. The pangenome, a comprehensive genetic pool encompassing all variations within a species, serves as an invaluable tool, unaffected by the confounding factors of intraspecific diversity. This allows for a more nuanced exploration of plant TE evolution. Results Here, we constructed a pangenome for diploid A-genome cotton using 344 accessions from representative geographical regions, including 223 from China as the main component. We found 511 Mb of non-reference sequences (NRSs) and revealed the presence of 5479 previously undiscovered protein-coding genes. Our comprehensive approach enabled us to decipher the genetic underpinnings of the distinct geographic distributions of cotton. Notably, we identified 3301 presence-absence variations (PAVs) that are closely tied to gene expression patterns within the pangenome, among which 2342 novel expression quantitative trait loci (eQTLs) were found residing in NRSs. Our investigation also unveiled contrasting patterns of transposon proliferation between diploid and tetraploid cotton, with long terminal repeat (LTR) retrotransposons exhibiting a synchronized surge in polyploids. Furthermore, the invasion of LTR retrotransposons from the A subgenome to the D subgenome triggered a substantial expansion of the latter following polyploidization. In addition, we found that TE insertions were responsible for the loss of 36.2% of species-specific genes, as well as the generation of entirely new species-specific genes. Conclusions Our pangenome analyses provide new insights into cotton genomics and subgenome dynamics after polyploidization and demonstrate the power of pangenome approaches for elucidating transposon impacts and genome evolution.

Abstract Background CRISPR/Cas-derived base editor enables precise editing of target sites and has been widely used for basic research and crop genetic improvement. However, the editing efficiency of base editors at different targets varies greatly. Results Here, we develop a set of highly efficient base editors in cotton plants. GhABE8e, which is fused to conventional nCas9, exhibits 99.9% editing efficiency, compared to GhABE7.10 with 64.9%, and no off-target editing is detected. We further replace nCas9 with dCpf1, which recognizes TTTV PAM sequences, to broaden the range of the target site. To explore the functional divergence of TERMINAL FLOWER 1 (TFL1), we edit the non-coding and coding regions of GhTFL1 with 26 targets to generate a comprehensive allelic population including 300 independent lines in cotton. This allows hidden pleiotropic roles for GhTFL1 to be revealed and allows us to rapidly achieve directed domestication of cotton and create ideotype germplasm with moderate height, shortened fruiting branches, compact plant, and early-flowering. Further, by exploring the molecular mechanism of the GhTFL1 L86P and GhTFL1 K53G+S78G mutations, we find that the GhTFL1 L86P mutation weakens the binding strength of the GhTFL1 to other proteins but does not lead to a complete loss of GhTFL1 function. Conclusions This strategy provides an important technical platform and genetic information for the study and creation of ideal plant architecture.

Introduction: Vitexin is a natural flavonoid compound extracted from Vitex leaves or seeds, exhibiting various pharmacological activities including anticancer, antihypertensive, anti-inflammatory, and spasmolytic effects. However, its protective effects on hypertensive nephropathy (HN) and the underlying mechanisms remain unclear. Methods: Spontaneous hypertension rats were fed a high-sugar and high-fat diet for 8 weeks to induce the disease HN model. From the 5th week, the rats were administered vitexin via gavage. Blood pressure was measured bi-weekly using the tail-cuff method. Histopathological changes were assessed using HE staining, and biochemical analyses were performed to evaluate the effects of vitexin on HN rats. The underlying mechanisms of vitexin treatment were investigated through western blotting. Results: The data demonstrated that vitexin significantly lowered systolic, diastolic, and mean arterial pressures, and ameliorated histopathological changes in HN rats. Biochemical analyses revealed that vitexin reduced the levels of creatinine (Cr), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), total protein (TP), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and advanced glycation end products (AGEs), while increasing the levels of albumin (ALB) and superoxide dismutase (SOD). Western blotting results indicated that vitexin treatment decreased the expression of TNF-α, IL-6, and nuclear factor kappa-B (NF-κB), while increasing the expression of SOD. Conclusion: The findings of this study suggest that vitexin exerts protective effects against HN, providing pharmacological evidence for its potential use in HN treatment.

This study investigated rice straw hydrothermal carbonization (HTC) in water, optimizing operating conditions to enhance solid carbon content and nitrogen content in hydrochar. Additionally, we conducted hydrothermal co-carbonization (co-HTC) of rice straw and acid whey, achieving significant improvements in hydrochar properties. Co-HTC resulted in a 53.6% increase in HHVs, 20.0% higher yield, and a 42.7% rise in carbon content, accompanied by notable reductions in ash content. Nitrogen content increased by 26.0%, P content by 12.7 times, and K content by 27.6%. Analytical techniques revealed promising modifications, indicating potential applications of hydrochar in solid fuel or organic fertilizers, thus contributing to a circular bioeconomy in agricultural waste management.

Soft tissue injuries (STIs) are the most common cause of extremity pain and motion dysfunction. Persistent inflammatory activation of immune cells characterized by senescence‐associated secretory phenotype (SASP) and mitochondrial stress are considered the primary causes of STIs, a pathological process also termed inflammaging. Meanwhile, scavenging excessive “cellular waste” in the inflammaging microenvironment and further activating tissue repair processes remain elusive. Herein, an anti‐inflammaging photothermal hydrogel microneedle patch for treating STIs is developed. Taurine‐loaded Prussian blue nanoparticles (Taurine@PB) are encapsulated in a methacrylate‐based hyaluronic acid hydrogel (HAMA) and further fabricated into taurine@PB@HAMA@microneedles (TPH@MN) patches. The acidic microenvironment of chronic inflammation and mild photothermal effects promote taurine release and anti‐inflammaging immunomodulation, inhibiting mitochondrial stress via the SIRT3‐NF‐κB axis to promote glycolytic metabolic microenvironment of neutrophils reprogramming toward oxidative phosphorylation metabolism. Furthermore, TPH@MN activates macrophage efferocytosis and initiates the process of tissue repair. In mouse models of chronic diabetic wounds and tibialis anterior (TA) muscle injury, TPH@MN inhibits SASP expression and promotes STIs healing through thermosensitized anti‐inflammaging immunomodulation. In summary, TPH@MN circumvents the side effects of systemic administration, providing new translatable options in the treatment modalities for patients suffering from STIs worldwide.

Abstract Hematoma, a risk factor of implant‐associated infections (IAIs), creates a Fe‐rich environment following implantation, which proliferates the growth of pathogenic bacteria. Fe metabolism is a major vulnerability for pathogens and is crucial for several fundamental physiological processes. Herein, a deferiprone (DFP)‐loaded layered double hydroxide (LDH)‐based nanomedicine (DFP@Ga‐LDH) that targets the Fe‐rich environments of IAIs is reported. In response to acidic changes at the infection site, DFP@Ga‐LDH systematically interferes with bacterial Fe metabolism via the substitution of Ga3+ and Fe scavenging by DFP. DFP@Ga‐LDH effectively reverses the Fe/Ga ratio in Pseudomonas aeruginosa, causing comprehensive interference in various Fe‐associated targets, including transcription and substance metabolism. In addition to its favorable antibacterial properties, DFP@Ga‐LDH functions as a nano‐adjuvant capable of delaying the emergence of antibiotic resistance. Accordingly, DFP@Ga‐LDH is loaded with a siderophore antibiotic (cefiderocol, Cefi) to achieve the antibacterial nanodrug DFP@Ga‐LDH‐Cefi. Antimicrobial and biosafety efficacies of DFP@Ga‐LDH‐Cefi are validated using ex vivo human skin and mouse IAI models. The pivotal role of the hematoma‐created Fe‐rich environment of IAIs is highlighted, and a nanoplatform that efficiently interferes with bacterial Fe metabolism is developed. The findings of the study provide promising guidance for future research on the exploration of nano‐adjuvants as antibacterial agents.

The treatment of osteoporotic implant failures tends to be challenging due to an imbalance in bone homeostasis. Recently, the accumulation of intracellular reactive oxygen species (ROS) and activation of the inflammasome containing nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3) protein have been shown to indirectly affect osteogenesis and osteoclastogenesis. Owing to the release of multi-metal ions from laponite (LAP), we fabricated a multifunctional LAP coating on a three-dimensional microporous sulfonated polyetheretherketone (SPEEK) surface via polydopamine (PDA) modification (SPEEK@PDA-LAP). The balance between osteogenesis and osteoclastogenesis was examined using macrophages in an osteo-immune microenvironment. Employing in vitro assays, we showed that the SPEEK@PDA-LAP alleviated intracellular ROS accumulation and inhibited the activation of NLRP3 inflammasome-mediated pyroptosis in macrophages, creating an osteoimmunomodulatory microenvironment to stimulate osteogenesis and inhibit osteoclastogenesis. The micro-computed tomography and histological results of in vivo experiments indicated that SPEEK@PDA-LAP implants reversed the balance between osteogenesis and osteoclastogenesis to promote the formation of new bone around the implant even under osteoporotic conditions. The results indicate that inhibiting the NLRP3 inflammasome and regulating intracellular ROS in macrophages can be an effective therapy for osteoporosis. These results highlight the potential of functional PEEK materials for bone regeneration in patients with osteoporosis.

Introduction: Sea-island cotton (Gossypium barbadense, Gb) is one of the major sources of high-grade natural fiber. Besides the common annual Gb cotton, perennial Gb cotton is also cultivated, but studies on perennial Gb cotton are rare. Objectives: We aimed to make a systematic analysis of perennial sea-island cotton and lay a foundation for its utilization in breeding, and try to identify the representative structural variations (SVs) in sea-island cotton, and to reveal the population differentiation and adaptive improvement of sea-island cotton. Methods: Through genome assembly of one perennial Gb cotton accession (named Gb_M210936) and comparative genome analysis, variations during Gb cotton domestication were identified by comparing Gb_M210936 with annual Gb accession 3–79 and with wild allotetraploid cotton G. darwinii. Six perennial Gb accessions combining with the resequenced 1,129 cotton accessions were used to conduct population and genetic analysis. Large haplotype blocks (haploblocks), generated from interspecific introgressions and intraspecific inversions, were identified and were used to analyze their effects on population differentiation and agronomic traits of sea-island cotton. Results: One reference genome of perennial sea-island cotton was assembled. Representative SVs in sea-island cotton were identified, and 31 SVs were found to be associated with agronomic traits. Perennial Gb cotton had a closer kinship with the wild-to-landrace continuum Gb cotton from south America where Gb cotton is originally domesticated. Haploblocks were associated with agronomic traits improvement of sea-island cotton, promoted sea-island cotton differentiation into three subgroups, were suffered from breeding selection, and may drive Gb cotton to be adapted to central Asian. Conclusion: Our study made up the lack of perennial Gb cotton genome, and clarified that exotic introgressions improved the traits of sea-island cotton, promoted the population differentiation, and drove sea-island cotton adaptive to central Asia, which will provide new insights for the genetic breeding improvement of sea-island cottons.

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.

The speckle noise inherent in synthetic aperture radar (SAR) imaging has long posed a challenge for SAR data processing, significantly affecting image interpretation and recognition. Recently, deep learning-based SAR speckle removal algorithms have shown promising results. However, most existing algorithms rely on convolutional neural networks (CNN), which may struggle to effectively capture global image information and lead to texture loss. Besides, due to the different characteristics of optical images and synthetic aperture radar (SAR) images, the results of training with simulated SAR data may bring instability to the real-world SAR data denoising. To address these limitations, we propose an innovative approach that integrates swin transformer blocks into the prediction noise network of the denoising diffusion probabilistic model (DDPM). By harnessing DDPM’s robust generative capabilities and the Swin Transformer’s proficiency in extracting global features, our approach aims to suppress speckle while preserving image details and enhancing authenticity. Additionally, we employ a post-processing strategy known as pixel-shuffle down-sampling (PD) refinement to mitigate the adverse effects of training data and the training process, which rely on spatially uncorrelated noise, thereby improving its adaptability to real-world SAR image despeckling scenarios. We conducted experiments using both simulated SAR image datasets and real SAR image datasets, evaluating our algorithm from subjective and objective perspectives. The visual results demonstrate significant improvements in noise suppression and image detail restoration. The objective results demonstrate that our method obtains state-of-the-art performance, which outperforms the second-best method by an average peak signal-to-noise ratio (PSNR) of 0.93 dB and Structural Similarity Index (SSIM) of 0.03, affirming the effectiveness of our approach.

Abstract Background The collapse index of inferior Vena Cava (IVC) and its diameter are important predictive tools for fluid responsiveness in patients, especially critically ones. The collapsibility of infraclavicular axillary vein (AXV) can be used as an alternative to the collapsibility of IVC (IVC-CI) to assess the patient’s blood volume. Methods A total of 188 elderly patients aged between 65 and 85 years were recruited for gastrointestinal surgery under general anesthesia. Ultrasound measurements AXV and IVC were performed before induction of general anesthesia. Patients were grouped in accordance to the hypotension after induction. ROC curves were used to analyze the predictive value of ultrasound measurements of AXV and IVC for hypotension after induction of anesthesia. Pearson linear correlation was used to assess the correlation of ultrasound measurements and decrease in mean arterial blood pressure (MAP). Results The maximum diameter of AXV(dAXVmax) and the maximum diameter of IVC (dIVCmax) were not related to the percentage decrease in MAP; the collapsibility of AXV (AXV-CI) and IVC-CI were positively correlated with MAP changes (correlation coefficients:0.475, 0.577, respectively, p

Introduction: Drought is the principal abiotic stress that severely impacts cotton (Gossypium hirsutum) growth and productivity. Upon sensing drought, plants activate stress-related signal transduction pathways, including ABA signal and mitogen-activated protein kinase (MAPK) cascade. However, as the key components with the fewest members in the MAPK cascade, the function and regulation of GhMKKs need to be elucidated. In addition, the relationship between MAPK module and the ABA core signaling pathway remains incompletely understood. Objective: Here we aim to elucidate the molecular mechanism of cotton response to drought, with a focus on mitogen-activated protein kinase (MAPK) cascades activating ABA signaling. Methods: Biochemical, molecular and genetic analysis were used to study the GhMAP3K62-GhMKK16-GhMPK32-GhEDT1 pathway genes. Results: A nucleus- and membrane-localized MAPK cascade pathway GhMAP3K62-GhMKK16-GhMPK32, which targets and phosphorylates the nuclear-localized transcription factor GhEDT1, to activate downstream GhNCED3 to mediate ABA-induced stomatal closure and drought response was characterized in cotton. Overexpression of GhMKK16 promotes ABA accumulation, and enhances drought tolerance via regulating stomatal closure under drought stress. Conversely, RNAi-mediated knockdown of GhMKK16 expression inhibits ABA accumulation, and reduces drought tolerance. Virus-induced gene silencing (VIGS)-mediated knockdown of either GhMAP3K62, GhMPK32 or GhEDT1 expression represses ABA accumulation and reduces drought tolerance through inhibiting stomatal closure. Expression knockdown of GhMPK32 or GhEDT1 in GhMKK16-overexpressing cotton reinstates ABA content and stomatal opening-dependent drought sensitivity to wild type levels. GhEDT1 could bind to the HD boxes in the promoter of GhNCED3 to activate its expression, resulting in ABA accumulation. We propose that the MAPK cascade GhMAP3K62-GhMKK16-GhMPK32 pathway functions on drought response through ABA-dependent stomatal movement in cotton.

Abstract Background Adelphocoris suturalis (Hemiptera: Miridae) is a notorious agricultural pest, which causes serious economic losses to a diverse range of agricultural crops around the world. The poor understanding of its genomic characteristics has seriously hindered the establishment of sustainable and environment-friendly agricultural pest management through biotechnology and biological insecticides. Results Here, we report a chromosome-level assembled genome of A. suturalis by integrating Illumina short reads, PacBio, 10x Chromium, and Hi-C mapping technologies. The resulting 1.29 Gb assembly contains twelve chromosomal pseudomolecules with an N50 of 1.4 and 120.6 Mb for the contigs and scaffolds, respectively, and carries 20,010 protein-coding genes. The considerable size of the A. suturalis genome is predominantly attributed to a high amount of retrotransposons, especially long interspersed nuclear elements (LINEs). Transcriptomic and phylogenetic analyses suggest that A. suturalis-specific candidate effectors, and expansion and expression of gene families associated with omnivory, insecticide resistance and reproductive characteristics, such as digestion, detoxification, chemosensory receptors and long-distance migration likely contribute to its strong environmental adaptability and ability to damage crops. Additionally, 19 highly credible effector candidates were identified and transiently overexpressed in Nicotiana benthamiana for functional assays and potential targeting for insect resistance genetic engineering. Conclusions The high-quality genome of A. suturalis provides an important genomic landscape for further investigations into the mechanisms of omnivory, insecticide resistance and survival adaptation, and for the development of integrated management strategies.

Abstract Background Somatic embryogenesis is a major process for plant regeneration. However, cell communication and the gene regulatory network responsible for cell reprogramming during somatic embryogenesis are still largely unclear. Recent advances in single-cell technologies enable us to explore the mechanism of plant regeneration at single-cell resolution. Results We generate a high-resolution single-cell transcriptomic landscape of hypocotyl tissue from the highly regenerable cotton genotype Jin668 and the recalcitrant TM-1. We identify nine putative cell clusters and 23 cluster-specific marker genes for both cultivars. We find that the primary vascular cell is the major cell type that undergoes cell fate transition in response to external stimulation. Further developmental trajectory and gene regulatory network analysis of these cell clusters reveals that a total of 41 hormone response-related genes, including LAX2, LAX1, and LOX3, exhibit different expression patterns in the primary xylem and cambium region of Jin668 and TM-1. We also identify novel genes, including CSEF, PIS1, AFB2, ATHB2, PLC2, and PLT3, that are involved in regeneration. We demonstrate that LAX2, LAX1 and LOX3 play important roles in callus proliferation and plant regeneration by CRISPR/Cas9 editing and overexpression assay. Conclusions This study provides novel insights on the role of the regulatory network in cell fate transition and reprogramming during plant regeneration driven by somatic embryogenesis.

When testing the nanoindentation hardness of the same sample with different Berkovich indenters, inconsistencies arise even when the frame stiffness and indenter tip area functions are regularly calibrated. This phenomenon has not been fully understood, making it challenging to accurately test and compare material hardness data from different laboratories. To address this issue, incremental test hardness caused by indenter tip defects and indentation size effects (ISE) is quantified. The ISE correction method proposed in this study is based on the Nix-Gao model for nanoindentation load-indentation depth (P-h) curves, and an area function equivalent modeling method is used to reproduce the geometry of Berkovich indenters in finite element (FE) analysis. Although the test hardness using different Berkovich indenters is inconsistent, their intrinsic hardness remains consistent. The proposed ISE correction method is validated by FE simulation results for A508-3 and 316 L steel that match perfectly with the ISE-corrected experimental P-h curves. The analysis of load increments shows that tip defects affect the test result through statistically stored dislocation (SSD) and geometrically necessary dislocation (GND). Indenter tip defects mainly affect the nanoindentation test results through GND. The smaller the indenter tip radius, the higher the GNDs, and the higher the test hardness. The different effects of indenter tip defects on GND lead to inconsistent hardness measurements using different Berkovich indenters.

Aims: The present study aimed to investigate whether patients with inflammatory bowel disease (IBD) undergoing joint arthroplasty have a higher incidence of adverse outcomes than those without IBD. Methods: A comprehensive literature search was conducted to identify eligible studies reporting postoperative outcomes in IBD patients undergoing joint arthroplasty. The primary outcomes included postoperative complications, while the secondary outcomes included unplanned readmission, length of stay (LOS), joint reoperation/implant revision, and cost of care. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model when heterogeneity was substantial. Results: Eight retrospective studies involving 29,738 patients with IBD were included. Compared with non-IBD controls, patients with IBD were significantly more likely to have overall complications (OR 2.11 (95% CI 1.67 to 2.66), p < 0.001), medical complications (OR 2.15 (95% CI 1.73 to 2.68), p < 0.001), surgical complications (OR 1.43 (95% CI 1.21 to 1.70), p < 0.001), and 90-day readmissions (OR 1.42 (95% CI 1.23 to 1.65), p < 0.001). The presence of IBD was positively associated with the development of venous thromboembolism (OR 1.60 (95% CI 1.30 to 1.97), p < 0.001) and postoperative infection (OR 1.95 (95% CI 1.51 to 2.51), p < 0.001). In addition, patients with IBD tended to experience longer LOS and higher costs of care. Conclusion: The findings suggest that IBD is associated with an increased risk of postoperative complications and readmission after joint arthroplasty, resulting in longer hospital stay and greater financial burden. Surgeons should inform their patients of the possibility of adverse outcomes prior to surgery and make appropriate risk adjustments to minimize potential complications. Cite this article: Bone Joint Res 2023;12(6):362–371.

Abstract Karakoram Highway (KKH) is frequently disrupted by geological hazards mainly landslides which pose a serious threat to its normal operation. Using documented inventory, optical imagery interpretation, and frequency-area statistics, the features of slope failure, the spatial distribution, and their link to numerous contributing factors have all been effectively explored along the KKH. An updated inventory for the area was recreated using the interferometric synthetic aperture radar (InSAR) persistent scatterer (PS) technology to further investigate millimetre-accurate measurements of slope deformation (Vslope). Utilizing the PS approach, Sentinel-1 data from Jan 2018 to Jan 2022 were processed by which we obtained a deformation rate (VSlope) that varies between 0 and 364 mm/year. A total number of 234 landslides were cited from the literature and classified while 29 new potential landslides were detected and several pre-existing landslides were redefined by the InSAR approach, which was incorporated to generate an updated landslide susceptibility model with 86.6% of prediction precision in the area under curve method. As previous studies done by applying the InSAR technique incorporated a short span temporally and they missed some highly deforming zones like Budalas and Khanabad landslides, contain mean velocities > 50 mm/yr, which we studied individually in this work. In this study, a comprehensive application of the InSAR technique to assessing its performance in detecting and analysing landslides has been applied. The deformation velocity (Vslope) model shows high displacement in some regions, which needed to be further investigated by geoscientists, and the updated developed landslide inventory and susceptibility map can be used for land use planning and landslide mitigation strategies.

Abstract Plant anthers are composed of different specialized cell types with distinct roles in plant reproduction. High temperature (HT) stress causes male sterility, resulting in crop yield reduction. However, the spatial expression atlas and regulatory dynamics during anther development and in response to HT remain largely unknown. Here, the first single‐cell transcriptome atlas and chromatin accessibility survey in cotton anther are established, depicting the specific expression and epigenetic landscape of each type of cell in anthers. The reconstruction of meiotic cells, tapetal cells, and middle layer cell developmental trajectories not only identifies novel expressed genes, but also elucidates the precise degradation period of middle layer and reveals a rapid function transition of tapetal cells during the tetrad stage. By applying HT, heterogeneity in HT response is shown among cells of anthers, with tapetal cells responsible for pollen wall synthesis are most sensitive to HT. Specifically, HT shuts down the chromatin accessibility of genes specifically expressed in the tapetal cells responsible for pollen wall synthesis, such as QUARTET 3 (QRT3) and CYTOCHROME P450 703A2 (CYP703A2), resulting in a silent expression of these genes, ultimately leading to abnormal pollen wall and male sterility. Collectively, this study provides substantial information on anthers and provides clues for heat‐tolerant crop creation.

Abstract Insects pose significant challenges in cotton‐producing regions. Here, they describe a high‐throughput CRISPR/Cas9‐mediated large‐scale mutagenesis library targeting endogenous insect‐resistance‐related genes in cotton. This library targeted 502 previously identified genes using 968 sgRNAs, generated ≈2000 T0 plants and achieved 97.29% genome editing with efficient heredity, reaching upto 84.78%. Several potential resistance‐related mutants (10% of 200 lines) their identified that may contribute to cotton‐insect molecular interaction. Among these, they selected 139 and 144 lines showing decreased resistance to pest infestation and targeting major latex‐like protein 423 (GhMLP423) for in‐depth study. Overexpression of GhMLP423 enhanced insect resistance by activating the plant systemic acquired resistance (SAR) of salicylic acid (SA) and pathogenesis‐related (PR) genes. This activation is induced by an elevation of cytosolic calcium [Ca2+]cyt flux eliciting reactive oxygen species (ROS), which their demoted in GhMLP423 knockout (CR) plants. Protein‐protein interaction assays revealed that GhMLP423 interacted with a human epidermal growth factor receptor substrate15 (EPS15) protein at the cell membrane. Together, they regulated the systemically propagating waves of Ca2+ and ROS, which in turn induced SAR. Collectively, this large‐scale mutagenesis library provides an efficient strategy for functional genomics research of polyploid plant species and serves as a solid platform for genetic engineering of insect resistance.

Objective In revision total hip arthroplasty (THA), reconstruction of severe acetabular bone defect continues to be problematic for orthopedic surgeons. This study reports the mid‐ to long‐term survivorship, radiological outcomes, and complications of impaction bone grafting (IBG) and metal mesh with a cemented acetabular component in the reconstruction of severe acetabular bone defects in revision THA. Methods This retrospective consecutive study included 26 patients (29 hips: type II B, four; type II C, three; type III A, 10; and type III B, 12) who underwent revision THA, which was performed using IBG and metal mesh, between 2007 and 2014 in our institution. All patients were followed up regularly for clinical and radiographical assessments. Migration and loosening of prosthesis graft integration and complications were observed and analyzed. Survival analysis was performed using a Kaplan–Meier survival analysis. Results At the time of revision, 75.9% of the hips (22 hips) were classified as type III bone defects. The average follow‐up period was 9.4 ± 2.8 (range, 2.4–14.0) years. Of the 29 hips, four hips (13.8%) were assessed as clinical failures; at the last follow‐up, two had undergone re‐revision THA, and two had not been scheduled for re‐revision THA despite radiological failure of the acetabular component. Among them, three clinical failures (10.3%) were due to aseptic loosening, and one (3.4%) was due to infection. Radiographic evaluation showed bone graft integration in all hips during the follow‐up. The Kaplan–Meier survivorship analysis revealed an acetabular reconstruction survival rate of 86.5% (95% confidence interval, 61.4%–95.7%) at 10 years. Conclusion IBG and metal mesh with a cemented acetabular component for revision THA is an effective technique for treating severe acetabular bone defects, with effective mid‐ to long‐term outcomes due to the solid reconstruction of the acetabular bone defect and restoration of the hip rotation center.

Abstract The ongoing coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused great public health concern and has been a global threat due to its high transmissibility and morbidity. Although the SARS‐CoV‐2 transmission mainly relies on the person‐to‐person route through the respiratory droplets, the possible transmission through the contaminated cold‐chain food and packaging to humans has raised widespread concerns. This review discussed the possibility of SARS‐CoV‐2 transmission via the contaminated cold‐chain food and packaging by tracing the occurrence, the survival of SARS‐CoV‐2 in the contaminated cold‐chain food and packaging, as well as the transmission and outbreaks related to the contaminated cold‐chain food and packaging. Rapid, accurate, and reliable diagnostics of SARS‐CoV‐2 is of great importance for preventing and controlling the COVID‐19 resurgence. Therefore, we summarized the recent advances on the emerging clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system‐based biosensing technology that is promising and powerful for preventing the possible COVID‐19 resurgence caused by the contaminated cold‐chain food and packaging during the COVID‐19 pandemic, including CRISPR/Cas system‐based biosensors and their integration with portable devices (e.g., smartphone, lateral flow assays, microfluidic chips, and nanopores). Impressively, this review not only provided an insight on the possibility of SARS‐CoV‐2 transmission through the food supply chain, but also proposed the future opportunities and challenges on the development of CRISPR/Cas system‐based detection methods for the diagnosis of SARS‐CoV‐2.

Cotton (Gossypium spp.) yield is reduced by stress. In this study, high temperature (HT) suppressed the expression of the jasmonic acid (JA) biosynthesis gene allene oxide cyclase 2 (GhAOC2), reducing JA content and causing male sterility in the cotton HT-sensitive line H05. Anther sterility was reversed by exogenous application of methyl jasmonate (MeJA) to early buds. To elucidate the role of GhAOC2 in JA biosynthesis and identify its putative contribution to the anther response to HT, we created gene knockout cotton plants using the CRISPR/Cas9 system. Ghaoc2 mutant lines showed male-sterile flowers with reduced JA content in the anthers at the tetrad stage (TS), tapetum degradation stage (TDS), and anther dehiscence stage (ADS). Exogenous application of MeJA to early mutant buds (containing TS or TDS anthers) rescued the sterile pollen and indehiscent anther phenotypes, while ROS signals were reduced in ADS anthers. We propose that HT downregulates the expression of GhAOC2 in anthers, reducing JA biosynthesis and causing excessive ROS accumulation in anthers, leading to male sterility. These findings suggest exogenous JA application as a strategy for increasing male fertility in cotton under HT.

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.

The patella's inferior pole transmits force generated by contraction of the quadriceps muscle to the tibial tuberosity through the attached patellar ligament, thus completing knee extension. Therefore, fractures of the patella's inferior pole disrupt the coherence of mechanical transmission in the lower extremities. There appears to be no consensus among trauma centers regarding the treatment of infrapatellar pole fractures, primarily because there is no consistent design or application of internal fixation for this type of fracture. We designed a new internal implant similar to the smile necklace based on our previous study. This smile‐necklace plate (SNP) has the advantage of both plate fixation and tension‐band wiring fixation, permitting early rehabilitation, especially in osteoporotic comminuted infrapatellar pole fractures. Finite element analysis helped verify the biomechanical advantages of the SNP in comparison with existing studies. Hence, this novel implant is a promising treatment option for inferior pole patellar fractures.

Nuclear technology has expanded from the original weapon of war to all aspects of social development, finding wide applications in various industries such as medical diagnostics, nuclear power plants and military. Although it brings infinite convenience to industrial and medical fields, the health hazards of nuclear radiation have always troubled the professionals. It has been a long-standing challenge to fabricate lightweight shielding composites with high shielding efficiency. Compared with traditional methods, recently, the new hybrid nanoparticles, orientation stack and controllable periodic distribution of fillers as well as spatially confined composites have aroused great interest of researchers. In this review, the newly emerged manufacturing and evaluation strategies, as well as recent advances on X-ray, γ-ray, and neutron shielding polymer composites are explored. Notably, the focus lies on the biomedical applications of radiation shielding polymer composites and novel polymer drugs for in vivo radioprotection. Additionally, a promising direction is highlighted for the comprehensive evaluation of the effectiveness of radiation shielding materials, considering both energy attenuation ability and radiation dose accumulation simultaneously. Topics regarding ray-interaction mechanism, radiation injury, structural design, manufacturing strategy and biomedical applications are also discussed in detail.

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.

The windward bend lattice frame structure (WB structure) is characterized by a high heat transfer coefficient and low friction factor. The WB structure can be applied for thermal protection system, protecting outer walls of afterburner and nozzles from being damaged by the heating load of hot gas, for air cooling system of the power battery module, dissipating the heat generated during its charging and discharging. In this paper, the heat transfer characteristics of the windward bend lattice frame structure have been comprehensively studied. A systematic 3D numerical simulation has been conducted to investigate the effects of the structural parameters of the WB structure, including the pitches in both flow direction and transverse direction, the diameter and the inclination angle of windward bend ligament, on its flow resistance and heat transfer enhancement, which has been evaluated by comparing its Nusselt number under an equal pumping power. Furthermore, the contribution of an important parameter, i.e., the ratio of the interstitial heat transfer rate to the end-wall heat transfer rate (RQ), to the overall heat transfer rate has been fully discussed. As a result, the case of 6 units in the longitudinal direction and 2.5 units in the transverse direction, i.e. (nx = 6, nz = 2.5) exhibits the best performance in the light of the value of the Nusselt number. Moreover, the structure with a ratio of RQ ranges in 4.5–5.0 achieves a better heat transfer performance. Finally, two color contour graphs showing an optimal range of Nusselt number coordinated by unit numbers (nx, nz) for pumping powers of 2500 and 3000 have been presented. The graphs correctly reflect the variation of Nusselt numbers of structures with different nx and nz, and the conclusions remain consistent with the discussion in sections 4.2 and 4.3, instructing the reasonable selection of structural parameters of a thermal protection system embedded with WB structure.

Abstract Background This study aimed at investigating the characteristics of clinical trials related to hip fractures that were registered at ClinicalTrials.gov. It also aimed to identify potential risk factors associated with completion. Main body We obtained 733 clinical studies related to hip fractures from the ClinicalTrials.gov database and included 470 studies in the analysis. These clinical trials were divided into behavioral, drug/biological, device, procedure, and other categories based on intervention types. Clinical trials investigating drugs or biologics were categorized based on the specific agents administered in each trial. Multiple logistic and Cox regression models were used to test the ability of 24 potential risk factors in predicting recruitment status and completion time, respectively. Among the included clinical trials, 44.89% (211/470) had complete recruitment status. The overall median completion time was 931.00 days (95% confidence interval [CI]: 822.56–1039.44 days). The results of only 8.94% (42/470) of clinical trials were presented on the ClinicalTrials.gov website. Bupivacaine (a local anesthetic) was most commonly investigated (in 25 clinical trials); this was followed by ropivacaine (another local anesthetic, 23 clinical trials) and tranexamic acid (a hemostatic, 21 clinical trials). Multivariate analysis showed that trials including children (P = 0.03) and having National Institutes of Health funds (P

MicroRNAs (miRNAs) play essential roles in plant defense responses, although such roles have not been identified in cotton in response to the plant pathogenic fungus Verticillium dahliae. In this study, the functions of miR398b and its target genes in cotton-V. dahliae interaction were investigated. The transcript levels of miR398b were down-regulated by V. dahliae infection and miR398b overexpression in cotton made the plants more susceptible to V. dahliae. The results suggest that miR398b negatively regulates cotton resistance to V. dahliae. This may occur by miR398b repression of some CC-NBS-LRR genes via translational inhibition, interfering with defense responses and leading to cotton susceptibility to V. dahliae. Alternatively, miR398b may guide the cleavage of the mRNAs of GhCSD1, GhCSD2 and GhCCS, each of which functions in reactive oxygen species (ROS) regulation and homeostasis, thereby causing excessive ROS accumulation in miR398b-overexpressing plants in response to V. dahliae infection. This study suggests conserved and novel roles of miR398b in the cotton–V. dahliae interaction. These discoveries may be coupled with new strategies in cotton breeding programs to improve resistance to V. dahliae.

Bacterial biofilm formation is a major risk of surgical implantation, and necessitates implant removal and aggressive antibiotic treatment. Here authors show that post-surgical application of Manganese-containing inorganic nanosheets reduces residual and recurrent infection by improving antigen presentation and humoral immune response against the biofilms.

Abstract Background Kidney disease progression rates vary among patients. Rapid and accurate prediction of kidney disease outcomes is crucial for disease management. In recent years, various prediction models using Machine Learning (ML) algorithms have been established in nephrology. However, their accuracy have been inconsistent. Therefore, we conducted a systematic review and meta-analysis to investigate the diagnostic accuracy of ML algorithms for kidney disease progression. Methods We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the Chinese Biomedicine Literature Database, Chinese National Knowledge Infrastructure, Wanfang Database, and the VIP Database for diagnostic studies on ML algorithms’ accuracy in predicting kidney disease prognosis, from the establishment of these databases until October 2020. Two investigators independently evaluate study quality by QUADAS-2 tool and extracted data from single ML algorithm for data synthesis using the bivariate model and the hierarchical summary receiver operating characteristic (HSROC) model. Results Fifteen studies were left after screening, only 6 studies were eligible for data synthesis. The sample size of these 6 studies was 12,534, and the kidney disease types could be divided into chronic kidney disease (CKD) and Immunoglobulin A Nephropathy, with 5 articles using end-stage renal diseases occurrence as the primary outcome. The main results indicated that the area under curve (AUC) of the HSROC was 0.87 (0.84–0.90) and ML algorithm exhibited a strong specificity, 95% confidence interval and heterogeneity (I2) of (0.87, 0.84–0.90, [I2 99.0%]) and a weak sensitivity of (0.68, 0.58–0.77, [I2 99.7%]) in predicting kidney disease deterioration. And the the results of subgroup analysis indicated that ML algorithm’s AUC for predicting CKD prognosis was 0.82 (0.79–0.85), with the pool sensitivity of (0.64, 0.49–0.77, [I2 99.20%]) and pool specificity of (0.84, 0.74–0.91, [I2 99.84%]). The ML algorithm’s AUC for predicting IgA nephropathy prognosis was 0.78 (0.74–0.81), with the pool sensitivity of (0.74, 0.71–0.77, [I2 7.10%]) and pool specificity of (0.93, 0.91–0.95, [I2 83.92%]). Conclusion Taking advantage of big data, ML algorithm-based prediction models have high accuracy in predicting kidney disease progression, we recommend ML algorithms as an auxiliary tool for clinicians to determine proper treatment and disease management strategies.

Curcumin could inhibit periprosthetic osteolysis induced by wear debris and adherent endotoxin, which commonly cause prosthesis loosening and negatively influence the long-term survival of joint arthroplasty. However, its limited water solubility and poor stability pose challenges for its further clinical application. To address these issues, we developed curcumin liposomes for intraarticular injection, as liposomes possess good lubricant capacity and pharmacological synergy with curcumin. Additionally, a nanocrystal dosage form was prepared to enable comparison with the liposomes based on their ability to disperse curcumin effectively. A microfluidic method was used for its controllability, repeatability, and scalability. The Box-Behnken Design was employed to screen the formulations and flow parameters, while computational fluid dynamics was used to simulate the mixing process and predict the formation of liposomes. The optimized curcumin liposomes (Cur-LPs) had a size of 132.9 nm and an encapsulation efficiency of 97.1%, whereas the curcumin nanocrystals (Cur-NCs) had a size of 172.3 nm. Both Cur-LPs and Cur-NCs inhibited LPS-induced pro-inflammatory polarization of macrophages and reduced the expression and secretion of inflammatory factors. The mouse air pouch model further demonstrated that both dosage forms attenuated inflammatory cell infiltration and inflammatory fibrosis in subcutaneous tissues. Interestingly, the anti-inflammatory effect of Cur-LPs was more potent than that of Cur-NCs, both in vitro and in vivo, although the cellular uptake of Cur-NCs was quicker. In conclusion, the results demonstrate that Cur-LPs have great potential for the clinical treatment of inflammatory osteolysis and that the therapeutic effect is closely related to the liposomal dosage form.

Abstract Background From an economic perspective, cotton is one of the most important crops in the world. The fertility of male reproductive organs is a key determinant of cotton yield. Anther dehiscence or indehiscence directly determines the probability of fertilization in cotton. Thus, rapid and accurate identification of cotton anther dehiscence status is important for judging anther growth status and promoting genetic breeding research. The development of computer vision technology and the advent of big data have prompted the application of deep learning techniques to agricultural phenotype research. Therefore, two deep learning models (Faster R-CNN and YOLOv5) were proposed to detect the number and dehiscence status of anthers. Result The single-stage model based on YOLOv5 has higher recognition speed and the ability to deploy to the mobile end. Breeding researchers can apply this model to terminals to achieve a more intuitive understanding of cotton anther dehiscence status. Moreover, three improvement strategies are proposed for the Faster R-CNN model, where the improved model has higher detection accuracy than the YOLOv5 model. We have made three improvements to the Faster R-CNN model and after the ensemble of the three models and original Faster R-CNN model, R2 of “open” reaches to 0.8765, R2 of “close” reaches to 0.8539, R2 of “all” reaches to 0.8481, higher than the prediction results of either model alone, which are completely able to replace the manual counting results. We can use this model to quickly extract the dehiscence rate of cotton anthers under high temperature (HT) conditions. In addition, the percentage of dehiscent anthers of 30 randomly selected cotton varieties were observed from the cotton population under normal conditions and HT conditions through the ensemble of the Faster R-CNN model and manual counting. The results show that HT decreased the percentage of dehiscent anthers in different cotton lines, consistent with the manual method. Conclusions Deep learning technology have been applied to cotton anther dehiscence status recognition instead of manual methods for the first time to quickly screen HT–tolerant cotton varieties. Deep learning can help to explore the key genetic improvement genes in the future, promoting cotton breeding and improvement.

Abstract Background Base editors (BEs) display diverse applications in a variety of plant species such as Arabidopsis, rice, wheat, maize, soybean, and cotton, where they have been used to mediate precise base pair conversions without the collateral generation of undesirable double-stranded breaks (DSB). Studies of single-nucleotide polymorphisms (SNPs) underpinning plant traits are still challenging, particularly in polyploidy species where such SNPs are present in multiple copies, and simultaneous modification of all alleles would be required for functional analysis. Allotetraploid cotton has a number of homoeologous gene pairs located in the A and D sub-genomes with considerable SNPs, and it is desirable to develop adenine base editors (ABEs) for efficient and precise A-to-G single-base editing without DSB in such complex genome. Results We established various ABE vectors based on different engineered adenosine deaminase (TadA) proteins fused to Cas9 variants (dCas9, nCas9), enabling efficient A to G editing up to 64% efficiency on-target sites of the allotetraploid cotton genome. Comprehensive analysis showed that GhABE7.10n exhibited the highest editing efficiency, with the main editing sites specifically located at the position A5 (counting the PAM as positions 21–23). Furthermore, DNA and RNA off-target analysis of cotton plants edited with GhABE7.10n and GhABE7.10d by whole genome and whole-transcriptome sequencing revealed no DNA off-target mutations, while very low-level RNA off-target mutations were detected. A new base editor, namely GhABE7.10dCpf1 (7.10TadA + dCpf1), that recognizes a T-rich PAM, was developed for the first time. Targeted A-to-G substitutions generated a single amino acid change in the cotton phosphatidyl ethanolamine-binding protein (GhPEBP), leading to a compact cotton plant architecture, an ideotype for mechanized harvesting of modern cotton production. Conclusions Our data illustrate the robustness of adenine base editing in plant species with complex genomes, which provides efficient and precise toolkit for cotton functional genomics and precise molecular breeding.