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Diabetic foot ulcers (DFUs), a serious and increasingly common chronic issue among diabetics, often do not respond well to generalized treatment strategies. Hypoxia and the overexpression of reactive oxygen species (ROS), resulting in inflammatory dysregulation and subsequent imbalance in macrophage phenotypes, are critical factors contributing to the prolonged non‐healing of DFU wounds. These two issues often interact in a continuous, problematic cycle. Presently, there is a lack of comprehensive strategies aimed at addressing both of these factors simultaneously to interrupt this detrimental cycle. Herein, an immunomodulatory hydrogel (PHG2) is developed for reshaping the hostile DFU microenvironment. The engineered PHG2 not only removes excess internally‐produced ROS but also generates O2, with its efficiency further boosted by local hyperthermia (42.5 °C) activated by near‐infrared light. Through both in vitro and in vivo studies, along with transcriptomic assessment, it is confirmed that PHG2 disrupts the detrimental feedback loop between ROS and inflammation while also lowering the M1/M2 macrophage ratio. Such discoveries contribute to a significant enhancement in the healing process of injuries that undergo a gradual increase in movement, covering wounds from the back, mouth, to the foot. Ultimately, this method provides an easy, safe, and highly effective solution for treating DFUs. [ABSTRACT FROM AUTHOR]

It is newly revealed that collagen works as a physical barrier to tumor immune infiltration, oxygen perfusion, and immune depressor in solid tumors. Meanwhile, after radiotherapy (RT), the programmed death ligand‐1 (PD‐L1) overexpression and transforming growth factor‐β (TGF‐β) excessive secretion would accelerate DNA damage repair and trigger T cell exclusion to limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective RT simultaneously, effectively, and easily. In this study, it is revealed that inducing mitochondria dysfunction by using oxidative phosphorylation inhibitors like Lonidamine (LND) can serve as a highly effective multi‐immune pathway regulation strategy through PD‐L1, collagen, and TGF‐β co‐depression. Then, IR‐LND is prepared by combining the mitochondria‐targeted molecule IR‐68 with LND, which then is loaded with liposomes (Lip) to create IR‐LND@Lip nanoadjuvants. By doing this, IR‐LND@Lip more effectively sensitizes RT by generating more DNA damage and transforming cold tumors into hot ones through immune activation by PD‐L1, collagen, and TGF‐β co‐inhibition. In conclusion, the combined treatment of RT and IR‐LND@Lip ultimately almost completely suppressed the growth of bladder tumors and breast tumors. [ABSTRACT FROM AUTHOR]

Currently, the typical combination therapy of programmed death ligand‐1 (PD‐L1) antibodies with radiotherapy (RT) still exhibits impaired immunogenic antitumor response in clinical due to lessened DNA damage and acquired immune tolerance via the upregulation of some other immune checkpoint inhibitors. Apart from this, such combination therapy may raise the occurrence rate of radiation‐induced lung fibrosis (RIPF) due to enhanced systemic inflammation, leading to the ultimate death of cancer patients (average survival time of about 3 years). Therefore, it is newly revealed that mitochondria energy metabolism regulation can be used as a novel effective PD‐L1 and transforming growth factor‐β (TGF‐β) dual‐downregulation method. Following this, IR‐TAM is prepared by conjugating mitochondria‐targeted heptamethine cyanine dye IR‐68 with oxidative phosphorylation (OXPHOS) inhibitor Tamoxifen (TAM), which then self‐assembled with albumin (Alb) to form IR‐TAM@Alb nanoparticles. By doing this, tumor‐targeting IR‐TAM@Alb nanoparticle effectively reversed tumor hypoxia and depressed PD‐L1 and TGF‐β expression to sensitize RT. Meanwhile, due to the capacity of heptamethine cyanine dye in targeting RIPF and the function of TAM in depressing TGF‐β, IR‐TAM@Alb also ameliorated fibrosis development induced by RT. [ABSTRACT FROM AUTHOR]

The treatment of diabetic periodontitis poses a significant challenge due to the presence of local inflammation characterized by excessive glucose concentration, bacterial infection, and high oxidative stress. Herein, mesoporous silica nanoparticles (MSN) are embellished with gold nanoparticles (Au NPs) and loaded with manganese carbonyl to prepare a carbon monoxide (CO) enhanced multienzyme cooperative hybrid nanoplatform (MSN‐Au@CO). The Glucose‐like oxidase activity of Au NPs catalyzes the oxidation of glucose to hydrogen peroxide (H2O2) and gluconic acid，and then converts H2O2 to hydroxyl radicals (•OH) by peroxidase‐like activity to destroy bacteria. Moreover, CO production in response to H2O2, together with Au NPs exhibited a synergistic anti‐inflammatory effect in macrophages challenged by lipopolysaccharides. The underlying mechanism can be the induction of nuclear factor erythroid 2‐related factor 2 to reduce reactive oxygen species, and inhibition of nuclear factor kappa‐B signaling to diminish inflammatory response. Importantly, the antibacterial and anti‐inflammation effects of MSN‐Au@CO are validated in diabetic rats with ligature‐induced periodontitis by showing decreased periodontal bone loss with good biocompatibility. To summarize, MSN‐Au@CO is fabricate to utilize glucose‐activated cascade reaction to eliminate bacteria, and synergize with gas therapy to regulate the immune microenvironment, offering a potential direction for the treatment of diabetic periodontitis. [ABSTRACT FROM AUTHOR]

The article focuses on advancing polypharmacological drug design through a dual-targeted approach for treating psychiatric disorders. Topics include the development of IHCH-7179, a compound targeting both 5-HT2AR and 5-HT1AR receptors simultaneously, demonstrating the potential of polypharmacology to enhance treatment efficacy. It highlighting its structural adaptability and cognitive impairments associated with diseases like dementia-related psychiatric disorders (DRP).

Patients with methicillin‐resistant Staphylococcus aureus (MRSA) infections may have higher death rates than those with non‐drug‐resistant infections. Nanozymes offer a promising approach to eliminating bacteria by producing reactive oxygen species. However, most of the conventional nanozyme technologies encounter significant challenges with respect to size, composition, and a naturally low number of active sites. The present study synthesizes a iron‐single‐atom structure (Fe‐SAC) via nitrogen doped‐carbon, a Fe‐N5 catalyst (Fe‐SAC) with a high metal loading (4.3 wt.%). This catalyst permits the development of nanozymes consisting of single‐atom structures with active sites resembling enzymes, embedded within nanomaterials. Fe‐SAC displays peroxidase‐like activities upon exposure to H2O2. This structure facilitates the production of hydroxyl radicals, well‐known for their strong bactericidal effects. Furthermore, the photothermal properties augment the bactericidal efficacy of Fe‐SAC. The findings reveal that Fe‐SAC disrupts the bacterial cell membranes and the biofilms, contributing to their antibacterial effects. The bactericidal properties of Fe‐SAC are harnessed, which eradicates the MRSA infections in wounds and improves wound healing. Taken together, these findings suggest that single Fe atom nanozymes offer a novel perspective on the catalytic mechanism and design, holding immense potential as next‐generation nanozymes. [ABSTRACT FROM AUTHOR]

This article discusses a study that aimed to identify specific plasma-derived exosomal microRNA (exo-miRNA) signatures associated with postmenopausal osteoporosis (PMOP) and evaluate their potential as biomarkers for early PMOP detection. The study included 272 postmenopausal women volunteers and used small RNA sequencing to analyze exo-miRNA profiles. The results revealed differentially expressed exo-miRNAs that were associated with PMOP and early-stage PMOP (osteopenia), suggesting their potential as biomarkers for detecting these conditions. The study also identified three exo-miRNAs (hsa-let-7d-3p, hsa-miR-24-3p, and hsa-miR-550a-3-5p) as potential biomarkers for PMOP detection and demonstrated their discriminative power in distinguishing PMOP and early-stage PMOP from healthy controls. The findings suggest that plasma-derived exo-miRNA profiling could be a minimally invasive and effective strategy for early PMOP detection. [Extracted from the article]

Treating the most widespread complication of diabetes: diabetic wounds poses a significant clinical obstacle due to the intricate nature of wound healing in individuals with diabetes. Here a novel approach is proposed using easily applicable injectable gelatin/metal/tea polyphenol double nanonetworks, which effectively remodel the wound microenvironment and accelerates the healing process. The gelatin(Gel) crosslink with metal ions (Zr4+) through the amino acids, imparting advantageous mechanical properties like self‐healing, injectability, and adhesion. The nanonetwork's biological functions are further enhanced by incorporating the tea polyphenol metal nanonetwork through in situ doping of the epigallocatechin gallate (EGCG) with great antibacterial, self‐healing, antioxidant, and anticancer capabilities. The in vitro and in vivo tests show that this double nanonetworks hydrogel exhibits faster cell migration and favorable anti‐inflammatory and antioxidant properties and can greatly reshape the microenvironment of diabetic wounds and accelerate the wound healing rate. In addition, this hydrogel is completely degraded after subcutaneous injection for 7 days, with nondetectable cytotoxicity in H&E staining of major mice organs and the serum level of liver function indicators. Considering the above‐mentioned merits of this hydrogel, it is believed that the injectable gelatin/metal/tea polyphenol double nanonetworks have broad biomedical potential, especially in diabetic wound repair and tissue engineering. [ABSTRACT FROM AUTHOR]

Wound repair, particularly chronic nonhealing wound repair, is a global health issue that affects millions of people worldwide. As an effective and safe therapeutic reagent, gas molecules in tissue repair have attracted considerable attention. Recent studies have shown that gas therapy (GT) plays an essential role in all phases of wound repair, including anti‐inflammatory and antimicrobial modulation, cell proliferation and migration, proangiogenesis, and extracellular matrix remodeling. This review aims to summarize recent progress in developing GT for wound repair. The characteristics of gas molecules with therapeutic functions, such as oxygen, nitric oxide, carbon monoxide, hydrogen sulfide, and others (such as sulfur dioxide, hydrogen, carbon dioxide, and plasma) in wound healing are introduced. GT has transitioned from pure gases to inorganic/organic materials as gas‐releasing materials, including gas‐producing and gas‐loaded materials, and controlled/long‐lasting stable‐releasing biomaterials. Finally, the limitations and prospects in the field of GT are analyzed and summarized. [ABSTRACT FROM AUTHOR]

Ocular injuries and their complications represent the most common causes of visual impairment. For ocular surgery, there is an unmet need for highly transparent bioadhesives with superior adhesion, biocompatibility, and regenerative properties. Herein, a novel high‐transparent bioadhesive hydrogel composed of gelatin methacryloyl (GelMA) and dopamine methacrylamide (DMA) is developed by in situ oxidative free‐radical polymerization. This bioadhesive hydrogel overcomes the fundamental weakness of mussel‐inspired adhesive copolymers in clinical practice by combining multiple favorable properties, including high light transmission, mechanical strength, adhesive strength, and biocompatibility. DMA significantly enhances corneal epithelial cells adhesion, proliferation, and migration on GelMA, and prevents the accumulation of reactive oxygen species (ROS) in corneal epithelial cells. In rabbit models of corneal and conjunctiva transplantation, the bioadhesive is able to decrease the inflammatory response and fibrosis formation induced by suture surgical trauma. In addition, the rabbit corneal stromal defect model reveals that the Gel/DMA bioadhesive could effectively seal corneal defects, accelerates corneal re‐epithelialization, and promotes wound healing. Thus, given the advantages of high bioactivity and simple preparation, the Gel/DMA bioadhesive represents a promising strategy for suture‐free ocular repair. [ABSTRACT FROM AUTHOR]

In order to overcome the formidable challenges posed by the intricate physiological barriers of the brain, the employment of intranasal administration (INA) has emerged as an unconventional method for drug delivery, offering distinct advantages such as non‐invasiveness and enhanced pharmacokinetic characteristics within the brain. Primarily exploiting the distinct conduit offered by the olfactory and/or trigeminal nerve systems, the INA route effectively delivers therapeutic agents. With introducing appropriate improvements to the drug formulation, such as the incorporation of nanocarriers, the efficacious delivery via the INA approach has gained considerable traction for the treatment of neurological disorders. This concise review highlights the notable progress in INA delivery and explores the potential therapeutic modalities inherent in this promising paradigm. [ABSTRACT FROM AUTHOR]

Regulating autophagy to control the homeostatic recycling process of cancer cells is a promising anticancer strategy. Golgi apparatus is a substrate of autophagy but the Golgi‐autophagy (Golgiphagy) mediated antitumor pathway is rarely reported. Herein, we have developed a novel Golgi‐targeted platinum (II) complex Pt3, which is ca. 20 times more cytotoxic to lung carcinoma than cisplatin and can completely eliminate tumors after intratumoral administration in vivo. Its nano‐encapsulated system for tail vein administration also features a good anti‐tumor effect. Mechanism studies indicate that Pt3 induces substantial Golgi stress, indicated by the fragmentation of Golgi structure, down‐regulation of Golgi proteins (GM130, GRASP65/55), loss of Golgi‐dependent transport and glycosylation. This triggers Golgiphagy but blocks the subsequent fusion of autophagosomes with lysosomes, that is a dual role in autophagy regulation, resulting in loss of proteostasis and apoptotic cell death. As far as we know, Pt3 is the first Golgi‐targeted Pt complex that can trigger Golgi stress‐mediated dual‐regulation of autophagic flux and autophagy‐apoptosis crosstalk for highly efficient cancer therapy. [ABSTRACT FROM AUTHOR]

Despite metal‐based photosensitizers showing great potential in photodynamic therapy for tumor treatment, the application of the photosensitizers is intrinsically limited by their poor cancer‐targeting properties. Herein, we reported a metal‐based photosensitizer‐bacteria hybrid, Ir‐HEcN, via covalent labeling of an iridium(III) photosensitizer to the surface of genetically engineered bacteria. Due to its intrinsic self‐propelled motility and hypoxia tropism, Ir‐HEcN selectively targets and penetrates deeply into tumor tissues. Importantly, Ir‐HEcN is capable of inducing pyroptosis and immunogenic cell death of tumor cells under irradiation, thereby remarkably evoking anti‐tumor innate and adaptive immune responses in vivo and leading to the regression of solid tumors via combinational photodynamic therapy and immunotherapy. To the best of our knowledge, Ir‐HEcN is the first metal complex decorated bacteria for enhanced photodynamic immunotherapy. [ABSTRACT FROM AUTHOR]

Scavenging excessively secreted cytokines from plasma is vital for treating cytokine storm syndrome (CSS). Therefore, appropriate adsorbent materials are highly desired for efficient and selectively capturing the plasma cytokines. For this purpose, injectable porous silicon particles (PSPs) are designed as scavenging adsorbents. The fabricated PSP features high porosity for large pore volume and high specific surface area. Polyethylene glycol is coated on the outer surface of PSP for a longer body circulation time, while antibodies are immobilized on the interior surface of PSP for the specific recognition of targeting biomacromolecules. The resultant injectable scavengers demonstrate satisfactory performance for sequestering tumor necrosis factor (TNF) or TNF receptor (TNFR) in serum and in vivo. The salient biocompatibility of the preparing scavenger is demonstrated through simulative hemoperfusion experiments and in vivo toxicology tests. Importantly, the scavengers are injected into mice like a drug to rapidly remove blood‐circulating endogenous TNFR. These features together with its facile fabrication present the silicon‐based porous particles as candidates in clinical application for relieving the infection‐induced CSS. [ABSTRACT FROM AUTHOR]

At present, radiotherapy (RT) still acquires limited success in clinical due to the lessened DNA damage under hypoxia and acquired immune tolerance owing to the amplified programmed death ligand‐1 (PD‐L1) expression. Incredibly, intracellular PD‐L1 expression depression is proven to better sensitize RT by inhibiting DNA damage repair. However, the disability of the clinically used antibodies in disrupting the extracellular PD‐L1function still limits the effectiveness of radio‐immunotherapy. Therefore, better PD‐L1 regulation strategies are still urgently needed to better sensitize radio‐immunotherapy. Hence, for this purpose, TPP‐LND is synthesized by linking mitochondrial‐targeted triphenylphosphine cations (TPP+) to the antineoplastic agent lonidamine (LND), which significantly reduces the dose needed for LND to induce effective oxidative phosphorylation inhibition (2 vs 300 µM). Then, TPP‐LND is wrapped with liposomes to form TPP‐LND@Lip nanoparticles. By doing this, TPP‐LND@Lip nanoparticles can sensitize RT by reversing the hypoxic microenvironment of tumors to generate more DNA damage and reducing the expression of PD‐L1 via enhancing the adenosine 5′‐monophosphate‐activated protein kinase activation. As expected, these well‐designed economical TPP‐LND@Lip nanoparticles are more effective than conventional anti‐PD‐L1 antibodies to some extent. [ABSTRACT FROM AUTHOR]

Antibiotic‐independent artificial nanozymes exhibit excellent biocatalytic activity, and can generate sufficient reactive oxygen species (ROS) for potential applications in the field of anti‐infective therapy. However, single nanozymes often catalyze the production of ROS with low yield and low utilization, resulting in low antibacterial activity. To address the above refractory concern, a spike‐like surface nanoparticles (CAC NPs) platform is built that possesses intrinsic dual enzyme‐like (oxidase and peroxidase‐like) activities and photothermal conversion capacity with near‐infrared irradiation (NIR‐I) to quickly capture and effectively eliminate the bacteria and biofilm. Upon NIR‐I irradiation, CAC NPs have exerted an excellent biocatalytic antibacterial effect through a hyperthermia‐amplified dual enzyme‐like activities strategy. As predicted, the results show CAC NPs can eradicate bacteria in the subcutaneous tissues of mice and promote the healing of inflamed tissues with no significant side effects in vivo. Collectively, this work reveals the potential of NIR‐assisted dual enzyme‐like activities for antimicrobial therapy and provides broad prospects for antimicrobial drugs and strategies. [ABSTRACT FROM AUTHOR]

Ultrasound (US)‐mediated sonodynamic therapy (SDT) has the advantages of non‐invasiveness and deep tissue penetration. Nanosystems are prominently used in sonosensitization; however, most nano‐sonosensitizers have a low reactive oxygen species (ROS) yield, thus restraining the application of SDT. Sodium molybdenum bronze nanoparticles (SMB NPs) with rich oxygen vacancies are developed and interlayer gaps of molybdenum trioxide nanobelts are expanded. Owing to the increased oxygen vacancy density and wide interlayer gap‐induced narrower band gap of SMB NPs, the electrons (e–) and holes (h+) generated by US are separated more rapidly, and oxygen vacancies prevent electrons–holes recombination under US irradiation. SMB NPs exhibit a second near‐infrared (NIR‐II) photothermal effect to promote the generation of ROS by the sonosensitizer. The SMB NPs system is successfully realized to eliminate Staphylococcus aureus (S. aureus) and dissipate biofilm. Therefore, multimodal therapy using SMB NPs serves as an effective and promising regimen for deep‐seated bacterial infections. The newly developed Mo‐based sonosensitizer is presented for the first time to demonstrate excellent antimicrobial activity through hyperthermia‐promoting SDT therapeutics. This work proposes a novel strategy in the field of NIR‐II photo‐amplified SDT with Mo‐based materials for bacterial eradication and other important biomedical applications. [ABSTRACT FROM AUTHOR]

Summary: Network resource scheduling and optimization require the acquisition of status information as a basis. High‐cost solutions lead to more resource consumption but only bring negligible benefits. To address this challenge, this paper proposes a novel statistics collection method adapted to OpenFlow‐based SDN, which can reduce the measurement cost while ensuring the statistical accuracy. First, based on the complex network theory, we propose multi‐path weighted closeness centrality (MWCC) to perform importance ranking on network switching nodes, which helps us select top‐k key nodes for statistical collection to reduce the overhead. Second, we propose an adaptive flow rule timeout mechanism AFRT. AFRT continuously optimizes the rule timeout values based on statistical results, further balancing flow table overhead and statistical accuracy. A series of simulation results on real network topologies verify the superiority of the proposed method in terms of communication cost, statistical accuracy, and time consumption, compared with the existing representative methods. [ABSTRACT FROM AUTHOR]

As one of the key performance metrics, path delay is of great significance for network policy making. Existing work has focused too much on the accuracy of delay measurement and neglected its timeliness. In response, in this paper, we propose a fast path delay measurement scheme using closeness centrality for software‐defined network. First, the node ranking method using closeness centrality is used to select the initial point for the delay measurement to enable fast forwarding of probe packets. On this basis, we assign link weights according to the delay measurement results, and readjust the measurement points to optimize the performance. A series of simulation experiments on different topologies and network state verifies the advantage of the proposed scheme in this paper in terms of time overhead for delay measurement, compared to existing work. [ABSTRACT FROM AUTHOR]

Pathogenic bacteria infection is a serious threat to human public health due to the high morbidity and mortality rates. Nano delivery system for delivering antibiotics provides an alternative option to improve the efficiency compared to conventional therapeutic agents. In addition to the drug loading capacity of nanocarriers, which is typically around 10%, further lowers the drug dose that pathological bacteria are exposed to. Moreover, nanocarriers that are not eliminated from the body may cause side effects. These limitations have motivated the development of self-delivery systems that are formed by the self-assembly of different therapeutic agents. In this study, a vehicle-free antimicrobial polymer polyhexamethylene biguanide (PHMB, with bactericidal and anti-biofilm functions) hybrid gold nanoparticle (Au NPs, with photothermal therapy (PTT)) platform (PHMB@Au NPs) is developed. This platform exhibits an excellent synergistic effect to enhance the photothermal bactericidal effect for Staphylococcus aureus under near-infrared irradiation. Furthermore, the results showed that PHMB@Au NPs inhibit the formation of biofilms, quickly remove bacteria to promote wound healing through PTT in infection model in vivo, and even mediate the transition of macrophages from M1 to M2 type, and accelerate tissue angiogenesis. PHMB@Au NPs will have promising value as highly effective antimicrobial agents for patient management. [ABSTRACT FROM AUTHOR]

Polydopamine (PDA) nanoparticles have emerged as an attractive biomimetic photothermal agent in photothermal antibacterial therapy due to their ease of synthesis, good biodegradability, long‐term safety, and excellent photostability. However, the therapeutic effects of PDA nanoparticles are generally limited by the low photothermal conversion efficiency (PCE). Herein, PDA@Ag nanoparticles are synthesized via growing Ag on the surface of PDA nanoparticles and then encapsulated into a cationic guar gum (CG) hydrogel network. The optimized CG/PDA@Ag platform exhibits a high PCE (38.2%), which is more than two times higher than that of pure PDA (16.6%). More importantly, the formulated CG/PDA@Ag hydrogel with many active groups can capture and kill bacteria through effective interactions between hydrogel and bacteria, thereby benefiting the antibacterial effect. As anticipated, the designed CG/PDA@Ag system combined the advantages of PDA@Ag nanoparticles (high PCE) and hydrogel (preventing aggregation of PDA@Ag nanoparticles and possessing inherent antibacterial ability) is demonstrated to have superior antibacterial efficacy both in vitro and in vivo. This study develops a facile approach to boost the PCE of PDA for photothermal antibacterial therapy, providing a significant step forward in advancing the application of PDA nano‐photothermal agents. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether preoperative histogram parameters of dynamic contrast‐enhanced MRI (DCE‐MRI) can assess the expression of Ki‐67 in prostate cancer (PCa). Materials and methods: A consecutive series of 76 patients with pathology‐proven PCa who underwent routine DCE‐MRI scans were retrospectively recruited. Quantitative parameters including the volume transfer constant (Ktrans), rate contrast (Kep), extracellular‐extravascular volume fraction (Ve), and plasma volume (Vp) by outlining the three‐dimensional volume of interest (VOI) of all lesions were processed. Then, the histogram analyses of these quantitative parameters were performed. The Spearman rank correlation analysis was used to evaluate the correlation of these parameters and Ki‐67 expression of PCa. Receiver operating characteristic (ROC) curve analysis was adopted to evaluate the efficacy of these quantitative histogram parameters in identifying high Ki‐67 expression from low Ki‐67 expression of PCa. Results: Eighty‐eight PCa lesions were enrolled in this study, including 31 lesions with high Ki‐67 expression and 57 lesions with low Ki‐67 expression. The median, mean, 75th percentile, and 90th percentile derived from Ktrans and Kep had a moderately positive correlation with Ki‐67 expression (r = 0.361–0.450, p < 0.05), in which both the median and mean of Ktrans had the highest positive correlation (r = 0.450, p < 0.05). The diagnostic efficacy of the Ktrans median, mean, 75th percentile, and 90th percentile, along with the Kep‐based median and mean was assessed by the ROC curve. The area under the curve (AUC) of the mean for Ktrans was the highest (0.826). When the cut‐off of the mean for Ktrans was ≥0.47/min, its Youden index, sensitivity, and specificity were 0.625, 0.871, and 0.754, respectively. The AUC of the median of Kep was the lowest (0.772). Conclusion: The histogram of DCE‐MRI quantitative parameters is correlated with Ki‐67 expression, which has the potential to noninvasively assess the expression of Ki‐67 with patients of PCa. [ABSTRACT FROM AUTHOR]

Success in anticancer immune therapy relies on stimulation of tumor antigen‐specific T lymphocytes and effective infiltration of the T cells into tumor tissue. Here, a therapeutic vaccine that promotes proliferation and tumor infiltration of antigen‐specific T cells in both inflamed and noninflamed tumor types is described. The vaccine consists of STING agonist 2′3′‐cGAMP, TLR9 ligand CpG, and tumor antigen peptides that are loaded into nanoporous microparticles (μGCVax). μGCVax is effective in inhibiting lung metastatic melanoma, primary breast cancer, and subcutaneous colorectal cancer in their respective murine models, including functional cure of HER2‐positive breast cancer. Mechanistically, μGCVax potently stimulates type I interferon expression in dendritic cells, and promotes CD8+ and CD103+ dendritic cell maturation and migration to lymph nodes and other lymphatic tissues. Antitumor responses are dependent on TLR9 and interferon α/β receptor signaling, and to a less extent on STING signaling. These results demonstrate a high potential for μGCVax in mediating antitumor immunity in personalized cancer therapy. [ABSTRACT FROM AUTHOR]

Herein, spindle‐shaped block copolymer (BCP) nanoparticles are used in seeded polymerization of methyl methacrylate as a novel approach to generating cylindrical nanostructures. The chain‐extension of BCP seeds by an amorphous coil‐type polymer within the seed core composed of semifluorinated liquid‐crystalline blocks triggers the deforming, stretching, and directional growth of the seeds along the long axis, eventually leads to nanorods. [ABSTRACT FROM AUTHOR]

The incidence of chronic graft-versus-host disease (cGVHD) is rising recent years, which has been the leading cause of non-transplantation mortality post allogenetic hematopoietic stem cell transplantation (HSCT). Imbalance of inflammatory cytokines and fibrosis plays critical roles in the pathogenesis of cGVHD. Recent studies showed that molecular hydrogen has anti-inflammatory, antioxidant, anti-fibrosis effects. Therefore, we hypothesized that molecular hydrogen may have therapeutic effects on cGVHD. To determine whether hydrogen could protect mice from cGVHD in an MHC-incompatible murine bone marrow transplantation (BMT) model, survival rates of mice were calculated, and skin lesions were also evaluated after BMT. This article demonstrated that administration of hydrogen-rich saline increased survival rate of cGVHD mice. Administration of hydrogen-rich saline after transplantation also reduced skin lesions of cGVHD mice. Previously, we reported the therapeutic effects of hydrogen on acute GVHD. However, there was no report on the therapeutic effects of hydrogen on cGVHD mice. It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on cGVHD. This study will provide new ideas on the treatment of cGVHD and has important theoretical values. [ABSTRACT FROM AUTHOR]

The overall response rates and long-term survival of primary central nervous system lymphoma ( PCNSL) are still significantly inferior to the results achieved in similar subtypes of extranodal non- Hodgkin's lymphoma. It is clearly necessary to investigate new therapeutic methods on PCNSL. We encountered three patients histologically documented PCNSL as diffuse large B-cell lymphoma ( DLBCL). They were treated with R- IDARAM which comprised rituximab, idarubicin, dexamethasone, cytarabine and methotrexate. Patient 1 received stereotactic brachytherapy ( SBT) prior to chemotherapy performed with iodine-125 seeds (cumulative therapeutic dose 50 Gy). After six cycles of R- IDARAM at 3-weekly intervals, radiotherapy was applied at a dosage of 2000-4000 cGy in conventional schedule (180 or 200 cGy/day) to whole brain or spinal cord in all patients. Complete remission ( CR) was achieved after first two cycles of R- IDARAM in all patients. All three patients remained in CR at the time of this report with a median duration of follow-up of 23 months (ranging from 13 to 41 months). Three patients have been alive for 41, 13, 16 months respectively until now. The patient with the longest survival time was the one given SBT prior to chemotherapy. This study suggests that R- IDARAM combining with radiotherapy maybe a high effective regimen in PCNSL patients especially those with primary central nervous system DLBCL. A comprehensive treatment combining internal radiotherapy by SBT, modified R- IDARAM and followed reduced external radiotherapy may be a new treatment concept for PCNSL with higher efficiency and lower toxicity. [ABSTRACT FROM AUTHOR]

Highlights: [•] SMAD4 docks to the cell membrane in the presence of TGF-β1. [•] SMAD4 displays two subpopulations with different membrane docking behaviors, which are regulated by clathrin and caveolin-1. [•] The subpopulations have opposing roles in the nuclear shuttling of SMAD4 and the subsequent transcriptional regulation. [ABSTRACT FROM AUTHOR]

Allogeneic haematopoietic stem cell transplantation ( HSCT) has been widely used for the treatment of haematological malignant and non-malignant haematologic diseases. However, acute graft-versus-host disease ( aGVHD) is a kind of severe complication of HSCT limiting its application. Cytokines such as tumour necrosis factor-α ( TNF-α), IL-6 play an extremely important role in the formation and development of aGVHD. Besides, the oxidation phenomena and/or the formation of free radicals have been suggested to be causally related to various haematological disorders including aGVHD. Reactive oxygen species ( ROS), such as hydroxyl radicals, play an important role in the formation and development of aGVHD. Hydrogen has been reported to have the ability to inhibit levels of cytokines such as TNF, IL-6 in vivo. Our recent studies provided evidence that hydrogen inhalation can selectively reduce cytotoxic oxygen radicals and exert antioxidant effects. Therefore, we suggested that hydrogen may have therapeutic effects on aGVHD. This hypothesis entails many experimentally testable predictions. We propose the experimental study by detecting complete blood counts ( CBC) and Clinic signs of aGVHD mice. We also propose to detect the levels of TNF-α, IL-2, IL-1β, IL-6 which play important roles in the pathogenesis of aGVHD. To discover potential mechanisms of the therapeutic effects of hydrogen on the aGVHD model, we will examine gene-expression profiles. This study will open a new therapeutic avenue combining the field of therapeutic medical gases and aGVHD. This theory is original and probably of importance, because therapeutic medical gases have never been used for aGVHD previously. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation ( HSCT) has been widely used for the treatment of hematologic malignant and non-malignant hematologic diseases and other diseases. However, acute graft-versus-host disease ( GVHD) is a life-threatening complication of allogeneic transplantation. Acute GVHD may occur in 30% of transplant recipients, which is a syndrome of erythematous skin eruption, cholestatic liver disease and intestinal dysfunction, resulting from the activation of donor T lymphocytes by host antigen-presenting cells, resulting in an immune-mediated inflammatory response. Recent scientific advances in the understanding of the pathogenesis involved in the development of acute GVHD and clinical investigation have provided more effective therapeutic strategies for acute GVHD. This review focuses on major scientific and clinical advances in the treatment of acute GVHD. [ABSTRACT FROM AUTHOR]

The 16p11.2 deletion is a recurrent genomic event and a significant risk factor for autism spectrum disorders (ASD). This genomic disorder also exhibits extensive phenotypic variability and diverse clinical phenotypes. The full extent of phenotypic heterogeneity associated with the 16p11.2 deletion disorder and the factors that modify the clinical phenotypes are currently unknown. Multiplex families with deletion offer unique opportunities for exploring the degree of heterogeneity and implicating modifiers. Here we reported the clinical and genomic characteristics of three 16p11.2 deletion carriers in a Chinese family. The father carries a de novo 16p11.2 deletion, and it was transmitted to the proband and sib. The proband presented with ASD, intellectual disability, learning difficulty, congenital malformations such as atrial septal defect, scoliosis. His dysmorphic features included myopia and strabismus, flat and broad nasal bridge, etc. While the father shared same neurodevelopmental problems as the proband, the younger brother did not show many of the proband's phenotypes. The possible unmasked mutation of TBX6 and MVP gene in this deleted region and the differential distribution of other genomic CNVs were explored to explain the phenotypic heterogeneity in these carriers. This report demonstrated the different developmental trajectory and discordant phenotypes among family members with the same 16p11.2 deletion, thus further illustrated the phenotypic complexity and heterogeneity of the 16p11.2 deletion., (Copyright © 2010 Wiley-Liss, Inc.)