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Abstract Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched‐chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high‐fat diet/low‐dose streptozotocin (HFD/STZ)‐induced T2DM and leptin receptor‐deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label‐free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L‐type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA‐deficiency‐induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

Abstract DNA damage plays a significant role in the tumorigenesis and progression of the disease. Abnormal DNA repair affects the therapy and prognosis of cancer. In this study, it is demonstrated that the deubiquitinase USP25 promotes non‐homologous end joining (NHEJ), which in turn contributes to chemoresistance in cancer. It is shown that USP25 deubiquitinates SHLD2 at the K64 site, which enhances its binding with REV7 and promotes NHEJ. Furthermore, USP25 deficiency impairs NHEJ‐mediated DNA repair and reduces class switch recombination (CSR) in USP25‐deficient mice. USP25 is overexpressed in a subset of colon cancers. Depletion of USP25 sensitizes colon cancer cells to IR, 5‐Fu, and cisplatin. TRIM25 is also identified, an E3 ligase, as the enzyme responsible for degrading USP25. Downregulation of TRIM25 leads to an increase in USP25 levels, which in turn induces chemoresistance in colon cancer cells. Finally, a peptide that disrupts the USP25‐SHLD2 interaction is successfully identified, impairing NHEJ and increasing sensitivity to chemotherapy in PDX model. Overall, these findings reveal USP25 as a critical effector of SHLD2 in regulating the NHEJ repair pathway and suggest its potential as a therapeutic target for cancer therapy.

Abstract Mechanistic target of rapamycin complex 1 (mTORC1) is a conserved serine/threonine kinase that integrates various environmental signals to regulate cell growth and metabolism. mTORC1 activation requires tethering to lysosomes by the Ragulator‐Rag complex. However, the dynamic regulation of the interaction between Ragulator and Rag guanosine triphosphatase (GTPase) remains unclear. In this study, that LAMTOR1, an essential component of Ragulator, is dynamically ubiquitinated depending on amino acid abundance is reported. It is found that the E3 ligase TRAF4 directly interacts with LAMTOR1 and catalyzes the K63‐linked polyubiquitination of LAMTOR1 at K151. Ubiquitination of LAMTOR1 by TRAF4 promoted its binding to Rag GTPases and enhanced mTORC1 activation, K151R knock‐in or TRAF4 knock‐out blocks amino acid‐induced mTORC1 activation and accelerates the development of inflammation‐induced colon cancer. This study revealed that TRAF4‐mediated LAMTOR1 ubiquitination is a regulatory mechanism for mTORC1 activation and provides a therapeutic target for diseases involving mTORC1 dysregulation.

Abstract How to improve the capacity of light‐harvesting is still an important point and essential strategy for the assembling of high‐efficiency quantum dot–sensitized solar cells (QDSCs). A believable approach is to implant new light absorption materials into QDSCs to stimulate the charge transfer. Herein, the few‐layer black phosphorus quantum dots (BPQDs) are synthesized by electrochemical intercalation technology using bulk BP as source. Then the obtained BPQDs are deposited onto the surface of Zn–Cu–In–S–Se (ZCISSe) QD‐sensitized TiO2 substrate to serve as another light‐harvesting material for the first time. The experimental results have shown that BPQDs can not only increase the absorption intensity by photoanode but also reduce unnecessary charge recombination processes at the interface of photoanode/electrolyte. Through optimizing the size and deposition process of BPQDs, the champion power conversion efficiency of ZCISSe QDSCs is increased to 15.66% (26.88 mA/cm2, Voc = 0.816 V, fill factor [FF] = 0.714) when compared with the original value of 14.11% (Jsc = 25.41 mA/cm2, Voc = 0.779 V, FF = 0.713).

Abstract Clear cell sarcoma of the kidney (CCSK) and primitive myxoid mesenchymal tumour of infancy (PMMTI) are paediatric sarcomas that most commonly harbour internal tandem duplications (ITDs) of exon 15 of the BCOR gene, in the range of 87–114 base pairs (bp). Some cases, instead, have BCOR‐CCNB3 or YWHAE‐NUTM2 gene fusions. About 10% of cases lack any of these genetic alterations when tested by standard methods. Two cases of CCSK and one PMMTI lacking the aforementioned mutations were analysed using Archer FusionPlex technology. Two related BCOR exon 15 RNA transcripts with ITDs of lengths 388 and 96 bp were detected in each case; only the 388 bp transcript was identified when genomic DNA was sequenced. In silico analysis of this transcript revealed acceptor and donor splice sites indicating that, at the RNA level, the 388‐bp transcript was likely spliced to form the 96‐bp transcript. The results were confirmed by Sanger sequencing using primers targeting the ITD breakpoint. This novel and unusually long ITD segment is difficult to identify by DNA sequencing using typical primer design strategies flanking entire duplicated segments because it exceeds the typical read lengths of most sequencing platforms as well as the usual fragment lengths obtained from formalin‐fixed paraffin‐embedded material. As diagnosis of CCSK and PMMTI may be challenging by morphology and immunohistochemistry alone, it is important to identify mutations in these cases. Knowledge of this novel BCOR ITD is important in relation to primer design for detection by sequencing, and using RNA versus DNA for sequencing.

Abstract Dysregulated maternal nutrition, such as vitamin deficiencies and excessive levels of glucose and fatty acids, increases the risk for congenital heart disease (CHD) in the offspring. However, the association between maternal amino‐acid levels and CHD is unclear. Here, it is shown that increased leucine levels in maternal plasma during the first trimester are associated with elevated CHD risk in the offspring. High levels of maternal leucine increase embryonic lysine‐leucylation (K‐Leu), which is catalyzed by leucyl‐tRNA synthetase (LARS). LARS preferentially binds to and catalyzes K‐Leu modification of lysine 339 within T‐box transcription factor TBX5, whereas SIRT3 removes K‐Leu from TBX5. Reversible leucylation retains TBX5 in the cytoplasm and inhibits its transcriptional activity. Increasing embryonic K‐Leu levels in high‐leucine‐diet fed or Sirt3 knockout mice causes CHD in the offspring. Targeting K‐Leu using the leucine analogue leucinol can inhibit LARS activity, reverse TBX5 K‐Leu modification, and decrease the occurrence of CHD in high‐leucine‐diet fed mice. This study reveals that increased maternal leucine levels increases CHD risk in the offspring through inhibition of embryonic TBX5 signaling, indicating that leucylation exerts teratogenic effects during heart development and may be an intervening target of CHD.

Abstract This study investigated the variations of the nucleotide sequences and ovarian expression levels of genes related to follicular development and atresia in prolific Jintang black goats and nonprolific Tibetan goats. Eight genes, FSHB, LHB, FSHR, LHCGR, ESR2, B4GANT2, BCL2 and BAX, were examined using reverse transcription‐polymerase chain reaction and quantitative real‐time PCR. The results showed that the nucleotide and deduced amino acid sequences of the LHB and BAX genes were not different, but there was one base change in the FSHR genes between the two breeds. There was one base change in the FSHB gene, which resulted in one amino acid substitution; there were nine base changes in the LHCGR gene, which resulted in five amino acid substitutions; and there were six base changes in the B4GANT2 gene, which resulted in four amino acid substitutions. The expression levels of the FSHR, LHCGR, ESR2, B4GANT2, BCL2 and BAX genes in the ovaries were not different between the two breeds. The plasma concentrations of FSH were not different, but the plasma concentrations of LH, P4 and E2 were lower in prolific Jintang black goats than in nonprolific Tibetan goats (P ˂ 0.05) at 40 hr after removal of the Controlled Internal Drug Release Devices. These results provide some foundations elucidating the endocrine and molecular mechanisms controlling ovulation rate in goats, but these need to be further verified.

Excessive vibration of temporary grandstand by the crowd has lateral rhythmic motions, which attracted increasing attention in the recent years. This paper focuses on experiments where a temporary grandstand occupied by 20 participants is oscillated by a shaking table with a series of random waves and the crowd-induced rhythmic swaying motions at lateral direction, respectively. The dynamic forces that were induced by participants who have swayed at 0.5–1.8 Hz are recorded by a tri-axial human biomechanics force plate. A new relationship between the annoyance rate and structural acceleration at logarithmic coordinate is investigated and proposed, and the swaying load model is given. Based on these experimental results, a simplified three-degree-of-freedom lumped dynamic model of the joint human–structure system is reinterpreted. Afterwards, combined with a feasible range of crowd/structural dynamic parameters, a series of interaction models are analyzed, the vibration dose value (VDV) of the structure is obtained and discussed, and the notable parameters for interaction model are predicted. The experimental results show that the lateral serviceability limit is 1.29 m/s1.75 and the upper boundary is 2.32 m/s1.75. The dynamic response of model indicated that the VDV of structure will be decreased with increasing the mass of static crowd and damping ratio of the dynamic crowd. The max response of the model is α ≤ 0.6, f2 = 1.8 Hz or α > 0.6, f2 = 1.5 Hz or f1 = 2.5–3.5 Hz. It may be used as a reference value in vibration safety and serviceability assessment of TDGs, to estimate realistically the vibration response on the occasions when the crowds are swaying.

An autonomous monitoring and control system of unmanned surface vehicle (USV) with mobile water quality monitoring, sampling, and oxygenation functions is constructed. The control hardware and monitoring configuration software of the system is designed, respectively, which can be installed on USV and its remote control and monitoring terminal. The kinematic modeling of USV, waypoint trajectory-tracking control, distributed controller, simulation of tracking control, and verification of software and hardware design are carried out. In order to reject the system noise and external noise, a states estimation method with fully observable states is considered in the control law design. The software and hardware are also implemented to verify the effectiveness of the monitoring platform. Through setting a series of monitoring target points and monitoring parameters in the configuration software of the remote user terminal or in the APP of the mobile user terminal, the USV can realize the automatic cruise monitoring using an autonomous navigation and tracking control algorithm, and quantitative water sampling collection. The reliability of the system is verified by the experiment of the shore test station, and the waypoint trajectory tracking and sensors data are replaying in a logview GUI of MOOS-Ivp and APP.

Abstract Steroid cell tumors not otherwise specified are one of the rare virilizing ovarian tumors. Most of the tumors are benign. This case report illustrates the challenge in managing steroid cell tumor not otherwise specified, which starts from determining its malignant potential, surveillance, and adjuvant treatment option.

In multiattribute group decision-making (MAGDM), due to quantity, fuzziness, and complexity of evaluation linguistic information on commodities, traditional distance measures need to be extended to the integration of evaluation information under a multigranular probabilistic linguistic environment. A more reasonable method is proposed to deal with the missing value in the evaluation information. On the basis of the generalized distance measures and filling in the missing evaluation information, some novel distance measures between two multigranular probabilistic linguistic term sets (PLTSs) are presented in this paper. Based on these distance measures, three extended decision-making (DM) algorithms based on TOPSIS, the extended TOPSIS, and VIKOR are proposed, which are MGPL-TOPSIS, MGPL-ETOPSIS, and MGPL-VIKOR, respectively. The case analyses on purchasing a car are provided to illustrate the application of the extended multiattribute group decision-making (MAGDM) algorithms. Then, sensitivity analyses based on PT are proposed as well. In particular, the extended TOPSIS method is presented. These results demonstrate the novelty, feasibility, and rationality of the distance measures between two multigranular PLTSs proposed in this paper.

This paper proposes a steel-wood composite beam with H-shaped steel beam webs glued to the wood. As a new type of composite beam, it combines the advantages of low energy consumption of wood, high permeability, and less pollution and the advantages of light weight and high strength of steel, high degree of assembly, short construction period, and less construction waste generated. Carrying out research is of great significance to improve the mechanical properties of steel-wood composite beams and promote the development of steel-wood composite structures. In this paper, three hot-rolled H-beam-larch composite beams and one pure steel beam were tested for bending capacity. The composite beams are divided into two different combinations of A and B types. The two sides of the web are connected with larch wood by structural glue to form a composite beam. The type B composite beam is a larch wood glued on both sides of the H-shaped steel web and penetrates the bolts at the same time. Through the three-point monotonic static grading loading of the composite beam, the deflection change, failure phenomenon, and form of the specimen during the experiment were observed. Under the circumstances, the ultimate bearing capacity of the test piece was changed to study the combined effect of larch and hot-rolled H-shaped steel. The results show that the overall performance of the H-shaped steel-larch composite beam is good. Bonding wooden boards on both sides of the steel beam web can improve the bearing capacity, and the form of the member is more reasonable and effective; increasing the cross-sectional size of the H-beam in the steel-wood composite beam can further improve the bearing capacity of the composite beam; adding bolt anchorage on the basis of the structural glue used in the composite beam can further improve the bearing capacity of the composite beam. The superposition principle is used to simplify the calculation of the ultimate bearing capacity of H-shaped steel-larch composite beams. Comparing the calculation results with the test results, the data are in good agreement, which can provide a design reference for the practical application of such composite beams.

The durability of concrete structures can effectively be enhanced by using stainless steel rather than ordinary steel reinforcements under harsh service conditions. Because the basic mechanical properties and stress-strain relationship of stainless steel reinforcements obviously differ from those of ordinary steel reinforcements, the current design codes for reinforced concrete structures are not appropriate for stainless steel-reinforced concrete. On the basis of the research works reported in the past decades, this paper systematically summarizes and analyzes the mechanical properties and corrosion resistance of stainless steel reinforcements, the properties of the bond between stainless steel reinforcements and concrete, the mechanical properties of stainless steel-reinforced concrete members, and the application of stainless steel reinforcements in practical engineering and proposes relevant problems which should be examined further. It is suggested that the design theory of stainless steel-reinforced concrete structures should be further improved to take full advantage of these structures.

Modern temporary demountable structures must be designed to withstand the dynamic forces which generated by crowd occupants. The human forces and that cause the dynamic responses of structure have become an important research topic. In this paper, the human swaying forces and responses of temporary demountable grandstand are studied through an experimental program. The dynamic forces that were induced by participants who have swayed 0.5–1.8 Hz are recorded by a triaxial human biomechanics force plate, and the structural dynamic responses of a temporary grandstand occupied twenty swaying human are investigated. The constraint parameters of swaying force model which derives from a semiempirical formula are developed and can be represented for crowd. Crowd can able to induce excessive lateral vibration of structure due to the lower frequency of temporary grandstand and make them in panic. The dynamic responses of a large temporary grandstand are predicted by finite element method, and the results show that a person was considered as a load with stiffness and damping, and the structural lateral dynamic responses are higher than the model of person just only considered as load.

This paper extends the conventional Model Reference Adaptive Control systems to fractional ones based on the theory of fractional calculus. A control law and an incommensurate fractional adaptation law are designed for the fractional plant and the fractional reference model. The stability and tracking convergence are analyzed using the frequency distributed fractional integrator model and Lyapunov theory. Moreover, numerical simulations of both linear and nonlinear systems are performed to exhibit the viability and effectiveness of the proposed methodology.