High-performance self-cascade nanoreactors for combined ferroptosis, photothermal therapy, and starving therapy.

Despite the great potential of starving therapy caused by nanoreactor based on glucose oxidase (GOX) in tumor therapy, efficiency and uncontrolled reaction rates in vivo lead to inevitable toxicity to normal tissues, which seriously hindering their clinical conversion. Herein, a cascade nanoreactor (GOX/Mn/MPDA) was constructed by coating mesoporous polydopamine nanoparticles (MPDA) with MnO2 shell and then depositing GOX into honeycomb-shaped manganese oxide nanostructures to achieve a combination of ferroptosis, photothermal therapy and starving therapy. Upon uptake of nanodrugs to cancer cells, the MnO2 shell would deplete glutathione (GSH) and produce Mn2+, while a large amount of H2O2 generated from the catalytic oxidation of glucose by GOX would accelerate the Fenton-like reaction mediated by Mn2+, producing high toxic •OH. More importantly, the cascade reaction between GOX and MnO2 would be further strengthened by localized hyperthermia caused by irradiated by near-infrared laser (NIR), inducing significant anti-tumor effects in vitro and in vivo. Regarding the effectiveness of tumor treatment in vivo, the tumor inhibition rate achieved an impressive 64.33%. This study provided a new strategy for anti-tumor therapeutic by designing a photothermal-enhanced cascade catalytic nanoreactor.

Synergistic antibacterial and antifouling wound dressings: Integration of photothermal-activated no release and zwitterionic surface modification.

Addressing the pervasive issue of bacteria and biofilm infections is crucial in the development of advanced antifouling wound dressings. In this study, a novel wound healing treatment using sulfobetaine (SBMA) decorated electrospun fibrous membrane based on polycaprolactone (PCL)/nitric oxide (NO) donors was developed. The fabrication involved a dual strategy, first integrating NO donors into mesoporous polydopamine (MPDA) and complexed with PCL/PEI to electrospin nanofibers. The fibrous membrane exhibited a potent antibacterial response upon irradiation at 808 nm, owing to a combination of NO and photothermal effect that effectively targets bacteria and disrupts biofilms. Surface functionalization of the membrane with PEI allowed for the attachment of SBMA via Michael addition, fabricating a zwitterionic surface, which significantly hinders protein adsorption and reduces biofilm formation on the wound dressing. In vitro and in vivo assessments confirmed the rapid bactericidal capabilities and its efficacy in biofilm eradication. Combining photothermal activity, targeted NO release and antifouling surface, this multifaceted wound dressing addresses key challenges in bacterial infection management and biofilm eradication, promoting efficient wound healing.

Research on the Low-Temperature Impact Toughness of a New 100-mm Ultra-Thick Offshore Steel Fabricated Using the Narrow-Gap Laser Wire Filling Welding Process.

Ultra-thick offshore steel, known for its high strength, high toughness, and corrosion resistance, is commonly used in marine platforms and ship components. However, when offshore steel is in service for an extended period under conditions of high pressure, extreme cold, and high-frequency impact loads, the weld joints are prone to fatigue failure or even fractures. Addressing these issues, this study designed a narrow-gap laser wire filling welding process and successfully welded a 100-mm new type of ultra-thick offshore steel. Using finite element simulation, EBSD testing, SEM analysis, and impact experiments, this study investigates the weld's microstructure, impact toughness, and fracture mechanisms. The research found that at -80 °C, the welded joint exhibited good impact toughness (>80 J), with the impact absorption energy on the surface of the weld being 217.7 J, similar to that of the base material (225.3 J), and the fracture mechanism was primarily a ductile fracture. The impact absorption energy in the core of the weld was 103.7 J, with the fracture mechanism mainly being a brittle fracture. The EBSD results indicated that due to the influence of the welding thermal cycle and the cooling effect of the narrow-gap process, the grains gradually coarsened from the surface of the welded plate to the core of the weld, which was the main reason for the decreased impact toughness at the joint core. This study demonstrates the feasibility of using narrow-gap laser wire filling welding for 100-mm new type ultra-thick offshore steel and provides a new approach for the joining of ultra-thick steel plates.

Boron Reduced Copper Excess-Induced Oxidative Damage in Citrus sinensis by Modulating Reactive Oxygen Species and Methylglyoxal Formation and Their Detoxification Systems.

Citrus is mainly cultivated in acid soil with low boron (B) and high copper (Cu). In this study, Citrus sinensis seedlings were submitted to 0.5 (control) or 350 µM Cu (Cu excess or Cu exposure) and 2.5, 10, or 25 µM B for 24 weeks. Thereafter, H2O2 production rate (HPR), superoxide production rate (SAPR), malondialdehyde, methylglyoxal, and reactive oxygen species (ROS) and methylglyoxal detoxification systems were measured in leaves and roots in order to test the hypothesis that B addition mitigated Cu excess-induced oxidative damage in leaves and roots by reducing the Cu excess-induced formation and accumulation of ROS and MG and by counteracting the impairments of Cu excess on ROS and methylglyoxal detoxification systems. Cu and B treatments displayed an interactive influence on ROS and methylglyoxal formation and their detoxification systems. Cu excess increased the HPR, SAPR, methylglyoxal level, and malondialdehyde level by 10.9% (54.3%), 38.9% (31.4%), 50.3% (24.9%), and 312.4% (585.4%), respectively, in leaves (roots) of 2.5 µM B-treated seedlings, while it only increased the malondialdehyde level by 48.5% (97.8%) in leaves (roots) of 25 µM B-treated seedlings. Additionally, B addition counteracted the impairments of Cu excess on antioxidant enzymes, ascorbate-glutathione cycle, sulfur metabolism-related enzymes, sulfur-containing compounds, and methylglyoxal detoxification system, thereby protecting the leaves and roots of Cu-exposed seedlings against oxidative damage via the coordinated actions of ROS and methylglyoxal removal systems. Our findings corroborated the hypothesis that B addition alleviated Cu excess-induced oxidative damage in leaves and roots by decreasing the Cu excess-induced formation and accumulation of ROS and MG and by lessening the impairments of Cu excess on their detoxification systems. Further analysis indicated that the pathways involved in the B-induced amelioration of oxidative stress caused by Cu excess differed between leaves and roots.

Boron-mediated amelioration of copper toxicity in Citrus sinensis seedlings involved reduced concentrations of copper in leaves and roots and their cell walls rather than increased copper fractions in their cell walls.

Little information is available on how boron (B) supplementation affects plant cell wall (CW) remodeling under copper (Cu) excess. 'Xuegan' (Citrus sinensis) seedlings were submitted to 0.5 or 350 µM Cu × 2.5 or 25 µM B for 24 weeks. Thereafter, we determined the concentrations of CW materials (CWMs) and CW components (CWCs), the degree of pectin methylation (DPM), and the pectin methylesterase (PME) activities and PME gene expression levels in leaves and roots, as well as the Cu concentrations in leaves and roots and their CWMs (CWCs). Additionally, we analyzed the Fourier transform infrared (FTIR) and X-ray diffraction (XRD) spectra of leaf and root CWMs. Our findings suggested that adding B reduced the impairment of Cu excess to CWs by reducing the Cu concentrations in leaves and roots and their CWMs and maintaining the stability of CWs, thereby improving leaf and root growth. Cu excess increased the Cu fractions in leaf and root pectin by decreasing DPM due to increased PME activities, thereby contributing to citrus Cu tolerance. FTIR and XRD indicated that the functional groups of the CW pectin, hemicellulose, cellulose, and lignin could bind and immobilize Cu, thereby reducing Cu cytotoxicity in leaves and roots.

Monocytes Release Pro-Cathepsin D to Drive Blood-to-Brain Transcytosis in Diabetes.

BACKGROUND: Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined. METHODS: High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter. In vivo 2-photon imaging, behavioral tests, immunofluorescence, transmission electron microscopy, Western blot analysis, vascular leakage assay, and single-cell RNA sequencing were performed to clarify the phenotype and elucidate the molecular mechanism. RESULTS: Monocytes expressed high-level CTSD in patients with type 2 diabetes. The transgenic mice expressing human CTSD in the monocytes showed increased brain microvascular permeability resembling the diabetic microvascular phenotype, accompanied by cognitive deficit. Mechanistically, the monocytes release nonenzymatic pro-CTSD to upregulate caveolin expression in brain endothelium triggering caveolae-mediated transcytosis, without affecting the paracellular route of brain microvasculature. The circulating pro-CTSD activated the caveolae-mediated transcytosis in brain endothelial cells via its binding with low-density LRP1 (lipoprotein receptor-related protein 1). Importantly, genetic ablation of CTSD in the monocytes exhibited a protective effect against the diabetes-enhanced brain microvascular transcytosis and the diabetes-induced cognitive impairment. CONCLUSIONS: These findings uncover the novel role of circulatory pro-CTSD from monocytes in the pathogenesis of cerebral microvascular lesions in diabetes. The circulatory pro-CTSD is a potential target for the intervention of microvascular complications in diabetes.

Exploring the impact of pericentric inversion of chromosome 9 on fertility in sperm donors.

ABSTRACT: Pericentric inversion of chromosome 9 (inv[9]) is a common chromosomal structural variant, but its impact on clinical outcomes remains debated. The screening criteria of sperm banks are rarely mentioned to individuals with inv(9). In this study, we evaluated the fertility of sperm donors with inv(9) who met eligibility criteria for sperm banks (inv[9]-eligible donors). From March 2004 to May 2022, chromosomal analysis of 16 124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province (Changsha, China) found that 251 (1.6%) had chromosome variations, with inv(9) being the most prevalent at 1.1%. All 169 inv(9)-eligible donors were contacted to collect fertility outcome data, along with 206 eligible donors without inv(9) as controls. In addition, semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization (FISH), mitochondrial membrane potential, DNA fragmentation index, acrosome integrity, reactive oxygen species (ROS), and sperm morphology. Results showed that inv(9) did not significantly increase reproductive risks overall. Despite detecting ROS level differences, the clinical impact may be insignificant. This study provides new data on the inv(9) population that can serve as a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individuals carrying inv(9) variant.

Long-term storage modifies the microRNA expression profile of cryopreserved human semen.

The global practice of cryopreservation of human semen is commonplace in Assisted Reproductive Technology (ART) labs and sperm banks. However, information on the effects of long-term cryopreservation on semen is limited to clinical data summaries and descriptions. For this study, we prepared 4 semen specimens of fresh semen, 4 specimens cryostored for at least 1 year, 3 specimens cryostored for at least 5 years, 4 specimens cryostored for at least 10 years, and 3 specimens cryostored for at least 15 years. Total RNA was extracted from each sample, amplified, labeled, and mapped to the known primary microRNA (miRNA) in the miRBase database, enabling the prediction of novel miRNAs. We found that cryopreservation can lead to changes in miRNA expression, and with the increase in storage time, these changes became more pronounced. Meanwhile, the expression of let-7d-3p, let-7c-5p and let-7i-3p miRNAs changed dynamically over cryostorage time in frozen-thawed human sperm. Furthermore, we analyzed the time-dependent dynamics of cryostorage-expressed miRNAs and their target mRNAs and found that half of the target genes were expressed in oocytes. These intersection genes were mainly enriched in cancer and cytoskeletal signaling pathways. Our findings showed that the miRNA expression profile of cryopreserved human semen is modified by long-term storage. Furthermore, as the storage time increases, the impact on human sperm becomes more pronounced in terms of miRNAs, which may have an effect on subsequent fertilization and embryonic development.

Efficacy and safety of daratumumab in the treatment of relapsed/refractory multiple myeloma: A meta-analysis of randomized controlled trials.

BACKGROUND: Daratumumab as a monoclonal antibody has shown promising results in the treatment of relapsed/refractory multiple myeloma (RRMM). However, the efficacy and safety of daratumumab-based regimens compared to control regimens have not been fully established. METHODS: The search was conducted using electronic databases (PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases) up to December 2022. We conducted a meta-analysis of randomized controlled trials that evaluated the efficacy and safety of daratumumab in the treatment of RRMM. Data were extracted from eligible studies and were presented as hazard ratio or risk ratio (RR) with 95% confidence interval (CI). RESULTS: A total of 5 randomized controlled trials comprising 2003 patients were included in this meta-analysis. The results showed that daratumumab-based regimens significantly improved progression-free survival compared to control regimens (hazard ratio = 0.44, 95% CI 0.32-0.60, P < .00001). Additionally, daratumumab-based regimens significantly improved overall response rate compared to control regimens (RR = 1.25, 95% CI 1.16-1.36, P < .00001). the rate of minimal residual disease was also significantly higher in the daratumumab-based regimens (RR = 6.10, 95% CI 4.09-9.11, P < .00001). However, there was an increased risk of pneumonia, upper respiratory tract infections, and diarrhea in the daratumumab-based regimens. CONCLUSION: Our results suggest that daratumumab-based regimens are effective in the treatment of RRMM, improving progression-free survival, minimal residual disease, and overall response rate. However, there is an increased risk of pneumonia, upper respiratory tract infections, and diarrhea. Further studies are needed to determine the long-term safety and efficacy of daratumumab in the treatment of multiple myeloma.

Artesunate carriers induced ferroptosis to overcome biological barriers for anti-cancer.

Artesunate (ART) has potent anticancer activity but it suffers from poor stability and low bioavailability in vivo due to the special endoperoxide moiety in the molecules. In this work, we fabricated programmable enzyme/reactive oxygen species (ROS) responsive ART complex carriers with size and charge adaptive regulation in order to improve stability and overcome biochemical hurdles of solid tumor. The complex carries (ART/AA-PAMAM@HA) were created by electrostatic interaction between dendrimer-ART/arachidonic acid (AA) (ART/AA-PAMAM) and hyaluronic acid (HA), which can proactively penetrate deeply into tumors and selective drug release. Specifically, ART induced Fenton reaction and produced a mass of ROS and lipid peroxides (LPO), leading to the depressing of GSH level and glutathione peroxidase 4 (GPX4) activity. Meanwhile, exogenous AA further promoted the accumulation of LPO by cascade regulating ferroptosis pathway. In the anti-tumor efficacy in vivo, the tumor inhibition ratio was achieved to 46.92%. This work shows a new anti-tumor strategy triggering ferroptosis via regulating redox homeostasis.

Genetic testing of sperm donors in China: a survey of current practices.

Background: The National Health and Family Planning Commission of China (NHFPCC) issued the "Measures for the Management of Human Sperm Banks," which was revised in 2003 and is still in effect today. One of the standard guidelines is that potential donors undergo laboratory testing to exclude infectious and genetic diseases and karyotype analysis. However, patient demands for donor genetic testing have also increased, and only karyotype analysis to exclude genetic diseases is not sufficient to meet these demands. Objective: To examine donor genetic screening practices at sperm banks in China and to evaluate the qualifications and skills of genetic counselors at the banks. Materials and methods: An electronic survey was distributed to twenty-seven sperm banks to examine donor genetic screening practices at sperm banks in China and to evaluate the qualifications and skills of genetic counselors at the banks. Twenty-six human sperm banks responded to a 32-question survey about their current practices related to genetic testing of sperm donors. Results: The 26 sperm banks reported that all qualified sperm donors undergo karyotype analysis; 22 banks (84.6%) collected three generations of family history from each qualified sperm donor; 10 (38.5%) reported that they attempted to accommodate special requests from donor semen recipients for particular genetic tests. Only 2 of the 26 (7.7%) sperm banks reported that they performed whole-exome sequencing. At all the sperm banks, consent for genetic testing was obtained as part of the overall contract for sperm donors. Nineteen (73.1%) sperm banks had genetic counselors on their staff, while six (23.1%) had no genetic counselors on their staff but had access to genetic counselors at the hospital. Only one (3.8%) sperm bank had no genetic counselors on their staff or at the hospital. Conclusions: The need for larger scale genetic testing of donors and recipients and an extensive panel of genetic tests specific to the Chinese population. Additionally, professionally trained geneticists must be employed as genetic counsellors so that the results of genetic tests and their implications can be explained to donors.

Ruthenium(II)-Catalyzed Remote C-H Sulfonylation of 2-Pyridones.

Herein, a ruthenium-mediated remote C-H mono- and disulfonylation of 2-pyridones with arylsulfonyl chlorides is developed. The catalytic system consisting of a [Ru(p-cymene)Cl2]2 catalyst and KOAc additive allows 2-pyridones to undergo C3,C5-disulfonylation in 1,4-dioxane, and C5-sulfonylation when the C3-position of 2-pyridones is blocked. The successful transformation of the products and late-stage modification of estrone further highlighted the potential utility and significance of this synthetic protocol. Preliminary mechanistic studies indicated that the remote regioselectivity might be dictated via chelation-assisted ruthenation.

Combined chemo and photo therapy of programmable prodrug carriers to overcome delivery barriers against nasopharyngeal carcinoma.

Indocyanine green (ICG) has been employed in medical diagnostics due to its superior photophysical characteristics. However, these advantages are offset by its quick body clearance and inferior photo-stability. In this work, programmable prodrug carriers for chemotherapy/PDT/PTT against nasopharyngeal carcinoma (NPC) were created in order to increase photo-stability and get around biochemical hurdles. The programmable prodrug carriers (PEG-PLA@DIT-PAMAM) that proactively penetrated deeply into NPC tumors and produced the deep phototherapy and selective drug release under laser irradiation was created by dendrimer-DOX/ICG/TPP (DIT-PAMAM) and PEGylated poly (α-lipoic acid) (PLA) copolymer. Long circulation times and minimal toxicity to mammalian cells are two benefits of PEG-coated carriers. The overexpressed GSH on the tumor cell or vascular endothelial cell of the NPC disintegrated the PEG-g-PLA chains and released the DIT-PAMAM nanoparticles after the carriers had reached the NPC tumor periphery. Small, positively charged DIT-PAMAM nanoparticles may penetrate tumors effectively and remain inside tumor for an extended period of time. In addition, the induced ROS cleaved the thioketal linkers for both DOX and nanoparticles and product hyperthermia (PTT) to kill cancer cells under laser irradiation, facilitating faster diffusion of nanoparticles and more effective tumor penetration with a programmable publication of DOX. The programmable prodrug carries showed high photo-stability high photo-stability, which enabled very effective PDT, PTT, and tumor-specific DOX release. With the goal of combining the effects of chemotherapy, PDT, and PTT against NPC, this research showed the great efficacy of programmable prodrug carriers.

[Effect of electroacupuncture at different time points on postoperative urination function in patients with mixed hemorrhoids surgery].

OBJECTIVE: To observe the effect of preoperative, intraoperative and postoperative electroacupuncture (EA) intervention on postoperative urination function in patients with mixed hemorrhoid surgery. METHODS: A total of 240 patients with mixed hemorrhoid surgery under lumbar anesthesia were randomly divided into an EA preconditioning group (group A, 60 cases, 9 cases dropped off), an intraoperative EA group (group B, 60 cases, 4 cases dropped off), a postoperative EA group (group C, 60 cases, 6 cases dropped off), and a non-acupuncture group (group D, 60 cases, 3 cases dropped off). In the groups A, B and C, EA was exerted at Zhongliao (BL 33) and Huiyang (BL 35) , with disperse-dense wave, 4 Hz/20 Hz in frequency, and lasting 30 min, at 30 min before lumbar anesthesia, immediately after lumbar anesthesia and 6 h after surgery, respectively. No EA intervention was performed in the group D. The postoperative urination smoothness score in each group was observed 24 h after surgery. The first urination time, first urination volume, urine residual volume after first urination were recorded, and incidence of indwelling catheterization, postoperative visual analogue scale (VAS) score, number of remedial analgesia, and the incidence of postoperative nausea and vomiting were observed in each group. RESULTS: In the groups A, B and C, the postoperative urination smoothness scores were superior to the group D (P<0.05), and the time of first urination was earlier than the group D (P<0.05). In the group C, the time of first urination was earlier than the group A and the group B (P<0.05), the first urination volume was higher than the group D (P<0.05), and the urine residual volume after first urination was lower than the group D (P<0.05). There was no significant difference in the incidence of indwelling catheterization and postoperative nausea and vomiting among the 4 groups (P>0.05). The VAS scores of the group A, B and C were lower than that in the group D (P<0.05), and the number of remedial analgesia cases was lower than that in the group D (P<0.05). CONCLUSION: EA intervention could promote the recovery of urination function and relieve postoperative pain in patients with mixed hemorrhoids surgery. Early postoperative EA intervention is more conducive to the recovery of urination function.

Comparison of Clinical Outcomes, Risks, and Costs for 20,910 Donor In Vitro Fertilization and 16,850 Donor Artificial Insemination Treatment Cycles: A Retrospective Analysis in China.

PURPOSE: To evaluate the effectiveness of donor in vitro fertilization (IVF-D) and donor artificial insemination (AI-D) in clinical outcomes, risks, and costs. METHODS: This study analyzed the cycle changes and clinical outcomes in 20,910 IVF-D and 16,850 AI-D cycles between 2013 and 2021 in the Reproductive and Genetic Hospital of CITIC-Xiangya. A cost-effectiveness analysis was performed to evaluate the costs per couple and per live birth cycle in the two treatment groups. RESULTS: IVF-D had higher pregnancy and live birth rates than AI-D (p < 0.001). The cumulative pregnancy and live birth rates for three AI-D cycles were 41.01% and 32.42%, respectively, higher than the rates for one or two AI-D cycles. The multiple birth and birth defect rate of AI-D was lower than that of IVF-D significantly. IVF-D mean cost per couple was higher than that of AI-D (CNY32,575 vs. CNY11,062, p < 0.001), with a mean cost difference of CNY21,513 (95% confidence interval, CNY20,517-22,508). The mean costs per live birth cycle for IVF-D and AI-D were CNY49,411 and CNY31,246, respectively. CONCLUSION: AI-D is more cost-effective and poses a lower risk for infertility couples than IVF-D, and patients should undergo three AI-D cycles to obtain the highest success rate.

Physiological and Ultrastructural Responses to Excessive-Copper-Induced Toxicity in Two Differentially Copper Tolerant Citrus Species.

Over-applied copper (Cu)-based agrochemicals are toxic to citrus trees. However, less information is available discussing the ultrastructural alterations in Cu-stressed citrus species. In the present study, seedlings of Citrus sinensis and Citrus grandis that differed in Cu-tolerance were sandy-cultured with nutrient solution containing 0.5 µM Cu (as control) or 300 µM Cu (as Cu toxicity) for 18 weeks. At the end of the treatments, the physiological parameters and ultrastructural features of the citrus leaves and roots were analyzed. The results indicate that Cu toxicity significantly decreased the ratio of shoot biomass to dry weight, the Cu translocation factor and the total chlorophyll of two citrus species. The anatomical and ultrastructural alterations verified that excessive Cu resulted in starch granules accumulated in the leaves and roots of the two citrus species. Under Cu toxicity, increased root flocculent precipitate and thickened root cell wall might reduce the Cu translocation from citrus roots to the shoots. Compared with C. sinensis, C. grandis maintained a relatively integral root cellular structure under Cu toxicity, which provided a structural basis for a higher Cu tolerance than C. sinensis. The present results increase our understanding of the physiological and ultrastructural responses to Cu toxicity in citrus species.

Lpp of Escherichia coli K1 inhibits host ROS production to counteract neutrophil-mediated elimination.

Escherichia coli (E. coli) is the most common Gram-negative bacterial organism causing neonatal meningitis. The pathogenesis of E. coli meningitis, especially how E. coli escape the host immune defenses, remains to be clarified. Here we show that deletion of bacterial Lpp encoding lipoprotein significantly reduces the pathogenicity of E. coli K1 to induce high-degree of bacteremia necessary for meningitis. The Lpp-deleted E. coli K1 is found to be susceptible to the intracellular bactericidal activity of neutrophils, without affecting the release of neutrophil extracellular traps. The production of reactive oxygen species (ROS), representing the primary antimicrobial mechanism in neutrophils, is significantly increased in response to Lpp-deleted E. coli. We find this enhanced ROS response is associated with the membrane translocation of NADPH oxidase p47phox and p67phox in neutrophils. Then we constructed p47phox knockout mice and we found the incidence of bacteremia and meningitis in neonatal mice induced by Lpp-deleted E. coli is significantly recovered by p47phox knockout. Proteomic profile analysis show that Lpp deficiency induces upregulation of flagellar protein FliC in E. coli. We further demonstrate that FliC is required for the ROS induction in neutrophils by Lpp-deleted E. coli. Taken together, these data uncover the novel role of Lpp in facilitating intracellular survival of E. coli K1 within neutrophils. It can be inferred that Lpp of E. coli K1 is able to suppress FliC expression to restrain the activation of NADPH oxidase in neutrophils resulting in diminished bactericidal activity, thus protecting E. coli K1 from the elimination by neutrophils.

A chiral BINOL-based supramolecular gel enabling sensitive enantioselective and chemoselective collapse toward histidine.

A chiral small molecule gelator (R)-H3L based on 1,1'-bi-2,2'-naphthol (BINOL)-phosphoric acid was designed and prepared, which spontaneously forms a stable water-induced gel. The gelation mechanism was revealed by single crystal X-ray diffraction analysis and a number of spectroscopic methods. Addition of Cu2+ improved the gelation ability, and the resultant metal organic gel realized visual enantioselective and chemoselective recognition toward L-histidine from enantiomers of 19 amino acids via gel collapse. The gel showed a highly sensitive response to L-histidine, and as low as 0.01 equiv. of L-histidine relative to the critical gelation concentration of (R)-H3L-Cu caused the gel to collapse. This strategy of regulating the assembly behavior through the interaction of amino acids and metal ions not only provides a simple and direct way to distinguish enantiomers, but also provides insight into how metal ions regulate the organization of biological supramolecular systems.

LOX-1 Regulation in Anti-atherosclerosis of Active Compounds of Herbal Medicine: Current Knowledge and the New Insight / 中国结合医学杂志

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) have recently been identified to be closely related to the occurrence and development of atherosclerosis (AS). A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating AS. In this review, the related research progress of AS and LOX-1 has been summarized. And the anti-AS effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed. As a potential biomarker and target for intervention in AS, LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention and treatment.

High pH Alleviated Sweet Orange (Citrus sinensis) Copper Toxicity by Enhancing the Capacity to Maintain a Balance between Formation and Removal of Reactive Oxygen Species and Methylglyoxal in Leaves and Roots.

The contribution of reactive oxygen species (ROS) and methylglyoxal (MG) formation and removal in high-pH-mediated alleviation of plant copper (Cu)-toxicity remains to be elucidated. Seedlings of sweet orange (Citrus sinensis) were treated with 0.5 (non-Cu-toxicity) or 300 (Cu-toxicity) µM CuCl2 × pH 4.8, 4.0, or 3.0 for 17 weeks. Thereafter, superoxide anion production rate; H2O2 production rate; the concentrations of MG, malondialdehyde (MDA), and antioxidant metabolites (reduced glutathione, ascorbate, phytochelatins, metallothioneins, total non-protein thiols); and the activities of enzymes (antioxidant enzymes, glyoxalases, and sulfur metabolism-related enzymes) in leaves and roots were determined. High pH mitigated oxidative damage in Cu-toxic leaves and roots, thereby conferring sweet orange Cu tolerance. The alleviation of oxidative damage involved enhanced ability to maintain the balance between ROS and MG formation and removal through the downregulation of ROS and MG formation and the coordinated actions of ROS and MG detoxification systems. Low pH (pH 3.0) impaired the balance between ROS and MG formation and removal, thereby causing oxidative damage in Cu-toxic leaves and roots but not in non-Cu-toxic ones. Cu toxicity and low pH had obvious synergistic impacts on ROS and MG generation and removal in leaves and roots. Additionally, 21 (4) parameters in leaves were positively (negatively) related to the corresponding root parameters, implying that there were some similarities and differences in the responses of ROS and MG metabolisms to Cu-pH interactions between leaves and roots.