A Chinese patent medicine's long-term efficacy on non-dialysis patients with CKD stages 3-5: a retrospective cohort study.

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

Pangenome analysis reveals transposon-driven genome evolution in cotton.

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.

Biofilm Microenvironment Activated Antibiotic Adjuvant for Implant-Associated Infections by Systematic Iron Metabolism Interference.

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.

High-quality Gossypium hirsutum and Gossypium barbadense genome assemblies reveal the landscape and evolution of centromeres.

Centromere positioning and organization are crucial for genome evolution; however, research on centromere biology is largely influenced by the quality of available genome assemblies. Here, we combined Oxford Nanopore and Pacific Biosciences technologies to de novo assemble two high-quality reference genomes for Gossypium hirsutum (TM-1) and Gossypium barbadense (3-79). Compared with previously published reference genomes, our assemblies show substantial improvements, with the contig N50 improved by 4.6-fold and 5.6-fold, respectively, and thus represent the most complete cotton genomes to date. These high-quality reference genomes enable us to characterize 14 and 5 complete centromeric regions for G. hirsutum and G. barbadense, respectively. Our data revealed that the centromeres of allotetraploid cotton are occupied by members of the centromeric repeat for maize (CRM) and Tekay long terminal repeat families, and the CRM family reshapes the centromere structure of the At subgenome after polyploidization. These two intertwined families have driven the convergent evolution of centromeres between the two subgenomes, ensuring centromere function and genome stability. In addition, the repositioning and high sequence divergence of centromeres between G. hirsutum and G. barbadense have contributed to speciation and centromere diversity. This study sheds light on centromere evolution in a significant crop and provides an alternative approach for exploring the evolution of polyploid plants.

Construction of Host Plant Insect-Resistance Mutant Library by High-Throughput CRISPR/Cas9 System and Identification of A Broad-Spectrum Insect Resistance Gene.

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.

Evolutionary insights into the organization of chromatin structure and landscape of transcriptional regulation in plants.

Development of complex traits necessitates the functioning and coordination of intricate regulatory networks involving multiple genes. Understanding 3D chromatin structure can facilitate insight into the regulation of gene expression by regulatory elements. This potential, of visualizing the role of chromatin organization in the evolution and function of regulatory elements, remains largely unexplored. Here, we describe new perspectives that arise from the dual considerations of sequence variation of regulatory elements and chromatin structure, with a special focus on whole-genome doubling or polyploidy. We underscore the significance of hierarchical chromatin organization in gene regulation during evolution. In addition, we describe strategies for exploring chromatin organization in future investigations of regulatory evolution in plants, enabling insights into the evolutionary influence of regulatory elements on gene expression and, hence, phenotypes.

Regulatory controls of duplicated gene expression during fiber development in allotetraploid cotton.

Polyploidy complicates transcriptional regulation and increases phenotypic diversity in organisms. The dynamics of genetic regulation of gene expression between coresident subgenomes in polyploids remains to be understood. Here we document the genetic regulation of fiber development in allotetraploid cotton Gossypium hirsutum by sequencing 376 genomes and 2,215 time-series transcriptomes. We characterize 1,258 genes comprising 36 genetic modules that control staged fiber development and uncover genetic components governing their partitioned expression relative to subgenomic duplicated genes (homoeologs). Only about 30% of fiber quality-related homoeologs show phenotypically favorable allele aggregation in cultivars, highlighting the potential for subgenome additivity in fiber improvement. We envision a genome-enabled breeding strategy, with particular attention to 48 favorable alleles related to fiber phenotypes that have been subjected to purifying selection during domestication. Our work delineates the dynamics of gene regulation during fiber development and highlights the potential of subgenomic coordination underpinning phenotypes in polyploid plants.

Association of infraclavicular axillary vein diameter and collapsibility index with general anesthesia-induced hypotension in elderly patients undergoing gastrointestinal surgery: an observational study.

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 < 0.001). The areas under the curve (AUC) was 0.824 (0.759-0.889) for AXV-CI, and 0.874 (0.820-0.928) for IVC-CI. The optimal threshold for AXV-CI was 31.25% (sensitivity 71.7%, specificity 90.1%), while for IVC-CI was 36.60% (sensitivity 85.9%, specificity 79.0%). Hypotension and down-regulation of MAP during induction can be accurately predicted by AXV-Cl after correction for confounding variables. CONCLUSION: Infraclavicular axillary vein diameter has no significant correlation with postanesthesia hypotension, whereas AXV-CI may predict postanesthesia hypotension during gastrointestinal surgery of the elderly. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of China on 05/06/2022 (ChiCTR2200060596).

The chromosome-scale reference genome of mirid bugs (Adelphocoris suturalis) genome provides insights into omnivory, insecticide resistance, and survival adaptation.

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.

Inflammatory bowel disease is associated with an increased risk of adverse events in patients undergoing joint arthroplasty.

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.

Gossypium mustelinum genome and an introgression population enrich interspecific genetics and breeding in cotton.

KEY MESSAGE: Genomic and genetic resources of G. mustelinum were effective for identifying genes for qualitative and quantitative traits. Gossypium mustelinum represents the earliest diverging evolutionary lineage of polyploid Gossypium, representing a rich gene pool for numerous desirable traits lost in cotton cultivars. Accurate information of the genomic features and the genetic architecture of objective traits are essential for the discovery and utilization of G. mustelinum genes. Here, we presented a chromosome-level genome assembly of G. mustelinum and developed an introgression population of the G. mustelinum in the background of G. hirsutum that contained 264 lines. We precisely delimited the boundaries of the 1,662 introgression segments with the help of G. mustelinum genome assembly, and 87% of crossover regions (COs) were less than 5 Kb. Genes for fuzzless and green fuzz were discovered, and a total of 14 stable QTLs were identified with 12 novel QTLs across four independent environments. A new fiber length QTL, qUHML/SFC-A11, was confined to a 177-Kb region, and GmOPB4 and GmGUAT11 were considered as the putative candidate genes as potential negative regulator for fiber length. We presented a genomic and genetic resource of G. mustelinum, which we demonstrated that it was efficient for identifying genes for qualitative and quantitative traits. Our study built a valuable foundation for cotton genetics and breeding.

Classification of Histological Types and Stages in Non-small Cell Lung Cancer Using Radiomic Features Based on CT Images.

Non-invasive diagnostic method based on radiomic features in patients with non-small cell lung cancer (NSCLC) has attracted attention. This study aimed to develop a CT image-based model for both histological typing and clinical staging of patients with NSCLC. A total of 309 NSCLC patients with 537 CT series from The Cancer Imaging Archive (TCIA) database were included in this study. All patients were randomly divided into the training set (247 patients, 425 CT series) and testing set (62 patients, 112 CT series). A total of 107 radiomic features were extracted. Four classifiers including random forest, XGBoost, support vector machine, and logistic regression were used to construct the classification model. The classification model had two output layers: histological type (adenocarcinoma, squamous cell carcinoma, and large cell) and clinical stage (I, II, and III) of NSCLC patients. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% confidence interval (CI) were utilized to evaluate the performance of the model. Seven features were selected for inclusion in the classification model. The random forest model had the best classification ability compared with other classifiers. The AUC of the RF model for histological typing and clinical staging of NSCLC patients in the testing set was 0.700 (95% CI, 0.641-0.759) and 0.881 (95% CI, 0.842-0.920), respectively. The CT image-based radiomic feature model had good classification ability for both histological typing and clinical staging of patients with NSCLC.

Self-Homeostasis Immunoregulatory Strategy for Implant-Related Infections through Remodeling Redox Balance.

Implant-related infections (IRIs) are catastrophic complications after orthopedic surgery. Excess reactive oxygen species (ROS) accumulated in IRIs create a redox-imbalanced microenvironment around the implant, which severely limits the curing of IRIs by inducing biofilm formation and immune disorders. However, current therapeutic strategies commonly eliminate infection utilizing the explosive generation of ROS, which exacerbates the redox imbalance, aggravating immune disorders and promoting infection chronicity. Herein, a self-homeostasis immunoregulatory strategy based on a luteolin (Lut)-loaded copper (Cu2+)-doped hollow mesoporous organosilica nanoparticle system (Lut@Cu-HN) is designed to cure IRIs by remodeling the redox balance. In the acidic infection environment, Lut@Cu-HN is continuously degraded to release Lut and Cu2+. As both an antibacterial and immunomodulatory agent, Cu2+ kills bacteria directly and promotes macrophage pro-inflammatory phenotype polarization to activate the antibacterial immune response. Simultaneously, Lut scavenges excessive ROS to prevent the Cu2+-exacerbated redox imbalance from impairing macrophage activity and function, thus reducing Cu2+ immunotoxicity. The synergistic effect of Lut and Cu2+ confers excellent antibacterial and immunomodulatory properties to Lut@Cu-HN. As demonstrated in vitro and in vivo, Lut@Cu-HN self-regulates immune homeostasis through redox balance remodeling, ultimately facilitating IRI eradication and tissue regeneration.

Mid- to Long-term Follow-up of Severe Acetabular Bone Defect after Revision Total Hip Arthroplasty Using Impaction Bone Grafting and Metal Mesh.

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.

Recent Progress on Toxicity and Detection Methods of Polychlorinated Biphenyls in Environment and Foodstuffs.

Polychlorinated biphenyls (PCBs), a class of synthetic organochlorine chemicals, were broadly employed in industrial and commercial applications in the last century due to their good thermal and chemical stability. However, PCBs have a great influence on both individual organism and the entire ecosystem. It has been proven that PCBs pose potential risks to human health with neurotoxicity, carcinogenicity, reproductive toxicity, immunotoxicity, hepatotoxicity, and cardiovascular toxicity. Moreover, PCBs exhibit the long-range transport effect on the global scale and bio-enrichment effect along the food chains. This review mainly encompasses recent progress on the toxicity and detection techniques of PCBs in environment and foodstuffs. First of all, we highlighted the latest improvements and achievements of the classification, source, distribution, and toxicity of PCBs. Then, comprehensive summaries of the current technologies for sample preparation (e.g., SPE, DSPE, SPME and SBSE) and analytical determination (e.g., GC-ECD, GC-MS, GC-HRMS, HPLC-MS/MS and sensing technologies) were given. In the end, the shortcomings and prospects of the pretreatment methods for PCBs analysis as well as the future opportunities and challenges are tentatively discussed.

Photothermal Nanozyme-Based Microneedle Patch against Refractory Bacterial Biofilm Infection via Iron-Actuated Janus Ion Therapy.

Owing to high antibiotic resistance and thermotolerance, bacterial biofilm infections (BBIs) are refractory to elimination. Iron is essential for bacterial growth and metabolism, and bacteria can thus accumulate iron from surrounding cells to maintain biofilm formation and survival. Consequently, iron deficiency in the biofilm microenvironment (BME) leads to the functional failure of innate immune cells. Herein, a novel antibiofilm strategy of iron-actuated Janus ion therapy (IJIT) is proposed to regulate iron metabolism in both bacterial biofilm and immune cells. A BME-responsive photothermal microneedle patch (FGO@MN) is synthesized by the growth of Fe3 O4  nanoparticles on graphene oxide nanosheets and then encapsulated in methacrylated hyaluronic acid needle tips. The catalytic product of ·OH by FGO@MN in BME disrupts the bacterial heat-shock proteins, coercing biofilm thermal sensitization. As synergistic mild photothermal treatment triggers iron uptake, the intracellular iron overload further induces ferroptosis-like death. Moreover, iron-nourished neutrophils around BME can be rejuvenated for reactivating the suppressed antibiofilm function. Thus, more than 95% BBIs elimination can be achieved by combining heat stress-triggered iron interference with iron-nutrient immune reactivation. Furthermore, in vivo experiments validate the scavenging of refractory BBI after 15 days, suggesting the promising perspective of IJIT in future clinical application.

Design and Validation of a Smile-Necklace Plate for Treating Inferior Patellar Pole Avulsion Fractures: A Review and Hypothesis.

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.

Transcriptome and metabolome profiling of interspecific CSSLs reveals general and specific mechanisms of drought resistance in cotton.

In order to understand the molecular mechanism of cotton's response to drought during the flowering and boll stage, transcriptomics and metabolomics were carried out for two introgression lines (drought-tolerant line: T307; drought-sensitive line: S48) which were screened from Gossypium hirsutum cv. 'Emian22' with some gene fragments imported from Gossypium barbadense acc. 3-79, under drought stress by withdrawing water at flowering and boll stage. Results showed that the basic drought response in cotton included a series of broad-spectrum responses, such as amino acid synthesis, hormone (abscisic acid, ABA) signal transduction, and mitogen-activated protein kinases signal transduction pathway, which activated in both drought-tolerant and drought-sensitive lines. However, the difference of their imported fragments and diminished sequences triggers endoplasmic reticulum (ER) protein processing, photosynthetic-related pathways (in leaves), and membrane solute transport (in roots) in drought-tolerant line T307, while these are missed or not activated in drought-sensitive line S48, reflecting the different drought tolerance of the two genotypes. Virus-induced gene silencing assay of drought-tolerant differentially expressed heat shock protein (HSP) genes (mainly in leaf) and ATP-binding cassette (ABC) transporter genes (mainly in roots) indicated that those genes play important role in cotton drought tolerant. Combined analysis of transcriptomics and metabolomics highlighted the important roles of ER-stress-related HSP genes and root-specific ABC transporter genes in plants drought tolerance. These results provide new insights into the molecular mechanisms underlying the drought stress adaptation in cotton.

Inorganic nanosheets facilitate humoral immunity against medical implant infections by modulating immune co-stimulatory pathways.

Strategies to manipulate immune cell co-inhibitory or co-activating signals have revolutionized immunotherapy. However, certain immunologically cold diseases, such as bacterial biofilm infections of medical implants are hard to target due to the complexity of the immune co-stimulatory pathways involved. Here we show that two-dimensional manganese chalcogenophosphates MnPSe3 (MPS) nanosheets modified with polyvinylpyrrolidone (PVP) are capable of triggering a strong anti-bacterial biofilm humoral immunity in a mouse model of surgical implant infection via modulating antigen presentation and costimulatory molecule expression in the infectious microenvironment (IME). Mechanistically, the PVP-modified MPS (MPS-PVP) damages the structure of the biofilm which results in antigen exposure by generating reactive oxidative species, while changing the balance of immune-inhibitory (IL4I1 and CD206) and co-activator signals (CD40, CD80 and CD69). This leads to amplified APC priming and antigen presentation, resulting in biofilm-specific humoral immune and memory responses. In our work, we demonstrate that pre-surgical neoadjuvant immunotherapy utilizing MPS-PVP successfully mitigates residual and recurrent infections following removal of the infected implants. This study thus offers an alternative to replace antibiotics against hard-to-treat biofilm infections.

Antiviral Treatment for Hepatitis C Is Associated With a Reduced Risk of Periprosthetic Joint Infection: A Meta-Analysis of Observational Studies.

BACKGROUND: Recently, preoperative antiviral therapies for hepatitis C virus (HCV) have become available for total joint arthroplasty (TJA) patients. The objective of this meta-analysis is to investigate the impact of anti-HCV treatment on the incidence of postoperative complications after primary TJAs. METHODS: We searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library databases for relevant studies from inception to March 5, 2022. The pooled odds ratios with 95% CI of the risk of postoperative complications were calculated using the random effects model. Subgroup analyses were conducted on the basis of surgery type, antiviral regimes, and duration of follow-up. RESULTS: Eight retrospective cohort studies fulfilled the inclusion and exclusion criteria, involving 9,703 subjects. Overall, antiviral therapy for HCV was associated with a reduced risk of all-type complications and surgical complications. Moreover, we found that HCV-infected patients without treatment had substantially higher rates of periprosthetic joint infection at any surgery type and follow-up time point. There was a tendency for favoring a lower pooled revision/reoperation rate and mechanical complication rate in treated patients compared with untreated patients, but the differences failed to reach statistical significance. When limiting analysis to patients receiving preoperative direct acting antiviral-based therapy, untreated patients still had a higher surgical complication rate and joint infection rate. CONCLUSION: This meta-analysis demonstrated that antiviral therapy for HCV appears to be associated with a reduced risk of surgical complications in TJA patients, particularly periprosthetic joint infection. Thus, direct-acting antiviral therapy could be recommended for patients diagnosed with HCV.