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BACKGROUND: Low protein intake (LPI) has been suggested as a treatment for chronic kidney disease (CKD). However, protein intake is essential for bone health. METHODS: We studied the database of the National Health and Nutrition Examination Survey, 2005-2010. Basic variables, metabolic diseases, and bone density of different femoral areas were stratified into four subgroups according to different protein intake (DPI) (that is, 1.2 g/kg/day). RESULTS: Significant differences were found among all lumbar area bone mineral density (BMD) and T-scores (p 1.2 g/day/kg over L2 (relative risk (RR)=1.326, 95% confidence interval (CI)=1.062-1.656), subgroup >1.2 g/day/kg over L3 (RR = 1.31, 95%CI = 1.057-1.622), subgroup 1.2 g/day/kg over all L spines (RR = 0.333, 95%CI = 1.098-1.618). However, a higher risk of osteoporosis was observed only in the non-CKD group. There was an apparent trend of higher DPI coexisting with lower BMD and T scores in patients with CKD. For osteoporosis (reference:0.8-1.0 g/day/kg), lower (1.2 g/day/kg) was associated with higher risks in the non-CKD group, but not in the CKD group. CONCLUSIONS: In the CKD group, LPI for renal protection was safe without threatening L spine bone density and without causing a higher risk of osteoporosis.

Deep coalbed methane (CBM) possesses enormous resource potential and is essential for increasing unconventional natural gas reserves and production on a large scale in China. To understand the current status of CBM research and development in China, systematic retrieval and classification of deep CBM-related publications are conducted using the China National Knowledge Infrastructure (CNKI) database and Wanfang Data Knowledge Service Platform. Based on this analysis, the status of deep CBM research in China is reviewed, and its development trends are discussed, providing insights into adaptive exploration and development technologies for deep CBM. The results indicate that the temporal distribution of publications reflects the evolution of China's deep CBM research and industrial development, which can be divided into four stages: the initial exploration stage (1994 to 2005), the slow development stage (2006 to 2015), the steady progress stage (2016 to 2020), and the rapid development stage (since 2021). Geological and engineering "dual sweet spot" prediction is a key research focus for deep CBM research. Conducting geology and engineering integrated research for deep CBM exploration and development, based on the quantitative characterization of geological and engineering parameters and using three-dimensional geological and geomechanical modeling, is a critical pathway to ensuring profitable development. The production state and development degree of natural fractures in coal reservoirs significantly affect fracturing transformation. The connectivity of fracture networks before and after fracturing is an important indicator for determining the performance of deep CBM development. The development of deep CBM technologies and their applicability are the key areas to be explored in the future. Deepening theoretical understanding, quantitatively characterizing geological and engineering conditions, and comprehensively analyzing influencing factors are fundamental and crucial for the further rapid development of deep CBM in China. Deep and ultra-deep CBM in basins such as the Ordos, Junggar, Sichuan, and Tarim basins will be the research focus and the key exploration and development areas.

Abstract N6-methyladenosine (m6A) is among the most abundant mRNA modifications, yet its cell-type-specific regulatory roles remain unclear. Here we show that m6A methyltransferase-like 14 (METTL14) differentially regulates transcriptome in brown versus white adipose tissue (BAT and WAT), leading to divergent metabolic outcomes. In humans and mice with insulin resistance, METTL14 expression differs significantly from BAT and WAT in the context of its correlation with insulin sensitivity. Mettl14-knockout in BAT promotes prostaglandin secretion, improving systemic insulin sensitivity. Conversely, Mettl14-knockout in WAT triggers adipocyte apoptosis and systemic insulin resistance. m6A-seq and RNA-seq integration revealed upregulated prostaglandin biosynthesis pathways in BAT and apoptotic pathways in WAT with Mettl14 deficiency. Stable METTL14-knockout hBAs/hWAs show METTL14-mediated m6A promotes mRNA decay of PTGES2 and CBR1 in hBAs and TRAIL and TNFR1 in hWAs. These data shed light on the ability of m6A to impact metabolism in a cell-type-specific manner with implications for influencing the pathophysiology of metabolic diseases.

Hedgehog (Hh) signaling relies on the primary cilium, a cell surface organelle that serves as a signaling hub for the cell. Using proximity labeling and quantitative proteomics, we identify Numb as a ciliary protein that positively regulates Hh signaling. Numb localizes to the ciliary pocket and acts as an endocytic adaptor to incorporate Ptch1 into clathrin-coated vesicles, thereby promoting Ptch1 exit from the cilium, a key step in Hh signaling activation. Numb loss impedes Sonic hedgehog (Shh)-induced Ptch1 exit from the cilium, resulting in reduced Hh signaling. Numb loss in spinal neural progenitors reduces Shh-induced differentiation into cell fates reliant on high Hh activity. Genetic ablation of Numb in the developing cerebellum impairs the proliferation of granule cell precursors, a Hh-dependent process, resulting in reduced cerebellar size. This study highlights Numb as a regulator of ciliary Ptch1 levels during Hh signal activation and demonstrates the key role of ciliary pocket-mediated endocytosis in cell signaling.

Abstract Nonlinear optical responses in two-dimensional (2D) materials can build free-space optical neuromorphic computing systems. Ensuring the high performance and the tunability of the system is essential to encode diverse functions. However, common strategies, including the integration of external electrode arrays or photonic structures with 2D materials, and barely patterned 2D materials, exhibit a contradiction between performance and tunability. Because the unique band dispersions of 2D materials can provide hidden paths to boost nonlinear responses independently, here we introduced a new free-space optical computing concept within a bare molybdenum disulfide array. This system can preserve high modulation performance with fast speed, low energy consumption, and high signal-to-noise ratio. Due to the freedom from the restrictions of fixed photonic structures, the tunability is also enhanced through the synergistic encodings of the 2D cells and the excitation pulses. The computing mechanism of transition from two-photon absorption to synergistic excited states absorption intrinsically improved the modulation capability of nonlinear optical responses, revealed from the relative transmittance modulated by a pump-probe-control strategy. Optical artificial neural network (ANN) and digital processing were demonstrated, revealing the feasibility of the free-space optical computing based on bare 2D materials toward neuromorphic applications.

Abstract The interaction between germ cells and somatic cells in the ovaries plays a crucial role in establishing the follicle reserve in mammals. Turner syndrome (TS) predominantly affects females who have a partial or complete loss of one X chromosome. Our understanding of the role that granulosa cells (GCs) play in TS disease progression and pathogenesis remains limited. In this study, we achieved GC differentiation efficiency of up to 80% from iPSCs. When attempting to replicate the differentiation process of embryonic granulosa cells, we observed the downregulation of specific genes—GATA4, FOXL2, AMHR2, CYP19A1, and FSH—in Turner syndrome-derived granulosa cells (TS-GCs). Additionally, we identified dysregulation of the cell cycle in TS-GCs. To uncover the endogenous defects in TS-GCs, we compared global transcriptome patterns between iPSC-derived granulosa cells from healthy individuals and those with Turner syndrome. The apelin/APJ pathway exhibited differential signaling between the healthy and TS groups. Supplementation with apelin ligands and activation of apelin/APJ downstream signaling via Akt/PKB restored cell cycle progression and marker gene expression. We hypothesize that during early embryonic development, failures in apelin/APJ signaling in GCs of Turner syndrome patients lead to abnormalities in ovarian development, ultimately resulting in early oocyte loss and infertility.

ABSTRACT Background The vigour of our musculature wanes as the years advance, and prognosticating the concomitant trajectories throughout the course of life assumes paramount importance for judicious and timely interventions. In the present study, we aimed to establish age‐ and sex‐specific reference centiles for multiple muscle health metrics and reveal the distributions of these metrics throughout the aging process in the Asian population. Methods By using cross‐sectional pooled data of community dwellers aged 20 years or older in eight cohorts from Taiwan, Japan and Malaysia, normative values for muscle health metrics (calf circumference (cm), relative appendicular skeletal muscle (RASM) (kilogram per square metre), body mass index (BMI)–adjusted appendicular skeletal muscle mass (kilogram/(kilogram per square metre)), handgrip strength (kilogram), five‐time chair stand (seconds) and gait speed (metre per second)) in men and women, categorized by age groups, are calculated. The mean values, along with the 5th, 25th, 50th, 75th and 95th percentiles of these muscle health metrics, are also delineated for both sexes. Results Among 34 265 (16 164 men, 18 101 women) participants from eight cohorts, calf circumference declined in age groups from 60 years onward. RASM values declined from the 50s in men but were stable in women until the 80s. ASM/BMI values showed declines in older age groups for both sexes. Handgrip strength declined similarly from 40 years of age in both sexes. Five‐time chair stand performance declined from the 30s. Gait speed peaked at 1.6 m/s in men in their 50s and then declined, while it declined in women in their 60s. The inflection points for decline differed by metric and sex. The 20th percentile cutoffs for individuals aged 65–69 years were as follows: calf circumference, 33.0 cm (men) and 31.5 cm (women); RASM, 7.0 kg/m2 (men) and 5.5 kg/m2 (women); ASM/BMI, 0.78 kg/(kg/m2) (men) and 0.56 kg/(kg/m2) (women); handgrip strength, 30.4 kg (men) and 18.1 kg (women); five‐time chair stand, 9.4 s (men) and 10.0 s (women); and gait speed, 0.9 m/s (both). Those in the fifth percentile of all muscle health metrics faced earlier declines than their 95th percentile counterparts did, highlighting the critical roles in identifying these high‐risk groups. Conclusion The pooled analysis of eight Asian cohorts clearly outlined the age‐related changes in various muscle health metrics, with the inflection point of accelerated decline showing age‐ and sex‐specific characteristics. Defining trajectories of muscle health metrics across life stages facilitates timely interventions to mitigate age‐related risks and promote healthy longevity.

In the process of oil and gas exploration, development and production, reservoir pressure plays a crucial role in the accumulation, distribution and migration of oil and gas. Abnormally high-pressure reservoirs can lead to drilling accidents such as wellbore collapse, kicks and blowouts. Traditional methods for predicting reservoir pressure, mainly based on well logging calculations using empirical formula and effective stress methods, suffer from drawbacks including complex parameter identification and significant subjectivity. Consequently, the paper uses the DF block in the Yinggehai Basin as a case study, building a reservoir pressure prediction model based on real-time pressure data using both the BP neural network and convolutional neural network. This process established an implicit direct relationship between logging curves and real-time reservoir pressure, allowing for the prediction of reservoir pressure and an analysis of the causes of overpressure. The results of the study indicate that: (1) The established convolutional neural network model demonstrates high accuracy in predicting reservoir pressure, with a root mean square error of 0.27 MPa for the optimal model. (2) The predicted reservoir pressure range for the Huangliu Formation in the DF block of the Yinggehai Basin is 53.26-55.60 MPa, with an average pressure coefficient of 1.66-1.95, consistent with overpressure. (3) The mechanism behind the overpressure in the Huangliu Formation, DF block, is mainly due to fluid expansion, supplemented by undercompaction.

To clarify the mechanical characteristics of tight sandstone in the Cretaceous Bashijiqike Formation of Kuqa Depression in Tarim Basin, and address field issues in deep and ultra-deep oil and gas exploration and development, triaxial compression experiments were used to quantitatively study the patterns of changes in rock mechanical properties influenced by confining pressure, fluid, and loading rate, with a preliminary analysis of their causes. The results showed that the maximum principal stress difference and elastic modulus of the sandstone samples increased significantly with confining pressure. The micro-reason was that the increase in confining pressure reduced the distance between particles inside the rock, enhancing the rock's cohesion and making particle dispersion less likely. Sandstone samples exhibited a progression from brittleness under low confining pressure to brittle-ductile transformation, and to ductile deformation under high confining pressure. Compared with dry sandstone samples, the reduction in the elastic modulus of samples soaked in pure water, 150 g/L solution, 250 g/L solution, and 350 g/L solution were 67.71%, 61.45%, 64.69%, and 57.32%, respectively, with pure water soaking causing the greatest reduction. Increasing fluid salinity could mitigate the weakening trend in rock mechanical parameters. Crystallization on crystal surfaces and changes in the electric double layer thickness were important controlling factors for these patterns. At lower loading rates, the values for maximum principal stress difference, elastic modulus, and Poisson's ratio of the sandstone samples were smaller, but they increased faster with increasing loading rates. When the loading rate reached a certain critical value (around 0.05 mm/min in this experiment), the rate of increase in rock mechanical parameters slowed down.

Efficient exploration and development of ultra-deep oil and gas reservoirs are key objectives in current global energy geological research. The concept of "geomechanical strata and oil and gas exploration and development" represents a cutting-edge research area internationally. Establishing an effective method for dividing geomechanical layers holds both theoretical and practical significance for the efficient exploration and economical development of ultra-deep oil and gas reservoirs. Currently, the state of in-situ stress affects the effectiveness of natural fractures, while the development and distribution of fractures impact the mechanical properties of rocks, which influence the the distribution of in-situ stress. However, the existing "rock mechanical stratigraphy theory" fails to comprehensively cover the coupling relationships among these three factors. In response, this study introduced a method for the quantitative division of geomechanical strata based on six parameters: minimum horizontal principal stress, difference in horizontal stress, elastic modulus, angle between the current dominant stress orientation and the natural fracture orientation, natural fracture density, and stress concentration factor. An analysis of well W in the Dabei area of the Kelasu structural belt, Kuqa Depression, Tarim Basin, demonstrated that the target layers at the Cretaceous Bashijiqike Formation exhibited strong vertical geomechanical heterogeneity. The geomechanical strata of the reservoir correlated well with the development sections of the gas layers. Therefore, with the results of geomechanical strata division, it is possible to guide the optimization of sweet spots in ultra-deep oil and gas reservoirs.

Abstract Recognizing an individual’s preference state for potential romantic partners based on electroencephalogram (EEG) signals holds significant practical value in enhancing matchmaking success rates and preventing romance fraud. Despite some progress has been made in this field, challenges such as high-dimensional feature space and channel redundancy limited the technology’s practical application. The aim of this study is to explore the most discriminative EEG features and channels, in order to enhance the recognition performance of the system, while maximizing the portable and practical value of EEG-based systems for recognizing romantic attraction. To achieve this goal, we first conducted an interesting simulated dating experiment to collect the necessary data. Next, EEG features were extracted from various dimensions, including band power and asymmetry index features. Then, we introduced a novel method for EEG feature and channel selection that combines the sequential forward selection (SFS) algorithm with the frequency-based feature subset integration (FFSI) algorithm. Finally, we used the random forest classifier (RFC) to determine a person's preference state for potential romantic partners. Experimental results indicate that the optimal feature subset, selected using the SFS-FFSI method, attained an average classification accuracy of 88.42%. Notably, these features were predominantly sourced from asymmetry index features of electrodes situated in the frontal, parietal, and occipital lobes.

BackgroundEmerging research indicates that gut microbiota (GM) are pivotal in the regulation of immune-mediated bone diseases. Nonunion, a bone metabolic disorder, has an unclear causal relationship with GM and immune cells. This study aims to elucidate the causal relationship between GM and nonunion using Mendelian Randomization (MR) and to explore the mediating role of immune cells.MethodsUsing a two-step, two-sample Mendelian randomization approach, this study explores the causal link between GM and nonunion, as well as the mediating role of immune cells in this relationship. Data were sourced from multiple cohorts and consortiums, including the MiBioGen consortium. GM data were derived from a recently published dataset of 473 gut microbiota, and nonunion data were obtained from genome-wide association studies (GWAS).ResultsMR analysis identified 12 bacterial genera with protective effects against nonunion and seven bacterial genera associated with a higher risk of nonunion, including Agathobacter sp000434275, Aureimonas, Clostridium M, Lachnospirales, Megamonas funiformis, and Peptoccia. Reverse MR analysis indicated that nonunion does not influence GM. Additionally, MR analysis identified 12 immune cell types positively associated with nonunion and 14 immune cell types negatively associated with nonunion. Building on these findings, we conducted mediation MR analysis to identify 24 crucial GM and immune cell-mediated relationships affecting nonunion. Notably, Campylobacter D, Megamonas funiformis, Agathobacter sp000434275, Lachnospirales, Clostridium E sporosphaeroides, and Clostridium M significantly regulated nonunion through multiple immune cell characteristics.ConclusionsTo our knowledge, our research results are the first to emphasize a causal relationship between the gut microbiome and nonunion, potentially mediated by immune cells. The correlations and mediation effects identified in our study provide valuable insights into potential therapeutic strategies targeting the gut microbiome, informing global action plans.

Background Low protein intake (LPI) has been suggested as a treatment for chronic kidney disease (CKD). However, protein intake is essential for bone health.Methods We studied the database of the National Health and Nutrition Examination Survey, 2005–2010. Basic variables, metabolic diseases, and bone density of different femoral areas were stratified into four subgroups according to different protein intake (DPI) (that is, 1.2 g/kg/day).Results Significant differences were found among all lumbar area bone mineral density (BMD) and T-scores (p 1.2 g/day/kg over L2 (relative risk (RR)=1.326, 95% confidence interval (CI)=1.062–1.656), subgroup >1.2 g/day/kg over L3 (RR = 1.31, 95%CI = 1.057–1.622), subgroup 1.2 g/day/kg over all L spines (RR = 0.333, 95%CI = 1.098–1.618). However, a higher risk of osteoporosis was observed only in the non-CKD group. There was an apparent trend of higher DPI coexisting with lower BMD and T scores in patients with CKD. For osteoporosis (reference:0.8–1.0 g/day/kg), lower (1.2 g/day/kg) was associated with higher risks in the non-CKD group, but not in the CKD group.Conclusions In the CKD group, LPI for renal protection was safe without threatening L spine bone density and without causing a higher risk of osteoporosis.

Background: Elevated circulatory phosphate levels are linked to age-related muscle dysfunction, yet the mechanisms remain unclear. This study investigated the hypothesis that inflammation plays a role in connecting elevated phosphate levels to muscular dysfunction in middle-aged and older individuals and explored potential sex-based differences in these associations. Methods: The study, based on the I-Lan Longitudinal Aging Study Cohort, analyzed individuals' serum phosphate and hsCRP levels. Sex-specific analyses explored links between circulatory phosphate, inflammation, and muscle profiles (mass, handgrip strength, and walking speed). The study also examined potential mediation or synergistic effects of inflammation in the circulatory phosphate-muscle relationship. Results: The study included 2006 participants (mean age: 65.5 ± 6.5 years; 49.8 % men). Women exhibited higher circulatory phosphate levels than men. Linear analyses revealed that higher phosphate levels were significantly associated with weaker handgrip strength but not with reduced muscle mass in both men and women. In women, circulatory phosphate was not associated with inflammation (hsCRP levels), while in men, higher phosphate levels were significantly associated with higher hsCRP levels. In men, a synergistic effect was observed, where the combination of high hsCRP and elevated phosphate levels had a more pronounced impact on reducing handgrip strength than either factor alone. Conclusions: This study highlights a sex-specific association of inflammation in the mechanisms of hyperphosphatemia-related muscle weakness. The findings emphasize the importance of managing both hyperphosphatemia and chronic inflammation to mitigate their collective impact on muscle function, particularly in older men. Addressing these factors is crucial for promoting muscle health in later life.

Introduction Knee osteoarthritis (OA) represents a leading cause of disability globally. Exercise has been demonstrated to improve pain and function in people with knee OA. However, when in pain, commencement of exercise is difficult, and clinical effects with such interventions are often modest. Recently, transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, has been shown to bolster the pain-relieving effect of exercise in experimental settings. While promising, the utility of employing this approach beyond the research environment is yet to be elucidated. Therefore, this pilot study aims to investigate the feasibility, safety, adherence, tolerability and preliminary efficacy of tDCS and exercise in home-based settings to improve pain and function in people with knee OA.Methods and analysis This protocol is for a pilot randomised, double-blinded, sham-controlled trial. 24 individuals with idiopathic knee OA will be randomised to receive either active tDCS+exercise (Intervention) or sham tDCS+exercise (Control) at home. Participants will receive 20 min of tDCS 5 days per week for the first 2 weeks of this 8-week trial. Participants in both groups will complete a lower limb strengthening programme 3 days per week for the entire 8 weeks. Outcome measures of feasibility (acceptability, satisfaction, retention), safety, adherence and tolerability will be assessed throughout the trial period, with clinical outcomes of pain and function assessed before and following the intervention. Feasibility, safety, adherence and tolerability outcomes will be explored descriptively using frequencies and percentages. To examine preliminary efficacy, within-group and between-group changes in pain and functional measures will be analysed.Ethics and dissemination This protocol obtained ethical approval from the Queensland University of Technology Human Research Ethics Committee (HREA 2024-8302-20200). All participants will provide written informed consent. The findings of the study will be disseminated via journal publications and international conference proceedings.Trial registration number ACTRN12624000397516p.

Objectives: We investigated the associations of mean levels of leisure-time physical activity (LTPA) and latent LTPA trajectories with all-cause mortality risk. Methods: Trajectories of LTPA were established using group-based trajectory analysis with a latent class growth model in a population-based cohort between 1996 and 2014. A Cox-proportional hazard model was conducted to examine the associations of LTPA quintiles and LTPA trajectories with all-cause mortality. Results: A total of 21,211 participants (age 18-90 years) were analyzed (median follow-up 16.8 years). The study participants were divided into five groups according to percentiles of LTPA (

We report a detailed characterization of two inductively coupled superconducting fluxonium qubits for implementing high-fidelity cross-resonance gates. Our circuit stands out because it behaves very closely to the case of two transversely coupled spin- $1/2$ systems. In particular, the generally unwanted static ZZ -term due to the non-computational transitions is nearly absent despite a strong qubit–qubit hybridization. Spectroscopy of the non-computational transitions reveals a spurious LC -mode arising from the combination of the coupling inductance and the capacitive links between the terminals of the two-qubit circuit. Such a mode has a minor effect on the present device, but it must be carefully considered for optimizing future multi-qubit designs.

This study aimed to evaluate the impact of music technology on the attitudes and engagement level of preschool children. The desired outcome of the study is to formulate recommendations to improve the teaching curriculum through the use of physical activities at the preschool level. The strategy tested involved integrating technology, music, and images into children's physical activities to enhance their willingness to learn, preference, and motor skills. The study used music and images created through technology instruments to stimulate multiple senses, including vision, hearing, and touch sensations. It was expected to enhance learning interests and motor skills among children in physical activities. The innovative courses were developed jointly by qualified and senior preschool teachers, a physical fitness trainer, and a music therapist. The regimen involved a set of lesson plans combining music technology with physical training for children. The study used 64 healthy children who were 5 years old and studied at a private preschool in Taiwan, who were divided into an experimental group that implemented the innovative courses and a control group that adopted traditional teaching. The physical training courses were implemented twice a week, with 45 min per session for 18 weeks. The results revealed a significant enhancement in the concentration, preference, and willingness of participation among children in the experimental group after participation in the course. However, these effects were not observed and were not found among the children in the control group. Additionally, it was also found that the positive impact of enhanced motor skills, such as dynamic balance, hopping, and jumping, was significantly better among children in the experimental group than those in the control group. Consequently, this research study supports the integration of music technology and images into physical courses for children. Clinically, it indicates a significantly improved enhancement effect towards learning mentality and motor skills among children. This innovative teaching approach suggests a high probability to substantially assist the preschool's course management strategy and methodical learning effects.