Structurally Diverse Macrolactams from an Antarctic Streptomyces Species.

Twelve new polyenic macrolactams, cyclamenols G-R (1 and 3-13), together with the known analogue cyclamenol A (2), were isolated from Streptomyces sp. OUCMDZ-4348. Their structures were elucidated by spectroscopic analysis, quantum chemical calculations, chemical derivatizations, and Mosher's methods. The sequenced genome of OUCMDZ-4348 revealed the putative biosynthetic gene cluster of cyclamenols. It was proposed that the polycyclic natural products, cyclamenols H-R, might be formed from cyclamenols A and G through nonenzymatic intramolecular cycloadditions and oxidative cyclizations.

Inhalable nanocatchers for SARS-CoV-2 inhibition.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.

Characterization of an α-L-fucosidase in marine bacterium Wenyingzhuangia fucanilytica: new evidence on the catalytic sites of GH95 family glycosidases.

BACKGROUND: α-l-Fucose confers unique functions for fucose-containing biomolecules such as human milk oligosaccharides. α-l-Fucosidases can serve as desirable tools in the application of fucosylated saccharides. Discovering novel α-l-fucosidases and elucidating their enzyme properties are always worthy tasks. RESULTS: A GH95 family α-l-fucosidase named Afc95A_Wf was cloned from the genome of the marine bacterium Wenyingzhuangia fucanilytica and expressed in Escherichia coli. It exhibited maximum activity at 40 °C and pH 7.5. Afc95A_Wf defined a different substrate specificity among reported α-l-fucosidases, which was capable of hydrolyzing α-fucoside in CNP-fucose, Fucα1-2Galß1-4Glc and Galß1-4(Fucα1-3)Glc, and showed a preference for α1,2-fucosidic linkage. It adopted Asp residue in the amino acid sequence at position 391, which was distinct from the previously acknowledged residue of Asn. The predicted tertiary structure and site-directed mutagenesis revealed that Asp391 participates in the catalysis of Afc95A_Wf. The differences in the substrate specificity and catalytic site shed light on that Afc95A_Wf adopted a novel mechanism in catalysis. CONCLUSION: A GH95 family α-l-fucosidase (Afc95A_Wf) was cloned and expressed. It showed a cleavage preference for α1,2-fucosidic linkage to α1,3-fucosidic linkage. Afc95A_Wf demonstrated a different substrate specificity and a residue at an important catalytic site compared with known GH95 family proteins, which revealed the occurrence of diversity on catalytic mechanisms in the GH95 family. © 2024 Society of Chemical Industry.

A repertoire of alginate lyases in the alginate polysaccharide utilization loci of marine bacterium Wenyingzhuangia fucanilytica: biochemical properties and action pattern.

BACKGROUND: Alginate lyases are important tools for alginate biodegradation and oligosaccharide production, which have great potential in food and biofuel fields. The alginate polysaccharide utilization loci (PUL) typically encode a series of alginate lyases with a synergistic action pattern. Exploring valuable alginate lyases and revealing the synergistic effect of enzymes in the PUL is of great significance. RESULTS: An alginate PUL was discovered from the marine bacterium Wenyingzhuangia fucanilytica CZ1127T , and a repertoire of alginate lyases within it was cloned, expressed and characterized. The four alginate lyases in PUL demonstrated similar optimal reaction conditions: maximum enzyme activity at 35-50 °C and pH 8.0-9.0. The results of action pattern indicated that they were two PL7 endolytic bifunctional enzymes (Aly7A and Aly7B), a PL6 exolytic bifunctional enzyme (Aly6A) and a PL17 exolytic M-specific enzyme (Aly17A). Ultra-performance liquid chromatography-mass spectrometry was employed to reveal the synergistic effect of the four enzymes. The end products of Aly7A were further degraded by Aly7B and eventually generated oligosaccharides, from disaccharide to heptasaccharide. The oligosaccharide products were completely degraded to monosaccharides by Aly6A, but it was unable to directly degrade alginate. Aly17A could also produce monosaccharides by cleaving the M-blocks of oligosaccharide products, as well as the M-blocks of polysaccharides. The combination of these enzymes resulted in the complete degradation of alginate to monosaccharides. CONCLUSION: A new alginate PUL was mined and four novel alginate lyases in the PUL were expressed and characterized. The four cooperative alginate lyases provide novel tools for alginate degradation and biological fermentation. © 2023 Society of Chemical Industry.

Discovery and characterization of a novel carbohydrate-binding module: a favorable tool for investigating agarose.

BACKGROUND: Agarose, mainly composed of 3,6-anhydro-α-l-galactopyranose (LA) and ß-d-galactopyranose (G) units, is an important polysaccharide with wide applications in food, biomedical and bioengineering industries. Carbohydrate-binding modules (CBMs) are favorable tools for the investigations of polysaccharides. Few agarose-binding CBMs have been hitherto reported, and their binding specificity is unclear. RESULTS: An unknown domain with a predicted ß-sandwich fold was discovered from a ß-agarase of the marine bacterium Wenyingzhuangia fucanilytica CZ1127T . The expressed protein WfCBM101 could bind to agarose and exhibited relatively weak affinity for porphyran, with no affinity for the other seven examined polysaccharides. The protein binds to the tetrasaccharide (LA-G)2 , but not to the major tetrasaccharide contained in porphyran. The sequence novelty and well-defined binding function of WfCBM101 shed light on a novel CBM family (CBM101). Furthermore, the feasibility of WfCBM101 for visualizing agarose in situ was confirmed. CONCLUSION: A novel CBM, WfCBM101, with a desired specificity for agarose was discovered and characterized, which represents a new CBM family. The CBM could be utilized as a promising tool for studies of agarose. © 2023 Society of Chemical Industry.

Inhaled Lipid Nanoparticles Alleviate Established Pulmonary Fibrosis.

Pulmonary fibrosis, a sequela of lung injury resulting from severe infection such as severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) infection, is a kind of life-threatening lung disease with limited therapeutic options. Herein, inhalable liposomes encapsulating metformin, a first-line antidiabetic drug that has been reported to effectively reverse pulmonary fibrosis by modulating multiple metabolic pathways, and nintedanib, a well-known antifibrotic drug that has been widely used in the clinic, are developed for pulmonary fibrosis treatment. The composition of liposomes made of neutral, cationic or anionic lipids, and poly(ethylene glycol) (PEG) is optimized by evaluating their retention in the lung after inhalation. Neutral liposomes with suitable PEG shielding are found to be ideal delivery carriers for metformin and nintedanib with significantly prolonged retention in the lung. Moreover, repeated noninvasive aerosol inhalation delivery of metformin and nintedanib loaded liposomes can effectively diminish the development of fibrosis and improve pulmonary function in bleomycin-induced pulmonary fibrosis by promoting myofibroblast deactivation and apoptosis, inhibiting transforming growth factor 1 (TGFß1) action, suppressing collagen formation, and inducing lipogenic differentiation. Therefore, this work presents a versatile platform with promising clinical translation potential for the noninvasive inhalation delivery of drugs for respiratory disease treatment.

Application of organic nanocarriers for intraocular drug delivery. / ç”¨äºŽçœ¼å† è¯ç‰©é€’é€çš„æœ‰æœºçº³ç±³è½½ä½“ç ”ç©¶.

The application of intraocular drug delivery is usually limited due to special anatomical and physiological barriers, and the elimination mechanisms in the eye. Organic nano-drug delivery carriers exhibit excellent adhesion, permeability, targeted modification and controlled release abilities to overcome the obstacles and improve the efficiency of drug delivery and bioavailability. Solid lipid nanoparticles can entrap the active components in the lipid structure to improve the stability of drugs and reduce the production cost. Liposomes can transport hydrophobic or hydrophilic molecules, including small molecules, proteins and nucleic acids. Compared with linear macromolecules, dendrimers have a regular structure and well-defined molecular mass and size, which can precisely control the molecular shape and functional groups. Degradable polymer materials endow nano-delivery systems a variety of size, potential, morphology and other characteristics, which enable controlled release of drugs and are easy to modify with a variety of ligands and functional molecules. Organic biomimetic nanocarriers are highly optimized through evolution of natural particles, showing better biocompatibility and lower toxicity. In this article, we summarize the advantages of organic nanocarriers in overcoming multiple barriers and improving the bioavailability of drugs, and highlight the latest research progresses on the application of organic nanocarriers for treatment of ocular diseases.

Methylene-bridged dimeric natural products involving one-carbon unit in biosynthesis.

Covering: up to February 2022Naturally occurring dimeric molecules attract considerable attention from both chemists and biologists. The methylene-bridged dimers with one-carbon (C1) unit in biosynthesis, which are a small class of structurally diverse natural products, are found in plants, microorganisms, and marine bryozoan. Some individual dimers showed more significant biological activities than the corresponding monomers. Focusing on these dimers with a methylene linker, we here reviewed associated progress in the isolation, biological activity, chemical synthesis, and the proposed dimerization mechanism. The structural characteristics of the monomeric substrates are summarized, which indicated that most of these dimers might be formed through nonenzymatic dimerization involving a strong electrophilic C1 unit such as formaldehyde. This kind of dimerization is an effective synthetic strategy for the discovery of new biologically active compounds.

Microfluidic Production of Zwitterion Coating Microcapsules with Low Foreign Body Reactions for Improved Islet Transplantation.

Islet transplantation is a promising strategy for type 1 diabetes mellitus (T1DM) treatment, whereas implanted-associated foreign body reaction (FBR) usually induces the necrosis of transplanted islets and leads to the failure of glycemic control. Benefiting from the excellent anti-biofouling property of zwitterionic materials and their successful application in macroscopic implanted devices, microcapsules with zwitterionic coatings may be promising candidates for islet encapsulation. Herein, a series of zwitterion-coated core-shell microcapsules is fabricated (including carboxybetaine methacrylate [CBMA]-coated gelatin methacrylate [GelMA] [CBMA-GelMA], sulfobetaine methacrylate [SBMA]-coated GelMA [SBMA-GelMA], and phosphorylcholine methacrylate [MPC]-coated GelMA [MPC-GelMA]) by one-step photopolymerization of inner GelMA and outer zwitterionic monomers via a handmade two-fluid microfluidic device and it is demonstrated that they can effectively prevent protein adsorption, cell adhesion, and inflammation in vitro. Interestingly, the zwitterionic microcapsules successfully resist FBR in C57BL/6 mice after intraperitoneal implantation for up to 4 months. After successfully encapsulating xenogeneic rat islets in the SBMA-GelMA microcapsules, sustained normoglycemia is further validated in streptozotocin (STZ)-induced mice for up to 3 months. The zwitterion-modified microcapsule using a microfluidic device may represent a platform for cell encapsulation treatment for T1DM and other hormone-deficient diseases.

Tetrahedral DNA-directed core-satellite assembly as SERS sensor for mercury ions at the single-particle level.

To monitor the deteriorating mercury emissions, it is imperative to propose methods for detecting mercury ions (Hg2+) with sensitivity and selectivity. The SERS spectral-resolved single-particle detection approach can be carried out using dark-field optical microscopy (DFM) combined with Raman spectroscopy. Herein, we have designed a novel yet convenient single-particle detection assay for quantifying Hg2+ using DFM-correlated Raman spectroscopy. In the assay, a tetrahedral DNA-directed core-satellite nanostructure is used as the SERS probe. Especially, one edge of the tetrahedron is made up of a single-stranded DNA containing a Hg2+ aptamer, which reconfigures upon the specific recognition of Hg2+. As a result, the interparticle distance reduces from 4.5 to 1.2 nm, thus generating Raman signal enhancement. As a proof of concept, Hg2+ was detected in a linear range from 1 to 100 nM based on the variation in SERS intensity. Furthermore, the experimental results were supported by the finite difference time domain (FDTD) calculations. Owing to its high sensitivity and selectivity, this method was further employed to detect Hg2+ in practical tap water and lake water samples, revealing that the single-particle detection strategy holds great promise for Hg2+ analysis in real environment analysis.

Increased long non-coding RNA NORAD reflects serious cardiovascular stenosis, aggravated inflammation status, and higher lipid level in coronary heart disease.

OBJECTIVE: Long non-coding RNA activated by DNA damage (lnc-NORAD) modulates inflammation, lipid level, and atherosclerosis in various cardiovascular diseases. This study intended to investigate the dysregulated expression of lnc-NORAD, and its linkage with clinical characteristics, inflammatory cytokines, and accumulating major adverse cardiovascular events (MACE) in coronary heart disease (CHD) patients. METHODS: Totally, 160 CHD patients, 30 disease controls (DCs), and 30 healthy controls (HCs) were included. The reverse transcription-quantitative polymerase chain reaction was used to detect lnc-NORAD expression in peripheral blood mononuclear cell samples from all participants. Enzyme-linked immunosorbent assay was applied to detect proinflammatory cytokines and adhesion molecules in CHD patients. Then, MACE was recorded during a median follow-up of 12 (range: 1.0-27.0) months. RESULTS: Lnc-NORAD was highest in CHD patients, followed by DCs, and lowest in HCs (p < 0.001). In CHD patients, lnc-NORAD was positively linked with Gensini score (p = 0.001). Meanwhile, lnc-NORAD was positively linked to C-reactive protein (p = 0.023), tumor necrosis factor-alpha (p = 0.016), interleukin (IL)-6 (p = 0.003), IL-8 (P = 0.018), and IL-17A (p = 0.029). No relation of lnc-NORAD with vascular cell adhesion molecule-1 (p = 0.094) and intercellular adhesion molecule-1 (p = 0.060) was found. Furthermore, lnc-NORAD was positively related to total cholesterol (p = 0.014) and low-density lipoprotein cholesterol (p = 0.004), whereas lnc-NORAD was not linked to triglyceride (p = 0.103) and high-density lipoprotein cholesterol (p = 0.533). However, lnc-NORAD (high vs. low), and its higher quartiles were both not linked to accumulating MACE rate (p > 0.05). CONCLUSION: Increased lnc-NORAD is linked with aggravated stenosis degree, inflammation status, and blood lipid in CHD patients. However, further validation is required.

Body mass index and pharmacodynamics of target-controlled infusion of propofol: A prospective non-randomized controlled study.

WHAT IS KNOWN AND OBJECTIVE: In our preliminary study, there were large individual variations at sedation levels during propofol target-controlled infusion (TCI). The present study aimed to assess the effects of body mass index (BMI) on the pharmacodynamic index of propofol TCI. METHODS: This prospective, non-randomized controlled trial evaluated 175 female patients undergoing breast lumpectomy. Anesthesia was induced with propofol using the TCI system embedded Schnider model. The effect compartment concentration was set to 3 µg/ml, and the start time of infusion was recorded. When the target concentration reached 3 µg/ml, the patient could not be awakened (Ramsay sedation score ≥4), and when the Bispectral Index (BIS) was <60, the infusion was discontinued, and the time point was recorded. The observation end-point was set at the Observer's Assessment of Alertness/Sedation (OAA/S) score of <4. The correlation between the BMI and the pharmacodynamic index of propofol was evaluated. RESULTS AND DISCUSSION: Propofol induction time was significantly correlated with the BMI (p < 0.001). The induction time of the underweight subjects was 10.14 ± 2.19 min, which was remarkably higher than that of normal weight (6.48 ± 3.44 min) and overweight (4.75 ± 2.53 min) individuals (p < 0.001). There were still significant differences after multivariable-adjusted regressions (p < 0.001). There were no significant differences in recovery time and sedative effect indicators, such as Ramsay score, BIS value, and effect compartment concentration, between the three groups (p > 0.05 for all). WHAT IS NEW AND CONCLUSION: These results suggest that the BMI is one of the critical factors affecting the pharmacodynamic index of propofol TCI, and the induction time decreased progressively with increasing BMI. The Schnider model might underpredict doses of propofol for underweight individuals.

Inhibition of the PERK/TXNIP/NLRP3 Axis by Baicalin Reduces NLRP3 Inflammasome-Mediated Pyroptosis in Macrophages Infected with Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) remains a significant threat to global health as it induces granuloma and systemic inflammatory responses during active tuberculosis. Mtb can induce macrophage pyroptosis, leading to the release of IL-1ß and tissue damage, promoting its spread. Here, we established an in vitro Mtb-infected macrophage model to seek an effective antipyroptosis agent. Baicalin, isolated from Radix Scutellariae, was found to reduce pyroptosis in Mtb-infected macrophages. Baicalin could inhibit activation of the PERK/eIF2α pathway and thus downregulates TXNIP expression and subsequently reduces activation of the NLRP3 inflammasome, resulting in reduced pyroptosis in Mtb-infected macrophages. In conclusion, baicalin reduced pyroptosis by inhibiting the PERK/TXNIP/NLRP3 axis and might thus be a new adjuvant host-directed therapy (HDT) drug.

Injectable Anti-inflammatory Nanofiber Hydrogel to Achieve Systemic Immunotherapy Post Local Administration.

Despite the great promise achieved by immune checkpoint blockade (ICB) therapy in harnessing the immune system to combat different tumors, limitations such as low objective response rates and adverse effects remain to be resolved. Here, an anti-inflammatory nanofiber hydrogel self-assembled by steroid drugs is developed for local delivery of antiprogrammed cell death protein ligand 1 (αPDL1). Interestingly, on the one hand this carrier-free system based on steroid drugs can reprogram the pro-tumoral immunosuppressive tumor microenvironment (TME) to antitumoral TME; on the other hand, it would serve as a reservoir for sustained release of αPDL1 so as to synergistically boost the immune system. By local injection of such αPDL1-loaded hydrogel, effective therapeutic effects were observed in inhibiting both local tumors and abscopal tumors without any treatment. This work presents a unique hydrogel-based delivery system using clinically approved drugs, showing promise in improving the objective response rate of ICB therapy and minimizing its systemic toxicity.

Bioresponsive Protein Complex of aPD1 and aCD47 Antibodies for Enhanced Immunotherapy.

Despite the promising efficacy of immune checkpoint blockade (ICB) in treating many types of cancers, the clinical benefits have often been restricted by the low objective response rates and systemic immune-related adverse events. Here, a bioresponsive ICB treatment is developed based on the reactive oxygen species (ROS)-sensitive protein complex for controlled sequential release of anti- "don't eat me" signal antibody (aCD47) and antiprogrammed cell death protein 1 (aPD1), by leveraging the abundant ROS in the tumor microenvironment (TME). These protein complexes can also act as scavengers of ROS in the TME to reverse the immunosuppressive responses, thereby enhancing antitumor efficacy in vivo. In a melanoma cancer model, the synergistic antitumor efficacy was achieved, which was accompanied by enhanced T cell immune responses together with reduced immunosuppressive responses.

Evaluation of clinical efficacy of Chemotherapy for Rhabdomyosarcoma in children.

OBJECTIVE: To investigate the clinical characteristics and treatment methods of rhabdomyosarcoma in children and the efficacy of the methods. METHODS: The clinical data of 30 children with rhabdomyosarcoma who were admitted to our hospital from August 2013 to August 2017 were retrospectively analyzed. The clinical characteristics were summarized, and the curative effect and prognosis were evaluated. RESULTS: Among all the children (N=30), there were 20 males and 10 females, with a median age of 3.5 years. As to the primary site, there were 13 cases of head and neck, 11 cases of trunk, three cases of urogenital system and three cases of limbs. There were 25 cases of embryonic type, 4 cases of alveolar type and one case of polymorphic type. As regards clinical stage, there were one case of stage I, 9 cases of stage II, 13 cases of stage III and 7 cases of stage IV. There were one case of low risk, 19 cases of medium risk and 10 cases of high risk. Eight cases received surgery alone, 22 cases received combined treatment of surgery and chemotherapy (the chemotherapeutics followed three schemes, low-risk group (VAC+VA), moderate risk group (VAC) and high risk group (alternating use of VDC and IE). Among all the cases (N=30), there were 14 cases of complete remission (CR), five cases of partial remission (PR), four cases of stable disease (SD), and 7 cases of progressive disease (PD). The CR rate was (N=14, 46.7%). The three-year overall survival (OS) rate was (N=19, 63.3%). The clinical efficacy and prognosis of children receiving surgery and chemotherapy were better than those of children receiving surgery alone, and the difference was statistically significant (P<0.05). CONCLUSION: Rhabdomyosarcoma in children frequently happens in the head, neck and trunk. Embryonic type is the main pathological type of rhabdomyosarcoma. Comprehensive and standardized treatment based on surgery and chemotherapy is an important way to improve the curative effect in the treatment of rhabdomyosarcoma in children.

Mitigation of Hydrophobicity-Induced Immunotoxicity by Sugar Poly(orthoesters).

Polymeric nanoparticles (NPs) derived from self-assemblies of amphiphilic polymers have demonstrated great potential in clinical applications. However, there are challenges ahead. Notably, immunotoxicity remains a major roadblock that deters the NPs from further applications. Studies suggested that the hydrophobic component is a primary cause, yet biocompatible hydrophobic carbohydrate-based polymers may help mitigate this issue. Herein we design and synthesize novel NP systems having glucose poly(orthoesters) hydrophobic scaffold and polyethylene glycol (PEG) hydrophilic shell. The new NPs exhibited low immunotoxicity both in vitro and in vivo, as measured by the induced cytokine levels. In contrast, when other polymers, such as polylactide (PLA) or polycaprolactone (PCL), were used as the hydrophobic scaffold, the cytokine levels were orders of magnitude higher. Results from our multiple immunological studies indicate that carbohydrate-based polymers can largely mitigate the hydrophobicity-induced immunotoxicity, and thereby they may be good candidate polymers to engineer low immunotoxic biomaterials for various biomedical studies.

Cloning, expression and characterization of an endo-acting bifunctional alginate lyase of marine bacterium Wenyingzhuangia fucanilytica.

Alginate is the major constituent of brown algae and a commercially important polysaccharide with wide applications. Alginate lyases are desired tools for degrading alginate. Based on the genome mining of marine bacterium Wenyingzhuangia funcanilytica, an alginate lyase Aly7B_Wf was discovered, cloned and expressed in Escherichia coli. Aly7B_Wf belonged to subfamily 6 of PL7 family. Its biochemical properties, kinetic constants, substrate specificity and degradation pattern were clarified. The enzyme is an endo-acting bifunctional alginate lyase, and preferably cleaved polymannuronate (polyM). The Km (0.0237 ±â€¯0.0004 µM, 0.0105 ±â€¯0.0002 mg/mL) and kcat/Km (1180.65 ±â€¯19.81 µM-1 s-1, 2654.34 ±â€¯44.54 mg-1 ml s-1) indicated relatively high substrate-binding affinity and catalysis efficiency of Aly7B_Wf. By using mass spectrometry, final products of alginate degraded by Aly7B_Wf were identified as alginate hexasaccharide to disaccharide, and final products of polyguluronate (polyG) and polyM were confirmed as tetrasaccharide to disaccharide. The most predominant oligosaccharide in the final products of polyG and polyM was trisaccharide and disaccharide respectively. The broad substrate specificity, endo-acting degradation pattern and high catalysis efficiency suggested that Aly7B_Wf could be utilizied as a potential tool for tailoring the size of alginate and preparing alginate oligosaccharides.

Pidotimod in the treatment of pediatric recurrent respiratory tract infection.

OBJECTIVE: To observe the clinical efficacy of pidotimod in the treatment of recurrent respiratory tract infection in children. METHODS: One hundred thirty-two patients with recurrent respiratory tract infection who received treatment in Tianan City Central Hospital were selected and divided into an observation group and a control group using random number table, 66 in each group. Patients in the control group were given conventional treatment, while patients in the observation group were given conventional treatment and pidotimod treatment; the clinical efficacy of the two therapies was compared. The levels of IgG and IgM were measured after treatment. RESULTS: The vital signs and the content of inflammatory mediator and Th1/Th2 in serum before and after treatment were compared, and the clinical efficacy of the two groups was evaluated. The fever, pulmonary rale, cough and antiadoncus of patients in the observation group disappeared earlier than those in the control group (P<0.05). The onset duration of respiratory tract infection and days of antibiotic application of the observation group were shorter than those of the control group after treatment (P<0.05). The times of infection of the observation group were less than that of the control group (P<0.05). Before treatment, the two groups had no significant difference in the content of inflammatory mediators and Th1/Th2 in the serum (P>0.05). The serum content of tumor necrosis factor (TNF)-α and interleukin (IL)-4 of the two groups one week after treatment was lower than that before treatment, and the content of interferon (IFN)-γ and IFN-γ/IL-4 were higher than that before treatment; moreover the observation group had lower serum content of TFN-α and IL-4 and lower content of IFN-γ and IFN-γ/IL-4 compared to the control group (P<0.05). The overall response rate of the observation group was 92.4%, much higher than 81.8% in the control group (P<0.05). CONCLUSION: Pidotimod has a remarkable efficacy in the treatment of pediatric recurrent respiratory tract infection because it can effectively inhibit the infection and optimize Th1/Th2 immune function.

Plasmonic Heterodimers with Binding Site-Dependent Hot Spot for Surface-Enhanced Raman Scattering.

A novel plasmonic heterodimer nanostructure with a controllable self-assembled hot spot is fabricated by the conjugation of individual Au@Ag core-shell nanocubes (Au@Ag NCs) and varisized gold nanospheres (GNSs) via the biotin-streptavidin interaction from the ensemble to the single-assembly level. Due to their featured configurations, three types of heterogeneous nanostructures referred to as Vertice, Vicinity, and Middle are proposed and a single hot spot forms between the nanocube and nanosphere, which exhibits distinct diversity in surface plasmon resonance effect. Herein, the calculated surface-enhanced Raman scattering enhancement factors of the three types of heterodimers show a narrow distribution and can be tuned in orders of magnitude by controlling the size of GNSs onto individual Au@Ag NCs. Particularly, the Vertice heterodimer with unique configuration can provide extraordinary enhancement of the electric field for the single hot spot region due to the collaborative interaction of lightning rod effect and interparticle plasmon coupling effect. This established relationship between the architecture and the corresponding optical properties of the heterodimers provides the basis for creating controllable platforms which can be exploited in the applications of plasmonic devices, electronics, and biodetection.