Interface Chirality: From Biological Effects to Biomedical Applications.

Chiral surface is a critical mediator that significantly impacts interaction with biological systems on regulating cell behavior. To better understand how the properties of interfacial Chirality affect cell behavior and address the limitations of chiral materials for biomedical applications, in this review, we mainly focus on the recent developments of chiral bio-interfaces for the controllable and accurate guidance of chiral biomedical phenomena. In particular, we will discuss how cells or organisms sense and respond to the chiral stimulus, as well as the chirality mediating cell fate, tissue repair, and organism immune response will be reviewed. In addition, the biological applications of chirality, such as drug delivery, antibacterial, antivirus and antitumor activities, and biological signal detection, will also be reviewed. Finally, the challenges of chiral bio-interfaces for controlling biological response and the further application of interface chirality materials for biomedical will be discussed.

A Novel Fluorescent Probe for the Detection of Hydrogen Peroxide.

Hydrogen peroxide (H2O2) is one of the important reactive oxygen species (ROS), which is closely related to many pathological and physiological processes in living organisms. Excessive H2O2 can lead to cancer, diabetes, cardiovascular diseases, and other diseases, so it is necessary to detect H2O2 in living cells. Since this work designed a novel fluorescent probe to detect the concentration of H2O2, the H2O2 reaction group arylboric acid was attached to the fluorescein 3-Acetyl-7-hydroxycoumarin as a specific recognition group for the selective detection of hydrogen peroxide. The experimental results show that the probe can effectively detect H2O2 with high selectivity and measure cellular ROS levels. Therefore, this novel fluorescent probe provides a potential monitoring tool for a variety of diseases caused by H2O2 excess.

NLRP3 inflammasome in peripheral blood monocytes as a risk factor for early -onset preeclampsia.

INTRODUCTION: As a leading cause of pregnancy and fetal mortality, pre-eclampsia impacts about 5-8% of pregnancies globally. To date, few studies have focused on the role played by (NOD)-like receptors protein 3 (NLRP3) in peripheral blood in early-onset pre-eclampsia (PE). In this study, we investigated whether NLRP3 expression in monocytes before 20 weeks of gestation was associated with an increased risk of early-onset PE. METHODOLOGY: During the study period from 2019 to 2021, women with singleton pregnancies were enrolled in this prospective study at the General Hospital of Northern Theater Command. A generalized additive model (GAM) and logistic regression models were applied to determine any association between NLRP3 and the risk of early-onset PE. RESULTS: In total, 571 and 48 subjects were included in the control and pre-eclampsia groups, respectively. The GAM and logistic regression models showed that NLRP3 was a significant factor for PE occurrence. The area under the curve, accuracy, specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.86, 0.82, 0.95, 0.72, 15.17, 0.29, and 52.0, respectively. CONCLUSION: The monitoring for NLRP3 in peripheral blood may be a potential, prospectively identifying risk factor for preeclampsia.

Elevated serum immunoglobulin level predicts high risk of 1-year recurrence in patients with Takayasu arteritis.

BACKGROUND: The mechanism of humoral immunity to Takayasu arteritis (TAK) is not clear. In our study, we aimed to investigate the correlation between immunoglobulins and disease activity and the relationship between immunoglobulins and the prognosis of TAK patients. METHODS: One hundred ninety TAK patients divided into two groups according to whether they had elevated immunoglobulins or not. We compared the demographic data and the clinical data between the two groups. Pearson correlation was used to analyze the relationship between immunoglobulin and disease activity, as well as the relationship between their changes. Immunohistochemical staining was used to compare the expression of humoral immune cells in TAK and atherosclerotic patients. One hundred twenty TAK patients who achieved remission within 3 months after discharge were followed up for 1 year. Logistic regression was used to explore the relationship between elevated immunoglobulins and recurrence. RESULTS: Disease activity and inflammatory factors were significantly higher in the group with elevated immunoglobulins than in the normal group [NIH (3.0 vs. 2.0, P = 0.001), ITAS-A (9.0 vs. 7.0, P = 0.006)]. Compared with atherosclerotic patients, CD138 + plasma cells were significantly increased in the aortic wall of patients with TAK (P = 0.021). Changes in IgG correlated well with CRP and ESR [CRP (r = 0.40, P = 0.027), ESR (r = 0.64, P < 0.001)]. For patients with TAK in remission, elevated immunoglobulins was associated with 1-year recurrence [OR95%, CI: 2.37 (1.03, 5.47), P = 0.042]. CONCLUSIONS: Immunoglobulins is of clinical value in evaluating disease activity in TAK patients. Moreover, the dynamic changes of IgG were correlated with the changes in inflammatory indicators in TAK patients.

Anaemia can be improved by controlling the disease activity of Takayasu's arteritis without iron administration.

BACKGROUND: Anaemia is a common clinical manifestation observed in Takayasu's arteritis (TAK), but few studies have been conducted. This study investigated whether improvement of inflammatory indicators was associated with improvement of anaemia in TAK. We also investigated whether iron supplement treatment could benefit in addition to immunosuppressant therapy in the anaemia patients with TAK. METHODS: This was a retrospective cohort study of 160 patients diagnosed with TAK. All patients were further assigned into anaemia group (67 cases) or non-anaemia group (93 cases) according to their haemoglobin levels. Fifty two anaemia patients completed follow-up (median 5.2 months). RESULTS: There were 67 (41.88%) anaemia patients among all 160 TAK patients. Compared to TAK patients without anaemia, the average age [32 (24, 45) vs. 40 (31, 48), p = 0.002], disease duration [36 (7, 120) vs. 72 (14, 162), p = 0.017] and BMI [21.43 (18.96, 23.81) vs. 22.86 (20.09, 25.81), p = 0.008] were significantly lower in TAK patients with anaemia. The levels of ESR [23 (15, 51) vs. 11 (5.5, 22), p = 0.0001] and CRP [9.33 (1.99, 27.8) vs. 1.99 (0.45, 6.68), p = 0.0001] were significantly increased in TAK patients who complicated with anaemia. After follow-up, decrease of ESR, CRP and disease activity score (NIH and ITAS) were significantly associated with improvement of anaemia. One unit decrease of ESR and CRP, the hazard ratio of the improvement rate of anaemia was 1.02 [95% CI (1.00, 1.03); p = 0.027] and 1.04 [95% CI (1.02, 1.07); p < 0.001] respectively. One point decrease of NIH and ITAS-A was associated with a higher probability of anaemia improvement [HR 95% CI: 1.25 (1.02, 1.41), p = 0.022, HR 95% CI: 1.62 (1.21, 2.17), p = 0.001]. These relationships were consistent between iron supplement treatment group and without iron supplement treatment group. We found no significant difference in cumulative hazard between the two groups (p = 0.692). CONCLUSION: Anaemia was a common complication in TAK. Decrease of ESR, CRP and disease activity score (NIH and ITAS) were significantly associated with improvement of anaemia, even after adjusting for various covariates. Moreover, these relationships were consistent between iron supplement treatment group and without iron supplement treatment group. There was no significant difference in the improvement of anaemia in patients receiving immunosuppressant therapy with or without iron supplement treatment.

Self-organization of zinc ions with a photosensitizer in vivo for enhanced antibiofilm and infected wound healing.

Antimicrobial materials have been developed to combat bacteria more effectively and promote infected wound healing. However, it is widely recognized that the potential toxic effects and complexity of the synthesis process hinder their practical applications. In this work, we introduced a strategy for fighting bacteria and promoting wound healing caused by Staphylococcus epidermidis (S. epidermidis) infection by the self-combination of Zn2+ and clinically applied 5-aminolevulinic acid hydrochloride (ALA) in the microbes. The clinical ALA could target and accumulate in the biofilm as well as contribute to the low-dose Zn2+ penetrating the biofilm due to the self-organized formation of Zn protoporphyrin IX in situ. Upon exposing to a 635 nm laser, the self-combination of ALA and Zn2+ significantly inhibited and eliminated the S. epidermidis biofilm via a synergistic biofilm eradication mechanism that enhanced photodynamic inactivation and aggravated cell wall/membrane disruption. In addition, the combination of ALA and Zn2+ could accelerate wound repair and reduce inflammatory response without causing cytotoxicity. The proposed strategy in this study illustrates the clinical prospects of eradicating biofilms and repairing infected wounds and demonstrates good biocompatibility towards infectious diseases.

Clinical features and risk factors of intracranial artery disease in patients with Takayasu arteritis.

OBJECTIVES: It has been known that aorta, subclavian, and extracranial arteries are commonly involved in Takayasu arteritis (TA). However, the involvement of intracranial artery in TA has not been well explored. The purpose of this study was to describe the clinical characteristics of intracranial artery lesions in TA patients and identify associated risk factors. METHODS: A total of 160 patients diagnosed with TA at Beijing Anzhen Hospital from November 2012 to November 2019 were retrospectively enrolled in this study and assigned to different groups according to the presence or absence of intracranial artery lesions. RESULTS: Our data showed that 20% of the enrolled 160 patients developed intracranial artery lesions and the right internal carotid artery (ICA) was the most common involved artery (53%). The average age of patients with intracranial artery lesions was significantly older compared to that of patients without intracranial artery involvement (43.56 ± 11.40 vs 36.41 ± 12.22, p = 0.003). In addition, more patients in the intracranial artery group had concomitant disease histories of stroke and/or hypertension (p = 0.010, 0.033). Chest tightness, chest pain, palpitation, coronary artery lesions, and extracranial segment lesions of ICA were more commonly observed in patients with intracranial artery lesions (p < 0.001, 0.017, 0.015, < 0.001, 0.003). Furthermore, we discovered that patients with coronary artery involvement, extracranial segment lesions of ICA, and higher Vasculitis Damage Index (VDI) score had an increased risk of developing intracranial artery lesions (p = 0.013, 0.019, 0.019). CONCLUSION: Our study showed that the intracranial artery disease was common in TA and was associated with coronary artery lesions, extracranial segment lesions of ICA, and higher VDI score. Key Points • Intracranial artery disease in TA patients had advanced age and higher triglyceride level. • Besides coronary artery lesions, intracranial artery disease in TA patients was associated with the extracranial segment lesions of ICA and higher VDI score.

Double molecular recognition strategy based on boronic acid-diol and NHS ester-amine for selective electrochemical detection of cerebral dopamine.

Electrochemical detection of dopamine (DA) usually depends on electrochemical oxidation of DA. This conventional method can hardly provide sufficient sensitivity and selectivity in the determination of the cerebral DA down to nanomolar level, because the ability of DA to be electrochemically oxidized is limited and many electroactive interferents are also oxidized at a similar potential with DA. Here, an electrochemical assay based on a double molecular recognition strategy has been proposed and proved to be of high sensitivity and selectivity for DA measurement in the cerebral system. 3,3'-Dithiodipropionic acid di(N-hydroxysuccinimide ester) (DSP) was anchored on the electrode surface to capture DA target through the specific reaction between N-hydroxysuccinimide (NHS) ester and amine. The captured DA endowed the electrode with a layer of diol groups, which further reacted with the boronic acid to trap of 4-mercaptophenylboronic acid (MBA) molecules, thus leading to the conjunction of electroactive thionine (Th) molecules on the electrode for signal readout. In addition, an Au nanostructure was employed to enhance signal amplification and facilitate the double molecular recognition process. As a consequence, this method was able to quantify DA from 1 to 300 nM with a detection limit of 0.74 nM, which exhibited a high specificity against cerebral interferents. Furthermore, the practicability of this platform was successfully demonstrated through determination of the dynamics of cerebral DA in the events of high K+ and nomifensine retromicrodialysis. Graphical abstract.

Comparison of Clinical Features at the Onset of Takayasu's Arteritis According to Age and Sex.

BACKGROUND: Takayasu's arteritis (TA) is a large-vessel vasculitis that predominantly affects the aorta, pulmonary artery, and its main branches. The cause of TA is still unclear. OBJECTIVE: To identify the clinical characteristics of TA at onset in different patient groups. METHODS: The clinical manifestations, laboratory, and angiographic findings of 53 patients with TA based on age at onset and sex were retrospectively analysed. RESULTS: The ratio of the incidence of TA in males and females was 1:4. Chest pain, reduced glomerular filtration rate (GFR), and multivessel involvement were the most common symptoms at TA onset in male patients. 17% of patients had an onset age >40 years, and the percentage of TA patients >40 years old with chest pain was significantly higher [6 (66.7%) vs 13 (29.5%) and p=0.031] than that in TA patients <40 years old. However, their renal artery involvement [1 (11.1%) vs 21 (47.7%)), p=0.042], abdominal aorta lesion [0 (0.0%) vs 16 (38.1%), p=0.030], and multiple vessel involvement [2 (22.2%) vs. 32 (72.7%), p=0.004] were significantly less evident. Multivariate analysis showed that hypertension and thoracic aortic lesion were predisposing factors for TA diagnosis [odds ratio (OR)=3.918, 95% confidence interval (CI)=1.616-1566.185, p=0.026]. For patients with aortic insufficiency (OR=3.674, 95% CI=2.734-567.621, p=0.007) or aneurysm formation (OR=7.255, 95% CI=1.23-1628.614, p=0.044), ascending aortic lesion was an independent risk factor. Furthermore, patients >40 years with chest pain but no brachial pulse should be suspected to have TA. CONCLUSION: Hypertension and thoracic aortic lesion are predisposing factors for the diagnosis of TA. Male with TA was more prone to present with chest pain, multivessel involvement, and reduced GFR.

On-line regeneration of electrochemical biosensor for in vivo repetitive measurements of striatum Cu2+ under global cerebral ischemia/reperfusion events.

The detection of Cu2+ ion, one of the metal ions substantial in cerebral physiology, is critical in studying brain activities and understanding brain functions. However, repetitive measurements of Cu2+ in the progress of physiological and pathological events is still challenging, because lack of the platform for repetitive on-line detection-regeneration cycle. Herein we report the design of a regenerated electrochemical biosensor combined with the in vivo microdialysis system. In this biosensor, hyperbranched polyethyleneimine (hPEI) acts as a regenerated recognition unit for Cu2+. Just by a simple rinse of ethylenediaminetetraacetic acid (EDTA) disodium salt, the Cu2+ and Cu+ ions on the biosensor interface were chelated with EDTA disodium salt, thus achieving the regeneration of the biosensor. In addition, 6-(ferrocenyl)hexanethiol (FcHT) serves as the inner reference moiety to elevate the sensing accuracy over regeneration cycles. As a result, this ratiometric electrochemical biosensor not only revealed high sensitivity and selectivity, but also exhibited excellent stability during multiple regeneration processing. This biosensor was capable of determining Cu2+ with a linear range between 0.05 and 12 µM and low detection limit (LOD) of 13 nM. Then, the platform has been successfully applied in repetitive Cu2+ analysis in rat brain under global cerebral ischemia/reperfusion events. The combination of results from 7 rats indicates global cerebral ischemia caused an obvious increase of the Cu2+ level, while reperfusion brought this level back to normal.

[Application of modern molecular biology techniques to study micro-ecosystem in the rumen].

The microbial community inhabiting in the rumen is characterized by its high population density, wide diversity and interactive complexity. However, until recently our knowledge of rumen microbiology was primarily based on classical culture based techniques (isolation, enumeration and nutritional characterization) which probably only account for 10% to 20% of the rumen microbial population. Modem molecular biology techniques provide effective methods to study the micro-ecosystem in the rumen. The use of molecular techniques based on nucleic acid probes is likely to revolutionize the approach to microbial ecology in the rumen and provide, not simply a refinement or increased understanding but a complete description of rumen community for the first time. Modem molecular techniques based on sequence comparisons of nucleic acids may be used to explore molecular characterization and provide a classification scheme which predicts natural evolutionary relationships. Genetic fingerprinting techniques that provide a pattern or profile of genetic diversity have been applied in a variety of environmental studies for the analysis of microbial communities. Whole-cell hybridization is a powerful technique which may be used to study the structure and function of microbial communities in situ and describe the expression of key enzymes. Real-time quantitative PCR technique may be conducted to accurately quantify the target microorganisms in the rumen. Development of these procedures and techniques will result in greater insights into community structure and activity of rumen microbial communities in relation to functional interactions, spatial and temporal relationships between different microorganisms and between microorganisms and feed particles. The successful development and application of these methods promise to provide the first opportunity to link distribution and identity of rumen microbes in their natural environment with their genetic potential and in situ activities.

Effects of tea saponins on in vitro ruminal fermentation and growth performance in growing Boer goat.

Two experiments were conducted to investigate the effects of tea saponins (TS) on in vitro ruminal fermentation and growth performance in growing Boer goats. In Experiment 1, the Reading Pressure Technique (RPT) system was used to investigate the effect of addition of TS (0, 0.2, 0.4 and 0.8 mg/ml) on the ruminal fermentation in vitro. The 24h gas production and methane emission were significantly decreased when 0.4 or 0.8mg TS was included, suggesting that the TS could inhibit the release of methane. Compared to the control, the TS had little effect on pH values and the concentration of total volatile fatty acids in the ruminal fluids. However, the fermentation patterns were changed, with lower acetate and higher proportions of propionate when TS was added. Ammonia-N concentration and protozoal counts were significantly reduced, while microbial protein yield was increased by the TS addition, suggesting that the TS could modify the ruminal fermentation. In Experiment 2, 27 growing Boer goats were used to evaluate the effects of the TS addition on growth performance. The animals received the same basal diets, and added TS at levels of 0 (C), 3 g (T1) and 6 g (T2) per day. The experiment lasted for 60 days with the first 15 days for adaptation. Blood samples were obtained by jugular venipuncture before the morning feeding on the final day of the experiment. During the whole periods, dry matter intake, average daily gain and feed efficiency in T1 were higher than in the other two. Serum total protein, albumin, high density lipoprotein cholesterol, Ca and P and alkaline phosphatase levels were higher in group T1 than in C and T2, whereas the blood urea nitrogen, creatinine and total cholesterol were lower in the TS-added groups. The concentrations of glucose, glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase were not affected by the TS. From the results obtained in this study, it is inferred that the TS could modify the ruminal fermentation and that proper doses of TS may have potential in improving the animal growth performance, whereas at high doses, it may have adverse effects on animal production.

Tea saponins affect in vitro fermentation and methanogenesis in faunated and defaunated rumen fluid.

The effect of tea saponins (TS) on rumen fermentation and methane emission was examined using an in vitro gas production technique named Reading Pressure Technique. Three levels of TS addition (0, 0.2, 0.4 mg/ml) were evaluated in the faunated and defaunated rumen fluid. Compared to the control, TS addition decreased the 24 h gas production in the faunated rumen fluid, but had a minor effect on gas yield in the defaunated rumen fluid. The TS significantly reduced methane production in vitro. In the faunated rumen fluid, 0.2 or 0.4 mg/ml TS decreased the 24 h methane emission by 12.7% or 14.0%, respectively. Rumen fluid pH value was affected neither by TS addition nor by defaunation. The TS addition had only minor effects on volatile fatty acids, but the yield and pattern of volatile fatty acids were greatly affected by defaunation. While the molar proportion of acetate was not affected by defaunation, the propionate was significantly increased and the butyrate significantly decreased. Ammonia-N concentration and microbial protein yield were influenced by TS inclusion and defaunation. Inclusion of 0.4 mg/ml TS increased the microbial protein mass by 18.4% and 13.8% and decreased the ammonia-N concentration by 8.3% and 19.6% in the faunated and defaunated rumen fluid, respectively. Protozoa counts were significantly reduced by TS inclusion. The current study demonstrated the beneficial effect of TS on methane production and rumen fermentation, and indicated that this may be due to the effect of the associated depression on protozoa counts.

[Methanogens and manipulation of methane production in the rumen].

Methanogens belong to the kingdom of Euryarchaeota in the domain of Archaea. They are characterized by their ability to produce methane under anaerobic conditions. Methane production in the rumen represents a loss of energy for the host animal, and, in addition, methane eructated by ruminants may contribute to a greenhouse effect or global warming. Reduction or elimination of methanogenesis in the rumen has been touted as a way of improving animal production and may marginally benefit to control of anthropogenic release of methane. More and more scientists focus on ruminal methanogens and methanogenesis recently. Authors summarized the manipulation of methanogenesis in the rumen, including defaunation, feed formulation, adding electron acceptors and stimulation of acetogens. The characteristics of methanogenic Archaea and the recent knowledge of the methanogenesis in the rumen were also reviewed in this article.