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The complex fracture network provides the main channel for coalbed methane seepage, and its structural characteristics significantly affect the productivity of coalbed methane. In view of the lack of fracture network connectivity in existing coalbed methane seepage models, based on topological graph theory, the connectivity characteristics of fracture network were analyzed, and the expression of power law relation of fracture branch length was derived. Combined with fractal geometry, a permeability model considering fracture network structure characteristics was established on the basis of classical cubic law. The model shows that the permeability of fracture network is a function of fractal dimension, porosity, tortuosity fractal dimension, scale coefficient, connectivity, maximum fracture branch length, azimuth angle, dip angle and feature length. The permeability evolution of fracture network under true triaxial stress was analyzed. The results show that with the increase of the principal stresses σ1, σ2 and σ3, the fractures in coal are gradually compressed and the gas seepage channel becomes narrow. The permeability of fracture network shows a negative exponential decrease with the increase of the principal stresses σ1, σ2 and σ3. Based on the experimental rules and results, the fracture network fractal permeability model and S&D model (Shi-Durucan) were combined to establish the fracture network permeability calculation model under true triaxial stress. The effectiveness of the model was verified by the experimental data. The obtained permeability variation trend is consistent with the process of loading the three principal stresses, which can reflect the influence trend of the change of three-way stress on the permeability. Compared with the S&D model, it can better reflect the anisotropy characteristics of the permeability of the fracture network.

Abstract Frataxin (FXN) is required for iron-sulfur cluster biogenesis, and its loss causes the early-onset neurodegenerative disease Friedreich ataxia (FRDA). Loss of FXN is a susceptibility factor in the development of diabetes, a common metabolic complication after myocardial hypertrophy in patients with FRDA. The underlying mechanism of FXN deficient-induced hyperglycemia in FRDA is, however, poorly understood. In this study, we confirmed that the FXN deficiency mouse model YG8R develops insulin resistance in elder individuals by disturbing lipid metabolic homeostasis in adipose tissues. Evaluation of lipolysis, lipogenesis, and fatty acid β-oxidation showed that lipolysis is most severely affected in white adipose tissues. Consistently, FXN deficiency significantly decreased expression of lipolytic genes encoding adipose triglyceride lipase (Atgl) and hormone-sensitive lipase (Hsl) resulting in adipocyte enlargement and inflammation. Lipolysis induction by fasting or cold exposure remarkably upregulated FXN expression, though FXN deficiency lessened the competency of lipolysis compared with the control or wild type mice. Moreover, we found that the impairment of lipolysis was present at a young age, a few months earlier than hyperglycemia and insulin resistance. Forskolin, an activator of lipolysis, or pioglitazone, an agonist of PPARγ, improved insulin sensitivity in FXN-deficient adipocytes or mice. We uncovered the interplay between FXN expression and lipolysis and found that impairment of lipolysis, particularly the white adipocytes, is an early event, likely, as a primary cause for insulin resistance in FRDA patients at later age.

In this paper, a hybrid integrated broadband Doherty power amplifier (DPA) based on a multi-chip module (MCM), whose active devices are fabricated using the gallium nitride (GaN) process and whose passive circuits are fabricated using the gallium arsenide (GaAs) integrated passive device (IPD) process, is proposed for 5G massive multiple-input multiple-output (MIMO) application. An inverted DPA structure with a low-Q output network is proposed to achieve better bandwidth performance, and a single-driver architecture is adopted for a chip with high gain and small area. The proposed DPA has a bandwidth of 4.4–5.0 GHz that can achieve a saturation of more than 45.0 dBm. The gain compression from 37 dBm to saturation power is less than 4 dB, and the average power-added efficiency (PAE) is 36.3% with an 8.5 dB peak-to-average power ratio (PAPR) in 4.5–5.0 GHz. The measured adjacent channel power ratio (ACPR) is better than −50 dBc after digital predistortion (DPD), exhibiting satisfactory linearity.

Nitrogen in digested swine wastewater is currently difficult to directly degrade by an activated sludge process in a sequencing batch reactor (SBR), with resulting failure of the effluent to meet emission standards. In this study, rice husk biochar was optionally added into SBR to enhance biochemical properties for digested swine wastewater, especially for nitrogen degradation. The relative nitrogen removal mechanism for microbial community was probed by means of high-throughput sequencing. The results indicated that chemical oxygen demand (COD), ammonia (NH4+-N), and total nitrogen (TN) removal efficiency of digested swine wastewater was separately at 85.3%, 81.3%, and 65.2% using rice husk biochar with biofilm, which was 3.5%, 24.4%, and 14.7% higher than that of activated sludge, under influent of 2609 mg·L-1 COD, 337.0 mg·L-1 NH4+-N, 344 mg/L TN, and 7.77 C/N. High-throughput sequencing revealed that rice husk biochar with biofilm contained Proteobacteria, Thauera, Comamonas, Acinetobacter, Pseudomonas, Flavobacterium, and Corynebacterium to enhance nitrogen removal of digested swine wastewater. The results not only provide theoretical support for biochar with biofilm to improve digested piggery wastewater treatment, but also have great significance in resource utilization of agricultural waste and eco-environmental protection.

Abstract miRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3’-untranslated regions (3’-UTR) in the mRNA of LYPD3. Consequently, this interaction accelerates the metastasis of HNSCC. Notably, clinical observations indicate a correlation between high expression of miR-151-5p and low levels of LYPD3 in clinical settings are correlated with poor prognosis of HNSCC patients. Furthermore, our investigation demonstrates that glycosylation of LYPD3 modulates its subcellular localization and reinforces its role in suppressing HNSCC metastasis. Additionally, we uncover a potential regulatory mechanism involving the facilitation of miR-151-5p maturation and accumulation through N6-methyladenosine (m6A) modification. This process is orchestrated by methyltransferase-like 3 (METTL3) and mediated by a newly identified reader, heterogeneous nuclear ribonucleoprotein U (hnRNP U). These findings collectively underscore the significance of the METTL3/miR-151-5p/LYPD3 axis serves as a prominent driver in the malignant progression of HNSCC.

Abstract Background Acute monocytic leukemia-M5 (AML-M5) remains a challenging disease due to its high morbidity and poor prognosis. In addition to the evidence mentioned earlier, several studies have shown that programmed cell death (PCD) serves a critical function in treatment of AML-M5. However, the role and relationship between ferroptosis and necroptosis in AML-M5 remains unclear. Methods THP-1 cells were mainly treated with Erastin and IMP-366. The changes of ferroptosis and necroptosis levels were detected by CCK-8, western blot, quantitative real-time PCR, and electron microscopy. Flow cytometry was applied to detect the ROS and lipid ROS levels. MDA, 4-HNE, GSH and GSSG were assessed by ELISA kits. Intracellular distribution of FSP1 was studied by immunofluorescent staining and western blot. Results The addition of the myristoylation inhibitor IMP-366 to erastin-treated acute monocytic leukemia cell line THP-1 cell not only resulted in greater susceptibility to ferroptosis characterized by lipid peroxidation, glutathione (GSH) depletion and mitochondrial shrinkage, as the FSP1 position on membrane was inhibited, but also increased p-RIPK1 and p-MLKL protein expression, as well as a decrease in caspase-8 expression, and triggered the characteristic necroptosis phenomena, including cytoplasmic translucency, mitochondrial swelling, membranous fractures by FSP1 migration into the nucleus via binding importin α2. It is interesting to note that ferroptosis inhibitor fer-1 reversed necroptosis. Conclusion We demonstrated that inhibition of myristoylation by IMP-366 is capable of switching ferroptosis and ferroptosis-dependent necroptosis in THP-1 cells. In these findings, FSP1-mediated ferroptosis and necroptosis are described as alternative mechanisms of PCD of THP-1 cells, providing potential therapeutic strategies and targets for AML-M5.

Abstract Imetelstat is a novel, first‐in‐class, oligonucleotide telomerase inhibitor in development for the treatment of hematologic malignancies including lower‐risk myelodysplastic syndromes and myelofibrosis. A nonlinear mixed‐effects model was developed to characterize the population pharmacokinetics of imetelstat and identify and quantify covariates that contribute to its pharmacokinetic variability. The model was developed using plasma concentrations from 7 clinical studies including 424 patients with solid tumors or hematologic malignancies who received single‐agent imetelstat via intravenous infusion at various dose levels (0.4–11.7 mg/kg) and schedules (every week to every 4 weeks). Covariate analysis included factors related to demographics, disease, laboratory results, renal and hepatic function, and antidrug antibodies. Imetelstat was described by a two‐compartment, nonlinear disposition model with saturable binding/distribution and dose‐ and time‐dependent elimination from the central compartment. Theory‐based allometric scaling for body weight was included in disposition parameters. The final covariates included sex, time, malignancy, and dose on clearance; malignancy and sex on volume of the central compartment; and malignancy and spleen volume on concentration of target. Clearance in females was modestly lower, resulting in nonclinically relevant increases in predicted exposure relative to males. No effects on imetelstat pharmacokinetics were identified for mild‐to‐moderate hepatic or renal impairment, age, race, and antidrug antibody status. All model parameters were estimated with adequate precision (relative standard error

Abstract Background Pancreatic cancer is one of the most lethal malignancies and the lack of treatment options makes it more deadly. Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has revolutionized cancer treatment and made great breakthroughs in treating hematological malignancies, however its success in treating solid cancers remains limited mainly due to the lack of tumor-specific antigens. On the other hand, the prolonged traditional manufacturing process poses challenges, taking 2 to 6 weeks and impacting patient outcomes. CD276 has recently emerged as a potential therapeutic target for anti-solid cancer therapy. Here, we investigated the efficacy of CD276 CAR-T and rapidly-manufactured CAR-T against pancreatic cancer. Methods In the present study, CD276 CAR-T was prepared by CAR structure carrying 376.96 scFv sequence, CD8 hinge and transmembrane domain, 4-1BB and CD3ζ intracellular domains. Additionally, CD276 rapidly-manufactured CAR-T (named CD276 Dash CAR-T) was innovatively developed by shortening the duration of ex vitro culture to reduce CAR-T manufacturing time. We evaluated the anti-tumor efficacy of CD276 CAR-T and further compared the functional assessment of Dash CAR-T and conventional CAR-T in vitro and in vivo by detecting the immunophenotypes, killing ability, expansion capacity and tumor-eradicating effect of CAR-T. Results We found that CD276 was strongly expressed in multiple solid cancer cell lines and that CD276 CAR-T could efficiently kill these solid cancer cells. Moreover, Dash CAR-T was successfully manufactured within 48–72 h and the functional validation was carried out subsequently. In vitro, CD276 Dash CAR-T possessed a less-differentiated phenotype and robust proliferative ability compared to conventional CAR-T. In vivo xenograft mouse model, CD276 Dash CAR-T showed enhanced anti-pancreatic cancer efficacy and T cell expansion. Besides, except for the high-dose group, the body weight of mice was maintained stable, and the state of mice was normal. Conclusions In this study, we proved CD276 CAR-T exhibited powerful activity against pancreatic cancer cells in vitro and in vivo. More importantly, we demonstrated the manufacturing feasibility, acceptable safety and superior anti-tumor efficacy of CD276 Dash CAR-T generated with reduced time. The results of the above studies indicated that CD276 Dash CAR-T immunotherapy might be a novel and promising strategy for pancreatic cancer treatment.

Abstract RNF214 is an understudied ubiquitin ligase with little knowledge of its biological functions or protein substrates. Here we show that the TEAD transcription factors in the Hippo pathway are substrates of RNF214. RNF214 induces non-proteolytic ubiquitylation at a conserved lysine residue of TEADs, enhances interactions between TEADs and YAP, and promotes transactivation of the downstream genes of the Hippo signaling. Moreover, YAP and TAZ could bind polyubiquitin chains, implying the underlying mechanisms by which RNF214 regulates the Hippo pathway. Furthermore, RNF214 is overexpressed in hepatocellular carcinoma (HCC) and inversely correlates with differentiation status and patient survival. Consistently, RNF214 promotes tumor cell proliferation, migration, and invasion, and HCC tumorigenesis in mice. Collectively, our data reveal RNF214 as a critical component in the Hippo pathway by forming a signaling axis of RNF214-TEAD-YAP and suggest that RNF214 is an oncogene of HCC and could be a potential drug target of HCC therapy.

With the rapid development of emerging photovoltaics technology in recent years, the application of building-integrated photovoltaics (BIPVs) has attracted the research interest of photovoltaic communities. To meet the practical application requirements of BIPVs, in addition to the evaluation indicator of power conversion efficiency (PCE), other key performance indicators such as heat-insulating ability, average visible light transmittance (AVT), color properties, and integrability are equally important. The traditional Si-based photovoltaic technology is typically limited by its opaque properties for application scenarios where transparency is required. The emerging PV technologies, such as organic and perovskite photovoltaics are promising candidates for BIPV applications, owing to their advantages such as high PCE, high AVT, and tunable properties. At present, the PCE of semitransparent perovskite solar cells (ST-PSCs) has attained 14% with AVT of 22–25%; for semitransparent organic solar cells (ST-OSCs), the PCE reached 13% with AVT of almost 40%. In this review article, we summarize recent advances in material selection, optical engineering, and device architecture design for high-performance semitransparent emerging PV devices, and discuss the application of optical modeling, as well as the challenges of commercializing these semitransparent solar cells for building-integrated applications.

Abstract Background Pretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug. Methods To investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020. Results We observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2–4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes. Conclusions Our results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.

Abstract Phosphoric acid doped proton exchange membranes often experience performance degradation above 200 °C due to membrane creeping and phosphoric acid evaporation, migration, dehydration, and condensation. To address these issues, here we present gel-state polybenzimidazole membranes with double cross-linked three-dimensional layered structures via a polyphosphoric acid sol-gel process, enabling stable operation above 200 °C. These membranes, featuring proton-conducting cross-linking phosphate bridges and branched polybenzimidazole networks, effectively anchor and retain phosphoric acid molecules, prevent 96% of its dehydration and condensation, improve creep resistance, and maintain excellent proton conductivity stability. The resulting membrane, with superior through-plane proton conductivity of 0.348 S cm−1, delivers outstanding peak power densities ranging from 1.20–1.48 W cm−2 in fuel cells operated at 200-240 °C and a low voltage decay rate of only 0.27 mV h−1 over a 250-hour period at 220 °C, opening up possibilities for their direct integration with methanol steam reforming systems.

Fe-C-Cr-Nb alloy steel surfacing layers with different contents of C and Cr were prepared on 45 steel base metal by selfshielded flux-cored wires with distinct amounts of high carbon chromium iron addition and melt arc surfacing. The composition and microstructure changes of the surfacing layer were tested and analyzed. The surfacing test plate was processed into a pulling specimen, and the bonding strength between the surfacing layer and the 45 steel base metal was tested with a self-designed pulling test method. The fracture location of the pulling specimen and fracture characteristics were observed by a metallurgical microscope and a scanning electron microscope. The result shows that with the increase of the amount of high carbon chromium iron added to flux-cored welding wire, the content of C and Cr in the surfacing layer increases, and the NbC hard phase disperses. The microstructure of the steel matrix changes from mixed martensite + residual austenite to high carbon martensite + residual austenite, and then independent austenite appears. The hardness of the surfacing layer first increases and then decreases. The bonding strength between the surfacing alloy and the 45 steel base metal first decreases and then increases, and the fracture location is at the bottom of the surfacing layer or the fusion zone with mostly quasi-cleavage characteristics. When the additional amount of high carbon chromium iron reaches 13%, thee pulling specimen exhibits significant deformation with the highest bonding strength, and the fracture is close to the fusion line, where there are numerous tearing edges and shallow dimples.

Abstract Large-scale marine heatwaves in the Northeast Pacific (NEP), identified here and previously as ‘warm blobs’, have devastating impacts on regional ecosystems. An anomalous atmospheric ridge over the NEP is known to be crucial for maintaining these warm blobs, also causing abnormally cold temperatures over North America during the cold season. Previous studies linked this ridge to teleconnections from tropical sea surface temperature anomalies. However, it was unclear whether teleconnections from the extratropics could also contribute to the ridge. Here we show that planetary wave trains, triggered by increased rainfall and latent heat release over the Mediterranean Sea accompanied by decreased rainfall over the North Atlantic, can transport wave energy to the NEP, guided by the westerly jet, and induce a quasi-barotropic ridge there. Our findings provide insights into extratropical teleconnections sustaining the NEP ridge, offering a source of potential predictability for the warm blobs and temperature fluctuations over North America.

Abstract Background Few studies are focusing on the mechanism of erastin acts on prostate cancer (PCa) cells, and essential ferroptosis-related genes (FRGs) that can be PCa therapeutic targets are rarely known. Methods In this study, in vitro assays were performed and RNA-sequencing was used to measure the expression of differentially expressed genes (DEGs) in erastin-induced PCa cells. A series of bioinformatic analyses were applied to analyze the pathways and DEGs. Results Erastin inhibited the expression of SLC7A11 and cell survivability in LNCaP and PC3 cells. After treatment with erastin, the concentrations of malondialdehyde (MDA) and Fe2+ significantly increased, whereas the glutathione (GSH) and the oxidized glutathione (GSSG) significantly decreased in both cells. A total of 295 overlapping DEGs were identified under erastin exposure and significantly enriched in several pathways, including DNA replication and cell cycle. The percentage of LNCaP and PC3 cells in G1 phase was markedly increased in response to erastin treatment. For four hub FRGs, TMEFF2 was higher in PCa tissue and the expression levels of NRXN3, CLU, and UNC5B were lower in PCa tissue. The expression levels of SLC7A11 and cell survivability were inhibited after the knockdown of TMEFF2 in androgen-dependent cell lines (LNCaP and VCaP) but not in androgen-independent cell lines (PC3 and C4-2). The concentration of Fe2+ only significantly increased in TMEFF2 downregulated LNCaP and VCaP cells. Conclusion TMEFF2 might be likely to develop into a potential ferroptosis target in PCa and this study extends our understanding of the molecular mechanism involved in erastin-affected PCa cells.

Abstract Precise diagnostic biomarkers of anticitrullination protein antibody (ACPA)‐negative and early‐stage RA are still to be improved. We aimed to screen autoantibodies in ACPA‐negative patients and evaluated their diagnostic performance. The human genome‐wide protein arrays (HuProt arrays) were used to define specific autoantibodies from the sera of 182 RA patients and 261 disease and healthy controls. Statistical analysis was performed with SPSS 17.0. In Phase I study, 51 out of 19,275 recombinant proteins covering the whole human genome were selected. In Phase II validation study, anti‐ANAPC15 (anaphase promoting complex subunit 15) exhibited 41.8% sensitivity and 91.5% specificity among total RA patients. There were five autoantibodies increased in ACPA‐negative RA, including anti‐ANAPC15, anti‐LSP1, anti‐APBB1, anti‐parathymosin, and anti‐UBL7. Anti‐parathymosin showed the highest prevalence of 46.2% (p = 0.016) in ACPA‐negative early stage (

Background: Chronic pelvic pain (CPP) in women is a critical challenge. Due to the complex etiology and difficulties in diagnosis, it has a greatly negative impact on women's physical and mental health and the healthcare system. At present, there is still a lack of research on the related factors and predictive models of chronic pelvic pain in women. Our study aims to identify risk factors associated with chronic pelvic pain in women and develop a predictive nomogram specifically tailored to high-risk women with CPP. Materials and methods: From May to October 2022, trained interviewers conducted face-to-face questionnaire surveys and pelvic floor surface electromyography assessments on women from community hospitals in Nanjing. We constructed a multivariate logistic regression-based predictive model using CPP-related factors to assess the risk of chronic pelvic pain and create a predictive nomogram. Both internal and external validations were conducted, affirming the model's performance through assessments of discrimination, calibration, and practical applicability using area under the curve, calibration plots, and decision curve analysis. Results: 1108 women were recruited in total (survey response rate:1108/1200), with 169 (15.3 %) being diagnosed as chronic pelvic pain. Factors contributing to CPP included weight, dysmenorrhea, sexual dysfunction, urinary incontinence, a history of pelvic inflammatory disease, and the surface electromyography value of post-baseline rest. In both the training and validation sets, the nomogram exhibited strong discrimination abilities with areas under the curve of 0.85 (95 % CI: 0.81–0.88) and 0.85 (95 % CI: 0.79–0.92), respectively. The examination of the decision curve and calibration plot showed that this model fit well and would be useful in clinical settings. Conclusions: Weight, dysmenorrhea, sexual dysfunction, history of urinary incontinence and pelvic inflammatory disease, and surface electromyography value of post-baseline rest are independent predictors of chronic pelvic pain. The nomogram developed in this study serves as a valuable and straightforward tool for predicting chronic pelvic pain in women.

Photocatalytic water splitting into hydrogen production provides a new avenue to produce clean chemical fuels. However, developing high‐efficiency photocatalytic materials still remains a challenge till now. Herein, multiobjective‐optimization MoS2/Cd‐ZnIn2S4/CdS (MS/CZIS/CS) composites are successfully constructed by an in situ structure‐tailored technique. Benefiting from the synergistic feature integrating sulfur vacancy, II‐type CZIS/CS heterojunction and Schottky‐type MS/CS heterojunction, such composites not only effectively steer photogenerated carrier transfer but also markedly expedite surface reaction kinetics for hydrogen reduction reaction. As a result, an optimal hydrogen evolution rate of 11.49 mmol g−1 h−1 is achieved over the MS/CZIS/CS catalysts, which is approximately 4.79 times higher than that of pristine ZIS (2.40 mmol g−1 h−1). This work provides some new inspirations for the steering of carrier transfer and the design of multiobjective‐optimization photocatalysts with high efficiency.

Background: Sarcoma mainly originate from bone and soft tissue and are highly aggressive malignant tumors. Cell division cycle-related protein 3 (CDCA3) is a protein involved in the regulation of the cell cycle, which is highly expressed in a variety of malignant tumors. However, its role in sarcoma remains unclear. This study aims to investigate the function and potential mechanism of CDCA3 in sarcoma and to elucidate its importance in sarcoma. Methods: We first studied the expression and prognosis of CDCA family members in sarcoma by Oncomine and the Gene Expression Profiling Interactive Analysis (GEPIA). The role of CDCA3 protein in sarcoma was further analyzed by the Cancer Genome Atlas Program (TCGA), the Cancer Cell Lineage Encyclopedia (CCLE), and Linke-dOmics. In addition, immunohistochemistry and Western blot were used to verify the expression of CDCA3 protein in clinical samples as well as sarcoma cell lines (U2OS, SAOS2, MG63, and HOS). Subsequently, in vitro experiments (cloning and scratching experiments) were performed using sh-NC as well as sh-CDCA3 group cells to reveal the biological functions of CDCA3. Results: We found that the CDCA family (CDCA3, CDCA4, and CDCA8) is highly expressed in sarcoma, and the expression level of CDCA3, CDCA4, and CDCA8 negatively correlates with the prognosis of sarcoma patients. CDCA3 mRNA was highly expressed in pan-cancer by CCLE and TCGA database analysis. KEGG analysis showed that CDCA3 was mainly enriched in the cell cycle signaling pathway (It promoted the transition of the cell cycle from the G0/G1 phase to the S phase). In the level of immune infiltration, CDCA3 was negatively correlated with pDC cells, CD8+T cells, and cytotoxic cells. Finally, patients with high CDCA3 expression in sarcoma were analyzed for resistance to NU7441 and others, while sensitive to Fulvestrant and Dihydrorotenone. Furthermore, we demonstrated high expression of CDCA3 protein in sarcoma tissues and cell lines by immunohistochemistry and Western blot experiments. Cloning, EDU, scratching, and migration experiments showed that the knockdown of CDCA3 inhibited the Proliferation and progression of sarcoma cells. Conclusion: These results suggest for the first time that knockdown of CDCA3 may inhibit sarcoma progression. CDCA3 may be an effective target for the treatment of sarcoma.

In order to explore the pressure relief and permeability enhancement effect around coal seam slot cut by diamond-bead wire saw, firstly, the mechanical model of a doubly clamped roof beam based on the stress of the slot roof was established to analyze the force characteristics of the roof beam and the characteristics of the sinking contact bottom of slot roof (referred to as the contact bottom). Besides, the self-designed physical similarity simulation test platform was used to carry out various similar simulation tests to analyze the stress and displacement changes of coal and rock strata above and below the slot after cutting the seam using wire saw with different process parameters. Finally, based on the FLAC3D numerical simulation and the development of a coal seam gas permeability calculation program, the distribution characteristics and periodic evolution laws of stress and permeability of coal and rock mass around the advancing slot of the coal working face were analyzed. The research shows that the wire saw cuts seams, which makes the stress around the slot redistribute, and the slot roof passes through three evolution forms of roof hanging, roof contact with the bottom, and continuous sinking with the advancement of the working face. When the roof does not touch the bottom, the upper and lower parts of the slot form a ‘U’-type pressure relief zone. The maximum deflection is at the center of the roof, which is also the first part to contact the bottom. After the roof contacts the bottom, the stress recovery occurs in the middle of the slot, which weakens the pressure relief and permeability enhancement effect of the slot. The larger the diameter of the diamond-bead wire saw is, the larger the ultimate span of the roof bottom is, the later the slot contacts the bottom, and the better the pressure relief effect is. With the same slot diameter, the second slot is added, and the pressure relief zone of the two slots is connected. The pressure relief effects promote each other, which weakens the stress recovery under the action of the two slots and increases the pressure relief range. When the slot advancing distance is long enough, due to the roof contacting the bottom, the pressure relief and permeability enhancement effect on both sides of the slot is better. The influence range of pressure relief is divided into stress concentration zone, pressure relief zone, stress recovery zone, pressure relief zone and stress concentration zone from left to right. The corresponding pressure relief zone and stress recovery zone have a better permeability enhancement effect.

Abstract Background DNA damage repair (DDR) may affect tumorigenesis and therapeutic response in hepatocellular carcinoma (HCC). Long noncoding RNAs (LncRNAs) can regulate DDR and play a vital role in maintaining genomic stability in cancers. Here, we identified a DDR-related prognostic signature in HCC and explored its potential clinical value. Methods Data of HCC samples were obtained from the Cancer Genome Atlas (TCGA), and a list of DDR-related genes was extracted from the Molecular Signatures database (MSigDB). A DDR-related lncRNAs signature associated to overall survival (OS) was constructed using the least absolute shrinkage and selection operator-cox regression, and was further validated by the Kaplan-Meier curve and receiver operating characteristic curve. A nomogram integrating other clinical risk factors was established. Moreover, the relationships between the signature with somatic mutation, immune landscape and drug sensitivity were explored. Results The prognostic model of 5 DDR-related lncRNAs was constructed and classified patients into two risk groups at median cut-off. The low-risk group had a better OS, and the signature was an independent prognostic indicator in HCC. A nomogram of the signature combined with TNM stage was constructed. TP53 gene was more frequently mutated in the high-risk group. Marked differences in immune cells were observed, such as CD4 + T cells, NK cells and macrophages, between the two groups. Moreover, an increase in the expression of immune checkpoint molecules was found in the high-risk group. The low-risk group presented with a significantly higher response to sorafenib or cisplatin. Finally, potential value of this signature was validated in real-world HCC patients. Conclusion Our findings provided a promising insight into DDR-related lncRNAs in HCC and a personalized prediction tool for prognosis and therapeutic response.

Abstract Background The capsule of the zygapophyseal joint plays an important role in motion segmental stability maintenance. Iatrogenic capsule injury is a common phenomenon in posterior approach lumbar interbody fusion operations, but whether this procedure will cause a higher risk of adjacent segment degeneration acceleration biomechanically has yet to be identified. Methods Posterior lumbar interbody fusion (PLIF) with different grades of iatrogenic capsule injury was simulated in our calibrated and validated numerical model. By adjusting the cross-sectional area of the capsule, different grades of capsule injury were simulated. The stress distribution on the cranial motion segment was computed under different loading conditions to judge the potential risk of adjacent segment degeneration acceleration. Results Compared to the PLIF model with an intact capsule, a stepwise increase in the stress value on the cranial motion segment can be observed with a step decrease in capsule cross-sectional areas. Moreover, compared to the difference between models with intact and slightly injured capsules, the difference in stress values was more evident between models with slight and severe iatrogenic capsule injury. Conclusion Intraoperative capsule protection can reduce the potential risk of adjacent segment degeneration acceleration biomechanically, and iatrogenic capsule damage on the cranial motion segment should be reduced to optimize patients’ long-term prognosis.

Objective This study aimed to assess the impact of the dilution ratio of Tris diluent, storage at 0°C, and long-distance transportation on the spermatozoa of Simmental cattle. It also validated the feasibility of the regional distribution of fresh semen. Methods In experiment 1, semen was diluted at four dilution ratios (1:6, 1:9, 1:12, and 1:15) to determine the optimal dilution ratio of Tris diluent. In experiment 2, we assessed sperm viability, progressive motility (objectively assessed by computer-assisted sperm analyzer), and acrosome intactness in Tris dilutions kept at constant 0°C for 1, 3, 6, 9, and 12 days. We compared them to Tianshan livestock dilutions (Commercial diluent). In experiment 3, semen was diluted using Tris diluent, and sperm quality was measured before and after long-distance transport. Artificial insemination of 177 Simmental heifers compared to 156 using Tianshan Livestock dilution. Results The outcomes demonstrated that 1:9 was the ideal Tris diluent dilution ratio. The sperm viability, Progressive Motility, and acrosome integrity of both Tris and Tianshan dilutions preserved at 0°C gradually decreased over time. sperm viability was above 50% for both dilutions on d 9, with a flat rate of decline. The decrease in acrosome integrity rate was faster for Tianshan livestock dilutions than for Tris dilutions when stored at 0°C for 1 to 6 days. There was no significant difference (p>0.05) in sperm viability between semen preserved in Tris diluent after long-distance transportation and semen preserved in resting condition. The conception rates for Tris dilution and Tianshan livestock dilution were 49.15% and 46.15% respectively, with no significant difference (p>0.05). Conclusion This shows that Tris diluent is a good long-term protectant. It has been observed that fresh semen can be successfully preserved for long-distance transport when stored under 0°C conditions. Additionally, it is feasible to distribute semen regionally.

Abstract Over the long history of evolution, nature has developed a variety of biological systems with switchable recognition functions, such as the ion transmissibility of biological membranes, which can switch their ion selectivities in response to diverse stimuli. However, developing a method in an artificial host-guest system for switchable recognition of specific guests upon the change of external stimuli is a fundamental challenge in chemistry because the order in the host-guest affinity of a given system hardly varies along with environmental conditions. Herein, we report temperature-responsive recognition of two similar gaseous guests, CO2 and C2H2, with selectivities switched by temperature change by a diffusion-regulatory mechanism, which is realized by a dynamic porous crystal featuring ultrasmall pore apertures with flip-flop locally-motive organic moiety. The dynamic local motion regulates the diffusion process of CO2 and C2H2 and amplifies their rate differences, allowing the crystal to selectively adsorb CO2 at low temperatures and C2H2 at high temperatures with separation factors of 498 (CO2/C2H2) and 181 (C2H2/CO2), respectively.

Abstract Background Fibrous scars frequently form at the sites of bone nonunion when attempts to repair bone fractures have failed. However, the detailed mechanism by which fibroblasts, which are the main components of fibrous scars, impede osteogenesis remains largely unknown. Results In this study, we found that fibroblasts compete with osteogenesis in both human bone nonunion tissues and BMP2-induced ectopic osteogenesis in a mouse model. Fibroblasts could inhibit the osteoblastic differentiation of mesenchymal stem cells (MSCs) via direct and indirect cell competition. During this process, fibroblasts modulated the nuclear-cytoplasmic shuttling of YAP in MSCs. Knocking down YAP could inhibit osteoblast differentiation of MSCs, while overexpression of nuclear-localized YAP-5SA could reverse the inhibition of osteoblast differentiation of MSCs caused by fibroblasts. Furthermore, fibroblasts secreted DKK1, which further inhibited the formation of calcium nodules during the late stage of osteogenesis but did not affect the early stage of osteogenesis. Thus, fibroblasts could inhibit osteogenesis by regulating YAP localization in MSCs and secreting DKK1. Conclusions Our research revealed that fibroblasts could modulate the nuclear-cytoplasmic shuttling of YAP in MSCs, thereby inhibiting their osteoblast differentiation. Fibroblasts could also secrete DKK1, which inhibited calcium nodule formation at the late stage of osteogenesis.

The free and bound phenolic profiles and their bioactivities of radix puerariae thomsonii (RPT) cultivars from 7 growing regions in China were investigated. Total phenolic and flavonoid contents were from 148.71 to 435.32 mg gallic acid equivalents /100 g dry weight and 561.93 to 826.11 mg catechin equivalents /100 g dry weight, respectively, with 20.64–38.28% and 32.77–47.29% contribution from bound fractions. Sixteen phenolic compounds were detected in RPTs. Bound fractions contributed 28.15–70.84% to the total antioxidant activities. The cultivars from Qiannan and Guangzhou showed much higher regulatory effects on carbohydrate hydrolyzing enzymes and alcohol metabolizing enzymes than the other cultivars. The bound fractions exhibited equivalent EC50 values for alcohol metabolizing enzymes and IC50 values for carbohydrate hydrolyzing enzymes to the free fractions in RPT cultivars. Therefore, bound phenolics significantly contributed to the potential health benefits of RPT. The results provided information for the utilization of RPT for health promoting purpose.

Abstract Background Paroxysmal kinesigenic dyskinesia (PKD) is the most prevalent kind type of paroxysmal Dyskinesia, characterized by recurrent and transient episodes of involuntary movements. Most PKD cases were attributed to the proline‐rich transmembrane protein 2 (PRRT2) gene, in which the c.649 region is a hotspot for known mutations. Even though some patients with PKD have been genetically diagnosed using whole‐exome sequencing (WES) and Sanger sequencing, there are still cases of missed diagnoses due to the limitations of sequencing technology and analytic methods on throughput. Methods Patients meeting the diagnosis criteria of PKD with negative results of PRRT2‐Sanger sequencing and WES were included in this study. Mutation screening and targeted high‐throughput sequencing were performed to analyze and verify the sequencing results of the potential mutations. Results Six patients with PKD with high mutation ratios of c.649dupC were screened using our targeted high‐throughput sequencing from 26 PKD patients with negative results of PRRT2‐Sanger sequencing and WES (frequency = 23.1%), which compensated for the comparatively shallow sequencing depth and statistical flaws in this region. Compared with the local normal population and other patients with PKD, the mutation ratios of c.649dupC of these six patients with PKD were much higher and also had truncated protein structures and differentially altered mRNA expression. Conclusion Based on the above studies, we emphasize the routine targeted high‐throughput sequencing of the c.649 site in the PRRT2 gene in so‐called genetic‐testing‐negative patients with PKD, and manually calculate the deletion and duplication mutations depth and ratios to lower the rate of clinical misdiagnosis.

IntroductionIntestinal transplantation (ITx) is the last remaining therapy for patients with intestinal failure once parenteral nutrition is no longer an option, however its use is limited by immunological complications, including high rates of rejection and morbidity associated with immunosuppression, such as infection and malignancy. We aimed to develop a large animal model of ITx with which to study the immune response to ITx and to design and test tolerance induction regimens.MethodsLearning from prior complications, we developed and progressively improved both surgical methods for the donor and recipient as well as postoperative management strategies. Methods of stoma generation, bowel positioning, vessel preparation, and fluid management were optimized. The immunosuppression strategy mirrored our clinical regimen.ResultsAs a result of our modifications, results improved from survival less than 1 month to consistent long-term survival with good graft function. We review several techniques that were developed to avoid pitfalls that were encountered, which can be used to optimize outcomes in this model.DiscussionAchieving long-term survival after swine orthotopic ITx permits immunological analysis and pre-clinical trials in a large animal model of ITx.

Abstract Nonfused ring electron acceptors (NFREAs) are promising candidates for future commercialization of organic solar cells (OSCs) due to their simple synthesis. Still, the power conversion efficiencies (PCEs) of NFREA‐based OSCs have large room for improvement. In this work, by merging end group halogenation and side chain engineering, we developed four A–D–A'–D–A type NFREAs, which we refer to as EH‐4F, C4‐4F, EH‐4Cl, and C4‐4Cl. Single crystal X‐ray diffraction revealed that multiple intermolecular S···F interactions between cyclopentadithiophene and 5,6‐difluoro‐3‐(dicyanomethylene)indanone could cause an unfavorable dimer formation, leading to ineffective π–π stackings in EH‐4F and C4‐4F, whereas no such dimer was found in EH‐4Cl and C4‐4Cl after replacing with 5,6‐dichloro‐3‐(dicyanomethylene)indanone. Moreover, although the shorter n‐butyl side chain resulted in a closer molecular packing in C4‐4Cl, EH‐4Cl (2‐ethylhexyl substitution) with proper crystallinity exhibited enhanced face‐on orientation in thin film, which is favorable for vertical charge transport and further reducing charge recombination. As a result, a PCE of 13.0% is obtained for EH‐4Cl‐based OSC with a fill factor of 0.70. This work highlights the importance of molecular packing and orientation control toward future high‐performance A–D–A'–D–A type NFREAs.

Spermatozoa cryopreservation has been practiced for decades and is a very useful technique for long-term preservation of sperm fertility. The capability for semen cryopreservation varies across species, seasons, latitudes, and even for different ejaculates from the same animal. This article summarizes research results on sperm cryotolerance biomarkers in several species, focusing on three areas: spermatozoa cryotolerance biomarkers, seminal plasma proteins cryotolerance biomarkers, and other cryotolerance biomarkers. We discovered that sperm cryoresistance biomarkers are primarily related to sperm plasma membrane stability, the presence of antioxidant substances in sperm or seminal plasma, sperm cell energy metabolism, water and small molecule transport channels in the sperm plasma membrane, and antistress substances in sperm or seminal plasma. The research conducted using diverse livestock models can be employed to enhance the basic and applied reproduction of other mammals through the study of sperm cryotolerance biomarkers, as well as the substantial similarities between livestock and other organisms, including endangered species.

Abstract Background The association between obesity and depression may partly depend on the contextual metabolic health. The effect of change in metabolic health status over time on subsequent depression risk remains unclear. We aimed to assess the prospective association between metabolic health and its change over time and the risk of depression across body mass index (BMI) categories. Methods Based on a nationally representative cohort, we included participants enrolled at the wave 2 (2004–2005) of the English Longitudinal Study of Ageing and with follow-up for depression at wave 8 (2016–2017). Participants were cross-classified by BMI categories and metabolic health (defined by the absence of hypertension, diabetes, and hypercholesterolemia) at baseline or its change over time (during waves 3–6). Logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of depression at follow-up stratified by BMI category and metabolic health status with adjustment for potential confounders. Results The risk of depression was increased for participants with metabolically healthy obesity compared with healthy nonobese participants, and the risk was highest for those with metabolically unhealthy obesity (OR 1.62, 95% CI 1.18–2.20). Particularly hypertension and diabetes contribute most to the increased risk. The majority of metabolically healthy participants converted to unhealthy metabolic phenotype (50.1% of those with obesity over 8 years), which was associated with an increased risk of depression. Participants who maintained metabolically healthy obesity were still at higher risk (1.99, 1.33–2.72), with the highest risk observed for those with stable unhealthy metabolic phenotypes. Conclusions Obesity remains a risk factor for depression, independent of whether other metabolic risk factors are present or whether participants convert to unhealthy metabolic phenotypes over time. Long-term maintenance of metabolic health and healthy body weight may be beneficial for the population mental well-being.

Background: Milk Fat Globule-Epidermal Growth Factor 8 (MFG-E8) has been reported to play an oncogenic role in a variety of tumors. However, its involvement in gastric cancer (GC) development has not been described. Methods: The cancer genome atlas (TCGA) and the gene expression omnibus database (GEO) databases were used to analyze the expression of MFG-E8 in GC. These findings were further validated using immunohistochemistry (IHC) and western blotting assay (WB). Kaplan-Meier method, univariate logistic regression, and Christopher Cox regression were used to study the relationship between MFG-E8 and clinical pathology. In addition, the potential signaling pathways involved in MFG-E8 and its potential correlation with levels of immune cell infiltration were investigated. Finally, the biological function of MFG-E8 in GC cells was revealed. Results: MFG-E8 was highly expressed in GC patients and cells, and the high level of MFG-E8 was associated with poor overall survival (OS). KEGG analysis indicated that MFG-E8 may play an important role in the cAMP signaling pathway. The expression of MFG-E8 was positively correlated with the infiltration of M2 macrophages. The patients with high MFG-E8 were easy to develop chemotherapy resistance. Furthermore, the knockdown of MFG-E8 significantly inhibited the proliferation and invasion of GC cells. Conclusion: MFG-E8 in GC may serve as a prognostic marker and a potential immunotherapy target for GC.

The traditional microstructure detecting methods such as metallography and electron backscatter diffraction are destructive to the sample and time-consuming and they cannot meet the needs of rapid online inspection. In this paper, a random forest regression microstructure characterization method based on a laser ultrasound technique is investigated for evaluating the microstructure of a titanium alloy (Ti-6Al-4V). Based on the high correlation between the longitudinal wave velocity of ultrasonic waves, the average grain size of the primary α phase, and the volume fraction of the transformed β matrix of the titanium alloy, and with the longitudinal wave velocity as the input feature and the average grain size of the primary α phase and the volume fraction of the transformed β matrix as the output features, prediction models for the average grain size of the primary α phase and the volume fraction of the transformed β matrix were developed based on a random forest regression. The results show that the mean values of the mean relative errors of the predicted mean grain size of the native α phase and the volume fraction of the transformed β matrix for the six samples in the two prediction models were 11.55% and 10.19%, respectively, and the RMSE and MAE obtained from both prediction models were relatively small, which indicates that the two established random forest regression models have a high prediction accuracy.

In the realm of thermal interface materials (TIMs), high thermal conductivity and low density are key for effective thermal management and are particularly vital due to the growing compactness and lightweight nature of electronic devices. Efficient directional arrangement is a key control strategy to significantly improve thermal conductivity and comprehensive properties of thermal interface materials. In the present work, drawing inspiration from natural leaf and branch structures, a simple-to-implement approach for fabricating oriented thermal conductivity composites is introduced. Utilizing carbon fibers (CFs), known for their ultra-high thermal conductivity, as branches, this design ensures robust thermal conduction channels. Concurrently, boron nitride (BN) platelets, characterized by their substantial in-plane thermal conductivity, act as leaves. These components not only support the branches but also serve as junctions in the thermal conduction network. Remarkably, the composite achieves a thermal conductivity of 11.08 W/(m·K) with just an 11.1 wt% CF content and a 1.86 g/cm3 density. This study expands the methodologies for achieving highly oriented configurations of fibrous and flake materials, which provides a new design idea for preparing high-thermal conductivity and low-density thermal interface materials.

Previous studies suggested that spring precipitation over the tropical western Pacific Ocean can influence the development of El Niño–Southern Oscillation (ENSO). To identify crucial precipitation patterns for post-spring ENSO evolution, a singular value decomposition (SVD) method was applied to spring precipitation and sea surface temperature (SST) anomalies, and three precipitation and ENSO types were obtained with each highlighting precipitation over the Maritime Continent (MC) or western north Pacific (WNP). High MC spring precipitation corresponds to the slow decay of a multi-year La Niña event. Low MC spring precipitation is associated with a rapid El Niño-to-La Niña transition. High WNP spring precipitation is related to positive north Pacific meridional mode and induces the El Niño initiation. Among the three ENSO types, ocean current and heat content behave differently. Based on these spring precipitation and oceanic factors, a statistical model was established aimed at predicting winter ENSO state. Compared to a full dynamical model, this model exhibits higher prediction skills in the winter ENSO phase and amplitude for the period of 1980–2022. The explained total variance of the winter Niño-3.4 index increases from 43% to 75%, while the root-mean-squared error decreases from 0.82 °C to 0.53 °C. The practical utility and limitations of this model are also discussed.

The leaf area of pak choi is a critical indicator of growth rate, nutrient absorption, and photosynthetic efficiency, and it is required to be precisely measured for an optimal agricultural output. Traditional methods often fail to deliver the necessary accuracy and efficiency. We propose a method for calculating the leaf area of pak choi based on an improved Mask R-CNN. We have enhanced Mask R-CNN by integrating an advanced attention mechanism and a two-layer fully convolutional network (FCN) into its segmentation branch. This integration significantly improves the model’s ability to detect and segment leaf edges with increased precision. By extracting the contours of reference objects, the conversion coefficient between the pixel area and the actual area is calculated. Using the mask segmentation output from the model, the area of each leaf is calculated. Experimental results demonstrate that the improved model achieves mean average precision (mAP) scores of 0.9136 and 0.9132 in detection and segmentation tasks, respectively, representing improvements of 1.01% and 1.02% over the original Mask R-CNN. The model demonstrates excellent recognition and segmentation capabilities for pak choi leaves. The error between the calculation result of the segmented leaf area and the actual measured area is less than 4.47%. These results indicate that the proposed method provides a reliable segmentation and prediction performance. It eliminates the need for detached leaf measurements, making it suitable for real-life leaf area measurement scenarios and providing valuable support for automated production technologies in plant factories.

The mechanism for the paradox of global warming and successive cold winters in mid-latitudes remains controversial. In this study, the connection between Arctic sea ice (ASI) loss and frequent cold air outbreaks in eastern Continental United States (CONUS) is explored. Two distinct periods of high and low ASI (hereafter high- and low-ice phases) are identified for comparative study. It is demonstrated that cold air outbreaks occur more frequently during the low-ice phase compared to that during the high-ice phase. The polar vortex is weakened and shifted southward during the low-ice phase. Correspondingly, the spatial pattern of 500 hPa geopotential height (GPH), which represents the mid-tropospheric circulation, shows a clear negative Arctic Oscillation-like pattern in the low-ice phase. Specifically, positive GPH anomalies in the Arctic region with two centers, respectively located over Greenland and the Barents Sea, significantly weaken the low-pressure system centered around the Baffin Island, and enhance Ural blocking in the low-ice phase. Meanwhile, the high ridge extending from Alaska to the west coast of North America further intensifies, while the low trough over eastern CONUS deepens. As a result, the atmospheric circulation in North America becomes more conductive to frigid Arctic air outbreaks. It is concluded that the ASI loss contributes to more cold air outbreaks in winter in eastern CONUS through the polar vortex weakening with southward displacement of the polar vortex edge, which lead to the weakening of the meridional potential vorticity gradient between the Arctic and mid-latitude and thus are conducive to the strengthening and long-term maintenance of the blocking high.