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The lithofacies and thermal maturity of the over-mature Lower Cambrian marine shale in the Northern Guizhou Region, and their impacts on reservoir properties in this shale were analyzed by combining geochemistry, mineralogy, and gas adsorption methods. Ten lithofacies were identified, and the dominant lithofacies in the studied shale are lean-total organic carbon (TOC) argillaceous-rich siliceous shale (LTAS), medium-TOC siliceous shale (MTSS), and rich-TOC siliceous shale (RTSS). Since the gas generation potential of organic matter was weak, meso- and macro-pores were compressed or filled during the thermal evolution stage with a vitrinite reflectance (RO) range of 3.0%–4.0%. The controlling factors for methane adsorption capacity in the shale samples are significantly influenced by TOC content rather than thermal maturity. Among the RTSS, MTSS, and LTAS samples, RTSS exhibits the highest favorability for preserving hydrocarbon gas, followed by MTSS. The shale types in this study play a significant role in determining the properties of shale reservoirs, serving as an effective parameter for evaluating shale gas development potential. The RTSS and MTSS with a RO range of 2.0%–3.0% stand out as the most favorable target shale types for shale gas exploration and development.

Obtaining a comprehensive understanding of solute transport in fractured rocks is crucial for various geoengineering applications, including waste disposal and construction of geo-energy infrastructure. It was realized that solute transport in fractured rocks is controlled by stochastic discrete fracture-matrix systems. However, the impacts and specific uncertainty caused by fracture network structures on solute transport in discrete fracture-matrix systems have yet not been fully understood. In this article, we aim to investigate the influence of fracture network structure on solute transport in stochastic discrete fracture-matrix systems. The fluid flow and solute transport are simulated using a three-dimensional discrete fracture matrix model with considering various values of fracture density and size (i.e., radius). The obtained results reveal that as the fracture density or minimum fracture radius increases, the corresponding fluid flow and solute transport channels increase, and the solute concentration distribution range expands in the matrix. This phenomenon, attributed to the enhanced connectivity of the fracture network, leads to a rise in the effluent solute concentration mean value from 0.422 to 0.704, or from 0.496 to 0.689. Furthermore, when solute transport reached a steady state, the coefficient of variation of effluent concentration decreases with the increasing fracture density or minimum fracture radius in different scenarios, indicating an improvement in the homogeneity of solute transport results. The presented analysis results of solute transport in stochastic discrete fracture-matrix systems can be helpful for uncertainty management in the geological disposal of high-level radioactive waste.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal infectious disease caused by the SFTS virus (SFTSV), posing a significant public health threat. This study aimed to construct a dynamic model for the early identification of SFTS patients at high risk of disease progression. Methods All eligible patients enrolled between April 2014 and July 2023 were divided into training and validation sets. Thirty-four clinical variables in the training set underwent analysis using least absolute shrinkage and selection operator (LASSO) logistic regression. Selected variables were then input into the multivariate logistic regression model to construct a dynamic nomogram. The model’s performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) in both training and validation sets. Kaplan-Meier survival analysis was utilized to evaluate prognostic performance. Results 299 SFTS patients entered the final investigation, with 208 patients in the training set and 90 patients in the validation set. LASSO and the multivariate logistic regression identified six significant prediction factors: age (OR, 1.060; 95% CI, 1.017–1.109; P = 0.007), CREA (OR, 1.017; 95% CI, 1.003–1.031; P = 0.019), PT (OR, 1.765; 95% CI, 1.175–2.752; P = 0.008), D-dimer (OR, 1.039; 95% CI, 1.005–1.078; P = 0.032), nervous system symptoms (OR, 8.244; 95% CI, 3.035–26.858; P

Hydraulic fracturing is a widely used technique for increasing the permeability of coal seams. Its impact on the production capacity of coalbed methane(CBM) wells is significant. This paper makes detailed observations on the exposed coal seams and fracture distribution of 5 CBM wells in Tunlan block of Xishan coalfield, and studies the distribution characteristics of coal structure, microfractures, quartz sand and coal fine by using stereoscopic microscope, scanning electron microscope, and micro CT. The fracturing effect and influencing factors of CBM wells are analysed by combining regional geostress and hydraulic fracturing construction parameters. The research results indicate that the macroscopic fractures morphology produced by hydraulic fracturing are complex and diverse, including horizontal, vertical, X and T-shaped fractures. The degree of coal body fragmentation increases with distance from the CBM well. The coal body closer to the CBM well is mainly composed of fragmented and granular coal, while the coal body further away is mainly composed of undeformed coal with primary fractures. The quartz sands are mainly deposited in horizontal fractures, with only a small amount in T-shaped fractures. Quartz sand rubs, collides, and embeds strongly with the coal fracture surface. The fracturing fluid is then superimposed to fracture the coal body, resulting in a large amount of coal fines. This causes the coal fines to wrap around the quartz sand and block the fractures. The coal fines within the macroscopic fracture are primarily a result of the fracturing of the coal body, the flushing of the coal body by fracturing fluid, and the friction between the quartz sand and the fracture surface during hydraulic fracturing. Coal fine generation in micro-fractures during coal body fracturing. Coal fines and quartz sand accumulate in the fractures, creating enormous resistance to the carrying fluid and preventing the quartz sand from migrating to the far end of the CBM well. The magnitude and direction of the geostress, as well as the strength of the coal seam roof and floor, are important factors that influence the opening and direction of the hydraulic fracturing fractures. The low viscosity of the carrying fluid cannot suspend quartz sand, and the accumulation of quartz sand and coal fine can block the fractures, easy to cause quartz sand and coal fine to aggregate and block fractures.

Sepsis-induced acute kidney injury (SI-AKI) is a common clinical syndrome that is associated with high mortality and morbidity. Effective timely detection may improve the outcome of SI-AKI. Kidney-derived cell-free DNA (cfDNA) may provide new insight into understanding and identifying SI-AKI. Plasma cfDNA from 82 healthy individuals, 7 patients with sepsis non-acute kidney injury (SN-AKI), and 9 patients with SI-AKI was subjected to genomic methylation sequencing. We deconstructed the relative contribution of cfDNA from different cell types based on cell-specific methylation markers and focused on exploring the association between kidney-derived cfDNA and SI-AKI.Based on the deconvolution of the cfDNA methylome: SI-AKI patients displayed the elevated cfDNA concentrations with an increased contribution of kidney epithelial cells (kidney-Ep) DNA; kidney-Ep derived cfDNA achieved high accuracy in distinguishing SI-AKI from SN-AKI (AUC = 0.92, 95% CI 0.7801–1); the higher kidney-ep cfDNA concentrations tended to correlate with more advanced stages of SI-AKI; strikingly, SN-AKI patients with potential kidney damage unmet by SI-AKI criteria showed higher levels of kidney-Ep derived cfDNA than healthy individuals. The autonomous screening of kidney-Ep (n = 24) and kidney endothelial (kidney-Endo, n = 12) specific methylation markers indicated the unique identity of kidney-Ep/kidney-Endo compared with other cell types, and its targeted assessment reproduced the main findings of the deconvolution of the cfDNA methylome. Our study first demonstrates that kidney-Ep- and kidney-Endo-specific methylation markers can serve as a novel marker for SI-AKI emergence, supporting further exploration of the utility of kidney-specific cfDNA methylation markers in the study of SI-AKI.

The Chinese medicine residue (CMR) is composed of wet substances, so using hydrothermal carbonization (HTC) to recover renewable energy from the residue is a suitable treatment method. Chromium (Cr), a kind of heavy metal element, is enriched in hydrochar and severely restricts its effective utilization. An in-depth analysis of the migration path and mechanism of Cr in hydrochar is helpful in promoting energy utilization for CMR. Here, licorice, a significant Chinese medicine, was selected as the example to analyze the evolutions of its pore and chemical structures and their effects on the migration mechanism of Cr during the HTC process. The products obtained under various HTC conditions were analyzed using nitrogen adsorption, FTIR, and 13C NMR. The results show that, considering reaction time and relevant reactions as the primary factors during the HTC process, the migration pathway of Cr in hydrochar undergoes two stages, and they are the accompanying migration stage and the recovery aggregation stage. Active adsorption sites for Cr may exist within the pore structure of hydrochar. In the HTC process, hydrolysis, decarboxylation, and decarbonylation reactions are the direct drivers of Cr migration, while aromatization is the underlying cause of Cr recovery and aggregation. It is hypothesized that Cr catalyzes the acetylene cyclotrimerization reaction, thereby promoting the formation of aromatic structures in hydrochar and integrating into the hydrochar carbon skeleton.

Summary: FOXA1 serves as a crucial pioneer transcription factor during developmental processes and plays a pivotal role as a mitotic bookmarking factor to perpetuate gene expression profiles and maintain cellular identity. During mitosis, the majority of FOXA1 dissociates from specific DNA binding sites and redistributes to non-specific binding sites; however, the regulatory mechanisms governing molecular dynamics and activity of FOXA1 remain elusive. Here, we show that mitotic kinase Aurora B specifies the different DNA binding modes of FOXA1 and guides FOXA1 biomolecular condensation in mitosis. Mechanistically, Aurora B kinase phosphorylates FOXA1 at Serine 221 (S221) to liberate the specific, but not the non-specific, DNA binding. Interestingly, the phosphorylation of S221 attenuates the FOXA1 condensation that requires specific DNA binding. Importantly, perturbation of the dynamic phosphorylation impairs accurate gene reactivation and cell proliferation, suggesting that reversible mitotic protein phosphorylation emerges as a fundamental mechanism for the spatiotemporal control of mitotic bookmarking.

Abstract Bacteria can be utilized for cancer therapy owing to their preferential colonization at tumor sites. However, unmodified non‐pathogenic bacteria carry potential risks due to their non‐specific targeting effects, and their anti‐tumor activity is limited when used as monotherapy. In this study, a biohybrid‐engineered bacterial system comprising non‐pathogenic MG1655 bacteria modified with CDH17 nanobodies on their surface and conjugated with photosensitizer croconium (CR) molecules is developed. The resultant biohybrid bacteria can efficiently home to CDH17‐positive tumors, including gastric, pancreatic, and colorectal cancers, and significantly suppress tumor growth upon irradiation. More importantly, biohybrid bacteria‐mediated photothermal therapy (PTT) induced abundant macrophage infiltration in a syngeneic murine colorectal model. Further, that the STING pathway is activated in tumor macrophages by the released bacterial nucleic acid after PTT is revealed, leading to the production of type I interferons. The addition of CD47 nanobody but not PD‐1 antibody to the PTT regimen can eradicate the tumors and extend survival. This results indicate that bacteria endowed with tumor‐specific selectivity and coupled with photothermal payloads can serve as an innovative strategy for low‐immunogenicity cancers. This strategy can potentially reprogram the tumor microenvironment by inducing macrophage infiltration and enhancing the efficacy of immunotherapy targeting macrophages.

Abstract Introduction Thrombosis in ANCA-associated vasculitis (AAV) was prevalent and has been neglected in Chinese patients. This study tried to describe the clinical characteristics, identify the risk factors, and investigate the causal relationship between AAV and venous thromboembolism (VTE) by two-sample Mendelian randomization (MR) analysis. Methods In this retrospective, observational study, we included all hospitalized AAV patients from Jan 2013 to Apr 2022 in Peking Union Medical College Hospital. We collected their clinical data for multivariate regression analysis to determine the risk factors for thrombosis. The nomogram was constructed by applying these risk factors to predict thrombosis in AAV patients. As for MR analysis, we selected single nucleotide polymorphisms (SNPs) related to AAV from published genome-wide association studies and extracted the outcome data containing deep vein thrombosis (DVT) and pulmonary embolism (PE) from the UK biobank. Results 1203 primary AAV patients were enrolled, and thrombosis occurred in 11.3%. Multivariate regression suggested that older than 65 years, EGPA, neurological involvement, lung involvement, significantly elevated serum creatinine (> 500µmol/L), and elevated D-dimer were associated with thrombosis in AAV patients. The model demonstrated satisfied discrimination with an AUC of 0.769 (95% CI, 0.726–0.812). MR analysis showed that EGPA could increase the risk of developing DVT and PE (OR = 1.0038, 95%CI = 1.0035–1.0041, P = 0.009). Conclusion Thrombosis was not rare in Chinese patients with AAV. Renal damage and old age emerged as critical risk factors for thrombosis. EGPA might have a potential causal relationship with DVT and PE.

Despite the availability of effective vaccines and treatments for SARS-CoV-2, managing COVID-19 in patients with systemic lupus erythematosus (SLE) remains challenging, particularly considering drug-drug interactions (DDIs). Here, we present a case of DDIs between Tacrolimus (Tac) and nirmatrelvir/ritonavir (NMV/r) in a 32-year-old male with SLE. Following self-administration of NMV/r and resumption of Tac after 5 days, the patient experienced acute nephrotoxicity and neurotoxicity, accompanied by supratherapeutic Tac levels, despite Tac being withheld during NMV/r. The primary cause of this acute toxicity is attributed to ritonavir’s inhibitory effect on both CYP3A4 enzymes and P-glycoprotein. Upon admission, Tac was discontinued, and supportive therapies were initiated. Phenytoin, a CYP3A4 inducer, was administered to lower Tac levels under the guidance of clinical pharmacists, effectively alleviating the patient’s acute toxic symptoms. The half-life of Tac during the treatment of phenytoin was calculated to be 55.87 h. And no adverse reactions to phenytoin were observed. This case underscores the persistence of enzyme inhibition effects and demonstrates the effectiveness and safety of utilizing CYP3A4 enzyme inducers to mitigate Tac concentrations. Furthermore, it emphasizes the importance of healthcare providers and patients being vigilant about DDIs in Tac recipients. Lastly, it highlights the indispensable role of pharmacist involvement in clinical decision-making and close monitoring in complex clinical scenarios. Although our findings are based on a single case, they align with current knowledge and suggest the potential of individualized combination therapy in managing challenging COVID-19 cases in immunocompromised patients.

Objective This study aims to explore the psychological distress course of Chinese amyotrophic lateral sclerosis (ALS) patients after the onset of the disease and to provide targeted nursing guidance.Design The interview content was analysed qualitatively. We used seven steps of Colaizzi’s method to analyse the participants’ data.Setting Wuhan, China, Traditional Chinese Medicine Hospital.Participants A semistructured face-to-face interview were performed among 22 people with ALS from the motor neuron disease rehabilitation centre of a tertiary Chinese medicine hospital in China.Result This study included a total of 22 participants, from whom three main themes regarding the psychological distress trajectory of ALS patients were extracted from the interview data: ‘Time begins to run out’ include tormented and restless waiting and shock and doubt in ALS disease confirmation, ‘Family out of control’ include the burden of stigma and function loss, the burden of missing family roles, the burden of marriage’s emotional needs and the burden of offspring health, ‘Way forward’ include struggle between live and death and struggle between quality of life and the value of life.Conclusion This study outlines the psychologically distressing journey of ALS patients. Studies have pointed out the need for targeted care to address patients’ various sources of psychological distress to improve their quality of life and coping ability, increase their psychological resilience and reconstruct their life beliefs.

Abstract In the process of drilling oil and gas wells, the shrinkage and falling of wellbore walls are often caused by the expansion of mud shale water. To date, conventional additives have been unable to plug the pore throats of shale rock with nanoscale pores and thus cannot effectively solve the problem of wellbore instability encountered in shale formation drilling. In view of this situation, the idea of using nanosilica to plug the nanopore throat of mud shale is proposed to reduce its permeability and to slow water intrusion. The influences of nanosilica on the properties of brine-base drilling fluid drilling fluid are evaluated by measuring the viscosity, filtration loss and swelling of the drilling fluid. The results of laboratory experiments show that the improvement in drilling fluid properties can only be achieved on the basis of salt resistance; that is, a salt-resistant soil slurry should be used. A concentration of 1–5% nanosilica can improve the viscosity of the drilling fluid by increasing the internal friction between particles. However, nanosilica materials are sensitive to salt concentration. Nanosilica particles can be deposited on the surface of a filter cake to block the pores of the filter paper, and the filtration loss reduction rate can reach 40.2%. Blocking the pores of the clay plays a role in preventing the clay from absorbing water and expanding. The optimal addition amount of silica is 3%, and its salt resistance can reach 16%. Considering the experimental results of filtration loss, swelling amount and cost performance, 3%NP + 4%NaCl + SWM-B is selected as the optimal formula. The results of this study can be applied to effectively improve the phenomenon of wellbore instability during drilling in shale formations, and it has important application value.

Abstract Imaging-guided photothermal therapy (PTT) for cancers recently gathered increasing focus thanks to its precise diagnosis and potent therapeutic effectiveness. Croconaine (CR) dyes demonstrate potential in expanding utility for near infrared (NIR) dyes in bio-imaging/theranostics. However, reports on CR dyes for PTT are scarce most likely due to the short of the efficacious delivery strategies to achieve specific accumulation in diseased tissues to induce PTT. Extracellular vesicles (EVs) are multifunctional nanoparticle systems that function as safe platform for disease theragnostics, which provide potential benefits in extensive biomedical applications. Here, we developed a novel delivery system for photothermal molecules based on a CR dye that exerts photothermal activity through CDH17 nanobody-engineered EVs. The formed CR@E8-EVs showed strong NIR absorption, excellent photothermal performance, good biological compatibility and superb active tumor-targeting capability. The CR@E8-EVs can not only visualize and feature the tumors through CR intrinsic property as a photoacoustic imaging (PAI) agent, but also effectively retard the tumor growth under laser irradiation to perform PTT. It is expected that the engineered EVs will become a novel delivery vehicle of small organic photothermal agents (SOPTAs) in future clinical PTT applications.

Objective: In order to improve the yield of oryzanol of rice bran. Methods: Rice bran was selected as the research subject, and Saccharomyces cerevisiae and Bacillus subtilis were selected as solid-state fermentation strains through single-factor experiments. The mixed bacterial solid-state fermentation process was optimized by Box-Behnken response surface method combined with the single factor experiments, based on the content of oryzanol. The antioxidant activity of the fermentation extracts was evaluated using DPPH and ABTS free radical scavenging assays. Scanning electron microscopy （SEM） was used to analyze the principle of oryzanol enrichment in mixed bacterial solid-state fermentation. Results: Under the of mixed bacterial treatment of saccharomyces cerevisiae and Bacillus subtilis, the optimal fermentation conditions for rice bran oryzanol was determined to be a fermentation time of 44 h, a fermentation temperature of 34 ℃, an inoculum size of 10%, and a moisture content of 40%. Under these conditions, the oryzanol content was （7.816±0.038） mg/g, which was 1.9 times higher than that of unfermented rice bran. The extracts prepared by mixed bacterial solid-state fermentation exhibited strong DPPH and ABTS free radical scavenging activity, with IC50 values of （0.220±0.007）, （0.409±0.014） mg/mL, respectively. These values represented a reduction of 28.6% and 39.7% compared to unfermented rice bran. SEM observation revealed showed that that the surface of rice bran tissue had less oil, a looser and more porous structure after mixed bacterial solid-state fermentation, which was more conducive to the release of rice bran oryzanol. Conclusion: Mixed solid-state fermentation of bacteria significantly increases the oryzanol content and antioxidant activity of rice bran.

In this paper, we consider a novel vector-valued rational interpolation algorithm and its application. Compared to the classic vector-valued rational interpolation algorithm, the proposed algorithm relaxes the constraint that the denominators of components of the interpolation function must be identical. Furthermore, this algorithm can be applied to construct the vector-valued interpolation function component-wise, with the help of the common divisors among the denominators of components. Through experimental comparisons with the classic vector-valued rational interpolation algorithm, it is found that the proposed algorithm exhibits low construction cost, low degree of the interpolation function, and high approximation accuracy.

Freeze–thaw damage significantly contributes to the degradation of concrete structures. A critical precondition for concrete to experience frost damage is reaching its critical saturation level. This study conducted freeze–thaw experiments on concrete specimens under both open and sealed moisture conditions to elucidate the mechanisms of freeze–thaw damage and the pivotal role of moisture. The research assessed concrete’s water absorption, ultrasonic pulse velocity, and compressive strength under restricted water conditions to study damage accumulation patterns. The findings indicate that implementing water limitation measures during freeze–thaw cycles can regulate concrete’s water absorption rate, reduce the loss of ultrasonic pulse velocity, and minimize strength degradation, with an observed strength increase of up to 36.22%. Consequently, these measures protect concrete materials from severe frost damage. Furthermore, a predictive model for concrete freeze–thaw deterioration was established based on regression analysis and relative dynamic modulus theory, confirming the critical role of water limitation in extending the service life of concrete structures in cold regions.

This study aims to synthesize composite materials using TC4 particles and AZ91D alloy through semi-solid stirring and hot extrusion techniques. The main objective is to investigate the microstructure, mechanical properties, wear resistance, and corrosion behavior of composites comprising a minor volume fraction (0, 2, and 5 vol%) of spherical TC4 particles. The findings showed that the dual synergistic effect of TC4 particles and the β-phase leads to a refinement in the grain size of the composite material. Moreover, the incorporation of TC4 particles enhances the hardness, yield strength (YS), and ultimate tensile strength (UTS) of the magnesium matrix, with almost no reduction observed in ductility. Additionally, the TC4/AZ91D composite displays lower wear rates and friction coefficients compared to the matrix when subjected to forces of 150 N and 300 N. However, the corrosion performance of the composite material deteriorates due to the influence of the galvanic effect between the particles and the matrix.

We analyzed a large amount of published petrological, mineralogical, and geochemical data from the Niutitang, Wufeng-Longmaxi, Dawuba, Liangshan, and Longtan organic-rich shales. These include marine shales and marine-continental transitional shales. The main marine organic-rich shales include the Niutitang, Wufeng-Longmaxi, and Dawuba shales, while the main marine-continental organic-rich transitional shales include the Liangshan and Longtan shales. The marine organic-rich shales were generally deposited under anoxic conditions, and are generally brittle siliceous-rich lithofacies, which is a type I organic-matter dominated. In contrast to the marine organic-rich shales, the marine-continental transitional organic-rich shales were most likely deposited under dysoxic to oxic conditions. They are generally less brittle argillaceous-rich lithofacies, that are type III organic-matter dominated. Of the five organic-rich shales, the Niutitang and Wufeng-Longmaxi organic-rich shales are over-mature shales, and the Dawuba, Liangshan, and Longtan organic-rich shales are high-maturity to over-mature shales. The spots with siliceous rock floor on the western edge of the Xuefeng uplift is a favorable area for future exploration of shale gas in the Niutitang organic-rich shale. The Chishui terrestrial basin and center of the aulacogen are the faverable areaa for shale gas expolation and development of the Wufeng-Longmaxi and Dawuba organic-rich shales, respectively. More basic geological research work is needed to select favorable areas for the Liangshan and Longtan organic-rich shales. To accurately guide future shale gas exploration and development, more research is needed on the relationship between the sedimentary environment, the lithofacies, and the reservoir properties of the shales.

As a typical 2-dimensional material, molybdenum disulfide (MoS2) has atomic thickness in longitudinal size, showing unique optical and electrical properties. MoS2 has become a research hotspot in the field of photodetection. The properties of MoS2 devices are highly dependent on their material characteristics, device structures, and fabrication techniques. Therefore, their photoresponse characteristics may be determined by multiple physical effects, which contribute to the development of MoS2-based broadband photodetectors. Here, we present an experimental study on the broadband MoS2 photodetector ranging from 410 to 1,550 nm, obviously wider than that of conventionally reported MoS2 photodetectors. Our results indicate that the performance of the MoS2 device is dependent on the fabrication procedures. Under the optimal process, the maximum responsivity is 33.75 A W−1 and the corresponding specific detectivity is 6.1 × 1011 cm Hz1/2 W−1 at 480-nm illumination. Through a series of electrical and optoelectronic experimental analysis, the working mechanisms of multiband photoresponse of the MoS2 device are clarified.

Functional nano-coatings have been a research hotspot in recent years. The nano-size composition units provide good volume effect and surface effect for functional nano-coatings, and greatly optimize the mechanical properties, corrosion resistance, oxidation resistance and wear resistance of the coatings. The preparation technology and properties of functional nano-coatings determine the application range of nano-coatings. However, most reviews focus on certain properties, preparation methods or applications of functional nano-coatings, and lack of reviews on the integrity of functional nano-coatings. Firstly, this work introduced the concept and classification of functional nano-coatings briefly. Secondly, the preparation techniques of functional nano-coatings were described in detail, including traditional chemical vapor deposition, physical vapor deposition and sol-gel method, the latest plasma spraying technology and other preparation techniques. Moreover, the principles, advantages and disadvantages of various nano-coatings preparation technologies and the application of nano-coatings in materials were analyzed and summarized. Finally, the latest and popular applications of functional nano-coatings were reviewed in detail, and the application prospect and potential of functional nano-coatings were prospected.

Abstract High-intensity interval training (HIIT) is a physical therapy that may benefit patients with osteoarthritis (OA). Cacna2d1 is a calcium channel subunit protein that plays an important role in the activity of nerve cells. However, there is currently no evidence on HIIT relieving OA-associate hyperalgesia by decreased Cacna2d1. Our study established the OA rat models with intra-articular injection of monosodium iodoacetate (MIA). This experiment was divided into two stages. The first stage comprised three groups: the control, OA, and OA-HIIT groups. The second stage comprised two groups, including the AAV-C and AAV-shRNA-Cacna2d1 groups. OA rats were positioned at the L5–L6 segments, and 20 µl of AAV virus was injected intrathecally. The pain threshold, cartilage analysis, Cacna2d1, and pain neurotransmitters were measured and compared. The pain threshold was significantly lower in OA rats than in control rats from the first to the tenth week. Starting from the sixth week, OA-HIIT rats exhibited significantly increased pain thresholds. The expression of Cacna2d1 increased in OA rats. Moreover, the knockdown of Cacna2d1 significantly down-regulated the expression of c-Fos, SP, and Vglut2 in the posterior horn of the spinal cord. In conclusion, HIIT attenuates OA-associated hyperalgesia, which may be related to the down-regulation of Cacna2d1.

Marine shales from the Niutitang Formation and marine–continental transitional shales from the Longtan Formation are two sets of extremely important hydrocarbon source rocks in South China. In order to quantitatively compare the pore complexity characteristics between marine and marine–continental transitional shales, the shale and kerogen of the Niutitang Formation and the Longtan Formation are taken as our research subjects. Based on organic petrology, geochemistry, and low-temperature gas adsorption analyses, the fractal dimension of their pores is calculated by the Frenkel–Halsey–Hill (FHH) and Sierpinski models, and the influences of total organic carbon (TOC), vitrinite reflectance (Ro), and mineral composition on the pore fractals of the shale and kerogen are discussed. Our results show the following: (1) Marine shale predominantly has wedge-shaped and slit pores, while marine–continental transitional shale has inkpot-shaped and slit pores. (2) Cylindrical pores are common in organic matter of both shale types, with marine shale having a greater gas storage space (CRV) from organic matter pores, while marine–continental transitional shale relies more on inorganic pores, especially interlayer clay mineral pores, for gas storage due to their large specific surface area and high adsorption capacity (CRA). (3) The fractal characteristics of marine and marine–continental transitional shale pores are influenced differently. In marine shale, TOC positively correlates with fractal dimensions, while in marine–continental shale, Ro and clay minerals have a stronger influence. Ro is the primary factor affecting organic matter pore complexity. (4) Our two pore fractal models show that the complexity of the shale in the Longtan Formation surpasses that of the shale in the Niutitang Formation, and type I kerogen has more complex organic matter pores than type III, aiding in evaluating pore connectivity and flow effectiveness in shale reservoirs.

Plasticized polyvinyl chloride (PVC) gel is a new soft and smart material, whose potential in electroactive variable stiffness can be used for vibration control in soft robotic systems. In this paper, a new semi-active vibration absorber is developed by stacking PVC gel actuator units. The absorption bandwidth of a single PVC gel absorber covers the range of three natural frequencies (76.5 Hz, 95 Hz, 124 Hz) of a rectangular steel plate in vibration attenuation. The maximum reduction percentage in acceleration amplitude is 63%. With stacked PVC gel actuator units, the absorption bandwidth can be shifted and obviously broadened.

Bone is one of the most vascular network-rich tissues in the body and the vascular system is essential for the development, homeostasis, and regeneration of bone. When segmental irreversible damage occurs to the bone, restoring its vascular system by means other than autogenous bone grafts with vascular pedicles is a therapeutic challenge. By pre-generating the vascular network of the scaffold in vivo or in vitro, the pre-vascularization technique enables an abundant blood supply in the scaffold after implantation. However, pre-vascularization techniques are time-consuming, and in vivo pre-vascularization techniques can be damaging to the body. Critical bone deficiencies may be filled quickly with immediate implantation of a supporting bone tissue engineered scaffold. However, bone tissue engineered scaffolds generally lack vascularization, which requires modification of the scaffold to aid in enhancing internal vascularization. In this review, we summarize the relationship between the vascular system and osteogenesis and use it as a basis to further discuss surgical and cytotechnology-based pre-vascularization strategies and to describe the preparation of vascularized bone tissue engineered scaffolds that can be implanted immediately. We anticipate that this study will serve as inspiration for future vascularized bone tissue engineered scaffold construction and will aid in the achievement of clinical vascularized bone.

This study aims to examine and compare clinical, radiological, and pathological data between colorectal cancer (CRC) patients with and without schistosomiasis and uncover distinctive CRC characteristics when accompanied by schistosomiasis. This retrospective study is based on data collected from 341 patients diagnosed with CRC post-surgery and pathology. Of these patients, 101 (Group A) were diagnosed with colorectal cancer co-occurring with schistosomiasis (CRC-S), while 240 patients (Group B) were diagnosed with colorectal cancer without concurrent schistosomiasis (CRC-NS). Both groups were compared and analyzed based on their clinical data, imaging-based TNM staging, lymph node metastasis, nerve invasion, vascular cancer thrombus, and histopathological differentiation. A Chi-squared test revealed a significant difference in gender distribution between the patients with CRC-S (Group A) and CRC-NS (Group B), with a p -value of 0.043 and χ2 = 4.115. Specifically, a higher incidence rate was observed among males in Group A. There was a difference in the overall distribution of TNM staging between the two groups (p = 0.034, χ2 = 6.764). After pairwise comparison, a statistically significant difference was observed in the T3 stage (p 0.05). Among the 101 patients with CRC-S, 87 (86%) showed linear calcification on CT imaging. Patients with CRC-S are mainly male, with tumor staging mostly in the middle stage, high tumor differentiation, and low malignancy. CT imaging can help identify the presence of lumps and linear calcification indicative of schistosome deposits. MRI can early clarify TNM staging and determine the presence of lymph node metastasis and nerve and vascular invasion.

The efficacy and safety of anticoagulant therapy in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF) remain uncertain. This study enrolled 431 AIS and AF patients from Nanjing Drum Tower Hospital between January 2019 and December 2021 and followed for 365 days to determine the associations between anticoagulants and clinical outcomes by assessing modified Rankin Scale (mRS) score, recurrent ischemic stroke/systemic embolism (IS/SE), all-cause mortality, intracranial hemorrhage (ICH) and major bleeding. Final analysis included 400 eligible patients and divided them into antiplatelet group (n = 191) and anticoagulant group (n = 209). Anticoagulant therapy was associated with excellent (mRS 0–1; adjusted odds ratio (aOR), 2.63; 95% confidence interval (CI), 1.61–4.30) and favorable functional outcomes (mRS 0–2; aOR, 2.82; 95% CI, 1.69–4.70) and lower risk of all-cause mortality (adjusted hazard ratio (aHR), 0.35; 95% CI, 0.21–0.57), ICH (aHR, 0.45; 95% CI, 0.23–0.87) and major bleeding (aHR, 0.51; 95% CI, 0.28–0.94), without increasing the risk of recurrent IS/SE (aHR, 0.75; 95% CI, 0.45–1.24). In conclusion, anticoagulant therapy may be a more effective and safer option than antiplatelet therapy for AIS patients with AF.

Most of current permeability evaluation models for shale gas reservoirs ignore the influence of imbibition during fracturing, moreover, several of the considerations are different from real conditions, for example, shale pore shape is circular and water film is with equal thickness, which is convenient for calculation but adverse to evaluation accuracy. In the study, shale pore shapes are closer to ellipse by statistically analyzing the scanning electron microscopy results, the thickness of water film is not equal on elliptical pore surface but related to the curvature. Based on these new insights, a quantitative model for determining the unequal thickness of water film was established, and then a new multi-scale elliptical pore permeability model, considering non-equal-thickness water film, wall roughness, stress sensibility, and retention effect, was established based on the multi-scale flow weighting theory. The prediction results of this permeability model are similar to the test results, and are more accurate than that of the previous models. Finally, factors analysis showed that the effect of roughness on permeability was small, but the negative impact of water film and stress sensitivity on permeability was significant.

Abstract Background Enhanced de novo lipogenesis is essential for hepatocellular carcinoma (HCC). Abnormally high cullin‐associated and neddylation‐dissociated 1 (CAND1) expression is associated with poor clinical prognosis in HCC. The SKP1‐Cullin‐1‐F‐box (SCF) complex consists of the SKP1, Cullin‐1 and F‐box proteins (FBPs) and performs multiple functions including adipogenesis. SCF complex was modulated by CAND1, but Whether and how the CAND1 promotes HCC by regulating SCF complex and lipogenesis are unknown. Methods HCC samples were used to analyze the correlations between CAND1 expression and clinicopathological characteristics such as survival and prognosis. The in vitro functions of CAND1, FBXO11 and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) were measured by cell proliferation, colony formation and migration assays. The in vivo functions were tested in multiple mouse liver cancer models including patient‐derived xenograft (PDX), cell line‐derived xenograft and AKT/NRASV12‐induced primary liver cancer models. Injections of adeno‐associated virus targeting CAND1 (AAV‐shCAND1) were performed to evaluate the therapeutic efficacy of targeting CAND1. RNA‐Seq and lipidomic assays followed by serial biochemical experiments including mass spectrometry, immunoprecipitation and GST pull‐down were performed to dissect the underlying mechanisms. Results CAND1 promoted the expression of lipid synthesis genes by disrupting SCF complex assembly and lipid accumulation. Furthermore, we identified hnRNPA2B1 as a novel F‐box protein 11 (FBXO11)‐binding partner. FBXO11 directly bound to hnRNPA2B1 and promoted hnRNPA2B1 ubiquitination and subsequent degradation. Our evaluations of the therapeutic efficacy of AAV‐shCAND1 injections confirmed that targeting the CAND1‐SCFFBXO11‐hnRNPA2B1A signalling axis was therapeutically effective. CAND1 downregulation significantly reduced the tumour burden in a primary mouse liver cancer model and a PDX model. Conclusions Our results highlight that CAND1 is associated with poor prognosis in HCC and regulates lipid metabolic reprogramming by dissociating the SCF complex. Targeting the CAND1‐SCFFBXO11‐hnRNPA2B1 axis may be a novel strategy for HCC treatment.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world, with a high likelihood of metastasis and a dismal prognosis. The reprogramming of glucose metabolism is critical in the development of HCC. The Warburg effect has recently been confirmed to occur in a variety of cancers, including HCC. However, little is known about the molecular biological mechanisms underlying the Warburg effect in HCC cells. In this study, we sought to better understand how methyltransferase 5, N6‐adenosine (METTL5) controls the development of HCC and the Warburg effect. Methods In the current study, quantitative real‐time polymerase chain reaction and Western blotting were used to detect the expression of METTL5 in HCC tissues and cell lines. Several different cell models and animal models were established to determine the role of METTL5 in glucose metabolism reprogramming and the underlying molecular mechanism of HCC. Glutathione‐S‐transferase pulldown, coimmunoprecipitation, RNA sequencing, non‐targeted metabolomics, polysome profiling, and luciferase reporter assays were performed to investigate the molecular mechanisms of METTL5 in HCC cells. Results We discovered that METTL5 drove glucose metabolic reprogramming to promote the proliferation and metastasis of HCC. Mechanistically, upregulation of METTL5 promoted c‐Myc stability and thus activated its downstream glycolytic genes lactate dehydrogenase A (LDHA), enolase 1 (ENO1), triosephosphate isomerase 1 (TPI1), solute carrier family 2 member 1 (SLC2A1), and pyruvate kinase M2 (PKM2). The c‐Box and ubiquitin binding domain (UBA) regions of ubiquitin specific peptidase 5 (USP5) binded to c‐Myc protein and inhibited K48‐linked polyubiquitination of c‐Myc. Further study revealed that METTL5 controled the USP5 translation process, which in turn regulated the ubiquitination of c‐Myc. Furthermore, we identified cAMP responsive element binding protein 1 (CREB1)/P300 as a critical transcriptional regulator of METTL5 that promoted the transcription of METTL5 in HCC. In patient‐derived tumor xenograft (PDX) models, adenovirus‐mediated knockout of METTL5 had a good antitumor effect and prolonged the survival of PDX‐bearing mice. Conclusions These findings point to a novel mechanism by which CREB1/P300‐METTL5‐USP5‐c‐Myc controls abnormal glucose metabolism and promotes tumor growth, suggesting that METTL5 is a potential therapeutic target and prognostic biomarker for HCC.

Abstract Globally, hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors. Studies have shown that alterations in the tumor immune microenvironment (TIME) play a significant role in the pathogenesis and progression of HCC, and notably, lipid metabolism has been shown to regulate TIME. Therefore, in predicting the prognosis and efficacy of immunotherapy in patients with HCC, lipid metabolism-related prognostic factors are highly relevant. mRNA expression data of HCC were obtained from the Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and gene expression omnibus (GEO) databases. and lipid metabolism-related genes were also obtained from the GSEA databases. Least absolute shrinkage and selection operator regression analysis, univariate and multivariate Cox proportional hazards analysis were used to explore lipid metabolism-related prognostic genes and further construct a prognostic signature in the training set, ICGC and GSE54236 were used to validate the accuracy of the signature. qRT-PCR was used to detect the mRNA levels of lipid metabolism-related prognostic genes in HCC tissues and their paired adjacent tissues. Nile red staining was used to demonstrate lipid content in HCC tissues. Immunofluores-cence and ELISA were used to detect immune cells and immune responses in HCC tissues and serum. Six lipid metabolism-related genes (ADH1C, APEX1, ME1, S100A10, ACACA and CYP2C9) were identified as independent prognostic factors, which were used for risk model construction for HCC patients. The areas under the 1-, 2-, and 3-year ROC curves for the TCGA cohort were 0.758, 0.701 and 0.671, respectively. Compared with paired paracancerous tissues, qRT-PCR revealed that APEX1, ME1, S100A10 and ACACA were up-regulated in HCC tissues, whereas ADH1C and CYP2C9 were down-regulated in HCC tissues. Nile red staining indicated that this study showed that both the HCC tissue and serum of patients in the high-risk group exhibited lipid accumulation. Our identified prognostic model comprising six lipid metabolism-related genes could provide survival prediction. Moreover, HCC drug therapy target selection and molecular marker research can be guided by our predictive model.

Background The chronic kidney disease-mineral and bone disorder（CKD-MBD) is known to be associated with increased mortality in dialysis patients, but whether current global guidelines for CKD-MBD, which were primarily developed from hemodialysis, are suitable for peritoneal dialysis (PD) patients practice require further investigation.Methods This is a single-center retrospective cohort study. In total 491 prevalent PD patients (median follow-ups: 34 months) from Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2017 were included and followed until 30 June 2018. In the first dialysis year, the average levels of serum calcium, albumin-corrected calcium (CorCa), phosphorus, and parathyroid hormone (PTH) levels were the interested predictors in Cox proportional regression model.Results Of these PD patients (age 58 ± 17 years), 52% were male and 36% had diabetic nephropathy. In Cox regression over first-year mean parameters, PTH

Abstract Background It is highly desirable to develop new therapeutic strategies for gastric cancer given the low survival rate despite improvement in the past decades. Cadherin 17 (CDH17) is a membrane protein highly expressed in cancers of digestive system. Nanobody represents a novel antibody format for cancer targeted imaging and drug delivery. Nanobody targeting CHD17 as an imaging probe and a delivery vehicle of toxin remains to be explored for its theragnostic potential in gastric cancer. Methods Naïve nanobody phage library was screened against CDH17 Domain 1-3 and identified nanobodies were extensively characterized with various assays. Nanobodies labeled with imaging probe were tested in vitro and in vivo for gastric cancer detection. A CDH17 Nanobody fused with toxin PE38 was evaluated for gastric cancer inhibition in vitro and in vivo. Results Two nanobodies (A1 and E8) against human CDH17 with high affinity and high specificity were successfully obtained. These nanobodies could specifically bind to CDH17 protein and CDH17-positive gastric cancer cells. E8 nanobody as a lead was extensively determined for tumor imaging and drug delivery. It could efficiently co-localize with CDH17-positive gastric cancer cells in zebrafish embryos and rapidly visualize the tumor mass in mice within 3 h when conjugated with imaging dyes. E8 nanobody fused with toxin PE38 showed excellent anti-tumor effect and remarkably improved the mice survival in cell-derived (CDX) and patient-derived xenograft (PDX) models. The immunotoxin also enhanced the anti-tumor effect of clinical drug 5-Fluorouracil. Conclusions The study presents a novel imaging and drug delivery strategy by targeting CDH17. CDH17 nanobody-based immunotoxin is potentially a promising therapeutic modality for clinical translation against gastric cancer. Graphical Abstract

PurposeIn clinical practice, the consolidation pattern of pulmonary mucosa-associated lymphoid tissue (C-MALT) was often misdiagnosed as pneumonic-type lung adenocarcinoma (P-LADC). However, the mainstay of treatment and prognosis of these two diseases are different. The purpose of this study was to distinguish C-MALT from P-LADC by pre-treatment chest computed tomography (CT) features.Patients and methodsA total of 31 patients with C-MALT (15 men and 16 women; mean age, 61.1 ± 11.2 years) and 58 patients with P-LADC (34 men and 24 women; mean age, 68.6 ± 7.4 years) confirmed by pathology who underwent contrast-enhanced chest CT were retrospectively enrolled from September 2014 to February 2023. Detailed clinical and CT characteristics of the two groups were evaluated. Logistic regression analysis was used to assess the effectiveness of statistically significant variables in distinguishing C-MALT from P-LADC.ResultsThe average age of C-MALT was younger than P-LADC patients (p

Plasma arc deposition as an additive manufacturing technology has unique advantages for producing parts with complex shapes through layer-by-layer deposition. It is critical to predict and control the temperature field during the production process due to the temperature distribution and gradients determining the properties and performance of the part. Numerical simulation approaches, such as the finite element method, which provides a large amount of data for machine learning modeling, thus reducing the overhead of experimental measurements, are widely used in machine learning. In this paper, we propose a neural network combined finite element method and process prediction workflow. A one-dimensional convolutional neural network model for predicting 2D temperature distribution is developed by training the collected data on the planar temperature field of titanium–aluminum twin-wire plasma arc additive manufacturing and the finite element method. The results show that the predicted temperature mean square error is only 0.5, with less than a 20 °C error in peak temperature and a relative error below 1%. The proposed transfer learning method achieves the same training loss and is 500 iterations faster than basic training, which improves the training speed by 25%. The current study confirms the accurate performance of the ML model and the effectiveness of the optimization method.

Abstract There is a potential correlation between G-protein-coupled receptor-associated sorting protein 1 (GASP1) and breast tumorigenesis. However, its biological function and underlying molecular mechanism in breast cancer have not been clearly delineated. Here, we demonstrated that GASP1 was highly expressed in breast cancers, and patients harboring altered GASP1 showed a worse prognosis than those with wild-type GASP1. Functional studies showed that GASP1 knockout significantly suppressed malignant properties of breast cancer cells, such as inhibition of cell proliferation, colony formation, migration, invasion and xenograft tumor growth in nude mice as well as induction of G1-phase cell cycle arrest, and vice versa. Mechanistically, GASP1 inhibited proteasomal degradation of insulin-like growth factor 1 receptor (IGF1R) by competitively binding to IGF1R with ubiquitin E3 ligase MDM2, thereby activating its downstream signaling pathways such as NF-κB, PI3K/AKT, and MAPK/ERK pathways given their critical roles in breast tumorigenesis and progression. IGF1, in turn, stimulated GASP1 expression by activating the PI3K/AKT pathway, forming a vicious cycle propelling the malignant progression of breast cancer. Besides, we found that GASP1 knockout obviously improved the response of breast cancer cells to paclitaxel. Collectively, this study demonstrates that GASP1 enhances malignant behaviors of breast cancer cells and decreases their cellular response to paclitaxel by interacting with and stabilizing IGF1R, and suggests that it may serve as a valuable prognostic factor and potential therapeutic target in breast cancer.

In the analogy where achieving the “carbon peaking and carbon neutrality” goals (the “dual carbon” goals) is compared to a battle, energy is the main battlefield, and electric power the main force. The low-carbon transformation path of the electric power industry exerts fundamental impact on progress towards carbon peaking and carbon neutrality of the whole society. Therefore, this paper first analyzes challenges and opportunities faced by the electric power industry to achieve the “dual carbon” goals; secondly, on the basis of deep low-carbon, zero-carbon and negative-carbon scenarios of the electric power industry, this paper quantifies and delves into the consumption structure of primary energy and final energy, as well as the future development positioning and trend of different categories of energy. Based on the research results, this paper proposes low-carbon transformation path of the electric power system at the stages of carbon peaking, deep low-carbon and carbon neutrality, and analyzes the trend of power supply cost changes in different scenarios. On this basis, a series of implementation key points and measures are proposed to adapt to green and low-carbon transformation of the electric power industry, covering areas such as coal-fired electric power development positioning, new energy development and utilization, diversified supply and demand, new energy industry chain, and power supply costs, and so forth.

Abstract High performance and durable electrodes are prerequisites for the stable operation of various optoelectronic devices, such as alternating current electroluminescence (ACEL) applications. As for the flexible electrodes based on ultrathin metals, which have attracted much attention in recent years, stability problems as evidenced by optically lossy and electrical degradation of the silver (Ag) layer in the service environment are the key issues to be solved before its practical application. This work prepares ultrathin and stable doped silver films by introducing a small amount of AlN during the sputtering process. The Ag‐AlN thin films exhibit a comprehensive stability promotion in terms of high temperature (250 °C in the air) and damp‐heat (85 °C, 85% relative humidity (RH) for 12 h) test compared with pure Ag counterpart. In addition, flexible ACEL devices based on AZO/Ag‐AlN/AZO/polyethylene terephthalate (PET) films with a luminance of 176.1 cd m−2 at 300 V and 400 Hz and excellent luminescence performance and mechanical flexibility under operating conditions are developed. Such ACEL devices based on these ultrathin and durable Ag‐AlN films are up‐and‐coming in practical, flexible electronics applications.

Abstract Despite of advances in treatment options, hepatocellular carcinoma (HCC) remains nearly incurable and has been recognized as the third leading cause of cancer-related deaths worldwide. As a deubiquitinating enzyme, the antitumor effect of ubiquitin-specific peptidase 53 (USP53) has been demonstrated on few malignancies. In this study, we investigated the potential antitumor role of USP53 in HCC. The results showed that USP53 was downregulated in HCC tissues as well as in HCC cell lines using both in silico data as well as patient samples. Furthermore, the ectopic expression of USP53 inhibited the proliferation, migration and invasion, and induced the apoptosis of HCC cells. Co-immunoprecipitation (CO-IP) assay and mass spectrometry (MS) combined with the gene set enrichment analysis (GSEA) identified cytochrome c (CYCS) as an interacting partner of USP53. USP53 overexpression increased the stability of CYCS in HCC cells following cycloheximide treatment. Finally, the overexpression of CYCS compensated for the decreased apoptotic rates in cells with USP53 knocked down, suggesting that USP53 induced the apoptosis in HCC cells through the deubiquitination of CYCS. To summarize, we identified USP53 as a tumor suppressor as well as a therapeutic target in HCC, providing novel insights into its pivotal role in cell apoptosis.

Abstract Background Mechanisms underlying ischemia/reperfusion injury-acute kidney injury (IRI-AKI) are not fully elucidated. We conducted an integrative analysis of IRI-AKI by bioinformatics methods. Methods We screened gene expression profiles of the IRI-AKI at early phase from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and enrichment pathways were conducted based on gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and Gene set enrichment analysis (GSEA). Immune cell infiltration analysis was performed to reveal the change of the microenvironment cell types. We constructed protein–protein interaction (PPI), and Cytoscape with plug-ins to find hub genes and modules. We performed robust rank aggregation (RRA) to combine DEGs and analyzed the target genes for miRNA/transcription factor (TF) and drug-gene interaction networks. Results A total of 239 and 384 DEGs were identified in GSE87024 and GSE34351 separately, with the 73 common DEGs. Enrichment analysis revealed that the significant pathways involve mitogen-activated protein kinase (MAPK) signaling, interleukin-17, and tumor necrosis factor (TNF) signaling pathway, etc. RRA analysis detected a total of 27 common DEGs. Immune cell infiltration analysis showed the plasma cells reduced and T cells increased in IRI-AKI. We identified JUN, ATF3, FOS, EGR1, HMOX1, DDIT3, JUNB, NFKBIZ, PPP1R15A, CXCL1, ATF4, and HSPA1B as hub genes. The target genes interacted with 23 miRNAs and 116 drugs or molecular compounds such as curcumin, staurosporine, and deferoxamine. Conclusion Our study first focused on the early IRI-AKI adopting RRA analysis to combine DEGs in different datasets. We identified significant biomarkers and crucial pathways involved in IRI-AKI and first construct the immune landscape and detected the potential therapeutic targets of the IRI-AKI by drug-gene network.

Abstract Mesenchymal stem cells (MSCs) are stem cells that exhibit self-renewal capacity and multi-directional differentiation potential. They can be extracted from the bone marrow and umbilical cord, as well as adipose, amnion, and other tissues. They are widely used in tissue engineering and are currently considered an important source of cells in the field of regenerative medicine. Since certain limitations, such as an insufficient cell source, mature differentiation, and low transplantation efficiency, are still associated with MSCs, researchers have currently focused on improving the efficacy of MSCs. Low-intensity pulsed ultrasound (LIPUS) has mechanical, cavitation, and thermal effects that can produce different biological effects on organs, tissues, and cells. It can be used for fracture treatment, cartilage repair, and stem cell applications. An in-depth study of the role and mechanism of action of LIPUS in MSC treatment would promote our understanding of LIPUS and promote research in this field. In this article, we have reviewed the progress in research on the use of LIPUS with various MSCs and comprehensively discussed the progress in the use of LIPUS for promoting the proliferation, differentiation, and migration of MSCs, as well as its future prospects.

Hot compression tests are carried out for the 2219 Al alloys, which are prepared by conventional direct chill casting and internal electromagnetic stirring direct chill casting respectively. The processing maps are constructed and the as-deformed microstructures are observed to investigate the effects of internal electromagnetic stirring on the hot deformation of 2219 Al alloy. The results show that the internal electromagnetic stirring expends of stability domain, especially increasing the corresponding range of strain temperature. The suitable deformation parameters of internal electromagnetic stirring direct chill casting 2219 Al alloy includes a relatively lower strain temperature and a relatively higher strain rate. The internal electromagnetic stirring promotes the formation of more homogeneous as-deformed microstructures and more dynamic recrystallization grains.

Abstract Background Mucosal-associated invariant T (MAIT) cells are systemically depleted in human immunodeficiency virus type 1 (HIV-1) infected patients and are not replenished even after successful combined antiretroviral therapy (cART). This study aimed to identify the mechanism underlying MAIT cell depletion. Methods In the present study, we applied flow cytometry, single-cell RNA sequencing and immunohistochemical staining to evaluate the characteristics of pyroptotic MAIT cells in a total of 127 HIV-1 infected individuals, including 69 treatment-naive patients, 28 complete responders, 15 immunological non-responders, and 15 elite controllers, at the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. Results Single-cell transcriptomic profiles revealed that circulating MAIT cells from HIV-1 infected subjects were highly activated, with upregulation of pyroptosis-related genes. Further analysis revealed that increased frequencies of pyroptotic MAIT cells correlated with markers of systemic T-cell activation, microbial translocation, and intestinal damage in cART-naive patients and poor CD4+ T-cell recovery in long-term cART patients. Immunohistochemical staining revealed that MAIT cells in the gut mucosa of HIV-1 infected patients exhibited a strong active gasdermin-D (GSDMD, marker of pyroptosis) signal near the cavity side, suggesting that these MAIT cells underwent active pyroptosis in the colorectal mucosa. Increased levels of the proinflammatory cytokines interleukin-12 (IL-12) and IL-18 were observed in HIV-1 infected patients. In addition, activated MAIT cells exhibited an increased pyroptotic phenotype after being triggered by HIV-1 virions, T-cell receptor signals, IL-12 plus IL-18, and combinations of these factors, in vitro. Conclusions Activation-induced MAIT cell pyroptosis contributes to the loss of MAIT cells in HIV-1 infected patients, which could potentiate disease progression and poor immune reconstitution.

Abstract To obtain a comprehensive scenario of T cell profiles and synergistic immune responses, we performed single-cell RNA sequencing (scRNA-seq) on the peripheral T cells of 14 individuals with chronic human immunodeficiency virus 1 (HIV-1) infection, including nine treatment-naive (TP) and eight antiretroviral therapy (ART) participants (of whom three were paired with TP cases), and compared the results with four healthy donors (HD). Through analyzing the transcriptional profiles of CD4+ and CD8+ T cells, coupled with assembled T cell receptor sequences, we observed the significant loss of naive T cells, prolonged inflammation, and increased response to interferon-α in TP individuals, which could be partially restored by ART. Interestingly, we revealed that CD4+ and CD8+ Effector-GNLY clusters were expanded in TP cases, and persistently increased in ART individuals where they were typically correlated with poor immune restoration. This transcriptional dataset enables a deeper understanding of the pathogenesis of HIV-1 infection and is also a rich resource for developing novel immune targeted therapeutic strategies.

ObjectiveTo analyze the epidemiological characteristics and spatial correlation distribution of mushroom poisoning in Yunnan Province from 2005 to 2019, and provide scientific evidence for the control and prevention strategy.MethodsData of mushroom poisoning incidents from 2005 to 2019 was collected from the China Information System for public health emergency report and management. The epidemiological characteristics of time, place of occurrence, spatial correlation, and types of poisonous mushrooms were described.ResultsFrom 2005 to 2019, Yunnan Province reported a total of 316 events of mushroom poisoning, the number of cases was 2 009, the number of deaths was 472, and the case fatality rate was 23.49%(472/2 009). The peak of poisoning incidents was from June to August each year, accounting for 83.86%(265/316) of the total number of incidents. Mushroom poisoning incidents occurred in all 16 prefectures in Yunnan Province. Wenshan, Chuxiong, Lincangy and Honghe were high-incidence areas. Among 129 counties, 91 counties reported mushroom poisoning incidents. Homes were the main place where mushroom poisoning occured, accounting for 84.49%(267/316) of the total number of poisoning incidents. The incidence of mushroom poisoning in rural areas was higher than that in urban areas, accounting for 87.97%(278/316). Picking and eating by mistake (78.80%, 249/316) was the main cause of poisonous mushroom poisoning. The main types of poisoning were Amanita exitialis (27.53%, 87/316), Russula subnigricans Hongo (17.09%, 54/316) and Heimioporus retisporus (13.29%, 42/316).ConclusionMushroom poisoning was the main cause of death from food poisoning incidents in Yunnan Province. In the "hot spot" areas where mushroom poisoning incidents occurred, prior to the high-incidence season, various forms of food safety and health education and food safety supervision of mushroom poisoning should be focused on rural areas and high risk mushroom species. Meantime, the ability of rural primary medical institutions should be improved to treat poisonous mushroom poisoning.

Two-dimensional (2D) materials have become more advantageous compared with traditional semiconductor materials for fabrication of modern photodetectors operating at room temperature and possessing small volume and low power consumption. However, the weak absorption caused by atomic thickness severely limits the performance of photodetectors employing 2D materials as active channels. Plasmonic nanomaterials can manipulate light at subwavelength scale and have been viewed as a powerful tool to achieve enhanced photoresponse in semiconductor devices. In this review, the rational design strategies of plasmon-enhanced 2D material photodetectors are comprehensively introduced, where the hybrid nanostructures are classified based on different coupling modes between plasmonic nanostructures and 2D materials. This review has a great chance to provide an instructive reference for understanding and engineering plasmonic effects toward high-performance 2D material photodetectors.

In anterior cervical discectomy and fusion (ACDF), an interbody fusion device is an essential implant. An unsuitable interbody fusion device can cause postoperative complications, including subsidence and nonunion. We designed a customized intervertebral fusion device to reduce postoperative complications and validated it by finite element analysis. Herein, we built a non-homogeneous model of the C3-7 cervical spine. Three implant models (customized cage, commercial cage, and bone graft cage) were constructed and placed in the C45 cervical segment after ACDF surgery. The simulated range of motion (ROM), stress at the cage-bone interface, and stress on the cage and implants were compared under different conditions. The commercial cage showed maximum stress peaks at 40.3 MPa and 43.2 MPa in the inferior endplate of C4 and superior endplate of C5 under rotational conditions, higher compared to 29.7 MPa and 26.4 MPa, respectively, in the customized cage. The ROM was not significantly different between the three cages placed after ACDF. The stresses on the commercial cage were higher compared to the other two cages under all conditions. The bone graft in the customized cage was subject to higher stress than the commercial cage under all conditions, particularly lateral bending, wherein the maximum stress was 5.5 MPa. These results showed that a customized cage that better conformed to the vertebral anatomy was promising for reducing the risk of stress shielding and the occurrence of subsidence.

Hydrogen production by electrolysis is considered an essential means of consuming renewable energy in the future. However, the current assessment of the potential of renewable energy electrolysis for hydrogen production is relatively simple, and the perspective is not comprehensive. Here, we established a Combined Wind and Solar Electrolytic Hydrogen system, considering the influence of regional wind-solar-load characteristics and transmission costs to evaluate the hydrogen production potential of 31 provincial-level regions in China in 2050. The results show that in 2050, the levelized cost of hydrogen (LCOH) in China’s provincial regions will still be higher than 10 ¥/kg, which is not cost-competitive compared to the current hydrogen production from fossil fuels. It is more cost-effective to deploy wind turbines than photovoltaic in areas with similar wind and solar resources or rich in wind resources. Wind-solar differences impact LCOH, equipment capacity configuration, and transmission cost composition, while load fluctuation significantly impacts LCOH and electricity storage configuration. In addition, the sensitivity analysis of 11 technical and economic parameters showed differences in the response performance of LCOH changes to different parameters, and the electrolyzer conversion efficiency had the most severe impact. The analysis of subsidy policy shows that for most regions (except Chongqing and Xizang), subsidizing the unit investment cost of wind turbines can minimize LCOH. Nevertheless, from the perspective of comprehensive subsidy effect, subsidy cost, and hydrogen energy development, it is more cost-effective to take subsidies for electrolysis equipment with the popularization of hydrogen.

Abstract Introduction Long-term exposure to ambient air pollution is related to major cardiovascular risk factors including diabetes, hypertension, hyperlipidemia and overweight, but with few studies in high-concentration nations like China so far. We aimed to investigate the association between long-term exposure to ambient fine particulate matter (particles with an aerodynamic diameter ≤ 2.5 μm, PM2.5) and major cardiovascular risk factors in China. Methods Adult participants with selected biochemical tests were recruited from the Chinese Physiological Constant and Health Condition (CPCHC) survey conducted from 2007 to 2011. Gridded PM2.5 data used were derived from satellite-observed data with adjustment of ground-observed data. District-level PM2.5 data were generated to estimate the association using multivariate logistic regression model and generalized additive model. Results A total of 19,236 participants from the CPCHC survey were included with an average age of 42.8 ± 16.1 years, of which nearly half were male (47.0%). The annual average PM2.5 exposure before the CPCHC survey was 33.4 (14.8–53.4) μg/m3, ranging from 8.0 μg/m3 (Xiwuqi) to 94.7 μg/m3 (Chengdu). Elevated PM2.5 was associated with increased prevalence of hypertension (odds ratio (OR) =1.022, 95% confidence interval (95%CI): 1.001, 1.043) and decreased prevalence of overweight (OR = 0.926, 95%CI: 0.910, 0.942). Education significantly interacted with PM2.5 in association with all the interesting risk factors. Each 10 μg/m3 increment of PM2.5 was associated with increased prevalence of diabetes (OR = 1.118, 95%CI: 1.037, 1.206), hypertension (OR = 1.101, 95%CI: 1.056, 1.147), overweight (OR = 1.071, 95%CI: 1.030, 1.114) in participants with poor education, but not in well-educated population. PM2.5 exposure was negatively associated with hyperlipidemia in all participants (OR = 0.939, 95%CI: 0.921, 0.957). The results were robust in all the sensitivity analyses. Conclusion Association between long-term PM2.5 exposure and cardiovascular risk factors might be modified by education. PM2.5 was associated with a higher prevalence of diabetes, hypertension, and overweight in a less-educated population with time-expose dependency. Long-term exposure to PM2.5 might be associated with a lower prevalence of hyperlipidemia.