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Abstract Background Mitochondria and endoplasmic reticulum (ER) contact sites (MERCS) constitute a functional communication platform for ER and mitochondria, and they play a crucial role in the lipid homeostasis of the liver. However, it remains unclear about the exact effects of MERCs on the neutral lipid synthesis of the liver. Methods In this study, the role and mechanism of MERCS in palmitic acid (PA)-induced neutral lipid imbalance in the liver was explored by constructing a lipid metabolism animal model based on yellow catfish. Given that the structural integrity of MERCS cannot be disrupted by the si-mitochondrial calcium uniporter (si-mcu), the MERCS-mediated Ca2+ signaling in isolated hepatocytes was intercepted by transfecting them with si-mcu in some in vitro experiments. Results The key findings were: (1) Hepatocellular MERCs sub-proteome analysis confirmed that, via activating Ip3r-Grp75-voltage-dependent anion channel (Vdac) complexes, excessive dietary PA intake enhanced hepatic MERCs. (2) Dietary PA intake caused hepatic neutral lipid deposition by MERCs recruiting Seipin, which promoted lipid droplet biogenesis. (3) Our findings provide the first proof that MERCs recruited Seipin and controlled hepatic lipid homeostasis, depending on Ip3r-Grp75-Vdac-controlled Ca2+ signaling, apart from MERCs’s structural integrity. Noteworthy, our results also confirmed these mechanisms are conservative from fish to mammals. Conclusions The findings of this study provide a new insight into the regulatory role of MERCS-recruited SEIPIN in hepatic lipid synthesis via Ip3r-Grp75-Vdac complex-mediated Ca2+ signaling, highlighting the critical contribution of MERCS in hepatic lipid homeostasis.

Abstract Characterizing the nature of hydrodynamical transport properties in quantum dynamics provides valuable insights into the fundamental understanding of exotic non-equilibrium phases of matter. Experimentally simulating infinite-temperature transport on large-scale complex quantum systems is of considerable interest. Here, using a controllable and coherent superconducting quantum simulator, we experimentally realize the analog quantum circuit, which can efficiently prepare the Haar-random states, and probe spin transport at infinite temperature. We observe diffusive spin transport during the unitary evolution of the ladder-type quantum simulator with ergodic dynamics. Moreover, we explore the transport properties of the systems subjected to strong disorder or a tilted potential, revealing signatures of anomalous subdiffusion in accompany with the breakdown of thermalization. Our work demonstrates a scalable method of probing infinite-temperature spin transport on analog quantum simulators, which paves the way to study other intriguing out-of-equilibrium phenomena from the perspective of transport.

Sleep is vital to our daily activity. Lack of proper sleep can impair functionality and overall health. While stress is known for its detrimental impact on sleep quality, the precise effect of pre-sleep stress on subsequent sleep structure remains unknown. This study introduced a novel approach to study the pre-sleep stress effect on sleep structure, specifically slow-wave sleep (SWS) deficiency. To achieve this, we selected forehead resting EEG immediately before and upon sleep onset to extract stress-related neurological markers through power spectra and entropy analysis. These markers include beta/delta correlation, alpha asymmetry, fuzzy entropy (FuzzEn) and spectral entropy (SpEn). Fifteen subjects were included in this study. Our results showed that subjects lacking SWS often exhibited signs of stress in EEG, such as an increased beta/delta correlation, higher alpha asymmetry, and increased FuzzEn in frontal EEG. Conversely, individuals with ample SWS displayed a weak beta/delta correlation and reduced FuzzEn. Finally, we employed several supervised learning models and found that the selected neurological markers can predict subsequent SWS deficiency. Our investigation demonstrated that the classifiers could effectively predict varying levels of slow-wave sleep (SWS) from pre-sleep EEG segments, achieving a mean balanced accuracy surpassing 0.75. The SMOTE-Tomek resampling method could improve the performance to 0.77. This study suggests that stress-related neurological markers derived from pre-sleep EEG can effectively predict SWS deficiency. Such information can be integrated with existing sleep-improving techniques to provide a personalized sleep forecasting and improvement solution.

In this article, a broadband 1-D high-gain beam steering solution to steer sum and difference patterns for tracking the optimum common scatter volume of troposcatter links at ${X}$ -band is presented. The novel steering arrangement consists of a $D = 70$ cm offset parabolic cylindrical (OPC) reflector fed by a triple-mode circular waveguide (TM-CW) horn antenna integrated with a two-element dielectric wedge-based Risley prism and a parabolic phase correcting dielectric lens (PCDL). The proposed hybrid beam steering reflector-feed obviates the need for complex 3-axes based gimbals to mechanically steer the conventional reflector-feed assembly. In the proposed hybrid reflector-feed arrangement, steering is achieved using a simple axial rotation of smaller Risley prism components at the feed. The broadband high-gain attribute required for an efficient troposcatter link is achieved by the proposed hybrid reflector-feed with much smaller and compact moving parts compared to traditional axial rotation-based mechanical steering arrangements. The simulated gain of the proposed antenna operating in TE11 mode at broadside is 25.7 dBi. A prototype of the proposed beam steering solution is built and tested in an anechoic chamber. The OPC reflector prototype is made of lightweight composite carbon fiber/fiber glass material thus reducing the overall antenna assembly weight. Experimental results show close agreement with the simulated ones. All three modes of TM-CW horn are steered by ±19° with TE11 mode patterns showing scan losses lower than 1 dB. The measured null depths for TM01 and TE21 modes are lower than −23 dB at 10 GHz. The peak of the sum and the nulls of the difference patterns are separated by a minimum difference of 25 dB at 10 GHz.

Molecularly targeted cancer therapy has improved outcomes for patients with cancer with targetable oncoproteins, such as mutant EGFR in lung cancer. Yet, the long-term survival of these patients remains limited, because treatment responses are typically incomplete. One potential explanation for the lack of complete and durable responses is that oncogene-driven cancers with activating mutations of EGFR often harbor additional co-occurring genetic alterations. This hypothesis remains untested for most genetic alterations that co-occur with mutant EGFR. Here, we report the functional impact of inactivating genetic alterations of the mRNA splicing factor RNA-binding motif 10 (RBM10) that co-occur with mutant EGFR. RBM10 deficiency decreased EGFR inhibitor efficacy in patient-derived EGFR-mutant tumor models. RBM10 modulated mRNA alternative splicing of the mitochondrial apoptotic regulator Bcl-x to regulate tumor cell apoptosis during treatment. Genetic inactivation of RBM10 diminished EGFR inhibitor-mediated apoptosis by decreasing the ratio of (proapoptotic) Bcl-xS to (antiapoptotic) Bcl-xL isoforms of Bcl-x. RBM10 deficiency was a biomarker of poor response to EGFR inhibitor treatment in clinical samples. Coinhibition of Bcl-xL and mutant EGFR overcame the resistance induced by RBM10 deficiency. This study sheds light on the role of co-occurring genetic alterations and on the effect of splicing factor deficiency on the modulation of sensitivity to targeted kinase inhibitor cancer therapy.

Food waste is a significant contributor to greenhouse gas emissions when it ends up in landfills. Composting turns out to be a sustainable solution to this problem, but it requires controlled and continuous airflow for optimal performance. This study focused on the effect of aeration rates and airflow directions on food waste composting using a closed system with forced aeration. Air was entered into the composting vessel in three directions, which were upward, downward, and a combination of both directions. Each direction was run at aeration rates of 0.1, 0.4, and 0.7 L/min. The findings showed that the compost pile aerated at 0.4 L/min by using two-directional airflow can reach the thermophilic temperature within half of the day. The compost pile achieved temperature of 40.94 °C after 10.5 h. Although the compost experienced slightly high in moisture loss (4.3%), the compost still attained the standard values for maturity. The compost produced from food waste could be applied in soil to improve its fertility.

In this work, the photothermal nonlinearity within a layered bismuth telluride (Bi2Te3) is studied in detail. The dynamics of the optical nonlinearity with increasing photothermal effect are investigated via pump-probe spectroscopy. The difference between the thermally-induced and photon-induced nonlinearities was clarified and the entire photothermal nonlinearity was therefore sketched. Furthermore, by removing the thermally-induced background signal, the n2 without accumulated heat can then be estimated. For example, the n2 value is 2.80 × 10−8 cm2/W at a peak intensity of 12.81 MW/cm2. The results are compared with those obtained from another measurement to validate the reliability of the estimation. The working range of the n2 value is also discussed. To provide further validation of the feasibility of the proposed method, the photothermal nonlinearity within monolayer graphene is provided and discussed. This work provides an alternative method to deal with optical nonlinearity measurements that are subject to the photothermal effect, paving the way toward further related research.

The rubber blends for rubber roller were prepared with natural rubber, styrene-butadiene rubber and trans-1,4-poly(butadiene-co-isoprene) rubber, the effects of trans-1,4-poly(butadiene-co-isoprene) rubber amount on the compatibility, curing characteristics, mechanical properties, wear resistance and aging resistance of the blends were investigated. The results showed that as the trans-1,4-poly(butadiene-co-isoprene) rubber amount increased from 0 to 20 phr (mass), the crosslinking density of the blend increased gradually and curing time shortened, tensile strength increased gradually, hardness increased slightly, compression permanent set showed a downward trend, and wear resistance improved. The compatibility of the three rubbers was good, and the dispersion of filler and aging resistance of the blending rubber were improved.

Abstract Background Mild cognitive impairment (MCI) is the stage between the expected cognitive decline of normal aging and the more serious decline of dementia. Previous studies have shown that regular exercise can improve cognition and physical performance in older adults. Walking is a low-technology and low-cost exercise that has been proven to improve cognition and mobility in healthy elderly individuals. However, no systematic review or meta-analysis has explored whether walking can improve cognitive function in older adults with MCI. This study aimed to explore the effects of walking interventions on cognitive functions in individuals with MCI. Methods In accordance with the PRISMA guidelines, MEDLINE, PubMed, SPORTDiscus, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, Airiti Library, and the National Digital Library of Theses and Dissertations in Taiwan were searched from inception to July 2023. Independent reviewers selected randomized clinical trials (RCT) that compared the effects of walking with no intervention or other exercises in individuals with MCI. The primary outcomes were cognitive functions, and the secondary outcome was walking endurance. Three reviewers independently conducted data extraction. The risk of bias was assessed using the Revised Cochrane Risk of Bias assessment tool. Results Fourteen RCTs were included in this review. The quality of evidence in these studies was rated as good to excellent. The results of the meta-analysis showed that the individuals with MCI had no significant improvement in cognitive function but had significant improvement in the 6-min walk test (Mean Difference=23.70, p=0.008) after walking interventions compared to no intervention or other exercises. Conclusion Walking intervention has no significant improvement on cognitive functions in older adults with MCI. However, walking induces beneficial effects on aerobic capacity. Trial registration This systematic review has the registration number CRD42021283753 on PROSPERO.

Abstract Quantum simulation enables study of many-body systems in non-equilibrium by mapping to a controllable quantum system, providing a powerful tool for computational intractable problems. Here, using a programmable quantum processor with a chain of 10 superconducting qubits interacted through tunable couplers, we simulate the one-dimensional generalized Aubry-André-Harper model for three different phases, i.e., extended, localized and critical phases. The properties of phase transitions and many-body dynamics are studied in the presence of quasi-periodic modulations for both off-diagonal hopping coefficients and on-site potentials of the model controlled respectively by adjusting strength of couplings and qubit frequencies. We observe the spin transport for initial single- and multi-excitation states in different phases, and characterize phase transitions by experimentally measuring dynamics of participation entropies. Our experimental results demonstrate that the recently developed tunable coupling architecture of superconducting processor extends greatly the simulation realms for a wide variety of Hamiltonians, and can be used to study various quantum and topological phenomena.

IntroductionIt is widely known that rural labor mobility is of the utmost importance for the livelihoods of families in rural areas of developing countries. While it increases the income and overall labor productivity of rural households, it also creates many inevitable rural recessions. Existing studies have different views on whether increasing income is the only reason for rural labor mobility.MethodsThis paper discusses the influencing factors of rural labor mobility and investigates research on the causes of rural labor mobility. To do so, the study analyzes micro-survey data of 47 villages in 13 cities in Heilongjiang province, China, from 2014 to 2019. Considering the basic situation of rural families and labor mobility, the actual demand for rural laborers in Heilongjiang province is also analyzed.ResultsThe research results show that increasing income is not the only reason for the flow of rural labor, and that rural labor mobility requires more than just rising incomes.DiscussionThis study's main contribution is identifying that increased income does have a positive and significant impact on rural labor mobility, but seeking job opportunities, pursuing better-quality education for children, and developing prospects are significant factors in the current rural labor mobility.

Summary: Gene-of-interest (GOI) knockout is an important technique to study the genetic mechanisms of T cells. Here, we present a protocol to generate GOI double allele gene knockouts in primary human T cells by CRISPR, thus depleting proteins of interest expressed intracellularly or extracellularly in primary T cells. We describe steps for gRNA selection and efficiency validation, homology-directed repair (HDR) DNA template design and cloning, and genome editing and HDR gene insertion. We then detail clone isolation and GOI knockout validation.For complete details on the use and execution of this protocol, please refer to Wu et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Numerous long noncoding RNAs (lncRNAs) are abnormally expressed in breast cancer (BC), but the underlying mechanisms remain large unknown. Here, we aimed to investigate the functions and mechanisms of lncRNA cancer susceptibility candidate 9 (CASC9) in BC. Western blotting and quantitative real‐time PCR (qRT‐PCR) were performed to assess gene and protein expression, respectively. The proliferative and metastatic abilities of BC cells were tested by cell counting kit‐8 and transwell assays, respectively. The formation of lymphatic vessels was detected by tube formation assay. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were performed to verify molecular interactions. CASC9 was found to be highly expressed in BC tissues and cell lines, and ectopic overexpression was positively associated with tumor volume, TNM stage, and lymph node metastasis. In addition, CASC9 silencing significantly inhibited the proliferation and invasion of BC cells, as well as BC‐associated invasion and formation of lymphatic vessels of human dermal lymphatic endothelial cells. Mechanical studies demonstrated that CASC9 could be transcriptionally activated by STAT3 and elevate SOX4 expression by enhancing the acetylation of its promoter region. Our results illustrated that STAT3‐activated CASC9 served as a tumor‐promoting gene involved in promoting BC invasion and BC‐associated formation of lymphatic vessels by upregulating SOX4 through altering H3K27ac level. This finding elucidated a new underlying network of CASC9 in the metastasis of BC.

Background/purpose: Suicide is a huge global health burden. High suicide rates with a low prevalence of major depressive disorder were reported in East Asia. This study aimed to investigate the prevalence of suicidal behaviors in relation to the demographic characteristics and major depressive disorder in Taiwan. Methods: This study was based on the Taiwan Psychiatric Morbidity Survey, conducted between 2003 and 2005, a survey of common psychiatric disorders in a nationally representative sample of non-institutionalized civilians aged 18 or above. Demographic data, major depressive disorder, and suicidal behaviors were ascertained by a face-to-face interview using the paper version of the World Mental Health Survey Composite International Diagnostic Interview. Results: According to the total sample of 10,135 participants, the lifetime prevalence of suicidal ideation, plans and attempts was 7.52% (S.E = 0.46%), 1.31% (S.E. = 0.16%) and 1.29% (S.E. = 0.16%), respectively. Among suicide ideators, the conditional probability of making a suicide plan was 17.39% (S.E. = 1.92%), and a suicide attempt 17.16% (S.E. = 2.15%). Age ≤ 40, female sex, and major depressive disorder were related to a higher risk of suicidal behaviors in the general population; the former two were associated with further developing suicide attempts and the latter one developing plans among ideators. Conclusion: Despite low prevalence, major depressive disorder remained a significant risk factor for suicidal behaviors in Taiwan.

This paper presents a passive 2-D beam steering solution comprising of a triple-mode circular waveguide horn antenna operating at Ka-band frequency of 30 GHz, a pair of identical dielectric lenses employing Risley prism and a parabolic phase correcting surface. The circular waveguide horn antenna generates ${\mathrm {TE}}_{11}, {\mathrm {TM}}_{01}$ and ${\mathrm {TE}}_{21}$ modes independently. The pair of identical dielectric lenses employing the Risley prism concept are axially rotated individually and/or simultaneously to steer the radiated beam. The parabolic phase correcting structure is used to further improve the performance of the steered patterns. Overall, this antenna structure steers ${\mathrm {TE}}_{11}, {\mathrm {TM}}_{01}$ and ${\mathrm {TE}}_{21}$ modes patterns which makes it an attracting solution for tracking and communication applications. The proposed antenna system has been prototyped and experimentally verified in a compact antenna test range (CATR) chamber. The measured conical scan angles for ${\mathrm {TE}}_{11}$ mode is found to be around $\pm 40{^\circ }$ with gain deviation less than 3 dB. The ${\mathrm {TM}}_{01}$ and ${\mathrm {TE}}_{21}$ modes are steered with a scan angle covering $\pm 30{^\circ }$ .

In this paper, investigations on heat sink property of a 4x2 wideband dual linear polarized phased array antenna comprised of 3D metal printed all metallic radiators, serving also as heat sink, is presented for X-band frequency. Two single radiators, each with a height nearly equal to ${\lambda }$ /2 corresponding to center frequency (9.50 GHz), shaped intuitively and placed orthogonal to each other and surrounded by a metal ring of square cross-section with overall dimension of ${\lambda }/2\times {\lambda }$ /2, constitutes the dual linear polarized radiating element. Both radiators are fed by an orthogonal arrangement of stripline feeds through a trapezium shaped metal plate, which in turn helps to integrate the antenna aperture with the beamforming network (BFN). A set of via fences are placed beneath each antenna element, which work as a thermal path between the BFN and antenna aperture. This radiating element resembles heat fins, and designed to cover 8.5-11.5 GHz impedance bandwidth. Good radiation pattern with low cross-polarization is obtained over the entire bandwidth, while the peak broadside gain is varying between 14–11 dBi. Beam scans are viable ±50° in ${\varphi }=0^{0}$ plane and ±30° in ${\varphi }=90^{0}$ plane. The array antenna aperture is built using 3D metal printing technology. The BFN is comprised of commercial silicon Radio Frequency Integrated Circuit (RFIC) chips which have been integrated with the antenna aperture. A beamforming algorithm is applied through serial peripheral interface (SPI) controller to achieve beam steering during the measurement process. The temperature reduction of 60°C is achieved with the heat sink structure when the temperature distribution of BFN with and without heat sink are compared for the 4x2 array. The temperature of the heat sink antenna is only 41°C and the temperature distribution is validated with an infrared (IR) camera.

IntroductionFerroptosis is associated with multiple pathophysiological processes. Inhibition of ferroptosis has received much concern for some diseases. Nonetheless, there is no study comprehensively illustrating functions of ferroptosis-related genes (FRGs) in psoriasis.MethodsIn this study, FRGs together with psoriasis-associated data were obtained in Ferroptosis Database (FerrDb) and gene expression omnibus (GEO) database separately. This work identified altogether 199 psoriasis-associated DE-FRGs, and they were tightly associated with immunity and autophagy modulation. Thereafter, the present study utilized SVM-RFE and LASSO algorithms to identify NR5A2, CISD1, GCLC, PRKAA2, TRIB2, ABCC5, ACSF2, TIMM9, DCAF7, PEBP1, and MDM2 from those 199 DE-FRGs to be marker genes. As revealed by later functional annotation, the marker genes possibly had important effects on psoriasis through being involved in diverse psoriasis pathogenesis-related pathways such as cell cycle, toll-like receptor (TLR), chemokine, and nod-like receptor (NLR) pathways. Moreover, altogether 37 drugs that targeted 11 marker genes were acquired. Besides, based on CIBERSORT analysis, alterations of immune microenvironment in psoriasis cases were possibly associated with PRKAA2, PEBP1, CISD1, and ACSF2.DiscussionTaken together, this work established the diagnostic potency and shed more lights on psoriasis-related mechanism. More investigations are warranted to validate its value in diagnosing psoriasis before it is applied in clinic.

Introduction: Although immune checkpoint inhibitors (ICIs) have dramatically improved outcomes for nononcogene-addicted NSCLC, monotherapy with programmed cell death protein-1 (PD1) inhibition has been associated with low efficacy in the EGFR-mutant setting. Given the potential for synergism with combination checkpoint blockade, we designed a trial to test the activity of combination nivolumab (N)-ipilimumab (NI) in EGFR-mutant NSCLC. Methods: This is a randomized phase 2 study (NCT03091491) of N versus NI combination in EGFR tyrosine kinase inhibitor (TKI)–resistant NSCLC, with crossover permitted on disease progression. The primary end point was the objective response rate, and the secondary end points included progression-free survival, overall survival, and safety of ICI after EGFR TKI. Results: Recruitment ceased owing to futility after 31 of 184 planned patients were treated. A total of 15 patients received N and 16 received NI combination. There were 16 patients (51.6%) who had programmed death-ligand (PDL1) 1 greater than or equal to 1%, and 15 (45.2%) harbored EGFR T790M. Five patients derived clinical benefits from ICI with one objective response (objective response rate 3.2%), and median progression-free survival was 1.22 months (95% confidence interval: 1.15–1.35) for the overall cohort. None of the four patients who crossed over achieved salvage response by NI. PDL1 and tumor mutational burden (TMB) were not able to predict ICI response. Rates of all grade immune-related adverse events were similar (80% versus 75%), with only two grade 3 events. Conclusions: Immune checkpoint inhibition is ineffective in EGFR TKI–resistant NSCLC. Whereas a small subgroup of EGFR-mutant NSCLC may be immunogenic and responsive to ICI, better biomarkers are needed to select appropriate patients.