Expanding the Hydrophobic Cavity Surface of Azocalix[4]arene to Enable Biotin/Avidin Affinity with Controlled Release.

The development of artificial receptors that combine ultrahigh-affinity binding and controllable release for active guests holds significant importance in biomedical applications. On one hand, a complex with an exceedingly high binding affinity can resist unwanted dissociation induced by dilution effect and complex interferents within physiological environments. On the other hand, stimulus-responsive release of the guest is essential for precisely activating its function. In this context, we expanded hydrophobic cavity surface of a hypoxia-responsive azocalix[4]arene, affording Naph-SAC4A. This modification significantly enhanced its aqueous binding affinity to 1013 M-1, akin to the naturally occurring strongest recognition pair, biotin/(strept-)avidin. Consequently, Naph-SAC4A emerges as the first artificial receptor to simultaneously integrate ultrahigh recognition affinity and actively controllable release. The markedly enhanced affinity not only improved Naph-SAC4A's sensitivity in detecting rocuronium bromide in serum, but also refined the precision of hypoxia-responsive doxorubicin delivery at the cellular level, demonstrating its immense potential for diverse practical applications.

Enantiopure Corral[4]BINOLs as Ultrastrong Receptors for Recognition and Differential Sensing of Steroids.

The precise recognition and sensing of steroids, a type of vital biomolecules, hold immense practical value across various domains. In this study, we introduced corral[4]BINOLs (C[4]BINOLs), a pair of enantiomeric conjugated deep-cavity hosts, as novel synthetic receptors for binding steroids. Due to the strong hydrophobic effect of their deep nonpolar, chiral cavities, the two enantiomers of C[4]BINOLs demonstrated exceptionally high recognition affinities (up to 1012 M-1) for 16 important steroidal compounds as well as good enantioselectiviy (up to 15.5) in aqueous solutions, establishing them as the most potent known steroid receptors. Harnessing their ultrahigh affinity, remarkable enantioselectivity, and fluorescence emission properties, the two C[4]BINOL enantiomers were employed to compose a fluorescent sensor array which achieved discrimination and sensing of 16 structurally similar steroids at low concentrations.

A Chiral Emissive Conjugated Corral for High-Affinity and Highly Enantioselective Recognition in Water.

Accurately distinguishing between enantiomeric molecules is a fundamental challenge in the field of chemistry. However, there is still significant room for improvement in both the enantiomeric selectivity (KR(S) /KS(R) ) and binding strength of most reported macrocyclic chiral receptors to meet the demands of practical application scenarios. Herein, we synthesized a water-soluble conjugated tubular host-namely, corral[4]BINOL-using a chiral 1,1'-bi-2-naphthol (BINOL) derivative as the repeating unit. The conjugated chiral backbone endows corral[4]BINOL with good fluorescent emission (QY=34 % ) and circularly polarized luminescence (|glum | up to 1.4×10-3 ) in water. Notably, corral[4]BINOL exhibits high recognition affinity up to 8.6×1010  M-1 towards achiral guests in water, and manifested excellent enantioselectivity up to 18.7 towards chiral substrates, both of which represent the highest values observed among chiral macrocycles in aqueous solution. The ultrastrong binding strength, outstanding enantioselectivity, and facile accessibility, together with the superior fluorescent and chiroptical properties, endow corral[4]BINOL with great potential for a wide range of applications.

Qingjie decoction attenuated E.coli-induced diarrhea by regulating energy metabolism and alleviating inflammation based on network analysis and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Diarrhea is a frequently encountered gastrointestinal complication in clinical practice, and E. coli is one of the main causative agents. Although Qingjie decoction (QJD) has been shown to be highly effective in treating diarrhea by eliminating heat-toxin, the underlying molecular mechanisms and pathways of QJD remain unclear. AIM OF REVIEW: The aim of this research was to explore the effects and fundamental mechanism of QJD on diarrhea induced by E.coli in rats. MATERIALS AND METHODS: Initially, we used UHPLC-MS/MS analysis to identify the chemical composition of QJD. Then, we constructed a visualization network using network pharmacology. Next, we utilized metabolomics to identify differentially expressed metabolites of QJD that are effective in treating diarrhea. RESULTS: The chemical composition of QJD was analyzed using UHPLC-MS/MS, which identified a total of 292 components. Using a network pharmacology approach, 127 bioactive compounds of QJD were screened, targeting 171 potential diarrhea treatment targets. TNF-α, IL-6, IL-1ß, and CAT were identified as important targets through visualizing the PPI network. Enrichment analysis demonstrated significant enrichment in the TNF signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. QJD showed beneficial effects, such as increased body weight, decreased fecal water content, and reduced inflammatory cell infiltration in the duodenum and colon, as well as maintaining the structure of the duodenum and colon. Metabolomic analysis revealed 32 differentially expressed metabolites in the control, model and QJD-H groups, including glucose, valine, and cysteine. Functional analysis indicated that differential metabolites were related to energy metabolism, including glucose metabolism, TCA cycle, and amino acid metabolism. CONCLUSION: QJD significantly increased body weight, decreased water content in feces, relieved inflammatory cell infiltration, maintained the structure of duodenum and colon. Combining network analysis and metabolomics, QJD exerted therapeutic effects by inhibiting inflammation and oxidative stress, regulating glucose metabolism, tricarboxylic acid metabolism, and amino acid metabolism.

Edible plant extracellular vesicles: An emerging tool for bioactives delivery.

The extracellular vesicles (EVs) in edible food have a typical saucer-like structure and are nanoparticles released by numerous cells. They have different components and interact with other biological samples in diverse ways. Therefore, these nanoparticles could be used to develop bioactives delivery nanoplatforms and anti-inflammatory treatments to meet the stringent demands of current clinical challenges. This review aims to summarize current researches into EVs from edible plants, particularly those that can protect siRNAs or facilitate drug transportation. We will discuss their isolation, characterization and functions, their regulatory effects under various physiological and pathological conditions, and their immune regulation, anti-tumor, regeneration, and anti-inflammatory effects. We also review advances in their potential application as bioactives carriers, and medicinal and edible plants that change their EVs compositions during disease to achieve a therapy propose. It is expected that future research on plant-derived EVs will considerably expand their application.

[Protective effect of polyenylphosphatidyl choline on liver in rat with sepsis].

OBJECTIVE: To investigate the protective effect of polyenylphosphatidyl choline (PPC) on liver in rat with sepsis. METHODS: A total of 50 healthy male SD rats were randomly divided into four groups according to random number table: normal control group (NS group, n=10), sepsis model group (LPS group, n=15), PPC control group (PPC group, n=10) and PPC protection group (P+L group, n=15). A single dose of lipopolysaccharide (LPS) 6 mg/kg was injected to the peritoneal cavity to reproduce the sepsis model, while in NS group and PPC group, same volume of normal saline was used. PPC 10 ml/kg (232.5 mg/kg) was injected 24 hours and 6 hours before LPS via the tail vein in PPC group and P+L group, while in NS group and LPS group 5% glucose solution in the same volume was given. Behavioral changes and mortality rate of rats were recorded, and all survived rats were sacrificed 24 hours after LPS injection. Venous blood was taken for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) determination. Ratios of liver weight/body weight (L/Wb) and wet weight/dry weight of liver (W/D) were calculated. Histopathology changes in liver tissue were observed with hematoxylin eosin (HE) stain, and intercellular adhesion molecule-1 (ICAM-1) expression with instant two-step immunohistochemistry. RESULTS: Twenty-four hours after LPS injection (LPS group), the rats became lethargic, with less activity and drinking, while rats in P+L group, showed much better mental status, water intake and activity than LPS group. The mortality rate of P+L group was significantly lower than that of LPS group [6.7% (1/15) vs. 46.7% (7/15),P<0.05]. Compared with LPS group, rats in P+L group had lower levels of plasma ALT and AST, L/Wb, W/D , and liver ICAM-1 positive expression ratio [ALT (U/L): 157.71 ± 32.63 vs. 225.63 ± 43.47; AST (U/L): 53.21 ± 13.85 vs. 85.25 ± 18.91; L/Wb: (4.09 ± 0.28)% vs. (4.50 ± 0.25)%; W/D : 3.52 ± 0.27 vs. 3.84 ± 0.18; ICAM-1 positive expression ratio: 35.7% (5/14) vs. 87.5 (7/8),P<0.05 or P <0.01]. All parameters were normal in NS group and PPC group, and no statistical significance was observed between them (all P >0.05). LPS-injection led to severe inflammatory reaction in hepatic tissue , including obvious edema of hepatic parenchymal cells, exudation and aggregation of inflammatory cells, while in P+L group, these morphological changes were milder than that in LPS group but more obvious than that of NS group. CONCLUSION: Pre-treatment of rats with PPC alleviates progressive inflammatory disturbances of hepatic tissue caused by endotoxin injection, and it attenuates liver edema and ICAM-1 expression, protects liver function and decreases mortality rate in rats with sepsis.

Comparison of 99mTc-DTPA and serum creatinine, cystatin C in detection of glomerular filtration rate: a retrospective clinical data analysis of 744 Chinese subjects.

BACKGROUND: To compare the accuracy of various equations for estimating glomerular filtration rate. METHODS: Chronic kidney disease was classified by Tc-DTPA scintigraphy (reference glomerular filtration rate), estimating glomerular filtration rate was estimated using various formulas. The similarity to reference glomerular filtration rate decide the accuracy of estimating glomerular filtration rate. RESULTS: Overall, the Fengscr-cys equation had significantly higher accuracy and correct proportion in chronic kidney disease stage classification than other equations. The subgroup analysis showed that Fengscr-cys equation was slightly more precise than other equations both in the male and female patients. Moreover, in patients older than 60 years or whose reference glomerular filtration rate was above 60 ml/min, Fengscr-cys equation also showed better accuracy. CONCLUSION: Our data suggest that estimating glomerular filtration rate equations evaluated by serum cystatin C were better than serum creatinine-based equations, estimating glomerular filtration rate equations evaluated by both serum creatinine and cystatin C were better than those evaluated by serum creatinine or cystatin C alone. Among all enrolled equations, Fengscr-cys equation might be the best one to evaluate glomerular filtration rate in general Chinese paticipants.

Perioperative comprehensive supportive care interventions for chinese patients with esophageal carcinoma: a prospective study.

OBJECTIVE: To assess the effects of perioperative comprehensive supportive care interventions on outcome of Chinese esophageal cancer patients in a prospective study. METHODS: 60 patients with primary esophageal carcinoma were randomized into an intervention group (IG, n=31) and a control group (CG, n=29). The Chinese version of symptom checklist-90 (SCL-90) was adopted to assess their psychological status. The interventions, including health education, psychological support, stress management, coping strategies and behavior training, were carried out in 3 phases (preoperative, postoperative I and postoperative II), and psychological effects were thereafter evaluated accordingly before surgery, and 1 week, 4 weeks and 24 weeks post-surgery. Medical costs were estimated at discharge. Survival of patients was estimated each year post-surgery. General health status and satisfaction-with-hospital were surveyed by a follow-up questionnaire 4 years post-surgery. RESULTS: All the subjects demonstrated higher scores in the preoperative phase than the normal range of Chinese population concerning 7 psychological domains including somatization, obsessive-compulsive, depression, anxiety, hostility, phobic anxiety and paranoid ideation. Although no significant difference was observed between the two groups at admission, the scores of IG, which tended to decrease at a faster rate, were generally lower than those of CG at weeks 1, 4 and 24 post-surgery. The length of hospital stay and medical costs of IG were significantly less than those of CG and satisfaction-with-hospital was better. However, there was no significant difference in 4-year survival or health status between two groups. CONCLUSIONS: Appropriate perioperative comprehensive supportive care interventions help to improve the psychological state of Chinese patients with esophageal carcinoma, to reduce health care costs and to promote satisfaction of patients and their families with hospital.

[The protective effect of Xuebijing injection pretreatment on hepatic ischemia reperfusion injury and coagulopathy after excision of liver cancer].

OBJECTIVE: To observe the protective effect of Xuebijing injection pretreatment on hepatic ischemia reperfusion (I/R) injury and coagulopathy in liver cancer patients undergoing excision of hepatic cancer after occlusion of hepatic blood flow. METHODS: A prospective randomly controlled study was conducted. Sixty patients with liver cancer classified as Child-Pugh class A undergoing hepatectomy in the Department of Hepatobiliary Surgery of Sun Yat-sen University Cancer Center from October 2011 to March 2013 were enrolled. The patients were randomized into control group and Xuebijing group (each patient received 100 mL Xuebijing injection added to 0.9% saline as a preoperative treatment for 3 days). Complete blood count, coagulation function, hepatic function, serum pro-inflammatory cytokines and alpha-fetoprotein (AFP) levels were determined before and after operation. RESULTS: Forty-five out of 60 patients were enrolled eventually, with 23 patients in control group and 22 in Xuebijing group, and among them 43 patients were positive for hepatitis B surface antigen (HBsAg) at admission. Compared with those before operation, the postoperative levels of alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) in control and Xuebijing groups were significantly elevated, prothrombin time (PT) and activated partial prothrombin time (AfYIT) were significantly prolonged, and white blood cells (WBC) , proportion of neutrophils (N) and C-reactive protein (CRP) were significantly increased (P<0.05 or P<0.01 ). Although the above indexes in Xuebijing group after operation were lower than those in control group in different degrees [ALT (U/L): 213.1 (80.4-796.6) vs. 265.8 (15.6-882.3), AST (UIL): 194.1 (65.4-914.2) vs. 264.3 (15.4-475.9), LDH (lg,U/L): 5.69 ± 0.72 vs. 5.71 ± 0.72, PT (s): 15.24 ± 2.16 vs. 14.41 ± 1.33, AfYIT (s): 31.51 ± 7.04 vs. 29.47 ± 4.90, WBC (x 109/L) : 13.4 7 ± 4.66 vs. 14.58 ± 4.40, N: 0.87 ± 0.06 vs. 0.87 ± 0.04, CRP (mg/L): 40.64 (16.93-189.59) vs. 45.64 ( 1.65-349.40) J, no statistical significance was found between the groups (all P>0.05 ). The preoperative levels of tumor necrosis factor-a (TNF -a) and interleukin-6 OL-6) were both less than 1.0 ng/L, and the postoperative levels of TNF-a showed no significant change, and IL-6 was increased to 485.10 (104.00-837.50) ng/L and 193.26 (95.10-385.20) ng/L in control and Xuebijing groups respectively (P<0.01). The serum high mobility group box-1 ( HMGB1 ) protein levels after operation were higher than those of preoperative in both groups (both P<0.01), but the postoperative HMGB1 in Xuebijing group were significantly lower than those in control group (j.Lg/L: 268.73 ± 5.56 vs. 277.12 ± 2.92, P<0.01). Acute physiology and chronic health evaluation ll (APACHE ll) score in Xuebijing group was significantly lower than that in control group (4.18 ± 3.75 vs. 4.53 ± 2.34, t=5.328, P=0.027), and the first passage of flatus and defecation after operation in Xuebijing group were significantly earlier than those in control group [exhaust time (days): 3 (2-4) vs. 3 (2-4), U=-2.023, P=0.043; defecation time (days): 4 (2-6) vs. 5 (3-8), U =-2.926, P=0.003 J. However, no difference was found between two groups in the postoperative and total hospital days. Spearman rank correlation analysis showed there were positive correlations between hepatitis B virus (HBV)-DNA levels and preoperative ALT (r=0.414, P=0.044) and AST (r=0.405, P=0.024) in 33 HBV-DNA positive patients, but there was no significant correlation between HBV -DNA levels or other preoperative liver function indicators. CONCLUSIONS: Hepatic I/R injury and coagulopathy may occur in liver cancer patients undergoing resection of cancer with occlusion of hepatic blood flow. Xuebijing injection may inhibit the release of serum pro-inflammatory cytokines, thereby alleviate hepatic I/R injury and promote the recovery of intestinal function. But it does not offer protective effect on coagulopathy.

[The discordant results in serum through reverse syphilis screening algorithm].

OBJECTIVE: The emerging reverse sequence on syphilis screening program generates special discordant results, characterized with the appearance of both positive treponemal test and negative nontreponemal test at the same time. The aim of this study was to analyze the characteristics of the discordant results among low syphilis prevalence population in China, to provide evidence for improving the process of reverse sequence syphilis screening program. METHODS: Laboratory data was retrospectively analyzed, under reverse sequence screening algorithm selecting ELISA as the initial screening test for syphilis. All the screening reactive samples were tested by TPPA for confirmation and by quantitative TRUST for the reactivity of syphilis. RESULTS: 666 out of a total of 21 049 serum samples were reactive under the screening program. Among the 666 reactive samples, 169 were reactive to TRUST. One in the 169 samples was confirmed negative on TPPA, and the faulse positive rate on ELISA was 0.6% (1/169). In those 666 reactive samples, 497 were nonreactive to TRUST. 74 in the 497 samples were confirmed negative to TPPA, with faulse positive rate of ELISA as 14.9% (74/497). In the group of 591 TPPA confirmed positive samples, the TRUST negative rate was found 71.6% (423/591), significantly higher than the TRUST positive rate(chi-square test, χ(2) = 110.025, P = 0.000). CONCLUSION: Among the results from reverse sequence syphilis screening program, majority of the samples which showed positive treponemal antibody, would have negative nontreponemal antibody. We therefore recommended a more reasonable reverse sequence syphilis algorithm to be used. Faulse positivity could be eliminated if TPPA was performed on all screening reactive samples by ELISA a first and then followed by quantitative TRUST on samples that were TPPA confirmed as positive.

[Distribution and drug resistance of pathogenic bacteria strains in nosocomial infection in Sun Yat-sen University Cancer Center from 2006 to 2007].

BACKGROUND AND OBJECTIVE: Tumor patients have an increased risk of nosocomial infection due to hypoimmunity. Infection may affect antitumor therapies and even lead to death. This study aimed to investigate the susceptible factors, the distribution and drug resistance of the pathogens from tumor patients who suffered from nosocomial infection. METHODS: Clinical records of 952 infected patients in Cancer Center of Sun Yat-sen University during 2006-2007 were reviewed. The infection rate, pathogen spectum and drug resistance of nosocomial infection were analyzed with EXCEL8.0 and SPSS10.0 software. RESULTS: Among the 952 patients, pathogens were detected in 794 patients, with a rate of 83.4%. Of the 794 patients, 321 (40.4%) had gram-negative bacilli (GNB) infection (mainly caused by Escherichia coli), 265 (33.4%) had fungi infection (mainly caused by Candida albicans), and 208 (26.2%) had gram-positive cocci (GPC) infection (mainly caused by staphylococcus and streptococcus species). According to drug sensitivity and resistance test, GNB were sensitive to imipenem and amikacin, but strongly resistant to ampicillin with a rate of >90%; GPC were sensitive to vancomycin, but highly resistant against ampicillin; the fungi were sensitive to amphotericin B, voriconazole and flucytosine, but less sensitive to fluconazol. CONCLUSIONS: GNB comprises the majority of pathogens separated from the hospitalized tumor patients in Cancer Center of Sun Yat-sen University from 2006 to 2007. Rational use of antibiotics based on drug sensitivity test could reduce fungi infection and drug resistance, therefore, help to prevent and control nosocomial infection effectively.

[Perioperative changes of coagulation functions in the local advanced liver cancer patients receiving liver transplantation].

BACKGROUND & OBJECTIVE: Liver transplantation is widely accepted as an effective therapy of hepatoma. Perioperative dynamic observation of coagulation function is important for graft-receivers. This study was to explore perioperative changes of coagulation functions in the local advanced liver cancer patients who received liver transplantation. METHODS: Clinical data of 31 local advanced liver cancer patients, underwent liver transplantation from Sep. 2003 to Jan. 2007, were analyzed. Platelet (PLT) counting, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib) and international normalized ratio (INR) before operation, at anhepatic phase and the first week after operation were analyzed to evaluate congulation function. RESULTS: The coagulation functions of most patients were normal before operation. The six parameters varied significantly at anhepatic phase and on most days of the first week after operation when compared with the preoperative levels (P<0.05). The elevation of PT, APTT, TT and INR and the decrease of Fib and PLT were more apparent at anhepatic phase when compared with the preoperative levels [PT: (19.51+/-3.78) s vs. (14.16+/-1.46) sû APTT: (77.01+/-30.51) s vs. (40.19+/-4.11) sû TT: (27.50+/-15.10) s vs. (19.46+/-3.05) sû INR: 1.61+/-0.37 vs. 1.11+/-0.16û Fib: (1.73+/-0.70) g/L vs. (3.38+/-1.00) g/Lû PLT: (108+/-60)x10(9)/L vs. (184+/-108)x10(9)/L, all P<0.01]. In the first week after operation, the elevated PT, APTT, TT and INR levels decreased gradually, APTT was even lower than the preoperative level [(32.05+/-6.50) s vs. (40.19+/-4.11) s, P<0.01]. These changes appeared usually on 1-2 days after operation. Decreased PLT and Fib regained slowly at the first week after operation when compared with the preoperative levels [Fib: (2.13+/-0.53) g/L vs. (3.38+/-1.00) g/L, P<0.01û PLT: (145+/-90)x10(9)/L vs. 184+/-108]x10(9)/L, P<0.05], but the values were normal. According to stratification analysis, the hypocoagulability was more obvious in the patients with moderate or severe cirrhosis and those with Child-Pugh B level than in their counterparts. CONCLUSIONS: The coagulation functions of local advanced liver cancer patients shift from hypocoagulatory to hypercoagulatory or normal in perioperative period, therefore, prevention of bleeding should be focused on at anhepatic phase and on 1-2 days after operation while prevention of thrombosis should be focused on after the first week after operation. The degree of liver cirrhosis and Child-Pugh level could help to evaluate postoperative coagulation disorder.