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Carbon (C) is one of the candidate light elements proposed to account for the density deficit of the Earth’s core. In addition, C significantly affects siderophile and chalcophile element partitioning between metal and silicate and thus the distribution of these elements in the Earth’s core and mantle. Derivation of the accretion and core–mantle segregation history of the Earth requires, therefore, an accurate knowledge of the C abundance in the Earth’s core. Previous estimates of the C content of the core differ by a factor of ∼20 due to differences in assumptions and methods, and because the metal–silicate partition coefficient of C was previously unknown. Here we use two-phase first-principles molecular dynamics to derive this partition coefficient of C between liquid iron and silicate melt. We calculate a value of 9 ± 3 at 3,200 K and 40 GPa. Using this partition coefficient and the most recent estimates of bulk Earth or mantle C contents, we infer that the Earth’s core contains 0.1–0.7 wt% of C. Carbon thus plays a moderate role in the density deficit of the core and in the distribution of siderophile and chalcophile elements during core–mantle segregation processes. The partition coefficients of nitrogen (N), hydrogen, helium, phosphorus, magnesium, oxygen, and silicon are also inferred and found to be in close agreement with experiments and other geochemical constraints. Contents of these elements in the core derived from applying these partition coefficients match those derived by using the cosmochemical volatility curve and geochemical mass balance arguments. N is an exception, indicating its retention in a mantle phase instead of in the core.

Background: Environmental metal exposure has been implicated in the development of digestive tract cancers, although the specific associations remain poorly defined. This study aimed to investigate the relationship between blood metal levels and the risk of digestive tract cancers among U.S. adults. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2011–2018, including 13,467 participants aged 20 years and older, were analyzed. Nine blood metals were measured. Multivariable logistic regression, restricted cubic spline models, and subgroup analyses were employed to assess the associations between metal levels and cancer risk. Additionally, a Random Forest (RF) model was used for cancer risk prediction. Results: Among the participants, 9 had esophagus cancer (EC), 11 had gastric cancer (GC), and 83 had colorectal cancer (CRC). Compared to healthy controls, EC patients exhibited significantly higher blood levels of potassium (K, 4.40 vs. 4.00 mmol/L), cadmium (Cd, 12.46 vs. 2.49 µg/L), and lead (Pb, 0.09 vs. 0.05 µg/L). GC patients had elevated Pb levels (0.08 vs. 0.05 µg/L), while CRC patients showed higher concentrations of Cd (3.11 vs. 2.49 µg/L) and Pb (0.06 vs. 0.04 µg/L). Logistic regression analysis revealed significant associations between higher K (odds ratio [OR] = 7.58, 95% CI: 3.48–16.48, P  < 0.0001), Cd (OR = 1.06, 95% CI: 1.04–1.08, P  < 0.0001), and Pb (OR = 7.60, 95% CI: 3.26–17.72, P  < 0.0001) levels and EC risk. Pb was also significantly associated with GC (OR = 5.26, 95% CI: 2.11–13.10, P  < 0.001). The RF model showed an accuracy of 76% in predicting cancer risk, with SHapley Additive exPlanations (SHAP) analysis highlighting Cd and iron (Fe) as key contributors. Conclusions: The study reveals a positive association between certain blood metals and digestive tract cancer risk, suggesting that limiting exposure to these metals may serve as a potential preventive measure.

Earth's core should contain light elements to account for the density deficit relative to pure iron as inferred from seismic observations. Of particular interest is hydrogen, as planetary accretion models predict the delivery of water possibly sequestered in the core. In this study, we investigate the partitioning of hydrogen across the inner‐core boundary using extensive atomistic simulations with machine learning potentials. While showing the tendency of hydrogen to dominantly remain in the liquid phase during inner core solidification, we find that the presence of oxygen would drive more hydrogen into the inner core, where 7 mol% oxygen even reverses the partitioning of hydrogen. By considering such mutual influences of partitioning among light elements in the core, we propose that the inner core can be an important reservoir of primordial hydrogen along with its growth. Plain Language Summary It is well known that Earth's core is composed of iron and nickel along with appreciable light elements such as silicon, oxygen, sulfur, carbon, and hydrogen. Among these candidates, hydrogen stands out given recent evidence for primordial H2O/H in Earth's core. In this study, by using extensive first principles simulations, we systematically investigate the thermodynamics of Fe–H–O systems. The partition coefficient of hydrogen across the inner‐core boundary has been quantified for different amounts of oxygen. It is found that the presence of oxygen in the outer core tends to drive more hydrogen into the inner core and even reverse the partitioning of hydrogen. This study thus demonstrates the importance of accounting for the mutual influences among light elements for unraveling the still enigmatic composition of Earth's core as well as how inner core solidification over time may have caused compositional changes that affect the evolution of the core, its seismic properties, and its ability to power the magnetic field. Key Points Oxygen exhibits a strong influence on hydrogen partitioning, driving more hydrogen into the solid inner core Partitioning of hydrogen across the ICB can be reversed from liquid to solid with 7 mol% oxygen in the core Mutual influences of partitioning among light elements are essential for understanding the composition and evolution of Earth's core

Current research reports that lactate affects Treg metabolism, although the precise mechanism has only been partially elucidated. In this study, we presented evidence demonstrating that elevated lactate levels enhanced cell proliferation, suppressive capabilities, and oxidative phosphorylation (OXPHOS) in human Tregs. The expression levels of Monocarboxylate Transporters 1/2/4 (MCT1/2/4) regulate intracellular lactate concentration, thereby influencing the varying responses observed in naive Tregs and memory Tregs. Through mitochondrial isolation, sequencing, and analysis of human Tregs, we determined that α-1,3-Mannosyl-Glycoprotein 2-β-N-Acetylglucosaminyltransferase (MGAT1) served as the pivotal driver initiating downstream N-glycosylation events involving progranulin (GRN) and hypoxia-upregulated 1 (HYOU1), consequently enhancing Treg OXPHOS. The mechanism by which MGAT1 was upregulated in mitochondria depended on elevated intracellular lactate that promoted the activation of XBP1s. This, in turn, supported MGAT1 transcription as well as the interaction of lactate with the translocase of the mitochondrial outer membrane 70 (TOM70) import receptor, facilitating MGAT1 translocation into mitochondria. Pretreatment of Tregs with lactate reduced mortality in a xenogeneic graft-versus-host disease (GvHD) model. Together, these findings underscored the active regulatory role of lactate in human Treg metabolism through the upregulation of MGAT1 transcription and its facilitated translocation into the mitochondria.

Programmed death-1 (PD-1) and its ligand PD-L1 are checkpoint molecules which regulate immune responses. Little is known about their functions in T cell migration and there are contradictory data about their roles in regulatory T cell (Treg) function. Here we show activated Tregs and CD4 effector T cells (Teffs) use PD-1/PD-L1 and CD80/PD-L1, respectively, to regulate transendothelial migration across lymphatic endothelial cells (LECs). Antibody blockade of Treg PD-1, Teff CD80 (the alternative ligand for PD-L1), or LEC PD-L1 impairs Treg or Teff migration in vitro and in vivo. PD-1/PD-L1 signals through PI3K/Akt and ERK to regulate zipper junctional VE-cadherin, and through NFκB-p65 to up-regulate VCAM-1 expression on LECs. CD80/PD-L1 signaling up-regulates VCAM-1 through ERK and NFκB-p65. PD-1 and CD80 blockade reduces tumor egress of PD-1 high fragile Tregs and Teffs into draining lymph nodes, respectively, and promotes tumor regression. These data provide roles for PD-L1 in cell migration and immune regulation. The Programmed death-1 (PD-1) and its ligand PD-L1 are critical checkpoints in the regulation of immune responses. Here the authors implicate PD-L1 signalling at lymphatic endothelium in the regulation of transendothelial migration of T cells.

Background Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, and the balance between surgical extent (particularly non-total thyroidectomy [non-TX]) and postoperative recurrence risk in the residual thyroid remains a key clinical concern. This single-center retrospective study analyzed 2512 patients with unilateral PTC who underwent non-TTx between January 2014 and December 2024 and completed 5–10 years of follow-up evaluations, aiming to determine the recurrence rate in residual thyroid and related risk factors. Methods The Kaplan-Meier method was used to calculate cumulative recurrence-free survival (RT-RFS) in the residual thyroid. Independent risk factors were identified through univariate χ² tests and multivariate logistic regression analysis. The effect size for between-group differences in continuous variables was calculated using Cohen’s d. Results The overall recurrence rate was 5.8% with 5- and 10-y RT-RFS rates of 95.4% and 94.2%, respectively. Univariate analysis demonstrated significant associations between recurrence and age > 55 y, increased tumor size (T1a-T3), multifocality, preoperative subclinical hypothyroidism, and postoperative TSH > 2.0 mIU/L (all P  < 0.05). Multivariate regression analysis confirmed tumor size (T1b/T2/T3 vs. T1a: OR = 2.253/5.053/19.452), multifocality (OR = 1.908), and postoperative TSH > 2.0 mIU/L (OR = 2.193) as independent risk factors for residual thyroid recurrence (all P  < 0.05). However, neither the surgical extent of non-TTx, nor age, gender, preoperative subclinical hypothyroidism, and coexisting Hashimoto’s thyroiditis are independent driving factors, and confirmed that there is no significant association between residual thyroid volume and postoperative recurrence risk. Conclusion For patients with unilateral, unifocal PTC classified as T1a, we propose that conformal thyroidectomy represents a clinically appropriate and feasible alternative to unilateral thyroid lobectomy.

IntroductionDespite advances in diagnostics, many patients with gastric cancer (GC) or oesophagogastric junction cancer present with advanced disease, most commonly peritoneal metastasis (PM), which conveys a poor prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) and anti-programmed cell death protein-1 (PD-1) therapy have each shown promise in GC. We describe the protocol for a study evaluating the efficacy and safety of combining HIPEC with the anti-PD-1 antibody tislelizumab and SOX (oxaliplatin+S-1) chemotherapy in patients with GC/oesophagogastric junction cancer and PM.Methods and analysisThis is a multicentre, single-arm, phase II trial conducted at 13 high-volume tertiary referral hospitals across China. We will enrol 50 adults (18–75 years) with histologically confirmed GC/oesophagogastric junction adenocarcinoma and PM diagnosed by laparoscopy. Participants will receive one laparoscopy-guided HIPEC cycle (paclitaxel, total dose: 175 mg/m2, 3000 mL of physiological saline at 43°C for 60 min, inflow rate 1.5 L/min, 10 min physiological saline preconditioning at 41°C) followed—after a 3-week interval—by up to three 3-week cycles of tislelizumab 200 mg plus SOX (oxaliplatin 130 mg/m² and S-1 dose-escalated by body surface area). HER2-positive patients will also receive trastuzumab. Primary endpoint: 1-year overall survival. Secondary endpoints: 1-year progression-free survival, completeness of Cytoreduction Score and objective response rate. Follow-up includes imaging and toxicity assessments every 3 months for at least 1 year.Ethics and disseminationThe protocol was approved by the Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (ID 2024-SR-198). All participants will provide written informed consent. Results will be disseminated via peer-reviewed publications; de-identified individual participant data will be available from the corresponding author on reasonable request after publication.Trial registration numberClinicalTrials.gov, NCT06427252

With the aim of achieving the goal of ecological livability in Chinese rural society, the issue of rural environmental governance has received great attention from the CCP and the government. However, due to local governments’ model of development in exchange for economic interests and the “urban and rural binary” structure of environmental governance, rural environmental governance faces many dilemmas, such as lack of normative standards, lack of environmental governance subjects, and lack of judicial security. In order to improve the development of rural ecological civilization and realize ecologically friendly agriculture, this paper proposes a solution path for rural environmental governance from the perspective of the idea of the community with a shared future for humanity. Specifically, this solution path includes establishing the concepts of cooperation and governance of environmental protection, improving villagers’ participation in environmental protection, balancing economic and environmental interests in rural environmental governance, and building a long-term mechanism for the rule of law in rural environmental governance.

DNA methylation represents a predominant epigenetic modification with broad implications in various biological functions. Its role is particularly significant in the process of collagen deposition, a fundamental aspect of dermal development in donkeys. Despite its critical involvement, the mechanistic insights into how DNA methylation influences collagen deposition in donkey skin remain limited. In this study, we employed whole genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) to investigate the epigenetic landscape and gene expression profiles in the dorsal skin tissues of Dezhou donkeys across three developmental stages: embryonic (YD), juvenile (2-year-old, MD), and mature (8-year-old, OD). Our analysis identified numerous differentially methylated genes that play pivotal roles in skin collagen deposition and overall skin maturation, including but not limited to COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, GLUL, SFRP2, FOSL1, SERPINE1, MMP1, MMP2, MMP9, and MMP13. Notably, we observed an inverse relationship between gene expression and DNA methylation proximal to transcription start sites (TSSs), whereas a direct correlation was detected in regions close to transcription termination sites (TTSs). Detailed bisulfite sequencing analyses of the COL1A1 promoter region revealed a low methylation status during the embryonic stage, correlating with elevated transcriptional activity and gene expression levels. Collectively, our findings elucidate key genetic markers associated with collagen deposition in the skin of Dezhou donkeys, underscoring the significant regulatory role of DNA methylation. This research work contributes to the foundational knowledge necessary for the genetic improvement and selective breeding of Dezhou donkeys, aiming to enhance skin quality attributes.

The magma ocean process in the early history of the Earth has a great influence on the light element identities and contents of the core which subsequently affect the energy of the geodynamo provided by the compositional convection and the inner core growth through their effect on the phase diagram of iron alloy. In the present work, a two‐phase ab‐initio molecular dynamics method is established to study the solubility of silicon and oxygen in liquid iron in equilibrium with silicate melt. The ab‐initio results are found to be in close agreement with experimental data. At the base of a deep magma ocean (39 GPa and 3116 K), liquid iron contains 2.7 wt% silicon and 0.5 wt% oxygen at the current bulk Earth composition. The oxygen content is low compared with its current estimate in the core, indicating a deeper magma ocean may need to be invoked.