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Abstract Background The present retrospective cohort study focused on evaluating the effects of fluctuations in serum uric acid (SUA) on a mildly reduced glomerular filtration rate (eGFR) in a population with a normal eGFR in Urumqi, China. Methods A total of 2,154 normal individuals with a normal eGFR were recruited from 2018 to 2021. This study included questionnaire surveys, physical measurements, and blood sampling. We deemed the mildly reduced eGFR to be 60–90 ml·min–1·(1.73 m2)–1. The relationship between changes in SUA levels and the eGFR was assessed. Results (1) During the 3-year follow-up period, 433 individuals (20.10%) presented mildly reduced eGFR. (2) After stratification by the degree to which uric acid changed into five groups, the group showing the greatest change in uric acid concentration had significantly lower eGFR values than the other four groups. As the uric acid concentration (ΔSUA) increased, the degree of mild eGFR reduction (ΔeGFR) also increased (P 0.05). Pearson correlation analysis showed a negative correlation between ΔSUA and ΔeGFR (r = -0.211, P

Abstract Chemotherapy, the standard of care treatment for cancer patients with advanced disease, has been increasingly recognized to activate host immune responses to produce durable outcomes. Here, in colorectal adenocarcinoma (CRC) we identify oxaliplatin-induced Thioredoxin-Interacting Protein (TXNIP), a MondoA-dependent tumor suppressor gene, as a negative regulator of Growth/Differentiation Factor 15 (GDF15). GDF15 is a negative prognostic factor in CRC and promotes the differentiation of regulatory T cells (Tregs), which inhibit CD8 T-cell activation. Intriguingly, multiple models including patient-derived tumor organoids demonstrate that the loss of TXNIP and GDF15 responsiveness to oxaliplatin is associated with advanced disease or chemotherapeutic resistance, with transcriptomic or proteomic GDF15/TXNIP ratios showing potential as a prognostic biomarker. These findings illustrate a potentially common pathway where chemotherapy-induced epithelial oxidative stress drives local immune remodeling for patient benefit, with disruption of this pathway seen in refractory or advanced cases.

Abstract Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts’ increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR.

Rampant C-to-U RNA editing drives the mutation and evolution of SARS-CoV-2. While much attention has been paid to missense mutations, the C-to-U events leading to AUG and thus creating novel ORFs were uninvestigated. By utilizing the public time-course mutation data from the worldwide SARS-CoV-2 population, we systematically identified the “AUG-gain mutations” caused by C-to-U RNA editing. Synonymous mutations were of special focus. A total of 58 synonymous C-to-U sites are able to create out-of-frame AUG in coding sequence (CDS). These 58 synonymous sites showed significantly higher allele frequency (AF) and increasing rate (dAF/dt) than other C-to-U synonymous sites in the SARS-CoV-2 population, suggesting that these 58 AUG-gain events conferred additional benefits to the virus and are subjected to positive selection. The 58 predicted new ORFs created by AUG-gain events showed the following advantages compared to random expectation: they have longer lengths, higher codon adaptation index (CAI), higher Kozak scores, and higher tRNA adaptation index (tAI). The 58 putatively novel ORFs have high expressibility and are very likely to be functional, providing an explanation for the positive selection on the 58 AUG-gain mutations. Our study proposed a possible mechanism of the emergence of de novo genes in SARS-CoV-2. This idea should be helpful in studying the mutation and evolution of SARS-CoV-2.

Abstract Organic–inorganic hybrid thermoelectric (TE) materials have attracted tremendous interest for harvesting waste heat energy. Due to their mechanical flexibility, inorganic‐organic hybrid TE materials are considered to be promising candidates for flexible energy harvesting devices. In this work, enhanced TE properties of Tellurium (Te) nanowires (NWs)‐ poly (3‐hexylthiophene‐2, 5‐diyl) (P3HT) hybrid materials are reported by improving the charge transport at interfacial layer mediated via controlled oxidation. A power factor of ≈9.8 µW (mK2)−1 is obtained at room temperature for oxidized P3HT‐TeNWs hybrid materials, which increases to ≈64.8 µW (mK2)−1 upon control of TeNWs oxidation. This value is sevenfold higher compared to P3HT‐TeNWs‐based hybrid materials reported in the literature. MD simulation reveals that oxidation‐free TeNWs demonstrate better templating for P3HT polymer compared to oxidized TeNWs. The Kang–Snyder model is used to study the charge transport in these hybrid materials. A large σE0 value is obtained which is related to better templating of P3HT on oxygen‐free TeNWs. This work provides evidence that oxidation control of TeNWs is critical for better interface‐driven charge transport, which enhances the thermoelectric properties of TeNWs‐P3HT hybrid materials. This work provides a new avenue to improve the thermoelectric properties of a new class of hybrid thermoelectric materials.

Abstract Wilms tumor (WT) is the most common renal malignancy of childhood. Despite improvements in the overall survival, relapse occurs in ~15% of patients with favorable histology WT (FHWT). Half of these patients will succumb to their disease. Identifying novel targeted therapies remains challenging in part due to the lack of faithful preclinical in vitro models. Here we establish twelve patient-derived WT cell lines and demonstrate that these models faithfully recapitulate WT biology using genomic and transcriptomic techniques. We then perform loss-of-function screens to identify the nuclear export gene, XPO1, as a vulnerability. We find that the FDA approved XPO1 inhibitor, KPT-330, suppresses TRIP13 expression, which is required for survival. We further identify synergy between KPT-330 and doxorubicin, a chemotherapy used in high-risk FHWT. Taken together, we identify XPO1 inhibition with KPT-330 as a potential therapeutic option to treat FHWTs and in combination with doxorubicin, leads to durable remissions in vivo.

Abstract The epidermal growth factor receptor, EGFR, is frequently activated in lung cancer and glioblastoma by genomic alterations including missense mutations. The different mutation spectra in these diseases are reflected in divergent responses to EGFR inhibition: significant patient benefit in lung cancer, but limited in glioblastoma. Here, we report a comprehensive mutational analysis of EGFR function. We perform saturation mutagenesis of EGFR and assess function of ~22,500 variants in a human EGFR-dependent lung cancer cell line. This approach reveals enrichment of erlotinib-insensitive variants of known and unknown significance in the dimerization, transmembrane, and kinase domains. Multiple EGFR extracellular domain variants, not associated with approved targeted therapies, are sensitive to afatinib and dacomitinib in vitro. Two glioblastoma patients with somatic EGFR G598V dimerization domain mutations show responses to dacomitinib treatment followed by within-pathway resistance mutation in one case. In summary, this comprehensive screen expands the landscape of functional EGFR variants and suggests broader clinical investigation of EGFR inhibition for cancers harboring extracellular domain mutations.

HIV disease remains prevalent in the USA and chronic kidney disease remains a major cause of morbidity in HIV-1-positive patients. Host double-stranded RNA (dsRNA)-activated protein kinase (PKR) is a sensor for viral dsRNA, including HIV-1. We show that PKR inhibition by compound C16 ameliorates the HIV-associated nephropathy (HIVAN) kidney phenotype in the Tg26 transgenic mouse model, with reversal of mitochondrial dysfunction. Combined analysis of single-nucleus RNA-seq and bulk RNA-seq data revealed that oxidative phosphorylation was one of the most downregulated pathways and identified signal transducer and activator of transcription (STAT3) as a potential mediating factor. We identified in Tg26 mice a novel proximal tubular cell cluster enriched in mitochondrial transcripts. Podocytes showed high levels of HIV-1 gene expression and dysregulation of cytoskeleton-related genes, and these cells dedifferentiated. In injured proximal tubules, cell-cell interaction analysis indicated activation of the pro-fibrogenic PKR-STAT3-platelet-derived growth factor (PDGF)-D pathway. These findings suggest that PKR inhibition and mitochondrial rescue are potential novel therapeutic approaches for HIVAN.

Genomic instability stands out as a pivotal hallmark of cancer, and PARP inhibitors (PARPi) emerging as a groundbreaking class of targeted therapy drugs meticulously crafted to inhibit the repair of DNA single-strand breaks(SSB) in tumor cells. Currently, PARPi have been approved for the treatment of ovarian cancer, pancreatic cancer, breast cancer, and prostate cancer characterized by homologous recombination(HR) repair deficiencies due to mutations in BRCA1/2 or other DNA repair associated genes and acquiring the designation of breakthrough therapy. Nonetheless, PARPi exhibit limited efficacy in the majority of HR-proficient BRCA1/2 wild-type cancers. At present, the synergistic approach of combining PARPi with agents that induce HR defects, or with chemotherapy and radiotherapy to induce substantial DNA damage, significantly enhances the efficacy of PARPi in BRCA wild-type or HR-proficient patients, supporting extension the use of PARPi in HR proficient patients. Therefore, we have summarized the effects and mechanisms of the combined use of drugs with PARPi, including the combination of PARPi with HR defect-inducing drugs such as ATRi, CHKi, HR indirectly inducing drugs like VEGFRi, CDKi, immune checkpoint inhibitors and drugs instigating DNA damage such as chemotherapy or radiotherapy. In addition, this review discusses several ongoing clinical trials aimed at analyzing the clinical application potential of these combined treatment strategies.

This study employed segmented variable-frequency ultrasound synergistic hot-air drying (SVFU-HAD) for Rhubarb slices, selected two sets of time nodes for frequency conversion (60 min, 120 min, and 90 min, 150 min), and two sequences of frequency conversion (high-frequency to low-frequency, and low-frequency to high-frequency). It aimed to investigate the effects of SVFU-HAD on the drying characteristics, quality, and heat transfer of Rhubarb slices. The findings indicated that segmented variable-frequency ultrasound has advantages in increasing drying rate and improving uniformity of cavitation effects compared to constant-frequency ultrasound. Analysis of physical properties revealed that the rehydration performance of dried products subjected to ultrasonic variable-frequency treatment (90 min, 150 min) according to the drying rate was better (RR > 3.3). The transition mode from high-frequency to low-frequency in variable-frequency ultrasonic treatment contributes to maintaining the overall color of Rhubarb. Analysis of chemical properties unveiled that Rhubarb treated with 40 kHz (0 min)–28 kHz (60 min)–25 kHz (120 min) segmented variable-frequency ultrasound contained overall higher levels of tannins, dianthrones and free anthraquinones content, which exceeded the average values by 3.24%, 26.65%, and 14.42%, respectively. In addition, thermal analysis results based on ANSYS Workbench software demonstrated that the drying uniformity of SVFU-HAD is superior to that of hot-air drying and constant-frequency ultrasound synergistic hot-air drying (CFU-HAD). Overall, the SVFU-HAD method employed in this study presents an innovative approach to ultrasound synergistic hot-air drying research with promising potential for enhancing the efficiency and quality characteristics of Rhubarb slices.

ABSTRACT Human cytomegalovirus (HCMV), a widely prevalent human beta-herpesvirus, establishes lifelong persistence in the host following primary infection. In healthy individuals, the virus is effectively controlled by HCMV-specific T cells and typically exhibits asymptomatic. The T cell immune response plays a pivotal role in combating HCMV infection, while HCMV employs various strategies to counteract it within the host. Previously, we reported that UL23, a tegument protein of HCMV, facilitates viral immune evasion from interferon-gamma (IFN-γ) responses, and it is well known that IFN-γ is mainly derived from T cells. However, the involvement of UL23 in viral immune evasion from T cell-mediated immunity remains unclear. Herein, we present compelling evidence that UL23 significantly enhances viral resistance against T cell-mediated cytotoxicity during HCMV infection from the co-culture assays of HCMV-infected cells with T cells. We found that IFN-γ plays a major role in regulating T cell cytotoxicity mediated by UL23. More interestingly, we demonstrated that UL23 not only regulates the IFN-γ downstream responses but also modulates the IFN-γ secretion by regulating T cell activities. Further experiments indicate that UL23 upregulates the expression and signaling of programmed death ligand 1 (PD-L1), which is responsible for inhibiting multiple aspects of T cell activities, including activation, apoptosis, and IFN-γ secretion, as determined through RNA-seq analysis and inhibitor-blocking experiments, ultimately facilitating viral replication and spread. Our findings highlight the potential role of UL23 as an alternative antagonist in suppressing T cell cytotoxicity and unveil a novel strategy for HCMV to evade T cell immunity.IMPORTANCET cell immunity is pivotal in controlling primary human cytomegalovirus (HCMV) infection, restricting periodic reactivation, and preventing HCMV-associated diseases. Despite inducing a robust T cell immune response, HCMV has developed sophisticated immune evasion mechanisms that specifically target T cell responses. Although numerous studies have been conducted on HCMV-specific T cells, the primary focus has been on the impact of HCMV on T cell recognition via major histocompatibility complex molecules. Our studies show for the first time that HCMV exploits the programmed death ligand 1 (PD-L1) inhibitory signaling pathway to evade T cell immunity by modulating the activities of T cells and thereby blocking the secretion of IFN-γ, which is directly mediated by HCMV-encoded tegument protein UL23. While PD-L1 has been extensively studied in the context of tumors and viruses, its involvement in HCMV infection and viral immune evasion is rarely reported. We observed an upregulation of PD-L1 in normal cells during HCMV infection and provided strong evidence supporting its critical role in UL23-induced inhibition of T cell-mediated cytotoxicity. The novel strategy employed by HCMV to manipulate the inhibitory signaling pathway of T cell immune activation for viral evasion through its encoded protein offers valuable insights for the understanding of HCMV-mediated T cell immunomodulation and developing innovative antiviral treatment strategies.

Abstract Surgical resection remains the mainstream treatment for malignant melanoma. However, challenges in wound healing and residual tumor metastasis pose significant hurdles, resulting in high recurrence rates in patients. Herein, a bioactive injectable hydrogel (BG‐Mngel) formed by crosslinking sodium alginate (SA) with manganese‐doped bioactive glass (BG‐Mn) is developed as a versatile platform for anti‐tumor immunotherapy and postoperative wound healing for melanoma. The incorporation of Mn2+ within bioactive glass (BG) can activate the cGAS‐STING immune pathway to elicit robust immune response for cancer immunotherapy. Furthermore, doping Mn2+ in BG endows system with excellent photothermal properties, hence facilitating STING activation and reversing the tumor immune‐suppressive microenvironment. BG exhibits favorable angiogenic capacity and tissue regenerative potential, and Mn2+ promotes cell migration in vitro. When combining BG‐Mngel with anti‐PD‐1 antibody (α‐PD‐1) for the treatment of malignant melanoma, it shows enhanced anti‐tumor immune response and long‐term immune memory response. Remarkably, BG‐Mngel can upregulate the expression of genes related to blood vessel formation and promote skin tissue regeneration when treating full‐thickness wounds. Overall, BG‐MnGel serves as an effective adjuvant therapy to regulate tumor metastasis and wound healing for malignant melanoma.

Nongxiangxing Baijiu distiller’s grains are rich in lactic acid. Pichia kudriavzevii is the dominant yeast. The effects of lactic acid on the solid-state fermentation characteristics of Nongxiangxing Baijiu of the dominant yeast were explored under lactic acid stress of different concentrations. The growth and metabolism changes of Pichia kudriavzevii (PY1) were investigated from the aspects of carbon source consumption, growth factor utilization, high temperature tolerance and main metabolite production. Results showed that, the lactic acid stress had no significant effect on the colony and cell morphology of P. kudriavzevii, but had a certain inhibition on the growth of cell. This reversible inhibition could be weakened by amino acids and vitamins. When the culture temperature exceeds 44 ℃, the effect of lactic acid on the growth of the strain was gradually replaced by temperature. In metabolism, lactic acid could improve the utilization rate of glucose, galactose, maltose, fructose and sucrose, increase the production of ethanol and esters, and reduce the production of higher alcohols. In summary, the lactic acid could affect the flavor formation of Nongxiangxing Baijiu by affecting the growth and metabolism of yeast, and could be used as the fermentation regulation factor of Nongxiangxing Baijiu.

Abstract Dravet syndrome (DS), previously known as severe myoclonic epilepsy in infancy (SMEI), is considered the most serious “epileptic encephalopathy.” Here, we present a man with a de novo SCN1A mutation who was diagnosed with DS at the age of 29. In addition to pharmaco‐resistant seizures and cognitive delay, he also developed moderate to severe motor and gait problems, such as crouching gait and Pisa syndrome. Moreover, it deteriorated significantly following an epileptic seizure. The patient presented with severe flexion of the head and trunk in the sagittal plane and fulfilled the diagnostic criteria for camptocormia and antecollis. After a week, it spontaneously alleviated partially. We applied levodopa to the patient and had a good response. Functional Gait Assessment (FGA) was assessed at three different times: 4 days after the seizure, 1 week after the seizure, and after taking levodopa for 2 years. The results were 4, 12, and 19 points, respectively. We postulated that: (1) gait and motor deficits are somehow influenced by recurrent epileptic episodes;(2) the nigrostriatal dopamine system is involved. To our knowledge, we were the ones who first reported this phenomenon.

IntroductionAccurate detection of potato seedlings is crucial for obtaining information on potato seedlings and ultimately increasing potato yield. This study aims to enhance the detection of potato seedlings in drone-captured images through a novel lightweight model.MethodsWe established a dataset of drone-captured images of potato seedlings and proposed the VBGS-YOLOv8n model, an improved version of YOLOv8n. This model employs a lighter VanillaNet as the backbone network in-stead of the original YOLOv8n model. To address the small target features of potato seedlings, we introduced a weighted bidirectional feature pyramid network to replace the path aggregation network, reducing information loss between network layers, facilitating rapid multi-scale feature fusion, and enhancing detection performance. Additionally, we incorporated GSConv and Slim-neck designs at the Neck section to balance accuracy while reducing model complexity. ResultsThe VBGS-YOLOv8n model, with 1,524,943 parameters and 4.2 billion FLOPs, achieves a precision of 97.1%, a mean average precision of 98.4%, and an inference time of 2.0ms. Comparative tests reveal that VBGS-YOLOv8n strikes a balance between detection accuracy, speed, and model efficiency compared to YOLOv8 and other mainstream networks. Specifically, compared to YOLOv8, the model parameters and FLOPs are reduced by 51.7% and 52.8% respectively, while precision and a mean average precision are improved by 1.4% and 0.8% respectively, and the inference time is reduced by 31.0%.DiscussionComparative tests with mainstream models, including YOLOv7, YOLOv5, RetinaNet, and QueryDet, demonstrate that VBGS-YOLOv8n outperforms these models in terms of detection accuracy, speed, and efficiency. The research highlights the effectiveness of VBGS-YOLOv8n in the efficient detection of potato seedlings in drone remote sensing images, providing a valuable reference for subsequent identification and deployment on mobile devices.

Confined array jet boiling can achieve high heat flux in a compact space and its flow resistance characteristics are critical to the design of cooling systems. The boiling images of distributed confined jet of HFE-7100 is recorded by a high-speed camera in this study. The effects of jet mass flux, jet height and surface structure of two-phase jet flow characteristics on micro-pin-finned surfaces are studied. A benefit from the distributed configuration of the jet array, in contrast to previous studies, is that the jet boiling pressure drop is independent of the heat flux, but only related to the jet mass flux. The effect of the surface structure on the pressure drop is negligible. Jet flow instability will be triggered by intermittently blockage of the jet inlet and outlet by large vapor masses in certain heated surfaces. Reducing the jet height can suppress two-phase flow instabilities while keeping the pressure drop almost constant and the CHF to slightly increase. The COP of distributed jet impingement boiling cooler proposed in this work can be up to 6 times higher than that of the conventional jet boiling cooler, and more than 2 times higher that of the microchannel heat sink.

Abstract The structural connectivity and kinematic relationship between the Altyn Tagh sinistral strike‐slip fault (ATF) and Qilian Shan fold‐and‐thrust belt along the north Tibetan margin east of 96°E is an important question for tectonicists interested in the evolving active deformation field of Central Asia and associated earthquake hazards of China's Hexi Corridor region. New results from a detailed 130‐km‐long N‐S magnetotelluric (MT) survey from the Qilian Shan to Beishan elucidates the locations and down‐dip orientations of major faults. Importantly, the results indicate that the Heishan‐Jinta’Nanshan fault system roots steeply into the lower crust, is unconnected to the Qilian Shan thrust wedge, and has reactivated the margin of the North China Craton and an older, regional ductile shear belt. The structurally linked ATF‐Heishan‐Jinta’Nanshan system defines a fundamental kinematic boundary in central Asia between the NE directed Qilian Shan thrust belt to the south and the eastwardly extruding Beishan‐Alxa Block to the north.

Abstract Pressure engineering in semiconductors leads to a variety of novel physical phenomena and has recently received considerable attention. Here, we report on pressure-induced superconductivity in III–V gallium phosphide (GaP), a commercially important semiconductor that exhibits excellent optical performance. We show that the emergence of superconductivity is accompanied by the concurrence of piezochromic transition and metallization and can be correlated to a structural transition from the cubic to orthorhombic phase. In line with the structural origin of superconductivity, the critical temperature T c monotonically decreases with increasing pressure up to ~50 GPa. Moreover, the superconductivity could be preserved toward ambient pressure because of the irreversibility of the structural transition. Nevertheless, the superconducting transition displays evident broadening associated with the presence of amorphization in the depressurized sample. The synchronous evolution of the structural and electronic properties not only shows a vivid structure-property relationship but also could facilitate the exploration of novel functionalities by means of pressure treatment.

In order to enrich potato staple products and improve the sensory quality of scones, the rheological properties of mixed dough of potato flour and wheat flour were studied. With sensory score and texture characteristics as evaluation indexes, the formulation of potato flour scone was optimized by single factor experiments and orthogonal test. The results showed that potato flour could improve the water absorption of wheat flour and shorten the formation time of dough, but it would lead to a decline in the elasticity and strength of the dough, resulting in a decrease in its quality. Therefore, the appropriate substitution ratio for whole potato flour was considered to be 20%. The best process recipe for scones was based on a mixture of wheat flour and whole potato flour quality, with 20% whole potato flour added, 68% water added, 0.8% yeast added and 6% sugar added. The hardness of the scone prepared under the optimal condition was 342.63 g, and the chewiness was 106.76 N. The research results provided a theoretical basis for the quality improvement of the scones and the development of whole potato flour products.

With the increasing complexity of applications, many delay-sensitive and compute-intensive services have posed significant challenges to mobile devices. Addressing how to efficiently allocate heterogeneous network resources to meet the computing and delay requirements of terminal services is a pressing issue. In this paper, a new cooperative twin delayed deep deterministic policy gradient and deep-Q network (TD3-DQN) algorithm is introduced to minimize system latency by optimizing computational offloading and caching placement asynchronously. Specifically, the task-partitioning technique divides computing tasks into multiple subtasks, reducing the response latency. A DQN intelligent algorithm is presented to optimize the offloading path to edge servers by perceiving network resource status. Furthermore, a TD3 approach is designed to optimize the cached content in the edge servers, ensuring dynamic popularity content requirements are met without excessive offload decisions. The simulation results demonstrate that the proposed model achieves lower latency and quicker convergence in asymmetrical cloud–edge collaborative networks compared to other benchmark algorithms.

Natural bone is a composite tissue made of organic and inorganic components, showing piezoelectricity. Whitlockite (WH), which is a natural magnesium-containing calcium phosphate, has attracted great attention in bone formation recently due to its unique piezoelectric property after sintering treatment and sustained release of magnesium ion (Mg2+). Herein, a composite scaffold (denoted as PWH scaffold) composed of piezoelectric WH (PWH) and poly(ε-caprolactone) (PCL) was 3D printed to meet the physiological demands for the regeneration of neuro-vascularized bone tissue, namely, providing endogenous electric field at the defect site. The sustained release of Mg2+ from the PWH scaffold, displaying multiple biological activities, and thus exhibits a strong synergistic effect with the piezoelectricity on inhibiting osteoclast activation, promoting the neurogenic, angiogenic, and osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) in vitro. In a rat calvarial defect model, this PWH scaffold is remarkably conducive to efficient neo-bone formation with rich neurogenic and angiogenic expressions. Overall, this study presents the first example of biomimetic piezoelectric scaffold with sustained Mg2+ release for promoting the regeneration of neuro-vascularized bone tissue in vivo, which offers new insights for regenerative medicine.

IntroductionThis paper examines the association between the dietary inflammatory index (DII) and the risk of metabolic syndrome (MS) and its components among Uygur adults in Kashi, Xinjiang.MethodsThe study used the multi-stage random cluster sampling method to investigate the adult residents of Uighu aged over 18 years old in one county and one township/street of three cities in Kashi between May and June 2021. All dietary data collected were analyzed for energy and nutrient intake with a nutritional analysis software, followed by a calculation of DII. Logistic regression was used to estimate the association between DII and the risks of MS and its components.ResultsThe maximum DII value across our 1,193 respondents was 4.570 to 4.058, with an average value of 0.256. When we analyzed the DII as a continuous variable, we determined the anti-inflammatory diet has been identified as a mitigating factor for metabolic syndrome (OR = 0.586, 95% CI = 0.395–0.870), obesity (OR = 0.594, 95% CI = 0.395–0.870), elevated fasting glucose levels (OR = 0.422, 95% CI = 0.267–0.668), and hypertension (OR = 0.698, 95% CI = 0.488–0.996). When the model was adjusted by sex, age, and occupation, we found a significant correlation between high- and low-density lipoproteinemia and DII (OR = 1.55, 95% CI = 1.040–2.323). The present study identified four distinct dietary patterns among the population under investigation. There was a linear trend in the incidence of MS and hypertension across low, middle, and high levels of fruits and milk dietary pattern model (p = 0.027; p = 0.033), within this dietary pattern may serve as protective factors against MS and hypertension, suggesting that fruits and milk within this dietary pattern may serve as protective factors against MS and hypertension. And the linear trend in the incidence of elevated fasting glucose and obesity across the low, medium, and high scores of meet and eggs dietary pattern (p = 0.006; p

Background & Aims: The immune tolerance induced by hepatitis B virus (HBV) is a major challenge for achieving effective viral clearance, and the mechanisms involved are not well-understood. One potential factor involved in modulating immune responses is mesencephalic astrocyte-derived neurotrophic factor (MANF), which has been reported to be increased in patients with chronic hepatitis B. In this study, our objective is to examine the role of MANF in regulating immune responses to HBV. Methods: We utilized a commonly used HBV-harboring mouse model, where mice were hydrodynamically injected with the pAAV/HBV1.2 plasmid. We assessed the HBV load by measuring the levels of various markers including hepatitis B surface antigen, hepatitis B envelope antigen, hepatitis B core antigen, HBV DNA, and HBV RNA. Results: Our study revealed that following HBV infection, both myeloid cells and hepatocytes exhibited increased expression of MANF. Moreover, we observed that mice with myeloid-specific MANF knockout (ManfMye-/-) displayed reduced HBV load and improved HBV-specific T cell responses. The decreased HBV-induced tolerance in ManfMye-/- mice was associated with reduced accumulation of myeloid-derived suppressor cells (MDSCs) in the liver. Restoring MDSC levels in ManfMye-/- mice through MDSC adoptive transfer reinstated HBV-induced tolerance. Mechanistically, we found that MANF promoted MDSC expansion by activating the IL-6/STAT3 pathway. Importantly, our study demonstrated the effectiveness of a combination therapy involving an hepatitis B surface antigen vaccine and nanoparticle-encapsulated MANF siRNA in effectively clearing HBV in HBV-carrier mice. Conclusion: The current study reveals that MANF plays a previously unrecognized regulatory role in liver tolerance by expanding MDSCs in the liver through IL-6/STAT3 signaling, leading to MDSC-mediated CD8+ T cell exhaustion.

Abstract Bladder cancer (BC) is one of the most prevalent malignancies in men. Understanding molecular characteristics via studying signaling pathways has made tremendous breakthroughs in BC therapies. Thus, targeted therapies including immune checkpoint inhibitors (ICIs), antibody–drug conjugates (ADCs), and tyrosine kinase inhibitor (TKI) have markedly improved advanced BC outcomes over the last few years. However, the considerable patients still progress after a period of treatment with current therapeutic regimens. Therefore, it is crucial to guide future drug development to improve BC survival, based on the molecular characteristics of BC and clinical outcomes of existing drugs. In this perspective, we summarize the applications and benefits of these targeted drugs and highlight our understanding of mechanisms of low response rates and immune escape of ICIs, ADCs toxicity, and TKI resistance. We also discuss potential solutions to these problems. In addition, we underscore the future drug development of targeting metabolic reprogramming and cancer stem cells (CSCs) with a deep understanding of their signaling pathways features. We expect that finding biomarkers, developing novo drugs and designing clinical trials with precisely selected patients and rationalized drugs will dramatically improve the quality of life and survival of patients with advanced BC.

AbstractBackground Chronic kidney disease-associated pruritus (CKD-aP) is very common and sometimes refractory to treatment in hemodialysis patients. In a trial conducted in Japan, nalfurafine, effectively reduced itching of treatment-resistant CKD-aP. Our present bridging study aimed to evaluate the efficacy and safety of nalfurafine in Chinese cohort with refractory CKD-aP.Methods In this phase III, multicenter bridging study conducted at 22 sites in China, 141 Chinese cases with refractory CKD-aP were randomly (2:2:1) assigned to receive 5 μg, 2.5 μg of nalfurafine or a placebo orally for 14 days in a double-blind manner. The primary end point was the mean decrease in the mean visual analogue scale (VAS) from baseline.Results A total of 141 patients were included. The primary endpoint analysis based on full analysis set (FAS), the difference of mean VAS decrease between 5 μg nalfurafine and placebo group was 11.37 mm (p = .041); the difference of mean VAS decrease between 2.5 μg and placebo group was 8.81 mm (p = .110). Both differences were greater than 4.13 mm, which met its predefined success criterion of at least 50% efficacy of the key Japanese clinical trial. The per protocol set (PPS) analysis got similar results. The incidence of adverse drug reactions (ADRs) was 49.1% in 5μg, 38.6% in 2.5 μg and 33.3% in placebo group. The most common ADR was insomnia, seen in 21 of the 114 nalfurafine patients.Conclusions Oral nalfurafine effectively reduced itching with few significant ADRs in Chinese hemodialysis patients with refractory pruritus.

Abstract Background Flavor contributes to the sensory quality of fruits, including taste and aroma aspects. The quality of foods is related to their flavor-associated compounds. Pear fruits have a fruity sense of smell, and esters are the main contributor of the aroma. Korla pear are well known due to its unique aroma, but the mechanism and genes related to volatile synthesis have not been fully investigated. Results Flavor-associated compounds, including 18 primary metabolites and 144 volatiles, were characterized in maturity fruits of ten pear cultivars from five species, respectively. Based on the varied metabolites profiles, the cultivars could be grouped into species, respectively, by using orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 14 volatiles were selected as biomarkers to discriminate Korla pear (Pyrus sinkiangensis) from others. Correlation network analysis further revealed the biosynthetic pathways of the compounds in pear cultivars. Furthermore, the volatile profile in Korla pear throughout fruit development was investigated. Aldehydes were the most abundant volatiles, while numerous esters consistently accumulated especially at the maturity stages. Combined with transcriptomic and metabolic analysis, Ps5LOXL, PsADHL, and PsAATL were screened out as the key genes in ester synthesis. Conclusion Pear species can be distinguished by their metabolic profiles. The most diversified volatiles as well as esters was found in Korla pear, in which the enhancement of lipoxygenase pathway may lead to the high level of volatile esters at maturity stages. The study will benefit the fully usage of pear germplasm resources to serve fruit flavor breeding goals.

Abstract Background To examine the association between elevated serum uric acid (SUA) levels and the rapid decline in kidney function by conducting a retrospective cohort study on a physically healthy population in Urumqi, China. Methods A cohort study of 2,802 physically healthy people with a normal estimated glomerular filtration rate (eGFR) was investigated from 2018 to 2021. The examination procedure included using questionnaires, taking physical measurements, and blood sampling. The rapid decline in kidney function was defined as eGFR > 5 mL·min–1 ·(1.73 m2 )–1 year. The relationship between elevated SUA levels and the rapid decline in kidney function was assessed. Results When performing the three-year retrospective analysis, 688 (28.55%) cases experienced a rapid decline in kidney function, and 52 (1.9%) cases developed chronic kidney disease (CKD). They were divided into the stable group and the rapidly declining kidney function group according to eGFR > 15 mL·min–1·(1.73 m2 )–1. The comparison revealed a greater increase in uric acid in the rapidly declining kidney function group [0.30 (-0.29, 0.82) mg/dL vs. − 0.07(-0.54, 0.37) mg/dL, Z = − 8.822, P

Abstract Intense debate persists about the timing and magnitude of the wet phases in the East Asia deserts since the late Pleistocene. Here we show reconstructions of the paleohydrology of the East Gobi Desert since the last interglacial using satellite images and digital elevation models (DEM) combined with detailed section analyses. Paleolakes with a total area of 15,500 km2 during Marine Isotope Stage 5 (MIS 5) were identified. This expanded lake system was likely coupled to an 800–1000 km northward expansion of the humid region in East China, associated with much warmer winters. Humid climate across the Gobi Desert during MIS 5 likely resulted in a dustier MIS 4 over East Asia and the North Pacific. A second wet period characterized by an expanded, albeit smaller, lake area is dated to the mid-Holocene. Our results suggest that the East Asian Summer Monsoon (EASM) might have been much weaker during MIS 3.

Abstract Noncanonical epitopes presented by Human Leucocyte Antigen class I (HLA-I) complexes to CD8+ T cells attracted the spotlight in the research of novel immunotherapies against cancer, infection and autoimmunity. Proteasomes, which are the main producers of HLA-I-bound antigenic peptides, can catalyze both peptide hydrolysis and peptide splicing. The prediction of proteasome-generated spliced peptides is an objective that still requires a reliable (and large) database of non-spliced and spliced peptides produced by these proteases. Here, we present an extended database of proteasome-generated spliced and non-spliced peptides, which was obtained by analyzing in vitro digestions of 80 unique synthetic polypeptide substrates, measured by different mass spectrometers. Peptides were identified through invitroSPI method, which was validated through in silico and in vitro strategies. The peptide product database contains 16,631 unique peptide products (5,493 non-spliced, 6,453 cis-spliced and 4,685 trans-spliced peptide products), and a substrate sequence variety that is a valuable source for predictors of proteasome-catalyzed peptide hydrolysis and splicing. Potential artefacts and skewed results due to different identification and analysis strategies are discussed.

Abstract To characterize the gut bacteriome, mycobiome and serum metabolome profiles in polycystic ovary syndrome (PCOS) patients with normal/overweight individuals and evaluate a potential microbiota-related diagnostic method development for PCOS, 16S rRNA and ITS2 gene sequencing using 88 fecal samples and 87 metabolome analysis from serum samples are conducted and PCOS classifiers based on multiomics markers are constructed. There are significant bacterial, fungal community and metabolite differences among PCOS patients and healthy volunteers with normal/overweight individuals. Healthy individuals with overweight/obesity display less abnormal metabolism than PCOS patients and uniquely higher abundance of the fungal genus Mortierella. Nine bacterial genera, 4 predicted pathways, 11 fungal genera and top 30 metabolites are screened out which distinguish PCOS from healthy controls, with AUCs of 0.84, 0.64, 0.85 and 1, respectively. The metabolite-derived model is more accurate than the microbe-based model in discriminating normal BMI PCOS (PCOS-LB) from normal BMI healthy (Healthy-LB), PCOS-HB from Healthy-HB. Featured bacteria, fungi, predicted pathways and serum metabolites display higher associations with free androgen index (FAI) in the cooccurrence network. In conclusion, our data reveal that hyperandrogenemia plays a central role in the dysbiosis of intestinal microecology and the change in metabolic status in patients with PCOS and that its effect exceeds the role of BMI. Healthy women with high BMI showed unique microbiota and metabolic features.The priority of predictive models in discriminating PCOS from healthy status in this study were serum metabolites, fungal taxa and bacterial taxa.

In this study, a total of 16 LAB strains, isolated from soy sauce residue in the early stage of our research group, were evaluated for their antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, the bacteriostatic substances and growth characteristics of these strains were investigated. The results showed that LAB strains ZW2, ZW9 and ZW14 exhibited high antibacterial activity against E. coli and S. aureus, of which ZW9 had the best antibacterial effect. After eliminating the interference factors such as the organic acids and hydrogen peroxides, three strains still maintained antimicrobial activity. However, the inhibitory activity decreased by the treatment with trypsin, pepsin, proteinase K, α-amylase, alkaline protease and neutral protease (P

On 1 June 2022, a magnitude 6.1 earthquake struck the southern segment of the Longmenshan fault zone on the eastern edge of the Tibetan Plateau, once again causing casualties and economic losses. Understanding the deep-seated dynamic mechanisms that lead to seismic events in the Lushan earthquake area and assessing the potential hazards in seismic gap areas are of significant importance. In this study, we utilized 118 magnetotelluric datasets collected from the Lushan earthquake area and employed three-dimensional electromagnetic inversion with topographic considerations to characterize the deep-seated three-dimensional resistivity structure of the Lushan earthquake area. The results reveal that the Shuangshi–Dachuan fault in the Lushan earthquake area can be divided into two relatively low-resistivity zones: a western zone dipping southeastward and an eastern zone with a steeper slightly northwestern dip. These two zones intersect at a depth of approximately 20 km, forming an extensional pattern resembling a “Y” shape. The epicenters of both the 2013 and 2022 Lushan earthquakes are primarily located in the upper constricted portion of the pocket-like low-resistivity body at depth. The distribution of seismic aftershocks is confined within the region enclosed by the high-resistivity body, following the pattern of the Y-shaped low-resistivity zone.

Pear black spot disease, caused by Alternaria alternata, is a devastating disease in pears and leads to enormous economic losses worldwide. In this investigation, we isolated a Streptomyces odonnellii SZF-179 from the rhizosphere soil of pear plants in China. Indoor confrontation experiments results showed that both SZF-179 and its aseptic filtrate had excellent inhibitory effects against A. alternata. Afterwards, the main antifungal compound of SZF-179 was identified as polyene, with thermal and pH stability in the environment. A microscopic examination of A. alternata mycelium showed severe morphological abnormalities caused by SZF-179. Protective studies showed that SZF-179 fermentation broth could significantly reduce the diameter of the necrotic lesions on pear leaves by 42.25%. Furthermore, the potential of fermentation broth as a foliar treatment to control black leaf spot was also evaluated. Disease indexes of ‘Hosui’ and ‘Wonwhang’ pear plants treated with SZF-179 fermentation broth were lower than that of control plants. Overall, SZF-179 is expected to be developed into a safe and broad-spectrum biocontrol agent. No studies to date have evaluated the utility of S. odonnellii for the control of pear black spot disease; our study fills this research gap. Collectively, our findings provide new insights that will aid the control of pear black spot disease, as well as future studies of S. odonnellii strains.

The polyphenol compounds in red jujube were extracted by ultrasonic-assisted extraction process. The methanol concentration, ultrasonic time, ultrasonic temperature and solid-liquid ratio were selected to conduct the single factor experiments. On this basis, the response surface methodology was used to optimize the process parameters, and the high-resolution liquid-mass spectrometer was used to determine the polyphenol components in red jujube to evaluate the antioxidant activity of the polyphenol based on its ability to remove DPPH and superoxide anion radicals. The results showed that, the optimal ultrasonic-assisted extraction conditions were as follows: Methanol concentration 70%, ultrasonic time 40 min, ultrasonic temperature 60℃, solid-liquid ratio 1:40 (g/mL). Under these conditions, the polyphenol yield was 1.397%±0.08%. A high-resolution liquid chromatography-mass spectrometry (HPLC-MS) method was developed for the determination of 19 components in jujube polyphenols, including phenolic acids and their derivatives, flavonoids and triterpenoids. The results of antioxidant experiments showed that the maximum clearance of DPPH was 77.63% when the polyphenol concentration of jujube was 0.3 mg/mL. The maximum clearance of superoxide anion radical was 82.48% when the concentration was 0.8 mg/mL, and with the increasing of polyphenol concentration, the clearance was close to VC, indicating that the polyphenol compound extracted from jujube had strong antioxidant activity and was a natural antioxidant with great development potential.

In this work, the authors report a sophisticated combination of genetic, biophysical, and biochemical analyses to identifies the cycling conformational states of PPM1D. The findings reveal how an allosteric inhibitor locks the protein into a conformationally inactive state, and explain the distribution of PPM1D activating mutations in cancer.

PurposeSpermatogonial stem cells (SSCs) are essential for maintaining reproductive function in males. B-lymphoma Mo-MLV insertion region 1 (BMI1) is a vital transcription repressor that regulates cell proliferation and differentiation. However, little is known about the role of BMI1 in mediating the fate of mammalian SSCs and in male reproduction. This study investigated whether BMI1 is essential for male reproduction and the role of alpha-tocopherol (α-tocopherol), a protective agent for male fertility, as a modulator of BMI1 both in vitro and in vivo.MethodsMethyl thiazolyl tetrazolium (MTT) and 5-ethynyl-2′-deoxyuridine (EDU) assays were used to assess the effect of BMI1 on the proliferative ability of the mouse SSC line C18-4. Real-time polymerase chain reaction (PCR), western blotting, and immunofluorescence were applied to investigate changes in the mRNA and protein expression levels of BMI1. Male mice were used to investigate the effect of α-tocopherol and a BMI1 inhibitor on reproduction-associated functionality in vivo.ResultsAnalysis revealed that BMI1 was expressed at high levels in testicular tissues and spermatogonia in mice. The silencing of BMI1 inhibited the proliferation of SSCs and DNA synthesis and enhanced the levels of γ-H2AX. α-tocopherol enhanced the proliferation and DNA synthesis of C18-4 cells, and increased the levels of BMI1. Notably, α-tocopherol rescued the inhibition of cell proliferation and DNA damage in C18-4 cells caused by the silencing of BMI1. Furthermore, α-tocopherol restored sperm count (Ctrl vs. PTC-209, p = 0.0034; Ctrl vs. PTC-209 + α-tocopherol, p = 0.7293) and normalized sperm malformation such as broken heads, irregular heads, lost and curled tails in vivo, as demonstrated by its antagonism with the BMI1 inhibitor PTC-209.ConclusionAnalysis demonstrated that α-tocopherol is a potent in vitro and in vivo modulator of BMI1, a transcription factor that plays an important role in in SSC proliferation and spermatogenesis. Our findings identify a new target and strategy for treating male infertility that deserves further pre-clinical investigation.

Abstract A major reason for the high mortality of patients with bladder cancer (BC) is that chemotherapy and surgery are only effective for very limited patients. Thus, developing novel treatment options becomes an urgent need for improving clinical outcomes and the quality of life for BC patients. Here, we demonstrated that proguanil significantly inhibited the growth of BC in vitro and in vivo. Importantly, our results indicated that the sensitivity of BC cells to proguanil is positively correlated with the expression of epidermal growth factor receptor (EGFR). Mechanistically, proguanil specifically targeted EGFR and promoted EGFR binding to Caveolin-1, enhanced its endocytosis in a Clathrin-independent manner, and then recruited c-Cbl to promote EGFR ubiquitination and degradation through the lysosomal pathway. Further studies suggested that proguanil induced autophagy by destabilizing EGFR and inhibiting its downstream signaling pathway. Thus, this study reveals the novel mechanism of proguanil on anticancer activity and implies the potential benefits of this drug in the treatment of BC.

Combinatorial CRISPR screens can be utilized to identify genetic interactions and functional redundancies of multiple genes. Here, the authors benchmark ten digenic CRISPR technologies and identify novel Cas9 tracrRNA combinations that show superior performance.

Our previous study found that the intravesical perfusion of metformin has excellent inhibitory effects against bladder cancer (BC). However, this administration route allows the drug to be diluted and excreted in urine. Therefore, increasing the adhesion of metformin to the bladder mucosal layer may prolong the retention time and increase the pharmacological activity. It is well known that chitosan (Cs) has a strong adhesion to the bladder mucosal layer. Thus, this study established a novel formulation of metformin to enhance its antitumor activity by extending its retention time. In this research, we prepared Cs freeze-dried powder and investigated the effect of metformin-loaded chitosan hydrogels (MLCH) in vitro and in vivo. The results showed that MLCH had a strong inhibitory effect against proliferation and colony formation in vitro. The reduction in BC weight and the expression of tumor biomarkers in orthotopic mice showed the robust antitumor activity of MLCH via intravesical administration in vivo. The non-toxic profile of MLCH was observed as well, using histological examinations. Mechanistically, MLCH showed stronger functional activation of the AMPKα/mTOR signaling pathway compared with metformin alone. These findings aim to make this novel formulation an efficient candidate for managing BC via intravesical administration.

Stock market volatility research has long been the focus of industry and academia, and stock trend forecasting is challenging. Existing research focuses more on how to aggregate historical price features into graph networks, ignoring the effects of other information such as news and current events on forecasts. Most existing graph-based learning methods create stock graphs by manually constructing stock relationships, ignoring the complexity of stock relationships. Based on these, we propose a novel multilevel graph attention network (ML-GAT) for predicting the stock market trends. To be more specific, we initialize the node representations captured by each feature extraction module, then update the stock nodes in the isomorphic graph converted from Wikidata using ML-GAT, selectively aggregate the information of various relation types, aggregate the information to the node representation, and finally feed the result to a particular forecast layer for forecasting, completing the trend forecast of 423 stocks in the S&P 500 index and 286 stocks in the CSI 300 index. By comparing 5 popular approaches, the experimental research verifies ML-GAT’S state-of-the-art performance in prediction tasks. In comparison with the best performance benchmark model, the F1-score and accuracy increased by 11.82% and 12.6%, respectively, and the average daily return and Sharpe rate rose by 5.06 percent and 94.81 percent, respectively. More significantly, our model’s stock linkages are interpretable and consistent with real-world interactions.

Abstract Background Bladder cancer is the second most common genitourinary malignancy and the eleventh most common cancer worldwide. Dihydroartemisinin (DHA), a first-line antimalarial drug, has been found to have potent antitumor activity. In our previous study, a novel dihydroartemisinin derivative Mito-DHA5 synthesized in our laboratory has a stronger anti-tumor activity than DHA. In this study, we investigated the apoptotic effect of Mito-DHA5 on bladder cancer T24 cells and molecular mechanisms underlying. Methods Antitumor activity in vitro was evaluated by MTT, wound healing and cloning formation assays. Mitochondrial membrane potential (MMP) was detected by JC-1 probe and ROS levels were measured by specific kit. The expression of caspase-3, cleaved-caspase3, mitochondrial Cyt-C, Bcl-2, Bax and PARP in T24 cells was evaluated by Western blotting. Results The results showed that Mito-DHA5 reduced cell viability with an IC50 value of 3.2 µM and induced T24 cell apoptosis in a dose-dependent manner, increased the production of ROS and decreased MMP. Mito-DHA5 could down-regulate the expression of Bcl-2, mitochondrial Cyt-C, Caspase-3, PARP and up-regulate the expression of Bax and cleaved Caspase-3. Conclusions These data suggested that Mito-DHA5 had a potent inhibitory effect on T24 bladder cancer cell growth and induced these cells apoptosis associated with mitochondrial pathway.

Abstract Hydrophilic polyethylene glycol monomethyl ether (mPEG) was grafted onto Icariin (ICA) by succinic anhydride to form a polyethylene glycol-Icariin (mPEG-ICA) polymer. The structure of the polymer was characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). mPEG-ICA nanoparticles loaded with ICA were prepared by physical embedding of ICA by dialysis. The particle size was determined to be (220 ± 13.7) nm, and the ζ potential was (2.30 ± 1.33) mV by dynamic light scattering (DLS). Under a transmission electron microscope (TEM), the nanoparticles were spherical, and the morphology was regular. In the medium with pH 7.4, the drug release rate of mPEG-ICA nanoparticles reached (52.80 ± 1.70)% within 72 h. At pH 6.8, the cumulative drug release of nanoparticles reached (75.66 ± 0.17)% within 48 h. Treatment of the nanoparticles with LPS-treated H9c2 cells maintained cell viability, reduced LDH release and exerted antiapoptotic effects. Moreover, ICA-loaded mPEG-ICA nanoparticles significantly decreased the mRNA expression of the myocardial inflammatory cytokines TNF-α, IL-1β and IL-6M. In conclusion, ICA-loaded mPEG-ICA nanoparticles protected against LPS-induced H9c2 cell injury.

Because of the coupling of CO2 absorption and treatment, conventional carbon capture power plants lack the flexibility of power plant operation. This paper provides a liquid storage carbon capture power plant (LSCCPP) with solution storage, analyzes the “energy time-shift” features of the solution storage, and creates a joint operating model of the LSCCPP and Power to Gas(P2G) based on this. Taking into account the carbon market trading mechanism, this paper develops a low-carbon economic dispatch model for an integrated electric-gas energy system with the LSCCPP, with the goal of achieving the lowest overall system cost. Moreover, the proposed dispatch model is solved by transforming the model into a mixed-integer linear programing problem and calling CPLEX. Finally, a modified example system is used to demonstrate the validity of the proposed model. The results show that the suggested low-carbon dispatch model has a significant reference for enhancing the system’s use of wind power and accomplishing the low-carbon efficient functioning of the integrated electric-gas energy system.

BackgroundColon cancer (CC) is a common tumor, but its pathogenesis is still not well understood. Competitive endogenous RNA (ceRNA) theory, ferroptosis and tumor immune infiltration may be the mechanisms of the development of cancer. The purpose of the study is to seek genes connected with both immunity and ferroptosis, and provide important molecular basis for early noninvasive diagnosis and immunotherapy of CC.MethodsWe extracted messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA) data of CC from The Cancer Genome Atlas database (TCGA), identified the differentially expressed mRNA (DEmRNA), miRNA (DEmiRNA) and lncRNA (DElncRNA), then constructed a ceRNA network. Venn overlap analysis was used to identify genes associated with immunity and ferroptosis in ceRNA network. The expression and prognosis of target genes were analyzed via Gene Expression Profiling Interactive Analysis (GEPIA) and PrognoScan database, and we analysed the related functions and signaling pathways of target genes by enrichment analysis. The correlation between target genes and tumor immune infiltrating was explored by CIBERSORT and spearman correlation analysis. Finally, the expression of target genes was detected via quantitative reverse transcription-PCR (qRT-PCR) in CC and normal colon tissues.ResultsResults showed that there were 4 DElncRNA, 4 DEmiRNA and 126 DEmRNA in ceRNA network. NADPH oxidase 4 protein (NOX4) was a DEmRNA associated with immunity and ferroptosis in ceRNA network. NOX4 was highly expressed in CC and connected with unfavourable prognosis. NOX4 was obviously enriched in pathways connected with carcinogenesis and significantly correlated with six kinds of immune cells. Immune checkpoints and NOX4 spearman correlation analysis showed that the expression of NOX4 was positively related to programmed cell death protein 1 (PD-1)-PDCD1, programmed cell death-Ligand 1 (PD-L1)-CD274 and cytotoxic T-lymphocyte-associated protein 4 (CTLA4).ConclusionsTo conclude, our study suggests that NOX4 is associated with both ferroptosis and tumor immunity, and might be a biomarker associated with the carcinogenesis, prognosis of CC and a potential target of CC immunotherapy.

Abstract This paper focuses on finite‐time synchronization and parameters identification in the Markovian switching complex delayed network with multiple weights. Considering the control cost required for network synchronization, finite‐time control technique and pinning control strategy are adopted. Based on these methods, when finite‐time synchronization of the network is achieved, the unknown parameters of the system can also be identified in finite time. In addition, in order to solve the problem of the network performance change caused by network topology switching, an Optimal Nodes Selection Control Strategy (ONSCS) is proposed. On the one hand, finite‐time synchronization and identification of the network can be realized faster, on the other hand, it also further reduces the energy consumption and control cost of the network. Finally, two sets of comparative numerical simulations are given to prove the superiority and applicability of the proposed ONSCS.

Abstract As an essential component of power transformers, the detection and diagnosis of incipient partial discharge (PD) activities of bushings are of great significance. A 35‐kV oil‐impregnated paper (OIP) bushing is investigated. The bushing is modelled by coaxial theory and electromagnetic (EM) simulation. As the paths of PD‐induced ultra‐high frequency (UHF) signal propagating in the bushing are OIPs and oil gap, small attenuation during signal propagation is seen. Since OIP is composed of heterogeneous media compared with pure oil, there will be relatively less UHF signal leakage from OIPs, whereas more leakage from the oil gap. This leakage provides the possibility of non‐contact detection outside the bushing by UHF method. PD measurements with UHF method are carried out on the bushing. Then, the minimum energy method is used to extract time‐difference‐of‐arrival (TDOA), and Chan algorithm is adopted to locate points of UHF signal radiation. High accuracy locating with a small error of 15 cm has been achieved. The contactless UHF method‐based tests have demonstrated the effectiveness of online monitoring and locating of bushing PD.