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Abstract This paper investigates the robust model predictive load frequency control problem for smart grids with wind power under cyber attacks. To accommodate intermittent power generation, the demand response of the system is considered by involving the air conditioning loads in the frequency regulation. In addition, the system uncertainties produced by the air conditioning load users and wind turbines when replacing traditional generator sets are considered. By using the cone complementary linearization algorithm and the linear matrix inequality technique, a resilience robust model predictive control strategy with mixed H2/H∞ performance indexes is proposed. Furthermore, a rigorous derivation of the recursive feasibility of robust model predictive control is given. Finally, the simulation results of the two‐area load frequency control scheme show that the proposed model predictive control strategy is capable of realizing the load frequency control of the multi‐area smart grid and is robust to the parameter uncertainties and frequency regulation of the system. The results also show that the proposed model predictive control strategy has some resistance to cyber attacks and external disturbances.

Abstract Background A high body mass index (hBMI) is one of the major risk factors for ischemic stroke (IS), although independent estimates of the global burden and trend of IS attributable to hBMI are unclear. Methods Study data were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study and analysed by age, sex, year, and geographical location. The sociodemographic index (SDI) and the human development index (HDI) were used as indicators of national socioeconomic status. Geographic distributions and trends were assessed by calculating the estimated annual percentage change (EAPC). Associations between the age-standardized death rate (ASMR) or disability-adjusted life year rate (DALY) and socioeconomic status were analysed. Results Deaths and DALYs increased worldwide from 1990–2021, with increases of 95.74% for the former and 133.00% for the latter; the ASMR and ASDR decreased, with an ASMR and ASDR-related EAPCs of -1.10 (95% CI: -1.24–-0.96) and 0.04 (95% CI:-0.47–0.55), respectively; women had greater numbers of deaths and DALYs, and the majority of deaths and DALYs were shared by those aged ≥ 70. The highest burden rates were shared by Eastern Europe, North Africa, the Middle East, and Central Asia. The ASMR-related EAPCs were associated with the ASMR in 1990 (R = -0.35, P

Abstract To scientifically and effectively manage exhaust pollution in underground confined spaces and reduce hazards from personnel exhaust exposure, a systematic study of the distribution characteristics of diesel locomotive exhaust emissions in mines is needed. Aiming at large underground coal mining operations, an experimental platform for the physical simulation of vehicle exhaust transport in restricted spaces is designed and created. The Hongliulin Coal Mine in Shaanxi Province, China, is used as a prototype, and the platform consists of a coal mining face system, ventilation system, exhaust emission system, monitoring and surveillance system, and control platform. The experimental platform with carbon dioxide simulation of diesel exhaust pollution, in the role of different wind speed, the concentration of carbon dioxide is a downward trend, the wind speed is in the low wind speed on the 0.2 m of the concentration difference of 25.75%; the experimental platform exhaust transport process presents a clear “three-zone” change rule; experimental platform carbon dioxide concentration and the field nitrogen dioxide concentration change trend is consistent. The platform functions and features can provide guidance for mine exhaust management and exhaust exposure hazard prevention and control.

Abstract Background The influence of the small Rho GTPase Rif (RHOF) on tumor growth, glycolysis, endothelial–mesenchymal transition (EMT), and the potential mechanism of RHOF in pancreatic cancer (PC) were explored. Methods RHOF expression in PC tissues and cells was assessed by qRT-PCR and western blotting. The viability, proliferation, apoptosis, migration, and invasion of PC cells were assessed using CCK-8, colony formation, EdU, flow cytometry, scratch, and Transwell assays. The expression of EMT- and glycolysis-related proteins was determined using western blotting. The potential mechanisms of action of RHOF in PC were identified using bioinformatic analysis. The effects of RHOF were assessed in vivo using a xenograft mouse model. Results PC cell proliferation, migration, and invasion are accelerated by RHOF overexpression, which inhibited apoptosis. RHOF overexpression promoted EMT and glycolysis as evidenced by a decrease in E-cadherin expression and an increase in N-cadherin, Vimentin, HK2, PKM2, and LDHA expression. Bioinformatic analysis indicated that RHOF activated EMT, glycolysis, and Myc targets and that c-Myc could bind to the PKM2 promoter. RHOF overexpression promotes the lactylation and nuclear translocation of Snail1. Silencing Snail1 reversed the promoting effects of RHOF and lactate on cell migration, invasion, and EMT. Moreover, in vivo tumor growth and EMT were inhibited by RHOF silencing. Conclusion RHOF plays an oncogenic role in PC. c-Myc is upregulated by RHOF and promotes PKM2 transcription. PKM2 further induces glycolysis, and the lactate produced by glycolysis causes the lactylation of Snail1, ultimately promoting EMT.

Chikungunya virus (CHIKV) infection, responsible for chikungunya fever and occasionally severe symptoms, has emerged as an increasing global health concern following several large-scale outbreaks from Africa, Asia, Europe, and America. Over the past two decades, South and Southeast Asia regions have gradually become hot spots for outbreaks involving multiple CHIKV lineages. In China, most CHIKV infections are imported, making it crucial to trace the origins and transmission routes for effective prevention and control. In January 2024, a case of imported chikungunya fever was confirmed in Guangzhou City, Guangdong Province, China. However, the serum CHIKV viral concentration was too low for cultivation [reverse transcription-polymerase chain reaction (RT-PCR) detection, cycle threshold = 32.62]. Despite this, we successfully obtained the viral genome sequence directly from the whole blood sample using an optimized metatranscriptomic sequencing strategy, achieving a full-length viral genome with an average depth of 54.3X. Further analysis confirmed that the CHIKV virus belonged to the Asian lineage, traced to Timor-Leste, where an endemic CHIKV outbreak had been reported in January 2024, consistent with the patient’s travel history. Finally, we analyzed genetic evolutionary trends and amino acid site variations. This study highlights the identification of a CHIKV infection origin using direct whole-blood metatranscriptomic sequencing, a valuable method for rapidly sequencing low viral-load samples.

Esophageal squamous cell carcinoma (ESCC), a malignancy of the digestive system, is highly prevalent and the primary cause of cancer-related deaths worldwide due to the lack of early diagnostic biomarkers and effective therapeutic targets. Dysregulated ribonucleotide reductase (RNR) expression has been confirmed to be causally linked to tumorigenesis. This study demonstrated that ribonucleotide reductase small subunit M2 (RRM2) is significantly upregulated in ESCC tissue and that its expression is negatively correlated with clinical outcomes. Mechanistically, HuR promotes RRM2 mRNA stabilization by binding to the adenine/uridine (AU)-rich elements (AREs) within the 3′UTR, resulting in persistent overexpression of RRM2. Furthermore, bifonazole is identified as an inhibitor of HuR via computational screening and molecular docking analysis. Bifonazole disrupts HuR-ARE interactions by competitively binding to HuR at F65, R97, I103, and R153 residues, resulting in reduced RRM2 expression. Furthermore, bifonazole exhibited antitumor effects on ESCC patient-derived xenograft (PDX) models by decreasing RRM2 expression and the dNTP pool. In summary, this study reveals the interaction network among HuR, RRM2, and bifonazole and demonstrated that bifonazole is a potential therapeutic compound for ESCC through inhibition of the HuR/RRM2 axis.

Abstract No-tillage and subsoiling can improve soil aggregate structure and realize a synergistic effect of soil carbon and nitrogen retention compared with deep tillage. This study aimed to investigate the effects of different tillage methods on the microbiome and metabolites in wheat rhizosphere. Results indicated that no significant differences in the diversity of soil bacterial and fungal communities were observed among the tillage methods. Analysis revealed that no-tillage enriched specific genera such as Cryptosporangium, Crossiella, Rhodothermaceae, Leptothrix, Stilbella, Diutina, and Pyrenochaetopsis, while subsoiling was associated with Rubrobacter, Latescibacteraceae, Nitrospira, Rokubacteriales, and Ctenomyces. Deep tillage, on the other hand, showed significant associations with Nocardia, Aeromicrobium, Sphingopyxis, Cordyceps, and Subulicystidium. Metabolomic analysis identified differential metabolites involved in various pathways, including the biosynthesis of plant secondary metabolites, ABC transporters, and starch and sucrose metabolism. Correlation analysis revealed a significant interaction between microorganisms and metabolites in wheat rhizosphere. Bacteria at the genus level exhibited greater associations with differential metabolites. In conclusion, different tillage practices can alter the composition of microbial communities and metabolites in wheat rhizosphere, and their interactions may affect soil fertility and wheat growth.

Abstract Antibody-dependent enhancement (ADE) is a potential concern for the development of Zika virus (ZIKV) vaccines. Cross-reactive but poorly neutralizing antibodies, usually targeting viral pre-membrane or envelope (E) proteins, can potentially enhance dengue virus (DENV) infection. Although E domain III (EDIII) contains ZIKV-specific epitopes, its immunogenicity is poor. Here, we show that dimeric EDIII, fused to human IgG1 Fc fragment (EDIII-Fc) and encoded by circular RNA (circRNA), induces better germinal center reactions and higher neutralizing antibodies compared to circRNAs encoding monomeric or trimeric EDIII. Two doses of circRNAs encoding EDIII-Fc and ZIKV nonstructural protein NS1, another protective antigen, prevent lethal ZIKV infection in neonates born to immunized C57BL/6 mice and in interferon-α/β receptor knockout adult C57BL/6 mice. Importantly, a single-dose optimized circRNA vaccine with improved antigen expression confers potent and durable protection without inducing obvious DENV ADE in mice, laying the groundwork for developing flavivirus vaccines based on circRNAs encoding EDIII-Fc and NS1.

Abstract Ependymal cells are arranged along the inner surfaces of the ventricles and the central canal of the spinal cord, providing anatomical, physiological and immunological barriers that maintain cerebrospinal fluid (CSF) homeostasis. Based on this, studies have found that alterations in gene expression, cell junctions, cytokine secretion and metabolic disturbances can lead to dysfunction of ependymal cells, thereby participating in the onset and progression of central nervous system (CNS) infections. Additionally, ependymal cells can exhibit proliferative and regenerative potential as well as secretory functions during CNS injury, contributing to neuroprotection and post-injury recovery. Currently, studies on ependymal cell primarily focus on the basic investigations of their morphology, function and gene expression; however, there is a notable lack of clinical translational studies examining the molecular mechanisms by which ependymal cells are involved in disease onset and progression. This limits our understanding of ependymal cells in CNS infections and the development of therapeutic applications. Therefore, this review will discuss the molecular mechanism underlying the involvement of ependymal cells in CNS infections, and explore their potential for application in clinical treatment modalities.

Abstract Background Currently, the synthesis of compounds based on microbial cell factories is rapidly advancing, yet it encounters several challenges. During the production process, engineered strains frequently encounter disturbances in the cultivation environment or the impact of their metabolites, such as high temperature, acid-base imbalances, hypertonicity, organic solvents, toxic byproducts, and mechanical damage. These stress factors can constrain the efficiency of microbial fermentation, resulting in slow cell growth, decreased production, significantly increased energy consumption, and other issues that severely limit the application of microbial cell factories. Results This study demonstrated that sterol engineering in Kluyveromyces marxianus, achieved by overexpressing or deleting the coding genes for the last five steps of ergosterol synthase (Erg2-Erg6), altered the composition and ratio of sterols in its cell membrane, and affected its multiple tolerance. The results suggest that the knockout of the Erg5 can enhance the thermotolerance of K. marxianus, while the overexpression of the Erg4 can improve its acid tolerance. Additionally, engineering strain overexpressed Erg6 improved its tolerance to elevated temperature, hypertonic, and acid. YZB453, obtained by overexpressing Erg6 in an engineering strain with high efficiency in synthesizing xylitol, produced 101.22 g/L xylitol at 45oC and 75.11 g/L xylitol at 46oC. Using corncob hydrolysate for simultaneous saccharification and fermentation (SSF) at 46oC that xylose released from corncob hydrolysate by saccharification with hemicellulase, YZB453 can produce 45.98 g/L of xylitol, saving 53.72% of the cost of hemicellulase compared to 42oC. Conclusions This study elucidates the mechanism by which K. marxianus acquires resistance to various antifungal drugs, high temperatures, high osmolarity, acidity, and other stressors, through alterations in the composition and ratio of membrane sterols. By employing sterol engineering, the fermentation temperature of this unconventional thermotolerant K. marxianus was further elevated, ultimately providing an efficient platform for synthesizing high-value-added xylitol from biomass via the SSF process at temperatures exceeding 45 °C.

Abstract Nocardia farcinica is the most pathogenic Nocardia, which is easy to disseminate. It can be caused by trauma, and even lead to severe lung or central nervous system infection. This report covers a case of Nocardia brain abscess in an HIV patient, who underwent resection of the brain abscess, followed by anti-infective therapy with sulfamethoxazole and meropenem, and eventually made a good recovery. The mortality rate of Nocardia farcinica brain abscess has been attributed to the severity of the underlying disease, the difficulty in identifying the pathogen, and its inherent resistance to antibiotics, leading to inappropriate or late initiation of treatment. Medication should follow the principle of sufficient dosage and sufficient course of treatment.

Abstract The purpose of this study was to investigate early stage dynamic changes in relevant indicators in neurocritical patients to identify biomarkers that can predict a poor prognosis at an early stage (1–4 days after admission). This study retrospectively collected clinical data, inflammatory indicators, and nutritional indicators from 77 patients at the neurology intensive care unit. The 3-month modified Rankin scale score was used as the outcome indicator. A linear mixed model was used to analyze changes in inflammatory indicators and nutritional indicators in neurocritical patients over time from 1–4 days after admission. Logistic regression was used to determine the independent risk factors for a poor prognosis in neurocritical patients and to construct a predictive model. The predictive efficacy of the model was verified using leave-one-out cross-validation and decision curve analysis methods. The analysis results showed that 1–4 days after admission, the inflammatory indicators of white blood cell and absolute monocyte counts and the nutritional indicators of body cell mass(BCM), fat-free mass, body cell mass/phase angle (BCM/PA), intracellular water, extracellular water, and skeletal muscle index increased overall, while the nutritional indicators of albumin and visceral fat area decreased overall. The logistic multivariate regression model showed that the Charlson comorbidity index (CCI) (odds ratio (OR) = 2.526, 95% CI [1.202, 5.308]), hemoglobin (Hb)(on admission)-Hb(min) (OR = 1.049, 95% CI [1.015, 1.083), BCM(on admission) (OR = 0.794, 95% CI [0.662, 0.952]), and the change in BCM/PA 1–4 days after admission (OR = 1.157, 95% CI [1.070, 1.252]) were independent risk factors for a poor prognosis in neurocritical patients. The predictive analysis showed that the predictive power of Model 1 with BCM/PA (area under the curve (AUC) = 0.95, 95% CI (0.90, 0.99)) was 93%, 65%, 141%, and 133% higher than that of Model 2 without BCM/PA, the CCI, the APACHE II score, and the NRS2002 score (all P

Abstract Coxiella burnetii (C. burnetii) is the causative agent of Q fever, a type of zoonoses withwidespread distribution. In 2019, a case of Q fever was diagnosed by metagenomic next-generation sequencing (mNGS) method in Xuyi County (Jiangsu province, China). The seroprevalence of previous fever patients and the molecular epidemiology of Coxiella in wild hedgehogs and harbouring ticks around the confirmed patient were detected to reveal the genetic characteristics and pathogenicity of the Coxiella strains. Four of the 90 serum samples (4.44%) were positive for specific C. burnetii IgM antibody, suggesting that local humans are at risk of Q fever. The positive rates of C. burnetii in hedgehogs and ticks were 21.9% (7/32) and 70.5% (122/173), respectively. At least 3 strains of Coxiella were found prevalent in the investigated area, including one new genotype of pathogenic C. burnetii (XYHT29) and two non-pathogenic Coxiella-like organisms (XYHT19 and XYHT3). XYHT29 carried by ticks and wild hedgehogs successfully infected mice, imposing a potential threat to local humans. XYHT19, a novel Coxiella-like microorganism, was first discovered in the world to co-infect with C. burnetii in Haemaphysalis flava. The study provided significant epidemic information that could be used for prevention and control strategies against Q fever for local public health departments and medical institutions.

Abstract Chemical derivatization is a powerful strategy to enhance sensitivity and selectivity of liquid chromatography-mass spectrometry for non-targeted analysis of chemicals in complex mixtures. However, it remains impossible to obtain large sets of reference spectra for chemically derived molecules (CDMs), representing a major barrier in real-world applications. Herein, we describe a deep learning approach that enables accurate prediction of electrospray ionization tandem mass spectra for CDMs (DeepCDM). DeepCDM is established by transfer learning from a generic spectrum predicting model using a small set of experimentally acquired tandem mass spectra of CDMs, which converts a generic model with low predictability for CDMs into a specialized model with high predictability. We demonstrate DeepCDM by predicting electrospray ionization tandem mass spectra of dansylated molecules. The success in establishing Dns-MS further enables the development of DnsBank, a dansylation-specialized in silico spectral library. DnsBank achieves significant increases of accurate annotation rates of dansylated molecules, facilitating discovery of new hazardous pollutants from an environmental study of leather industrial wastewater. DeepCDM is also highly versatile for other classes of CDMs. Therefore, we envision that DeepCDM will pave a way for high-throughput identification of CDMs in non-targeted analysis to dig unknowns with potential health impacts from emerging anthropogenic chemicals.

Abstract Background Glucose fluctuations may be involved in the pathophysiological process of cardiomyocyte apoptosis, but the exact mechanism remains elusive. This study focused on exploring the mechanisms related to glucose fluctuation-induced cardiomyocyte apoptosis. Methods Diabetic rats established via an injection of streptozotocin were randomized to five groups: the controlled diabetic (CD) group, the uncontrolled diabetic (UD) group, the glucose fluctuated diabetic (GFD) group, the GFD group rats with the injection of 0.9% sodium chloride (NaCl) (GFD + NaCl) and the GFD group rats with the injection of N-acetyl-L-cysteine (NAC) (GFD + NAC). Twelve weeks later, cardiac function and apoptosis related protein expressions were tested. Proteomic analysis was performed to further analyze the differential protein expression pattern of CD and GFD. Results The left ventricular ejection fraction levels and fractional shortening levels were decreased in the GFD group, compared with those in the CD and UD groups. Positive cells tested by DAB-TUNEL were increased in the GFD group, compared with those in the CD group. The expression of Bcl-2 was decreased, but the expressions of Bax, cleaved caspase-3 and cleaved caspase-9 were increased in response to glucose fluctuations. Compared with CD, there were 527 upregulated and 152 downregulated proteins in GFD group. Txnip was one of the differentially expressed proteins related to oxidative stress response. The Txnip expression was increased in the GFD group, while the Akt phosphorylation level was decreased. The interaction between Txnip and Akt was enhanced when blood glucose fluctuated. Moreover, the application of NAC partially reversed glucose fluctuations-induced cardiomyocyte apoptosis. Conclusions Glucose fluctuations lead to cardiomyocyte apoptosis by up-regulating Txnip expression and enhancing Txnip-Akt interaction.

Abstract Reactive capture of carbon dioxide (CO2) offers an electrified pathway to produce renewable carbon monoxide (CO), which can then be upgraded into long-chain hydrocarbons and fuels. Previous reactive capture systems relied on hydroxide- or amine-based capture solutions. However, selectivity for CO remains low (

Purpose: Although magnesium sulfate (MgSO4) is widely used as an analgesic adjuvant to peripheral analgesic cocktails, its efficacy in total knee arthroplasty (TKA) is still controversial. Therefore, we systematically reviewed and meta-analyzed the literature to assess the analgesic efficacy of MgSO4 as an adjuvant to the analgesic cocktail in TKA. Methods: The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched. The meta-analysis was performed according to the PRISMA guidelines. Data were qualitatively synthesized or meta-analyzed using a random-effects model. Results: Five randomized controlled trials involving 432 patients were included. Meta-analyses detected significant differences between the MgSO4 and control groups in the visual analog scale (VAS) pain scores (rest) at 6, 12, and 24 h postoperatively; VAS pain scores (motion) at 12, 24, and 48 h postoperatively; morphine consumption within 24 h, 24–48 h, and during the total hospitalization period; time to first rescue analgesia after TKA; and length of hospital stay. Regarding the functional recovery, the meta-analysis demonstrated significant differences between groups in terms of knee range of motion on postoperative day 1; daily mobilization distance on postoperative day 1; and daily mobilization distance. There was no significant intergroup difference in surgical complications. Conclusion: The findings suggest that MgSO4 is a promising adjunct to the analgesic cocktail, achieving significant improvements in pain scores and total opioid consumption during the early postoperative period after TKA.

As the number of high-density buildings has increased, the management of property with complex condominium ownership has become an ongoing challenge in property registration and management. The three-dimensional (3D) modeling of condominium ownership has emerged as an effective means of meeting this challenge and has attracted great attention from fields such as geographical information science, urban planning and management, and property administration. Much progress has been made in building 3D models of condominium ownership; however, existing studies are all on a case-by-case basis and have left some critical issues unsolved, such as vague ownership boundaries, spatial rights without physical counterparts, and the unfixed spatial extent. The purpose of this study is to construct a 3D building ownership model with multiple levels of detail in the context of Chinese law to overcome the defects of 3D models above. This 3D model is presented in a case study of China by subdividing ownership boundaries based on clarifying the internal structure of condominium ownership, embedding the apportionment mechanism, and integrating the semantics, attributes, and geometry associated with the physical and legal entity of the condominium. The proposed 3D model is implemented by extending Building Information Modeling (BIM) based on the Industry Foundation Classes (IFC) and inheriting legal information from Land Administration Domain Model (LADM). In this study, examples of condominium ownership from three real legal dispute cases in China are analyzed and tested. The study clearly demonstrates that the proposed model can provide a better cognitive understanding of the legal space of property by rendering unambiguous ownership boundaries and presenting the spatial internal structure of ownership, which offers solid technical support for dealing with property registration and many legal dispute cases about condominium ownership.

Abstract Energy-band gradient halide perovskites are highly desired candidates for fabricating high performance optoelectronic devices. Here, we demonstrate that a mixed halide perovskite single crystal undergoes phase segregation in the longitudinal direction under above-bandgap light illumination. As a result, a micron thick layer with vertically gradient halide composition and thus graded valence band edge is generated at the crystal surface. The resultant gradient structure can facilitate the hole extraction at its interface with a hole transport layer. The longitudinal phase segregation of mixed halide perovskite single crystal is likely driven by abundant defects at the surface. Moreover, the segregation rate is increased in air compared to nitrogen probably due to the combined effect of oxygen and moisture. These findings not only deepen the understanding of phase segregation mechanism in mixed halide perovskite, but also indicate a promising avenue of fabricating vertically energy-band gradient perovskite and enhancing the perovskite-based optoelectronic device performance.

Abstract Background TCbHP (taxane + carboplatin + trastuzumab + pertuzumab) is the preferred neoadjuvant therapy regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, no consensus exists regarding whether specific populations may be exempt from carboplatin, allowing for de-escalation to the THP (taxane + trastuzumab + pertuzumab) regimen. Additionally, the optimal number of cycles for neoadjuvant THP remains unclear. We compared the efficacy and safety of neoadjuvant TCbHP and THP regimens, providing clinicians with a nuanced perspective to guide their treatment regimen selection. Methods This multicenter real-world study included patients with HER2-positive breast cancer undergoing neoadjuvant TCbHP or THP between March 2019 and February 2023. Efficacy was assessed through the pathological complete response (pCR) rate, while safety was evaluated through monitoring adverse events. Results Among 220 patients, 103 received 6 cycles of TCbHP (TCbHP×6), 83 received 6 cycles of THP (THP×6), and 34 received 4 cycles of THP (THP×4). The TCbHP×6 cohort exhibited a 66% pCR rate compared with 53% in the THP×6 cohort (P = 0.072). Subgroup analysis revealed that in patients aged ≤ 50 years, those with hormone receptor (HR)-negative status, and those with clinical stage T2, the pCR rate of the TCbHP×6 regimen was significantly higher than the THP×6 regimen (P 50, ≤60 years with HR-negative status or clinical stage T2-4. For patients in compromised general condition or lacking the specified indications, the THP×6 regimen emerges as a lower-toxicity alternative with satisfactory efficacy. To ensure treatment efficacy, a minimum of 6 cycles of neoadjuvant THP is required.

Abstract Background Obesity is a global health issue with detrimental effects on various human organs, including the reproductive system. Observational human data and several lines of animal experimental data suggest that maternal obesity impairs ovarian function and early embryo development, but the precise pathogenesis remains unclear. Methods We established a high-fat diet (HFD)-induced obese female mouse model to assess systemic metabolism, ovarian morphology, and oocyte function in mice. For the first time, this study employed single-cell RNA sequencing to explore the altered transcriptomic landscape of preimplantation embryos at different stages in HFD-induced obese mice. Differential gene expression analysis, enrichment analysis and protein-protein interactions network analysis were performed. Results HFD-induced obese female mice exhibited impaired glucolipid metabolism and insulin resistance. The ovaries of HFD mice had a reduced total follicle number, an increased proportion of atretic follicles, and irregular granulosa cell arrangement. Furthermore, the maturation rate of embryonic development by in vitro fertilization of oocytes was significantly decreased in HFD mice. Additionally, the transcriptional landscapes of preimplantation embryos at different stages in mice induced by different diets were significantly distinguished. The maternal-to-zygotic transition was also affected by the failure to remove maternal RNAs and to turn off zygotic genome expression. Conclusions HFD-induced obesity impaired ovarian morphology and oocyte function in female mice and further led to alterations in the transcriptional landscape of preimplantation embryos at different stages of HFD mice.

Abstract Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48–0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

Abstract Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Abstract Acidic microenvironments is a cancer progression driver, unclear core mechanism hinders the discovery of new diagnostic or therapeutic targets. ASIC3 is an extracellular proton sensor and acid-sensitive, but its role in acidic tumor microenvironment of colorectal cancer is not reported. Functional analysis data show that colorectal cancer cells respond to specific concentration of lactate to accelerate invasion and metastasis, and ASIC3 is the main actor in this process. Mechanism reveal de novo lipid synthesis is a regulatory process of ASIC3, down-regulated ASIC3 increases and interacts with ACC1 and SCD1, which are key enzymes in de novo lipid synthesis pathway, this interaction results in increased unsaturated fatty acids, which in turn induce EMT to promote metastasis, and overexpression of ASIC3 reduces acidic TME-enhanced colorectal cancer metastasis. Clinical samples of colorectal cancer also exhibit decreased ASIC3 expression, and low ASIC3 expression is associated with metastasis and stage of colorectal cancer. This study is the first to identify the role of the ASIC3-ACC1/SCD1 axis in acid-enhanced colorectal cancer metastasis. The expression pattern of ASIC3 in colorectal cancer differs significantly from that in other types of cancers, ASIC3 may serve as a novel and reliable marker for acidic microenvironmental in colorectal cancer, and potentially a therapeutic target.

Objective To correctly identify the blood group of ABO and study its molecular biological characteristics. Methods Blood samples from blood donors with discrepancies in forward and reverse typing using the microplate method were subjected to both saline tube agglutination test for serological identification and polymerase chain reaction-sequence specific primers (PCR-SSP) for genotyping. Additionally, direct sequencing of exons 1 to 7 of the ABO gene was performed on some donor samples to analyze their blood phenotype, genotype and gene sequence. Results For 256 samples showing discrepancy between forward and reverse typing in microwell method, 119 were identified as normal ABO blood types, 90 were weakened ABO antibodies and 47 were ABO subtypes by serology tube test. According to the PCR-SSP genotyping test, 233 of 256 (91.02%) were consistent with serological phenotype and genotype, 17 of 256 (6.64%) were inconsistent, and 6 samples can′t read genotype based on the kit result typing table.A total of 17 genotypes were identified in 250 samples as AO1 in 56, AO2 in 58, AA in 50, BO1 in 31, BO2 in 17, BB in 8, O1O1 in 2, O1O2 in 7, AB in 13, AO4 in 1, A205O2 in 1, A205A in 1, A201A in 1, O1O4 in 1, O2O2 in 1, A201B in 1 and A205B in 1. Sequencing of exons 1 to 7 of the ABO gene was carried out in 78 samples, and 29 ABO alleles were detected, seven of which were common alleles (*A101, *A102, *A104, *B101, *O01, *O02, *O04), 22 of which were rare alleles (*A201, *A205, *Ax01, *Ax03, *Ax13, *Ax19, *Ax22, *Ael10, *B305, *Bel03, *Bel06/*Bx02, *Bw07, *Bw12, *Bw17, *Bw37, *O05, *O26, *O61, *B(A)04, *B(A)07, *cisAB01 and*cisAB01var). In addition, six rare allele mutation sites were identified (c.101A>G; c. 103_106delG; c. 146_147insGC; c. 259G>T; c. 322C>T; c. 932T>C). Conclusion The identification of ambiguous ABO blood group requires the combination of serological testing and molecular biological examination to correctly identify the blood type and ensure the safety of clinical blood transfusion.

Abstract The measurement of linguistic complexity has been a heated topic in linguistics. While previous studies have mainly centered around English and other European languages, Chinese seems neglected to some extent, and the existing Chinese linguistic complexity metrics have room for improvement. Against these backdrops, the present study applied an information-theoretic approach - the Kolmogorov complexity system - to measure Chinese linguistic complexity and examined its reliability and validity. To this end, a corpus of c.a. 60 million characters was compiled, based on which the morphological, syntactical and overall Kolmogorov complexity metrics and 18 other complexity metrics used in previous studies were calculated and subjected to a series of correlation analyses. The results show that the three Kolmogorov complexity metrics are significantly correlated with each other and with most of the previously-used metrics at the character, lexical, syntactic and collocation tiers, indicating that the Kolmogorov complexity metrics are reliable in measuring Chinese. In terms of validity, a comparison between the Kolmogorov complexity of Chinese and nine European languages and a comparison between the Kolmogorov complexity of Chinese L1 and L2 of different proficiencies show that the Kolmogorov complexity precisely and parsimoniously captured the linguistic features of Chinese. The morphological Kolmogorov complexity reflects the richness of Chinese morphemes and the flexibility of word formation, and the syntactic Kolmogorov complexity supports the view that Chinese is a topic-prominent language. This study both extends the generalizability of Kolmogorov complexity and refines the measurement of the Chinese language.

Abstract Background This study investigates the obesity paradox, where obesity is linked to lower mortality in certain patient groups, focusing on its impact on long-term mortality in chronic critically ill (CCI) patients. Methods We retrospectively analyzed CCI patients from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database’s Intensive Care Unit, categorizing them into six groups based on Body Mass Index (BMI). Using stepwise multivariable Cox regression and restricted cubic spline models, we examined the association between BMI and 90 day mortality, accounting for confounding variables through subgroup analyses. Results The study included 1996 CCI patients, revealing a 90 day mortality of 34.12%. Overweight and obese patients exhibited significantly lower mortality compared to normal-weight individuals. Adjusted analysis showed lower mortality risks in overweight and obese groups (HRs 0.60 to 0.72, p

Abstract Background Obstructed labor (OL) and uterine rupture (UR) are common obstetric complications. This study explored the burden, risk factors, decomposition, and health inequalities associated with OL and UR to improve global maternal health. Methods This was a cross-sectional analysis study including data on OL and UR from the Global Burden of Diseases, and Risk Factors Study (GBD) 2019. The main outcome measures included the number and age-standardized rate (ASR) of incidence, disability-adjusted life years (DALYs), prevalence, and deaths. Results The global burden of OL and UR has declined, with a decrease in incidence (number in 2019: 9,410,500.87, 95%UI 11,730,030.94 to 7,564,568.91; ASR in 2019: 119.64 per 100,000, 95%UI 149.15 to 96.21; estimated annual percentage change [EAPC] from 1990 to 2019: -1.34, 95% CI -1.41 to -1.27) and prevalence over time. However, DALYs (number in 2019: 999,540.67, 95%UI 1,209,749.35 to 817,352.49; ASR in 2019: 12.92, 95%UI 15.63 to 10.56; EAPC from 1990 to 2019: -0.91, 95% CI -1.26 to -0.57) and deaths remain significant. ASR of DALYs increased for the 10–14 year-old age group (2.01, 95% CI 1.53 to 2.5), the 15–19 year-old age group (0.07, 95% CI -0.47 to 0.61), Andean Latin America (3.47, 95% CI 3.05 to 3.89), and Caribbean (4.16, 95% CI 6 to 4.76). Iron deficiency was identified as a risk factor for OL and UR, and its impact varied across different socio-demographic indices (SDIs). Decomposition analysis showed that population growth primarily contributed to the burden, especially in low SDI regions. Health inequalities were evident, the slope and intercept for DALYs were − 47.95 (95% CI -52.87 to -43.02) and − 29.29 (95% CI -32.95 to -25.63) in 1990, 39.37 (95%CI 36.29 to 42.45) and 24.87 (95%CI 22.56 to 27.18) in 2019. Concentration indices of ASR-DALYs were − 0.2908 in 1990 and − 0.2922 in 2019. Conclusion This study highlights the significant burden of OL and UR and emphasizes the need for continuous efforts to reduce maternal mortality and morbidity. Understanding risk factors and addressing health inequalities are crucial for the development of effective interventions and policies to improve maternal health outcomes globally.

Abstract Virus‒host protein‒lncRNA interaction (VHPLI) predictions are critical for decoding the molecular mechanisms of viral pathogens and host immune processes. Although VHPLI interactions have been predicted in both plants and animals, they have not been extensively studied in viruses. For the first time, we propose a new deep learning-based approach that consists mainly of a convolutional neural network and bidirectional long and short-term memory network modules in combination with transfer learning named CBIL‒VHPLI to predict viral–host protein‒lncRNA interactions. The models were first trained on large and diverse datasets (including plants, animals, etc.). Protein sequence features were extracted using a k-mer method combined with the one-hot encoding and composition–transition–distribution (CTD) methods, and lncRNA sequence features were extracted using a k-mer method combined with the one-hot encoding and Z curve methods. The results obtained on three independent external validation datasets showed that the pre-trained CBIL‒VHPLI model performed the best with an accuracy of approximately 0.9. Pretraining was followed by conducting transfer learning on a viral protein–human lncRNA dataset, and the fine-tuning results showed that the accuracy of CBIL‒VHPLI was 0.946, which was significantly greater than that of the previous models. The final case study results showed that CBIL‒VHPLI achieved a prediction reproducibility rate of 91.6% for the RIP-Seq experimental screening results. This model was then used to predict the interactions between human lncRNA PIK3CD-AS2 and the nonstructural protein 1 (NS1) of the H5N1 virus, and RNA pull-down experiments were used to prove the prediction readiness of the model in terms of prediction. The source code of CBIL‒VHPLI and the datasets used in this work are available at https://github.com/Liu-Lab-Lnu/CBIL-VHPLI for academic usage.

Abstract Neoadjuvant therapy (NAT) is an important treatment for patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC), but neoadjuvant resistance affects the overall treatment outcome. Therefore, it is particularly important to accurately screen the population for NAT and explore the mechanism of resistance. Usually, different chemotherapy regimens cause different drug resistance mechanisms. Prior to combining immunotherapy with chemotherapy, extensive research has been conducted on previous drug resistance mechanisms. Currently, the mainstream NAT for ESCC involves chemotherapy combined with immunotherapy. We have witnessed the remarkable effect of this combination therapy; however, there are still a considerable number of patients whose tumor tissues show no change or even progress after NAT, and their drug resistance mechanisms remain unclear. Hence, we aim to identify relevant evidence that can distinguish and predict the effectiveness of NAT from a clinical perspective in order to provide a clinical basis for future screening of suitable populations for NAT and discovery of drug resistance mechanisms. This study is based in China's high incidence area of esophageal cancer, where enrolled patients all receive the current mainstream NAT regimen resulting in more reliable outcomes.

Abstract Tumor-draining lymph nodes (TDLNs) are usually the first station of tumor metastasis in lung cancer. TDLNs+ have distinct pathomorphologic and tumor microenvironment (TME)-compositional patterns, which still need to be thoroughly investigated in lung adenocarcinoma (LUAD). Here, we enrolled 312 LUAD patients with TDLNs+ from our institution between 2015 and 2019. 3DHISTECH was used to scan all of the TDLNs+. Based on morphologic features, TDLNs+ patterns were classified as polarized-type or scattered-type, and TME-compositional patterns were classified as colloid-type, necrosis-type, specific-type, and common-type. Multivariate analysis revealed an increased risk of early recurrence associated with scattered-type (HR 2.37, 95% CI: 1.06–5.28), colloid-type (HR 1.95, 95% CI: 1.03–3.67), and necrosis-type (HR 2.21, 95% CI: 1.13–4.89). NanoString transcriptional analysis revealed an immunosuppression and vascular invasion hallmark in scattered and necrosis patterns and an immunoactivated hallmark in polarized and common patterns. According to imaging mass cytometry (IMC), the scattered and necrosis patterns revealed that germinal centers (GC) were compromised, GCB cell and T cell proliferation were deficient, tumor cells had the potential for proliferation, and the immune attack may be weaker. In this study, we present evidence that LUAD patients have distinct patterns and immune hallmarks of TDLNs+ related to their prognosis.

BackgroundBacteria are the most diverse and widely sourced microorganisms in the indoor air of subway stations, where pathogenic bacteria can spread through the air, leading to increased health risks. ObjectiveTo understand the status and distribution characteristics of indoor air bacterial pollution in subway stations and compartments in a city of Central South China, and to provide a scientific basis for formulating intervention measures to address indoor air bacteria pollution in subways. MethodsThree subway stations and the compartments of trains parking there in a city in Central South China were selected according to passenger flow for synchronous air sampling and monitoring. Temperature, humidity, wind speed, carbon dioxide (CO2), fine particulate matter (PM2.5), and inhalable particulate matter (PM10) were measured by direct reading method. In accordance with the requirements of Examination methods for public places-Part 3: Airborne microorganisms (GB/T 18204.3-2013), air samples were collected at a flow rate of 28.3 L·min−1, and total bacterial count was estimated. Bacterial microbial species were identified with a mass spectrometer and pathogenic bacteria were distinguished from non-pathogenic bacteria according to the Catalogue of pathogenic microorganisms transmitted to human beings issued by National Health Commission. Kruskal-Wallis H test was used to compare the subway hygiene indicators in different regions and time periods, and Bonferroni test was used for pairwise comparison. Spearman correlation test was used to evaluate the correlation between CO2 concentration and total bacterial count. ResultsThe pass rates were 100.0% for airborne total bacteria count, PM2.5, and PM10 in the subway stations and train compartments, 94.4% for temperature and wind speed, 98.6% for CO2, but 0% for humidity. The overall median (P25, P75) total bacteria count was 177 (138,262) CFU·m−3. Specifically, the total bacteria count was higher in station halls than in platforms, and higher during morning peak hours than during evening peak hours (P

Abstract Background The short-term prognosis of stroke patients is mainly influenced by the severity of the primary disease at admission and the trend of disease development during the acute phase (1–7 days after admission). Objective The aim of this study is to explore the relationship between the bioelectrical impedance analysis (BIA) parameter trajectories during the acute phase of stroke patients and their short-term prognosis, and to investigate the predictive value of the prediction model constructed using BIA parameter trajectories and clinical indicators at admission for short-term prognosis in stroke patients. Methods A total of 162 stroke patients were prospectively enrolled, and their clinical indicators at admission and BIA parameters during the first 1–7 days of admission were collected. A Group-Based Trajectory Model (GBTM) was employed to identify different subgroups of longitudinal trajectories of BIA parameters during the first 1–7 days of admission in stroke patients. The random forest algorithm was applied to screen BIA parameter trajectories and clinical indicators with predictive value, construct prediction models, and perform model comparisons. The outcome measure was the Modified Rankin Scale (mRS) score at discharge. Results PA in BIA parameters can be divided into four separate trajectory groups. The incidence of poor prognosis (mRS: 4–6) at discharge was significantly higher in the “Low PA Rapid Decline Group” (85.0%) than in the “High PA Stable Group “ (33.3%) and in the “Medium PA Slow Decline Group “(29.5%) (all P

Abstract The upper respiratory tract is the initial site of SARS-CoV-2 infection. Nasal spike-specific secretory immunoglobulin A (sIgA) correlates with protection against Omicron breakthrough infection. We report that intranasal vaccination using human adenovirus serotype 5 (Ad5) vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing sIgA in the nasal passage. Nasal sIgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40% of total proteins in nasal mucosal lining fluids (NMLFs). A low-level IgG could also be detected in NMLFs but not IgM, IgD, and IgE. After a complete nasal wash, sIgA in the nasal passage could be replenished rapidly within a few hours. A comparison of purified paired serum IgA, serum IgG, and nasal sIgA from the same individuals showed that sIgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron subvariants. Serum IgG and IgA failed to neutralize XBB and BA.2.86, while nasal sIgA retained potent neutralization against these newly emerged variants. Further analysis showed that sIgA was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB challenge. Using a sIgA monoclonal antibody as a reference, we estimated that the total nasal sIgA contains about 2.6–3.9% spike-specific sIgA in NMLFs collected approximately one month after intranasal vaccination. Our study provided insights for developing intranasal vaccines that can induce sIgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.

Abstract Colorectal carcinogenesis and progression are associated with aberrant alternative splicing, yet its molecular mechanisms remain largely unexplored. Here, we find that Microrchidia family CW-type zinc finger 2 (MORC2) binds to RRM1 domain of RNA binding motif protein 39 (RBM39), and RBM39 interacts with site 1 of pre-CDK5RAP2 exon 32 via its UHM domain, resulting in a splicing switch of cyclin-dependent kinase 5 regulatory subunit associated protein 2 (CDK5RAP2) L to CDK5RAP2 S. CDK5RAP2 S promotes invasion of colorectal cancer cells in vitro and metastasis in vivo. Mechanistically, CDK5RAP2 S specifically recruits the PHD finger protein 8 to promote Slug transcription by removing repressive histone marks at the Slug promoter. Moreover, CDK5RAP2 S, but not CDK5RAP2 L, is essential for the promotion of epithelial-mesenchymal transition induced by MORC2 or RBM39. Importantly, high protein levels of MORC2, RBM39 and Slug are strongly associated with metastasis and poor clinical outcomes of colorectal cancer patients. Taken together, our findings uncover a novel mechanism by which MORC2 promotes colorectal cancer metastasis, through RBM39-mediated pre-CDK5RAP2 alternative splicing and highlight the MORC2/RBM39/CDK5RAP2 axis as a potential therapeutic target for colorectal cancer.

Abstract Inflammatory bowel disease (IBD) is a chronic disease that includes Crohn’s disease (CD) and ulcerative colitis (UC). Although genome-wide association studies (GWASs) have identified many relevant genetic risk loci, the impact of these loci on protein abundance and their potential utility as clinical therapeutic targets remain uncertain. Therefore, this study aimed to investigate the pathogenesis of IBD and identify effective therapeutic targets through a comprehensive and integrated analysis. We systematically integrated GWAS data related to IBD, UC and CD (N = 25,305) by the study of de Lange KM with the human blood proteome (N = 7213) by the Atherosclerosis Risk in Communities (ARIC) study. Proteome-wide association study (PWAS), mendelian randomisation (MR) and Bayesian colocalisation analysis were used to identify proteins contributing to the risk of IBD. Integrative analysis revealed that genetic variations in IBD, UC and CD affected the abundance of five (ERAP2, RIPK2, TALDO1, CADM2 and RHOC), three (VSIR, HGFAC and CADM2) and two (MST1 and FLRT3) cis-regulated plasma proteins, respectively (P

Abstract Objective To study the effects of chemotherapy on cognitive function in breast cancer patients, and to investigate the relationship of MemTrax test of memory and related functions to the FACT-Cog functional self-assessment for the evaluation and management of chemobrain. Methods In this prospective cohort study, clinical information of pathologically confirmed female breast cancer patients who decided to receive chemotherapy were collected in a questionnaire which was developed for this study and provided as a supplementary file. The FACT-Cog self-assessment and MemTrax test were administered before and after the chemotherapy treatments. Patients with chemobrain were identified using published criteria based on FACT-Cog scores, and MemTrax scores from chemobrain patients were analyzed. Results Fifty-six patients participated in this study, of which 41 participants completed 4 or more cycles of chemotherapy and were included in the final analyses here. Using the reported high end of minimal clinical differences (10.6 points) of FACT-Cog before and after chemotherapy, 18 patients suffered from chemobrain in this study. In these 18 chemobrain patients, no cognitive impairments were detected by MemTrax, which paradoxically demonstrated an improvement in the normal cognitive range. Conclusion The cognitive impairment induced by chemotherapy in breast cancer patients is detectable by the FACT-Cog in a Chinese cohort but is not detected by the MemTrax memory test. The fact that the more objective MemTrax could not detect the impairment could alleviate patients’ concerns which in turn would be beneficial for patients’ mental health.

Abstract A large number of slopes appear along the line during railway construction, which will pose a threat to railway safety operation. Slope monitoring plays an important role in ensuring the safety of railway operation. Aiming at the difficulties of sensor multiplexing, low accuracy, and large disturbance by trains, this paper proposes a railway slope monitoring method based on integrated fusion detection of inclination and vibration. Instability and failure characteristics of the K3 slope in Shuohuang Railway and dynamic characteristics under the excitation of the train load are analyzed by the finite element method (FEM) analysis. Based on the above analysis, a slope monitoring system is established utilizing the self-developed dual-parameter fiber Bragg grating (FBG) sensor. The monitoring data of the past four years show that the slope is in a relatively stable state at present. The monitoring data are consistent with the results of the FEM. The feasibility of the damage identification method based on inclination and vibration characteristics is verified, which provides a new method for railway slope monitoring.

Abstract As the largest organ in the human body, skeletal muscle is essential for breathing support, movement initiation, and maintenance homeostasis. It has been shown that programmed cell death (PCD), which includes autophagy, apoptosis, and necrosis, is essential for the development of skeletal muscle. A novel form of PCD called ferroptosis is still poorly understood in relation to skeletal muscle. In this study, we observed that the activation of ferroptosis significantly impeded the differentiation of C2C12 myoblasts into myotubes and concurrently suppressed the expression of OTUB1, a crucial deubiquitinating enzyme. OTUB1-silenced C2C12 mouse myoblasts were used to investigate the function of OTUB1 in ferroptosis. The results show that OTUB1 knockdown in vitro significantly increased C2C12 ferroptosis and inhibited myogenesis. Interestingly, the induction of ferroptosis resulting from OTUB1 knockdown was concomitant with the activation of autophagy. Furthermore, OTUB1 interacted with the P62 protein and stabilized its expression by deubiquitinating it, thereby inhibiting autophagy-dependent ferroptosis and promoting myogenesis. All of these findings demonstrate the critical role that OTUB1 plays in controlling ferroptosis, and we suggest that focusing on the OTUB1-P62 axis may be a useful tactic in the treatment and prevention of disorders involving the skeletal muscle.

Abstract Background The potential involvement of circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification in the progression of Wilms tumor (WT) has not been fully elucidated. This study investigates the regulatory mechanisms and clinical significance of m6A-modified circMARK2 and its role in WT progression. Methods We identified dysregulated circRNAs through deep sequencing and validated their expression by qRT-PCR in WT tissues. The biological functions of circMARK2 were assessed using clone formation, transwell migration, and orthotopic animal models. To dissect the underlying mechanisms, we employed RNA immunoprecipitation, RNA pull-down, dual-luciferase reporter assays, Western blotting, and immunofluorescence and immunohistochemical staining. Results CircMARK2, upregulated in WT tissues, was found to be m6A-modified and promoted cytoplasmic export. It facilitated WT progression by stabilizing LIN28B mRNA through the circMARK2/IGF2BP2 interaction. In vitro and in vivo studies demonstrated that circMARK2 enhances the malignant behavior of WT cells. Clinically, higher circMARK2 levels in tumor tissues of WT patients were linked to increased tumor aggressiveness and reduced survival rates. Conclusions Our study provides the first comprehensive evidence that m6A-modified circMARK2 contributes to WT progression by enhancing LIN28B mRNA stability, promoting cellular aggressiveness. CircMARK2 emerges as a potential biomarker for prognosis and a promising target for therapeutic intervention in WT, underscoring the clinical relevance of m6A modification in pediatric renal cancer.

Abstract Background Sublobar resection (wedge resection and segmentectomy) has been established as an oncologically equivalent option to lobectomy for early‐stage patients with non‐small cell lung cancer (NSCLC) ≤ 2 cm. However, the optimal approach of sublobar resection remains subject to debate. In the present study we aimed to compare the oncological outcomes of wedge resection and segmentectomy in these patients. Methods We identified patients with pT1a‐bN0M0 NSCLC who underwent wedge resection and segmentectomy from the Surveillance, Epidemiology, and End Results database between 2010 and 2020. A Cox regression model and propensity‐score matching (PSM) analysis were used. Overall survival (OS) and lung cancer‐specific survival (LCSS) were compared using the Kaplan–Meier method. Results A total of 4190 patients met our selection criteria, including wedge resection in 3137 and segmentectomy in 1053. Patients undergoing wedge resection were less likely to have total lymph nodes resected (4 vs. 7, p

ABSTRACT: In this study, milk fat globule membrane (MFGM) ingredients enriched in polar lipids were prepared using membrane filtration, including microfiltration, diafiltration, and ultrafiltration from butter serum powder. Polar lipids (phospholipids, sterols, and gangliosides) in prepared MFGM ingredients were analyzed by 31P nuclear magnetic resonance spectroscopy, GC-MS, and ultra-performance liquid chromatography (UPLC)-MS/MS, respectively. The lipolysis degree and microstructure of MFGM ingredient and soybean lecithin (SL) emulsions during in vitro digestion were also analyzed. Microfiltration showed higher concentration efficiency than ultrafiltration, which increased by 2.16% and 2.73% in phospholipids, respectively. Moreover, diafiltration concentrated more polar lipids (6.39% of phospholipids) than microfiltration. Milk fat globule membrane ingredients had high levels of sphingomyelin (1.27%–1.36%) and ratio of GD3 to GM3 is 9.25- to 9.88-fold. The different lipolysis behaviors between MFGM ingredient emulsions and SL emulsions were correlated with their different polar lipid compositions. Phospholipids from both MFGM ingredients and SL could help maintain the initial structure during the gastric digestion. These results could provide a scientific basis for developing high-polar-lipids food, particularly infant formulas and special functional foods.

Abstract Background Bitter taste receptors (Tas2rs) are generally considered to sense various bitter compounds to escape the intake of toxic substances. Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in vivo. Methods To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues, multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene‐editing technique. A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes. Then, T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds. Perception to taste substance was also studied using two‐bottle preference tests. Results We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique. Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice. But qRT‐PCR results revealed the changed expression profile of mTas2rs gene in taste buds of these mutant mice. With two‐bottle preference tests, these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105. In addition, these mutant mice showed a loss of taste perception to quinine dihydrochloride, denatonium benzoate, and cucurbitacin B (CuB). Gnat3‐mediated taste receptor and its signal pathway contribute to CuB perception. Conclusions These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound–induced responses mediated by these TAS2Rs in many extraoral tissues.

According to studies by relevant scholars, the ground subsidence rate in Sanhe City, Hebei, increased gradually from 2003 to 2016, with the most severe subsidence observed in the Yanjiao area , which has become contiguous with the subsidence area in Tongzhou, Beijing. However, the development trend of ground subsidence disasters in Sanhe City after 2016 remains unclear. With the implementation of national policies such as the integration of Beijing-Tianjin-Hebei region and the construction of Beijing’s sub-center, it is crucial to identify the development and evolution characteristics of land subsidence disasters in Sanhe City and analyze their causes to ensure the urban safety and sustainable development of Sanhe City. In this context, the authors used SBAS-InSAR technology to interpret the evolution characteristics of ground subsidence in Sanhe City from 2018 to 2020, and analyzed several inducing factors that led to land subsidence in Sanhe City, summarizing the main causes. Through this study, the spatial distribution and evolutionary characteristics of land subsidence disasters in Sanhe City were grasped: the western part of the city exhibits severe subsidence, while the eastern part is less affected, with a focus on the overall characteristics of key subsidence areas. Two main subsidence areas were identified, namely, the Yanjiao Town subsidence area with three subsidence funnels and the DuanJialing town subsidence area with one subsidence funnel, with the former being the most severely affected. From 2018 to 2020, the overall trend of ground subsidence disasters in Sanhe City showed a slowdown. Through comparative analysis, it was determined that severe overexploitation of groundwater, soil properties, urbanization development, and population growth are the main factors contributing to the occurrence and development of ground subsidence disasters in Sanhe City. The research results of this paper will provide reference for the prevention and control of ground subsidence disasters in the region.

Recent trends in road engineering have explored the potential of incorporating recycled solid wastes into infrastructures that including pavements, bridges, tunnels, and accessory structures. The utilization of solid wastes is expected to offer sustainable solutions to waste recycling while enhancing the performance of roads. This review provides an extensive analysis of the recycling of three main types of solid wastes for road engineering purposes: industrial solid waste, infrastructure solid waste, and municipal life solid waste. Industrial solid wastes suitable for road engineering generally include coal gangue, fly ash, blast furnace slag, silica fume, and steel slag, etc. Infrastructure solid wastes recycled in road engineering primarily consist of construction & demolition waste, reclaimed asphalt pavements, and recycled cement concrete. Furthermore, recent exploration has extended to the utilization of municipal life solid wastes, such as incinerated bottom ash, glass waste, electronics waste, plastic waste, and rubber waste in road engineering applications. These recycled solid wastes are categorized into solid waste aggregates, solid waste cements, and solid waste fillers, each playing distinct roles in road infrastructure. Roles of solid waste acting aggregates, cements, and fillers in road infrastructures were fully investigated, including their pozzolanic properties, integration effects to virgin materials, modification or enhancement solutions, engineering performances. Utilization of these materials not only addresses the challenge of waste management but also offers environmental benefits aiming carbon neutral and contributes to sustainable infrastructure development. However, challenges such as variability in material properties, environmental impact mitigation, secondary pollution to environment by leaching, and concerns regarding long-term performance need to be further addressed. Despite these challenges, the recycled solid wastes hold immense potential in revolutionizing road construction practices and fostering environmental stewardship. This review delves into a bird’s-eye view of the utilization of recycled solid wastes in road engineering, highlighting advances, benefits, challenges, and future prospects.

Abstract Background Traumatic fractures occur frequently worldwide. However, research remains limited on the association between short-term exposure to temperature and traumatic fractures. This study aims to explore the impact of apparent temperature (AT) on emergency visits (EVs) due to traumatic fractures. Methods Based on EVs data for traumatic fractures and the contemporary meteorological data, a generalized Poisson regression model along with a distributed lag nonlinear model (DLNM) were undertaken to determine the impact of AT on traumatic fracture EVs. Subgroup analysis by gender and age and sensitivity analysis were also performed. Results A total of 25,094 EVs for traumatic fractures were included in the study. We observed a wide “J”-shaped relationship between AT and risk of traumatic fractures, with AT above 9.5 °C positively associated with EVs due to traumatic fractures. The heat effects became significant at cumulative lag 0–11 days, and the relative risk (RR) for moderate heat (95th percentile, 35.7 °C) and extreme heat (99.5th percentile, 38.8 °C) effect was 1.311 (95% CI: 1.132–1.518) and 1.418 (95% CI: 1.191–1.688) at cumulative lag 0–14 days, respectively. The cold effects were consistently non-significant on single or cumulative lag days across 0–14 days. The heat effects were higher among male and those aged 18–65 years old. The sensitivity analysis results remained robust. Conclusion Higher AT is associated with cumulative and delayed higher traumatic fracture EVs. The male and those aged 18–65 years are more susceptible to higher AT.

Background: The International Agency for Research on Cancer (IARC) released the latest estimates of the global burden of cancer. We present a comparison of cancer profiles between 2020 and 2022, leveraging data from the Global Cancer Statistics (GLOBOCAN). Methods: Cancer incidence and mortality data were sourced from two different years, 2020 and 2022, in the GLOBOCAN database. We tracked changes in age-standardized incidence and mortality rates, as well as estimated numbers of new cancer cases and deaths of the 15 most common cancer types globally and in China between 2020 and 2022. Additionally, we conducted comparisons to assess alterations in the cancer burden and variations in mortality-to-incidence ratio (MIR) across different regions and countries for both 2020 and 2022. Results: Lung cancer remained the most common cancer and the leading cause of cancer death worldwide. The new cases of thyroid cancer witnessed a sharp increase in 2022. Conversely, the numbers of new cancer cases and deaths from stomach and esophageal cancer decreased significantly in 2022. The geographic distribution of cancer incidence and mortality across six continents in 2022 largely mirrored that of 2020. Higher Human Development Index (HDI) levels in countries corresponded with elevated rates of cancer incidence and mortality, consistent with the previous year. Among 185 countries or territories, China's age-standardized incidence rate (ASIR) ranked 64th and its age-standardized mortality rate (ASMR) ranked 68th, aligning with global averages. Lung cancer continued to impose the greatest burden of incidence and mortality. Stomach, breast, and esophageal cancers showed declines in both case counts and ASIR. Noteworthy reductions in both ASMR and absolute mortality numbers were observed in liver, stomach, and esophageal cancers. The global MIR decreased from 0.516 in 2020 to 0.488 in 2022. MIR trends indicated an upward trajectory with decreasing HDI levels in both 2022 and 2020. While Canada, Germany, India, Italy, Japan, and the United Kingdom demonstrated increasing MIRs, China exhibited the most significant decrease, followed by Russia and the United States. Conclusions: The global landscape of cancer incidence and mortality in 2022 reflects ongoing trends observed in 2020. Cancer burdens vary notably across countries with differing socioeconomic statuses. Decreases in stomach, liver, and esophageal cancer cases and deaths signify progress in cancer control efforts. The decrease in the global MIRs highlights potential improvements in cancer management.

Abstract Background/Objectives Increased free fatty acid (FFA) promotes adiponectin secretion in healthy subjects and induces inflammation in diabetes. Given the potential pro-inflammatory role of adiponectin in “adiponectin paradox”, we performed this study in patients with type 2 diabetes mellitus (T2DM) to assess the association of FFA with adiponectin and to investigate whether adiponectin mediates FFA-related inflammation. Methods This cross-sectional study consisted of adult patients with T2DM. FFA, adiponectin, and tumor necrosis factor-α (TNF-α) were assayed from fasting venous blood after overnight fasting for at least 8 h. Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between FFA and adiponectin. Mediation analysis was performed to determine the mediating effect of adiponectin on the association between FFA and TNF-α. Results This study included 495 participants, with 332 males (67.1%) and a mean age of 47.0 ± 11.2 years. FFA was positively associated with adiponectin (b = 0.126, 95%CI: 0.036–0.215, P = 0.006) and was the main contributor to the increase of adiponectin (standardized b = 0.141). The RCS analysis demonstrated that adiponectin increased with FFA when FFA was less than 0.7 mmol/L but did not further increase thereafter (P overall