Application of PolyPRep tools on HIV protease polyproteins using molecular docking

Abstract In recent years, the development of high-throughput technologies for obtaining sequence data leveraged the possibility of analysis of protein data in silico. However, when it comes to viral polyprotein interaction studies, there is a gap in the representation of those proteins, given their size and length. The prepare for studies using state-of-the-art techniques such as Machine Learning, a good representation of such proteins is a must. We present an alternative to this problem, implementing a fragmentation and modeling protocol to prepare those polyproteins in the form of peptide fragments. Such procedure is made by several scripts, implemented together on the workflow we call PolyPRep, a tool written in Python script and available in GitHub. This software is freely available only for noncommercial users.

Resumo Nos últimos anos, o desenvolvimento de tecnologias de alto rendimento para obtenção de dados sequenciais potencializou a possibilidade de análise de dados proteicos in silico. No entanto, quando se trata de estudos de interação de poliproteínas virais, existe uma lacuna na representação dessas proteínas, devido ao seu tamanho e comprimento. Para estudos utilizando técnicas de ponta como o Aprendizado de Máquina, uma boa representação dessas proteínas é imprescindível. Apresentamos uma alternativa para este problema, implementando um protocolo de fragmentação e modelagem para preparar essas poliproteínas na forma de fragmentos de peptídeos. Tal procedimento é feito por diversos scripts, implementados em conjunto no workflow que chamamos de PolyPRep, uma ferramenta escrita em script Python e disponível no GitHub. Este software está disponível gratuitamente apenas para usuários não comerciais.

Application of PolyPRep tools on HIV protease polyproteins using molecular docking / Aplicação da ferramenta PolyPRep em poliproteínas de protease de HIV usando docking molecular

Abstract In recent years, the development of high-throughput technologies for obtaining sequence data leveraged the possibility of analysis of protein data in silico. However, when it comes to viral polyprotein interaction studies, there is a gap in the representation of those proteins, given their size and length. The prepare for studies using state-of-the-art techniques such as Machine Learning, a good representation of such proteins is a must. We present an alternative to this problem, implementing a fragmentation and modeling protocol to prepare those polyproteins in the form of peptide fragments. Such procedure is made by several scripts, implemented together on the workflow we call PolyPRep, a tool written in Python script and available in GitHub. This software is freely available only for noncommercial users.

Resumo Nos últimos anos, o desenvolvimento de tecnologias de alto rendimento para obtenção de dados sequenciais potencializou a possibilidade de análise de dados proteicos in silico. No entanto, quando se trata de estudos de interação de poliproteínas virais, existe uma lacuna na representação dessas proteínas, devido ao seu tamanho e comprimento. Para estudos utilizando técnicas de ponta como o Aprendizado de Máquina, uma boa representação dessas proteínas é imprescindível. Apresentamos uma alternativa para este problema, implementando um protocolo de fragmentação e modelagem para preparar essas poliproteínas na forma de fragmentos de peptídeos. Tal procedimento é feito por diversos scripts, implementados em conjunto no workflow que chamamos de PolyPRep, uma ferramenta escrita em script Python e disponível no GitHub. Este software está disponível gratuitamente apenas para usuários não comerciais.

TRANSIENT STRUCTURES FOR STREET VENDORS: VIABLE DESIGN INTERVENTIONS

The commercial sector in India is ever-changing with a visible divide in different aspects of the operations, this leads to the creation of different sectors of the economy namely the 'formal' and the 'informal sector'. There is a wide disparity in documentation and assessment needs of the commercial setups involved in different types of activities in such 'unorganized' or 'informal' units. The Government of NCT of Delhi data on street vendors indicates that Delhi has an estimate of over 4 lakh vendors who are working in the informal sector as street vendors, roadside tea sellers, small roadside nursery owners, etc. all these setups require a special type of planning & consideration as these vendors have limited resource availability, with many of these street vendors finding accommodations in their mobile carts, and unplanned roadside setups. The state of livelihood and resource access remains limited for these 'informal' vendors. Issues such as the access to 'safe' infrastructure, permits & certification to operate as street vendors limit their social and economic well-being. Such concerns require significant social and design interventions to ensure the social, physical, and economic well-being of the vendors on 'the streets'.

Qualitative ultrasound biomicroscopy of the normal anterior segment

Background: Ultrasound biomicroscopy (UBM) is a high?resolution ultrasound technique that allows noninvasive, in vivo imaging of the ocular anterior segment structures. Before interpreting the UBM images of the diseased eyes, it is essential to understand the structures seen in the UBM image of the normal eye. Purpose: This video is a compilation of short video clips that gives description of identification of the anterior segment structures in the axial scan, a cross?sectional view through the anterior chamber angle region of a normal subject in a radial scan, and identification of ciliary processes in the transverse scan. Synopsis: UBM provides two?dimensional, grayscale images of the various anterior segment structures and allows all these structures to be imaged simultaneously, in their normal state, as they occur in the living eye. The real?time image is displayed on a video monitor and can be recorded for qualitative and quantitative analysis. Highlights: The video gives an overview of identification of normal anterior segment structures on UBM.

Fatigue resistance of monolithic and multilayer zirconia crowns using veneer layering or CAD-on technique

Abstract This study aims to evaluate the fatigue resistance of monolithic zirconia (Yz) and multilayer ceramic structures using the CAD-on technique in different thicknesses. Fifty (N=50) standardized single crowns preparations were made in fiberglass-reinforced epoxy resin (NEMA grade G10), digitalized, and restorations were machined in CAD-CAM, composing 5 groups (n= 10): Control: 1.5 mm (milled zirconia framework + manual layered porcelain); Yz monolithic 1.5 mm; Yz monolithic 1.0 mm; CAD-on 1.5 mm; and CAD-on 1.0 mm (milled zirconia framework 0.5 mm thickness bonded by a low fuse ceramic to a milled lithium disilicate layer of 1.0 mm or 0.5 mm, respectively). The G10 bases were conditioned with 10% hydrofluoric acid; the crowns were air abraded with 110 μm alumina particles; and then luted onto each other with self-adhesive resin cement. A cyclic fatigue test was performed (initial load: 400N for 10,000 cycles, frequency of 20 Hz, step size of 200N) until failure, and the data was submitted to a survival statistical analysis. No failures were observed at Yz monolithic 1.5 mm. High and similar performance was observed for Cad-On groups and Yz monolithic 1.0 mm. The control group depicted the worst behavior. The Weibull modulus of CAD-on 1.5 mm was higher than the control while being similar to the other conditions. Both the monolithic systems and the CAD-on technique showed high and similar fatigue fracture behavior and survival rates, which were also higher than the control bilayer system. Both systems reduced the occurrence of delamination failures, making them suitable for clinical use.

Resumo Este estudo teve como objetivo avaliar o comportamento à fadiga de estruturas cerâmicas monolíticas de zircônia (Yz) e multicamadas utilizando a técnica CAD-on em diferentes espessuras. Cinquenta (N=50) preparos unitários padronizados foram confeccionados em resina epóxi reforçada com fibra de vidro (NEMA grau G10), digitalizados e as restaurações usinadas em CAD-CAM, compondo 5 grupos (n= 10): Controle: 1,5 mm (estrutura de zircônia fresada + porcelana estratificada manualmente); Yz monolítica 1,5 mm; Yz monolítica 1,0 mm; CAD-on em 1,5 mm; e CAD-on 1,0 mm (estrutura de zircônia fresada com 0,5 mm de espessura ligada por uma cerâmica de baixa fusão a uma camada de dissilicato de lítio fresado de 1,0 mm ou 0,5 mm, respectivamente). As bases do G10 foram condicionadas com ácido fluorídrico a 10%; as coroas foram jateadas com partículas de alumina de 110 μm; e então cimentadas uma sobre a outra com cimento resinoso autoadesivo. Foi realizado um teste de fadiga cíclica (carga inicial: 400N para 10.000 ciclos, frequência de 20 Hz, step de 200N) até a falha, e os dados foram submetidos a uma análise estatística de sobrevivência. Nenhuma falha foi observada para Yz monolítica de 1,5 mm. Desempenho alto e semelhante foi observado para os grupos Cad-On e Yz monolítica 1,0 mm. O grupo controle apresentou o pior comportamento. O módulo de Weibull do CAD-on 1,5 mm foi maior que o grupo controle, sendo semelhante às outras condições. Tanto os sistemas monolíticos quanto a técnica CAD-on apresentaram alto e semelhante desempenho mecânico e taxas de sobrevivência, que também foram superiores ao sistema bicamada de controle. Ambos os sistemas reduziram a ocorrência de falhas de delaminação, tornando-os adequados para uso clínico.

Human Telomeric i-motif: Its Structure‚ Recognition and Physiological Activity / 中国生物化学与分子生物学报

The human telomeric i-motif (htel-iM) is a unique higher-order DNA structure formed by the cytosine-rich (C) sequences at the end of human telomeres. Studies have shown that htel-iM plays a significant role in the transcriptional regulation of telomeric repeat-containing RNA (TERRA) ‚ maintenance of telomere function and inhibition of telomerase activity. Thus‚ it is closely related to the development and progression of many cancers and is a promising new target for cancer treatment therapy. Compared to other nucleic acid higher-order structures such as G-quadruplexes‚ the stability of htel-iM is much weaker and affected by many factors like buffer pH‚ ionic conditions and molecular crowding environments. Therefore the existence of the iM structures in near neutral physiological conditions has been uncertain for a long time. Recently‚ using in-vitro screened small molecule ligands to selectively recognize and stabilize htel-iM provides a new strategy for the exploration of the biological relevance of htel-iM. Thus it has become a research hotspot to take telomere as a cancer treatment target. However‚ so far the reported small molecule ligands selectively targeting the htel-iM are far from sufficient compared with those targeting other higher-order nucleic acid structures. In this review‚ the discovery and the characteristic of the iM structures are briefly described‚ with an emphasis on the in-vitro affecting factors of the htel-iM structure‚ the reported htel-iM ligands and its biological relevance and regulation mechanisms‚ which will be helpful in further exploration of the htel-iM structure and ligand screening in near physiological conditions‚ and understanding the mechanism and developing novel therapeutic strategies for cancer treatment targeting the htel-iM structures.

Urinary continence-related structures and intraoperative protective techniques in radical prostatectomy / 现代泌尿外科杂志

Radical prostatectomy (RP) is the standard treatment for patients with early-stage of prostate cancer,but often causes urinary incontinence and other complications, which harm patients’ quality of life. The protection and reconstruction of urinary continence-related structures during the operation are significant approaches to reduce the incidence of urinary incontinence and restore urinary continence. This article reviewed the surgical approaches of radical prostatectomy, anatomy of urinary continence-related structures (bladder neck, functional urethra, supporting structures, nerves and vessels) and the protective skills,hoping to provide reference for the treatment of early-stage prostate cancer.

Effect of PD1-TCF1+CD8+ Stem-like Memory T Cells on Immunotherapy Prognosis and Tertiary Lymphoid Structures in Tumors / 肿瘤防治研究

Objective To investigate the impact of PD1-TCF1+CD8+ stem-like memory T cells on immunotherapy prognosis and tertiary lymphoid structure in tumors. Methods Pathological tissue sections were collected from 33 patients treated with immunotherapy, 18 cases of NSCLC and 15 cases of ESCC. The expression of PD1-TCF1+CD8+T cells was detected through quantitative analysis by multiplex immunofluorescence. Survival curves were described by the Kaplan-Meier method. Pearson's correlation test was used for correlation analysis. Results The high levels of PD1-TCF1+CD8+T cells had a better PFS in NSCLC and ESCC cohorts. In the NSCLC cohort, high levels of PD1-TCF1+CD8+ T cells were significantly and positively correlated with the number (P=0.0151) and size (P=0.0007) of TLSs. Conclusion In patients with NSCLC and ESCCs, high PD1-TCF1+CD8+ stem-like memory T cell expression indicates improved prognosis and immune response and is associated with the formation of TLSs in the tumor microenvironment of NSCLC.

Design and validation of a novel knee biomechanical test method / 生物医学工程学杂志

A novel structural dynamics test method and device were designed to test the biomechanical effects of dynamic axial loading on knee cartilage and meniscus. Firstly, the maximum acceleration signal-to-noise ratio of the experimental device was calculated by applying axial dynamic load to the experimental device under unloaded condition with different force hammers. Then the experimental samples were divided into non-specimen group (no specimen loaded), sham specimen group (loaded with polypropylene samples) and bovine knee joint specimen group (loaded with bovine knee joint samples) for testing. The test results show that the experimental device and method can provide stable axial dynamic load, and the experimental results have good repeatability. The final results confirm that the dynamic characteristics of experimental samples can be distinguished effectively by this device. The experimental method proposed in this study provides a new way to further study the biomechanical mechanism of knee joint structural response under axial dynamic load.

α/Sulfono-γ-AA peptide hybrids agonist of GLP-1R with prolonged action both in vitro and in vivo

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t 1/2 > 14 days) compared to t 1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.

Application of StrucGP in medical immunology: site-specific N-glycoproteomic analysis of macrophages / 医学前沿

The structure of N-glycans on specific proteins can regulate innate and adaptive immunity via sensing environmental signals. Meanwhile, the structural diversity of N-glycans poses analytical challenges that limit the exploration of specific glycosylation functions. In this work, we used THP-1-derived macrophages as examples to show the vast potential of a N-glycan structural interpretation tool StrucGP in N-glycoproteomic analysis. The intact glycopeptides of macrophages were enriched and analyzed using mass spectrometry (MS)-based glycoproteomic approaches, followed by the large-scale mapping of site-specific glycan structures via StrucGP. Results revealed that bisected GlcNAc, core fucosylated, and sialylated glycans (e.g., HexNAc4Hex5Fuc1Neu5Ac1, N4H5F1S1) were increased in M1 and M2 macrophages, especially in the latter. The findings indicated that these structures may be closely related to macrophage polarization. In addition, a high level of glycosylated PD-L1 was observed in M1 macrophages, and the LacNAc moiety was detected at Asn-192 and Asn-200 of PD-L1, and Asn-200 contained Lewis epitopes. The precision structural interpretation of site-specific glycans and subsequent intervention of target glycoproteins and related glycosyltransferases are of great value for the development of new diagnostic and therapeutic approaches for different diseases.

The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications

Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our understanding of the dynamic regulation of histone methylation. Here, we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases), with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs. These structural studies inform HKMTs' roles in tumorigenesis and provide the foundations for developing new therapeutic approaches targeting HKMTs in cancers.

Clinical characteristics of pseudopapilledema combined with peripapillary hyper-reflective ovoid mass-like structures in children / 中华眼底病杂志

Objective:To observe the clinical characteristics and optical coherence tomography (OCT) features of pseudopapilledema (PPE) combined with peripapillary hyper-reflective ovoid mass-like structures (PHOMS) in children.Methods:A retrospective observational study. From October 2019 to May 2021, total 22 eyes from 12 children diagnosed as PPE combined with PHOMS in the Neuro-ophthalmology Department of The First Hospital of Xi’an (Affiliated of The First Hospital of Northwest University) were recruited. Among the children, 6 were male and 6 were female. The average age was (10.6±2.7) years. The average course from disease onset to diagnosis of PPE combined with PHOMS was (8.0±7.5) months. All patients underwent best corrected visual acuity (BCVA), relative afferent papillary defect (RAPD), Ishihara's test, fundus photography, OCT, fundus autofluorescence (FAF), ocular B-mode ultrasound, visual field and patternvisual evoked potential (P-VEP). The clinical and OCT characteristics of the patients were observed.Results:The anterior segments of the patients were normal. The intraocular pressures and Ishihara's test were all normal. All RAPD were negative. Total 22 eyes, BCVA was 1.0 in 21 eyes and one eye was 0.12. The fundus photography revealed blurred optic discs margin, showing mild to moderate edema-like elevation with more prominent in the nasal parts, presenting as a "C" shape halo. No obvious abnormal fluorescence was observed in FAF. The OCT scan of involvement eyes showed an elevated appearance in vary degrees, and the sharply marginated ovoid hyper-reflective mass-like structures which laterally herniated into the peripapillary region under retinal nerve fiber layer and above the Bruch membrane were detected with consecutive nasal enlargement scanning, corresponding to the nasal parts in the fundus photography. The higher degree of elevation, the larger the volume. Macular retina pigment epithelium layer and ganglion cell thickness were normal. Ocular B-mode ultrasound showed that the head of the optic nerve in the posterior wall of the eyeball (in front of the optic disc) was elevated in all affected eyes, and there was no strong signal echo in it. Visual field examination showed physical blind spot enlargement in 3 eyes and visual field defect in 2 eyes. P-VEP examination showed that the peak was slightly delayed in 3 eyes and the amplitude was slightly reduced in 3 eyes.Conclusions:Enlarged nasal optic disc OCT scan can improve the detection rate of PHOMS. PHOMS were detected bilaterally in the cases with binocular PPE while only in the effected eye in the cases of monocular PPE; the higher degree of PPE, the lager volume of PHOMS. PHOMS were could contribute to the diagnosis of PPE in children.

Role of tertiary lymphoid structures in tumor immune microenvironment regulation and anti-tumor therapy / 国际肿瘤学杂志

Tertiary lymphoid structures (TLSs) is important channel for tumor immune cell infiltration. The existence of tumor TLSs is not only related to the prognosis of patients, but also to the efficacy of a variety of anti-tumor therapies. To explore the function and immunomodulatory mechanism of TLSs and its potential value as a tumor prognostic biomarker in comprehensive anti-tumor therapy will provide new ideas for follow-up research.

Contaminação parasitária em hortaliças comercializadas no município de Jataí-GO / Parasitic contamination in vegetables commercialized in the city of Jataí-GO

Introdução: a prevalência de doenças parasitárias transmitidas por alimentos tem apresentado um aumento significativo em nível mundial, destacando principalmente as hortaliças, consumidas in natura, em razão da sociedade moderna que procura hábitos de vida mais saudáveis. Objetivo:avaliar a contaminação de hortaliças comercializadas no município de Jataí, GO, por enteroparasitos. Metodologia: foi realizada uma pesquisa experimental para detecção de estruturas parasitárias em hortaliças de cultivo tradicional e hidropônico, obtidas de nove estabelecimentos: três supermercados, três hortas e três feiras livres. Foram obtidas 54 amostras de alface (Lactuca sativa), 54 de rúcula (Chicarium sp.) e 18 de agrião (Nasturtiumofficinale). As amostras foram lavadas com água destilada e solução Tween 80 e submetidas as técnicas de sedimentação espontânea e por centrifugação. Foi realizado um mapeamento da área de estudo para identificação da localização dos estabelecimentos. Resultados: a positividade para estruturas parasitárias foi de 94,4% (119/126). A alface apresentou maior prevalência de parasitos 96,2% (52/54). Foi observada diferença estatística significativa ao comparar o emprego das duas técnicas (p < 0,05). Ashortaliças submetidas a técnica de sedimentação espontânea apresentaram maior positividade 115/126 (91,3%). Não foi observada diferença estatística significante quanto ao tipo de cultivo, porém, houve forte associação em relação ao local de cultivo e contaminação das hortaliças (OR: 3,625). Verificou-se maior percentual de positividade nos estabelecimentos localizados próximos aos rios. Conclusão: a positividade de enteroparasitos detectada nas hortaliças foi alta, ressaltando a necessidade de implementar medidas que visam a conscientização da população, em relação às práticas de higienização das hortaliças antes do consumo.

Introduction: the prevalence of parasitic diseases transmitted by food has shown a significant increase worldwide, especially vegetables, consumed in natura, due to modern society that seeks healthier lifestyles. Objective: to evaluate the contamination of vegetables commercialized in the city of Jataí, GO, by enteroparasites. Methodology: an experimental research was carried out to detect parasitic structures in vegetables of traditional and hydroponic cultivation, obtained from nine establishments: three supermarkets, three vegetable gardens and three street markets. Fifty four samples of lettuce (Lactuca sativa), 54 of arugula (Chicarium sp.) and 18 of watercress (Nasturtium officinale) were obtained. The samples were washed with distilled water and Tween 80 solution and submitted to spontaneous sedimentation and centrifugation techniques. A mapping of the study area was carried out to identify the location of the establishments. Results: positivity for parasitic structures was 94.4% (119/126). Lettuce had a higher prevalence of parasites 96.2% (52/54). A statistically significant difference was observed when comparing the use of the two techniques (p < 0.05). Vegetables submitted to the spontaneous sedimentation technique showed higher positivity 115/126 (91.3%). There was no statistically significant difference regarding the type of cultivation, however, there was a strong association in relation to the place of cultivation and contamination of vegetables (OR: 3.625). There was a higher percentage of positivity in establishments located near the rivers. Conclusion: the positivity of intestinal parasites detected in vegetables was high, highlighting the need to implement measures aimed at raising awareness of the population regarding the practices of cleaning vegetables before consumption.

Challenges in the use of nanostructures as carriers of nucleic acids in clinical practice

ABSTRACT The delivery of nucleic acids to cells is considered a crucial step for the success of genetic modifications aimed at therapeutic purposes or production of genetically modified animals. In this context, nanotechnology is one of the most promising fields of science, with the potential to solve several existing problems. Nanostructures have desirable characteristics to be used as carriers, such as nanometric size, large surface area, cell internalization capacity, prolonged and controlled release, among others. Genetically modified animals can contribute to the production of biopharmaceuticals, through the expression of high-associated-value molecules. The production of these animals, also known as biofactories, further enhances Brazilian agribusiness, since it allows adding value to the final product, and favors the integration between the agricultural market and the pharmaceutical sector. However, there is a growing concern about the safety and possible harmful effects of nanostructures, since data on the safe use of these materials are still insufficient. The objective of this review was to address aspects of the use of nanostructures, mainly carbon nanotubes as nucleic acid carriers, aiming at the production of genetically modified animals, with the certainty that progress in this field of knowledge depends on more information on the mechanisms of interaction between nanostructures, cells and embryos, as well as on its toxicity.

Effect of 1 064-nm Q-switched Nd:YAG laser on cell viability, protease activity and structures of Malassezia furfur / 中华皮肤科杂志

Objective:To investigate the effect of 1 064-nm Q-switched Nd:YAG laser at different energy settings on cell viability, protease activity and structures of Malassezia furfur. Methods:Cultured standard strains of Malassezia furfur were divided into several groups to be irradiated with 1 064-nm Q-switched Nd:YAG laser at different energies of 0 (control group) , 500, 600, 700, 800 and 900 mJ, respectively. Then, fungal suspensions in the above groups were inoculated onto the Leeming & Notman medium separately. After 7-day culture, the diameter and number of colonies were measured to evaluate the fungal cell viability, the protease activity was measured by using the whole-milk plate medium, and the ultrastructure of Malassezia furfur in each group was observed by transmission electron microscopy. One-way analysis of variance was used for comparisons among multiple groups, least significant difference- t test for multiple comparisons, and Pearson correlation analysis for analyzing correlations of laser energy with colony diameter, number and protease activity. Results:The colony diameter and number both significantly differed among the control group, 500-, 600-, 700-, 800- and 900-mJ groups (colony diameter: 4.05 ± 0.69, 3.76 ± 0.51, 3.28 ± 0.41, 3.09 ± 0.72, 2.54 ± 0.64 and 2.43 ± 0.41 mm, respectively; colony number: 4 787 ± 597, 4 287 ± 761, 1 879 ± 275, 1 082 ± 248 and 209 ± 42, 72 ± 31 colony-forming units, respectively; F = 14.83, 231.85, respectively, both P < 0.05) , and were significantly decreased in the 600-, 700-, 800- and 900-mJ groups compared with the control group (all P < 0.05) . The laser energy was negatively correlated with the colony diameter and number ( r = -0.67, -0.91, respectively, both P < 0.05) . The protease activity significantly differed among the control group, 500-, 700- and 900-mJ groups ( F = 346.60, P < 0.05) , and was significantly lower in the 700- and 900-mJ groups than in the control group (both P < 0.05) . There was a negative correlation between the laser energy and protease activity ( r = -0.94, P < 0.05) . Transmission electron microscopy showed intact fungal structures in the control group, relatively intact fungal structures in the 500-mJ group, and obviously damaged fungal structures in the 600- to 900-mJ groups, and the greater the laser energy, the more severely the fungal structures were damaged. Conclusion:The 1 064-nm Q-switched Nd:YAG laser could affect the cell viability of and protease activity in Malassezia furfur, and damage its structures.

Research progress of tertiary lymphatic structure in head and neck squamous cell carcinoma / 国际外科学杂志

Head and neck squamous cell carcinoma is the sixth most common malignant carcinoma worldwide, about 60% of patients are in advanced stage at the time of visit, the incidence rate is increasing gradually while the 3-year-survival rate has not been improved .Since most patients have reached advanced stage at the time of diagnosis, it brings great difficulties to treatment and leads to poor prognosis. In recent years, many articles have found out that Tertiary lymphoid structures are in and around samples of HNSCC patients and are positively related to disease progession and outcome of patients. In-depth analysis of TLS in the formation of HNSCC and the function in tumor micro environment can help estimate the prognosis of patients and provide guidance for future treatment In this article, the compositions, functions, current research of TLS with its prognostic factors and its influence on future treatment in HNSCC will be reviewed.

Recent advances in the application of nanobody technology: a review / 生物工程学报

As a malleable and novel tool for antigen recognition and modulation, nanobodies have the advantages of small size, easiness of expression, screening and modification, as well as high affinity and stability. Nanobodies are capable of recognizing more cryptic antigenic epitopes that are difficult to be recognized by traditional antibodies, making them increasingly used in the diagnosis and treatment of various diseases and assays. Nanobodies are also playing an irreplaceable role in the basic research. This review summarized the recent development of nanobodies and their derivatives in the detection of small molecules, pathogenic microorganisms and diagnosis of diseases, as well as in the fields of targeted therapies, cellular and molecular imaging. Broad prospects of nanobodies in the field of protein conformation studies were also reviewed.

Consideraciones didácticas para la instrumentación de la Estadística en la formación investigativa del médico general integral / Didactic Considerations for the Instrumentation of Statistics in the Research Training of the Comprehensive General Doctor

Introducción: Estudios realizados en los últimos años señalan dificultades en torno al componente investigativo del programa de formación del médico general integral destacando la inadecuada utilización de la Estadística por parte de sus especialistas en estrecha relación con insuficiencias que tienen lugar durante su formación. Objetivo: Proponer algunas consideraciones didácticas para dar solución a las inconsistencias que presenta la formación de la dimensión investigativa de los especialistas en medicina general integral en relación a la utilización de la Estadística. Material y Métodos: Revisión documental de artículos y trabajos referentes al estado actual del uso de la Estadística en la actividad científica de médicos generales integrales y su relación con insuficiencias durante la formación de la dimensión investigativa de estos especialistas. Las fuentes de información consultadas fueron accedidas a través de diferentes buscadores y bases de datos, entre ellas SciELO, Google Académico, Medline y Pubmed. Resultados y discusión: Los trabajos analizados demuestran que el proceso de formación de la dimensión investigativa de los especialistas de medicina general integral manifiesta insuficiencias durante la aplicación de la Estadística, determinado por una inadecuada instrumentación de sus contenidos en el programa docente. Conclusiones: Existe una instrumentación inadecuada de la Estadística en el programa docente para el desarrollo de la dimensión investigativa de los especialistas de medicina general integral. Se sugieren algunas consideraciones didácticas para la instrumentación de la Estadística en la formación del médico general integral(AU)

Introduction: Studies carried out in recent years indicate difficulties around the investigative component of the comprehensive general practitioner training program, highlighting the inadequate use of Statistics by its specialists in close relation to shortcomings that occur during their training. Objective: To propose some didactic considerations to solve the inconsistencies presented by the training of the investigative dimension of specialists in comprehensive general medicine in relation to the use of Statistics. Material and Methods: Documentary review of articles and works referring to the current state of the use of Statistics in the scientific activity of comprehensive general practitioners and its relationship with deficiencies during the training of the investigative dimension of these specialists. The sources of information consulted were accessed through different search engines and databases, including SciELO, Google Academic, Medline and Pubmed. Results and Discussion: The analyzed works show that the process of formation of the investigative dimension of the specialists of integral general medicine shows insufficiencies during the application of the Statistics, determined by an inadequate instrumentation of its contents in the teaching program. Conclusions: There is an inadequate instrumentation of Statistics in the teaching program for the development of the investigative dimension of specialists in general comprehensive medicine. Some didactic considerations are suggested for the instrumentation of Statistics in the training of the comprehensive general practitioner(AU)