Investigating the shared genetic architecture between breast and ovarian cancers.

High heritability and strong correlation have been observed in breast and ovarian cancers. However, their shared genetic architecture remained unclear. Linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics (ρ-HESS) were applied to estimate heritability and genetic correlations. Bivariate causal mixture model (MiXeR) was used to qualify the polygenic overlap. Then, stratified-LDSC (S-LDSC) was used to identify tissue and cell type specificity. Meanwhile, the adaptive association test called MTaSPUsSet was performed to identify potential pleiotropic genes. The Single Nucleotide Polymorphisms (SNP) heritability was 13% for breast cancer and 5% for ovarian cancer. There was a significant genetic correlation between breast and ovarian cancers (rg=0.21). Breast and ovarian cancers exhibited polygenic overlap, sharing 0.4 K out 2.8 K of causal variants. Tissue and cell type specificity displayed significant enrichment in female breast mammary, uterus, kidney tissues, and adipose cell. Moreover, the 74 potential pleiotropic genes were identified between breast and ovarian cancers, which were related to the regulation of cell cycle and cell death. We quantified the shared genetic architecture between breast and ovarian cancers and shed light on the biological basis of the co-morbidity. Ultimately, these findings facilitated the understanding of disease etiology.

Functional biomacromolecules-based microneedle patch for the treatment of diabetic wound.

Diabetic wounds are a common complication of diabetes. The prolonged exposure to high glucose and oxidative stress in the wound environment increases the risk of bacterial infection and abnormal angiogenesis, leading to amputation. Microneedle patches have shown promise in promoting the healing of diabetic wounds through transdermal drug delivery. These patches target the four main aspects of diabetic wound treatment: hypoglycemia, antibacterial action, inflammatory regulation, and tissue regeneration. By overcoming the limitations of traditional administration methods, microneedle patches enable targeted therapy for deteriorated tissues. The design of these patches extends beyond the selection of needle tip material and biomacromolecule encapsulated drugs; it can also incorporate near-infrared rays to facilitate cascade reactions and treat diabetic wounds. In this review, we comprehensively summarize the advantages of microneedle patches compared to traditional treatment methods. We focus on the design and mechanism of these patches based on existing experimental articles in the field and discuss the potential for future research on microneedle patches.

Acellular fish skin grafts in the treatment of diabetic wounds: Advantages and clinical translation.

Diabetic wounds cannot undergo normal wound healing due to changes in the concentration of hyperglycemia in the body and soon evolve into chronic wounds causing amputation or even death of patients. Diabetic wounds directly affect the quality of patients and social medical management; thus researchers started to focus on skin transplantation technology. The acellular fish skin grafts (AFSGs) are derived from wild fish, which avoids the influence of human immune function and the spread of the virus through low-cost decellularization. AFSGs contain a large amount of collagen and omega-3 polyunsaturated fatty acids and they have an amazing effect on wound regeneration. However, after our search in major databases, we found that there were few research trials in this field, and only one was clinically approved. Therefore, we summarized the advantages of AFSGs and listed the problems faced in clinical use. The purpose of this paper is to enable researchers to better carry out original experiments at various stages.

Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis.

OBJECTIVE: Ferroptosis has been reported to play a role in rheumatoid arthritis (RA). Sulfasalazine, a common clinical treatment for ankylosing spondylitis, also exerts pathological influence on the progression of rheumatoid arthritis including the induced ferroptosis of fibroblast-like synoviocytes (FLSs), which result in the perturbated downstream signaling and the development of RA. The aim of this study was to investigate the underlying mechanism so as to provide novel insight for the treatment of RA. METHODS: CCK-8 and Western blotting were used to assess the effect of sulfasalazine on FLSs. A collagen-induced arthritis mouse model was constructed by the injection of collagen and Freund's adjuvant, and then, mice were treated with sulfasalazine from day 21 after modeling. The synovium was extracted and ferroptosis was assessed by Western blotting and immunofluorescence staining. RESULTS: The results revealed that sulfasalazine promotes ferroptosis. Compared with the control group, the expression levels of ferroptosis-related proteins such as glutathione peroxidase 4, ferritin heavy chain 1, and solute carrier family 7, member 11 (SLC7A11) were lower in the experimental group. Furthermore, deferoxamine inhibited ferroptosis induced by sulfasalazine. Sulfasalazine-promoted ferroptosis was related to a decrease in ERK1/2 and the increase of P53. CONCLUSIONS: Sulfasalazine promoted ferroptosis of FLSs in rheumatoid arthritis, and the PI3K-AKT-ERK1/2 pathway and P53-SLC7A11 pathway play an important role in this process.

Fast Organic Cation Exchange in Colloidal Perovskite Quantum Dots toward Functional Optoelectronic Applications.

Colloidal quantum dots with lower surface ligand density are desired for preparing the active layer for photovoltaic, lighting, and other potential optoelectronic applications. In emerging perovskite quantum dots (PQDs), the diffusion of cations is thought to have a high energy barrier, relative to that of halide anions. Herein, we investigate the fast cross cation exchange approach in colloidal lead triiodide PQDs containing methylammonium (MA+) and formamidinium (FA+) organic cations, which exhibits a significantly lower exchange barrier than inorganic cesium (Cs+)-FA+ and Cs+-MA+ systems. First-principles calculations further suggest that the fast internal cation diffusion arises due to a lowering in structural distortions and the consequent decline in attractive cation-cation and cation-anion interactions in the presence of organic cation vacancies in mixed MA+-FA+ PQDs. Combining both experimental and theoretical evidence, we propose a vacancy-assisted exchange model to understand the impact of structural features and intermolecular interaction in PQDs with fewer surface ligands. Finally, for a realistic outcome, the as-prepared mixed-cation PQDs display better photostability and can be directly applied for one-step coated photovoltaic and photodetector devices, achieving a high photovoltaic efficiency of 15.05% using MA0.5FA0.5PbI3 PQDs and more precisely tunable detective spectral response from visible to near-infrared regions.

[Research Progress and Design Strategy of Hemostatic Adhesives].

Adhesives have emerged as an effective method for wound closure, hemostasis and tissue engineering in recent years, which not only are suitable for the adhesion of wet tissues, but also can adapt to the peristalsis and mechanical stretching of tissues and organs, especially for arteries and organize bleeding. With the further development of technology, existing adhesives can be modified through different strategies, and new materials are explored, giving new properties and uses to adhesives, such as drug delivery, temperature sensitivity, light sensitivity and so on. Nevertheless, there are many questions about the design and practical clinical application of adhesives in the future. The recent research progress of traditional adhesives and their application in hemostasis is reviewed, and the design and development ideas of future adhesives are discussed in the study.

A mussel inspired polyvinyl alcohol/collagen/tannic acid bioadhesive for wet adhesion and hemostasis.

Bioadhesives are useful in surgery for hemostasis, tissue sealing and wound healing. However, most bioadhesives have limitations such as weak adhesion in wet conditions, insufficient sealing and poor clotting performance. Inspired by the adhesion mechanism of marine mussels, a novel bioadhesive (PCT) was developed by simply combining polyvinyl alcohol (PVA), collagen (COL) and tannic acid (TA) together. The results showed that the adhesion, sealing and blood coagulation properties boosted with the increase of tannic acid content in PCT. The wet shear adhesion strength of PCT-5 (the weight ratio of PVA:COL:TA=1:1:5) was 60.8 ± 0.6 kPa, the burst pressure was 213.7 ± 0.7 mmHg, and the blood clotting index was 39.3% ± 0.6%, respectively. In rat heart hemostasis tests, PCT-5 stopped bleeding in 23.7 ± 3.2 s and reduced bleeding loss to 83.0 ± 19.1 mg, which outperformed the benchmarks of commercial gauze (53.3 ± 8.7 s and 483.0 ± 15.0 mg) and 3 M adhesive (Type No.1469SB, 35.3 ± 5.0 s and 264.0 ± 14.2 mg). The as-prepared bioadhesive could provide significant benefits for tissue sealing and hemorrhage control along its low cost and facile preparation process.

Huang Gan Formula Alleviates Systemic Inflammation and Uremia in Adenine-Induced Chronic Kidney Disease Rats May Associate with Modification of Gut Microbiota and Colonic Microenvironment.

Purpose: This study aims to investigate the effects of Huang Gan formula (HGF), a Chinese herbal prescription used for chronic kidney disease (CKD), on the regulation of the gut microbiota and colonic microenvironment of CKD. Methods: CKD rats were induced by 150 mg/kg adenine gavage for 4 weeks, then orally treated with or without 3.6 g/kg or 7.2 g/kg of HGF for 8 weeks. The renal function and structure were analyzed by biochemical detection, hematoxylin and eosin, Masson's trichrome, Sirius red and immunochemical staining. Average fecal weight and number in the colon were recorded to assess colonic motility. Further, the changes in the gut microbiota and colonic microenvironment were evaluated by 16S rRNA sequencing, RT-PCR or immunofluorescence. The levels of inflammatory cytokines, uremic toxins, and NF-κB signaling pathway were detected by RT-PCR, ELISA, chloramine-T method or Western blotting. Redundancy analysis biplot and Spearman's rank correlation coefficient were used for correlation analysis. Results: HGF significantly improved renal function and pathological injuries of CKD. HGF could improve gut microbial dysbiosis, protect colonic barrier and promote motility of colonic lumens. Further, HGF inhibited systemic inflammation through a reduction of TNF-α, IL-6, IL-1ß, TGF-ß1, and a suppression of NF-κB signaling pathway. The serum levels of the selected uremic toxins were also reduced by HGF treatment. Spearman correlation analysis suggested that high-dose HGF inhibited the overgrowth of bacteria that were positively correlated with inflammatory factors (eg, TNF-α) and uremic toxins (eg, indoxyl sulfate), whereas it promoted the proliferation of bacteria belonging to beneficial microbial groups and was positively correlated with the level of IL-10. Conclusion: Our results suggest that HGF can improve adenine-induced CKD via suppressing systemic inflammation and uremia, which may associate with the regulations of the gut microbiota and colonic microenvironment.

Study on the Effect of Type III Recombinant Humanized Collagen on Human Vascular Endothelial Cells.

The effect and mechanism of type III recombinant humanized collagen (hCOLIII) on human vascular endothelial EA.hy926 cells at the cellular and molecular levels were investigated. The impact of hCOLIII on the proliferation of EA.hy926 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid assay, the effect of hCOLIII on cell migration was investigated by scratch assay, the impact of hCOLIII on cell cycle and apoptosis was detected by flow cytometry, the ability of hCOLIII to induce angiogenesis of EA.hy926 cells was evaluated by angiogenesis assay, and the effect of hCOLIII on vascular endothelial growth factor (VEGF) expression was detected by real-time reverse transcription-polymerase chain reaction analysis. The hCOLIII at concentrations of 0.5, 0.25, and 0.125 mg/mL all showed specific effects on the proliferation and migration of human vascular endothelial cells. It could also affect the cell cycle, increase the proliferation index, and increase the expression level of VEGF in human vascular endothelial cells. In the meantime, hCOLIII at the concentration of 0.5 mg/mL also showed a promoting effect on vessel formation. hCOLIII can potentially promote the endothelization process of blood vessels, mainly by affecting the proliferation, migration, and vascular-like structure of human endothelial cells. At the same time, hCOLIII can promote the expression of VEGF. This collagen demonstrated its potential as a raw material for cardiovascular implants.

Pixel Self-Attention Guided Real-Time Instance Segmentation for Group Raised Pigs.

Instance segmentation is crucial to modern agriculture and the management of pig farms. In practical farming environments, challenges arise due to the mutual adhesion, occlusion, and dynamic changes in body posture among pigs, making accurate segmentation of multiple target pigs complex. To address these challenges, we conducted experiments using video data captured from varying angles and non-fixed lenses. We selected 45 pigs aged between 20 and 105 days from eight pens as research subjects. Among these, 1917 images were meticulously labeled, with 959 images designated for the training set, 192 for validation, and 766 for testing. To enhance feature utilization and address limitations in the fusion process between bottom-up and top-down feature maps within the feature pyramid network (FPN) module of the YOLACT model, we propose a pixel self-attention (PSA) module, incorporating joint channel and spatial attention. The PSA module seamlessly integrates into multiple stages of the FPN feature extraction within the YOLACT model. We utilized ResNet50 and ResNet101 as backbone networks and compared performance metrics, including AP0.5, AP0.75, AP0.5-0.95, and AR0.5-0.95, between the YOLACT model with the PSA module and YOLACT models equipped with BAM, CBAM, and SCSE attention modules. Experimental results indicated that the PSA attention module outperforms BAM, CBAM, and SCSE, regardless of the selected backbone network. In particular, when employing ResNet101 as the backbone network, integrating the PSA module yields a 2.7% improvement over no attention, 2.3% over BAM, 2.4% over CBAM, and 2.1% over SCSE across the AP0.5-0.95 metric. We visualized prototype masks within YOLACT to elucidate the model's mechanism. Furthermore, we visualized the PSA attention to confirm its ability to capture valuable pig-related information. Additionally, we validated the transfer performance of our model on a top-down view dataset, affirming the robustness of the YOLACT model with the PSA module.

Advances in NIR-Responsive Natural Macromolecular Hydrogel Assembly Drugs for Cancer Treatment.

Cancer is a serious disease with an abnormal proliferation of organ tissues; it is characterized by malignant infiltration and growth that affects human life. Traditional cancer therapies such as resection, radiotherapy and chemotherapy have a low cure rate and often cause irreversible damage to the body. In recent years, since the traditional treatment of cancer is still very far from perfect, researchers have begun to focus on non-invasive near-infrared (NIR)-responsive natural macromolecular hydrogel assembly drugs (NIR-NMHADs). Due to their unique biocompatibility and extremely high drug encapsulation, coupling with the spatiotemporal controllability of NIR, synergistic photothermal therapy (PTT), photothermal therapy (PDT), chemotherapy (CT) and immunotherapy (IT) has created excellent effects and good prospects for cancer treatment. In addition, some emerging bioengineering technologies can also improve the effectiveness of drug delivery systems. This review will discuss the properties of NIR light, the NIR-functional hydrogels commonly used in current research, the cancer therapy corresponding to the materials encapsulated in them and the bioengineering technology that can assist drug delivery systems. The review provides a constructive reference for the optimization of NIR-NMHAD experimental ideas and its application to human body.

Controllable Colloidal Synthesis of MAPbI3 Perovskite Nanocrystals for Dual-Mode Optoelectronic Applications.

This study demonstrates an acetate ligand (AcO-)-assisted strategy for the controllable and tunable synthesis of colloidal methylammonium lead iodide (MAPbI3) perovskite nanocrystals (PNCs) for efficient photovoltaic and photodetector devices. The size of colloidal MAPbI3 PNCs can be tuned from 9 to 20 nm by changing the AcO-/MA ratio in the reaction precursor. In situ observations and detailed characterization results show that the incorporation of the AcO- ligand alters the formation of PbI6 octahedral cages, which controls PNC growth. A well-optimized AcO-/MA ratio affords MAPbI3 PNCs with a low defect density, a long carrier lifetime, and unique solid-state isotropic properties, which can be used to fabricate solution-processed dual-mode photovoltaic and photodetector devices with a conversion efficiency of 13.34% and a detectivity of 2 × 1011 Jones, respectively. This study provides an avenue to further the precisely controllable synthesis of hybrid PNCs for multifunctional optoelectronic applications.

Managing intermediate phase transition of perovskite film with gearbox-like molecule for efficient and stable solar cells.

The smooth and dense light-absorbing layer is an essential factor in polycrystalline solar cells to achieve high photovoltaic performance, while it remains challenging in perovskite solar cells because of the difficulty balancing the speed of crystal nucleation and growth in a solution way. Here, we explored a perovskite nucleation/growth compatible model via manipulating the intermediate complex induced by n-hexylamine (NHA) molecule, guiding us to adjustments perovskite nucleation and growth process. We found that the NHA can act as a gearbox-like molecule to sequentially reduce the perovskite nucleation barrier, promote the nucleation velocity, and retard the perovskite growth simultaneously to obtain uniform perovskite films; correspondingly, this modulation also yields the buried interface with fewer voids and low defects density. In addition, the hydrophobic NHA with long alkyl chain improves the moisture tolerance of the perovskite. The treated solar cell power conversion efficiency was 21.91 %. Importantly, in âˆ¼ 70 % humidity at 25 °C for 30 days, the efficiency of the device declined less than 5 %, exhibiting a good stability performance.

Research progress of implantation materials and its biological evaluation.

With the development of modern material science, life science and medical science, implantation materials are widely employed in clinical fields. In recent years, these materials have also evolved from inert supports or functional substitutes to bioactive materials able to trigger or promote the regenerative potential of tissues. Reasonable biological evaluation of implantation materials is the premise to make sure their safe application in clinical practice. With the continual development of implantation materials and the emergence of new implantation materials, new challenges to biological evaluation have been presented. In this paper, the research progress of implantation materials, the progress of biological evaluation methods, and also the characteristics of biocompatibility evaluation for novel implantation materials, like animal-derived implantation materials, nerve contact implantation materials, nanomaterials and tissue-engineered medical products were reviewed in order to provide references for the rational biological evaluation of implantable materials.

Fabrication and performance evaluation of PLCL-hCOLIII small-diameter vascular grafts crosslinked with procyanidins.

Cardiovascular disease has become one of the main causes of death. It is the common goal of researchers worldwide to develop small-diameter vascular grafts to meet clinical needs. Collagen is a valuable biomaterial that has been used in the preparation of vascular grafts and has shown good results. Recombinant humanized collagen (RHC) has the advantages of clear chemical structure, batch stability, no virus hazard and low immunogenicity compared with animal-derived collagen, which can be developed as vascular materials. In this study, Poly (l-lactide- ε-caprolactone) with l-lactide/ε-caprolactone (PLCL) and type III recombinant humanized collagen (hCOLIII) were selected as raw materials to prepare vascular grafts, which were prepared by the same-nozzle electrospinning apparatus. Meanwhile, procyanidin (PC), a plant polyphenol, was used to cross-link the vascular grafts. The physicochemical properties and biocompatibility of the fabricated vascular grafts were investigated by comparing with glutaraldehyde (GA) crosslinked vascular grafts and pure PLCL grafts. Finally, the performance of PC cross-linked PLCL-hCOLIII vascular grafts were evaluated by rabbit carotid artery transplantation model. The results indicate that the artificial vascular grafts have good cell compatibility, blood compatibility, and anti-calcification performance, and can remain unobstructed after 30 days carotid artery transplantation in rabbits. The grafts also showed inhibitory effects on the proliferation of SMCs and intimal hyperplasia, demonstrating its excellent performance as small diameter vascular grafts.

A rapid screening platform for antibiotic susceptibility testing based on a simple colorimetric method.

Rapid screening platforms for antibiotic susceptibility testing (AST) are important in inhibiting bacterial resistance in clinical practice. Herein, a rapid screening platform is reported for AST, which is based on nanofiber membrane enrichment bacteria-assisted cell counting Kit-8 (CCK8) colorimetry. The absorbance of CCK8 formazan has a linear relationship with the number of bacteria. The interference of antibiotics in the absorbance of CCK8 formazan could be eliminated by separating planktonic bacteria from the culture medium using nanofiber membranes. The total detection time is 7-9 h, using the new screening platform, which is significantly shorter than that with the traditional method, and the limit of detection of this method is 10 CFU mL-1. The evaluation results of antibiotic susceptibility are identical when using the new screening method and traditional methods. This method meets the definition of "rapid testing" for antibiotic susceptibility by most microbiologists. Furthermore, the new screening platform for antibiotic susceptibility testing ability in vitro was proved using E. coli in urine and blood, and S. aureus in wound fluid as practical samples. All the results showed that the new screening platform is a promising method for rapid antibiotic susceptibility testing in vitro.

Modulating Crystallization and Defect Passivation by Butyrolactone Molecule for Perovskite Solar Cells.

The attainment of a well-crystallized photo-absorbing layer with minimal defects is crucial for achieving high photovoltaic performance in polycrystalline solar cells. However, in the case of perovskite solar cells (PSCs), precise control over crystallization and elemental distribution through solution processing remains a challenge. In this study, we propose the use of a multifunctional molecule, α-amino-γ-butyrolactone (ABL), as a modulator to simultaneously enhance crystallization and passivate defects, thereby improving film quality and deactivating nonradiative recombination centers in the perovskite absorber. The Lewis base groups present in ABL facilitate nucleation, leading to enhanced crystallinity, while also retarding crystallization. Additionally, ABL effectively passivates Pb2+ dangling bonds, which are major deep-level defects in perovskite films. This passivation process reduces recombination losses, promotes carrier transfer and extraction, and further improves efficiency. Consequently, the PSCs incorporating the ABL additive exhibit an increase in conversion efficiency from 18.30% to 20.36%, along with improved long-term environmental stability. We believe that this research will contribute to the design of additive molecular structures and the engineering of components in perovskite precursor colloids.

Achieving High Fill Factor in Efficient P-i-N Perovskite Solar Cells.

Lead halide perovskite solar cells (PSCs) have made unprecedented progress, exhibiting great potential for commercialization. Among them, inverted p-i-n PSCs provide outstanding compatibility with flexible substrates, more importantly, with silicon (Si) bottom devices for higher efficiency perovskite-Si tandem solar cells. However, even with recently obtained efficiency over 25%, the investigation of inverted p-i-n PSCs is still behind the n-i-p counterpart so far. Recent progress has demonstrated that the fill factor (FF) in inverted PSCs currently still underperforms relative to open-circuit voltage and short-circuit current density, which requires an in-depth understanding of the mechanism and further research. In this review article, the recent advancements in high FF inverted PSCs by adopting the approaches of interfacial optimization, precursor engineering as well as fabrication techniques to minimize undesirable recombination are summarized. Insufficient carrier extraction and transport efficiency are found to be the main factors that hinder the current FF of inverted PSCs. In addition, insights into the main factors limiting FF and strategies for minimizing series resistance in inverted PSCs are presented. The continuous efforts dedicated to the FF of high-performance inverted devices may pave the way toward commercial applications of PSCs in the near future.

The influence of Nav1.9 channels on intestinal hyperpathia and dysmotility.

The Nav1.9 channel is a voltage-gated sodium channel. It plays a vital role in the generation of pain and the formation of neuronal hyperexcitability after inflammation. It is highly expressed in small diameter neurons of dorsal root ganglions and Dogiel II neurons in enteric nervous system. The small diameter neurons in dorsal root ganglions are the primary sensory neurons of pain conduction. Nav1.9 channels also participate in regulating intestinal motility. Functional enhancements of Nav1.9 channels to a certain extent lead to hyperexcitability of small diameter dorsal root ganglion neurons. The hyperexcitability of the neurons can cause visceral hyperalgesia. Intestinofugal afferent neurons and intrinsic primary afferent neurons in enteric nervous system belong to Dogiel type II neurons. Their excitability can also be regulated by Nav1.9 channels. The hyperexcitability of intestinofugal afferent neurons abnormally activate entero-enteric inhibitory reflexes. The hyperexcitability of intrinsic primary afferent neurons disturb peristaltic waves by abnormally activating peristaltic reflexes. This review discusses the role of Nav1.9 channels in intestinal hyperpathia and dysmotility.