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Cell growth is controlled by a lysosomal signalling complex containing Rag small GTPases and mammalian target of rapamycin complex 1 (mTORC1) kinase. Here, we carried out a microscopy-based genome-wide human short interfering RNA screen and discovered a lysosome-localized G protein-coupled receptor (GPCR)-like protein, GPR137B, that interacts with Rag GTPases, increases Rag localization and activity, and thereby regulates mTORC1 translocation and activity. High GPR137B expression can recruit and activate mTORC1 in the absence of amino acids. Furthermore, GPR137B also regulates the dissociation of activated Rag from lysosomes, suggesting that GPR137B controls a cycle of Rag activation and dissociation from lysosomes. GPR137B-knockout cells exhibited defective autophagy and an expanded lysosome compartment, similar to Rag-knockout cells. Like zebrafish RagA mutants, GPR137B-mutant zebrafish had upregulated TFEB target gene expression and an expanded lysosome compartment in microglia. Thus, GPR137B is a GPCR-like lysosomal regulatory protein that controls dynamic Rag and mTORC1 localization and activity as well as lysosome morphology.

Abstract Background Autophagy is a conserved catabolic process, which plays an important role in regulating tumor cell motility and degrading protein aggregates. Chemotherapy-induced autophagy may lead to tumor distant metastasis and even chemo-insensitivity in the therapy of hepatocellular carcinoma (HCC). Therefore, a vast majority of HCC cases do not produce a significant response to monotherapy with autophagy inhibitors. Results In this work, we developed a biomimetic nanoformulation (TH-NP) co-encapsulating Oxaliplatin (OXA)/hydroxychloroquine (HCQ, an autophagy inhibitor) to execute targeted autophagy inhibition, reduce tumor cell migration and invasion in vitro and attenuate metastasis in vivo. The tumor cell-specific ligand TRAIL was bioengineered to be stably expressed on HUVECs and the resultant membrane vesicles were wrapped on OXA/HCQ-loaded PLGA nanocores. Especially, TH-NPs could significantly improve OXA and HCQ effective concentration by approximately 21 and 13 times in tumor tissues compared to the free mixture of HCQ/OXA. Moreover, the tumor-targeting TH-NPs released HCQ alkalized the acidic lysosomes and inhibited the fusion of autophagosomes and lysosomes, leading to effective blockade of autophagic flux. In short, the system largely improved chemotherapeutic performance of OXA on subcutaneous and orthotopic HCC mice models. Importantly, TH-NPs also exhibited the most effective inhibition of tumor metastasis in orthotopic HCCLM3 models, and in the HepG2, Huh-7 or HCCLM3 metastatic mice models. Finally, we illustrated the enhanced metastasis inhibition was attributed to the blockade or reverse of the autophagy-mediated degradation of focal adhesions (FAs) including E-cadherin and paxillin. Conclusions TH-NPs can perform an enhanced chemotherapy and antimetastatic effect, and may represent a promising strategy for HCC therapy in clinics. Graphical Abstract

Background: Postoperative nausea and vomiting are common complications after surgery, and female patients are more likely to experience these adverse events. The goal of this study was to explore the relationship between the CHRM3 rs2165870 polymorphism and postoperative vomiting incidence in female patients who underwent laparoscopic surgery. Methods: Two hundred female patients who underwent elective laparoscopic surgery with subsequent patient-controlled intravenous analgesia using dexmedetomidine and sufentanil were prospectively enrolled. The CHRM3 rs2165870 and KCNB2 rs349358 polymorphisms were genotyped using MassARRAY SNP typing technology. Demographic data and preoperative laboratory results of all patients were recorded. Postoperative analgesia-related information, incidence of postoperative nausea and vomiting, and other adverse events were followed up and recorded for analysis. Results: No significant differences were observed in any of the demographic characteristics of these patients among the different genotype carriers (P>0.05). The percentages of patients with each genotype of CHRM3 were 67% (GG), 28.5% (GA) and 4.5% (AA). We found that the AA or A allele of the CHRM3 rs2165870 polymorphism elevated the risk of postoperative vomiting (AA versus GG; OR, 6.94; 95% CI, 1.49–32.46; P = 0.014; A versus G; OR, 2.52; 95% CI, 1.22–5.19; P = 0.012). The percentages of patients with each genotype of KCNB2 were 84.5% (TT), 15.5% (CT) and 0% (CC). There were no significant differences in the postoperative nausea or vomiting rate across the KCNB2 rs349358 polymorphisms (P>0.05). Conclusion: The CHRM3 rs2165870 polymorphism is associated with the occurrence of postoperative vomiting in female patients who have undergone laparoscopic surgery. The AA genotype or A allele of the CHRM3 rs2165870 polymorphism elevates the risk of postoperative vomiting. Trial registration: www.chictr.org.cn, registration number: ChiCTR2200062425. [ABSTRACT FROM AUTHOR]

Summary This paper considers multiuser downlink transmission and detection in a multiple input‐multiple output (MIMO) visible light communication (VLC) system. We combine two promising techniques: space‐shift keying (SSK) and optical orthogonal codes (OOCs). Multiuser downlink transmission is realized by allowing each activated LED to transmit user‐specific OOC simultaneously. An OOC despreader is implemented at the front end of each user terminal (UT) to extract the desired signal and mitigate multiuser interference (MUI). The second part of UT receiver aims to extract the index of the corresponding active LED based on maximum likelihood (ML) or zero‐forcing (ZF) algorithm. The figure of merit we used to access the performance of the proposed downlink multiuser SSK system is the average symbol error rate (SER). Comprehensive Monte Carlo simulations have been undertaken for different system setup to evaluate SER at UT receiver. It is demonstrated that for a specified SER, the required SNR for ML‐based detection algorithm is 3 dB less than the ZF detector in the MUI‐free scenario. On the other hand, the ZF detector outperforms ML detector in the case with residual MUI and limited channel state information (CSI). Both algorithms are computationally attractive, hence can be put into practice in multiuser VLC MIMO system. [ABSTRACT FROM AUTHOR]

Simple Summary: Animal personalities could affect the behavior and physiology of both native and invasive species during biological invasion. However, little is known about the personality interaction effects on foraging behavior and growth between native and invasive species. We used the red-eared slider turtle and Chinese pond turtle as models to investigate how personality interactions effect the foraging behavior and growth of both these turtle species. The results showed that the foraging behavior of M. reevesii was mainly affected by the personality of T. scripta elegans. However, the foraging behavior of T. scripta elegans was effected by both their own personality and the personalities of M. reevesii. Additionally, the growth of both M. reevesii and T. scripta elegans were not effected by the personality combinations. The results revealed the mechanisms of personality interaction effects on the foraging behavior and growth of both native and invasive species during biological invasion. This study provides empirical evidence to help understand the effects of personalities on invasion dynamics. Animal personalities play a crucial role in invasion dynamics. During the invasion process, the behavioral strategies of native species vary among personalities, just as the invasive species exhibit variations in behavior strategies across personalities. However, the impact of personality interactions between native species and invasive species on behavior and growth are rarely illustrated. The red-eared slider turtle (Trachemys scripta elegans) is one of the worst invasive species in the world, threatening the ecology and fitness of many freshwater turtles globally. The Chinese pond turtle (Mauremys reevesii) is one of the freshwater turtles most threatened by T. scripta elegans in China. In this study, we used T. scripta elegans and M. reevesii to investigate how the personality combinations of native and invasive turtles would impact the foraging strategy and growth of both species during the invasion process. We found that M. reevesii exhibited bolder and more exploratory personalities than T. scripta elegans. The foraging strategy of M. reevesii was mainly affected by the personality of T. scripta elegans, while the foraging strategy of T. scripta elegans was influenced by both their own personality and personalities of M. reevesii. Additionally, we did not find that the personality combination would affect the growth of either T. scripta elegans or M. reevesii. Differences in foraging strategy may be due to the dominance of invasive species and variations in the superficial exploration and thorough exploitation foraging strategies related to personalities. The lack of difference in growth may be due to the energy allocation trade-offs between personalities or be masked by the slow growth rate of turtles. Overall, our results reveal the mechanisms of personality interaction effects on the short-term foraging strategies of both native and invasive species during the invasion process. They provide empirical evidence to understand the effects of personality on invasion dynamics, which is beneficial for enhancing comprehension understanding of the personality effects on ecological interactions and invasion biology. [ABSTRACT FROM AUTHOR]

Background: Patients with Parkinson's disease (PD) respond to deep brain stimulation (DBS) variably. However, how brain substrates restrict DBS outcomes remains unclear. Objective: In this article, we aim to identify prognostic brain signatures for explaining the response variability. Methods: We retrospectively investigated a cohort of patients with PD (n = 141) between 2017 and 2022, and defined DBS outcomes as the improvement ratio of clinical motor scores. We used a deviation index to quantify individual perturbations on a reference structural covariance network acquired with preoperative T1‐weighted magnetic resonance imaging. The neurobiological perturbations of patients were represented as z scored indices based on the chronological perturbations measured on a group of normal aging adults. Results: After applying stringent statistical tests (z > 2.5) and correcting for false discoveries (P < 0.01), we found that accelerated deviations mainly affected the prefrontal cortex, motor strip, limbic system, and cerebellum in PD. Particularly, a negative network within the accelerated deviations, expressed as "more preoperative deviations, less postoperative improvements," could predict DBS outcomes (mean absolute error = 0.09, R2 = 0.15). Moreover, a fusion of personal brain predictors and medical responses significantly improved traditional evaluations of DBS outcomes. Notably, the most important brain predictor, a pathway connecting the cognitive unit (prefrontal cortex) and motor control unit (cerebellum and motor strip), partially mediates DBS outcomes with the age at surgery. Conclusions: Our findings suggest that individual structural perturbations on the cognitive motor control circuit are critical for modulating DBS outcomes. Interventions toward the circuit have the potential for additional clinical improvements. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Herein, Li2MgxZrO3+x (x = 0–1) +2 wt.% LiF ceramics with a rock salt structure were prepared by the solid‐state reaction method. The phase transition mechanism was systematically investigated by X‐ray diffraction, and first‐principles calculations. With a gradual increase in MgO content, the samples underwent a monoclinic‐Li2ZrO3 to tetragonal‐Li2ZrO3 to tetragonal‐Li2MgZrO4 to cubic‐phase transition. The variations of the microwave dielectric properties due to the phase transition were systematically analyzed by the multi‐phase mixtures law. In addition, CO2 adsorption of the samples was quantitatively analyzed by X‐ray photoelectron spectroscopy, and the long‐term stability of the Q × f of the samples was investigated. The optimal microwave dielectric properties were obtained in Li2Mg0.2ZrO3.2 ceramic at 950°C: εr = 19.5, Q × f = 44 500 GHz, and τf = 2.6 ppm/°C. In addition, the ceramic samples were compatible with Ag, which indicates that Li2MgxZrO3+x (x = 0−1) +2 wt.% LiF is a promising material for low‐temperature co‐fired ceramics. [ABSTRACT FROM AUTHOR]

A novel terahertz polarization isolator using a two-dimensional square lattice tellurium rod array is numerically investigated at the interesting band of 0.22 THz in this short paper. The isolator is designed by inserting six hexagonal tellurium rods into a fully polarized photonic crystals waveguide with high efficiency of −0.34 dB. The TE and TM photonic band gaps of the 7 × 16 tellurium photonic crystals are computed based on the plane wave expansion method, which happen to coincide at the normalized frequency domain from 0.3859(a/λ) to 0.4033(a/λ), corresponding to the frequency domain from 0.2152 to 0.2249 THz. The operating bandwidth of the tellurium photonic crystals waveguide covers 0.2146 to 0.2247 THz, calculated by the finite element method. The six hexagonal tellurium rods with smaller circumradii of 0.16a serve to isolate transverse electric waves and turn a blind eye to transverse magnetic waves. The polarization isolation function and external characteristic curves of the envisaged structure are numerically simulated, which achieves the highest isolation of −33.49 dB at the central frequency of 0.2104 THz and the maximum reflection efficiency of 98.95 percent at the frequency of 0.2141 THz. The designed isolator with a unique function and high performance provides a promising approach for implementing fully polarized THz devices for future 6G communication systems. [ABSTRACT FROM AUTHOR]

Evolutionary algorithm is an important method for solving large-scale optimization problems, which is widely applied to machine learning, process control, engineering optimization, management science, and social sciences. However, when the traditional evolutionary algorithms are used to high-dimensional and computing-density task, the performance of corresponding applications is difficult to be satisfactory. Parallelization on supercomputer is a popular solution to solve this problem. This paper proposes a two-level parallel self-adaptive differential evolution algorithm with neighborhood search (SaNSDE) on the Sunway TaihuLight, which implements process-level and thread-level parallelism. In the process-level parallelism, the cooperative co-evolution model and pool model are implemented, which divide large-scale problems into multiple low-dimensional problems and distribute them in different processes. In the thread-level parallelism, fitness calculation is accelerated. Experimental results show that the algorithm using the cooperative co-evolution model and the pool model, compared with the traditional parallel algorithm, improves the convergence effect more obviously after multi-core expansion. Compared with the serial algorithm, the two-level parallel SaNSDE algorithm achieves the maximum speedup of 134.29, 186.05, 239.01 and 189.80 in the four benchmark functions, respectively.