Evaluation of Renal Microhemodynamics Heterogeneity in Different Strains and Sexes of Mice.

Addressing the existing gaps in our understanding of sex- and strain-dependent disparities in renal microhemodynamics, this study conducted an investigation into the variations in renal function and related biological oscillators. Using the genetically diverse mouse models BALB/c, C57BL/6, and Kunming, which serve as established proxies for the study of renal pathophysiology, we implemented laser Doppler flowmetry conjoined with wavelet transform analyses to interrogate dynamic renal microcirculation. Creatinine, urea, uric acid, glucose, and cystatin C levels were quantified to investigate potential divergences attributable to sex and genetic lineage. Our findings reveal marked sexual dimorphism in metabolite concentrations, as well as strain-specific variances, particularly in creatinine and cystatin C levels. Through the combination of Mantel tests and Pearson correlation coefficients, we delineated the associations between renal functional metrics and microhemodynamics, uncovering interactions in female BALB/c mice for creatinine and uric acid, and in male C57BL/6 mice for cystatin C. Histopathologic examination confirmed an augmented microvascular density in female mice and elucidating variations in the expression of estrogen receptor ß among the strains. These data collectively highlight the influence of both sex and genetic constitution on renal microcirculation, providing an understanding that may inform the etiologic exploration of renal ailments.

Ranolazine for improving coronary microvascular function in patients with nonobstructive coronary artery disease: a systematic review and meta-analysis with a trial sequential analysis of randomized controlled trials.

Background: Microvascular dysfunction in patients with nonobstructive coronary artery disease is increasingly being recognized as an important health issue. This systematic review and meta-analysis evaluated the effectiveness of ranolazine, an antianginal agent, in improving coronary microvascular function. Methods: We conducted a comprehensive literature search of the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, the Chinese BioMedical Literature Database, and gray literature databases until September 30, 2023. The included studies were randomized controlled trials (RCTs) published in the English or Chinese languages that screened for eligibility using two independent investigators. Risk of bias was evaluated with the Cochrane Collaboration tool. Subgroup and sensitivity analyses were used to identify sources of heterogeneity. Meta-analysis was performed using RevMan version 5.4 (Cochrane) and Stata version 16.0 (StataCorp). Results: From 1,470 citations, 8 RCTs involving 379 participants were included in this analysis. Our findings showed that ranolazine increased coronary flow reserve (CFR) over an 8 to 12-week follow-up period [standardized mean difference =1.16; 95% confidence interval (CI): 0.4-1.89; P=0.002]. Ranolazine increased the global myocardial perfusion reserve index (MPRI) [weighted mean difference (WMD) =0.18; 95% CI: 0.07-0.29; P=0.002] and the midsubendocardial MPRI (WMD =0.10; 95% CI: 0.02-0.19; P=0.02). Moreover, ranolazine improved 3 of the 5 Seattle Angina Questionnaire scores, namely, physical functioning (WMD =4.89; 95% CI: 0.14 to 9.64; P=0.04), angina stability (WMD =17.31; 95% CI: 7.13-27.49; P=0.0009), and quality of life (WMD =10.11; 95% CI: 3.57-16.65; P=0.0003). Trial sequential analysis showed that the meta-analysis of angina stability and quality of life scores had a sufficient sample size and statistical power. Conclusions: Our analysis suggests that ranolazine is associated with improvements in CFR, myocardial perfusion, and the Seattle Angina Questionnaire scores in patients with nonobstructive coronary artery disease. However, further large-scale RCTs with long-term follow-up are recommended to validate these findings and provide a more comprehensive understanding of the effects of ranolazine on coronary microvascular function.

Dynamic immuno-nanomedicines in oncology.

Anti-cancer therapeutics have achieved significant advances due to the emergence of immunotherapies that rely on the identification of tumors by the patients' immune system and subsequent tumor eradication. However, tumor cells often escape immunity, leading to poor responsiveness and easy tolerance to immunotherapy. Thus, the potentiated anti-tumor immunity in patients resistant to immunotherapies remains a challenge. Reactive oxygen species-based dynamic nanotherapeutics are not new in the anti-tumor field, but their potential as immunomodulators has only been demonstrated in recent years. Dynamic nanotherapeutics can distinctly enhance anti-tumor immune response, which derives the concept of the dynamic immuno-nanomedicines (DINMs). This review describes the pivotal role of DINMs in cancer immunotherapy and provides an overview of the clinical realities of DINMs. The preclinical development of emerging DINMs is also outlined. Moreover, strategies to synergize the antitumor immunity by DINMs in combination with other immunologic agents are summarized. Last but not least, the challenges and opportunities related to DINMs-mediated immune responses are also discussed.

Genotype Impacts Axial Length Growth in Pseudophakic Eyes of Marfan Syndrome.

Purpose: The purpose of this study was to investigate the relationship between axial length (AL) growth and FBN1 genotype in patients with Marfan syndrome (MFS) after lens surgery and customize the selection of intraocular lens (IOL) power. Methods: Patients with MFS who had lens surgery and primary IOL implantation received panel-based next-generation sequencing (NGS). The rate of axial length growth (RALG) was calculated using pre- and postoperative AL measurements and corrected log10-transformed age. A multivariable regression model of RALG was developed after analyzing the effect of FBN1 genotypes and confounding factors. Results: A total of 139 probands of MFS with a median age at lens surgery of 6.25 years (interquartile range [IQR] = 4.67, 12.50 years) were followed up for a median duration of 2.08 years (IQR = 1.16, 3.00 years). The AL growth curve between the age of 3 and 15 years old was logarithmic. Dominant-negative (DN) variants affecting the disulfide-bridge forming cysteines and the conserved residues for calcium-binding had significantly higher RALG than DN variants affecting other structures (P = 0.001) but comparable to that of haplo-insufficiency variants (P = 1.000). Pre-operative AL (b = 0.563, P = 0.011) and genotype constant (b = 2.603, P = 0.011) were significantly associated with RALG in the final model. A Python-based calculator, Marfan IOL Calculator version 2.0, was programmed using the RALG to predict postoperative AL and customize IOL selection based on the ocular biometric parameters and FBN1 genotype. Conclusions: FBN1 genotype impacted the growth of AL in patients with MFS after IOL implantation. Knowing the FBN1 genotype could help cataract surgeons to customize IOL selection.

Emission characteristics of benzene series in FCC flue gas.

Benzene series are considered as air pollutants in refineries. However, the emissions of benzene series in fluid catalytic cracking (FCC) flue gas are poorly understand. In this work, we conduct stack tests on three typical FCC units. Benzene series, including benzene, toluene, xylene and ethyl benzene, are monitored in the flue gas. It shows that the coking degree of the spent catalysts affect the emissions of benzene series significantly, and there are four kinds of carbon-containing precursors in the spent catalyst. A fixed-bed reactor is used to conduct the regeneration simulation experiments, and the flue gas is monitored by TG-MS and FTIR. The emissions of toluene and ethyl benzene are mainly emitted in the early and middle stage of the reaction (250-650 °C), while the emission of benzene is mainly detected in the middle and late stage of the reaction (450-750 °C). Xylene group is not detected in the stack tests and regeneration experiments. Higher emissions of benzene series are released from the spent catalyst with lower C/H ratio during regeneration process. With the increase of oxygen content, the emissions of benzene series decrease, and the initial emission temperature is advanced. These insights can improve the refinery's awareness and control of benzene series in the future.

Genes cloning, sequencing and function identification of recombinant polyphenol oxidase isozymes for production of monomeric theaflavins from Camellia sinensis.

Theaflavins (TFs) are important quality compounds in black tea with a variety of biological activities. However, direct extraction of TFs from black tea is inefficient and costly. Therefore, we cloned two PPO isozymes from Huangjinya tea, termed HjyPPO1 and HjyPPO3. Both isozymes oxidized corresponding catechin substrates for the formation of four TFs (TF1, TF2A, TF2B, TF3), and the optimal catechol-type catechin to pyrogallol-type catechin oxidation rate of both isozymes was 1:2. In particular, the oxidation efficiency of HjyPPO3 was higher than that of HjyPPO1. The optimum pH and temperature of HjyPPO1 were 6.0 and 35 °C, respectively, while those of HjyPPO3 were 5.5 and 30 °C, respectively. Molecular docking simulation indicated that the unique residue of HjyPPO3 at Phe260 was more positive and formed a π-π stacked structure with His108 to stabilize the active region. In addition, the active catalytic cavity of HjyPPO3 was more conducive for substrate binding by extensive hydrogen bonding.

Antimicrobial cellulose paper tuned with chitosan fibers for high-flux oil/water separation.

Separating films with both high efficiency and large flux are desperately needed to meet the rising demand for the treatment of oily wastewater, while traditional oil/water separation papers with high separation efficiency usually suffered from low flux due to the unsuitable size of filtration pores. Herein, we report a bio-based porous, superhydrophobic, and antimicrobial hybrid cellulose paper with tunable porous structures for high flux oil/water separation. The size of pores in the hybrid paper can be tuned by both physical supports provided by the chitosan fibers and the chemical shielding supplied by the hydrophobic modification. The hybrid paper with increased porosity (20.73 µm; 35.15 %) and excellent antibacterial properties can efficiently separate a wide range of oil/water mixtures, solely by gravity, with outstanding flux (maximum of 23,692.69 L m-2 h-1), tiny oil interception, and high efficiency of over 99 %. This work provides new sights in the development of durable and low-cost functional papers for rapid and efficient oil/water separation.

Emission characteristics of condensable particulate matter (CPM) from FCC flue gas.

Particulate matter (PM) as a major air pollutant, generally includes filterable particulate matter (FPM) and condensable particulate matter (CPM). CPM has gradually attracted widespread attention recently, due to its increasing proportion in total PM emissions. Fluid catalytic cracking (FCC) units, the main emission source in refineries, mostly use wet flue gas desulfurization (WFGD), which will produce a large amount of CPM. However, CPM emission and composition of FCC units are actually unclear. In this work, we aimed to understand the emission characteristics of CPM in FCC flue gas and provide some potential control strategies. Here, the stack tests of three typical FCC units were conducted to monitor FPM and CPM, and the field monitoring FPM results are higher than the concentration provided by Continuous Emission Monitoring System (CEMS). The emission of CPM is at a high-level concentration from 28.88 to 86.17 mg/Nm3, divided into inorganic fraction and organic fraction. The inorganic fraction is mainly composed in CPM, where water-soluble ions including SO42-, Na+, NH4+, NO3-, CN-, Cl-, and F-, are the major contributors. Moreover, a variety of organic compounds are detected as qualitative analysis of organic fraction in CPM, which can be roughly classified into alkanes, esters, aromatics, and others. Finally, on the basis of the understanding of the characteristics of CPM, we have proposed two strategies for CPM control. This work is expected to advance CPM emission regulation and control in FCC units.

Predicting axial length in patients with Marfan syndrome and ectopia lentis after modified capsular tension ring and intraocular lens implantation.

PURPOSE: To predict the growth of axial length (AL) in patients with Marfan syndrome (MFS) and ectopia lentis (EL). SETTING: Eye and ENT Hospital of Fudan University, Shanghai, China. DESIGN: Consecutive retrospective case series. METHODS: Eyes were evaluated that had modified capsular tension ring and intraocular lens (IOL) implantation. The rate of AL growth (RALG) was calculated using AL divided by log10-transformed age. A multivariate linear regression model of RALG was developed after validation. RESULTS: 128 patients with MFS and EL were enrolled with a median follow-up duration of about 3 years. RALG was independent of age between 3 years and 15 years old ( P = .799) and decreased to 0 thereafter ( P = .878). Preoperative AL was associated with RALG in patients under 15 years old ( P = .003). Beta values for the final model of RALG were as below: intercept (-9.794) and preoperative AL (0.664). The postoperative AL was predicted as: postAL = preAL + RALG × log 10 ([postAge + 0.6]/[preAge + 0.6]). The mean prediction error was -0.003 (95% CI, -0.386 to 0.3791) mm and the mean absolute percentage error was 1.93% (95% CI, 0.73% to 3.14%). A Python-based calculator was developed to use the predicted AL in selecting IOL power and setting undercorrection. CONCLUSIONS: The AL growth of patients with MFS followed a logarithmic pattern and ceased at about age 15. A prediction model of postoperative AL was established for individual MFS patients between 3 and 15 years old, which could potentially optimize the IOL power selection.

The cortical regions and white matter tracts underlying auditory comprehension in patients with primary brain tumor.

The comprehension of spoken language is one of the most essential language functions in humans. However, the neurological underpinnings of auditory comprehension remain under debate. Here we used multi-modal neuroimaging analyses on a group of patients with low-grade gliomas to localize cortical regions and white matter tracts responsible for auditory language comprehension. Region-of-interests and voxel-level whole-brain analyses showed that cortical areas in the posterior temporal lobe are crucial for language comprehension. The fiber integrity assessed with diffusion tensor imaging of the arcuate fasciculus and the inferior longitudinal fasciculus was strongly correlated with both auditory comprehension and the grey matter volume of the inferior temporal and middle temporal gyri. Together, our findings provide direct evidence for an integrated network of auditory comprehension whereby the superior temporal gyrus and sulcus, the posterior parts of the middle and inferior temporal gyri serve as auditory comprehension cortex, and the arcuate fasciculus and the inferior longitudinal fasciculus subserve as crucial structural connectivity. These findings provide critical evidence on the neural underpinnings of language comprehension.

Clavien-Dindo classification and risk prediction model of complications after robot-assisted radical hysterectomy for cervical cancer.

Although significant progress has been made with surgical methods, the incidence of complications after minimally invasive surgery in patients with cervical cancer remains high. Established as a standardized system, Clavien-Dindo classification (CDC) has been applied in a variety of surgical fields. This study is designed to evaluate the complications after robot-assisted radical hysterectomy (RRH) for cervical cancer using CDC and further establish a prediction model. This is a study on the development of prediction model based on retrospective data. Patients with cervical cancer who received RRH treatment in our hospital from January 2016 to April 2019 were invited to participate in the study. The demographic data, laboratory and imaging examination results and postoperative complications were collected, and the logistic regression model was applied to analyze the risk factors possibly related to complications to establish a prediction model. 753 patients received RRH. The overall incidence of complications was 32.7%, most of which were grade I and grade II (accounting for 30.6%). The results of multivariate analysis showed that the preoperative neoadjuvant chemotherapy (OR = 1.693, 95%CI: 1.210-2.370, P = 0.002), preoperative ALT (OR = 1.028, 95%CI: 1.017-1.039, P < 0.001), preoperative urea nitrogen (OR = 0.868, 95%CI: 0.773-0.974, P = 0.016), preoperative total bilirubin (OR = 0.958, 95%CI: 0.925-0.993, P = 0.0.018), and preoperative albumin (OR = 0.937, 95%CI: 0.898-0.979, P = 0.003) were related to the occurrence of postoperative complications. The area under the curve (AUC) of receiver-operating characteristic (ROC) in the prediction model of RRH postoperative complications established based on these five factors was 0.827 with 95% CI of 0.794-0.860. In patients undergoing robot-assisted radical hysterectomy for cervical cancer, preoperative ALT level, urea nitrogen level, total bilirubin level, albumin level, and neoadjuvant chemotherapy were significantly related to the occurrence of postoperative complications. The regression prediction model established on this basis showed good prediction performance with certain clinical promotion and reference value.

Recent advances in bacteriophage-based therapeutics: Insight into the post-antibiotic era.

Antibiotic resistance is one of the biggest threats to global health, as it can make the treatment of bacterial infections in humans difficult owing to their high incidence rate, mortality, and treatment costs. Bacteriophage, which constitutes a type of virus that can kill bacteria, is a promising alternative strategy against antibiotic-resistant bacterial infections. Although bacteriophage therapy was first used nearly a century ago, its development came to a standstill after introducing the antibiotics. Nowadays, with the rise in antibiotic resistance, bacteriophage therapy is in the spotlight again. As bacteriophage therapy is safe and has significant anti-bacterial activity, some specific types of bacteriophages (such as bacteriophage phiX174 and Pyo bacteriophage complex liquid) entered into phase III clinical trials. Herein, we review the key points of the antibiotic resistance crisis and illustrate the factors that support the renewal of bacteriophage applications. By summarizing recent state-of-the-art studies and clinical data on bacteriophage treatment, we introduced (i) the pharmacological mechanisms and advantages of antibacterial bacteriophages, (ii) bacteriophage preparations with clinical potential and bacteriophage-derived anti-bacterial treatment strategies, and (iii) bacteriophage therapeutics aimed at multiple infection types and infection-induced cancer treatments. Finally, we highlighted the challenges and critical perspectives of bacteriophage therapy for future clinical development.

One- versus two-stage partial hepatectomy for large resectable solitary hepatocellular carcinomas determined preoperatively to have a narrow resection margin: a propensity score matching analysis.

Background: For patients with a large but resectable solitary hepatocellular carcinoma (HCC) of >5 cm in diameter, it is often difficult to achieve a sufficient resection margin. There is still no study on whether a two-stage hepatectomy to increase a narrow resection margin would be beneficial. Methods: From August 2014 to February 2017, patients with a large but resectable solitary HCC of >5 cm and a preoperative estimated resection margin of <1.0 cm were retrospectively studied. They were divided into one- and two-stage resection groups. A retrospective analysis was performed, followed by propensity score matching (PSM) analysis. Disease recurrence, survival, intraoperative and postoperative data were compared. Results: Before PSM, the 1-, 2-, 3-and 4-year recurrence-free survival rates for the one- and two-stage groups were 44.3%, 31.7%, 24.3%, 19.2% versus 60.6%, 45.4%, 43.5%, 32.3%, respectively (P=0.007). The corresponding OS rates were 61.0%, 45.2%, 43.8%, 38.4% versus 69.6%, 62.5%, 60.7%, 57.3%, respectively (P=0.029). After PSM, the 1-, 2-, 3-and 4-year recurrence-free survival rates for the one- and two-stage groups were 44.0%, 31.5%, 27.3%, 21.0% versus 60.6%, 45.4%, 43.5%, 32.3%, respectively (P=0.013). The corresponding OS rates were 62.5%, 41.1%, 41.1%, 37.5% versus 69.6%, 62.5%, 60.7%, 57.3%, respectively (P=0.038). Differences in the resection margins between the one- and two-stage groups before [0.3 (0-0.5) versus 1.2 (0.8-2.2) cm] and after [0.2 (0-0.5) versus 1.2 (0.8-2.2) cm] PSM were also significant. Conclusions: Two-stage hepatectomy allowed a wider resection margin for patients with a resectable but solitary HCC of >5 cm, and resulted in significantly better long-term survival outcomes after partial hepatectomy.

Utility of Large Diameter Visible Trephine in Percutaneous Endoscopic Lumbar Interbody Fusion: A Technical Report.

PURPOSE: In this study, a large diameter visible trephine was designed and used in percutaneous endoscopic lumbar interbody fusion to increase endoscopic bone decompression efficiency. Large diameter visible trephine-related technical notes and preliminary clinical experience are described. METHODS: A large diameter visible trephine was designed with normal diameter visible trephine as template. A total of 38 patients with lumbar degenerative diseases who underwent single-level percutaneous endoscopic lumbar interbody fusion with large or normal diameter visible trephine were included into a retrospective study. Operation time, bone decompression time, blood loss, intraoperative fluoroscopy, bone decompression fluoroscopy, and dura or nerve injury cases were recorded and analyzed statistically. Visual Analog Scale (VAS) scores and Oswestry Disability Index (ODI) were used to analyze the clinical outcomes of the 2 groups. RESULTS: The baseline data of the 2 groups were statistically similar. There was no significant difference in postoperative VAS and ODI scores between the 2 groups. Operation time and bone decompression time of large diameter visible trephine group were significantly shorter than that of normal diameter visible trephine group (P < 0.05). Intraoperative fluoroscopy times and bone decompression fluoroscopy times of large diameter visible trephine group were significantly more than that of normal diameter visible trephine group (P < 0.05). Blood loss of the 2 groups were not statistically different. There were no dura or nerve injury cases in the 2 groups. CONCLUSIONS: For percutaneous endoscopic lumbar interbody fusion, the large diameter visible trephine is a safe and efficient endoscopic bone decompression tool under fluoroscopic guidance.

Comparison of Accuracy in Keratometries Measured by Different Camera Devices for Predicting the Intraocular Lens Power in Lens-Dislocated Patients.

INTRODUCTION: This is a cross-sectional cohort study focused on assessing the influence of ocular biometric parameters of different camera devices for accurately predicting the intraocular lens (IOL) power in the congenital ectopia lentis (EL) patients. METHODS: This study includes a total of 91 eyes of 60 patients with congenital EL from June 2018 to April 2021. All patients underwent lens subluxation surgery with Cionni modified capsular tension rings (MCTR) implantation. Ocular parameters measured by partial coherence interferometry (IOLMaster 700, Carl Zeiss Meditec AG, Jena, Germany) and rotating Scheimpflug camera (Pentacam HR system, Oculus Optikgeräte GmbH, Wetzlar, Germany) were acquired from the database. The authenticity of the different keratometries (K) were analyzed by comparing the prediction error in spherical equivalent under controlled formula SRK/T, Haigis, and after Wang-Koch (WK) adjustment. RESULTS: We observed significant greater K values were obtained in IOLMaster than Pentacam, resulting in more significant hyperopia error while calculating SRK/T. The IOL power calculated with the total corneal refractive power (TCRP) from Pentacam revealed the highest prediction accuracy, indicating that TCRP is the closest to the actual refractive power of the cornea. However, in an exceptional case for long eye patients, total keratometry from IOLMaster was better recommended when using formula Haigis with WK adjustment. CONCLUSIONS: For most instances, TCRP is the best-recommended source of K value while calculating IOL power for EL patients. However, the total keratometry from IOLMaster preferably fits for long eye patients, who require WK adjustment for Haigis formula.

Study on emission factors of FCC flue gas pollutants in petroleum refineries.

Fluid catalytic cracking (FCC) unit is one of the means to lighten heavy oil in refineries, and its regenerated flue gas is also the main source of air pollutants from refinery. However, it is not clear about the type and amount of pollutants discharged from FCC units in China. The emissions of regenerated pollutants in the stack flue gases of three typical FCC units in China were investigated in this study, including a partial regeneration unit without a CO boiler (U1), a partial regeneration unit with a CO boiler (U2), and a full regeneration unit (U3). Different monitoring methods were used to analyze the concentration of sulfur dioxide (SO2) and nitrogen oxides (NOx), and the results showed that Fourier transform infrared spectroscopy (FTIR) monitoring results of SO2 and NOx are approximately 10 times and 5 times larger than those of the continuous emission monitoring system (CEMS) data, respectively. Also, the contents of characteristic pollutants such as NH3, C6H6, HCN, C8H8, C2H4, CH4, and CO were also monitored by FTIR, and the emission factors based on coke burn-off rate and throughput were investigated. The pollutants in U1 exhibited relatively higher contents with the NH3, HCN, and C6H6 of 116.99, 71.94, and 56.41 mg/Nm3 in flue gas, respectively. The emission of regenerated pollutants in U2 and U3 are significantly different from U1. Regeneration processes (including coke properties, operating modes, and presence or absence of CO boilers) affected pollutants' emission factors in varying degrees. At last, reasonable emission factors based on the different FCC regeneration processes contribute to the prediction, assessment, and control for the pollutant emission.

Interface Engineering on Cellulose-Based Flexible Electrode Enables High Mass Loading Wearable Supercapacitor with Ultrahigh Capacitance and Energy Density.

For practical energy storage devices, a bottleneck is to retain decent integrated performances while increasing the mass loading of active materials to the commercial level, which highlights an urgent need for novel electrode structure design strategies. Here, an active nitrogen-doped carbon interface with "high conductivity, high porosity, and high electrolyte affinity" on a flexible cellulose electrode surface is engineered to accommodate 1D active materials. The high conductivity of interface favors fast electron transport, while its high porosity and high electrolyte affinity properties benefit ion migration. As a result, the flexible anode accommodated by carbon nanotubes achieves an ultrahigh capacitance of 9501 mF cm-2 (315.6 F g-1 ) at a high mass loading of 30.1 mg cm-2 , and the flexible cathode accommodated by polypyrrole nanotubes realizes a remarkably high capacitance of 6212 mF cm-2 (248 F g-1 , 25 mg cm-2 ). The assembled flexible quasi-solid-state asymmetric supercapacitor delivers a maximum energy density of 1.42 mWh cm-2 (2.2 V, 2105 mF cm-2 ), representing the highest value among all reported flexible supercapacitors. This versatile design concept provides a new way to prepare high performance flexible energy storage devices.

Photoinduced Irreversible Intramolecular Proton Transfer of Arnebinones B, D, and E: The Case of Photoenolization at the p-Benzoquinone-CH2/CH-π System.

Arnebinones B, E, and D (1-3) have been found to be sensitive to light, generating complex and diverse proton transfer products when triggered by light. A unique two-step irreversible intramolecular proton transfer of 1 produced five scalemic mixtures, of which four possessed intriguing dual planar chirality. The unprecedented orientation epimerization equilibrium of the intra-annular double bond was first observed and researched in the homologous meroterpenoids by HPLC monitoring and DFT calculations. A "p-benzoquinone-CH2/CH-π" moiety in the structure was the common key feature for the occurrence of this type of photoenolization reaction. The product transformation processes and universality of this photoinduced irreversible proton transfer reaction were analyzed together with the cytotoxic activities of arnebinones B, D, and E, and their photoreaction products.

Both-In-One Hybrid Bacteria Suppress the Tumor Metastasis and Relapse via Tandem-Amplifying Reactive Oxygen Species-Immunity Responses.

Bacterial therapy, which targets the tumor site and aims at exerting an antitumor immune response, has displayed a great potential against malignant tumors. However, failure of the phase I clinical trial of Salmonella strain VNP20009 alone demonstrates that bacterial treatment alone can unsatisfy the requirements of high efficiency and biosafety. Herein, a strategy of both-in-one hybrid bacteria is proposed, wherein the chemotherapeutic drug doxorubicin (DOX) is integrated onto the surface of glucose dehydrogenase (GDH)-overexpressed non-pathogenic Escherichia coli (E. coli) strain, to potentiate the antitumor efficacy. Nicotinamide adenine dinucleotide phosphate (NADPH), which is produced by GDH from E. coli, promotes the generation of toxic reactive oxygen species (ROS) within the tumor, and ROS is then catalyzed by the DOX-activated NADPH oxidases. Importantly, the hybrid bacteria enhance stimulated systemic antitumor immune responses, thereby leading to effective tumor eradication. When this strategy is applied in four different tumor models, the hybrid bacteria significantly inhibited tumor metastasis, postsurgical regrowth, and primary/distal tumor relapse. The both-in-one ROS-immunity-boosted hybrid bacteria strategy provides knowledge for the rational design of bacteria-based synergistic cancer therapy.

Pure redox-sensitive paclitaxel-maleimide prodrug nanoparticles: Endogenous albumin-induced size switching and improved antitumor efficiency.

A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer. However, its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier. Herein, we report an albumin-bound tumor redox-responsive paclitaxel prodrugs nano-delivery strategy. Using diverse linkages (thioether bond and disulfide bond), paclitaxel (PTX) was conjugated with an albumin-binding maleimide (MAL) functional group. These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles (NPs) in aqueous solution without any excipients. By immediately binding to blood circulating albumin after intravenous administration, NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates in vivo, facilitating PTX prodrugs accumulation in the tumor region via albumin receptor-mediated active targeting. The tumor redox dual-responsive drug release property of prodrugs improves the selectivity of cytotoxicity between normal and cancer cells. Moreover, disulfide bond-containing prodrug/albumin nanoaggregates exhibit long circulation time and superior antitumor efficacy in vivo. This simple and facile strategy integrates the biomimetic characteristic of albumin, tumor redox-responsive on-demand drug release, and provides new opportunities for the development of the high-efficiency antitumor nanomedicines.