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Homologous to E6AP C‐terminus (HECT)‐type E3 ubiquitin ligase SMAD‐specific E3 ubiquitin protein ligase 1 (Smurf1) was originally identified to ubiquitinate Smad protein in the TGF‐β/BMP signaling pathway. Recently, Smurf1 has been reported to promote tumorigenesis by regulating multiple biological processes. High expression of Smurf1 plays a vital role in brain tumor progression by mediating aberrant cell signaling pathways. Previous reports have shown that Smurf1 is degraded mainly through the ubiquitin–proteasome system, but it remains unclear whether Smurf1 is degraded by autophagy in tumor cells. In this study, we show that autophagy activators promote Smurf1 degradation in glioblastoma (GB) cells. The autophagy receptor p62 colocalizes with ubiquitinated substrates to promote sequestration of cytoplasm cargo into the autophagosome. We report that autophagic degradation of Smurf1 is dependent on p62. Moreover, the autophagic degradation of Smurf1 is prevented in the absence of the HECT domain or E3 ubiquitin ligase activity. We further proved that activation of autophagy leads to a decrease of Smurf1 and the inhibition of the phosphoinositide 3‐kinase/protein kinase B signaling pathway in GB cells. Our results suggest that enhancement of autophagic degradation of Smurf1 may be a potential approach to treating GB.

Abstract On‐body propagation channels show significant polarization selectivity that has dominant impacts on the on‐body link quality in wireless body area networks. For on‐body relay channels over long distances across the body, the antenna polarization configurations of the relaying nodes are crucial to determine the relay performance, thereby requiring polarization optimization schemes. In this article, narrow band flat‐fading on‐body channels at 2.484 GHz are measured to analyse their polarization distribution above the skin under static postures. The measured on‐body channels show full‐space polarization convergence and dispersion, which are modelled by an extended 3 by 3 channel polarization matrix, and a statistical channel model is also proposed. Multi‐hop polarized on‐body relay channels are analysed on the relay link capacity, which shows polarization dependency between adjacent hop channels when relaying nodes are mounted by linearly polarized antennas. Both regular and iterative polarization selection algorithms are then designed to optimise the antenna polarization configuration of the nodes. Simulations based on the proposed polarization distribution model show significant link capacity increases for two‐hop and tfhree‐hop on‐body relay channels by the optimization algorithms. The results confirm the necessity of proper polarization selection schemes for on‐body relay channels.

The prognosis for osteosarcoma (OS) is dismal due to the aggressive tumor growth and high incidence of metastasis. The long noncoding RNA human homeobox A transcript at the distal tip (HOTTIP) and the transcription factor forkhead box C1 (FOXC1) present oncogenic activities in OS. Here, we aimed at gaining insights into the underlying mechanisms and their crosstalk. The expression of FOXC1 and HOTTIP in OS tissues or cell lines was examined by real‐time PCR (RT‐PCR) and western blot. The in vitro effects of FOXC1 or HOTTIP on cell viability, proliferation, migration, invasion, and expression of target genes were examined using MTT, colony‐forming assay, wound‐healing, Transwell invasion, and western blot, respectively; the in vivo effects were examined using xenograft and experimental metastasis models. Molecular control of HOTTIP on large tumor suppressor 2 (LATS2) or transactivation of FOXC1 or Sp1 on HOTTIP was assessed by combining RNA immunoprecipitation, qRT‐PCR, western blot, ChIP, and luciferase assay. Both FOXC1 and HOTTIP were potently up‐regulated in OS tissues and cell lines. FOXC1 and HOTTIP essentially maintained viability, proliferation, migration, and invasion of OS cells in vitro and contributed to xenograft growth or lung metastasis in vivo. Mechanistically, HOTTIP recruited enhancer of zeste homolog 2 (EZH2) and lysine‐specific demethylase 1 (LSD1) to silence LATS2 and thus activated YAP/β‐catenin signaling. Upstream, Sp1 activated FOXC1 and they both directly transactivated HOTTIP. In summary, we showed that the Sp1/FOXC1/HOTTIP/LATS2/YAP/β‐catenin cascade presented oncogenic activities in OS cells. Targeting FOXC1 or HOTTIP may therefore prove beneficial for OS treatment.

Abstract Resource polymorphism is a ubiquitous phenomenon in vertebrates and may represent a critical intermediate stage in speciation. Freshwater lakes in high‐altitude areas represent a natural system for understanding resource polymorphism in fishes benefiting from diverse lacustrine environments and species‐poor fish assemblages. We report resource polymorphism in a cyprinid fish, Schizopygopsis thermalis, in Lake Amdo Tsonak Co, a headwater lake in the upper Salween River system. Two discrete intraspecific morphs, planktivorous and benthivorous, were identified according to geometric morphometrics and traditional univariate linear measures. The planktivorous morph exhibits a longer head, longer upper and lower jaw, larger asymptotic standard length (L∞), lower growth rate (k), and higher growth performance index (φ) than the benthivorous morph. With respect to descriptive traits, the planktivorous morph possesses a large, terminal mouth and obvious mucus pores on the cheek and chin, while the benthivorous morph is characterized by a more inferior mouth with a sharpen horny edge on the lower jaw and unconspicuous mucus pores. The discrete pelagic–benthic resources and low interspecific competition in the lake system might drive the initial differentiation of the two morphs, and partial spatial reproductive isolation in breeding further maintains and reinforces the differences between them.

Abstract Background The impact of neoadjuvant chemoimmunotherapy on pulmonary resection and related outcomes had been poorly reported in previous studies. The present study aims to clarify the efficacy and safety of neoadjuvant chemoimmunotherapy, and intraoperative difficulty in the following surgery, in comparison with chemotherapy alone in non‐small cell lung cancer (NSCLC). Methods Patients with newly diagnosed clinical stages IB–IIIB(T3‐4N2) NSCLC, received neoadjuvant chemotherapy + PD‐1 inhibitors (PD‐1 + Chemo group) or chemotherapy alone (Chemo group) followed by surgery between December 2018 and December 2020 were included. The clinicopathological characteristics were retrospectively reviewed and analyzed. Results There were 69 NSCLC patients in the PD‐1 + Chemo group and 121 in the Chemo group. The major pathological response (MPR) rate in the PD‐1 + Chemo group was 49.3%, higher than that of 19.0% in the Chemo group (p 0.05). Conclusions Neoadjuvant chemoimmunotherapy for NSCLC is safe and feasible, with higher MPR rates, as well as favorable DFS than chemotherapy alone. Surgical complexity might be increased in certain patients, with comparable perioperative morbidity and mortality.

Abstract On the premise of security, it is necessary to ensure good operational performance and technical indicators for nonlethal weapons such as flash detonation bombs. To make the weight of a flash detonation grenade more convenient for hand throwing and material costs save, the outer dimensions of the grenade body are fixed, and the optimal parameters of outer shell thickness of the vertigo grenade are explored. Based on the maximum deformation energy theorem, the strength of the shell with the obtained maximum thickness of 8 mm is checked, and then the optimal shell thickness under the ideal air explosion condition is obtained by reducing the thickness; Then check the thread strength to obtain the inner casing fracture, shock wave, and sound pressure level. The fragmentation performance test, detonation test, and sound pressure level test were carried out for the projectiles involving the shell thickness of 4 and 5 mm, and the simulation results were verified from three aspects of sound intensity, shell strength, and fragments. The results show that the maximum equivalent stress is 232.6 MPa and the maximum deformation is 1.07 × 10−4 mm when the outer shell thickness of the vertigo grenade is 5 mm, which is less than the material failure strength standard and no plastic deformation could occur. The structural connection strength of the missile body meets the standard. Most of the fragments are trapped in the cavity. The average sound pressure level at 1.5 m can reach 159.7 dB. The relative error between the sound pressure level at 3 m and the live ammunition test results is 4.8%, which meets the expected operational technical indicators and has good safety performance. The results of the numerical simulation can provide a reference for the design optimization and performance evaluation of similar vertigo grenades.

Abstract Sevoflurane has been the most widely used inhaled anesthetics with a favorable recovery profile; however, the precise mechanisms underlying its anesthetic action are still not completely understood. Here the authors show that sevoflurane activates a cluster of urocortin 1 (UCN1+)/cocaine‐ and amphetamine‐regulated transcript (CART+) neurons in the midbrain involved in its anesthesia. Furthermore, growth hormone secretagogue receptor (GHSR) is highly enriched in sevoflurane‐activated UCN1+/CART+ cells and is necessary for sleep induction. Blockade of GHSR abolishes the excitatory effect of sevoflurane on UCN1+/CART+ neurons and attenuates its anesthetic effect. Collectively, their data suggest that anesthetic action of sevoflurane necessitates the GHSR activation in midbrain UCN1+/CART+ neurons, which provides a novel target including the nucleus and receptor in the field of anesthesia.

The location and capacity of express distribution centers and delivery point allocation are mixed-integer programming problems modeled as capacitated location and allocation problems (CLAPs), which may be constrained by the position and capacity of distribution centers and the assignment of delivery points. The solution representation significantly impacts the search efficiency when applying swarm-based algorithms to CLAPs. In a traditional encoding scheme, the solution is the direct representation of position, capacity, and assignment of the plan and the constraints are handled by punishment terms. However, the solutions that cannot satisfy the constraints are evaluated during the search process, which reduces the search efficiency. A general encoding scheme that uses a vector of uniform range elements is proposed to eliminate the effect of constraints. In this encoding scheme, the number of distribution centers is dynamically determined during the search process, and the capacity of distribution centers and the allocation of delivery points are determined by the random proportion and random key of the elements in the encoded solution vector. The proposed encoding scheme is verified on particle swarm optimization, differential evolution, artificial bee colony, and powerful differential evolution variant, and the performances are compared to those of the traditional encoding scheme. Numerical examples with up to 50 delivery points show that the proposed encoding scheme boosts the performance of all algorithms without altering any operator of the algorithm.

Objective. To investigate the association between gender and gastrointestinal (GI) dysfunctions, as well as gender and other motor symptoms/nonmotor symptoms, in a sample of PD patients. Methods. 186 patients with PD were recruited into this study and divided into male PD group (M-PD) and female PD group (FM-PD). Demographic and PD-related clinical information of the participants were collected by the same neurologist. PD patients were objectively assessed by a spectrum of rating scales of motor symptoms and nonmotor symptoms (including GI dysfunctions). The data were analyzed by SPSS 20 statistical software. Results. Totally 95 cases (51.08%) were in the M-PD group and 91 cases (48.92%) in the FM-PD group. There were no significant differences in age, BMI, and lifestyles between the two groups (P > 0.05). Males had higher educational level (P = 0.002). Females were more likely to have early satiety and loss of appetite (P = 0.025, P = 0.001). There were no significant differences in LED disease duration, age of motor symptoms onset, types of motor symptoms onset, location of motor symptoms onset, and phenotype of motor symptoms between the two groups (P > 0.05). Females had significantly higher UPDRS-III and HAMD scores than males (P = 0.037, P = 0.034). There were no significant differences in PQSI, ESS, RLS, RBD, HAMA, HAMD, and MoCA scores between the two groups. Gender was associated with HAMD (OR = 0.682, P = 0.019). Conclusions. Gender is a risk factor for depression, but not for GI dysfunctions in patients with PD.

Purpose. To identify the molecular etiology of a Chinese family with nonsyndromic macular dystrophy. Methods. Ophthalmic examinations were performed, and genomic DNA was extracted from available family members. Whole exome sequencing of two members (the proband and her unaffected mother) and Sanger sequencing in available family members were performed to screen potential pathogenic variants. Results. Novel compound heterozygous variants, c.1066C>T (p.Pro356Ser) and c.1102+2T>C, in the major facilitator superfamily domain containing 8 gene (MFSD8) were suspected to be involved in this family’s macular dystrophy phenotype. The novel c.1066C>T variant in the MFSD8 gene probably resulted in substitution of serine for proline at the 356th residue and was predicted to be “uncertain significance” through in silico analyses. The novel c.1102+2T>C variant in the MFSD8 gene was likely to affect the splicing form and predicted to be “pathogenic.” Conclusion. The novel compound heterozygous variants, c.1066C>T (p.Pro356Ser) and c.1102+2T>C, in the MFSD8 gene are likely responsible for the isolated macular dystrophy phenotype in this family. This study enlarged the MFSD8 gene mutant spectrum and might provide more accurate genetic counseling for this family.