Precision tools for spatiotemporal control of cytoskeletal motor function are needed to dissect fundamental biological processes ranging from intracellular transport to cell migration and division. Direct optical control of motor speed and direction is one promising approach, but it remains a challenge to engineer controllable motors with desirable properties such as the speed and processivity required for transport applications in living cells. Here, we develop engineered myosin motors that combine large optical modulation depths with high velocities, and create processive myosin motors with optically controllable directionality. We characterize the performance of the motors using in vitro motility assays, single-molecule tracking and live-cell imaging. Bidirectional processive motors move efficiently toward the tips of cellular protrusions in the presence of blue light, and can transport molecular cargo in cells. Robust gearshifting myosins will further enable programmable transport in contexts ranging from in vitro active matter reconstitutions to microfabricated systems that harness molecular propulsion.Radial artery forearm free-flap (RAFFF) phalloplasty is considered by most authors as the gold-standard technique for genital gender-affirming surgery (GGAS). RAFFF surgical complications have rarely been investigated, and the aim of this study and literature review is to analyse and focus on the surgical technique and its postoperative vascular complications. From May 2016 to January 2020, a consecutive series of 25 transgender men who underwent GGAS were enrolled in the present study. Age, BMI and smoking habits were recorded for all patients. Overall, vascular flap complications occurred in 20% of cases. Complete flap loss due to acute arterial thrombosis was recorded in a single case (4%). In 8% of cases, limited ventro-proximal arterial ischaemia was detected, while in the remaining 8% of cases, venous ventral ischaemia was reported. https://www.selleckchem.com/products/bupivacaine.html These results were compared with the current literature results. Indeed, from our analysis, the number of flap veins ( less then 2) was the only predictive factor for vascular complications. In conclusion, RAFFF represents a reliable option for total phallic construction, leading to satisfactory results in terms of flap survival. To optimize the surgical outcomes, venous vascular drainage should be recommended.Extracorporeal treatment with low intensity shock-wave therapy (LI-ESWT) is a recently introduced non-invasive method which purposes the restoration of the pathophysiological alterations at the base of vasculogenic ED in male patients. The evidence in favour of the neoangiogenic potential of this treatment derived from in vitro studies and on animal models. The purpose of this study, in which the Power Doppler method was applied, is to demonstrate 'objectively' the real efficacy of LI-ESWT at the level of the microcirculation of the corpora cavernosa (neoangiogenesis) in patients affected by vasculogenic ED. Data from this study show, for the first time, that LI-ESWT treatment promotes neovascularisation of the functional arteries in patients affected by vasculogenic ED.Men with anxiety disorders have been identified as high risk of developing erectile dysfunction (ED). The aim of this review is to define the prevalence and severity of ED in the male anxiety disorder population. A literature search of three electronic databases (PubMed, Embase and PsychINFO) and a grey literature registry was conducted. Inclusion criteria were studies that investigated adult males, documented diagnosis of anxiety disorders made by a qualified psychiatrist and use of a validated tool to diagnose ED such as International Index of Erectile Function or ICD-10/DSM-IV. The search yielded 1220 articles and 12 studies were selected. The anxiety disorders investigated were post-traumatic stress disorder, obsessive-compulsive disorder, social phobia/social anxiety disorder and panic disorder. We found that the median [IQR] prevalence of ED was 20.0 [5.1-41.2]% and the median [IQR] International Index of Erectile Function-5 scores were 17.62 [13.88-20.88], indicating a mild to moderate severity. Our review suggests a high prevalence of ED in the anxiety disorder population and ED may be more severe in this cohort, therefore advocating this is an important clinical topic. However, the evidence is limited due to the high heterogeneity between the studies and more research is required in this field.Ipilimumab improves clinical outcomes when combined with nivolumab in metastatic non-small cell lung cancer (NSCLC), but its efficacy and impact on the immune microenvironment in operable NSCLC remain unclear. We report the results of the phase 2 randomized NEOSTAR trial (NCT03158129) of neoadjuvant nivolumab or nivolumab + ipilimumab followed by surgery in 44 patients with operable NSCLC, using major pathologic response (MPR) as the primary endpoint. The MPR rate for each treatment arm was tested against historical controls of neoadjuvant chemotherapy. The nivolumab + ipilimumab arm met the prespecified primary endpoint threshold of 6 MPRs in 21 patients, achieving a 38% MPR rate (8/21). We observed a 22% MPR rate (5/23) in the nivolumab arm. In 37 patients resected on trial, nivolumab and nivolumab + ipilimumab produced MPR rates of 24% (5/21) and 50% (8/16), respectively. Compared with nivolumab, nivolumab + ipilimumab resulted in higher pathologic complete response rates (10% versus 38%), less viable tumor (median 50% versus 9%), and greater frequencies of effector, tissue-resident memory and effector memory T cells. Increased abundance of gut Ruminococcus and Akkermansia spp. was associated with MPR to dual therapy. Our data indicate that neoadjuvant nivolumab + ipilimumab-based therapy enhances pathologic responses, tumor immune infiltrates and immunologic memory, and merits further investigation in operable NSCLC.The genus Orthonairovirus, which is part of the family Nairoviridae, includes the important tick-transmitted pathogens Crimean-Congo hemorrhagic fever virus and Nairobi sheep disease virus, as well as many other poorly characterized viruses found in ticks, birds and mammals1,2. In this study, we identified a new orthonairovirus, Songling virus (SGLV), from patients who reported being bitten by ticks in Heilongjiang Province in northeastern China. SGLV shared similar genomic and morphological features with orthonairoviruses and phylogenetically formed a unique clade in Tamdy orthonairovirus of the Nairoviridae family. The isolated SGLV induced cytopathic effects in human hepatoma cells in vitro. SGLV infection was confirmed in 42 hospitalized patients analyzed between 2017 and 2018, with the main clinical manifestations being headache, fever, depression, fatigue and dizziness. More than two-thirds (69%) of patients generated virus-specific antibody responses in the acute phase. Taken together, these results suggest that this newly discovered orthonairovirus is associated with human febrile illness in China.