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The goal of this study was to evaluate the diagnostic performance of 3D amide proton transfer-weighted (3D-APTW) imaging and 3D pseudocontinuous arterial spin labelling (3D-pCASL) alone and in combination in grading gliomas (low-grade glioma (LGG) vs. high-grade glioma (HGG)) and correlating isocitrate dehydrogenase (IDH) mutation status.Preoperatively, 81 patients with pathologically confirmed gliomas underwent 3.0-T magnetic resonance imaging (MRI) examinations. The APTW, relative APTW (rAPTW), cerebral blood flow (CBF), and relative CBF (rCBF) values were calculated to evaluate the solid components of the tumours. The MRI parameters were compared in the classification of gliomas by independent- and paired-samples t tests. A receiver operating characteristic (ROC) curve was constructed, and the area under the ROC curve (AUC) was calculated to assess the diagnostic performance of each parameter and the combination of the rAPTW and rCBF values.Patients with HGG showed significantly higher APTW, rAPTW, CBF, and rCBF values than those with LGG (all p 0.001). In the ROC curve analysis, the AUC of rAPTW was the highest at 0.90. By adding the rAPTW signal to the rCBF values, the diagnostic ability of the combined parameters improved from 0.90 to 0.96. The rAPTW value yielded the highest AUC (0.92) in correlating the IDH mutation status, and the diagnostic ability improved to 0.96 by adding it to the rCBF value.3D-APTW imaging combined with 3D-pCASL imaging may be used to aid assessment of grading glioma and IDH mutation status.

For different heat treatments, the changes in overall performance features such as tenacity, modulus, load at 5% strain and elongation at a load of 4.0 cN/dtex of high modulus low shrinkage poly (ethylene terephthalate) industrial fibers were compared. The variations in the mechanical behavior were linked to adjustments in the microstructure, as determined by Fourier transform infrared spectroscopy, wide-angle X-ray diffraction and small-angle X-ray scattering. The results confirmed that the tenacity of the fibers is less dependent on the heat treatment conditions, whereas the modulus, load at 5% strain and elongation at a load of 4.0 cN/dtex differ significantly, which could reflect the stability of the fibers in use. The intact crystal structure and the constrained conformation adjustment of molecular chains in amorphous after heat treatment are responsible for the excellent tenacity retention of high modulus low shrinkage poly (ethylene terephthalate) fibers. With a low pre-tension and a higher heating temperature, the molecular chains in the amorphous region relax and disorient, resulting in a lower modulus and load at 5% strain. Instead, in the case of high pre-tension, heat treatment prolongation or temperature increase helps to rearrange the amorphous region into an ordered structure, which can improve the initial modulus and load at 5% strain of the fibers.

A nondegenerate hypersurface in a pseudo-Euclidean space $ \mathbb{E}^{n+1}_{s} $ is called to have proper mean curvature vector if its mean curvature $ \vec{H} $ satisfies $ \Delta \vec{H} = \lambda \vec{H} $ for a constant $ \lambda $. In 2013, Arvanitoyeorgos and Kaimakamis conjectured [1]: any hypersurface satisfying $ \Delta \vec{H} = \lambda \vec{H} $ in pseudo-Euclidean space $ \mathbb E_{s}^{n+1} $ has constant mean curvature. This paper will give further support evidences to this conjecture by proving that a linear Weingarten hypersurface $ M^{n}_{r} $ in $ \mathbb E^{n+1}_{s} $ satisfying $ \Delta \vec{H} = \lambda \vec{H} $ has constant mean curvature if $ M^{n}_{r} $ has diagonalizable shape operator with less than seven distinct principal curvatures.

Lung cancer is one of the leading causes of cancer death and impose an enormous economic burden on patients. It is important to develop an accurate risk assessment model to determine the appropriate treatment for patients after the initial diagnosis of lung cancer. The Cox proportional hazards model is mostly utilized in survival analysis. However, real-world medical data is always incomplete, which poses a great challenge to the application of the Cox proportional hazards model. The commonly used imputation methods cannot achieve sufficient accuracy in the issue of missing data, which drives us to investigate the novel imputation methods for the development of clinical prediction models. In this article, we present a novel missing data imputation method: Bayesian networks for inferring missing covariates. We collected a total of 5,240 patients diagnosed with lung cancer from Weihai Municipal Hospital, China. Then we applied a joint model that combined a Bayesian network and a Cox model to predict mortality risk in individual patients with lung cancer. The established prognostic model achieved a good predictive performance in discrimination and calibration. Through experiments, we proved that the Bayesian network methodology is a robust and accurate approach to addressing the issue of missing data. We showed that combining the Bayesian network with the Cox proportional hazards model is highly beneficial, providing a more efficient tool for risk prediction.

BACKGROUND Composite grafts have previously been reported to achieve a good outcome for nasal defect repair, but composite grafts have greater metabolic needs than simple skin. Therefore, the traditionally recommended size of a composite graft for nasal reconstruction is less than 1.5 cm in diameter. However, the distal nose is generally well supplied with blood vessels, which might support the use of larger composite grafts in such a highly vascularized recipient site. The aim of the article is to investigate whether a large skin-fat-fascia composite graft (larger than 2.0 cm) is viable for the repair of partial-thickness nasal defects. METHODS From October 2017 to December 2019, 13 patients with partial-thickness nasal defects underwent nasal reconstruction using a large postauricular skin-fat-fascia composite graft. Cases were followed up for 3 to 14 months postoperatively. The aesthetic outcome was evaluated in comparison with preoperative digital images. RESULTS Skin-fat-fascia composite grafts survived without graft necrosis, dermal fibrosis, or skin contraction in all cases. Favorable aesthetic outcomes were obtained in all patients, and no further revision surgery was need. CONCLUSIONS A postauricular composite graft larger than 2.0 cm is a safe and effective reconstruction approach for partial-thickness nasal defects. This technique offers significant advantages in terms of no additional facial scar, no visible asymmetry on the face, no additional surgery for revision, and with mild scar in the donor site of the postauricular region.

To assess and compare the diagnostic performance of 3D amide proton-transfer-weighted (3D-APTW) imaging, 3D pseudocontinuous arterial spin-labeling (3D-PcASL) imaging, and diffusion-weighted imaging in distinguishing true progression (TP) from treatment response (TR) in posttreatment malignant glioma patients.Forty-eight patients with suspected tumor recurrence were prospectively enrolled. Histological or longitudinal routine MRI follow-up over six months was assessed to confirm lesion type. The apparent diffusion coefficient (ADC), relative APTWThe TP group showed a significantly higher rAPTW and rCBF than the TR group; the AUCs of rAPTW and rCBF to distinguish between TP and TR were 0.911 (with sensitivity of 90.3% and specificity of 82.4%) and 0.852 (with sensitivity of 80.6% and specificity of 82.4%), respectively. By adding the rAPTW values to rCBF values, the diagnostic ability was improved from 0.852 to 0.951. ADC showed no significant differences between the TP and TR groups, with an AUC lower than 0.70.Both 3D-PcASL and 3D-APTW imaging could distinguish TP from TR, and 3D-APTW had a better diagnostic performance. Combining the rAPTW values and rCBF values achieved a better diagnostic performance.

Stretchable conductive fibers offer unparalleled advantages in the development of wearable strain sensors for smart textiles due to their excellent flexibility and weaveability. However, the practical applications of these fibers in wearable devices are hindered by either contradictory properties of conductive fibers (high stretchability versus high sensing stability), or lack of manufacturing scalability. Herein, we present a facile approach for highly stretchable self-crimping fiber strain sensors based on a polyether-ester (TPEE) elastomer matrix using a side-by-side bicomponent melt-spinning process involving two parallel but attached components with different shrinkage properties. The TPEE component serves as a highly elastic mechanical support layer within the bicomponent fibers, while the conductive component (E-TPEE) of carbon black (CB), multiwalled carbon nanotubes (MCNTs) and TPEE works as a strain-sensitive layer. In addition to the intrinsic elasticity of the matrix, the TPEE/E-TPEE bicomponent fibers present an excellent form of elasticity due to self-crimping. The self-crimping elongation of the fibers can provide a large deformation, and after the crimp disappears, the intrinsic elastic deformation is responsible for monitoring the strain sensing. The reliable strain sensing range of the TPEE/E-TPEE composite fibers was 160%–270% and could be regulated by adjusting the crimp structure. More importantly, the TPEE/E-TPEE fibers had a diameter of 30–40 µm and tenacity of 40–50 MPa, showing the necessary practicality. This work introduces new possibilities for fiber strain sensors produced in standard industrial spinning machines.

Supercapacitors (SCs) are drawing considerable attention because of their remarkable power density, long cycling stability, quick charging/discharging, and environmentally friendly characteristics. They are currently applied in electronic devices and wearable energy storage systems. Recently, the use of asymmetric supercapacitors (ASCs) has been acknowledged as a valid strategy to improve energy density of SCs due to the combination of electric double-layered anodes and redox-schemed cathodes. Here, mesoporous hollow NiCo2S4 sub-microspheres and porous graphene/single-walled carbon nanotubes are synthesized by a simple and elegant method without any use of templates. The as-synthesized products exhibit improved capacitive performance and extraordinary stability. An assembled asymmetric supercapacitor with graphene/single-walled carbon nanotubes and NiCo2S4 as its negative and positive electrodes, respectively, delivers a maximum energy density of 45.3 W h kg−1 (at 800 W kg−1) and an outstanding cycling life (87.5% over 20,000 cycles). This suggests that the obtained products possess huge potential to become the next generation of electrode materials for future energy storage devices.

To explore the feasibility of developing bio-based elastic fibers, bio-based polylactide (PLA) and polytrimethylene terephthalate (PTT) were selected for fabrication of side-by-side bicomponent fibers using bi-constituent melt-spinning technology. The structure development and performance of PLA/PTT bicomponent fibers was investigated using thermal mechanical analysis, differential scanning calorimetry, and wide-angle X-ray diffraction in order to evaluate the crimp formability of PLA/PTT bicomponent fibers. The PLA and PTT components could form regular boundary structure and exhibit excellent interface compatibility by regulation of the rheological behavior of the two melts. In the fiber forming process, the PTT component in PLA/PTT bicomponent fibers experienced higher tensile stress, and thereby enhanced the crystal and oriented structure development, while the structural evolution of the PLA component was inhibited. The difference in the structure of the two components causes the imbalance force existence in the PLA/PTT fibers, which is the main reason of fiber crimp. In addition, the crimp formability of the PLA/PTT fibers could be enhanced by expanding the shrinkage stress difference between the two components, which could be realized by increasing the PTT ratio in PLA/PTT bicomponent fiber or draw ratio. The maximum crimp extension that could be achieved was 85% for the bicomponent fibers with PLA30/PTT70 ratio at a draw ratio of 4.2.

The flySAM/CRISPRa system has recently emerged as a powerful tool for gain-of-function studies in Drosophila melanogaster. This system includes Gal4/UAS-driven dCas9 activators and U6 promoter-controlled sgRNA. Having established dCas9 activators superior to other combinations, to further enhance the efficiency of the targeting activators we systematically optimized the parameters of the sgRNA. Interestingly, the most efficient sgRNAs were found to accumulate in the region from -150bp to -450bp upstream of the transcription start site (TSS), and the activation efficiency showed a strong positive correlation with the GC content of the sgRNA targeting sequence. In addition, the target region is dominant to the GC content, as sgRNAs targeting areas beyond -600bp from the TSS lose efficiency even when containing 75% GC. Surprisingly, when comparing the activities of sgRNAs targeting to either DNA strand, sgRNAs targeting to the non-template strand outperform those complementary to the template strand, both in cells and in vivo. In summary, we define criteria for sgRNA design which will greatly facilitate the application of CRISPRa in gain-of-function studies.

Cardiovascular disease is the leading cause of global mortality, with anticoagulant therapy being the main prevention and treatment strategy. Recombinant hirudin (r-hirudin) is a direct thrombin inhibitor that can potentially prevent thrombosis via subcutaneous (SC) and intravenous (IV) administration, but there is a risk of haemorrhage via SC and IV. Thus, microneedle (MN) provides painless and sanitary alternatives to syringes and oral administration. However, the current technological process for the micro mould is complicated and expensive. The micro mould obtained via three-dimensional (3D) printing is expected to save time and cost, as well as provide a diverse range of MNs. Therefore, we explored a method for MNs array model production based on 3D printing and translate it to micro mould that can be used for fabrication of dissolving MNs patch. The results show that r-hirudin-loaded and hyaluronic acid (HA)-based MNs can achieve transdermal drug delivery and exhibit significant potential in the prevention of thromboembolic disease without bleeding in animal models. These results indicate that based on 3D printing technology, MNs combined with r-hirudin are expected to achieve diverse customizable MNs and thus realize personalized transdermal anticoagulant delivery for minimally invasive and long-term treatment of thrombotic disease.

The COVID-19 disease caused by the SARS-CoV-2 virus is a health crisis worldwide. While developing novel drugs and vaccines is long, repurposing existing drugs against COVID-19 can yield treatments with known preclinical, pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter clinical trials. In this study, we present a novel network-based drug repurposing platform to identify candidates for the treatment of COVID-19. At the time of the initial outbreak, knowledge about SARS-CoV-2 was lacking, but based on its similarity with other viruses, we sought to identify repurposing candidates to be tested rapidly at the clinical or preclinical levels. We first analyzed the genome sequence of SARS-CoV-2 and confirmed SARS as the closest virus by genome similarity, followed by MERS and other human coronaviruses. Using text mining and database searches, we obtained 34 COVID-19-related genes to seed the construction of a molecular network where our module detection and drug prioritization algorithms identified 24 disease-related human pathways, five modules, and 78 drugs to repurpose. Based on clinical knowledge, we re-prioritized 30 potentially repurposable drugs against COVID-19 (including pseudoephedrine, andrographolide, chloroquine, abacavir, and thalidomide). Our work shows how in silico repurposing analyses can yield testable candidates to accelerate the response to novel disease outbreaks.

MXenes are an emerging class of highly conductive two-dimensional (2D) materials with electrochemical storage features. Oriented macroscopic Ti3C2Tx fibers can be fabricated from a colloidal 2D nematic phase dispersion. The layered conductive Ti3C2Tx fibers are ideal candidates for constructing high-speed ionic transport channels to enhance the electrochemical capacitive charge storage performance. In this work, we assemble Ti3C2Tx fibers with a high degree of flake orientation by a wet spinning process with controlled spinning speeds and morphology of the spinneret. In addition to the effects of cross-linking of magnesium ions between Ti3C2Tx flakes, the electronic conductivity and mechanical strength of the as-prepared fibers have been improved to 7200 S cm-1 and 118 MPa, respectively. The oriented Ti3C2Tx fibers present a volumetric capacitive charge storage capability of up to 1360 F cm-3 even in a Mg-ion based neutral electrolyte, with contributions from both nanofluidic ion transport and Mg-ion intercalation pseudocapacitance. The oriented 2D Ti3C2Tx driven nanofluidic channels with great electronic conductivity and mechanical strength endows the MXene fibers with attributes for serving as conductive ionic cables and active materials for fiber-type capacitive electrochemical energy storage, biosensors, and potentially biocompatible fibrillar tissues.

Background and purpose Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer. Nevertheless, thrombin expression in non-small cell lung cancer (NSCLC) primary tumour tissues and the association between prognosis of NSCLC patients remain largely unknown. Experimental approach Clinical pathological analysis was performed to determine the relationship between thrombin and tumour progression. Effects of r-hirudin and direct thrombin inhibitor peptide (DTIP) on cancer progression were evaluated. Western blotting, immunohistochemistry, and immunofluorescence were used to explore the inhibition mechanism of r-hirudin and DTIP. The therapeutic effect of the combination of DTIP and chemotherapy was determined. Key results Thrombin expression in NSCLC tissues was closely related to clinicopathological features and the prognosis of patients. Thrombin deficiency inhibited tumour progression. The novel thrombin inhibitors, r-hirudin and DTIP, inhibited cell invasion and metastasis in vitro. They inhibited tumour growth and metastasis in orthotopic lung cancer model, inhibited cell invasion, and prolonged survival after injection of tumour cells via the tail vein. They also inhibited angiogenesis and spontaneous metastases from subcutaneously inoculated tumours. The promotion by thrombin of invasion and metastasis was abolished in PAR-1-deficient NSCLC cells. r-hirudin and DTIP inhibited tumour progression through the thrombin-PAR-1-mediated RhoA and NF-κB signalling cascades via inhibiting MMP9 and IL6 expression. DTIP potentiated chemotherapy-induced growth and metastatic inhibition and inhibited chemotherapy-induced resistance in mice. Conclusions and implications Thrombin makes a substantial contribution, together with PAR-1, to NSCLC malignancy. The anti-coagulants, r-hirudin and DTIP, could be used in anti-tumour therapy and a combination of DTIP and chemotherapy might improve therapeutic effects.

Benefiting from the development of network pharmacology, Traditional Chinese Medicine (TCM) shows great potential in modern drug discovery. Recently, more and more TCM-related databases have been established for both academic and industry research, but they are still insufficient in data standardization, integrity, and precision. To better accelerate the TCM research and overcome these shortcomings, we construct a web-based TCM platform, LTM-TCM, which is currently the most comprehensive TCM database that includes the following advantages: (1) High-quality data integration from fourteen TCM authoritative databases, especially with additional manual collected 41,025 clinical treatment records and 213 ancient Chinese medical books. (2) Accurate correction of multi-source TCM interactions (between symptoms, prescriptions, herbs, ingredients and targets) through in-house Biomedical Natural Language Processing (BioNLP) approaches in more than 30 million articles. (3) Diverse cross-field pipelines (e.g., bioactive ingredients screening, targets prediction, and mechanism prediction, etc.) help integrating traditional medicine with modern science in common aspects at both the molecular and phenotypic levels. In summary, LTM-TCM contains 1928 symptoms, 48,126 prescriptions, 9122 plants, 34,967 ingredients, 13,109 targets and 1170,133 interactions among all TCM related components. LTM-TCM has both Chinese and English interfaces, and it is accessible at http://cloud.tasly.com/#/tcm/home.

With the development of laryngeal microsurgery, the requirements for the flexibility and convenience of surgical instruments are increasing. The research on related instruments has important value for the clinical application of laryngeal microsurgery. We have redesigned a gun-type tube-guide device of laser fiber by comparing the shortcomings of existing laser fiber introducers. The innovation of this design lies in its rotating nut device with adjustable laser angle and pre-bent tip. The corresponding

The COVID-2019 disease caused by the SARS-CoV-2 virus (aka 2019-nCoV) has raised significant health concerns in China and worldwide. While novel drug discovery and vaccine studies are long, repurposing old drugs against the COVID-2019 epidemic can help identify treatments, with known preclinical, pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter Phase 3 or 4 or can be used directly in clinical settings. In this study, we presented a novel network based drug repurposing platform to identify potential drugs for the treatment of COVID-2019. We first analysed the genome sequence of SARS-CoV-2 and identified SARS as the closest disease, based on genome similarity between both causal viruses, followed by MERS and other human coronavirus diseases. Using our AutoSeed pipeline (text mining and database searches), we obtained 34 COVID-2019-related genes. Taking those genes as seeds, we automatically built a molecular network for which our module detection and drug prioritization algorithms identified 24 disease-related human pathways, five modules and finally suggested 78 drugs to repurpose. Following manual filtering based on clinical knowledge, we re-prioritized 30 potential repurposable drugs against COVID-2019 (including pseudoephedrine, andrographolide, chloroquine, abacavir, and thalidomide) . We hope that this data can provide critical insights into SARS-CoV-2 biology and help design rapid clinical trials of treatments against COVID-2019.

In situ studies of structure and performance changes in aromatic copolysulfonamide (co-PSA) fibers during stretching at different thermal exposure temperature range from room temperature to 300 °C were carried out using synchrotron small angle X-ray scattering and wide angle X-ray scattering techniques. Results showed that the optimum microstructure and mechanical property of co-PSA fibers were achieved when stretched at 200 °C, the fibril length, fibril misorientation, crystal sizes L002 reached minimum, the long period became maximum at the same strain indicating that lamella and fibrils aligned perfectly, fiber structure compactness at 200 °C. During stretching at RT to 200 °C, at low strain, fibril length, crystal size L002 increased, fibrils oriented along stretching direction, the long period was enlarged; the opposite trend evolution of structure appeared under high strain. But stretching at 300 °C, L002 increased, fibril orientation became poor, the lamellae destroyed easily resulting in the decreasing strength. It can be concluded that co-PSA fibers remain good property under thermal at 200 °C, external force use environment.

Cellulose/aromatic polysulfonamide (PSA) alloy fibers with good flame retardant properties were successfully prepared by changing the viscosity ratio of cellulose and PSA solutions. To reduce the content of PSA in the alloy fibers, cellulose and PSA with different molecular weight were adopted to prepare the alloy fibers. From the results of the limiting oxygen index(LOI) and the self-extinguishing time away from the flame, it was shown that the flame retardant properties of the alloy fibers were improved as the viscosity of PSA/[BMIM]Cl solution was lowered. The contact angle and the water retention values of the alloy fibers showed that the moisture absorption was strengthened with the addition of cellulose. To verify the properties of the alloy fiber, phase morphologies were characterized by laser scanning confocal microscope (LSCM). An analogous “sheath-core” structure in the cross section of the alloy fibers was shown when the viscosity of PSA/[BMIM]Cl solution was lower enough than that of cellulose/[BMIM]Cl solution. The lower viscosity PSA component was observed to migrate to the outer layer of the fiber, while the higher viscosity cellulose remained within the inner core of the fiber during the spinning process. This behavior improved the flame retardant properties of the alloy fibers at certain weight ratios. This work provides an effective way to prepare cellulose/PSA alloy fibers with improved flame retardancy, hygroscopic behavior, and mechanical strength by the regulating the phase morphology.

The aim of our study was to analyze the related factors of asymmetrical cortical vein sign (ACVS) and asymmetrical medullary vein sign (AMVS) on susceptibility-weighted imaging (SWI) in patients with acute middle cerebral artery (MCA) stroke and whether their presence can be used as an independent predictor for clinical outcome.According to the presence of ACVS and AMVS on SWI, 124 patients with acute MCA stroke within 3 days were divided into several different groups. In addition, those patients were also divided into good and poor outcome group by using the modified Rankin Scale at 3 months after stroke. We investigated respectively the differences in magnetic resonance imaging findings and the clinical data among those different groups.The ACVS was demonstrated in 90 of 124 patients. Of the 90 patients, 47 were accompanied with the AMVS. The rest of 34 patients showed no ACVS and AMVS. The infarct size and MCA status showed significant differences among the ACVS+, AMVS+ group; ACVS+, AMVS- group; and ACVS-, AMVS- group (all P .001). Moreover, the ACVS, AMVS, and MCA occlusion were more common in the poor outcome group (all P .001). In the multivariate logistic regression, AMVS (P = .027; odds ratio, 2.37; 95% confidence interval, 1.23-8.73) was associated with poor outcome.The ACVS and AMVS were correlated to the status of MCA steno-occlusion and infarct size, whereas the AMVS was proved to be independently related to the stroke severity and poor outcome rather than the ACVS.

Objective: This research was aimed to explore the efficacy of narrow-band imaging (NBI) on distinguishing the degree of dysplasia of vocal fold leukoplakia.Methods: Patients were examined by flexible endoscopy, under white light endoscopy (WLE) and NBI. 78 lesions were divided into two groups according to the NBI classification. Group 1: non-dysplasia (ND), including squamous hyperplasia with hyperkeratosis or parakeratosis; Group 2: squamous hyperplasia with mild or moderate dysplasia (MD) or severe dysplasia (SD), or carcinoma in situ (CIS).Results: The diagnostic accuracy of NBI for Group 1 and Group 2 was 69.70% (23/33) and 95.56% (43/45), respectively, and the kappa index was 0.711 and a p value

The coexistence of persistent Mullerian duct syndrome (PMDS) with transverse testicular ectopia (TTE) is extremely rare. Due to a lack of distinctive clinical features in the early stages, PMDS coexists with TTE is usuallydiagnosed when patients are examined for other diseases,including cryptorchidism and inguinal hernia. We present a case of a 51-year-old man who presented with a recurrent left indirect inguinal hernia for 2 years and right congenital cryptorchidism. The patient was diagnosed as PMDS with TTE by preoperative magnetic resonance imaging and underwent laparoscopic resection of the right transverse ectopic testis and Mullerian duct residues.

Drug repurposing has attracted increased attention, especially in the context of drug discovery rates that remain too low despite a recent wave of approvals for biological therapeutics (e.g. gene therapy). These new biological entities-based treatments have high costs that are difficult to justify for small markets that include rare diseases. Drug repurposing, involving the identification of single or combinations of existing drugs based on human genetics data and network biology approaches represents a next-generation approach that has the potential to increase the speed of drug discovery at a lower cost. This Pharmacological Perspective reviews progress and perspectives in combining human genetics, especially genome-wide association studies, with network biology to drive drug repurposing for rare and common diseases with monogenic or polygenic etiologies. Also, highlighted here are important features of this next generation approach to drug repurposing, which can be combined with machine learning methods to meet the challenges of personalized medicine.

The Transgenic RNAi Project (TRiP), a Drosophila melanogaster functional genomics platform at Harvard Medical School, was initiated in 2008 to generate and distribute a genome-scale collection of RNA interference (RNAi) fly stocks. To date, it has generated >15,000 RNAi fly stocks. As this covers most Drosophila genes, we have largely transitioned to development of new resources based on CRISPR technology. Here, we present an update on our libraries of publicly available RNAi and CRISPR fly stocks, and focus on the TRiP-CRISPR overexpression (TRiP-OE) and TRiP-CRISPR knockout (TRiP-KO) collections. TRiP-OE stocks express single guide RNAs targeting upstream of a gene transcription start site. Gene activation is triggered by coexpression of catalytically dead Cas9 fused to an activator domain, either VP64-p65-Rta or Synergistic Activation Mediator. TRiP-KO stocks express one or two single guide RNAs targeting the coding sequence of a gene or genes. Cutting is triggered by coexpression of Cas9, allowing for generation of indels in both germline and somatic tissue. To date, we have generated >5000 TRiP-OE or TRiP-KO stocks for the community. These resources provide versatile, transformative tools for gene activation, gene repression, and genome engineering.

This study assessed the utility of narrow band imaging (NBI) in patients with symptoms of laryngopharyngeal reflux (LPR) and tried to quantitatively evaluate the signs found under the NBI Laryngoscope.Patients with and without LPR symptoms completed reflux symptom index (RSI) questionnaires prior to enrolment. The throat was examined by standard white light endoscopy followed by NBI. LPR status was determined using the reflux finding score and the RSI. Laryngoscope images and videos from 70 subjects with LPR and 70 control subjects without LPR were obtained. Features seen only by NBI were compared between the two groups. Then the RGB values of the throat mucosa of the two groups were measured by Photoshop software, and finally statistical analysis was performed.In total, 140 patients were eligible for final analysis (LPR group mean age = 50.0, 47 males; control group mean age = 44.8, 45 males). A significantly higher proportion of patients with LPR had increased vascularity, green spots, contact ulcers and granulomas. Of these, increased vascularity and green spots can only be found under NBI, and the prevalence rates in the LPR group were found to be 92.8% and 88.6% (P 0.05), respectively. In the control group, the prevalence rates of increased vascularity and green spots were 21.4% and 7.1%, respectively (P 0.05). The RGB value of the LPR group was generally higher than that of the control group. The difference is statistically significant (P 0.05).LPR presents vascularity and green spots with high specificity and sensitivity under NBI which can play a role in the auxiliary diagnosis of LPR.

Liquid-solid transition is a widely used strategy to shape polymeric materials and encode their microstructures. However, it is still challenging to fully exploit liquid behaviors of material precursors. In particular, the dynamic and static liquid behaviors naturally conflict with each other, which makes it difficult to integrate their advantages in the same materials. Here, by utilizing a shear-thinning phenomenon in the dynamic hybrid hydrogels, we achieve a hydrodynamic alignment of cellulose nanocrystals (CNC) and preserve it in the relaxed hydrogel networks due to the much faster relaxation of polymer networks (within 500 s) than CNC after the unloading of external force. During the following drying process, the surface tension of hydrogels further enhances the orientation index of CNC up to 0.872 in confined geometry, and these anisotropic microstructures demonstrate highly tunable birefringence (up to 0.004 14). Due to the presence of the boundaries of dynamic hydrogels, diverse xerogels including fibers, films, and even complex three-dimensional structures with variable anisotropic microstructures can be fabricated without any external molds.

Bacground and purpose Tumor chemotherapy and radiotherapy induces hematopoietic cell damage, resulting in thrombocytopenia. Conventional platelet transfusion strategies or drug therapies are used to treat thrombocytopenia. However, these therapies may result in a several side effects, including heightened susceptibility to infectious diseases and the formation of anti-TPO-antibodies. Therefore, a more secure strategy should be explored to overcome and compensate for the shortcomings of conventional strategies. Experimental approach Effects of rhTyrRS(Y341A) on the expression of VCAM-1 on the surface of HUVECs were determined by analysing mRNA expression, promoter activity, protein expression. The molecular mechanisms of the effects of rhTyrRS(Y341A) on the expression of VCAM-1 on the surface of HUVECs were investigated by determining the activation of VEGF-R II/NF-κB pathway. Key results Our results provide evidence that rhTyrRS (Y341A) activates NF-κB to upregulate VCAM-1 in a VEGF-R II/NF-κB pathway-dependent, resulting in megakaryocyte adhering to PVECs to induce platelet production. Conclusions This study suggested that rhTyrRS (Y341A), a novel human tyrosyl-tRNA synthetase mutation, increased the platelet count under normal conditions. Further more, we confirmed that an NF-κB-mediated mechanism is involved in rhTyrRS (Y341A)-induced thrombopoiesis, which involves its interaction with VEGF-R II.

Summary Septins are GTP-binding proteins involved in several membrane remodeling mechanisms. They associate with membranes, presumably using a polybasic domain (PB1) that interacts with phosphoinositides (PIs). Membrane-bound septins assemble into microscopic structures that regulate membrane shape. How septins interact with PIs and then assemble and shape membranes is poorly understood. Here, we found that septin 9 has a second polybasic domain (PB2) conserved in the human septin family. Similar to PB1, PB2 binds specifically to PIs, and both domains are critical for septin filament formation. However, septin 9 membrane association is not dependent on these PB domains, but on putative PB-adjacent amphipathic helices. The presence of PB domains guarantees protein enrichment in PI-contained membranes, which is critical for PI-enriched organelles. In particular, we found that septin 9 PB domains control the assembly and functionality of the Golgi apparatus. Our findings offer further insight into the role of septins in organelle morphology., Graphical Abstract, Highlights • Two polybasic domains mediate septin 9 interactions with PIs • Human septins have amphipathic helices suitable for membrane binding • Septin 9 polybasic domains mediate the formation of septin higher-order structures • The mutation or depletion of septin polybasic domains induces Golgi fragmentation, Membrane Architecture; Molecular Interaction; Cell Biology; Functional Aspects of Cell Biology