Exosomal miR-93 derived from hepatocellular carcinoma cell promotes the sorafenib resistance of hepatocellular carcinoma through PTEN/PI3K/Akt pathway.

Exosomal microRNAs (miRNAs) derived from cancer cell is an important regulatory molecule that mediates the formation of tumor drug resistance, but function and mechanisms of exosomal miRNA in sorafenib resistance of hepatocellular carcinoma (HCC) have not been studied. We detected the level and prognosis of miR-93 in HCC by using TCGA HCC database. For confirming the extracted exosome, transmission electron microscopy was used. Cy3-labeled miR-93 and quantitative reverse transcription-polymerase chain reaction were used to prove that exosomal miR-93 derived from HCC cell can be transferred to sensitive HCC cells. CCK8, EdU, and flow cytometer assay were used to confirm the function of exosomal miR-93 in sorafenib resistance of HCC. Bioinformatics software and luciferase reporter assay was used to confirm the direct targeting relationship between PTEN and miR-93. Western blot was used to validate downstream pathways. We found that miR-93 is overexpressed and a prognostic risk factor for the HCC patients. miR-93 was overexpressed in sorafenib resistant HCC cells compared with sensitive cells, and miR-93 contributed to sorafenib resistance of HCC cells through targeting PTEN. miR-93 was enriched in exosomes that secreted from sorafenib resistant cells, and these exosomal miR-93 promote the spread of sorafenib resistant through targeting PTEN to reactivate PI3K/AKT pathway. Therefore, miR-93 can act as a potential therapeutic target for advanced patients with acquired sorafenib resistance.

Two De Novo Mosaic Variants Within the Same Site of PHEX Gene in a Girl with X-Linked Hypophosphatemic Rickets.

X-linked hypophosphatemic rickets (XLH) is the most common form of hypophosphatemic rickets, which is caused by the deficiencies of PHEX gene with an X-linked dominant inheritance pattern. As at least several thousands of XLH patients have been diagnosed, only several males and fewer females with mosaicism of PHEX gene were found. Here we describe an XLH girl with two de novo mosaic variants within the same site of PHEX gene. To rapidly screen all of the causative genes of hypophosphatemic rickets and rule out other diseases, DNA samples were initially analyzed using whole exome sequencing (WES). Interestingly, two different pathogenic mosaic variants, a known c.1809G > A(p.W603*) variant and a novel c.1809G > T(p.W603C) variant within the same site of PHEX gene, were identified in the proband by WES. Subsequent Sanger sequencing confirmed the presence and de novo pattern of these two mosaic variants in the proband, which were absent in her healthy parents. This is the first case to report two different mosaic variants of PHEX gene in an XLH individual. This XLH girl has a de novo mosaic genotype of c.1809 = /G > T/G > A in PHEX gene. Our report adds an unusual mocaicism case for XLH and expands the mutational event and spectrum of PHEX gene. Our report also alerts clinicians and geneticists to be cautious about mocaicism and detection methods.

Determination of Cervical Lymph Nodes Metastasis and Extra Nodal Extension Status by Quantitative Assessment of Border Irregularity and Apparent Diffusion Coefficient in Patients With Tongue Squamous Cell Carcinoma.

OBJECTIVE: The objective of this study was to determine the diagnostic value of quantitative border irregularity assessment and apparent diffusion coefficient (ADC) in patients with squamous cell carcinoma of the tongue (SCCT). METHODS: Cervical lymph nodes (n = 192) from 63 patients with SCCT were examined preoperatively by magnetic resonance imaging, including routine head and neck sequences, dynamic contrast-enhanced magnetic resonance imaging, diffusion-weighted imaging, ADC, surface regularity (SR), and visually assessed variables, and evaluated pathologically after surgery. RESULTS: Necrosis, lymphatic hilum, unclear margin, higher SR, long to short axis ratio, and ADC were associated with metastasis in cervical lymph nodes (M-cLNs) and extranodal extension (ENE), and thickened nodal rim with ENE alone. Apparent diffusion coefficient, SR, unclear margin, and visible necrosis were strongly associated with M-cLN, whereas SR, unclear margin, and visible necrosis were associated with ENE status on logistic regression analysis. CONCLUSIONS: Quantitative SR and ADC data greatly improved diagnosis of M-cLNs and ENE, relative to visible variables alone in patients with SCCT.

Splenic Artery Pseudoaneurysm in Chronic Pancreatitis Causing Obstructive Jaundice: Endovascular Management.

BACKGROUND: Splenic artery pseudoaneurysm (SAP) around the pancreatic head causing obstructive jaundice is an extremely rare complication but can be life threatening once occurs. This case report is to raise awareness of this catastrophic complication and share our experience of successful endovascular management. METHODS: A 47-year-old male with a history of chronic pancreatitis clinically presented with epigastric pain and jaundice. Proximal SAP complicated with obstructive jaundice was confirmed by laboratory and imaging investigations. The SAP was successfully treated by transarterial coil embolization, and the jaundice subsequently improved. RESULTS: Abdominal contrast-enhanced computed tomography 11 months after embolization showed complete occlusion and reduction in the volume of the SAP as well as normal biliary tract. CONCLUSIONS: SAP complicated with obstructive jaundice should be managed timeously and aggressively once diagnosed, given its potential adverse consequences. Transarterial embolization using the isolation technique may be a safe and effective strategy for treating this disease.

Endovascular Management of Isolated Superior Mesenteric Artery Dissecting Aneurysm by Retrograde Catheterization Via Collaterals from the Celiac Artery.

Isolated superior mesenteric artery (SMA) dissecting aneurysm is frequently symptomatic and potentially catastrophic; thus, it usually requires endovascular treatment. The endovascular management can be challenging in certain cases as catheterization of the collapsed true lumen is often very difficult. This case report is to describe a new approach for catheterization of the true lumen of the SMA in a case of isolated SMA dissecting aneurysm. A 63-year-old male with an SMA dissecting aneurysm underwent stent-graft placement for treatment. Catheterization of the true lumen via the anterograde approach was unsuccessful because of angulation and collapse of the SMA true lumen as a result of the dissecting aneurysm. A guidewire was passed through the collaterals from the celiac artery and retrogradely passed across the collapsed SMA true lumen into the aorta. We then used a snare that had been delivered through the contralateral femoral access to capture and retrieve the guidewire. A delivery system was advanced into the SMA, and a stent graft was successfully deployed to occlude the dissecting aneurysm. This report introduces a new feasible retrograde approach that provides access to the SMA true lumen via celiac collaterals in cases of difficult antegrade catheterization of an SMA dissecting aneurysm.

Predicting necrosis in adnexal torsion in women of reproductive age using magnetic resonance imaging.

PURPOSE: To identify the diagnostic performance of magnetic resonance (MR) imaging for patients with adnexal torsion and to develop a predictive model for necrosis related to torsion. METHODS: The institutional ethics committee approved this retrospective study. A total of 56 women with a preoperative pelvic MR scan and a surgical and pathologic diagnosis of adnexal torsion were enrolled from five institutions. Three radiologists reviewed the MR images independently. The kappa value of interrater agreement was assessed. Differences between patients treated with conservative surgery and adnexectomy were evaluated by univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was used to assess the ability of the model to predict ovarian necrosis. RESULTS: Fifty-six patients were divided into the conservative surgery group (24/56, 42.9%) or the adnexectomy group (32/56, 57.1%) depending on the surgical outcomes. The radiographic features related to torsion were interpreted by three raters retrospectively with substantial interrater agreement (kappa > 0.60). Older reproductive age and pedicle hemorrhagic infarction were significantly associated with adnexectomy (p < 0.05). At multivariate analysis, pedicle hemorrhagic infarction (odds ratio = 10.476 [95% confidence interval 1.103, 99.504; p = 0.041]) was associated with adnexectomy. Using the predictive model (older reproductive age and pedicle hemorrhagic infarction), a receiver operating characteristic curve was generated with an area under the curve (AUC = 0.870 ± 0.049). CONCLUSION: The presence of pedicle hemorrhagic infarction and older reproductive age can predict necrosis of adnexal torsion and may be used to guide the optimal treatment strategy. KEY POINTS: • Pedicle hemorrhagic infarction and older reproductive age are predictors of necrosis in adnexal torsion in patients of reproductive age (AUC = 0.870 ± 0.049). • Cystic wall thickening, enlarged vascular pedicle, tubal thickening, and uterine deviation are associated with a high risk for adnexal torsion, occurring in more than half of the cases in this study. • MR findings are useful for the definitive diagnosis of adnexal torsion and for the prediction of adnexal necrosis.

Long noncoding RNA 00460 (LINC00460) promotes glioma progression by negatively regulating miR-320a.

OBJECTIVE: Long noncoding RNA 00460 (LINC00460) has been reported to contribute to tumorigenesis in multiple types of human malignancies. However, the biological role and the underlying molecular mechanism of LINC00460 in glioma remain unclear. The aim of this study was to investigate the clinical value, the biological function, and the potential mechanism of LINC00460 in glioma. METHODS: The expression level of LINC00460 in glioma tissues and cell lines was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8, flow cemetery, wound healing, and transwell invasion assays were used to explore the effect of LINC00460 on glioma cell proliferation, apoptosis, migration, and invasion. qRT-PCR and reporter assays were used to further verify the regulatory mechanism of LINC00460 in glioma progression. RESULTS: LINC00460 expression was upregulated in glioma tissues and cell lines compared with non-tumor brain samples and astrocyte cell line (NHA), respectively. Moreover, increased LINC00460 expression was closely associated with glioma tumor grade. Loss-of-function assays revealed that knockdown of LINC00460 significantly inhibited glioma cell proliferation, induced cell apoptosis, and suppressed migration and invasion. The mechanistic assays disclosed that LINC00460 binded to miR-320a in a sequence-specific manner and regulated its expression. Moreover, miR-320 inhibition partially attenuated LINC00460 knockdown-mediated suppressive effects on glioma cell proliferation, migration, and invasion. CONCLUSION: These findings suggested that LINC00460 might function as an oncogenic lncRNA in glioma development and could be explored as a potential therapeutic target for glioma.

Identification of Rice Varieties and Transgenic Characteristics Based on Near-Infrared Diffuse Reflectance Spectroscopy and Chemometrics.

BACKGROUND: In recent years, genetically modified technology has developed rapidly, and the potential impact of genetically modified foods on human health and the ecological environment has received increasing attention. The currently used methods for testing genetically modified foods are cumbersome, time-consuming, and expensive. This paper proposed a more efficient and convenient detection method. METHODS: Near-infrared diffuse reflectance spectroscopy (NIRDRS) combined with multivariate calibration methods, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and support vector machines (SVM), were used for identification of different rice varieties and transgenic (Bt63)/non-transgenic rice. Spectral pretreatment methods, including Norris-Williams smooth (NWS), standard normal variate (SNV), multiplicative scatter correction (MSC), and Savitzky-Golay 1st derivative (SG 1st-Der), were used for spectral noise reduction and effective information enhancement. Accuracy was used to evaluate the qualitative discriminant models. RESULTS: The results showed that the SG 1st-Der pretreatment method, combined with the SVM, provided the optimal model to distinguish different rice varieties. The accuracy of the optimal model was 98.33%. For the discrimination model of transgenic/non-transgenic rice, the SNV-SVM model, MSC-SVM model, and SG 1st-Der-PLS-DA model all achieved good analysis results with the accuracy of 100%. CONCLUSION: The results showed that portable NIR spectroscopy combined with chemometrics methods could be used to identify rice varieties and transgenic characteristics (Bt63) due to its fast, non-destructive, and accurate advantages.

Real-time PCR tests to specifically detect IHHNV lineages and an IHHNV EVE integrated in the genome of Penaeus monodon.

Infectious hypodermal and hematopoietic necrosis virus (IHHNV) can cause mass mortalities in western blue shrimp Penaeus stylirostris, runt deformity syndrome in Pacific white shrimp P. vannamei and scalloped abdominal shell deformities in black tiger shrimp P. monodon. In P. monodon, however, PCR-based diagnosis of IHHNV can be complicated by the presence of a chromosome-integrated, non-replicating endogenous viral element (EVE). To facilitate high-throughput screening of P. monodon for IHHNV infection and/or EVE sequences, here we report real-time PCR tests designed to specifically detect IHHNV Lineage I, II and III but not EVE Type A sequences and vice versa. Using 108 dsDNA copies of plasmid (p)DNA controls containing either IHHNV or EVE-Type A sequences, both tests displayed absolute specificity. The IHHNV-q309 PCR reliably detected down to ≤10 copies of pDNA, at which levels a 309F/R PCR amplicon was just detectable, and the presence of an IHHNV-EVE sequence did not significantly impact its sensitivity. The IHHNV-qEVE PCR was similarly sensitive. Testing of batches of P. monodon clinical samples from Vietnam/Malaysia and Australia identified good diagnostic concordance between the IHHNV-q309 and 309F/R PCR tests. As expected for a sequence integrated into host chromosomal DNA, IHHNV-qEVE PCR Ct values were highly uniform among samples from shrimp in which an EVE was present. The highly specific and sensitive IHHNV-q309 and IHHNV-qEVE real-time PCR tests described here should prove useful for selecting broodstock free of IHHNV infection and in maintaining breeding populations of P. monodon specific pathogen free for IHHNV, and if desired, also free of IHHNV-EVE sequences.

Genetic polymorphisms of 20 autosomal STR loci in the Vietnamese population from Yunnan Province, Southwest China.

The genetic polymorphisms of 20 autosomal short tandem repeat (STR) loci included in the PowerPlex® 21 kit were evaluated in 522 healthy unrelated Vietnamese from Yunnan, China. All of the loci reached the Hardy-Weinberg equilibrium. These loci were examined to determine allele frequencies and forensic statistical parameters. The combined discrimination power and probability of excluding paternity of the 20 STR loci were 0.999999999999999999999991 26 and 0.999999975, respectively. Results suggested that the 20 STR loci are highly polymorphic, which is suitable for forensic personal identification and paternity testing.

Genetic polymorphisms of 24 Y-STR loci in Hani ethnic minority from Yunnan Province, Southwest China.

In the present study, 24 Y-chromosomal short tandem repeat (Y-STR) loci were analyzed in 250 unrelated Hani male individuals from Lvchun county, Honghe Hani and Yi Autonomous Prefecture, Yunnan Province, Southwest China. The gene diversity of the 24 Y-STR loci in the studied Hani group ranged from 0.2683 (DYS437) to 0.8837 (DYS447). According to haplotypic analysis of the 24 Y-STR loci, 204 different haplotypes were obtained, 174 of which were unique. The haplotype diversity and discrimination capacity in Hani group were 0.9977 and 0.8160 at 24 STR loci, respectively. Six single non-fraction off-ladder alleles were observed at DYS447 in 103 samples, in addition to the alleles 19 to 28 included in the allelic ladder, alleles 13, 14, 15, 16, 17, and 18 were also observed at DYS447. One intermediate allele 20.2 was observed in one individual at DYS527a/b. We analyzed interpopulation differentiations by making comparisons between Yunnan Hani group and other 17 groups. The results of pairwise genetic distances, multidimensional scaling plot, and neighbor-joining tree at the same set of 17 Y-filer loci indicated that Yunnan Hani group had the closer genetic relationships with Yunnan Han group. The present results may provide useful information for paternal lineages in forensic cases and can also increase our understanding of the genetic relationships between Hani and other groups.

Cervical disc arthroplasty versus anterior cervical discectomy and fusion for treatment of symptomatic cervical disc disease: a meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this study is to compare the effectiveness and safety of cervical disc arthroplasty with anterior cervical discectomy and fusion for treatment of symptomatic cervical disc disease. Anterior cervical discectomy and fusion (ACDF) is the conventional surgical treatment for symptomatic cervical disc disease. Recently, cervical disc arthroplasty (CDA) has been developed to address some of the shortcomings associated with ACDF by preserving function of the motion segment. Controversy still surrounds regarding whether CDA is better. METHODS: We systematically searched six electronic databases (Medline, Embase, Clinical, Ovid, BIOSIS and Cochrane registry of controlled clinical trials) to identify randomized controlled trials (RCTs) published up to April 2014 in which CDA was compared with ACDF for the treatment of symptomatic cervical disc disease. Effective data were extracted after the assessment of methodological quality of the trials. Then, we performed the meta-analysis. RESULTS: Eighteen relevant RCTs with a total of 4061 patients were included. The results of the meta-analysis indicated that CDA was superior to ACDF regarding better neurological success (P < 0.00001), greater motion preservation at the operated level (P < 0.00001), fewer secondary surgical procedures (P < 0.00001), and fewer rates of adverse events (P < 0.00001) but inferior to ACDF regarding operative times (P < 0.00001). No significant difference was identified between the two groups regarding blood loss (P = 0.87), lengths of hospital stay (P = 0.76), neck pain scores (P = 0.11) and arm pain scores (P = 0.78) reported on a visual analog scale. CONCLUSION: The meta-analysis revealed that CDA demonstrated superiorities in better neurological success, greater motion preservation at the operated level, lower rate of adverse events and fewer secondary surgical procedures compared with ACDF. However, the benefits of blood loss, lengths of hospital stay, neck and arm pain functional recovery are still unable to be proved.

Artificial total disc replacement versus fusion for lumbar degenerative disc disease: a meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this study is to compare the effectiveness and safety of artificial total disc replacement (TDR) with fusion for the treatment of lumbar degenerative disc disease (DDD). Spinal fusion is the conventional surgical treatment for lumbar DDD. Recently, TDR has been developed to avoid the negative effects of the fusion by preserving function of the motion segment. Controversy still surrounds regarding whether TDR is better. METHODS: We systematically searched six electronic databases (Medline, Embase, Clinical, Ovid, BIOSIS and Cochrane registry of controlled clinical trials) to identify randomized controlled trials (RCTs) published up to March 2013 in which TDR was compared with the fusion for the treatment of lumbar DDD. Effective data were extracted after the assessment of methodological quality of the trials. Then, we performed the meta-analysis. RESULTS: Seven relevant RCTs with a total of 1,584 patients were included. TDR was more effective in ODI (MD -5.09; 95% CI [-7.33, -2.84]; P < 0.00001), VAS score (MD -5.31; 95% CI [-8.35, -2.28]; P = 0.0006), shorter duration of hospitalization (MD -0.82; 95% CI [-1.38, -0.26]; P = 0.004) and a greater proportion of willing to choose the same operation again (OR 2.32; 95% CI [1.69, 3.20]; P < 0.00001). There were no significant differences between the two treatment methods regarding operating time (MD -44.16; 95% CI [-94.84, 6.52]; P = 0.09), blood loss (MD -29.14; 95% CI [-173.22, 114.94]; P = 0.69), complications (OR 0.72; 95% CI [0.45, 1.14]; P = 0.16), reoperation rate (OR 0.83; 95% CI [0.39, 1.77]; P = 0.63) and the proportion of patients who returned to full-time/part-time work (OR 1.10; 95% CI [0.86, 1.41]; P = 0.47). CONCLUSION: TDR showed significant safety and efficacy comparable to lumbar fusion at 2 year follow-up. TDR demonstrated superiorities in improved physical function, reduced pain and shortened duration of hospitalization. The benefits of operating time, blood loss, motion preservation and the long-term complications are still unable to be proved.

5-HT-treated mouse B cells alleviate ulcerative colitis via RIPK1: Insights from proteomic and phosphoproteomic analyses.

5-hydroxytryptamine (5-HT) exerts various physiological effects on the intestine through different signaling pathways and molecular transmission mechanisms, including pro- and anti-inflammatory effects. Adoptive transfer of regulatory B cells (Bregs) into colitis mice has exhibited significant therapeutic benefits. We aimed to elucidate the mechanism through which 5-HT-treated B cells alleviate ulcerative colitis. To this end, we analyzed the proteomic and phosphoproteomic profiles of 5-HT-stimulated B cells from naïve mice. We identified 3124 phosphorylation sites in proteins via tandem mass tagging and found 110 differential peptides after protein phosphorylation. Furthermore, we obtained three differential proteins, RIPK1, ATXN2l, and Q8C5K5 through integration of both proteomic datasets. We discovered and validated that 5-HT binds to 5-HT7R and increases the expression of RIPK1 in B cells. We propose a theoretical and experimental basis for further research on the RIPK1 signaling pathway, kinase prediction, and phosphorylation sites in ulcerative colitis. SIGNIFICANCE: Some researchers demonstrated that 5-HT can effectively suppress colitis through a variety of molecular mechanisms. Our study discovered and consistently validated the 5-HT/5-HT7R/RIPK1 pathway, further clarifying the molecular mechanism through which 5-HT stimulates B cells to alleviate intestinal inflammation.

Exosomal miR-19a derived from melanoma cell promotes the vemurafenib resistance of malignant melanoma through directly targeting LRIG1 to reactivate AKT and MAPK pathway.

Exosomes derived from neighboring v-raf murine sarcoma viral oncogene homolog B1 inhibitor (BRAFi)-resistant melanoma cells mediate the formation of resistance in melanoma cells sensitive to BRAFi. The function and molecular mechanisms of exosomal miRNA in BRAFi resistance of melanoma have not been studied. We found that the expression of miR-19a in BRAFi resistant melanoma cells was significantly higher than that in sensitive cells, and miR-19a contributes to the resistance of melanoma cells to BRAFi by targeting immunoglobulin-like domains protein 1 (LRIG1). miR-19a was highly enriched in exosomes secreted from BRAFi resistant melanoma cells, and these exosomal miR-19a promote the spread of BRAFi resistant. The reactivation of Protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) pathways is the main reason for the BRAFi resistant of melanoma cells. We demonstrated that exosomal miR-19a derived from melanoma cell promotes the formation and spread of BRAFi resistant in melanoma through targeting LRIG1 to reactivate AKT and MAPK pathway. Therefore, miR-19a may serve as a potential therapeutic target in melanoma patients with acquired drug resistance.

Reduced-Toxicity and Highly Luminescent Germanium-Lead Perovskites Enabled by Strain Reduction for Light-Emitting Diodes.

Germanium-lead (Ge-Pb) perovskites provide a promising solution for perovskite optoelectronic devices with reduced toxicity. However, Ge-Pb perovskite light-emitting diodes (PeLEDs) with >30 mol % Ge showed low emission efficiencies [Yang, D.; Zhang, G.; Lai, R.; Cheng, Y.; Lian, Y.; Rao, M.; Huo, D.; Lan, D.; Zhao, B.; Di, D. Germanium-Lead Perovskite Light-Emitting Diodes. Nat. Commun. 2021, 12 (1), 4295]. Here, we apply strain engineering to effectively improve the light emission efficiency and stability of Ge-Pb perovskite films and PeLEDs with 30 and 60 mol % Ge, through A-site modulation. The maximum external quantum efficiencies of the Ge-Pb PeLEDs with 30 and 60 mol % Ge are 8.5% and 3.0% at 3.32 mA cm-2 (∼922 cd m-2) and 0.53 mA cm-2 (∼60 cd m-2), respectively. Time-resolved transient absorption spectroscopy analysis of Ge-Pb perovskite films on different hole-transport layers shows that incorporating 30 mol % Ge into the perovskite with mixed A-site cations can effectively suppress trap-assisted recombination. Further analysis of their current density-voltage (J-V) curves reveals the efficiency loss mechanisms of Ge-Pb PeLEDs with high Ge fractions, indicating the possibility of further improvements.

5-HT induces regulatory B cells in fighting against inflammation-driven ulcerative colitis.

Serotonin (5-hydroxytryptamine or 5-HT) is a neuroendocrine peptide endowed with immunomodulatory functions. Regulatory B cells (Bregs) play an important role in maintaining intestinal immune homeostasis. We analyzed the differences of 5-HT and Bregs between peripheral blood of ulcerative colitis (UC) and healthy controls (HC). Besides, 5-HT-treated B cells were adoptively transferred into colitis mice to elucidate the role of 5-HT in regulating Bregs. The level of serum 5-HT and IL-10 in UC patients was lower and both were negatively correlated with disease activity. 5-HT7 receptor (5-HT7R) was higher expressed on Bregs in UC. 5-HT promoted IL-10 production in Bregs through the activation of STAT3. And adoptive transfer of 5-HT-treated B cells alleviated intestinal inflammation via inducing IL-10-producing B cells in mice. Our results suggest that 5-HT/5-HT7R signaling pathway facilitate functional Bregs in constraining inflammation in UC, which may be a new potential prospect in the treatment of UC.

Modified nusinersen intrathecal injection method: inclusion of a septal needle-free closed infusion connector.

Objective: Nusinersen, an extremely expensive biologic drug (around 100,000 US$ per dose) that needs to be administered intrathecally, is approved for the treatment of 5q-spinal muscular atrophy (SMA). Because of the low muscle tone of the back muscles of pediatric SMA patients, especially type 1 SMA patients, the safe, effective, and fast execution of sheath injection is needed. Therefore, a modified intrathecal injection method was developed accordingly. This paper aims to describe the applicability and safety of this modified method. Methods: The modified intrathecal injection method (MIIM) mainly includes a septal needle-free closed infusion connector between the lumbar puncture needle and the syringe, besides the procedures of routine lumbar puncture. Its applicability and safety were evaluated through clinical observation. Results: A total of 92 children with SMA have successfully received nusinersen treatment at our hospital using the modified method since 2019 without obvious adverse events related to the modified injection method. Based on the clinical feedback of operators, the advantages of the modified method include successfully injecting the total dose of nusinersen with constant injection rate and a more stable fixation of the puncture needle, as well as making the operator more relaxed. However, compared with the routine method, the procedure of the modified method has additional steps. Conclusion: The modified intrathecal injection method is an effective and safe method to inject nusinersen when weighing the pros and cons, and it may also be used for administering intrathecal injections of other expensive medicines or for patients with other strict requirements for intrathecal injection.

Study on the absorption uniformity of optical thin films based on the photothermal detuning technique.

Absorption loss in optical components, particularly in optical coatings, is a limiting factor in high-power laser applications. The uniformity of optical coatings becomes more and more important as large-diameter optical devices are used widely. In this paper, the photothermal detuning technique used for absorption uniformity measurement of optical thin films is developed for the first time. Experiments are conducted with a highly reflective coating used in 514 nm to measure the photothermal detuning signal and to evaluate the absorption at 514 nm by detecting the spectral shift with a probe beam at a wavelength of 632.8 nm. The relative absorption at different points on the sample surface can be measured by moving the sample two-dimensionally, and we use the measured data to make the absorption image. The results show that the designed experimental system can be used to analyze the absorption uniformity of optical coatings. The obtained images reflect the absorption uniformity of the sample well. The absorption uniformities of the two samples analyzed in this experiment are different. The film coated on fused silica is better. The research provides a powerful and convenient tool for absorption uniformity measurement of optical thin film.

Biosynthesis of new lipopentapeptides by an engineered strain of Streptomyces sp.

Arylomycins are type I signal peptidase inhibitors and have a potential as a new type of antibiotics. They were identified from the broth of Streptomyces sp. HCCB10043. The arylomycin biosynthetic gene cluster in this strain was identical to that in S. roseosporus. Within the gene cluster, aryC, encoding a P450 enzyme, was deduced to be responsible for biaryl bond formation in, the arylomycins. Inactivation of aryC abolished arylomycin production and led to the generation of two novel linear lipopentapeptides lacking the aryl-aryl linkage. These derivatives had lost their antibacterial activities against Staphylococcus epidermidis which is sensitive to arylomycins A2 and A4.