Correction: Phospholipid scramblase 1 interacts with influenza A virus NP, impairing its nuclear import and thereby suppressing virus replication.

[This corrects the article DOI: 10.1371/journal.ppat.1006851.].

Ribosomal protein RPL11 haploinsufficiency causes anemia in mice via activation of the RP-MDM2-p53 pathway.

Recent discovery of the ribosomal protein (RP) RPL11 interacting with and inhibiting the E3 ubiquitin ligase function of MDM2 established the RP-MDM2-p53 signaling pathway, which is linked to biological events, including ribosomal biogenesis, nutrient availability, and metabolic homeostasis. Mutations in RPs lead to a diverse array of phenotypes known as ribosomopathies in which the role of p53 is implicated. Here, we generated conditional RPL11-deletion mice to investigate in vivo effects of impaired RP expression and its functional connection with p53. While deletion of one Rpl11 allele in germ cells results in embryonic lethality, deletion of one Rpl11 allele in adult mice does not affect viability but leads to acute anemia. Mechanistically, we found RPL11 haploinsufficiency activates p53 in hematopoietic tissues and impedes erythroid precursor differentiation, resulting in insufficient red blood cell development. We demonstrated that reducing p53 dosage by deleting one p53 allele rescues RPL11 haploinsufficiency-induced inhibition of erythropoietic precursor differentiation and restores normal red blood cell levels in mice. Furthermore, blocking the RP-MDM2-p53 pathway by introducing an RP-binding mutation in MDM2 prevents RPL11 haploinsufficiency-caused p53 activation and rescues the anemia in mice. Together, these findings demonstrate that the RP-MDM2-p53 pathway is a critical checkpoint for RP homeostasis and that p53-dependent cell cycle arrest of erythroid precursors is the molecular basis for the anemia phenotype commonly associated with RP deficiency.

Albumin Nanoparticles Increase the Efficacy of Doxorubicin Hydrochloride Liposome Injection Based on Threshold Theory.

One of the most significant reasons hindering the clinical translation of nanomedicines is the rapid clearance of intravenously injected nanoparticles by the mononuclear phagocyte system, particularly by Kupffer cells in the liver, leading to an inefficient delivery of nanomedicines for tumor treatment. The threshold theory suggests that the liver's capacity to clear nanoparticles is limited, and a single high dose of nanoparticles can reduce the hepatic clearance efficiency, allowing more nanomedicines to reach tumor tissues and enhance therapeutic efficacy. Building upon this theory, researchers have conducted numerous validation studies based on the same nanoparticle carrier systems. These studies involve the use of albumin nanoparticles to improve the therapeutic efficacy of albumin nanomedicines as well as polyethylene glycol (PEG)-modified liposomal nanoparticles to enhance the efficacy of PEGylated liposomal nanomedicines. However, there is no research indicating the feasibility of the threshold theory when blank nanoparticles and nanomedicine belong to different nanoparticle carrier systems currently. In this study, we prepared two different sizes of albumin nanoparticles by using bovine serum albumin. We used the marketed nanomedicine liposomal doxorubicin hydrochloride injection (trade name: LIBOD, manufacturer: Shanghai Fudan-zhangjiang Biopharmaceutical Co., Ltd.), as the representative nanomedicine. Through in vivo experiments, we found that using threshold doses of albumin nanoparticles still can reduce the clearance rate of LIBOD, prolong its time in vivo, increase the area under the plasma concentration-time curve (AUC), and also lead to an increased accumulation of the drug at the tumor site. Furthermore, evaluation of in vivo efficacy and safety further indicates that threshold doses of 100 nm albumin nanoparticles can enhance the antitumor effect of LIBOD without causing harm to the animals. During the study, we found that the particle size of albumin nanoparticles influenced the in vivo distribution of the nanomedicine at the same threshold dose. Compared with 200 nm albumin nanoparticles, 100 nm albumin nanoparticles more effectively reduce the clearance efficiency of LIBOD and enhance nanomedicine accumulation at the tumor site, warranting further investigation. This study utilized albumin nanoparticles to reduce hepatic clearance efficiency and enhance the delivery efficiency of nonalbumin nanocarrier liposomal nanomedicine, providing a new avenue to improve the efficacy and clinical translation of nanomedicines with different carrier systems.

Neglected immunoregulation: M2 polarization of macrophages triggered by low-dose irradiation plays an important role in bone regeneration.

Current studies have found that low-dose irradiation (IR) can promote bone regeneration. However, mechanism studies of IR-triggered bone regeneration mainly focus on the effects of osteoblasts, neglecting the role of the surrounding immune microenvironment. Here in this study, in vitro proliferation experiments showed that low-dose IR ≤2 Gy could promote the proliferation of bone marrow mesenchymal stem cells (BMSCs), and qRT-PCR assay showed that low-dose IR ≤2 Gy could exert the M2 polarization of Raw264.7 cells, while IR >2 Gy inhibited BMSC proliferation and triggered M1 polarization in Raw264.7 cells. The ALP and mineralized nodules staining showed that low-dose IR ≤2 Gy not only promoted osteoblast mineralization through IR-triggered osteoblast proliferation but also through M2 polarization of Raw264.7 cells, while high-dose IR >2 Gy had the opposite effect. The co-incubation of BMSC with low-dose IR irradiated Raw264.7 cell supernatants increased the mRNA expression of BMP-2 and Osx. The rat cranial defects model revealed that low-dose IR ≤2 Gy gradually promoted bone regeneration, while high-dose IR >2 Gy inhibited bone regeneration. Detection of macrophage polarity in peripheral blood samples showed that low-dose IR ≤2 Gy increased the expression of CD206 and CD163, but decreased the expression of CD86 and CD80 in macrophages, which indicated M2 polarization of macrophages in vivo, while high-dose IR had the opposite effect. Our finding innovatively revealed that low-dose IR ≤2 Gy promotes bone regeneration not only by directly promoting the proliferation of osteoblasts but also by triggering M2 polarization of macrophages, which provided a new perspective for immune mechanism study in the treatment of bone defects with low-dose IR.

Supramolecular Architectures Bearing Half-Sandwich Iridium- or Rhodium-Based Carboranes: Design, Synthesis, and Applications.

The utilization of carboranes in supramolecular chemistry has attracted considerable attention. The unique spatial configuration and weak interaction forces of carboranes can help to explore the properties of supramolecular complexes, particularly via host-guest chemistry. Additionally, certain difficulties encountered in carborane development─such as controlled B-H bond activation─can be overcome by judiciously selecting metal centers and their adjacent ligands. However, few studies are being conducted in this nascent research area. With advances in this field, novel carborane-based supramolecular complexes will likely be prepared, structurally characterized, and intrinsically investigated. To expedite these efforts, we present major findings from recent studies, including π-π interactions, host-guest associations, and steric effects, which have been leveraged to implement a regioselective process for activating B(2,9)-, B(2,8)-, and B(2,7)-H bonds of para-carboranes and B(4,7)-H bonds of ortho-carboranes. Future studies should clarify the unique weak interactions of carboranes and their potential for enhancing the utility of supramolecular complexes. Although carboranes exhibit several unique weak interactions (such as dihydrogen-bond [Bδ+-Hδ-···Hδ+-Cδ-], Bδ+-Hδ-···M+, and Bδ+-Hδ-···π interactions), the manner in which they can be utilized remains unclear. Supramolecular complexes, particularly those based on host-guest chemistry, can be utilized as a platform for demonstrating potential applications of these weak interactions. Owing to the importance of alkane separation, applications related to the recognition and separation of alkane isomers via dihydrogen-bond interactions are primarily summarized. Advances in the research of unique weak interactions in carboranes will certainly lead to more possibilities for supramolecular chemistry.

"Cage Walking" Synthetic Strategy for Unusual Unsymmetrical Supramolecular Cages.

Developing novel assembly methods for supramolecular compounds has long been a research challenge. Herein, we describe how to integrate the B-C coupling reaction and "cage walking" process into coordination self-assembly to construct supramolecular cages. In this strategy, dipyridine linkers containing alkynes react with the metallized carborane backbone through B-C coupling and then "cage walking" resulting in metallacages. However, dipyridine linkers without alkynyl groups can form only metallacycles. We can regulate the size of metallacages based on the length of the alkynyl bipyridine linkers. When tridentate-pyridine linkers participate in this reaction, a new type of ravel is formed. The metallization of carboranes, the B-C coupling reaction, and especially the "cage walking" process of carborane cages play a vital role in this reaction. This work provides a promising principle for the synthesis of metallacages and opens up a novel opportunity in the supramolecular field.

Genetic and biological properties of H7N9 avian influenza viruses detected after application of the H7N9 poultry vaccine in China.

The H7N9 avian influenza virus (AIV) that emerged in China have caused five waves of human infection. Further human cases have been successfully prevented since September 2017 through the use of an H7N9 vaccine in poultry. However, the H7N9 AIV has not been eradicated from poultry in China, and its evolution remains largely unexplored. In this study, we isolated 19 H7N9 AIVs during surveillance and diagnosis from February 2018 to December 2019, and genetic analysis showed that these viruses have formed two different genotypes. Animal studies indicated that the H7N9 viruses are highly lethal to chicken, cause mild infection in ducks, but have distinct pathotypes in mice. The viruses bound to avian-type receptors with high affinity, but gradually lost their ability to bind to human-type receptors. Importantly, we found that H7N9 AIVs isolated in 2019 were antigenically different from the H7N9 vaccine strain that was used for H7N9 influenza control in poultry, and that replication of these viruses cannot, therefore, be completely prevented in vaccinated chickens. We further revealed that two amino acid mutations at positions 135 and 160 in the HA protein added two glycosylation sites and facilitated the escape of the H7N9 viruses from the vaccine-induced immunity. Our study provides important insights into H7N9 virus evolution and control.

Viral RNA-binding ability conferred by SUMOylation at PB1 K612 of influenza A virus is essential for viral pathogenesis and transmission.

Posttranslational modifications, such as SUMOylation, play specific roles in the life cycle of invading pathogens. However, the effect of SUMOylation on the adaptation, pathogenesis, and transmission of influenza A virus (IAV) remains largely unknown. Here, we found that a conserved lysine residue at position 612 (K612) of the polymerase basic protein 1 (PB1) of IAV is a bona fide SUMOylation site. SUMOylation of PB1 at K612 had no effect on the stability or cellular localization of PB1, but was critical for viral ribonucleoprotein (vRNP) complex activity and virus replication in vitro. When tested in vivo, we found that the virulence of SUMOylation-defective PB1/K612R mutant IAVs was highly attenuated in mice. Moreover, the airborne transmission of a 2009 pandemic H1N1 PB1/K612R mutant virus was impaired in ferrets, resulting in reversion to wild-type PB1 K612. Mechanistically, SUMOylation at K612 was essential for PB1 to act as the enzymatic core of the viral polymerase by preserving its ability to bind viral RNA. Our study reveals an essential role for PB1 K612 SUMOylation in the pathogenesis and transmission of IAVs, which can be targeted for the design of anti-influenza therapies.

Genetic analysis and biological characterization of H10N3 influenza A viruses isolated in China from 2014 to 2021.

The H10 subtypes of avian influenza viruses pose a continual threat to the poultry industry and human health. The sporadic spillover of H10 subtypes viruses from poultry to humans is represented by the H10N8 human cases in 2013 and the recent H10N3 human infection in 2021. However, the genesis and characteristics of the recent reassortment H10N3 viruses have not been systemically investigated. In this study, we characterized 20 H10N3 viruses isolated in live poultry markets during routine nationwide surveillance in China from 2014 to 2021. The viruses in the recent reassortant genotype acquired their hemagglutinin (HA) and neuraminidase (NA) genes from the duck H10 viruses and H7N3 viruses, respectively, whereas the internal genes were derived from chicken H9N2 viruses as early as 2019. Receptor-binding analysis indicated that two of the tested H10N3 viruses had a higher affinity for human-type receptors than for avian-type receptors, highlighting the potential risk of avian-to-human transmission. Animal studies showed that only viruses belonging to the recent reassortant genotype were pathogenic in mice; two tested viruses transmitted via direct contact and one virus transmitted by respiratory droplets in guinea pigs, though with limited efficiency. These findings emphasize the need for enhanced surveillance of H10N3 viruses.

Advances of Amifostine in Radiation Protection: Administration and Delivery.

Amifostine (AMF, also known as WR-2721) is the only approved broad-spectrum small-molecule radiation protection agent that can combat hematopoietic damage caused by ionizing radiation and is used as an antitumor adjuvant and cell protector in cancer chemotherapy and radiotherapy. Amifostine is usually injected intravenously before chemotherapy or radiotherapy and has been used in the treatment of head and neck cancer. However, the inconvenient intravenous administration and its toxic side effects such as hypotension have severely limited its further application in clinic. In order to reduce the toxic and side effects, scientists are trying to develop a variety of drug administration methods and are devoted to developing a wide application of amifostine in radiation protection. This paper reviews the research progress of amifostine for radiation protection in recent years, discusses its mechanism of action, clinical application, and other aspects, with focus on summarizing the most widely studied amifostine injection administration and drug delivery systems, and explored the correlation between various administrations and drug efficacies.

Marine biomaterials in biomedical nano/micro-systems.

Marine resources in unique marine environments provide abundant, cost-effective natural biomaterials with distinct structures, compositions, and biological activities compared to terrestrial species. These marine-derived raw materials, including polysaccharides, natural protein components, fatty acids, and marine minerals, etc., have shown great potential in preparing, stabilizing, or modifying multifunctional nano-/micro-systems and are widely applied in drug delivery, theragnostic, tissue engineering, etc. This review provides a comprehensive summary of the most current marine biomaterial-based nano-/micro-systems developed over the past three years, primarily focusing on therapeutic delivery studies and highlighting their potential to cure a variety of diseases. Specifically, we first provided a detailed introduction to the physicochemical characteristics and biological activities of natural marine biocomponents in their raw state. Furthermore, the assembly processes, potential functionalities of each building block, and a thorough evaluation of the pharmacokinetics and pharmacodynamics of advanced marine biomaterial-based systems and their effects on molecular pathophysiological processes were fully elucidated. Finally, a list of unresolved issues and pivotal challenges of marine-derived biomaterials applications, such as standardized distinction of raw materials, long-term biosafety in vivo, the feasibility of scale-up, etc., was presented. This review is expected to serve as a roadmap for fundamental research and facilitate the rational design of marine biomaterials for diverse emerging applications.

Postoperative Adjuvant Treatment in Women with Stage I Endometrial Cancer: A Retrospective Study.

Objective: To evaluate whether postoperative adjuvant treatment is beneficial for patient survival after surgery for early stage endometrial cancer (EC). We analyzed the outcomes of patients treated with radiotherapy, chemotherapy, or progestagen combined with other adjuvant treatments. Methods: We analyzed the outcomes of patients treated with radiotherapy alone, chemotherapy alone, or progestagen treatment with other adjuvant treatments. Women without any adjuvant treatment after operation were used as controls. We retrospectively examined disease-free survival (DFS), overall survival (OS), and high-risk factors that affected the survival status of all patients who received different postoperative adjuvant therapies. Results: In all 192 patients, the total relapse and mortality rates were 5.57% and 1.68%, respectively. Fourteen patients (7.29%) developed isolated local recurrence, and 2 patients died (1.04%) of recurrence during the follow-up period. The 5-year DFS and OS rates of all patients were 95.83% and 93.75%, respectively. No significant differences were observed in the 5-year DFS, 5-year OS, OS, or DFS among the four groups of patients with FIGO stage I endometrial cancer (P=0.9849, 0.7430, 0.9754, and 0.4534, respectively). The differences in the log-rank test results of the estimates of the 5-year DFS, 5-year OS, DFS, and OS of patients with different disease stages and different ages were all significant, but no differences were observed in these parameters among patients with varying degrees of differentiation. Histologic grade, CA125 level, ER and PR status, and adjuvant therapy had no significant effect on the DFS and OS of all patients according to univariate and multivariate regression analyses, but a significant effect on DFS and OS was found when the patients were stratified by age. Conclusion: This retrospective study showed that adjuvant therapy after surgery was not significantly associated with improved DFS or OS in patients with early stage endometrial cancer. However, FIGO stage and age affected the survival of patients with stage I endometrial cancer.

Factors for incidence risk and prognosis of synchronous brain metastases in pulmonary large cell carcinoma patients: a population-based study.

BACKGROUND: Patients with pulmonary large cell carcinoma (LCC) have a high incidence of synchronous brain metastases (SBM) and a poor prognosis. Our study was to evaluate the predictive and prognostic value of the clinical characteristics of pulmonary LCC patients with SBM at initial diagnosis by utilizing the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: LCC patients, diagnosed from 2010 to 2019, were identified from the latest SEER database which was released in April 2022. Logistic regression and Cox regression were used to identify the predictive and prognostic factors for LCC patients with SBM. Propensity score matching (PSM) and Kaplan-Meier analyses were applied to assess different therapy modalities. RESULTS: A total of 1375 LCC patients were enrolled in this study and 216 (15.7%) of them had SBM at the initial diagnosis. The median overall survival (OS) of LCC patients with SBM was 4 months. Multivariate Cox regression identified age 60-79 (OR 0.57; 95% CI 0.41-0.78; p < 0.001), age ≥ 80 (OR 0.23; 95% CI 0.12-0.45; p < 0.001) and bone metastases (OR 1.75; 95% CI 1.22-2.51; p < 0.001) as significant independent predictors for developing SBM. Multivariable Cox regression revealed that age 60-79, T stage, bone metastases and chemotherapy were independent prognostic factor for OS. The surgery combined with chemotherapy and radiotherapy group, in which all patients were N0 stage and had no other site-specific metastases, exhibited the best median OS of 15 months. CONCLUSIONS: LCC patients with age < 60 or bone metastases were more likely to have SBM at initial diagnosis. Age, T stage, bone metastases and chemotherapy were independent prognostic factors for OS of LCC patients with SBM. Highly selected patients might achieve the best survival benefit from surgery combined with chemotherapy and radiotherapy.

Analysis of avian influenza A (H3N8) viruses in poultry and their zoonotic potential, China, September 2021 to May 2022.

BackgroundTwo human cases of avian influenza A (H3N8) virus infection were reported in China in 2022.AimTo characterise H3N8 viruses circulating in China in September 2021-May 2022.MethodsWe sampled poultry and poultry-related environments in 25 Chinese provinces. After isolating H3N8 viruses, whole genome sequences were obtained for molecular and phylogenetic analyses. The specificity of H3N8 viruses towards human or avian receptors was assessed in vitro. Their ability to replicate in chicken and mice, and to transmit between guinea pigs was also investigated.ResultsIn total, 98 H3N8 avian influenza virus isolates were retrieved from 38,639 samples; genetic analysis of 31 representative isolates revealed 17 genotypes. Viruses belonging to 10 of these genotypes had six internal genes originating from influenza A (H9N2) viruses. These reassorted viruses could be found in live poultry markets and comprised the strains responsible for the two human infections. A subset of nine H3N8 viruses (including six reassorted) that replicated efficiently in mice bound to both avian-type and human-type receptors in vitro. Three reassorted viruses were shed by chickens for up to 9 days, replicating efficiently in their upper respiratory tract. Five reassorted viruses tested on guinea pigs were transmissible among these by respiratory droplets.ConclusionAvian H3N8 viruses with H9N2 virus internal genes, causing two human infections, occurred in live poultry markets in China. The low pathogenicity of H3N8 viruses in poultry allows their continuous circulation with potential for reassortment. Careful monitoring of spill-over infections in humans is important to strengthen early-warning systems and maintain influenza pandemic preparedness.

Synthesis of Carborane-Backbone Metallacycles for Highly Selective Capture of n-Pentane.

The specific recognition and separation of alkanes with similar molecular structures and close boiling points face significant scientific challenges and industrial demands. Here, rectangular carborane-based metallacycles were designed to selectively encapsulate n-pentane from n-pentane, iso-pentane, and cyclo-pentane mixtures in a simple-to-operate and more energy-efficient way. Metallacycle 1, bearing 1,2-di(4-pyridyl) ethylene, can selectively separate n-pentane from these three-component mixtures with a purity of 97%. The selectivity is ascribed to the capture of the preferred guest with matching size, C-H···π interactions, and potential B-Hδ-···Hδ+-C interactions. Besides, the removal of n-pentane gives rise to original guest-free carborane-based metallacycles, which can be recycled without losing performance. Considering the variety of substituted carborane derivatives, metal ions, and organic linkers, these new carborane-based supramolecular coordination complexes (SCCs) may be broadly applicable to other challenging recognition and separation systems with good performance.

Highly Selective Separation of Benzene and Cyclohexane in a Spatially Confined Carborane Metallacage.

Separation of light hydrocarbons (C1-C9) represents one of the "seven chemical separations to change the world". Boron clusters can potentially play an important role in chemical separation, due to their unique three-dimensional structures and their ability to promote a potentially rich array of weak noncovalent interactions. Herein, we report the rational design of metallacages with carborane functionality and cooperative dihydrogen binding sites for the highly selective capture of cyclohexane molecules. The metallacage 1, bearing the ligand 2,4,6-tris(4-pyridyl)-1,3,5-triazine (TPT), can produce cyclohexane with a purity of 98.5% in a single adsorption-desorption cycle from an equimolar mixture of benzene and cyclohexane. In addition, cyclohexene molecules can be also encapsulated inside the metallacage 1. This selective encapsulation was attributed to spatial confinement effects, C-H···π interactions, and particularly dihydrogen-bond interactions. This work suggests exciting future applications of carborane cages in supramolecular chemistry for the selective adsorption and separation of alkane molecules and may open up a new research direction in host-guest chemistry.

Down Syndrome Candidate Region 1 Isoform 1L regulated tumor growth by targeting both angiogenesis and tumor cells.

Angiogenesis is critical for solid tumor growth beyond its minimal size. Previously, we reported that Down Syndrome Candidate Region 1 isoform 1L (DSCR1-1L) was one of the most up-regulated genes in endothelial cells induced by VEGF and histamine, and regulated endothelial cell proliferation, migration and angiogenesis. However, it was not known whether DSCR1-1L played a role in tumor growth. In this study, we found that DSCR1-1L shRNAs significantly inhibited the growth of transplanted melanoma in mice and its associated tumoral angiogenesis. In the gain of function assay, overexpression of DSCR1-1L cDNA in mouse endothelium is sufficient to significantly increase the tumor initiation induced by carcinogen, the growth of xenografted tumor, and the tumor metastasis in our endothelially-expressed DSCR1-1L transgenic mice, in which angiogenesis was induced. It was the first time to find that DSCR1-1L was also expressed in various tumor cells. DSCR1-1L shRNAs inhibited, but overexpression of DSCR1-1L cDNA increased, the tumor cell proliferation and migration. Most recently, we reported that DSCR1-1L modulated angiogenesis by down-regulation of VE-cadherin expression. Here, we found that DSCR1-1L down-regulated the expression of E-cadherin. Hence, DSCR1-1L is an excellent therapeutic target for cancers by regulation of both the endothelial and tumor cells through down-regulating (V)E-cadherin. DSCR1-1L shRNAs have the potential to be developed for clinical application.

A Facile Way To Improve the Bioavailability of Nanomedicine Based on the Threshold Theory.

One of the most significant barriers to the clinical transformation of nanomedicines is low drug distribution in solid tumors due to quick clearance of nanomedicine after injection. Studies have revealed that the distribution of nanomedicine in tumor sites can be considerably improved when the number of nanoparticles supplied in a short period surpasses the threshold. Most routinely employed nanomaterials have dose-related safety concerns. To resolve this problem, we use highly biocompatible albumin to construct blank nanoparticles and doxorubicin loading nanoparticles. Under the guidance of the threshold theory, when the quantity of drug loading nanoparticles is constant, the drug delivery effectiveness improves with the addition of blank nanoparticles. This enhanced impact was verified both in vitro and in vivo. The area under the curve of the high dose group (19.5 × 1011) is 2.5 times higher than that of the low dose group (6.5 × 1011). In addition, the drug distribution of the high dose group at the tumor site was also improved by 1.5 times compared with the low dose group. The results of histopathological sections also showed that the administration of excess blank nanoparticles within 24 h has no damage to the animals. This study contributes to the clinical transition of nanomedicine by providing fresh ideas for anticancer nanomedicine research.

Mild Hyperthermia Induced by Hollow Mesoporous Prussian Blue Nanoparticles in Alliance with a Low Concentration of Hydrogen Peroxide Shows Powerful Antibacterial Effect.

The emergence of superbacteria as well as the drug resistance of the current bacteria gives rise to worry regarding a bacterial pandemic and also calls for the development of novel ways to combat the bacteria. Here in this article, we demonstrate that mild hyperthermia induced by hollow mesoporous Prussian blue nanoparticles (HMPBNPs) in alliance with a low concentration of hydrogen peroxide (H2O2) shows a powerful inhibition effect on bacteria. Our results demonstrate that this therapeutic regime could realize almost full growth inhibition of both Gram-positive (Staphylococcus aureus, S. aureus) and -negative bacteria (Escherichia coli, E. coli), as well as potent inhibition/elimination of the S. aureus biofilm. The wound healing results indicate that combination regime of the antibacterial system could be conveniently used for wound disinfection in vivo and could promote wound healing. To our limited knowledge, this is one of the few pioneer works to apply mild hyperthermia for the combat of bacteria, which provides a novel strategy to inspire future studies.

Progress in Intradermal and Transdermal Gene Therapy with Microneedles.

Gene therapy is one of the most widely studied treatments and has the potential to treat a variety of intractable diseases. The skin's limited permeability, as the body's initial protective barrier, drastically inhibits the delivery effect of gene medicine. Given the potential adverse effects and physicochemical features of the medications, improving generic drug penetration into the skin barrier and achieving an effective level of target tissues remains a challenge. Microneedles have made tremendous improvements in aided gene transfer and medication delivery as a unique method. Microneedles offer the advantage of being minimally invasive and painless, as well as the ability to distribute gene medicines straight through the stratum corneum. Microneedles have been used to penetrate skin tissue with various nucleic acids and medicines in recent years, allowing for a wide range of applications in the treatment of skin ailments. This review focuses on skin-related disorders and immunity, and it primarily discusses the progress of microneedle transdermal gene therapy in recent years. It also complements the current major vectors and related microneedle gene therapy applications.