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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis, which is lethal in approximately 90% of cases despite advanced standard therapies. A typical feature of PDAC is the immunosuppressive tumor microenvironment with multiple immunosuppressive factors including neurotransmitters. Recently, neuromedin U (NMU), a highly conserved neuropeptide with many physiological functions, has attracted attention for its roles in tumorigenesis and metastasis in several types of cancers. However, whether NMU affects PDAC progression remains unclear. In this study, using an orthotopic mouse model of PDAC in combination with bioinformatics analysis, we found that NMU was upregulated in tumor tissues from the patients with PDAC and positively correlated with a poor prognosis of the disease. Interestingly, knockout of the Nmu gene in mice enhanced the anti‐tumor functions of tumor‐infiltrating CD8+ T cells in an NMU receptor 1‐dependent manner. Additionally, NMU promoted the glycolytic metabolism of mouse PDAC tumors. The activities of pyruvate kinase (PK) and lactate dehydrogenase (LDH), pivotal enzymes involved in the regulation of lactate production, were markedly reduced in tumor tissues from NMU‐knockout mice. In vitro the presence of LDHA inhibitor can reduce the production of lactic acid stimulated by NMU, which can increase the anti‐tumor activity of CD8+ T cells. Moreover, treatment of the pancreatic cancer cells with a phosphoinositide 3‐kinase (PI3K) inhibitor diminished NMU‐induced lactate production and the activities of PK and LDH, suggesting that NMU might regulate glycolysis via the PI3K/AKT pathway. We found that neuromedin U (NMU) may act as a poor prognostic factor for patients with PADC, and it can inhibit the anti‐tumor activity of tumor‐infiltrating CD8+ T cells directly in an NMU receptor 1‐dependent manner. NMU may also enhance glycolysis in tumors, resulting in increased lactate concentration in the tumor microenvironment, which may further contribute to decreased CD8+ T‐cell anti‐tumor activity.

As key organelles involved in cellular metabolism, mitochondria frequently undergo adaptive changes in morphology, components and functions in response to various environmental stresses and cellular demands. Previous studies of mitochondria research have gradually evolved, from focusing on morphological change analysis to systematic multiomics, thereby revealing the mitochondrial variation between cells or within the mitochondrial population within a single cell. The phenomenon of mitochondrial variation features is defined as mitochondrial heterogeneity. Moreover, mitochondrial heterogeneity has been reported to influence a variety of physiological processes, including tissue homeostasis, tissue repair, immunoregulation, and tumor progression. Here, we comprehensively review the mitochondrial heterogeneity in different tissues under pathological states, involving variant features of mitochondrial DNA, RNA, protein and lipid components. Then, the mechanisms that contribute to mitochondrial heterogeneity are also summarized, such as the mutation of the mitochondrial genome and the import of mitochondrial proteins that result in the heterogeneity of mitochondrial DNA and protein components. Additionally, multiple perspectives are investigated to better comprehend the mysteries of mitochondrial heterogeneity between cells. Finally, we summarize the prospective mitochondrial heterogeneity-targeting therapies in terms of alleviating mitochondrial oxidative damage, reducing mitochondrial carbon stress and enhancing mitochondrial biogenesis to relieve various pathological conditions. The possibility of recent technological advances in targeted mitochondrial gene editing is also discussed.

During application, energetic materials may suffer different temperature environmental stimulation. In order to study the influence of temperature environmental on performance of HNIW/FOX-7 based PBXs, HNIW/FOX-7 based PBX modeling powders and PBX columns were treated by LT (low temperature), HT (high temperature), HLC (high-low temperature cycle) and HLS (high-low temperature shock). Then scanning electron microscope (SEM), infrared spectra (IR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to study the variation of PBX modeling powders after LT, HT, HLC and HLS treatments; in addition, the mass, size and mechanical properties of PBX columns were characterized after different temperature adaptability treatments as well. The results indicate that the change ratios of mass and size of HNIW/FOX-7 based PBX columns are less than 1%, illustrating that mass and size of PBX columns are at acceptable level after different temperature adaptability treatments. The unevenness degree of the surface of PBX modeling powders followed the order of HLC > HT > LT > HLS, which agrees well with mass loss order. Moreover, IR and XRD results indicated that the molecular structure and crystal form of HNIW and FOX-7 did not change after different temperature adaptability treatments. Additionally, thermal stabilities of PBX modeling powders are decreased after different temperature adaptability treatments, among which HLS has the largest influence on HNIW/FOX-based PBX modeling powders. The compression strengths and elastic moduli of HNIW/FOX-based PBX columns are enhanced after different temperature adaptability treatments, among which the strength of PBX columns after HLC has the maximum increase, indicating that HLC has more significant effect on mechanical property.

High-hardness thermoplastic polyurethane (HD-TPU) presents a high matrix modulus, low-temperature durability, and remarkable abrasion resistance, and has been used in many advanced applications. However, the fabrication of microcellular HD-TPU foam is rarely reported in the literature. In this study, the foaming behavior of HD-TPU with a hardness of 75D was investigated via a pressure-quenching foaming process using CO2 as a blowing agent. Microcellular HD-TPU foam with a maximum expansion ratio of 3.9-fold, a cell size of 25.9 μm, and cell density of 7.8 × 108 cells/cm3 was prepared, where a high optimum foaming temperature of about 170 °C had to be applied with the aim of softening the polymer’s matrix modulus. However, the foaming behavior of HD-TPU deteriorated when the foaming temperature further increased to 180 °C, characterized by the presence of coalesced cells, microcracks, and a high foam density of 1.0 g/cm3 even though the crystal domains still existed within the matrix. The cell morphology evolution of HD-TPU foam was investigated by adjusting the saturation time, and an obvious degradation occurred during the high-temperature saturation process. A cell growth mechanism of HD-TPU foams in degradation environments was proposed to explain this phenomenon based on the gas escape through the defective matrix.

This paper presents the design and control of a quadruped robot equipped with a six-degree-of-freedom (6-DOF) bionic active torso based on a parallel mechanism. Inspired by the compliant and flexible torsos of quadrupedal mammals, the proposed torso structure enhances locomotion performance by enabling coordinated motion between the torso and legs. A complete kinematic model of the bionic torso and the whole body of the quadruped robot is developed. To address the variation in inertial properties caused by torso motion, a model predictive control (MPC) strategy with a variable center of mass (CoM) is proposed for integrated whole-body motion control. Comparative simulations under trot gait are conducted between rigid-torso and active-torso configurations. Results show that the active torso significantly improves gait flexibility, postural stability, and locomotion efficiency. This study provides a new approach to enhancing biomimetic locomotion in quadruped robots through active torso-leg coordination.

Primary hyperparathyroidism (PHPT) has initially been implicated in adverse maternal and neonatal outcomes, while subsequent population studies have failed to show an association. This work aimed to compare maternal, pregnancy, and neonatal outcomes in patients with and without PHPT. A retrospective matched-cohort study (2005-2020) was conducted at an integrated health-care delivery system in Southern California. Women aged 18 to 44 years were included. Patients with a biochemical diagnosis of PHPT were matched 1:3 with eucalcemic controls (non-PHPT). Main outcome measures included achievement of pregnancy, pregnancy outcomes (including rates of abortion, maternal complications), and neonatal outcomes (including hypocalcemia, need for intensive care). The cohort comprised 386 women with PHPT and 1158 age-matched controls. Pregnancy rates between PHPT and control groups were similar (10.6% vs 12.8%). The adjusted rate ratio of pregnancy was 0.89 (95% CI, 0.64-1.24) (PHPT vs non-PHPT). Twenty-nine pregnancies occurred in women with coexisting PHPT and 191 pregnancies occurred in controls, resulting in 23 (79.3%) and 168 (88.0%) live births, respectively (P = .023). Neonatal outcomes were similar. Live birth rates were similar (86.4%, 80%, 79.2%) for those undergoing parathyroidectomy prior (n = 22), during (n = 5), or after pregnancy/never (n = 24). Among patients who underwent parathyroidectomy during pregnancy, no spontaneous abortions occurred in women entering pregnancy with peak calcium less than 11.5 mg/dL (2.9 mmol/L). We observed no difference in pregnancy rates between women with or without PHPT. Performing parathyroidectomy before pregnancy or during the second trimester appears to be a safe and successful strategy, and adherence to this strategy may be most critical for patients with higher calcium levels (≥11.5 mg/dL [2.9 mmol/L]).

This study examines the socio-ecological impacts of soybean cultivation in the Brazilian Amazon, a region of critical importance for global climate regulation and biodiversity conservation. It explores how the expansion of soybean cultivation in this region since the 1990s, driven by international demand and domestic policies, has triggered a series of unsustainable socio-ecological consequences, such as deforestation, overuse of agrochemicals, displacement of indigenous communities, and land tenure conflicts. Inadequate governance, at both national and international levels, has exacerbated these challenges, undermining efforts to balance soybean cultivation with sustainable development in Brazilian Amazon. Through a mixed analysis method, this study proposes pathways for sustainable soybean production in the Amazon, including extending the Soy Moratorium to the Cerrado, strengthening indigenous land rights, enhancing international cooperation, and adopting sustainable agricultural practices such as agroforestry. These findings contributes to reconciling soybean cultivation with sustainable development in the Brazilian Amazon.

The Pooled Cohort Equations (PCEs) do not accurately estimate atherosclerotic cardiovascular disease (ASCVD) risk in certain populations. The 2018 AHA/ACC cholesterol guideline identified risk-enhancing factors as a supplement to PCEs-based risk assessment. However, the role of each risk-enhancing factor in ASCVD risk assessment has not been well quantified. Further, social determinants of health (SDOH) are not included in the PCEs nor considered as risk-enhancing factors in the US cholesterol guideline. We sought to evaluate ASCVD risk associated with each risk-enhancing factor and commonly collected SDOH including education, income, and employment status, and to assess if adding risk-enhancing factors and SDOH to the PCEs improve ASCVD risk prediction. We included individuals aged 40 to 75 years, without ASCVD or diabetes at baseline, and with low-density lipoprotein cholesterol 70-189 mg/dL from two contemporary prospective cohort studies (MESA and REGARDS) and from Kaiser Permanente Southern California (KPSC). The primary endpoint was incident ASCVD defined as nonfatal myocardial infarction, fatal coronary heart disease, or fatal or nonfatal stroke over a 10-year period (median follow-up 10 years). We used Cox proportional hazards models to estimate associations between risk-enhancing factors and SDOH with ASCVD. We also assessed changes in model performance after adding risk-enhancing factors and SDOH to the PCEs. We included 13,863 adults (mean age 60.7 years) from the prospective cohorts and 307,931 adults (mean age 54.8 years) from KPSC. Risk-enhancing factors including hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, and chronic kidney disease were associated with a higher ASCVD risk, independent of 10-year risk estimated by the PCEs. Low education, low income, and unemployment were also associated with higher ASCVD risk. While adding individual risk-enhancing factors or SDOH to the PCEs had limited impact on model performance, adding multiple risk-enhancing factors and SDOH simultaneously led to modest improvements in discrimination (C-index increased by up to 0.07), calibration (integrated Brier score reduced by up to 2.3%), and net reclassification improvement up to 41.4%. These findings suggest including SDOH and risk-enhancing factors may improve ASCVD risk assessment.

This review introduces an innovative technology termed “Micro-Extrusion Foaming (MEF)”, which amalgamates the merits of physical foaming and 3D printing. It presents a groundbreaking approach to producing porous polymer fibers and parts. Conventional methods for creating porous materials often encounter obstacles such as the extensive use of organic solvents, intricate processing, and suboptimal production efficiency. The MEF technique surmounts these challenges by initially saturating a polymer filament with compressed CO2 or N2, followed by cell nucleation and growth during the molten extrusion process. This technology offers manifold advantages, encompassing an adjustable pore size and porosity, environmental friendliness, high processing efficiency, and compatibility with diverse polymer materials. The review meticulously elucidates the principles and fabrication process integral to MEF, encompassing the creation of porous fibers through the elongational behavior of foamed melts and the generation of porous parts through the stacking of foamed melts. Furthermore, the review explores the varied applications of this technology across diverse fields and imparts insights for future directions and challenges. These include augmenting material performance, refining fabrication processes, and broadening the scope of applications. MEF technology holds immense potential in the realm of porous material preparation, heralding noteworthy advancements and innovations in manufacturing and materials science.

Despite their safety and effectiveness, lipid-lowering therapy (LLT) remains underutilized among adults with and at-risk for atherosclerotic cardiovascular disease (ASCVD) in terms of prescriber-guideline concordance and patient adherence. We examined LLT use, adherence, and outcomes among primary and secondary prevention populations. Adults ≥21 years of age in Kaiser Permanente Southern California with a history of ASCVD or intermediate (≥7.5% to <20%) or high (≥20%) 10-year ASCVD risk between January 1, 2015 and March 31, 2021 were included. LLT use was described within subgroups including baseline risk. LLT adherence trajectories were determined using group-based trajectory modeling over 12 months. Hazard ratios (HR) were calculated for the association of adherence with ASCVD outcomes, identified starting in month 13 until death, disenrollment, or March 31, 2023. Among 730,941 adults (mean age 63 years; 42.1% female; 33.7% Hispanic and 41.3% non-Hispanic White), 30.3% and 47.4%, respectively, were intermediate- and high-risk for ASCVD, and 22.3% had ASCVD. Overall, 21% were not taking LLT, including 24% with ASCVD, and 32.4% of LLT users discontinued treatment at 12 months. High, intermediate, and low LLT adherence trajectories accounted for 64.1%, 24.3%, and 11.6% of the population, respectively. Adherence to LLT was associated with risk of ASCVD regardless of baseline statin intensity: adjusted HR of composite ASCVD associated with low and intermediate adherence was 1.20 (95% CI 1.16, 1.23) and 1.13 (95% CI 1.11, 1.15), respectively compared to patients with high adherence. LLT was underutilized in this contemporary population within an integrated health system in Southern California. In conclusion, addressing clinical inertia, enhancing medication management and lipid testing, and assessing clinical quality and metrics around guideline-appropriate care are critical given the persistent burden of CVD.