Advances in biosynthesis and downstream processing of diols.

Diols are important platform chemicals with a wide range of applications in the fields of chemical and pharmaceutical industries, food, feed and cosmetics. In particular, 1,3-propanediol (PDO), 1,4-butanediol (1,4-BDO) and 1,3-butanediol (1,3-BDO) are appealing monomers for producing industrially important polymers and plastics. Therefore, the commercialization of bio-based diols is highly important for supporting the growth of biomanufacturing for the fiber industry. This review focuses primarily on the microbial production of PDO, 1,4-BDO and 1,3-BDO with respect to different microbial strains and biological routes. In addition, metabolic platforms which are designed to produce various diols using generic bioconversion strategies are reviewed for the first time. Finally, we also summarize and discuss recent developments in the downstream processing of PDO according to their advantages and drawbacks, which is taken as an example to present the prospects and challenges for industrial separation and purification of diols from microbial fermentation broth.

Advances in the Pathogenesis of Steroid-Associated Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a refractory orthopedic condition characterized by bone cell ischemia, necrosis, bone trabecular fracture, and clinical symptoms such as pain, femoral head collapse, and joint dysfunction that can lead to disability. The disability rate of ONFH is very high, which imposes a significant economic burden on both families and society. Steroid-associated osteonecrosis of the femoral head (SANFH) is the most common type of ONFH. However, the pathogenesis of SANFH remains unclear, and it is an urgent challenge for orthopedic surgeons to explore it. In this paper, the pathogenesis of SANFH and its related signaling pathways were briefly reviewed to enhance comprehension of the pathogenesis and prevention of SANFH.

A super-hydrophilic graphite directly from lignin enabled by a room-temperature cascade catalytic carbonization.

A cost-effective, and low-energy room-temperature cascade catalytic carbonization strategy is demonstrated for converting lignin into graphite with a high yield of 87 %, a high surface potential of -37 eV and super-hydrophilicity. This super-hydrophilic feature endows the lignin-derived graphite to be dispersed in a variety of polar solvents, which is important for its future applications. Encapsulating of liquid metals with the graphite for electrical circuit patterning on flexible substrates is also advocated. These written patterns show superb conductivity of 4.9 × 106 S/m, offering good performance stability and reliability while being repeatedly stretched, folded, twisted, and bent. This will offer new designs for flexible electronic devices, sensors, and biomedical devices.

The influence of Life's Essential 8 on the link between socioeconomic status and depression in adults: a mediation analysis.

BACKGROUND: Individuals with low socioeconomic status (SES) are at a higher risk of developing depression. However, evidence on the role of cardiovascular health (CVH) in this chain is sparse and limited. The purpose of this research was to assess the mediating role of Life's Essential 8 (LE8), a recently updated measurement of CVH, in the association between SES and depression according to a nationally representative sample of adults. METHODS: Data was drawn from the National Health and Nutrition Examination Survey (NHANES) in 2013-2018. Multivariate logistic regression analysis was applied to analyze the association of SES (measured via the ratio of family income to poverty (FIPR), occupation, educational level, and health insurance) and LE8 with clinically relevant depression (CRD) (evaluated using the Patient Health Questionnaire (PHQ-9)). Multiple linear regression analysis was performed to analyze the correlation between SES and LE8. Mediation analysis was carried out to explore the mediating effect of LE8 on the association between SES and CRD. Moreover, these associations were still analyzed by sex, age, and race. RESULTS: A total of 4745 participants with complete PHQ-9 surveys and values to calculated LE8 and SES were included. In the fully adjusted model, individuals with high SES had a significantly higher risk of CRD (odds ratio = 0.21; 95% confidence interval: 0.136 to 0.325, P < 0.01) compared with those with low SES. Moreover, LE8 was estimated to mediate 22.13% of the total association between SES and CRD, and the mediating effect of LE8 varied in different sex and age groups. However, the mediating effect of LE8 in this chain was significant in different sex, age, and racial subgroups except for Mexican American (MA) individuals. CONCLUSION: The results of our study suggest that LE8 could mediate the association between SES and CRD. Additionally, the mediating effect of LE8 in this chain could be influenced by the race of participants.

Compression of EEG signals with the LSTM-autoencoder via domain adaptation approach.

The successful implementation of neural network-based EEG signal compression has led to significant cost reductions in data transmission. However, a major obstacle in this process arises from the decline in performance when compressing EEG signals from multiple subjects. This challenge arises due to the notable feature shift of EEG signals between subjects, which poses an impediment to the neural network's efficient concurrent acquisition of information from multiple subjects. To address this limitation and enable more effective utilization of data for improving the performance on target domain, we propose a Domain Adaptation (DA) framework based on LSTM-autoencoder. Our experiments encompassed the following: (1) A comparison between LSTM-autoencoder, GRU-autoencoder, and the commonly used convolutional autoencoder (CAE) in EEG compression. (2) A comparison between our proposed DA method and the MMD-based DA method, as well as Fine-tuning transfer learning. The results demonstrate the following: (1) LSTM-autoencoder outperforms other models in both subject-specific and cross-subject scenarios. (2) Using transfer learning improves the performance of LSTM-autoencoder on the target subject. (3) Our proposed method outperforms maximum mean discrepancy (MMD)-based domain adaptation and fine-tuning approaches, resulting in a more significant enhancement.

mRNA-responsive two-in-one nanodrug for enhanced anti-tumor chemo-gene therapy.

The combination of chemotherapy and gene therapy holds great promise for the treatment and eradication of tumors. However, due to significant differences in physicochemical properties between chemotherapeutic agents and functional nucleic acid drugs, direct integration into a single nano-agent is hindered, impeding the design and construction of an effective co-delivery nano-platform for synergistic anti-tumor treatments. In this study, we have developed an mRNA-responsive two-in-one nano-drug for effective anti-tumor therapy by the direct self-assembly of 2'-fluoro-substituted antisense DNA against P-glycoprotein (2'F-DNA) and chemo drug paclitaxel (PTX). The 2'-fluoro modification of DNA could significantly increase the interaction between the therapeutic nucleic acid and the chemotherapeutic drug, promoting the successful formation of 2'F-DNA/PTX nanospheres (2'F-DNA/PTX NSs). Due to the one-step self-assembly process without additional carrier materials, the prepared 2'F-DNA/PTX NSs exhibited considerable loading efficiency and bioavailability of PTX. In the presence of endogenous P-glycoprotein mRNA, the 2'F-DNA/PTX NSs were disassembled. The released 2'F-DNA could down-regulate the expression of P-glycoprotein, which decreased the multidrug resistance of tumor cells and enhanced the chemotherapy effect caused by PTX. In this way, the 2'F-DNA/PTX NSs could synergistically induce the apoptosis of tumor cells and realize the combined anti-tumor therapy. This strategy might provide a new tool to explore functional intracellular co-delivery nano-systems with high bioavailability and exhibit potential promising in the applications of accurate diagnosis and treatment of tumors.

Association between the American Heart Association's new "Life's Essential 8" metrics and kidney stone.

PURPOSE: The incidence of kidney stone disease has increased worldwide, resulting in high medical costs and social burden. Kidney stone disease shares some common features with the risk factors of cardiovascular diseases (CVDs). We investigated the association between cardiovascular health (CVH) based on the Life's Essential 8 (LE8) score developed by the American Heart Association and the incidence of kidney stone disease. METHODS: We analyzed the data of 29,469 US adults aged 20 years or above from the National Health and Nutrition Examination Survey, 2007-2018. According to the LE8 score, CVH was divided into three categories: poor, intermediate, and ideal. Logistic regression was used to determine the association between CVH and the incidence of kidney stone disease by estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The average age of the participants was 48.6 years, and 50% of the participants were women. The numbers of participants with poor, intermediate, and ideal CVH were 4149, 19,782, and 5538, respectively. After adjusting for related confounding factors, ideal CVH was associated with a reduction in the odds of kidney stone occurrence as compared to poor CVH (adjusted OR [aOR]: 0.45, 95% CI: 0.35-0.57, p < 0.001). Moreover, if the ideal CVH metrics was ≥ 6, the odds of kidney stone occurrence decreased by up to 61% (aOR: 0.39, 95% CI: 0.30-0.51). CONCLUSIONS: In the present study, ideal CVH, a factor indicative of a healthy lifestyle, was associated with lower odds of kidney stone occurrence.

Design, Evaluation, and Implementation of Synthetic Isopentyldiol Pathways in Escherichia coli.

Isopentyldiol (IPDO) is an important raw material in the cosmetic industry. So far, IPDO is exclusively produced through chemical synthesis. Growing interest in natural personal care products has inspired the quest to develop a biobased process. We previously reported a biosynthetic route that produces IPDO via extending the leucine catabolism (route A), the efficiency of which, however, is not satisfactory. To address this issue, we computationally designed a novel non-natural IPDO synthesis pathway (route B) using RetroPath RL, the state-of-the-art tool for bioretrosynthesis based on artificial intelligence methods. We compared this new pathway with route A and two other intuitively designed routes for IPDO biosynthesis from various perspectives. Route B, which exhibits the highest thermodynamic driving force, least non-native reaction steps, and lowest energy requirements, appeared to hold the greatest potential for IPDO production. All three newly designed routes were then implemented in the Escherichia coli BL21(DE3) strain. Results show that the computationally designed route B can produce 2.2 mg/L IPDO from glucose but no IPDO production from routes C and D. These results highlight the importance and usefulness of in silico design and comprehensive evaluation of the potential efficiencies of candidate pathways in constructing novel non-natural pathways for the production of biochemicals.

Efficient Precoding and Power Allocation Techniques for Maximizing Spectral Efficiency in Beamspace MIMO-NOMA Systems.

Beamspace MIMO-NOMA is an effective way to improve spectral efficiency. This paper focuses on a downlink non-orthogonal multiple access (NOMA) transmission scheme for a beamspace multiple-input multiple-output (MIMO) system. To increase the sum rate, we jointly optimize precoding and power allocation, which presents a non-convex problem. To solve this difficulty, we employ an alternating algorithm to optimize the precoding and power allocation. Regarding the precoding subproblem, we demonstrate that the original optimization problem can be transformed into an unconstrained optimization problem. Drawing inspiration from fraction programming (FP), we reconstruct the problem and derive a closed-form expression of the optimization variable. In addition, we effectively reduce the complexity of precoding by utilizing Neumann series expansion (NSE). For the power allocation subproblem, we adopt a dynamic power allocation scheme that considers both the intra-beam power optimization and the inter-beam power optimization. Simulation results show that the energy efficiency of the proposed beamspace MIMO-NOMA is significantly better than other conventional schemes.

The weekend effect in kidney transplantation outcomes: A meta-analysis.

OBJECTIVE: To determine whether kidney transplants performed during weekends have worse outcomes than those performed during weekdays. METHODS: For this systematic review, PubMed, EMBASE, and the Cochrane Library (January 2000 to January 2023) were searched. We examined the survival rates of patients and grafts for hospital inpatients admitted during weekends and those admitted during weekdays. To be included, the study had to be in English and had to provide discrete survival data around weekends versus weekdays, including patients who were admitted as inpatients over the weekend. RESULTS: Five studies (n = 163,506 patients) were examined. The hazards ratio (HR) of the survival rate of patients with weekend transplantation was 1.01 (95% confidence interval [CI], 0.96 to 1.06) when compared with patients with weekday transplantation. Patients who had renal transplant on weekends had an overall allograft survival HR of 1.01 (95% CI, 0.99 to 1.03) and death-censored allograft survival HR of 1.01 (95% CI, 0.98 to 1.04). Comparison of length of hospital stay, rejection, surgical complications, and vascular complications between renal transplants on weekends and those on weekdays showed no statistical difference. CONCLUSION: Hospital inpatients admitted for renal transplantation during weekends have a survival rate similar to that of inpatients admitted during weekdays. The weekend effect of renal transplantation was very weak; hence, transplantations done during weekends and weekdays are both appropriate.

The role of periodontitis in the link between alpha-tocopherol intake and cognitive performance: A mediation analysis in older adults.

Background: Epidemiological evidence on alpha (α)-tocopherol intake and cognitive performance in older individuals is controversial and the effect of periodontitis in this chain is sparse and limited. The goal of this study was to characterize the association between α-tocopherol intake and cognitive performance and the mediating role of periodontitis in a nationally representative sample of older adults. Methods: Data from the National Health and Nutrition Examination Survey (NHANES), 2011-2014, were used. Multivariate logistic regression analysis was performed to explore the association of α-tocopherol intake, periodontal measures (mean attachment loss [AL] and mean probing depth [PD]), and clinical periodontitis defined by the European Workshop in Periodontology with poor cognitive performance evaluated by Consortium to Establish a Registry for Alzheimer's disease (CERAD); the animal fluency test (AFT); and the Digit Symbol Substitution test (DSST) and the correlation between α-tocopherol intake and clinical periodontitis. Multiple linear regression analysis was used to explore the relationship between α-tocopherol intake and periodontal measures. Mediation analysis was used to test the effects of periodontal measures on the association between α-tocopherol intake and cognitive measures. Results: A total of 1,749 older participants (≥60 years of age) with complete periodontal diagnosis, dietary retrospective survey, and cognitive tests were included. In the fully adjusted model, the odds ratio (OR) with 95% confidence interval (CI) of CERAD score, AFT score and DSST score were 0.214 (0.137-0.327), 0.378 (0.241-0.585) and 0.298 (0.169-0.512) for the highest versus lowest tertile of α-tocopherol intake, respectively. And participants with clinical periodontitis were more likely to exhibit lower DSST score (OR = 1.689; 95 CI%: 1.018-2.771) than those without periodontitis. Mean AL (OR = 1.296; 95 CI%: 1.102-1.524) and PD (OR = 1.667; 95 CI%: 1.18-2.363) were negatively correlated with DSST, and were estimated to mediate 9.1 and 8.2% of the total association between α-tocopherol intake and cognitive performance, respectively. Conclusion: Finding of the present study suggested that participants with low α-tocopherol intake were at higher risk for developing cognitive decline. Moreover, periodontitis mediated the association between α-tocopherol intake and cognitive performance.

Advanced bioactive nanomaterials for diagnosis and treatment of major chronic diseases.

With the rapid innovation of nanoscience and technology, nanomaterials have also been deeply applied in the medical and health industry and become one of the innovative methods to treat many diseases. In recent years, bioactive nanomaterials have attracted extensive attention and have made some progress in the treatment of some major chronic diseases, such as nervous system diseases and various malignant tumors. Bioactive nanomaterials depend on their physical and chemical properties (crystal structure, surface charge, surface functional groups, morphology, and size, etc.) and direct produce biological activity and play to the role of the treatment of diseases, compared with the traditional nanometer pharmaceutical preparations, biological active nano materials don't exert effects through drug release, way more directly, also is expected to be more effective for the treatment of diseases. However, further studies are needed in the evaluation of biological effects, fate in vivo, structure-activity relationship and clinical transformation of bionanomaterials. Based on the latest research reports, this paper reviews the application of bioactive nanomaterials in the diagnosis and treatment of major chronic diseases and analyzes the technical challenges and key scientific issues faced by bioactive nanomaterials in the diagnosis and treatment of diseases, to provide suggestions for the future development of this field.

Efficacy analysis of 26 cases of ejaculatory duct obstruction treated by prostatic utricle neck endoscopy.

Objective: To evaluate the safety and efficacy of transvesical incision in the treatment of ejaculatory duct obstruction. Methods: The clinical data of 26 male infertile patients with ejaculatory duct obstruction were retrospectively analysed at the First Affiliated Hospital of Zhengzhou University from June 2020 to August 2021. All patients were treated with seminal vesicle neck incision for ejaculatory duct obstruction. The general clinical characteristics, intraoperative conditions and postoperative effects on the patients were recorded, and the therapeutic effect was evaluated. Results: The ejaculatory duct was found through fenestration, and the seminal vesicle gland was smoothly entered in 25 patients (96.2%). Among them, 22 cases underwent bilateral endoscopy and three underwent unilateral endoscopy. Sperm appeared in 23 cases (88.5%) 3 months after surgery. The sperm concentration and motility postoperatively at 6 months were higher than that at 3 months postoperatively. No postoperative complications, such as epididymitis or retrograde ejaculation, occurred. Conclusion: Searching for the ejaculatory duct via the neck of the prostatic utricle, assisted by a low-energy holmium laser, is a new method for the treatment of ejaculatory duct obstruction. Microscopic vision is clear using this approach and the postoperative complications are few, which has high value for clinical application.

Multifunctional Hollow MnO2 @Porphyrin@Bromelain Nanoplatform for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) has been showing great potential in cancer treatment. However, the efficacy of PDT is always limited by the intrinsic hypoxic tumor microenvironment (TME) and the low accumulation efficiency of photosensitizers in tumors. To address the issue, a multifunctional hollow multilayer nanoplatform (H-MnO2 @TPyP@Bro) comprising manganese dioxide, porphyrin (TPyP) and bromelain (Bro), is developed for enhanced photodynamic therapy. MnO2 catalyzes the intracellular hydrogen peroxide (H2 O2 ) to produce oxygen (O2 ), reversing the hypoxic TME in vivo. The generated O2 is converted into singlet oxygen (1 O2 ) by the TPyP shell under near-infrared light, which can inhibit tumor proliferation. Meanwhile, the Bro can digest collagen in the extracellular matrix around the tumor, and can promote the accumulation of H-MnO2 @TPyP@Bro in the deeper tumor tissue, further improving the therapeutic effect of PDT. In addition, MnO2 can react with the overexpressed glutathione in TME to release Mn2+ . Consequently, Mn2+ not only induces chemo-dynamic therapy based on Fenton reaction by converting H2 O2 into hydroxyl radicals, but also activates the Mn2+ -based magnetic resonance imaging. Therefore, the developed H-MnO2 @TPyP@Bro nanoplatform can effectively modulate the unfavorable TME and overcome the limitations of conventional PDT for cancer diagnostic and therapeutic.

A Comparative Study on the Success Rates of Two Approaches for Seminal Vesiculoscopy.

This study aimed to compare the success rates of two approaches for seminal vesiculoscopy: through the interior of the prostatic utricle and through the neck of the prostatic utricle. The patients were divided into two groups based on the seminal vesiculoscopy used. Group A was an interior of the prostatic utricle group (152 cases), and group B was a neck of the prostatic utricle group (146 cases). The general clinical data, intraoperative conditions and surgical results of the two groups were compared. Compared with group A, group B had a higher surgical success rate (94.5% vs. 62.5%, p < .001), a shorter operation time (33 min vs. 45 min, p < .001), less blood loss (0.5 ml vs. 2 ml, p < .001), a higher pain relief rate (86.6% vs. 52.3%, p < .001), a higher remission rate of haemospermia (82.2% vs. 58.5%, p = .011), a lower recurrence rate of pain (10.4% vs. 35.4%, p < .001), a lower recurrence rate of haemospermia (15.6% vs. 37.7%, p = .014), a higher symptom remission rate of the lower urinary tract (90.9% vs. 50.0%, p = .030), a higher remission rate of scrotal moisture (84.6% vs. 45.5%, p = .042) and a higher remission rate of frequent spermatorrhea (80.0% vs. 55.6%, p = .033). Seminal vesiculoscopy undertaken through the neck of the prostatic utricle has the characteristics of high success rate, short operation time and good surgical effect and is worthy of promotion and application.

Electroacupuncture attenuates brain injury through α7 nicotinic acetylcholine receptor-mediated suppression of neuroinflammation in a rat model of asphyxial cardiac arrest.

We determined whether electroacupuncture (EA) ameliorated brain injury following asphyxial cardiac arrest (CA) and evaluated the role of the α7 nicotinic acetylcholine receptor (α7nAChR)-mediated anti-inflammatory pathway. In CA-induced rats, EA reduced brain injury and promoted behavioral recovery. Morris water maze escape latency time reduced after Baihui (GV20) and Shuigou (DU26) stimulation. EA reduced α7nAChR downregulation after cardiopulmonary resuscitation (CPR), reducing tumor necrosis factor alpha, interleukin-1, and interleukin-6 expression and ionized calcium binding adapter molecule 1 production. The α7nAChR antagonist methyllycaconitine reversed EA effect. EA stimulation of acupuncture points alleviated brain damage after CPR and reduced the inflammatory response via α7nAChR activation.

Biosynthesizing structurally diverse diols via a general route combining oxidative and reductive formations of OH-groups.

Diols encompass important bulk and fine chemicals for the chemical, pharmaceutical and cosmetic industries. During the past decades, biological production of C3-C5 diols from renewable feedstocks has received great interest. Here, we elaborate a general principle for effectively synthesizing structurally diverse diols by expanding amino acid metabolism. Specifically, we propose to combine oxidative and reductive formations of hydroxyl groups from amino acids in a thermodynamically favorable order of four reactions catalyzed by amino acid hydroxylase, L-amino acid deaminase, α-keto acid decarboxylase and aldehyde reductase consecutively. The oxidative formation of hydroxyl group from an alkyl group is energetically more attractive than the reductive pathway, which is exclusively used in the synthetic pathways of diols reported so far. We demonstrate this general route for microbial production of branched-chain diols in E. coli. Ten C3-C5 diols are synthesized. Six of them, namely isopentyldiol (IPDO), 2-methyl-1,3-butanediol (2-M-1,3-BDO), 2-methyl-1,4-butanediol (2-M-1,4-BDO), 2-methyl-1,3-propanediol (MPO), 2-ethyl-1,3-propanediol (2-E-1,3-PDO), 1,4-pentanediol (1,4-PTD), have not been biologically synthesized before. This work opens up opportunities for synthesizing structurally diverse diols and triols, especially by genome mining, rational design or directed evolution of proper enzymes.

Effect of Acupuncture on Polycystic Ovary Syndrome in Animal Models: A Systematic Review.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. As a widely used complementary and alternative therapy, acupuncture is increasingly used to treat PCOS. However, the effect of acupuncture in treating PCOS is uncertain, and the mechanisms are unclear. This systematic review aims to determine the efficacy of acupuncture on PCOS in animal preclinical models. METHODS: Experimental animal studies of acupuncture in PCOS animal models were searched in PubMed, Web of Science, China National Knowledge Infrastructure, and the Chinese Science and Technology Periodical Database from inception to December 2020. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. RESULTS: A total of 358 studies were screened based on the title and abstract, and 31 studies were included. A total of 722 animals were involved, and all studies used either Wistar rats or SD rats. Twenty-six studies used electroacupuncture, 9 studies used manual acupuncture, and 5 of them employed both electroacupuncture and manual acupuncture. A total of 22 acupoints were involved; 7 studies followed the modern acupuncture pattern, and the rest followed classic acupuncture theory. CONCLUSIONS: The present review summarizes the current evidence of the effects of acupuncture on PCOS in animal models. Unfortunately, we could not draw a definite conclusion due to the methodological weakness of the included studies and the high heterogeneity. Well-designed studies are needed in the future to fill this gap.

Multistage Cooperative Nanodrug Combined with PD-L1 for Enhancing Antitumor Chemoimmunotherapy.

Combinatorial CpG oligonucleotide (CPG) and chemotherapy drug represent a promising approach to reactivate immune system. However, these two agents possess different physicochemical properties, hindering the application of direct self-assembly of these two cargos into a single nanostructure. Here, a multistage cooperative nanodrug is developed by the direct self-assembly of cis-platinum (CDDP, Pt), l-arginine (l-Arg, R), and CPG (defined as PtR/CPG) for antitumor chemoimmunotherapy. First, the CDDP can induce cell apoptosis. Meanwhile, CDDP also promotes the production of H2 O2 , catalyzing the conversion of l-Arg into nitric oxide (NO). The generated NO decreases the multidrug resistance of cells toward CDDP. Thus, the synergistic effects of CDDP and NO can trigger immunogenic cell death to produce tumor-associated antigens (TAAs). The TAAs and CPG will induce the maturation of dendritic cells (DCs) and enhance antigen presentation ability of DCs. In this way, the PtR/CPG can reverse the immunosuppressive microenvironment, sensitizing tumors to immune checkpoint inhibitors mediated by the programmed death-ligand 1 (PD-L1) antibody. Furthermore, the PtR/CPG combined with the PD-L1 antibody decreases the exhaustion and dysfunction of cytotoxic T lymphocytes to elicit durable systemic immune response. As a result, the prepared PtR/CPG nanodrug in combination with PD-L1 may be highly significant for cancer immunotherapy.

A Cyanine-Mediated Self-Assembly System for the Construction of a Two-in-One Nanodrug.

The combination of gene therapy and chemotherapy provides a We developed a simple and versatile approach to prepare a series of two-in-one nanodrugs through direct self-assembly of cyanine-labeled single-stranded DNA (Cys-DNA) and different types of drug molecules. Molecular dynamics simulation showed that the Cys introduced into the DNA could enhance the noncovalent interaction between Cys-DNA and drug molecules. More drug molecules were incorporated into Cys-DNA, tending to spontaneously form hybrid Cys-DNA/drug nanosphere. Such nanospheres serve as both carriers and cargoes, excluding the extra use of nontherapeutic excipients and showing ultrahigh drug loading capacity. Following this approach, an antisense oligonucleotides/doxorubicin nanodrug model was constructed, demonstrating the significant synergistic anti-tumor therapeutic effect. As a proof of the concept, our study establishes a simple and reproducible two-in-one nucleic acid-based drug formulation.