UV-enhanced photorefractive response rate in a thin-film lithium niobate microdisk.

The photorefractive (PR) effect plays a critical role in emerging photonic technologies, including dynamic volume holography and on-chip all-optical functionalities. Nevertheless, its slow response rate has posed a significant obstacle to its practical application. Here, we experimentally demonstrate the enhancement of the PR response rate in a high-Q thin-film lithium niobate (TFLN) microdisk under UV light irradiation. At an irradiation intensity of 30 mW/cm2, the PR effect achieves a high response bandwidth of approximately 256 kHz. By employing this UV-assisted PR effect, we have achieved rapid laser-cavity locking and self-stabilization, where perturbations are automatically compensated. This technique paves the way toward real-time dynamic holography, editable photonic devices on a lithium niobate platform, and high-speed all-optical information processing.

Enhanced Frequency Conversion in Parity-Time Symmetry Line.

Non-Hermitian degeneracies reveal intriguing and nontrivial behaviors in open physical systems. Examples like parity-time (PT) symmetry breaking, topological encircling chirality, and enhanced sensing near an exceptional point (EP) are often associated with the abrupt nature of the phase transition around these degeneracies. Here we experimentally observe a cavity-enhanced second-harmonic frequency (SHG) conversion on a PT symmetry line, i.e., a set consisting of open-ended isofrequency or isoloss lines, both terminated at EPs on the Riemann surface in parameter space. The enhancement factor can reach as high as 300, depending on the crossing point whether in the symmetry or the broken phase of the PT line. Moreover, such enhancement of SHG enables sensitive distance sensing with a nanometer resolution. Our works may pave the way for practical applications in sensing, frequency conversion, and coherent wave control.

Erdheim-Chester disease with bilateral orbital masses and multi-systemic symptoms: two case reports.

BACKGROUND: Erdheim-Chester disease (ECD) is a rare histiocytic disorder characterized by multisystem xanthogranulomatous infiltration by lipid-laden histiocytes. We report two cases of ECD involving the orbit and describe their clinicopathologic factors, treatments, and prognosis. One was a rare case of ECD complicated with primary thrombocytosis. CASE PRESENTATION: This study describes two patients with bilateral orbital ECD. Both presented with proptosis and visual loss; imaging findings showed bilateral intraorbital masses. Both had different degrees of systemic symptoms (pleural effusion, pericardial effusion, ascites, and heart failure) before the ocular symptoms and did not find the cause before ophthalmic tumor resection and pathological biopsy. The diagnosis of ECD was confirmed after pathological biopsy and detection of BRAFV600E mutation. Patient 2 also with primary thrombocytosis and had a CALR mutation as well as the BRAFV600E mutation. Both patients were recommended to receive targeted therapy. Patient 1 refused targeted therapy for financial reasons and was discharged after local radiotherapy only. The patient had no light perception in either eye and no improvement in systemic symptoms. Patient 2 began targeted treatment after diagnosis and reached the discharge criteria 2 weeks later. He is in good condition at present, but unfortunately, his eyesight has not improved because of the irreversible damage to his visual function. CONCLUSION: ECD is easily misdiagnosed and missed because of its rarity and diverse clinical manifestations. Orbital involvement is common in ECD, and surgery is the most frequently employed approach. Despite the surgical resection is not curative, its significance lies in biopsy to establish diagnosis and/or surgical debulking to relieve mass effect, minimizing further impairment of visual function. Targeted therapy is the most effective treatment for patients with a positive BRAF mutation gene. Evaluation of a concomitant myeloid neoplasm is also critical before initiating targeted therapies for refractory ECD.

Clinical characteristics and treatment outcomes of secondary ocular adnexal lymphoma.

BACKGROUND: To describe the clinical characteristics and treatment outcomes of secondary ocular adnexal lymphoma (OAL), and emphasise the impact of timely biopsy and systemic evaluation on the diagnosis and treatment. METHODS: The data of patients with secondary OAL in our hospital from January 2010 to June 2021 were retrospectively reviewed. RESULTS: A total of 54 patients (30 men and 24 women) were included in the study. The mean age at presentation was 60 years (median 62 years; range 37-83 years). The main symptoms included ocular mass (74%), periorbital swelling (43%), and proptosis (39%). The main histopathological types were mucosa-associated lymphoid tissue lymphoma (30%), diffuse large B-cell lymphoma (28%), and natural killer/T-cell lymphoma (18%). In particular, three patients exhibited different pathological types of ocular lymphoma compared to previously diagnosed systemic lymphoma. The most common site of ocular and systemic involvement was the orbit (85%) and lymph nodes (56%), respectively, and 25 (46%) patients had occult extraocular lesions. Additionally, the 5-year overall survival rate of the entire cohort was 56%, and significant differences were observed between the three main pathological types and stages of the disease (all p < 0.001). CONCLUSIONS: Secondary OAL is a rare disease with a poor prognosis. That the disease is associated with a more aggressive pathological type is well established, indolent lymphoma is not uncommon. Furthermore, OAL and previously diagnosed systemic lymphoma may be pathologically distinct in some patients. Therefore, we recommend a prompt excision biopsy and a thorough systemic evaluation of patients with suspected OAL.

Research on the Effect of Carbon Defects on the Hydrophilicity of Coal Pyrite Surface from the Insight of Quantum Chemistry.

To investigate the effect of carbon defects on the hydrophilicity of the whole surface of the coal pyrite, the adsorption of the single H2O molecule at different sites of the coal pyrite surface was studied with the DFT calculation. It was found that, like the ideal pyrite, the single H2O molecule can stably adsorb at the doping-position, the ortho-position and the meta-position of the coal pyrite. The covalent bond and anti-bond were formed between O (water molecule) and Fe (the coal pyrite) through the Fe 3d orbital and O 2p orbital. Meanwhile, the S-H bond was replaced by the C-H bond. But away from the carbon defect centre, the adsorption of the single H2O molecule increased gradually and the Fe-O covalent bond strength between the single H2O molecule and the pyrite strengthened, which eventually became close to that of the undoped coal pyrite surface.

Cross-Entropy Pruning for Compressing Convolutional Neural Networks.

The success of CNNs is accompanied by deep models and heavy storage costs. For compressing CNNs, we propose an efficient and robust pruning approach, cross-entropy pruning (CEP). Given a trained CNN model, connections were divided into groups in a group-wise way according to their corresponding output neurons. All connections with their cross-entropy errors below a grouping threshold were then removed. A sparse model was obtained and the number of parameters in the baseline model significantly reduced. This letter also presents a highest cross-entropy pruning (HCEP) method that keeps a small portion of weights with the highest CEP. This method further improves the accuracy of CEP. To validate CEP, we conducted the experiments on low redundant networks that are hard to compress. For the MNIST data set, CEP achieves an 0.08% accuracy drop required by LeNet-5 benchmark with only 16% of original parameters. Our proposed CEP also reduces approximately 75% of the storage cost of AlexNet on the ILSVRC 2012 data set, increasing the top-1 errorby only 0.4% and top-5 error by only 0.2%. Compared with three existing methods on LeNet-5, our proposed CEP and HCEP perform significantly better than the existing methods in terms of the accuracy and stability. Some computer vision tasks on CNNs such as object detection and style transfer can be computed in a high-performance way using our CEP and HCEP strategies.

Prevalence of Cleft Lip/Palate in the Fangshan District of Beijing, 2006-2012.

OBJECTIVE: To estimate the cleft lip with or without cleft palate (CL/P) prevalence among births between 2006 and 2012 in Fangshan district of Beijing, China. DESIGN: Surveillance data analysis. SETTING: All hospitals that provide obstetric services in the district. PATIENTS: The CL/P cases presented for this report were from 13 weeks' gestation to 7 days postpartum. MAIN OUTCOME MEASURES: The CL/P prevalence was defined as the number of cases per 10 000 births, including live births and stillbirths at 28 weeks' gestation or beyond. RESULTS: The overall CL/P prevalence was 18.9 (95% confidence interval [CI]: 15.1-22.7) per 10 000 births. From 2006 to 2012, the CL/P prevalence was 19.3, 20.2, 10.9, 16.1, 17.5, 25.4, and 22.3 per 10 000 births; annually, no significant change was noted ( Pfor trend = .311). The prevalence of cleft palate, cleft lip, and cleft lip and palate were 3.4 (95% CI: 2.0-5.4), 6.2 (95% CI: 4.2-8.8), and 9.4 (95% CI: 6.9-12.4) per 10 000 births, respectively. The CL/P prevalence among the nonpermanent residents (31.4 per 10 000 births) was 2.31 times that of permanent residents (13.6 per 10 000 births). Among nonpermanent residents, the CL/P prevalence showed an upward trend over the study period ( Pfor trend = .036), that increased from 38.8 (95% CI: 16.5-76.6) per 10 000 births in 2006 to 54.6 (95% CI: 25.7-100.4) per 10 000 births in 2012. CONCLUSIONS: The overall CL/P prevalence was stable in the Fangshan district. However, the CL/P prevalence of the nonpermanent residents increased significantly.

Thermal stability of photoluminescence in Cu-doped Zn-In-S quantum dots for light-emitting diodes.

The photoluminescence (PL) properties of the Cu:Zn-In-S core quantum dots (QDs) and core-shell QDs were systematically investigated by using steady-state and time-resolved PL spectra at temperatures ranging from 80 to 400 K. The effects of the shell structure and the host bandgap on the thermal stability of Cu dopant emissions were studied by measuring the change in the PL intensity and the lifetime. It was found that the PL intensities and lifetimes of the core and core/shell QDs with green, yellow, and red emissions almost decrease with increasing temperatures while their PL was quenched at 300 K and 400 K, respectively, indicating the shell-enhanced thermal stability of the PL. The emission wavelength of the QDs as a function of temperature was also provided. The mechanisms of Cu dopant emission and thermal quenching were discussed. Finally, the green, yellow, red, and white light emitting light emitting diodes (LEDs) were fabricated based on Cu:Zn-In-S QDs.

Synthesis and antibacterial activity of novel 4-bromo-1H-indazole derivatives as FtsZ inhibitors.

A series of novel 4-bromo-1H-indazole derivatives as filamentous temperature-sensitive protein Z (FtsZ) inhibitors were designed, synthesized, and assayed for their in vitro antibacterial activity against various phenotypes of Gram-positive and Gram-negative bacteria and their cell division inhibitory activity. The results indicated that this series showed better antibacterial activity against Staphylococcus epidermidis and penicillin-susceptible Streptococcus pyogenes than the other tested strains. Among them, compounds 12 and 18 exhibited 256-fold and 256-fold more potent activity than 3-methoxybenzamide (3-MBA) against penicillin-resistant Staphylococcus aureus, and compound 18 showed 64-fold better activity than 3-MBA but 4-fold weaker activity than ciprofloxacin in the inhibition of S. aureus ATCC29213. Particularly, compound 9 presented the best activity (4 µg/mL) against S. pyogenes PS, being 32-fold, 32-fold, and 2-fold more active than 3-MBA, curcumin, and ciprofloxacin, respectively, but it was four times less active than oxacillin sodium. In addition, some synthesized compounds displayed moderate inhibition of cell division against S. aureus ATCC25923, Escherichia coli ATCC25922, and Pseudomonas aeruginosa ATCC27853, sharing a minimum cell division concentration of 128 µg/mL.

Construction of Mn doped Cu7S4 nanozymes for synergistic tumor therapy in NIR-I/II bio-windows.

In photothermal therapy (PTT) and chemodynamic therapy (CDT) of cancer, poor performance of nanoagents severely impaired the therapeutic effect of cancer. To solve the problem, we proposed and constructed a novel Mn doped Cu7S4 phothermal nanoagent both in the first near-infrared (NIR-I) and the second near- infrared (NIR-II) windows in this work, which exhibited high photothermal conversion efficiency of 40.3% at 808 nm (NIR-I window) and 33.4% at 1064 nm (NIR-II window), as well as outstanding pH-sensitive catalytic performance (peroxidase-like catalytic activity and Fenton-like catalytic activities). The as-prepared Mn doped Cu7S4 could be used to load chemotherapy drug doxorubicin (DOX) after modified by folic acid. Both in vitro and in vivo studies indicated that it could be used as nanoagent for chemodynamic therapy (CDT)/photothermal therapy (PTT)/ chemotherapy of cervical carcinoma. This study thus provided an NIR-I/NIR-II/pH responsive nanoagent for potential synergistic therapy of deep-seated tumors.

Validity of A Novel Simulator for Percutaneous Transforaminal Endoscopic Discectomy.

BACKGROUND: Percutaneous transforaminal endoscopic discectomy (PTED) has steep learning curves and a high incidence of complications, but currently, efficient and economical training methods are lacking. This study aimed to validate a novel simulator for PTED. METHODS: The simulated PTED included puncturing and establishing the working channel (PEWC) and endoscopic discectomy, with the PEWC being the tested module. Eleven experts and 21 novices were included and introduced to the simulator and tasks; all participants completed the PEWC. Outcomes included: total operation time, number of fluoroscopy for positioning the working sheath, number of spinal risk region invasion, Global Rating Scale (GRS) and a modified GRS, etc. The Mann-Whitney U test was used to compare 2 groups. Spearman's correlation coefficient analyzed continuous variables. RESULTS: Experts outperformed novices in total operation time (P = 0.001), requiring fewer number of fluoroscopies for positioning the working sheath (P = 0.003). Additionally, experts had a lower number of spinal risk region invasions (P = 0.016) and higher scores on both the GRS (P < 0.001) and modified GRS (P < 0.001). PTED experience correlated with GRS scores (P = 0.001) and modified GRS (P < 0.001). The overall realism scored a median of 4 (3.75-5), and educational value had a median of 4 (range 3-5). CONCLUSIONS: This study demonstrates the validity of the novel simulator, revealing significant associations between PTED experience and performance metrics in a simulated PEWC setting. Furthermore, the PEWC module also offers a good realistic design and high education value according to experts.

The effect of combined antihypertensive treatment (felodipine with either irbesartan or metoprolol) on erectile function: a randomized controlled trial.

OBJECTIVES: This study aimed to determine whether combining a calcium channel blocker with either an angiotensin II receptor blocker or a ß-blocker would have similar effects on sexual function in men with hypertension. METHODS: This prospective, randomized study (ClinicalTrials.gov: NCT01​238705) included 218 male participants with untreated hypertension. Patients were randomized to treatment with felodipine combined with irbesartan or metoprolol for 48 weeks. Sexual function was evaluated at baseline and after 48 weeks of therapy. The levels of serum sex hormones and markers of oxidative stress were measured at the same time. RESULTS: There was no significant difference in the prevalence of erectile dysfunction before and after treatment in either group (p > 0.05). There were also no differences in the levels of serum testosterone, sex hormone-binding globulin or 4-hydroxynonenal before and after treatment in either group (p > 0.05). In the felodipine-irbesartan group, sexual desire scores rose after treatment (p = 0.022) and the concentrations of serum 8-hydroxy-2'-deoxyguanosine and malondialdehyde declined (p < 0.001 and p = 0.002, respectively). The between-group differences for 8-hydroxy-2'-deoxyguanosine and malondialdehyde were not significant (p > 0.05, respectively). CONCLUSION: The results suggest that felodipine-irbesartan may be more beneficial to the sexual desire of hypertensive male patients than felodipine-metoprolol. This effect was possibly relevant to irbesartan, which prevents oxidative stress to some extent.

Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17+ γδ T cells. / çŸ­é“¾è„‚è‚ªé ¸é€šè¿‡è°ƒèŠ‚è°ƒèŠ‚æ€§T细胞和IL-17+ γδ T细胞的平衡来改善脊髓损伤的恢复.

Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen's method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)|-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17+ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17+ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the "gut-spinal cord-immune" axis may be one of the mechanisms regulating neural repair after SCI.

Free-Standing Carbon Nanofiber Composite Networks Derived from Bacterial Cellulose and Polypyrrole for Ultrastable Potassium-Ion Batteries.

Carbon materials derived from bacterial cellulose have been studied in lithium-ion batteries due to their low cost and flexible characteristics. However, they still face many intractable problems such as low specific capacity and poor electrical conductivity. Herein, bacterial cellulose is used as the carrier and skeleton to creatively realize the composite of polypyrrole on its nanofiber surface. After carbonization treatment, three-dimensional carbon network composites with a porous structure and short-range ordered carbon are obtained for potassium-ion batteries. The introduction of nitrogen doping from polypyrrole can increase the electrical conductivity of carbon composites and provide abundant active sites, improving the comprehensive performance of anode materials. The carbonized bacterial cellulose@polypyrrole (C-BC@PPy) anode exhibits a high capacity of 248 mA h g-1 after 100 cycles at 50 mA g-1 and a capacity retention of 176 mA h g-1 even over 2000 cycles at 500 mA g-1. Combined with density functional theory calculations, these results indicate that the capacity of C-BC@PPy is contributed by N-doped and defect carbon composite materials as well as pseudocapacitance. This study provides a guideline for the development of novel bacterial cellulose composites in the energy storage field.

High-efficient mineralization of formaldehyde by three-dimensional "PIZZA"-like bismuth molybdate-titania/diatomite composite.

The application of TiO2-based photocatalysts in air pollution control has attracted much attention thanks to their advantageous green and sustainable performance. However, how to improve the degradation efficiency under visible light is still challenging. Herein, we report a ternary three-dimensional "PIZZA"-like Bi2MoO6-TiO2/diatomite (BTD) composite with high-efficient mineralization and recycling performance towards gaseous formaldehyde (HCHO) under visible light. The high-efficient adsorption-photocatalysis collaborative system with intimate interface combination is successfully established among Bi2MoO6 (BMO), TiO2 and diatomite. The HCHO mineralization rate constant of BTD-1:2 composite is up to around 4.03 times and 2.18 times higher than those of bare BMO and binary Bi2MoO6-TiO2 composite, respectively. It is indicated that the introduction of diatomite increases active sites and plays the vital role in the improvement of photocatalysis. In addition, the photogenerated holes (h+) and hydroxyl radical (OH) are proved to be the main active species for HCHO mineralization. Furthermore, there is a competitive adsorption relationship between water (H2O) molecules and HCHO molecules, and both H2O molecules and oxygen (O2) molecules participated in the reaction of HCHO mineralization based on in-situ DRIFTs spectra analysis. Our work would give a new perspective on gaseous HCHO purification.

Changes in the gut microbiota of osteoporosis patients based on 16S rRNA gene sequencing: a systematic review and meta-analysis.

BACKGROUND: Osteoporosis (OP) has become a major public health issue, threatening the bone health of middle-aged and elderly people from all around the world. Changes in the gut microbiota (GM) are correlated with the maintenance of bone mass and bone quality. However, research results in this field remain highly controversial, and no systematic review or meta-analysis of the relationship between GM and OP has been conducted. This paper addresses this shortcoming, focusing on the difference in the GM abundance between OP patients and healthy controls based on previous 16S ribosomal RNA (rRNA) gene sequencing results, in order to provide new clinical reference information for future customized prevention and treatment options of OP. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we comprehensively searched the databases of PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI). In addition, we applied the R programming language version 4.0.3 and Stata 15.1 software for data analysis. We also implemented the Newcastle-Ottawa Scale (NOS), funnel plot analysis, sensitivity analysis, Egger's test, and Begg's test to assess the risk of bias. RESULTS: This research ultimately considered 12 studies, which included the fecal GM data of 2033 people (604 with OP and 1429 healthy controls). In the included research papers, it was observed that the relative abundance of Lactobacillus and Ruminococcus increased in the OP group, while the relative abundance for Bacteroides of Bacteroidetes increased (except for Ireland). Meanwhile, Firmicutes, Blautia, Alistipes, Megamonas, and Anaerostipes showed reduced relative abundance in Chinese studies. In the linear discriminant analysis Effect Size (LEfSe) analysis, certain bacteria showed statistically significant results consistently across different studies. CONCLUSIONS: This observational meta-analysis revealed that changes in the GM were correlated with OP, and variations in some advantageous GM might involve regional differences.

[Effect of different combined antihypertensive regimen on the erectile function in male hypertensive patients].

OBJECTIVE: To compare the effects of felodipine combined irbesartan regimen with that of felodipine combined metoprolol regimen on the sexual function in male hypertensive patients. METHOD: One hundred and twenty-three male hypertensive patients (age 25 to 60) were randomly assigned to felodipine (5 mg/d) plus irbesartan (150 mg/d, n = 64) group and felodipine (5 mg/d) plus metoprolol (47.5 mg/d, n = 59) group. Dosage of felodipine were doubled after 4 weeks if the blood pressure were > or = 140/ 90 mm Hg (1 mm Hg = 0.133 kPa). At the baseline and post 24th week treatment, sexual function of patients was assessed by the International Index of Erectile Function (IIEF) Questionaire. Serum testosterone (T), sex hormone binding globulin (SHBG), 4-hydroxynonenal (HNE), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and Malonaldehyde (MDA) were measured by Radioimmunoassay (RIA), ELISA and TBA respectively. RESULTS: Total prevalence of erectile dysfunction (ED), T, SHBG and HNE were similar between pre- and post-treatment in two groups (P > 0.05). On the other hand, the scores of the mild ED and sexual desire (SD) were improved and both serum 8-OHdG and MDA in patients with ED decreased [(146.02 +/- 60.54) ng/L vs. (139.89 +/- 62.03) ng/L, P = 0.048 and (6.59 +/- 1.75) micromol/L vs. (5.51 +/- 1.65) micromol/L, P = 0.039] in Felodipine plus Irbesartan group. CONCLUSION: The results suggested that Felodipine + Irbesartan regimen may be superior to Felodipine + metoprolol regimen for male hypertensive patients with mild ED.

Primary orbital ganglioneuroblastoma: A case report.

BACKGROUND: Ganglioneuroblastoma (GNB) is a neoplasm that arises from the primitive cells of the sympathetic nervous system during childhood. The current case is very unique because of the initial primary tumor manifestation in the orbit and an adrenal tumor being observed later during follow-up. CASE PRESENTATION: A 2-year-old girl presented to the Ophthalmology Department of our hospital complaining of swelling of the left upper eyelid for approximately one month. Orbital computed tomography (CT) revealed a left orbital mass with bone destruction. Thoracic and abdominal CT indicated no abnormalities. The mass was surgically resected, and histopathological analysis confirmed it as GNB. During follow-up, abdominal CT detected an adrenal tumor with internal calcification, a calcified nodule on the left side of the abdominal aorta, and mesenteric lymph nodes. Accordingly, primary orbital GNB and metastatic adrenal GNB were the possible considerations. We removed the adrenal tumor, and the patient underwent chemotherapy. However, the patient died 18 months after the ophthalmic surgery. CONCLUSION: Primary orbital GNB in children is easily misdiagnosed because of its rare occurrence and atypical clinical findings. Imaging methods combined with histopathological examination contribute to the detection and diagnosis of primary and metastatic GNBs. Thus, timely surgery combined with adjuvant chemotherapy and long-term follow-up is essential for controlling the metastasis of GNB and improving the survival rate of patients.

Dual Oxidase System Genes Defects in Children With Congenital Hypothyroidism.

PURPOSE: The objectives of this study were to analyze the distribution of dual oxidase (DUOX) system genes (containing DUOX2, DUOX1, DUOXA2, and DUOXA1) variants in children with congenital hypothyroidism (CH) and their phenotypes. METHODS: Target region sequencing technology was performed on DUOX system genes among 606 CH subjects covering all the exon and intron regions. Detailed clinical data were collected for statistical analysis. RESULTS: A total of 95 suspected pathogenic variants were detected in the DUOX system genes, showing a 39.11% rate in variant carrying (237/606). DUOX2 had the highest rate in this study. There were statistical differences in maximum adjusted dose and current dose of levothyroxine between the DUOX system genes nonmutated group with the mutated group (both Ps < 0.001). The cases in the DUOX system genes mutated group were more likely to develop into transient CH (χ 2 = 23.155, P < 0.001) and more likely to manifested as goiter or gland-in-situ (χ 2 = 66.139, P < 0.001). In addition, there was no significant difference in clinical characteristics between DUOX system genes monoallelic and non-monoallelic. Although 20% of the variants affected the functional domain regions (EF hand, flavin adenine dinucleotide and nicotinamide adenine dinucleotide binding sites), there was no significant effect on the phenotype severity whether the variation is located in the functional domain regions. CONCLUSIONS: Our results showed the high variation rate of DUOX2 in the DUOX system genes among Chinese CH patients. The complex genotype-phenotype relationship of DUOX system genes broadened the understanding of CH phenotype spectrum.

Synthesis and antibacterial activity of novel 4''-O-arylalkylcarbamoyl and 4''-O-((arylalkylamino)-4-oxo-butyl)carbamoyl clarithromycin derivatives.

Novel series of novel 4''-O-arylalkylcarbamoyl and 4''-O-((arylalkylamino)-4-oxo-butyl)carbamoyl clarithromycin derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. These derivatives retained excellent activity against the erythromycin-susceptible strains and showed significantly improved activity against all of the tested erythromycin-resistant strains. Among them, compound 4c was the most effective (0.06 microg/mL) against Streptococcus pneumonia encoded by the erm gene and compound 4a was had the most potent activity (0.25 microg/mL) against S. pneumonia encoded by the erm and mef genes.