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Promoting the high-quality development of the marine economy is an inevitable choice for building a maritime power, and technological innovation can provide strong impetus for the high-quality development of the marine economy. Therefore, it is urgent to clarify the impact mechanism of technological innovation on the high-quality development of the marine economy, and promote the high-quality development of the marine economy. This study employs panel data from 11 coastal provinces and municipalities (autonomous regions) in China, spanning the years 2006 to 2020. The objective is to empirically evaluate the mechanism through which scientific and technical innovation impacts the high-quality development of the marine economy. This is achieved by utilizing the PVAR model and the mediation effect model. The research findings indicate that there is a noteworthy impact of enhancing scientific and technological innovation on the marine economy of China. Moreover, there exists a significant reciprocal relationship between scientific and technological innovation and the pursuit of high-quality development in the marine economy. It is observed that scientific and technological innovation not only has a positive influence on the high-quality development of the marine economy by enhancing green total factor productivity and optimizing the industrial structure, but it also facilitates the advancement of the marine economy through the chain mediation path of “improving green total factor productivity and optimizing industrial structure”.

BackgroundFungal co-infection is prevalent in critically ill patients with COVID-19. The conventional approach applied to fungal identification has relatively low sensitivity and is time-consuming. The metagenomic next-generation sequencing (mNGS) technology can simultaneously detect a variety of microorganisms, and is increasingly being used for the rapid detection and diagnosis of pathogens.MethodsIn this single-center retrospective study, we described the clinical presentation and outcomes of COVID-19 and mNGS positive for fungi in pulmonary critically ill patients during the outbreak of Omicron infection from December 2022 to January 2023.ResultsAmong 43 COVID-19 patients with acute respiratory distress syndrome (ARDS) on a single intensive care unit (ICU), 10 were reported to be fungal positive using the mNGS test. The number of pathogenic microorganisms detected by mNGS was significantly higher than that via traditional methods, especially in the detection of fungi and viruses. Aspergillus infection was dominant, and most of these patients also had concurrent bacterial or viral infections. Probable or possible COVID-19-associated pulmonary aspergillosis (CAPA) was diagnosed in all 10 patients, and the prognosis was poor.ConclusionPatients with COVID-19 may be at increased risk of developing fungal infections as well as concurrent bacterial or viral infections, and mNGS can be a powerful tool in identifying these infections. Clinicians should be aware of the increased risk of fungal infections in COVID-19 patients, particularly those who have underlying immunocompromising conditions, and should monitor for early signs of infection.

The midgut, a vital component of the digestive system in arthropods, serves as an interface between ingested food and the insect’s physiology, playing a pivotal role in nutrient absorption and immune defense mechanisms. Distinct cell types, including columnar, enteroendocrine, goblet and regenerative cells, comprise the midgut in insects and contribute to its robust immune response. Enterocytes/columnar cells, the primary absorptive cells, facilitate the immune response through enzyme secretions, while regenerative cells play a crucial role in maintaining midgut integrity by continuously replenishing damaged cells and maintaining the continuity of the immune defense. The peritrophic membrane is vital to the insect’s innate immunity, shielding the midgut from pathogens and abrasive food particles. Midgut juice, a mixture of digestive enzymes and antimicrobial factors, further contributes to the insect’s immune defense, helping the insect to combat invading pathogens and regulate the midgut microbial community. The cutting-edge single-cell transcriptomics also unveiled previously unrecognized subpopulations within the insect midgut cells and elucidated the striking similarities between the gastrointestinal tracts of insects and higher mammals. Understanding the intricate interplay between midgut cell types provides valuable insights into insect immunity. This review provides a solid foundation for unraveling the complex roles of the midgut, not only in digestion but also in immunity. Moreover, this review will discuss the novel immune strategies led by the midgut employed by insects to combat invading pathogens, ultimately contributing to the broader understanding of insect physiology and defense mechanisms.

Currently kiwifruit picking process mainly leverages manual labor, which has low productivity and high labor intensity, meanwhile, the existing kiwifruit picking machinery also has low picking efficiency and easily damages fruits. In this regard, a kiwifruit picking robot suitable for orchard operations was developed in this paper for kiwifruit grown in orchard trellis style. First, based on the analysis of kiwifruit growth pattern and cultivation parameters, the expected design requirements and objectives of a kiwifruit picking robot were proposed, and the expected workflow of the robot in the kiwifruit orchard environment was given, which in turn led to a multi-fruit envelope-cutting kiwifruit picking robot was designed. Then, the D-H method was used to establish the kinematic Equations of the kiwifruit-picking robot, the forward and inverse kinematic calculations were carried out, and the Monte Carlo method was used to analyze the workspace of the robot. By planning the trajectory of the robotic arm and calculating critical nodes in the picking path, the scheme of trajectory planning of the robot was given, and MATLAB software was applied to simulate the motion trajectory as well as to verify the feasibility of the trajectory planning scheme and the picking strategy. Finally, a kiwifruit picking test bed was set up to conduct picking tests in the form of fruit clusters. The results show that the average time to pick each cluster of fruit was 9.7s, the picking success rate was 88.0%, and the picking damage rate was 7.3%. All the indicators met the requirements of the expected design of the kiwifruit-picking robot.

Purpose: To investigate the pharmacokinetics and tissue distribution of VGB racemate and its single enantiomers, and explore the potential of clinic development for single enantiomer S-VGB. Methods: In the pharmacokinetics study, male Sprague-Dawley rats were gavaged with VGB racemate or its single enantiomers dosing 50, 100 or 200 mg/kg, and the blood samples were collected during 12 h at regular intervals. In the experiment of tissue distribution, VGB and its single enantiomers were administered intravenously dosing 200 mg/kg, and the tissues including heart, liver, spleen, lung and kidney, eyes, hippocampus, and prefrontal cortex were separated at different times. The concentrations of R-VGB and S-VGB in the plasma and tissues were measured using HPLC. Results: Both S-VGB and R-VGB could be detected in the plasma of rats administered with VGB racemate, reaching Cmax at approximately 0.5 h with t1/2 2–3 h. There was no significant pharmacokinetic difference between the two enantiomers when VGB racemate was given 200 mg/kg and 100 mg/kg. However, when given at the dose of 50 mg/kg, S-VGB presented a shorter t1/2 and a higher Cl/F than R-VGB, indicating a faster metabolism of S-VGB. Furthermore, when single enantiomer was administered respectively, S-VGB presented a slower metabolism than R-VGB, as indicated by a longer t1/2 and MRT but a lower Cmax. Moreover, compared with the VGB racemate, the single enantiomers S-VGB and R-VGB had shorter t1/2 and MRT, higher Cmax and AUC/D, and lower Vz/F and Cl/F, indicating the stronger oral absorption and faster metabolism of single enantiomer. In addition, regardless of VGB racemate administration or single enantiomer administration, S-VGB and R-VGB had similar characteristics in tissue distribution, and the content of S-VGB in hippocampus, prefrontal cortex and liver was much higher than that of R-VGB. Conclusions: Although there is no transformation between S-VGB and R-VGB in vivo, those two enantiomers display certain disparities in the pharmacokinetics and tissue distribution, and interact with each other. These findings might be a possible interpretation for the pharmacological and toxic effects of VGB and a potential direction for the development and optimization of the single enantiomer S-VGB.

Thanks to the rapidly increasing time-domain facilities, we are entering a golden era of research on gamma-ray bursts (GRBs). In this Letter, we report our observations of GRB 240529A with the Burst Optical Observer and Transient Exploring System, the 1.5 m telescope at Observatorio de Sierra Nevada, the 2.5 m Wide Field Survey Telescope of China, the Large Binocular Telescope, and the Telescopio Nazionale Galileo. The prompt emission of GRB 240529A shows two comparable energetic episodes separated by a quiescence time of roughly 400 s. Combining all available data on the GRB Coordinates Network, we reveal the simultaneous apparent X-ray plateau and optical rebrightening around 10 ^3 –10 ^4 s after the burst. Rather than the energy injection from the magnetar as widely invoked for similar GRBs, the multiwavelength emissions could be better explained as two shocks launched from the central engine separately. The optical peak time and our numerical modeling suggest that the initial bulk Lorentz factor of the later shock is roughly 50, which indicates that the later jet should be accretion driven and have a higher mass loading than a typical one. The quiescence time between the two prompt emission episodes may be caused by the transition between different accretion states of a central magnetar or black hole, or the fallback accretion process. A sample of similar bursts with multiple emission episodes in the prompt phase and sufficient follow-up could help to probe the underlying physics of GRB central engines.

This study delves into the impact of digital inclusive finance on environmental pollution, with a specific focus on air pollution. Utilizing data from 265 Chinese cities, advanced econometric methods such as the bi-directional fixed effects model, threshold model, spatial Durbin model, and multi-period difference-in-differences model are employed, incorporating a variety of control variables. The empirical findings indicate that digital inclusive finance significantly reduces air pollution. This mechanism chiefly operates through enhancing public environmental consciousness and fostering green technological innovation. The study also uncovers the spatial spillover effect and non-linear characteristics of digital inclusive finance on air pollution, along with its interactive effects with specific policies (e.g., smart city pilot policies and the "major protection, no major development" initiative). Moreover, heterogeneity analysis reveals regional variations in the environmental effects of digital inclusive finance. These insights provide a novel perspective on the relationship between financial technology and environmental protection and offer crucial guidance for policymaking.

Natural polysaccharides extracted from plants have received increasing attention due to their rich bioactivity. In our study, peach gum polysaccharides (PGPs) were extracted by water extraction-alcohol precipitation method. PGPs are typical pyranose polysaccharides with a mean molecular weight of 3.68 × 106 g/mol. The antioxidant activity and hepatoprotective capacity of PGPs were studied. In vitro, assays showed that PGPs scavenged DPPH, OH, and O2– in a dose-dependent manner. PGPs exhibited antioxidative properties against alcohol-induced HL7702 cells, as evidenced by the normalization of MDA, SOD, ROS, and GSH levels. To further elucidate the hepatoprotective mechanism of PGPs, we carried out in vivo experiments in male mice. PGPs exerted hepatoprotective effects in alcohol liver disease (ALD) mice by exerting antioxidant effects, decreasing the inflammatory response and modulating lipid metabolism. In addition, metabolomic analysis indicated that PGPs mainly regulate D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and arginine biosynthesis to promote hepatic metabolism and maintain body functions. Overall, this study revealed that the hepatoprotective mechanism of PGPs against ALD might be associated with the regulation of oxidative stress and lipid metabolism.

The aroma types of cream cheese affect its commercial value and consumer acceptability. However, the types of volatile substances and sensory characteristics of cream cheese at different fermentation stages are still unclear. Therefore, in this study, headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) and headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) were used to analyze the volatile substances in cream cheese fermentation. Orthogonal partial least squares discriminant analysis (OPLS-DA), odor activity value (OAV), relative odor activity value (ROAV) and variable projection importance (VIP) were used to identify the characteristic flavor substances in cream cheese fermentation. Finally, the relationship between key flavor substances and sensory characteristics was determined by partial least squares (PLS) analysis. A total of 34 and 36 volatile organic compounds were identified by HS-SPME-GC-MS and HS-GC-MS, respectively, and 14 characteristic flavor substances were found, based on VIP, ROAV and OAV models. Combined with sensory analysis and flavor substance changes, it was found that the cream cheese fermented for 15 d had the best flavor and taste. This study reveals the characteristics and contribution of volatile substances in cream cheese at different fermentation stages, which provides new insights into improving flavor and quality control.

It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003-2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We further analyzed the impact of TPP1 expression on the overall survival of cervical cancer patients by calculating the hazard ratio (HR) with 95% confidence intervals (CIs) using the multivariable-adjusted Cox regression model. Compared to the normal cervix, high TPP1expression was significantly associated with CIN 3 and cervical cancers (P

Background and Aims. Recurrence of gastroesophageal varices (GEVs) after sclerotherapy is a public health problem. However, mass screening of recurrence of GEVs through gastroscopy is a high-cost procedure. We aim to evaluate the changes in liver stiffness (LS) over time after endoscopic injection sclerotherapy (EIS) and determine its value in predicting the recurrence of GEVs. Methods. One hundred and thirty-five patients with GEVs who underwent EIS treatment were included in this study. The patients were divided into two groups, namely, the nonrecurrence and recurrence groups, based on endoscopic findings at 6 months after discharge. LS measurements were obtained on five occasions. Repeated measure analysis of variance was employed to assess LS differences at different time points and compare them between the two groups. Results. The LS values during the 6-month postdischarge period were consistently higher than the baseline value (measured on the day of hospitalization). The recurrence group demonstrated sustained elevated LS levels throughout the 6-month follow-up period, while the nonrecurrence group showed a gradual decline in LS. The difference in LS trend between the two groups was statistically significant (P=0.04). The area under the curve (AUC) values for LS differences were 0.806, with a corresponding 95% confidence interval (CI) of 0.640-0.918 and a cut-off value of 0.556, indicating their potential utility in predicting GEV recurrence. Conclusions. Longitudinal assessment of LS values in post-EIS patients can provide valuable information for predicting the recurrence of GEVs.

BackgroundExtensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and the underlying mechanism remains unclear. This study was designed to investigate the association between C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness.MethodsA comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens.ResultsCompared to C. sinensis (-) HCC patients, C. sinensis (+) HCC patients exhibited advanced Barcelona Clinic Liver Cancer (BCLC) stage, higher male prevalence and more liver cirrhosis as well as elevated alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM.ConclusionHCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC.Author summaryClonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis and HCC, such as gender, BCLC stage, liver cirrhosis, MVI, AFP, CA19-9, circulating eosinophils and complements. Furthermore, we found that the co-occurrence of C. sinensis exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. Our results provide a more comprehensive comprehension of the interplay between C. sinensis and HCC, shedding fresh light on the carcinogenic potential of C. sinensis.

Adenine nucleotide translocator (ANT) is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner membrane. It plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the cytoplasm. The isoform ANT1 predominately expresses in cardiac and skeletal muscles. Mutations or dysregulation in ANT1 have been implicated in various mitochondrial disorders and neuromuscular diseases. We aimed to examine whether ANT1 deletion may affect mitochondrial redox state in our established ANT1-deficient mice. Hearts and quadriceps resected from age-matched wild type (WT) and ANT1-deficient mice were snap-frozen in liquid nitrogen. The Chance redox scanner was utilized to perform 3D optical redox imaging. Each sample underwent scanning across 3–5 sections. Global averaging analysis showed no significant differences in the redox indices (NADH, flavin adenine dinucleotide containing-flavoproteins Fp, and the redox ratio Fp/(NADH+Fp) between WT and ANT1-deficient groups. However, quadriceps had higher Fp than hearts in both groups ([Formula: see text] and 0.01, respectively). Furthermore, the quadriceps were also more oxidized (a higher redox ratio) than hearts in WT group ([Formula: see text]). NADH levels were similar in all cases. Our data suggest that under non-stressful physical condition, the ANT1-deficient muscle cells were in the same mitochondrial state as WT ones and that the significant difference in the mitochondrial redox state between quadriceps and hearts found in WT might be diminished in ANT1-deficient ones. Redox imaging of muscles under physical stress can be conducted in future.

The potential adverse effects of the plant-based dietary pattern on bone health have received widespread attention. However, the biological mechanisms underlying the adverse effects of plant-based diets on bone health remain incompletely understood. The objective of this study was to identify potential biomarkers between plant-based diets and bone loss utilizing metabolomic techniques in the Taizhou Imaging Study (TIS) (N = 788). Plant-based diet indexes (overall plant-based diet index (PDI), healthy plant-based diet index (hPDI), and unhealthy plant-based diet index (uPDI)) were calculated using the food frequency questionnaire, and bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. A multinomial logistic regression was used to explore the associations of plant-based diet indexes with bone loss. Furthermore, mediation analysis and exploratory factor analysis (EFA) were performed to explore the mediated effects of metabolites on the association of plant-based diets with BMD T-score. Our results showed that higher hPDI and uPDI were positively associated with bone loss. Moreover, nineteen metabolites were significantly associated with BMD T-score, among them, seven metabolites were associated with uPDI. Except for cholesterol esters in VLDL-1, the remaining six metabolites significantly mediated the negative association between uPDI and BMD T-score. Interestingly, we observed that the same six metabolites mediated the positive association between fresh fruit and BMD T-score. Collectively, our results support the deleterious effects of plant-based diets on bone health and discover the potential mediation effect of metabolites on the association of plant-based diets with bone loss. The findings offer valuable insights that could optimize dietary recommendations and interventions, contributing to alleviate the potential adverse effects associated with plant-based diets.

Abstract Proton‐conducting solid oxide fuel cells (H‐SOFCs) have the potential to be a promising technology for energy conversion and storage. To achieve high chemical compatibility and catalytic activity, nickel‐doped barium ferrate with triple conducting ability is developed as cathodes for H‐SOFCs, presenting an impressive electrochemical performance at intermediate temperatures. The cell performance with the optimized BaCe0.26Ni0.1Fe0.64O3–δ (BCNF10) composite cathode reaches an outstanding performance of 1.04 W cm−2 at 600 °C. The high electrocatalytic capacity of the nickel‐doped barium ferrate cathode can be attributed to its significant proton conductivity which is confirmed through hydrogen permeation experiments. Density functional theory (DFT) calculations are further conducted to reveal that the presence of nickel can enhance processes of hydration formation and proton migration, leading to improve proton conductivity and electro‐catalytic activity.

Metal–insulator transition has long been one of the key subjects in condensed matter systems. Herein, the emergence of a large energy gap (Eg, 0.8–1.0 eV) in Bi(110) two‐atomic‐layer nanoribbons grown on a SnSe(001) substrate is reported, which normally has an intrinsic semimetal‐like characteristic. The existence of this abnormally large Eg in Bi(110) is, however, determined by Bi coverage. When coverage is above ≈64 ± 2%, Eg vanishes, and instead, a Bi(110) semimetal‐like phase appears through a singular insulator–metal transition. Measurements using qPlus atomic force microscopy demonstrate that either insulating or semimetal‐like Bi(110) possesses a distorted black phosphorous structure with noticeable atomic buckling. Density function theory fully reproduces the semimetal‐like Bi(110) on SnSe(001). However, none of the insulating phases with this large Eg could be traced. Although the underlying mechanism of the large Eg and the insulator‐metal transition requires further exploration, experiments demonstrate that similar results can be achieved for Bi grown on SnS, the structural analog of SnSe, exhibiting an even larger Eg of ≈2.3 eV. The experimental strategy may be generalized to utilization of group‐IV monochalcogenides to create Bi(110) nanostructures with properties unachievable on other surfaces, providing an intriguing platform for exploring the interesting quantum electronic phases.

Summary: Ubiquitination modification is an important post-translational modification that regulates the stability and function of proteins. Here, we present a protocol to detect the K27-linked polyubiquitination of exogenous and endogenous mitochondrial antiviral signaling protein. We describe steps for detecting ubiquitination of exogenous protein, transfecting the encoding plasmid of the protein, and immunoprecipitating the target protein with an antibody. We then detail procedures for detecting ubiquitin of the target protein by western blot. This protocol applies to other proteins of interest.For complete details on the use and execution of this protocol, please refer to Jiang et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

ABSTRACTCurrent unprecedented mpox outbreaks in non-endemic regions represent a global public health concern. Although two live-attenuated vaccinia virus (VACV)-based vaccines have been urgently approved for people at high risk for mpox, a safer and more effective vaccine that can be available for the general public is desperately needed. By utilizing a simplified manufacturing strategy of mixing DNA plasmids before transcription, we developed two multi-antigen mRNA vaccine candidates, which encode four (M1, A29, B6, A35, termed as Rmix4) or six (M1, H3, A29, E8, B6, A35, termed as Rmix6) mpox virus antigens. We demonstrated that those mpox multi-antigen mRNA vaccine candidates elicited similar potent cross-neutralizing immune responses against VACV, and compared to Rmix4, Rmix6 elicited significantly stronger cellular immune responses. Moreover, immunization with both vaccine candidates protected mice from the lethal VACV challenge. Investigation of B-cell receptor (BCR) repertoire elicited by mpox individual antigen demonstrated that the M1 antigen efficiently induced neutralizing antibody responses, and all neutralizing antibodies among the top 20 frequent antibodies appeared to target the same conformational epitope as 7D11, revealing potential vulnerability to viral immune evasion. Our findings suggest that Rmix4 and Rmix6 from a simplified manufacturing process are promising candidates to combat mpox.

Abstract Diabetic retinopathy (DR) is one of the most prevalent retinal disorders worldwide, and it is a major cause of vision impairment in individuals of productive age. Research has demonstrated the significance of autophagy in DR, which is a critical intracellular homeostasis mechanism required for the destruction and recovery of cytoplasmic components. Autophagy maintains the physiological function of senescent and impaired organelles under stress situations, thereby regulating cell fate via various signals. As the retina's functional and fundamental unit, the retinal neurovascular unit (NVU) is critical in keeping the retinal environment's stability and supporting the needs of retinal metabolism. However, autophagy is essential for the normal NVU structure and function. We discuss the strong association between DR and autophagy in this review, as well as the many kinds of autophagy and its crucial physiological activities in the retina. By evaluating the pathological changes of retinal NVU in DR and the latest advancements in the molecular mechanisms of autophagy that may be involved in the pathophysiology of DR in NVU, we seek to propose new ideas and methods for the prevention and treatment of DR.

Abstract Background Cataract is commonly observed in patients with primary angle-closure glaucoma; however, its underlying pathological mechanisms remain unclear. This study aimed to improve our knowledge on the pathological processes involved in primary angle-closure glaucoma (PACG) by identifying potential prognostic genes associated with cataract progression. Methods Thirty anterior capsular membrane samples were collected from PACG patients with cataracts and age-related cataracts. Differentially expressed genes (DEGs) between these two cohorts were analyzed using high-throughput sequencing. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to screen the DEGs, and potential prognostic markers and their coexpression network were then predicted by bioinformatic analyses. The DEGs were further validated by reverse transcription-quantitative polymerase chain reaction. Results A total of 399 DEGs were found to be specifically associated with cataracts development in PACG patients, among which 177 and 221 DEGs were upregulated and downregulated, respectively. STRING and Cytoscape network analyses revealed seven genes—CTGF, FOS, CAV1, CYR61, ICAM1, EGR1, and NR4A1—that were remarkably enriched and mainly involved in the MAPK, PI3K/Akt, Toll-like receptor, and TNF signaling pathways. RT-qPCR-based validation further confirmed that the sequencing results were accurate and reliable. Conclusions Herein, we identified seven genes and their signaling pathways that may contribute to cataract progression in patients with high intraocular pressure. Taken together, our findings highlight new molecular mechanisms that may explain the high incidence of cataracts in PACG patients. In addition, the genes identified herein may represent new foundations for the development of therapeutic strategies for PACG with cataract.

Abstract Background During the COVID-19 pandemic, it is vital for individuals to comply with the government’s prevention and control measures. This study aims to explore determinants of college students’ compliance behaviour during the COVID-19 pandemic. Methods This study conducted an online survey among 3,122 individuals aged 18 and above from March to November 2022 in China. Individuals’ compliance behaviour was divided into protective behaviour (that includes wearing a mask, maintaining a physical distance, and getting vaccinated) and restrictive behaviour (that includes offering health codes and a nucleic acid test certificate). Individuals’ compliance motivation was divided into calculated motivation (including the fear of being infected, the fear of being published, and previous experience of pandemic prevention) and normative motivation (including the sense of social responsibility and trust in government). We defined young people aged between 18 and 24 with a college degree as young elites, and constructed ordinary least squares linear regression to compare their compliance behaviour with young people without a college degree (young non-elites), and non-young people with a college degree (non-young elites). Results Almost three years after the outbreak of the pandemic, Chinese individuals retained a high degree of compliance with COVID-19 prevention and control policies, particularly with respect to the provision of health codes. Young elites were more compliant with getting vaccinated, wearing a mask, providing health codes and testing results than their counterparts. The sense of social responsibility and trust in government were the major drivers of young elites’ compliance behaviour during the pandemic. Young elites who were male, had a rural “hukou”, and were not a member of the China Communist Party were more compliant with COVID-19 prevention and control measures. Conclusion This study found that young elites in China had high policy compliance during the COVID-19 pandemic. These young elites’ compliance behaviour was driven by their sense of social responsibility and trust in government rather than the fear of being infected and the fear of being punished as a result of violating the regulations. We suggest that in the context of managing health crises, in stead of introducing punitive measures to enforce citizens to comply with the management measures, promoting citizens’ sense of social responsibility and building a trusting relationship with citizens contrite to the enhancement of citizens’ policy compliance.

Abstract Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first‐ and second‐line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow‐up of TETs.

Abstract Animal models play crucial roles in the rapid development of vaccines/drugs for the prevention and therapy of COVID-19, but current models have some deficits when studying the pathogenesis of SARS-CoV-2 on some special tissues or organs. Here, we generated a human ACE2 and SARS-CoV-2 NF/F knockin mouse line that constitutively expresses human ACE2 and specifically expresses SARS-CoV-2 N gene induced by Cre-recombinase. By crossing with Cre transgenic lines allowing for lung-specific and constitutive expression, we generated lung-specific (Sftpc-hACE2-NF/F) and constitutive SARS-CoV-2 N (EIIa-hACE2-NF/F) expressing mice. Upon intranasal infection with a SARS-CoV-2 GFP/ΔN strain which can only replicate in SARS-CoV-2 N expressed cells, we demonstrated that both the Sftpc-hACE2-NF/F and EIIa-hACE2-NF/F mice support viral replication. Consistent with our design, viral replication was limited to the lung tissues in Sftpc-hACE2-NF/F mice, while the EIIa-hACE2-NF/F mice developed infections in multiple tissues. Furthermore, our model supports different SARS-CoV-2 variants infection, and it can be successfully used to evaluate the effects of therapeutic monoclonal antibodies (Ab1F11) and antiviral drugs (Molnupiravir). Finally, to test the effect of SARS-CoV-2 infection on male reproduction, we generated Sertoli cell-specific SARS-CoV-2 N expressed mice by crossing with AMH-Cre transgenic line. We found that SARS-CoV-2 GFP/ΔN strain could infect Sertoli cells, led to spermatogenic defects due to the destruction of blood-testis barrier. Overall, combining with different tissue-specific Cre transgenic lines, the human ACE2 and SARS-CoV-2 NF/F line enables us to evaluate antivirals in vivo and study the pathogenesis of SARS-CoV-2 on some special tissues or organs.

Abstract Background Several risk factors of immune checkpoint inhibitors (ICIs)-associated acute kidney injury (AKI) have been reported sporadically. To identify the risk factors of ICIs-associated AKI in a large-scale population, therefore we conducted a systematic review and a real-world retrospective study. Methods We search literature concerning risk factors of ICIs-associated AKI in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to January 2022. Meta-analysis was performed by using odds ratios (ORs) with 95%CIs. In a separate retrospective pharmacovigilance study by extracting data from US FDA Adverse Event Reporting System (FAERS) database, disproportionality was analyzed using the reporting odds ratio (ROR). Results A total of 9 studies (5927 patients) were included in the meta-analysis. The following factors were associated with increased risk of ICIs-associated AKI, including proton pump inhibitors(PPIs) (OR = 2.07, 95%CI 1.78–2.42), angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) (OR = 1.56, 95%CI 1.24–1.95), nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 1.29, 95%CI 1.01–1.65), diuretics (OR = 2.00, 95%CI 1.38–2.89), diabetes mellitus (OR = 1.28, 95%CI 1.04–1.57), genitourinary cancer (OR = 1.46, 95%CI 1.15–1.85), combination therapy of ICIs (OR = 1.93, 95%CI 1.25–2.97) and extrarenal immune-related adverse events(irAEs) (OR = 2.51, 95%CI 1.96–3.20). Furthermore, analysis from FAERS database verified that concurrent exposures of PPIs (ROR = 2.10, 95%CI 1.91–2.31), ACEIs/ARBs (ROR = 3.25, 95%CI 2.95–3.57), NSAIDs (ROR = 3.06, 95%CI 2.81–3.32) or diuretics (ROR = 2.82, 95%CI 2.50–3.19) were observed significant signals associated with AKI in ICIs-treated patients. Conclusions Concurrent exposures of PPIs, ACEIs/ARBs, NSAIDs or diuretics, diabetes mellitus, genitourinary cancer, combination therapy, and extrarenal irAEs seem to increase the risk of AKI in ICIs-treated patients.

Abstract Aim To analyze the changes of chronotypes in patients with depression before and after treatment, and explore the effects of different chronotypes on antidepressant treatment and the dimensions of common symptoms in patients with depression. Methods 180 patients with depression were selected from 10 tertiary psychiatric hospitals in Zhejiang province, according to the scores of morningness-eveningness questionnaire (MEQ), the patients were divided into three groups: early-type group, middle-type group and late-type group. The 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale anxiety Scale (HAMA), Snaith Hamilton Pleasure Scale (SHAPS), multidimensional fatigue inventory-20(MFI-20) and Pittsburgh sleep quality index (PSQI) were measured at baseline and at the end of the 2nd, 4th, 8th and 12th weeks, the variance analysis of repeated measures was used to analyze the change of each index in the study. The remission rate of depression at each time point was statistically analyzed. Results Of the 180 patients included in the study, 26 were lost to follow-up, and 154 were finally included in the analysis. At baseline, 14.93%, 56.5% and 28.57% of the subjects were diagnosed as middle-late type, middle-late type and early-late type respectively, the total scores of Shaps and MFI-20 in the early-type group were higher than those in the late-type group and the middle-type group (p 0.05) . Conclusion The disorder of chronotypes is common in patients with depression. The time effect of different time type on different symptom dimension of depression was affected, but the effect on remission rate of depression was not significant. To strengthen the management of biological chronotype rhythm in patients with depression may be of great significance in the treatment of depression.

Extending the interval between doses of mRNA Covid-19 vaccines has been linked with a reduced risk of myocarditis in children and adolescents, but impacts on vaccine effectiveness are not known. Here, the authors perform a nested case-control study using data from Hong Kong and find evidence of reduced risk of infection following a longer dosing interval.

With the rapid development of energy, power electronic equipment plays a crucial role in renewable energy. Modular multilevel converter (MMC) has turned into cutting-edge inverter topology in flexible HVDC and offshore wind power situations. However, under the conditions of high humidity and high voltage, the internal submodules lifetime of MMC might be affected. The system reliability mainly depends on good running of the submodules, so stable performance of the submodules serious threat to the normal operation of the inverter. Therefore, this paper proposes a model based on Peck accelerated life predictable model, and model predictive control (MPC) strategy is improved, at the same time without affecting the external characteristics can better control the submodule voltage fluctuations. What is more, real time monitoring of the working environment of the converter through the optical fiber sensing module. Finally, the experimental and simulative outcomes show that the proposed control strategy can effectively reduce the voltage fluctuations in the small module, and the life parameters of the submodules can be obtained in real time by bringing the results into the proposed life prediction model. By comparing the results, the results can be obtained the proposed control strategy can effectively increase the reliability of the submodule.

Abstract Adiponectin, one of the most ubiquitous adipokines found in the blood, plays a major role in glucolipid metabolism and energy metabolism and regulation. In recent years, a growing body of research indicates that adiponectin also plays a significant role in diabetic retinopathy. In the present review, we specifically address the protective effects of adiponectin on the development and progression of diabetic retinopathy through improvement in insulin resistance, alleviation of oxidative stress, limiting of inflammation, and prevention of vascular remodeling, with the aim to explore new potential approaches and targets for the prevention and treatment of diabetic retinopathy.

Abstract Background Studies have not systematically compared the ability to verify performance of prognostic transcripts in paired bulk mononuclear cells versus viable CD34-expressing leukemic blasts from patients with acute myeloid leukemia. We hypothesized that examining the homogenous leukemic blasts will yield different biological information and may improve prognostic performance of expression biomarkers. Methods To assess the impact of cellular heterogeneity on expression biomarkers in acute myeloid leukemia, we systematically examined paired mononuclear cells and viable CD34-expressing leukemic blasts from SWOG diagnostic specimens. After enrichment, patients were assigned into discovery and validation cohorts based on availability of extracted RNA. Analyses of RNA sequencing data examined how enrichment impacted differentially expressed genes associated with pre-analytic variables, patient characteristics, and clinical outcomes. Results Blast enrichment yielded significantly different expression profiles and biological pathways associated with clinical characteristics (e.g., cytogenetics). Although numerous differentially expressed genes were associated with clinical outcomes, most lost their prognostic significance in the mononuclear cells and blasts after adjusting for age and ELN risk, with only 11 genes remaining significant for overall survival in both cell populations (CEP70, COMMD7, DNMT3B, ECE1, LNX2, NEGR1, PIK3C2B, SEMA4D, SMAD2, TAF8, ZNF444). To examine the impact of enrichment on biomarker verification, these 11 candidate biomarkers were examined by quantitative RT/PCR in the validation cohort. After adjusting for ELN risk and age, expression of 4 genes (CEP70, DNMT3B, ECE1, and PIK3CB) remained significantly associated with overall survival in the blasts, while none met statistical significance in mononuclear cells. Conclusions This study provides insights into biological information gained/lost by examining viable CD34-expressing leukemic blasts versus mononuclear cells from the same patient and shows an improved verification rate for expression biomarkers in blasts.

Abstract Background Prenatal diagnosis of cleft palate is still challenging. To describe a practical and efficient method, sequential sector-scan through oral fissure (SSTOF), to evaluate palate. Methods According to the characteristics of the fetal oral anatomy and ultrasonic directivity, we designed a practical method, sequential sector-scan through oral fissure, to evaluate the fetal palate, and the approach was verified efficiently by following up results of those fetuses with orofacial cleft who were induced because of their accompanied lethal malformations. Then, the 7098 fetuses were evaluated using sequential sector-scan through oral fissure. Fetuses were followed up after birth or induction to validate and analyze prenatal diagnosis. Result According to the scanning design, sequential sector-scan through oral fissure was performed successfully from the soft palate to the upper alveolar ridge in induced labor fetuses, and the structures were displayed clearly. Among 7098 fetuses, satisfactory images were obtained for 6885 fetuses and the remaining 213 fetuses’ images were unsatisfactory because of fetuses’ positions and pregnant women with high BMI. Among 6885 fetuses, 31cases were diagnosed CLP or CP, which were confirmed after delivery or termination. There were no missing cases. Conclusions SSTOF is a practical and efficient method to diagnose cleft palate, which might be applied to evaluate the fetal palate in prenatal diagnosis.

This paper investigates the influence of the concentration and particle size of h-BN nanoparticles in a nanofluid on the surface integrity of 304 austenitic stainless steel during turning, focusing on the cutting force, friction coefficient, cutting temperature, surface roughness, surface residual stress, work hardening capacity, and 3D surface topography. The results show that, compared to dry cutting, the addition of 3 wt.% h-BN nanofluid can reduce the friction coefficient on the rake face by 38.9%, lower the cutting temperature by 43.5%, decrease the surface roughness by 53.8%, decrease the surface residual stress by 61.6%, and reduce the work hardening degree by 27.5%. Two-dimensional profiles and the 3D surface topography display a more balanced peak–valley distribution. Furthermore, by studying the effect of different h-BN particle sizes in nanofluids on the surface integrity of the machined workpiece, it was found that nanoscale particles have a greater tendency to penetrate the tool–chip interface than submicron particles. Moreover, the h-BN particles in the nanofluid play a “rolling effect” and “microsphere” effect, and the sesame oil will also form a lubricating oil film in the knife-chip contact area, thereby reducing the friction coefficient, reducing the cutting force, and improving the machining surface quality.

Attention deficit hyperactivity disorder (ADHD) is a neuro-developmental disorder that affects approximately 5–10% of school-aged children worldwide. Early diagnosis and intervention are essential to improve the quality of life of patients and their families. In this study, we propose ConvMixer-ECA, a novel deep learning architecture that combines ConvMixer with efficient channel attention (ECA) blocks for the accurate diagnosis of ADHD using electroencephalogram (EEG) signals. The model was trained and evaluated using EEG recordings from 60 healthy children and 61 children with ADHD. A series of experiments were conducted to evaluate the performance of the ConvMixer-ECA. The results showed that the ConvMixer-ECA performed well in ADHD recognition with 94.52% accuracy. The incorporation of attentional mechanisms, in particular ECA, improved the performance of ConvMixer; it outperformed other attention-based variants. In addition, ConvMixer-ECA outperformed state-of-the-art deep learning models including EEGNet, CNN, RNN, LSTM, and GRU. t-SNE visualization of the output of this model layer validated the effectiveness of ConvMixer-ECA in capturing the underlying patterns and features that separate ADHD from typically developing individuals through hierarchical feature learning. These outcomes demonstrate the potential of ConvMixer-ECA as a valuable tool to assist clinicians in the early diagnosis and intervention of ADHD in children.

Summary: Mixed-dimensional heterostructures have drawn significant attention due to their intriguing physical properties and potential applications in electronic and optoelectronic nanodevices. However, limited by the lattice matching, the preparation of heterostructures is experimentally difficult and the underlying growth mechanism has not been well established. Here, we report a three-step seeding epitaxial growth strategy for synthesizing mixed-dimensional heterostructures of one-dimensional microwire (MW) and two-dimensional atomic thin film. Our growth strategy has successfully realized direct epitaxial growth of WSe2 film on WOx MW and significantly improves the quality of the epitaxial WSe2 monolayer, which is evidenced by the remarkably enhanced photoluminescence (PL). More intriguingly, the as-synthesized WOx MWs exhibit a strong nonlinear optical response due to the enhancement effect of the core (WOx)-shell (WSe2) nanocavity. Our work provides a feasible route for direct growth of WOx-based mixed-dimensional heterostructures, which possess potential applications in high-performance optoelectronic devices.

Enhancing corporate green innovation is a crucial pathway towards achieving a green economic transformation. Diverging from the literature focusing on government environmental regulations and hard regulatory approaches, this study investigates how market soft regulation intervenes in corporate green innovation. From the perspective of informal environmental governance, this paper employs a multi-period difference-in-differences empirical model to examine the impact of ESG ratings on corporate green innovation. The findings reveal that ESG ratings have a positive influence on corporate green innovation. Specifically, ESG ratings encourage firms to increase the number of green patents application and authorization, thereby stimulating investment and innovation activities in the realm of green innovation. These conclusions remain robust after undergoing various statistical tests. In the analysis of moderating effects, this paper discovers a negative inhibitory effect of financing constraints on the relationship between ESG ratings and corporate green innovation. Additionally, the study finds that ESG ratings exhibit a more pronounced promotion effect on green innovation among high-pollution and high-quality information disclosure firms. The research emphasizes the importance for enterprises to undertake proactive strategic adjustments and provides insights for optimizing existing green development policies.

BackgroundCOVID-19 has the potential to greatly impact an individual mental well-being. However, an individual’s psychological resilience, combined with support from their community and government disaster relief efforts can aid individuals in confronting crises with a positive mindset. The purpose of this study is to investigate how individuals, across three dimensions of individual resilience perception, community resilience perception, and government trust perception, mitigate individual anxiety during COVID-19.MethodsThis study employed an online survey method that was not restricted by geographical location. Data collection took place from January 2022 to June 2022, and the valid questionnaires covered all 31 provinces, autonomous regions, and municipalities in China. The assessment of community resilience was conducted employing the Conjoint Community Resilience Assessment Measure-10 (CCRAM-10). Structural Equation Modeling (SEM) was also used to examine the relationship between community resilience, government trust, individual psychological resilience, and anxiety.ResultsThe SEM results reveal that individual psychological resilience is significantly negatively correlated with anxiety (b = −0.099, p

The incidence of hyperuricemia is on the rise in China, primarily due to dietary habits. However, limited data exists regarding dietary purine intake in the country. This study aimed to estimate the daily dietary purine intake among Chinese residents from 2014 to 2021 and evaluate the temporal trend using joinpoint regression analysis. The analysis revealed an annual percentage change (APC) of 0.8% (95% CI: 0.1–1.5%) in dietary purine intake prior to the joinpoint (2014–2019). Following the joinpoint (2019–2021), the APC significantly increased to 6.5% (95% CI: 3.3–9.8%), indicating a noteworthy upward trend (p = 0.045). Furthermore, the average daily purine intake varied significantly among different regions of China, with the southern region showing the highest dietary intake of purines. Considering the diverse contributions of various food sources to dietary purine intake, it was observed that meat consumption had the greatest impact, accounting for 36.2% of purine intake, followed by cereals consumption (25.3%) and vegetables and edible fungi (24.2%). These findings hold significance for dietary intervention and management strategies aimed at reducing purine intake among the population.

Purpose This study aims to determine the optimal cut-off value of Ki-67 to better predict the recurrence of early low-risk endometrial cancer (EC). Methods Seven hundred and forty-eight patients diagnosed with low-risk EC from West China Second Hospital of Sichuan University and the First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The receiver operating characteristic curve (ROC) and Youden index were used to calculate the optimal cut-off value of Ki-67 expression. The clinicopathological indexes between two groups divided by cut-off value of Ki-67 were compared. The univariate and multivariate regression analyses were performed to investigate risk factors connected to the recurrence of early low-risk EC. The survival analysis was shown in Kaplan–Meier curve. Result Thirty-three patients were detected with tumor recurrence after primary surgery (4.4%); 33% was the optimal cut-off value of the Ki-67 index. A high Ki-67 was significantly associated with age ( P = .002), myometrial invasion ( P < .001), and the expression of P53 ( P = .007). The multivariate regression analysis verified that Ki67 ≥ 33% was an independent prognostic factor for predicting recurrence. The recurrence-free survival (RFS) and the overall survival (OS) in high Ki-67 group was significantly lower than that in low Ki-67 group ( P < .001 and P = .029, respectively). The prognostic values of ER, PR, and P53 in combination with Ki-67 were superior to each single predictor. Conclusions The optimal cut-off value of Ki-67 for predicting recurrence is 33%, which quantitatively defines the specific value of Ki-67 that causes high-risk recurrence in early low-risk EC.

Introduction Chronic low back pain (cLBP) is one of the largest and most frequent public health problems worldwide. Tuina is a physical therapy commonly used in China to treat musculoskeletal diseases. Compared with traction, there is little high-quality scientific evidence that can demonstrate the effectiveness of Tuina in the treatment of patients with cLBP. Therefore, the purpose of this clinical trial is to evaluate the effect of massage on cLBP patients compared with traction.Methods and analyses This is a single-centre, assessor-blinded and analyst-blinded prospective randomised controlled trial with two parallel arms. Ninety-four patients with cLBP will be recruited. Three treatments were given every week for a total of 4 weeks. In the Traction group, participants were given traction therapy in the Tuina group, participants will receive a four-step physiotherapy including kneading, rolling, plucking and oblique pulling. The outcomes will be measured at baseline, at the end of treatment, as well as 1 and 2 months after treatment. The primary outcome will be the Hamilton Anxiety Scale after 12 sessions of treatment. The secondary outcomes will be the Visual Analogue Scale, the medical outcomes study Short Form 36, Serum Quantitative Index and genetic testing after 12 sessions of treatment.Ethics and dissemination The study was approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated with Shanghai University of Traditional Chinese Medicine.Trial registration number ChiCTR2200065448.

To better serve the public, urban attractions must understand the public's likes and dislikes and continually adapt and optimize their service in response. However, traditional methods for gauging public opinion, such as questionnaires and individual interviews, cannot meet the need for large-scale, time-efficient, and high-precision public preference surveys: only large volumes of online tourist review data will suffice. This study takes Beijing and Shenzhen, the two top-tier cities in North and South China, as subjects to conduct an online review of visitor data for urban attractions in the two cities. Specifically, the influence of attraction features on public perception is quantitatively analyzed from three dimensions—spatial, temporal and resource type—which are combined with Natural Language Processing (NLP), Textual Data Mining, and Econometric analysis. The results show that the influence of four types of features—First impression, Economical, Service and Environmental features—on public perception remains largely consistent under different model conditions. However, different landscape types and attributes affect preferences in different ways. To be precise, water has radically different effects on public preferences in the north and south, with water features in urban attractions in the south contributing less to positive public perceptions. Meanwhile, water features significantly increase preferences for natural landscapes. Furthermore, public perceptions were found to be heavily influenced by public health emergencies (COVID-19). In the two cities studied, the proportion of positive reviews was higher after 2020 than before, as were the regression model indices. Drawing on these results, several suggestions are put forward for the optimization and adaptation of urban attractions.

BTK inhibitors, Bcl-2 inhibitors, and other targeted therapies have significantly improved the outcomes of patients with chronic lymphocytic leukemia (CLL). With increased survivorship, monitoring disease and deciphering potential mechanisms of resistance to these agents are critical for devising effective treatment strategies. We used duplex sequencing, a technology that enables detection of mutations at ultra-low allelic frequencies, to identify mutations in five genes associated with drug resistance in CLL and followed their evolution in two patients who received multiple targeted therapies and ultimately developed disease progression on pirtobrutinib. In both patients we detected variants that expanded and reached significant cancer cell fractions (CCF). In patient R001, multiple known resistance mutations in both BTK and PLCG2 appeared following progression on zanubrutinib (BTK p.L528W, p.C481S; PLCG2 S707F, L845F, R665W, and D993H). In contrast, patient R002 developed multiple BTK mutations following acalabrutinib treatment, including known resistance mutations p.C481R, p.T474I and p.C481S. We found that pirtobrutinib was able to suppress, but not completely eradicate, BTK p.C481S mutations in both patients, but other resistance mutations such as mutations in PLCG2 and new BTK mutations increased while the patients were receiving pirtobrutinib. For example, BTK p.L528W in patient R001 increased in frequency more than 1,000-fold (from a CCF of 0.02% to 35%), and the CCF in p.T474I in patient R002 increased from 0.03% to 4.2% (more than 100-fold). Our data illuminate the evolutionary dynamics of resistant clones over the patients’ disease course and under selective pressure from different targeted treatments.

Solid oxide fuel cells (SOFCs) are widely recognized as efficient energy sources that have the potential to shape the future of energy development. Among various types of SOFCs, the low-temperature operation of proton-conducting SOFCs (H–SOFCs) offers distinct advantages for wide commercialization compared to oxygen-ion conducting SOFCs (O–SOFCs). However, the commercialization of H–SOFCs is hindered by several challenges, including slow oxygen reduction kinetics and long-term instability of cathode materials. The electrochemical performance of the cathode system in H–SOFCs is limited by the poor proton conductivity of the cathode material and the scarcity of surface reaction sites. Additionally, the presence of undesirable phases induced by elements such as Cr and CO2 adversely affects the chemical stability and catalytic activity of the cathode. Thermal stress arising from the mismatch in coefficient of thermal expansion between the cathode and electrolyte further adds to the challenges. Therefore, this comprehensive review presents underlying mechanisms and potential solutions to overcome the challenges in H–SOFCs, leading to higher efficiency and wider commercialization of H–SOFCs.

Inflammatory bowel disease (IBD) is a serious global public health concern. Although the pathogenesis of the disease is currently unknown, it has been reported to be associated with both intestinal microbiota and inflammatory mediators. There is evidence suggesting that the feces of the Plateau pika is useful for treating gastrointestinal injuries and pain. Although fecal microbiota transplantation is highly efficacious intervention for IBD prevention, however, potential the transfer of pathogenic microbes or toxic substances is potentially hazardous. Fortunately, micropore filtering of the donor feces can minimize the risk of bacterial infection allowing retention of the therapeutic effects of the residual bacteriophages. Here, we demonstrated that Plateau pika feces not only alleviated the IBD symptoms but also promoted optimal structure and composition of the intestinal microbiota. Additionally, Plateau pika feces transfer also enhanced phenotypic features, such as, body-weight, disease activity index, and histological scores. In conclusion, Plateau pika feces was found to protect mice against colitis induced by dextran sodium sulfate by reducing inflammation and regulating microbial dysbiosis. These findings suggest the potential of Plateau pika feces as an alternative therapy for IBD.