•Review of Synaptojanin1 from synaptic to autophagic membrane trafficking•Figure that illustrates all known SYNJ1 disease mutations in the coding region•Highlight on the experimental model and cell ...type-specific roles of Synj1•Perspectives on future directions that guide SYNJ1-related disease investigation.
This mini-review aims to summarize a growing body of literature on synaptojanin 1 (Synj1), a phosphoinositide phosphatase that was initially known to have a prominent role in synaptic vesicle recycling. Synj1 is coded by the SYNJ1 gene, whose mutations and variants are associated with an increasing number of neurological disorders. To better understand the mechanistic role of Synj1 in disease pathogenesis, we review details of phosphoinositide signaling pathways and the reported involvement of Synj1 in membrane trafficking with a specific focus on Parkinson’s disease (PD). Recent studies have tremendously advanced our understanding of Synj1 protein structure and function while broadening our view of how Synj1 regulates synaptic membrane trafficking and endosomal trafficking in various organisms and cell types. A growing body of evidence points to inefficient membrane trafficking as key pathogenic mechanisms in neurodegenerative diseases associated with abnormal Synj1 expression. Despite significant progress made in the field, the mechanism by which Synj1 connects to trafficking, signaling, and pathogenesis is lacking and remains to be addressed.
Agricultural drought can have long-lasting and harmful impacts on both the ecosystem and economy. Therefore, it is important to monitor and predict agricultural drought accurately. Soil moisture is ...the key variable to define the agricultural drought index. However, in situ soil moisture observations are inaccessible in many areas of the world. Remote sensing techniques enrich the surface soil moisture observations at different tempo-spatial resolutions. In this study, the Level 2 L-band radiometer soil moisture dataset was used to estimate the Soil Water Deficit Index (SWDI). The Soil Moisture Active Passive (SMAP) dataset was evaluated with the soil moisture dataset obtained from the China Land Soil Moisture Data Assimilation System (CLSMDAS). The SMAP-derived SWDI (SMAP_SWDI) was compared with the atmospheric water deficit (AWD) calculated with precipitation and evapotranspiration from meteorological stations. Drought monitoring and comparison were accomplished at a weekly scale for the growing season (April to November) from 2015 to 2017. The results were as follows: (1) in terms of Pearson correlation coefficients (R-value) between SMAP and CLSMDAS, around 70% performed well and only 10% performed poorly at the grid scale, and the R-value was 0.62 for the whole basin; (2) severe droughts mainly occurred from mid-June to the end of September from 2015 to 2017; (3) severe droughts were detected in the southern and northeastern Xiang River Basin in mid-May of 2015, and in the northern basin in early August of 2016 and end of November 2017; (4) the values of percentage of drought weeks gradually decreased from 2015 to 2017, and increased from the northeast to the southwest of the basin in 2015 and 2016; and (5) the average value of R and probability of detection between SMAP_SWDI and AWD were 0.6 and 0.79, respectively. These results show SMAP has acceptable accuracy and good performance for drought monitoring in the Xiang River Basin.
Background: Dupilumab is the first approved IL-4Rα inhibitor for the treatment of atopic dermatitis at present with good efficacy and safety. However, there have been several reports of psoriasis and ...psoriasiform manifestations occurring after dupilumab therapy in recent years, showing a new paradoxical cutaneous reaction associated with biologics. Summary: This is a scoping review in order to summarize the demographics and epidemiology, clinical manifestations, diagnosis, potential pathogenesis, and promising management of dupilumab-associated psoriasis and psoriasiform manifestations.
To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to ...determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy.
This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in China. Patients aged 18–75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3–4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43·5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio <1·883). This trial is registered at ClinicalTrials.gov, number NCT00793962.
Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58·5 months (IQR 39·2–81·8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8·3% (90% CI 5·8–10·7) in the hypofractionated radiotherapy group and 8·1% (90% CI 5·4–10·6) in the conventional fractionated radiotherapy group (absolute difference 0·2%, 90% CI −3·0 to 2·6; hazard ratio 1·10, 90% CI 0·72 to 1·69; p<0·0001 for non-inferiority). There were no significant differences between the groups in acute and late toxicities, except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group (14 3% of 401 patients vs 32 8% of 409 patients; p<0·0001).
Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients.
National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China.
In this article, a new type of Vivaldi antenna with heat dissipation enhancement is proposed and manufactured based on 3-D printing and printed circuit board (PCB) technologies. A longitudinal slot ...on substrate integrated waveguide (SIW) is employed to feed Vivaldi radiation structure, which replaces the balun structure of traditional Vivaldi antennas. The measured 10 dB bandwidth of antenna element reaches up to 34.48% (21.77-30.39 GHz) and the in-band realized boresight gain is 6.5-8.8 dBi. The <inline-formula> <tex-math notation="LaTeX">1\times 4 </tex-math></inline-formula> Vivaldi antenna array with 28.72% (21.63-28.81 GHz) bandwidth and a gain range of 10.5-12.5 dBi is achieved. The fin-shaped structure of the antenna array further enhances the heat dissipation while increasing the gain up to the range of 13.4-15.5 dBi. The measured results are in good agreement with the simulated ones. The proposed antenna array has important application potential in 5G millimeter-wave systems.
Gonorrhea remains one of the most common sexually transmitted diseases worldwide. Successful treatment has been hampered by emerging resistance to each of the antibiotics recommended as first-line ...therapies. We retrospectively analyzed the susceptibility of gonorrhea to azithromycin and ceftriaxone using data from the China Gonococcal Resistance Surveillance Programme (China-GRSP) in order to provide evidence for updating the treatment recommendations in China.
In this study, we included 3,849 isolates collected from patients with a confirmed positive Neisseria gonorrhoeae (N. gonorrhoeae) culture at clinic visits during the period of 1 January 2013 through 31 December 2016 in 7 provinces. Antimicrobial susceptibility testing of gonorrhea isolates using agar dilution was conducted to determine minimum inhibitory concentration (MIC). Resistance to azithromycin (RTA) was defined as MIC ≥ 1.0 mg/l, and decreased susceptibility to ceftriaxone (DSC) was defined as MIC ≥ 0.125 mg/l. The prevalence of isolates with RTA was 18.6% (710/3,827; 95% CI 17.4%-19.8%). The percentage of patients with DSC fluctuated between 9.7% and 12.2% over this period. The overall prevalence of isolates with both RTA and DSC was 2.3% (87/3,827; 95% CI 1.9%-2.8%) and it increased from 1.9% in 2013 to 3.3% in 2016 (chi-squared test for trend, P = 0.03). Study limitations include the retrospective study design and potential biases in the sample, which may overrepresent men with symptomatic infection, coastal residents, and people reporting as heterosexual.
To our knowledge, this is the first national study on susceptibility of N. gonorrhoeae to azithromycin and ceftriaxone in China. Our findings indicate high rates of RTA and DSC from 2013 to 2016. Although dual therapy with azithromycin and ceftriaxone has been recommended by WHO and many countries to treat gonorrhea, reevaluation of this therapy is needed prior to its introduction in China.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Aims
Surgical resection is the primary treatment for HCC; however, it is associated with a high rate of recurrence and death. We conducted this phase 2 study to investigate the ...efficacy and safety of postoperative intensity‐modulated radiotherapy (IMRT) for HCC after narrow‐margin hepatectomy.
Approach and Results
We designed a single‐arm, prospective phase 2 trial to evaluate overall survival (OS), disease‐free survival (DFS), recurrence patterns, and toxicity in patients receiving adjuvant radiotherapy. The eligibility criteria included the following: pathological diagnosis of HCC after hepatectomy, with narrow pathological margins (< 1 cm); age > 18 years; and Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients received IMRT within 4‐6 weeks after surgical resection. This trial was registered at ClinicalTrials.gov (NCT01456156). Between 2008 and 2016, a total of 76 eligible patients who underwent narrow‐margin resection were enrolled. The median follow‐up duration was 70 months; the 3‐year OS and DFS rates were 88.2% and 68.1%, respectively; and the 5‐year OS and DFS rates were 72.2% and 51.6%, respectively. Intrahepatic recurrence was the primary recurrence pattern. No marginal recurrence was found. Intrahepatic, extrahepatic, and combined recurrences at the first relapse were found in 33, 5, and 1 patient, respectively. The most common radiation‐related grade‐3 toxicities were leukopenia (7.9%), elevated alanine aminotransferase (3.9%) and aspartate aminotransferase (2.6%) levels, and thrombocytopenia (1.3%). Classical or nonclassical radiation‐induced liver disease was not noted.
Conclusions
Adjuvant radiotherapy is an effective, well‐tolerated, and promising adjuvant regimen in patients with HCC who have undergone narrow‐margin hepatectomy. Our trial provides evidence and a rationale for planning a future phase 3 trial.
Reductive carboxylation of organo (pseudo)halides with CO2 is a powerful method to provide carboxylic acids quickly. Notably, the catalytic reductive carbo‐carboxylation of unsaturated hydrocarbons ...via CO2 fixation is a highly challenging but desirable approach for structurally diverse carboxylic acids. There are only a few reports and no examples of alkenes via transition metal catalysis. We report the first asymmetric reductive carbo‐carboxylation of alkenes with CO2 via nickel catalysis. A variety of aryl (pseudo)halides, such as aryl bromides, aryl triflates and inert aryl chlorides of particular note, undergo the reaction smoothly to give important oxindole‐3‐acetic acid derivatives bearing a C3‐quaternary stereocenter. This transformation features mild reaction conditions, wide substrate scope, facile scalability, good to excellent chemo‐, regio‐ and enantioselectivities. The method highlights the formal synthesis of (−)‐Esermethole, (−)‐Physostigmine and (−)‐Physovenine, and the total synthesis of (−)‐Debromoflustramide B, (−)‐Debromoflustramine B and (+)‐Coixspirolactam A; thereby, opening an avenue for the total synthesis of chiral natural products with CO2.
A strategy is presented for nickel‐ catalyzed asymmetric reductive carbo‐carboxylation of alkenes with CO2. A variety of aryl (pseudo)halides react to produce oxindole‐3‐acetic acid derivatives bearing a C3‐quaternary stereocenter. Notably, synthesis of a range of bioactive pyrroloindolines was achieved.
A miniaturized laminated resonator antenna (LRA) array with periodic irises is proposed in this article. By means of the distinguished slow wave property of the periodic iris-loaded waveguide (IWG), ...a compact LRA element with a dimension of only <inline-formula> <tex-math notation="LaTeX">0.36\lambda _{0} \times 0.26\lambda _{0} \times 0.08\lambda _{0} </tex-math></inline-formula> is designed, where <inline-formula> <tex-math notation="LaTeX">\lambda _{0} </tex-math></inline-formula> is the wavelength in the free space at 60 GHz. The small transverse size makes it possible to construct an antenna array with the element spacing of less than <inline-formula> <tex-math notation="LaTeX">0.5\lambda _{0} </tex-math></inline-formula>, which is rather beneficial to the scanning arrays and multiple-input-multiple-output (MIMO) systems. For demonstration, a series-fed <inline-formula> <tex-math notation="LaTeX">1\times6 </tex-math></inline-formula> antenna array in the E-plane with the element spacing of <inline-formula> <tex-math notation="LaTeX">0.38\lambda _{0} </tex-math></inline-formula> is designed and fabricated with the low-temperature co-fired ceramic (LTCC) process. The measured relative impedance bandwidth is 9.2% (from 56.3 to 61.8 GHz). The measured peak gain and 3-dB gain bandwidth are 10.6 dBi and 5.3 GHz, respectively. Furthermore, the scanning arrays are fabricated to demonstrate the scanning performance, with an element spacing of <inline-formula> <tex-math notation="LaTeX">0.45\lambda _{0} </tex-math></inline-formula> in the H-plane. They support a measured maximum scanning angle of 43° while the gain drop is within 2.5 dB.
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