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Graphene has attracted much interest in many scientific fields because of its high specific surface area, Young’s modulus, fracture strength, carrier mobility and thermal conductivity. In particular, the graphene oxide (GO) prepared by chemical exfoliation of graphite has achieved low-cost and large-scale production and is one of the most promising for Cu matrix composites. Here, we prepared a high strength, high electrical conductivity and high thermal conductivity reduced graphene oxide (RGO)/Cu composite by directly heating the GO/copper formate. The oxygen-containing functional groups and defects of RGO are significantly reduced compared with those of GO. The tensile yield strength and thermal conductivity of RGO/Cu composite with RGO volume fraction of 0.49 vol.% are as high as 553 MPa and 364 W/(m·K) at room temperature, respectively. The theoretical value of the tensile yield strength of the composite is calculated according to the strengthening mechanism, and the result shows that it agrees with the experimental value. After hot-rolling treatment, the ductility and conductivity of the composite materials have been greatly improved, and the ductility of the RGO/Cu composite with RGO volume fraction of 0.49 vol.% has been increased to four times the original. This work provides a highly efficient way to fabricate a high-performance RGO-reinforced Cu composite for commercial application.

Cross-scene classification focuses on setting up an effective domain adaptation (DA) way to transfer the learnable knowledge from source to target domain, which can be reasonably achieved through the pseudo-label propagation procedure. However, it is hard to bridge the objective existing severe domain discrepancy between source and target domains, and thus, there are several unreliable pseudo-labels generated in target domain and involved into pseudo-label propagation procedure, which would lead to unreliable error accumulation to deteriorate the performance of cross-scene classification. Therefore, in this paper, a novel Masked Image Modeling Auxiliary Pseudo-Label Propagation called MIM-AP2 with clustering central rectification strategy is proposed to improve the quality of pseudo-label propagation for cross-scene classification. First, in order to gracefully bridge the domain discrepancy and improve DA representation ability in-domain, a supervised class-token contrastive learning is designed to find the more consistent contextual clues to achieve knowledge transfer learning from source to target domain. At the same time, it is also incorporated with a self-supervised MIM mechanism according to a low random masking ratio to capture domain-specific information for improving the discriminability in-domain, which can lay a solid foundation for high-quality pseudo-label generation. Second, aiming to alleviate the impact of unreliable error accumulation, a clustering central rectification strategy is designed to adaptively update robustness clustering central representations to assist in rectifying unreliable pseudo-labels and learning a superior target domain specific classifier for cross-scene classification. Finally, extensive experiments are conducted on six cross-scene classification benchmarks, and the results are superior to other DA methods. The average accuracy reached 95.79%, which represents a 21.87% improvement over the baseline. This demonstrates that the proposed MIM-AP2 can provide significantly improved performance.

Although the effect of campus landscape space on stress relief among college students has been confirmed, few existing studies have considered the impact on stress recovery from the perspective of factor combination, and the key visual elements and the most effective combination of visual elements to relieve stress are still unclear. This study attempts to conduct a natural experiment within Chinese campuses, measuring physiological indicators of stress such as heart rate (HR), frequency domain index of heart rate variability (LF/HF), skin conductance level (SCL), skin temperature (SKT), and respiratory rate (RESP) using physiological instruments. It explored the effects of visual elements and their combinations in campus landscape spaces on short-term stress relief among college students through semantic segmentation, multifactorial analysis of variance, and post hoc multiple comparison methods. Research results demonstrate that the presence of water elements in the field of vision can effectively improve the stress relief effects of landscape spaces. Reasonable combinations of natural landscape elements and artificial landscape elements in the design can also effectively promote stress relief among students. Building facade area and sky area, water area and sky area, and plant species and pavement area are three combinations of factors with the strongest interactive effects. “Natural water scenery” and “exquisite artificial” are two campus landscape design patterns most conducive to short-term stress relief.

Waterborne polyurethane, renowned for its lightweight properties, excellent insulation capabilities, and corrosion resistance, has found extensive application in fields such as construction, automotive, leather, and thermal insulation. Nevertheless, during operational usage, waterborne polyurethane materials, akin to other polymeric substances, are susceptible to oxidative aging manifestations like yellowing, cracking, and diminished mechanical performance, significantly curtailing their utility. Consequently, the synthesis of yellowing-resistant polyurethane assumes pivotal significance. This study integrates dynamic reversible reactions into the synthesis process of polyurethane by introducing the dynamic reversible compound 2-hydroxyethyl disulfide as a chain extender, alongside the incorporation of a UV absorber to enhance the polyurethane’s resistance to yellowing. When the disulfide bonds absorb heat, they undergo cleavage, yielding thiols that spontaneously recombine into disulfide bonds at ambient temperatures, allowing for the continuous breaking and reformation of disulfide bonds to absorb heat. Concurrently, in collaboration with the UV absorber, the detrimental effects of ultraviolet radiation on the polyurethane material are mitigated, thereby augmenting its resistance to yellowing. This study scrutinizes the positioning of UV absorber addition, the quantity of UV absorber, and the molar ratio of 1,4-butanediol to 2-hydroxyethyl disulfide, characterizing the functional groups of polyurethane through infrared and Raman spectroscopy. It is observed that the successful preparation of yellowing-resistant polyurethane is achieved, and evaluations on the modified polyurethane through color difference, tensile, and centrifugal tests reveal that the optimal yellowing resistance is attained by adding a UV absorber at a mass fraction of 1% to 3% prior to chain extension, resulting in a color change grade of 2, denoting slight discoloration. Simultaneously, the other properties of polyurethane exhibit relative stability. Notably, when the molar ratio of 1,4-butanediol to 2-hydroxyethyl disulfide is 3:2, the overall performance of the polyurethane remains stable, with exceptional yellowing resistance capabilities attaining a color change grade of 2.

Abstract Information encryption technique has broad applications in individual privacy, military confidentiality, and national security, but traditional electronic encryption approaches are increasingly unable to satisfy the demands of strong safety and large bandwidth of high-speed data transmission over network. Optical encryption technology could be more flexible and effective in parallel programming and multiple degree-of-freedom data transmitting application. Here, we show a dual-layer optical encryption fluorescent polymer waveguide chip based on optical pulse-code modulation technique. Fluorescent oligomers were doped into epoxy cross-linking SU-8 polymer as a gain medium. Through modifying both the external pumping wavelength and operating frequency of the pulse-code modulation, the sender could ensure the transmission of vital information is secure. If the plaintext transmission is eavesdropped, the external pumping light will be switched, and the receiver will get warning commands of ciphertext information in the standby network. This technique is suitable for high-integration and high-scalability optical information encryption communications.

Objective p66Shc, a 66 kDa protein isoform encoded by the proto-oncogene SHC, is an essential intracellular redox homeostasis regulatory enzyme that is involved in the regulation of cellular oxidative stress, apoptosis induction and the occurrence of multiple age-related diseases. This study investigated the expression profile and functional characteristics of p66Shc during preimplantation embryo development in sheep. Methods The expression pattern of p66Shc during preimplantation embryo development in sheep at the mRNA and protein levels were studied by quantitative real-time polymerase chain reaction (RT-qPCR) and immunofluorescence staining. The effect of p66Shc knockdown on the developmental potential were evaluated by cleavage rate, morula rate and blastocyst rate. The effect of p66Shc deficiency on reactive oxygen species (ROS) production, DNA oxidative damage and the expression of antioxidant enzymes (e.g., catalase and manganese superoxide dismutase [MnSOD]) were also investigated by immunofluorescence staining. Results Our results showed that p66Shc mRNA and protein were expressed in all stages of sheep early embryos and that p66Shc mRNA was significantly downregulated in the 4- to 8-cell stage (p

Abstract Under the carbon neutrality goal, coal enterprises must seek breakthroughs from abandoned mines, develop new resources in the new era, turn problems into countermeasures, and participate in the carbon emissions market, for contributing to the accomplishment of the national strategic goal of carbon neutrality. To this end, we investigated the relevant national policies and regulations to clarify the boundaries disclosed by the carbon information of enterprises, understood the development direction of carbon storage in abandoned mines, and clarified the transformation and development of carbon storage in abandoned mines. We made a few suggestions: (1) China should learn from its past experience and other countries to develop the energy industry with Chinese characteristics and reform the economic system. (2) Coal enterprises must actively respond to the national carbon information disclosure policy, clarify their own responsibilities and carbon emission boundaries. (3) It is necessary to proactively obtain advanced knowledge and plan carbon storage pathways for abandoned mines. (4) Development problems of coal enterprises should be deduced using cases. The ‘dual carbon’ goals should be achieved steadily step-by-step. (5) Three measures, i.e. improving the existing resource structure, coordinating the information of abandoned mines, and promoting the cultivation of scientific and technological talents.

Health education plays an important role in cultivating people's awareness of participating in physical exercise. In this paper, a new differential equation model is established to dynamically demonstrate the different impact of mass communication and interpersonal communication in health education on people's participation in physical exercise. Theoretical analysis shows that health education does not affect the system threshold, but individual participation does. The combination of the two leads to different equilibria and affects the stability of equilibria. When mass communication, interpersonal communication and individual participation satisfy different conditions, the system will obtain different positive equilibrium with different number of sports population. If the interpersonal transmission rate of information is bigger, there is a positive equilibrium with a large number of sports population in the system. Sensitivity and optimal design analysis show some interesting results. First, increasing interpersonal communication and mass communication can both increase the number of conscious non-sports population and sports population. For increasing the number of conscious non-sports population, the effect of mass communication is better than that of interpersonal communication. For increasing the number of sports population, the effect of interpersonal communication is better than that of mass communication. However, individual participation has the best effect on increasing the sports population. Second, increasing the daily fixed amount of new information will be more helpful for media information dissemination. Finally, the three control measures need to be implemented simultaneously for a period of time at first, and then health education and participation of sports people need to be implemented periodically in order to maximize the sports population.

Abstract Objective To investigate the possible association between AT1R gene polymorphisms and major adverse cardiovascular and cerebrovascular events (MACCEs) in hypertension patients combined with or without coronary artery disease (CAD) in Xinjiang. Methods 374 CAD patients and 341 non-CAD individuals were enrolled as study participants and all of them have a hypertension diagnosis. AT1R gene polymorphisms were genotyped by SNPscan™ typing assays. During the follow-up in the clinic or by telephone interview, MACCEs were recorded. Kaplan–Meier curves and Cox survival analyses were used to explore the association between AT1R gene polymorphisms and the occurrence of MACCEs. Results AT1R gene rs389566 was associated with MACCEs. The TT genotype of the AT1R gene rs389566 had a significantly higher probability of MACCEs than the AA + AT genotype (75.2% vs. 24.8%, P = 0.033). Older age (OR = 1.028, 95% CI: 1.009–1.0047, P = 0.003) and TT genotype of rs389566 (OR = 1.770, 95% CI: 1.148–2.729, P = 0.01) were risk factors of MACCEs. AT1R gene rs389566 TT genotype may be a predisposing factor for the occurrence of MACCEs in hypertensive patients. Conclusion We should also pay more attention to the prevent of MACCEs in hypertension patients combined with CAD. Especially those elderly hypertensive patients carrying AT1R rs389566 TT genotype requires avoidance of unhealthy lifestyle, better management of blood pressure control and reduce the occurrence of MACCEs.

In this study, we investigate the differences between two transient, three-dimensional, thermomechanically coupled ice-sheet models, namely, a first-order approximation model (FOM) and a ‘full’ Stokes ice-sheet model (FSM) under the same numerical framework. For all numerical experiments, we take the FSM outputs as the reference values and calculate the mean relative errors in the velocity and temperature fields for the FOM over 100 years. Four different boundary conditions (ice slope, geothermal heat flux, basal topography and basal sliding) are tested, and by changing these parameters, we verify the thermomechanical behavior of the FOM and discover that the velocity and temperature biases of the FOM generally increase with increases in the ice slope, geothermal heat flux, undulation amplitude of the ice base, and with the existence of basal sliding. In addition, the model difference between the FOM and FSM may accumulate over time, and the spatial distribution patterns of the relative velocity and temperature errors are in good agreement.

In this study, the antibacterial effects of six plant essential oils against four common bacteria in the vapor phase was investigated by plate fumigation method with the measurement of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The combination of essential oils with better bactericidal effect was studied and applied to keep fresh of capsicum frutescens. The antibacterial mechanism of cinnamon essential oil against Escherichia coli (E. coli) was also determined by transmission electron microscopy (TEM) and electric conductivity. The results showed that citronella essential oil, cinnamon essential oil and basil essential oil had more significant antibacterial effect, which could inhibit all tested bacteria at the concentration of 0.125 μL/mL. Citronella essential oil and cinnamon essential oil had better bactericidal effect, which could kill all the tested bacteria except Pseudomonas aeruginosa at the concentration of 0.125 μL/mL. Blended essential oils with the ratio of citronella essential oil, cinnamon essential oil and basil essential oil being 4:1:8, demonstrated the best antibacterial activity. The blended essential oils showed synergistic effects on E. coli and Salmonella, but antagonistic effect on Staphylococcus aureues. GC-MS indicated that the antibacterial ability of citronella essential oil mainly came from citronellal, geraniol and citronellol, cinnamon essential oil came from cinnamaldehyde and basil essential oil came from estragole and linalool. The application of blended essential oil in modified atmosphere preservation of capsicum frutescens had a better preservative and fresh-keeping effects when the spatial concentration of blended essential oil was 0.125 μL/mL. TEM showed morphological changes and cell membrane shrinkage of E. coli after fumigation with cinnamon essential oil. The conductivity test showed that the membrane permeability of E. coli increased after fumigation, which resulted in electrolyte leakage. In conclusion, the possible antibacterial mechanism of vapor-phase cinnamon essential oil against E. coli is to change the cell morphology and membrane permeability.

Abstract Background Renal fibrosis is the late stage of many chronic kidney diseases (CKD). Clinically, there is almost no effective treatment for renal fibrosis except dialysis. Renshen Guben oral liquid (RSGB) is a Chinese patent medicine approved by National Medical Products Administration (NMPA), which is suitable for clinical patients with chronic nephritis. Currently, the chemical constituents of RSGB remains unclear, and its efficacy and mechanism on renal fibrosis have not been reported. Methods In our research, ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was employed to describe the chemical profile of RSGB, unilateral ureteral obstruction (UUO) model in mice was established to evaluate the beneficial effect of RSGB on renal fibrosis by biochemical indexes, HE and Masson staining. RNA sequencing and “constituents-targets-pathways” multi-dimensional network was established to mine the mechanisms of RSGB. Key targets were verified by quantitative real-time PCR (qRT-PCR) and western bolt (WB). Results A total of 201 constituents were identified or tentatively characterized, 15 of which were confirmed with standards. The number of triterpenes was the highest with 49, followed by phenols with 46. RSGB ameliorated the blood urea nitrogen (BUN) and serum creatinine (Scr) levels in serum, normalizing pathological structure of kidney tissue. RNA sequencing revealed that RSGB regulates 226 differential genes, which were involved in kidney development. According to the “constituents-targets-pathways” network, 26 key active constituents may mainly regulate the inflammatory immune system through 88 corresponding targets. qRT-PCR and WB results showed that RSGB inhibited the activation of the Tgfβ1/Smad2/3 pathway, Wnt4/β-Catenin pathway and NGFR/NF-κB pathway. Conclusions Overall, our study, for the first time, characterized 201 chemical constituents in RSGB, and 26 of them were screened out to alleviates renal fibrosis mainly through Tgfβ1/Smad2/3 pathway, Wnt4/β-catenin pathway and NGFR/NF-κB pathway, which may provide a new research strategy for research on the mechanism of traditional Chinese Medicine.

In long-range missions based on angle-of-arrival positioning, the angle measurement error of unmanned aerial vehicles is a major source of error. Therefore, reducing the unmanned aerial vehicle angle measurement error is crucial to achieve accurate remote positioning. In this paper, we propose a space vector–based method to correct the space vector of the target for the unmanned aerial vehicles when there are fewer than three available reference points, which in turn corrects the angular value of the target relative to the unmanned aerial vehicles. Simulation results show that when the distance between the reference point and the unmanned aerial vehicles is smaller than the distance between the target and the unmanned aerial vehicles, the azimuth measurement error can be reduced to 55% of the original error for the case of a single reference point, while the pitch angle measurement error remains almost unchanged. In the case of more than two reference points, the azimuth measurement error can be reduced to 1e5 and the pitch angle measurement error can be reduced to 30% of the original error. This method can be adapted to the rapid positioning task for high-speed and high-mobility targets without iteration, low computation, good correction effect, and the need of prior known data set reference.

Abstract Nanotransfer printing of colloidal nanoparticles is a promising technique for the fabrication of functional materials and devices. However, patterning nonplanar nanostructures pose a challenge due to weak adhesion from the extremely small nanostructure‐substrate contact area. Here, the study proposes a thermal‐assisted nonplanar nanostructure transfer printing (NP‐NTP) strategy for multiscale patterning of polystyrene (PS) nanospheres. The printing efficiency is significantly improved from ≈3.1% at low temperatures to ≈97.2% under the glass transition temperature of PS. Additionally, the arrangement of PS nanospheres transitioned from disorder to long‐range order. The mechanism of printing efficiency enhancement is the drastic drop of Young's modulus of nanospheres, giving rise to an increased contact area, self‐adhesive effect, and inter‐particle necking. To demonstrate the versatility of the NP‐NTP strategy, it is combined with the intaglio transfer printing technique, and multiple patterns are created at both micro and macro scales at a 4‐inch scale with a resolution of ≈2757 pixels per inch (PPI). Furthermore, a multi‐modal anti‐counterfeiting concept based on structural patterns at hierarchical length scales is proposed, providing a new paradigm of imparting multiscale nanostructure patterning into macroscale functional devices.

This swift progression of urbanization has led to increasingly prominent conflicts over the use of land, particularly around its supply and demand. Researchers, both in China and internationally, have underscored the inherent interconnection between urbanization and land utilization. This relationship has gradually become more complex with the development of urbanization. With the implementation of the Yellow River Basin's strategy to preserve the environment while ensuring high-quality development, the Yellow River Basin has become a focal point of attention for numerous scholars. This study centers on the 57 county-level administrative divisions within the Gansu segment of the Yellow River Basin. We employed an extensive array of methodologies, such as GIS technology, the entropy method, data envelopment analysis, the coupling coordination degree model, and the panel vector autoregressive model. We established an index system and a measurement model to evaluate the degree of urbanization and the efficiency of land use. We also investigated the coupling coordinated dynamics between these two variables, to further explore the dynamic interplay between urbanization and land use and reveal their underlying mechanisms. The conclusions are as follows. The urbanization level and efficiency of land use in the Gansu section of the Yellow River Basin have exhibited a consistent upward trajectory, albeit at levels that are not particularly high, indicating substantial room for improvement in the future. The level of coupling coordination between urbanization and land use efficiency in the Gansu section of the Yellow River Basin has shown a generally upward trend. However, the overall coordination level remains relatively low, characterized by an imbalance, with "high coupling but low coordination". Regarding spatial distribution patterns, considerable disparities exist in the level of coordination development, which generally decreases from the eastern toward the western regions. A strong reciprocal and interactive relationship exists between the urbanization level and land use efficiency. An elevated level of economic urbanization can initially stimulate land use efficiency. Similarly, the improvement in the level of population urbanization, social urbanization, and ecological urbanization tends to exert a restraining influence on the augmentation of land use efficiency. Conversely, the enhancement of land use efficiency makes a distinct contribution to promoting the elevation of the urbanization level.

Angiogenesis is regulated by various signal molecules, which can be found in many pathological processes, such as tumors. Endothelial cells (ECs) are target cells of multiple angiogenesis signaling pathways and play a critical role in angiogenesis. Exploration of ECs' role in angiogenesis has provided multiple research directions for angiogenesis mechanism studies. In recent years, research showed that EC lipid metabolism was closely correlated with angiogenesis. Therefore, we summarized the related regulatory molecules of EC lipid uptake, essential enzymes of lipid metabolism, and endothelium-derived phospholipids during angiogenesis. Moreover, we focused on their relationships with angiogenesis and the role of EC lipid metabolism in tumor angiogenesis.

Advanced mobile functions and empowered smartphones have provided tourists with various location-based service apps that reshaped the business model of the tourism sector. Despite their importance to tourists, l-apps still have limitations, such as ignorance of tourist preferences and the mismatch between app introduction and tourist experience, therefore affecting tourist loyalty to destinations. Understanding tourist-oriented factors thus becomes critical for l-app designers and service providers. This study integrates the technology-acceptance model (TAM) into a unique context to examine the roles of digital literacy, perceived ease of use, perceived autonomy, virtual-content congruence, and tourist engagement on tourist loyalty. Our empirical test of a structural equation model based on a randomly recruited 319 customers found that tourists' digital literacy influences their engagement and perceived ease of use, which mediates the relationship between digital literacy and engagement; tourists' perceived autonomy influences their engagement. Moreover, we found the moderating role of information-experience congruency between digital literacy, perceived ease of use, and perceived autonomy and tourist engagement, thus contributing to the boundary conditions of the TAM model. Finally, tourist engagement contributes to tourist loyalty. The study contributes to the integration of the technology acceptance model with a tourist orientation. The findings also offer meaningful, practical implications and recommendations on l-app design to stakeholders of tourist destinations.

The increased frequency of human infectious disease outbreaks caused by RNA viruses worldwide in recent years calls for enhanced public health surveillance for better future preparedness. Wastewater-based epidemiology (WBE) is emerging as a valuable epidemiological tool for providing timely population-wide surveillance for disease prevention and response complementary to the current clinical surveillance system. Here, we compared the analytical performance and practical applications between predominant molecular detection methods of RT-qPCR and RT-ddPCR on SARS-CoV-2 detection in wastewater surveillance. When pure viral RNA was tested, RT-ddPCR exhibited superior quantification accuracy at higher concentration levels and achieved more sensitive detection with reduced variation at low concentration levels. Furthermore, RT-ddPCR consistently demonstrated more robust and accurate measurement either in the background of the wastewater matrix or with the presence of mismatches in the target regions of the consensus assay. Additionally, by detecting mock variant RNA samples, we found that RT-ddPCR outperformed RT-qPCR in virus genotyping by targeting specific loci with signature mutations in allele-specific (AS) assays, especially at low levels of allele frequencies and concentrations, which increased the possibility for sensitive low-prevalence variant detection in the population. Our study provides insights for detection method selection in the WBE applications for future infectious disease outbreaks.

Japanese encephalitis is one of the most important insect-borne infectious disease with public health concern. The virus can break the blood–brain barrier and cause death or long-term sequela in infected humans or animals. Viral encephalitis is an important clinical feature of JEV infection. In recent studies, CircRNAs and related ceRNAs data illustrated the regulative role in many aspects of biological process and disease duration. It is believed that CircRNA regulates JEV infection in a ceRNA-dependent mechanism. In this study, brain tissues of experimental mice were sequenced and analysised. 61 differentially expressed circRNAs, 172 differentially expressed miRNAs and 706 differentially expressed mRNAs were identified by RNA-Sequencing and statistical analysis. CX3CR1 was determined as a key host factor impact JEV infection by microRNA interference measurement. CX3CR1 interaction network indicated circStrbp/miR709/CX3CR1 as a functional regulation axis. Further sequencing in BV2 cell shown CX3CR1 is a special target of miR-709 only during JEV infection. In summary, our study presented a new ceRNA pathway that impact JEV infection in vivo and in vitro, which could be a therapeutic target to fight against JEV.

PurposeOngoing Monkeypox (MPX) outbreaks in countries outside Africa have unique characteristics. However, data on cohorts of confirmed cases in China is limited. The study provides important epidemiological, diagnostic, and clinical information about this disease in China.MethodsWe report a series of Chinese individuals with confirmed MPX infections identified at Beijing Youan Hospital (China) from June 10 to July 15, 2023. Samples were taken from the skin, anus, throat, and blood. An epidemiological questionnaire was used to collect demographic and clinical data. Further, we compared the MPX viral (MPXV) loads across different anatomical sites.Results66 samples were collected from 20 patients, all of whom were cisgender men. Median patient age was 29 years. Notably, 19 (95%) patients reported unprotected sexual encounters with men in the preceding month, and 13 (65%) were human immunodeficiency virus (HIV)-positive. Among those with HIV, 12 (92%) were receiving antiretroviral therapy, and 11 (85%) had well-controlled infections (HIV viral load

Summary: Investigating immune memory to vaccinia virus and pre-existing immunity to mpox virus (MPXV) among the population is crucial for the global response to this ongoing mpox epidemic. Blood was sampled from vaccinees inoculated with vaccinia virus Tiantan (VTT) strain born before 1981 and unvaccinated control subjects born since 1982. After at least 40 years of the inoculation, 60% or 5% VTT vaccinees possess neutralizing antibodies (NAbs) to VTT or MPXV, with at least 50% having T cell memory to VTT protein antigens. Notably, 46.7% vaccinees show pre-existing T cell responses to MPXV. Broad pre-existing CD8+ T cell reactivities to MPXV are detected not only against conserved epitopes but also against variant epitopes between VTT and MPXV. Persistent NAbs and T cell memory to VTT among vaccinees, along with pre-existing T cells to MPXV among both vaccinees and the unvaccinated population, indicate a particular immune barrier to mpox.

ABSTRACT The dissemination of antibiotic resistance genes (ARGs) driven by mobile genetic elements (MGEs), especially among pathogenic bacteria, is of increasing global concern. Different from other well-characterized MGEs, integrative and conjugative elements (ICEs) have been lacking a comprehensive understanding of their roles in ARG propagation across bacterial phylogenies. Through genomic study based on a large collection of bacterial complete genomes and further comparative analysis with two prominent MGEs to spread ARGs—conjugative plasmids and class 1 integrons, we, for the first time, demonstrated that ICEs are indeed overlooked “hot” vectors from the aspects of mobility and pathogenicity: (i) ICEs exhibited broader phylogenetic distribution among two dominant phyla with high ARG diversity and (ii) ARG-carrying ICEs were significantly enriched in potential human pathogens covering all the six “ESKAPE” species, of which some displayed typical co-occurrence patterns with ARGs and virulence factors. Moreover, this first genomic comparative study also deciphered the distinct ARG profiles harbored by these three essential MGE groups in terms of diversity and prevalence, with characteristic ARG preference to each MGE group. Overall, our findings concerning the MGE-specific performance for ARG transmission, in particular, the historically understudied ICEs, could shed light on control strategy optimization to antibiotic resistance crises.IMPORTANCEDifferent from other extensively studied mobile genetic elements (MGEs) whose discoveries were initiated decades ago (1950s–1980s), integrative and conjugative elements (ICEs), a diverse array of more recently identified elements that were formally termed in 2002, have aroused increasing concern for their crucial contribution to the dissemination of antibiotic resistance genes (ARGs). However, the comprehensive understanding on ICEs’ ARG profile across the bacterial tree of life is still blurred. Through a genomic study by comparison with two key MGEs, we, for the first time, systematically investigated the ARG profile as well as the host range of ICEs and also explored the MGE-specific potential to facilitate ARG propagation across phylogenetic barriers. These findings could serve as a theoretical foundation for risk assessment of ARGs mediated by distinct MGEs and further to optimize therapeutic strategies aimed at restraining antibiotic resistance crises.

BackgroundInosine monophosphate (IMP) is naturally present in poultry muscle and plays a key role in improving meat flavour. However, IMP deposition is regulated by numerous genes and complex molecular networks. In order to excavate key candidate genes that may regulate IMP synthesis, we performed proteome and metabolome analyses on the leg muscle, compared to the breast muscle control of 180-day-old Jingyuan chickens (hens), which had different IMP content. The key candidate genes identified by a differential analysis were verified to be associated with regulation of IMP-specific deposition.ResultsThe results showed that the differentially expressed (DE) proteins and metabolites jointly involve 14 metabolic pathways, among which the purine metabolic pathway closely related to IMP synthesis and metabolism is enriched with four DE proteins downregulated (with higher expression in breast muscles than in leg muscles), including adenylate kinase 1 (AK1), adenosine monophosphate deaminase 1 (AMPD1), pyruvate kinase muscle isoenzyme 2 (PKM2) and phosphoglucomutase 1 (PGM1), six DE metabolites, Hypoxanthine, Guanosine, L-Glutamine, AICAR, AMP and Adenylsuccinic acid. Analysis of PGM1 gene showed that the high expression of PGM1 promoted the proliferation and differentiation of myoblasts and inhibited the apoptosis of myoblasts. ELISA tests have shown that PGM1 reduced adenosine triphosphate (ATP) and IMP and uric acid (UA), while enhancing the biosynthesis of hypoxanthine (HX). In addition, up-regulation of PGM1 inhibited the expression of purine metabolism pathway related genes, and promoted the IMP de novo and salvage synthesis pathways.ConclusionThis study preliminarily explored the mechanism of action of PGM1 in regulating the growth and development of myoblasts and specific IMP deposition in Jingyuan chickens, which provided certain theoretical basis for the development and utilization of excellent traits in Jingyuan chickens.

Purpose: This study aims to preserve the volatile components of Linggui Zhugan (LGZG) decoction, offering an experimental foundation for subsequent preparations efforts. Methods: Two modern sample preparation processes were compared with the traditional method approach using HPLC fingerprints. After identifying the main volatile components in LGZG aqueous decoction, the inclusion method of inclusion compounds (IC-LGZG) was established and optimized at laboratory, pilot and production scales. Characterization, stability testing of IC-LGZG, and experiments on gastric ulcer rats were conducted to validate the transferability of chemical composition and pharmaceutical efficacy. Results: The study focused on preserving the volatile components in LGZG modern preparations. HPLC analysis revealed cinnamaldehyde (CA) as the main volatile component in LGZG decoction. The optimized IC-LGZG preparation involved heating aromatic water to 40 °C, adding 20 g/L of β-Cyclodextrin (β-CD), keeping warm and stirring at 300 r for 30 min. This process exhibited good repeatability across different verification tests at varying scales. IC-LGZG obtained effectively transferred CA molecules into the β-CD molecules via encapsulation, remaining stable when stored in sealed and dark conditions. Finally, CA, IC-LGZG and M−LGZG (a mixture of IC-LGZG and water-soluble extract powder) effectively prevented the formation of gastric ulcer by mitigating reductions in IL-10, SOD and the increase of TNF-α, NO, MDA in serum. Conclusion: The IC-LGZG prepared using this process successfully transfers volatile components, both chemically and pharmacologically, making it suitable for modern preparations of LGZG.

IntroductionObesity is a chronic disease in which the body stores excess energy in the form of fat, and intestinal bacterial metabolism and inflammatory host phenotypes influence the development of obesity. Walnut peptide (WP) is a small molecule biopeptide, and the mechanism of action of WP against metabolic disorders has not been fully elucidated. In this study, we explored the potential intervention mechanism of WP on high-fat diet (HFD)-induced obesity through bioinformatics combined with animal experiments.MethodsPPI networks of Amino acids and their metabolites in WP (AMWP) and “obesity” and “inflammation” diseases were searched and constructed by using the database, and their core targets were enriched and analyzed. Subsequently, Cytoscape software was used to construct the network diagram of the AMWP-core target-KEGG pathway and analyze the topological parameters. MOE2019.0102 was used to verify the molecular docking of core AMWP and core target. Subsequently, an obese Mice model induced by an HFD was established, and the effects of WP on obesity were verified by observing weight changes, glucose, and lipid metabolism levels, liver pathological changes, the size of adipocytes in groin adipose tissue, inflammatory infiltration of colon tissue, and intestinal microorganisms and their metabolites.ResultsThe network pharmacology and molecular docking showed that glutathione oxide may be the main active component of AMWP, and its main targets may be EGFR, NOS3, MMP2, PLG, PTGS2, AR. Animal experiments showed that WP could reduce weight gain and improve glucose-lipid metabolism in HFD-induced obesity model mice, attenuate hepatic lesions reduce the size of adipocytes in inguinal adipose tissue, and reduce the inflammatory infiltration in colonic tissue. In addition, the abundance and diversity of intestinal flora were remodeled, reducing the phylum Firmicutes/Bacteroidetes (F/B) ratio, while the intestinal mucosal barrier was repaired, altering the content of short-chain fatty acids (SCFAs), and alleviating intestinal inflammation in HFD-fed mice. These results suggest that WP intervenes in HFD-induced obesity and dyslipidemia by repairing the intestinal microenvironment, regulating flora metabolism and anti-inflammation.DiscussionOur findings suggest that WP intervenes in HFD-induced obesity and dyslipidemia by repairing the intestinal microenvironment, regulating flora metabolism, and exerting anti-inflammatory effects. Thus, WP may be a potential therapeutic strategy for preventing and treating metabolic diseases, and for alleviating the intestinal flora disorders induced by these diseases. This provides valuable insights for the development of WP therapies.

ABSTRACT Human immunodeficiency virus (HIV) infection leads to severe deficiency in host immunity by depletion of CD4+ T-cells, resulting in an imbalance between the human microbiome and host immune response. Alterations in both gut and oral microbiomes have been observed in people living with HIV (PLWH). However, the impact of an altered gut and oral microbiome on HIV disease progression and the relationship between them in PLWH have not been explored. In this longitudinal study, we enrolled acute HIV-infected men who have sex with men (MSM) (n = 15), chronic HIV-infected MSM (n = 15), and HIV-uninfected MSM controls (n = 15). We collected anal and throat swab samples at recruitment (W0) from all participants and at 12 wk after antiretroviral therapy (ART) (W12) from the patients and performed 16S rRNA gene sequencing of genomic DNAs extracted from these swabs. In HIV-infected individuals with CD4 T-cell counts < 350 cells/µL, the increase in abundance of Streptococcus in the oral microbiome was inversely correlated with that of Streptococcus in the gut microbiome (r = −0.490, P = 0.039). In addition, the lower CD4+ T-cell counts (

Marine ecosystems in the Northwest Pacific (NWP) are being threatened by marine heatwaves (MHWs), which are abnormally high sea-surface temperature (SST) lasting for more than 5 days. However, there is limited research on the predictability of these MHWs. In this study, we investigate the predictability of NWP MHWs in summer using daily data from the coupled climate forecast system (version 1.0) of the Nanjing University of Information Science and Technology (NUIST-CFS1.0) for the period of 1984–2020. We demonstrate that the NUIST-CFS1.0 hindcasts can predict the spatial pattern of the total MHW days (HWD) over the NWP in summer with a lead time of up to eight months. Moreover, the linear trend and interannual variability can be predicted at lead times of up to nine and three months, respectively. We reveal that the interannual variability of HWD is strongly correlated with the preceding El Niño-Southern Oscillation (ENSO); and its predictability also shows significant interannual variability, with MHWs being more predictable in the decaying years of stronger El Niño events. In the El Niño decaying summers, there is an increase in the occurrence of MHWs; the spatial distribution of HWD can be predicted at lead times of up to 19 months, and its forecasting accuracy is far superior to that of the other years. The occurrence of MHWs during El Niño decaying summers is closely linked to strengthened NWP subtropical anticyclone (NWPSA), which increases solar radiation reaching the ocean surface and suppresses surface evaporation, leading to increased SST and thereby MHWs. The remarkable predictability of the MHWs in the NWP region during El Niño decaying summers can be attributed to the high skill at predicting ENSO and its associated NWPSA anomalies.

Combining diamond with GaN can significantly improve the heat dissipation performance of GaN-based devices. However, how to avoid the destructive damage to the GaN epi-layer caused by high-temperature hydrogen plasma during the diamond growth is still a problem. This study employed a Si transition layer and double-substrate structure microwave plasma chemical vapor deposition (MPCVD) to prepare diamond film on GaN epi-layer. The effects of double-substrate structure on the diamond growth were studied. The microwave plasma parameters of both single-substrate structure and double-substrate structure MPCVD diagnosed by emission spectra were comparatively investigated. It has been found that the microwave plasma energy of double-substrate structure MPCVD is relatively more concentrated and has higher radicals activity, which is beneficial to the diamond growth. The impacts of the Si transition layer on the diamond growth were also investigated. It demonstrates that the Si transition layer can effectively protect the GaN epi-layer from being etched by hydrogen plasma and improve the diamond growth. The relationship between the thickness of the Si transition layer and the diamond growth and the relationship between diamond film thickness and adhesion has been studied in detail.

It is recognized that collagen peptides can promote osteoblast mineralization; however, the responsible peptides are not clearly identified. To this end, the peptides obtained from bovine bone collagen hydrolysates with stimulatory effects on osteoblast mineralization were fractionated using a series of chromatographic methods. Six peptides from the fraction possessing the most powerful mineralization stimulation ability were identified via LC-MS-MS analysis. Six peptides exhibited enhanced bioactivity-inducing properties. Moreover, it was found that the interaction between peptides and integrinα5β1 may be responsible for osteoblast mineralization stimulation activity.

AbstractInduction of oral tolerance by vaccination with type 1 diabetes mellitus (T1DM)-associated autoantigens exhibits great potential in preventing and treating this autoimmune disease. However, antigen degradation in the gastrointestinal tract (GIT) limits the delivery efficiency of oral antigens. Previously, bacterium-like particles (BLPs) have been used to deliver a single-chain insulin (SCI-59) analog (BLPs-SCI-59) or the intracellular domain of insulinoma-associated protein 2 (IA-2ic) (BLPs-IA-2ic). Both monovalent BLPs vaccines can suppress T1DM in NOD mice by stimulating the corresponding antigen-specific oral tolerance, respectively. Here, we constructed two bivalent BLPs vaccines which simultaneously deliver SCI-59 and IA-2ic (Bivalent vaccine-mix or Bivalent vaccine-SA), and evaluated whether there is an additive beneficial effect on tolerance induction and suppression of T1DM by treatment with BLPs-delivered bi-autoantigens. Compared to the monovalent BLPs vaccines, oral administration of the Bivalent vaccine-mix could significantly reduce morbidity and mortality in T1DM. Treatment with the bivalent BLPs vaccines (especially Bivalent vaccine-mix) endowed the mice with a stronger ability to regulate blood glucose and protect the integrity and function of pancreatic islets than the monovalent BLPs vaccines treatment. This additive effect of BLPs-delivered bi-autoantigens on T1DM prevention may be related to that SCI-59- and IA-2-specific Th2-like immune responses could be induced, which was more beneficial for the correction of Th1/Th2 imbalance. In addition, more CD4+CD25+Foxp3+ regulatory T cells (Tregs) were induced by treatment with the bivalent BLPs vaccines than did the monovalent BLPs vaccines. Therefore, multiple autoantigens delivered by BLPs maybe a promising strategy to prevent T1DM by efficiently inducing antigen-specific immune tolerance.

Spleen tyrosine kinase (Syk) is reported to be involved in activating the autophagy. Recently, a homologue of Syk was identified from Pacific oyster Crassostrea gigas (defined as CgSyk). In the present study, the molecular characteristics of CgSyk and its regulation mechanism in autophagy were investigated in oyster C. gigas. The full-length cDNA of CgSyk was of 4566 bp with an open reading frame (ORF) of 1989 bp. CgSyk encoded a polypeptide of 662 amino acids, containing two Src homology 2 (SH2) domains and one tyrosine kinase catalytic (TyrKc) domain. The deduced amino acid sequence of CgSyk shared low similarity with the previously identified Syks from other species. In the phylogenetic tree, CgSyk was first clustered with Crassostrea virginica CvSyk, and then classified into a branch of invertebrate Syks. In CgSyk-RNAi oysters, the mRNA expressions of CgLC3, CgP62, CgBeclin-1 and CgATG5 in haemocytes decreased significantly at 12 h after Vibrio splendidus stimulation. At the same time, the abundance of CgLC3Ⅱ in haemocytes, and the autophagy rate of haemocytes in CgSyk-RNAi oysters decreased significantly at 12 h after V. splendidus stimulation. All the results collectively suggested that CgSyk regulated the autophagy through inducing the mRNA expressions of autophagy-related genes and the cleavage of CgLC3 to defend against bacterial invasion in oysters.

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment—(1) Assessing Laboratory Work and Scientific Thinking; (2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; (3) Appraising Forms of Scientific Communication; and (4) Metacognition of Learning—along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students’ ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education.

ObjectiveTo compare the ultrasound guidance and traditional methods in femoral artery puncture.MethodsWe searched the databases to evaluate the rate of success on first attempt and the incidence of hematoma. The random effects model was used for performing a meta-analysis to estimate the odds ratio (ORs), mean difference (MD), and 95% confidence interval (CI).ResultsA total of nine articles including 2,361 patients were included in this meta-analysis. The rate of success on first attempt were 79.6% (1,289/1,619) and 54.1% (883/1,644) in patients of the ultrasound group and traditional method group, respectively [OR = 3.14 (95% CI = 2.30–4.28), combined OR value Z = 7.23 (P

ObjectivesThe treatment of locally advanced oral or oropharyngeal squamous cell carcinoma (LAOOPSCC) is surgery and radiotherapy or chemoradiotherapy but with unsatisfactory survival rate. Neoadjuvant programmed death-1 (PD-1) therapy are being used in several clinical trials. Therefore, in this retrospective study we aimed to determine the feasibility of neoadjuvant tislelizumab plus chemotherapy followed by surgery for LAOOPSCC.Materials and methodsThe clinical data of 33 patients with LAOOPSCC who received neoadjuvant PD-1 inhibitors and chemotherapy between April 2021 and October 2022 were retrospectively analyzed. Patients with stage III-IV LAOOPSCC received tislelizumab, albumin-bound paclitaxel, and cisplatin every 3 weeks (Q3W) for two cycles, followed by surgery and adjuvant radiotherapy or concurrent chemoradiotherapy. A median follow-up period was 20 months.ResultsThe objective response rate (ORR) was 66.7%, with the major pathological response (MPR) rate at 54.5%, and the pathological complete response (pCR) rate was 33.3%. Sixteen patients underwent limited surgeries, and 15 patients were remitted from undergoing mandibulectomy and 9 patients were remitted from undergoing near total glossectomy or total glossectomy. A significant difference in the overall survival (OS) and disease-free survival (DFS) was observed in patients who achieved major pathological response (MPR) than who did not. The most common adverse events in neoadjuvant therapy were alopecia, decreased appetite or anorexia, leukopenia, and fatigue.ConclusionNeoadjuvant PD-1 inhibitors combined with chemotherapy are feasible and safe, with a high pathological response and possible organ preservation in oral or oropharyngeal squamous cell carcinoma. However, further studies with a larger cohort of patients and longer follow-up period is required to strengthen our findings and evaluate the survival benefits of the treatment.

C11H19N7O9, orthorhombic, P212121 (no. 19), a = 6.2578(2) Å, b = 15.4188(5) Å, c = 17.6841(7) Å, V = 1706.30(1) Å3, Z = 4, Rgt(F) = 0.0428, wRref(F2) = 0.0972, T = 100 K.

Grouting reinforcement is an effective method for controlling the stability of engineering rock mass. The mechanism is mainly to inject or infiltrate the grout into the fracture of rock mass to form a grouting entity, and strengthen the stability of rock mass and the ability to resist failures. In order to realize the calculation of the whole process of grouting diffusion and consolidation in broken surrounding rock, a diffusion-consolidation mechanism of grouting based on discrete element method was proposed. Also, the model checking and example analysis were carried out, and the results show that: ① In the full-length grouting of single fracture scenario, the shear peak strength of the post-fractured rock mass is higher than that of the non-grouting fracture, which depends on the frictional resistance generated by the solidification and cohesion of the slurry. ② In the point grouting simulation experiment, as the grouting pressure increases, the grout continues to diffuse. Therefore, the pre-peak shear yielding and post-peak phases of the rock mass are strengthened. ③ For the engineering-scale simulation test, as the grouting pressure increases, the diffusion radius increases in two stages. When the grout expands to the high-stress area, it needs to overcome a greater compressive stress to achieve flow. After reaching a relative higher grouting pressure, the diffusion area of adjacent boreholes is superimposed to form a grouting whole body that surrounds the roadway. When the solidification bond strength of the grout is low, the failure of contact is still the main controlling factor to determine the failure and instability of the roadway.

Abstract Background Polycyclic aromatic hydrocarbon (PAH) contamination has been a worldwide environmental issue because of its impact on ecosystems and human health. Biodegradation plays an important role in PAH removal in natural environments. To date, many PAH-degrading strains and degradation genes have been reported. However, a comprehensive PAH-degrading gene database is still lacking, hindering a deep understanding of PAH degraders in the era of big data. Furthermore, the relationships between the PAH-catabolic genotype and phenotype remain unclear. Results Here, we established a bacterial PAH-degrading gene database and explored PAH biodegradation capability via a genome-function relationship approach. The investigation of functional genes in the experimentally verified PAH degraders indicated that genes encoding hydratase-aldolase could serve as a biomarker for preliminarily identifying potential degraders. Additionally, a genome-centric interpretation of PAH-degrading genes was performed in the public genome database, demonstrating that they were ubiquitous in Proteobacteria and Actinobacteria. Meanwhile, the global phylogenetic distribution was generally consistent with the culture-based evidence. Notably, a few strains affiliated with the genera without any previously known PAH degraders (Hyphomonas, Hoeflea, Henriciella, Saccharomonospora, Sciscionella, Tepidiphilus, and Xenophilus) also bore a complete PAH-catabolic gene cluster, implying their potential of PAH biodegradation. Moreover, a random forest analysis was applied to predict the PAH-degrading trait in the complete genome database, revealing 28 newly predicted PAH degraders, of which nine strains encoded a complete PAH-catabolic pathway. Conclusions Our results established a comprehensive PAH-degrading gene database and a genome-function relationship approach, which revealed several potential novel PAH-degrader lineages. Importantly, this genome-centric and function-oriented approach can overcome the bottleneck of conventional cultivation-based biodegradation research and substantially expand our current knowledge on the potential degraders of environmental pollutants.

Abstract Expression of the long non-coding RNA (lncRNA) keratin-7 antisense (KRT7-AS) is downregulated in various types of cancer; however, the impact of KRT7-AS deficiency on tumorigenesis and apoptosis is enigmatic. We aim to explore the influence of KRT7-AS in carcinogenesis and apoptosis. We found that KRT7-AS was deficient in breast and lung cancers, and low levels of KRT7-AS were a poor prognostic factor in breast cancer. Cellular studies showed that silencing of KRT7-AS in lung cancer cells increased oncogenic Keratin-7 levels and enhanced tumorigenesis, but diminished cancer apoptosis of the cancer cells; by contrast, overexpression of KRT7-AS inhibited lung cancer cell tumorigenesis. Additionally, KRT7-AS sensitized cancer cells to the anti-cancer drug cisplatin, consequently enhancing cancer cell apoptosis. In vivo, KRT7-AS overexpression significantly suppressed tumor growth in xenograft mice, while silencing of KRT7-AS promoted tumor growth. Mechanistically, KRT7-AS reduced the levels of oncogenic Keratin-7 and significantly elevated amounts of the key tumor suppressor PTEN in cancer cells through directly binding to PTEN protein via its core nucleic acid motif GGCAAUGGCGG. This inhibited the ubiquitination-proteasomal degradation of PTEN protein, therefore elevating PTEN levels in cancer cells. We also found that KRT7-AS gene transcription was driven by the transcription factor RXRα; intriguingly, the small molecule berberine enhanced KRT7-AS expression, reduced tumorigenesis, and promoted apoptosis of cancer cells. Collectively, KRT7-AS functions as a new tumor suppressor and an apoptosis enhancer in lung and breast cancers, and we unraveled that the RXRα-KRT7-AS-PTEN signaling axis controls carcinogenesis and apoptosis. Our findings highlight a tumor suppressive role of endogenous KRT7-AS in cancers and an important effect the RXRα-KRT7-AS-PTEN axis on control of cancer cell tumorigenesis and apoptosis, and offer a new platform for developing novel therapeutics against cancers.

Abstract Objective The purpose of this study was to explore whether miR-494-3p inhibits the occurrence of mitochondrial autophagy in cardiomyocytes by inhibiting the expression of PGC1-α and to supplement the theoretical basis for the role of autophagy in cardiac injury induced by hypoxia/reperfusion (H/R). Methods The expression of miR-494-3p was detected by RT‒qPCR, and the expression of PGC1-α, autophagy-related proteins (LC3, Beclin 1), apoptosis-related proteins (Bax and Bcl-2), PINK1/Parkin signaling pathway-related proteins (PINK1, Parkin) and mitochondrial change-related proteins (Mfn1, Mfn2, OPA1) was detected by Western blotting. The changes in mitochondrial membrane potential were detected by JC-1 staining (ΔΨm). The formation of autophagosomes was observed by transmission electron microscopy. Cell proliferation activity was detected by CCK-8, and cell apoptosis was detected by flow cytometry. A dual-luciferase gene reporter assay identified a targeted binding site between miR-494-3p and PGC1-α. Results The results showed that miR-494-3p and PGC1-α were differentially expressed in H/R cardiomyocytes; that is, the expression of miR-494-3p was downregulated, and the expression of PGC1-α was upregulated. In addition, mitochondrial autophagy occurred in H/R cardiomyocytes. That is, LC3-II/LC3-I, Beclin 1, PINK1, and Parkin expression was upregulated, Mfn1, Mfn2, and OPA1 expression was downregulated, and the mitochondrial membrane potential was decreased. The transfection of miR-494-3p mimic can significantly improve the cell proliferation activity of cardiomyocytes and inhibit the occurrence of cardiomyocyte apoptosis and autophagy, while the transfection of miR-494-3p inhibitor has the opposite result. After transfection of the miR-494-3p mimic, treatment with autophagy inhibitors and activators changed the effects of miR-494-3p on cardiomyocyte proliferation and apoptosis. At the same time, the overexpression of PGC1-α reversed the promoting effect of miR-494-3p on cardiomyocyte proliferation and the inhibitory effect on apoptosis and autophagy. Conclusion MiR-494-3p can target and negatively regulate the expression of PGC1-α to inhibit mitophagy in cardiomyocytes.

Abstract Objectives The current study compared the safety and efficacy of long-term dual antiplatelet therapy (DAPT, aspirin plus clopidogrel) and intensive rosuvastatin with short-term DAPT for acute ischemic stroke (AIS). Methods A total of 220 patients were enrolled 72 h after the onset of mild to moderate AIS, and divided into a control group treated with 21-day DAPT and a study group treated with intensive rosuvastatin with 7-day DAPT on a voluntary basis. The primary outcome was recurrent ischemic stroke and hemorrhage during a 90-day follow-up period in an intention-to-treat analysis. The secondary outcome was clinical efficacy with respect to alleviating existing focal nerve defect symptoms. A Cox proportional-hazards model was used to evaluate treatment differences. Results Clinical efficacy was evident in 87.3% of patients in the study group, compared with 84.3% in the control group (p = 0.042). Recurrent ischemic stroke occurred in 9 patients (7.6%) in the study group and in 9 (8.8%) in the control group (p = 0.767). Hemorrhage occurred in 6 patients (5.1%) in the study group and in 15 (14.7%) in the control group (p = 0.023). In comparisons of levels of ALT, AST, LDH, and CK in the two groups before and 2 weeks after therapy, only CK differed significantly (p

Abstract Intertwined spin and charge orders have been widely studied in high-temperature superconductors, since their fluctuations may facilitate electron pairing; however, they are rarely identified in heavily electron-doped iron selenides. Here, using scanning tunneling microscopy, we show that when the superconductivity of (Li0.84Fe0.16OH)Fe1-x Se is suppressed by introducing Fe-site defects, a short-ranged checkerboard charge order emerges, propagating along the Fe-Fe directions with an approximately 2aFe period. It persists throughout the whole phase space tuned by Fe-site defect density, from a defect-pinned local pattern in optimally doped samples to an extended order in samples with lower T c or non-superconducting. Intriguingly, our simulations indicate that the charge order is likely driven by multiple-Q spin density waves originating from the spin fluctuations observed by inelastic neutron scattering. Our study proves the presence of a competing order in heavily electron-doped iron selenides, and demonstrates the potential of charge order as a tool to detect spin fluctuations.

Abstract The present study aimed to estimate the infection fatality risk (IFR) and ascertainment bias of SARS-CoV-2 for six epidemic waves in Japan from February 2020 to January 2022. We used two types of datasets: (i) surveillance-based datasets containing the cumulative numbers of confirmed cases and deaths in each epidemic wave and (ii) seroepidemiological datasets conducted in a serial cross-sectional manner. Smoothing spline function was employed to reconstruct the age-specific cumulative incidence of infection. We found that IFR was highest during the first wave, and the second highest during the fourth wave, caused by the Alpha variant. Once vaccination became widespread, IFR decreased considerably among adults aged 40 years plus during the fifth wave caused by the Delta variant, although the epidemic size of fifth wave was the largest before the Omicron variant emerged. We also found that ascertainment bias was relatively high during the first and second waves and, notably, RT-PCR testing capacity during these early periods was limited. Improvements in the ascertainment were seen during the third and fourth waves. Once the Omicron variant began spreading, IFR diminished while ascertainment bias was considerably elevated.

Objectives: This study aimed to investigate the factors associated with maintenance of viral suppression after antiretroviral therapy (ART) discontinuation. Methods: Databases were searched for studies published between January 01, 2011, and July 01, 2022, that correlated the time of virus rebound with treatment interruption (TI). The corresponding data were extracted from these studies. A fixed-effects model was used to calculate pooled estimates. Results: Thirty-one studies were included in this analysis. Results showed that patients who started ART during acute or early infection had longer viral control than those who started ART during chronic infection. It has been reported that some broadly neutralizing HIV-1-specific antibodies can significantly prolong viral inhibition. The study also found that approximately 7.2% of patients achieved post-treatment control (PTC) approximately a year after TI. Conclusion: ART initiation in the acute or early phases can delay viral rebound after TI. Cell-associated HIV RNA and HIV DNA have been difficult to prove as able to predict viral rebound time. Many vaccines and antibodies have also been shown to be effective in prolonging viral control in people without PTC, and more research is needed to develop alternative ART therapies that can effectively inhibit or even eliminate HIV.

Abstract Introduction There is a high prevalence of intermittent exotropia and exophoria in myopic populations, and orthokeratology is one of the effective interventions to control myopia progression in children. However, it is still obscure whether intermittent exotropia and exophoria children could wear orthokeratology without experiencing aggravated lens decentration. Methods This was a multi-center, prospective cohort study. A total of 123 myopic participants aged 8–14 years were recruited, where conditions of deviation included intermittent exotropia, exophoria, and orthophoria. Uncorrected visual acuity and corneal topography data were obtained at baseline and after 1 month of wearing orthokeratology lens. Lens decentration was analyzed in a MATLAB program. Magnitude of deviation and refractive errors were evaluated prior to orthokeratology treatment. Fisher’s exact test, ANOVA test, and univariate and multivariate linear regression models were established to evaluate the role of magnitude of deviation in lens decentration. Results There was no significant difference in magnitude and direction of lens decentration among three groups (magnitude: F = 1.25, P = 0.289; direction: Fisher = 9.91, P = 0.078). According to scale division of decentration, 1 (2.6%) intermittent exotropia subject, 2 (3.8%) exophoria subjects, and 1 (3.0%) orthophoria subject experienced severe decentration (Fisher = 1.10, P = 0.947). Inferotemporal decentration was most common among all subjects (intermittent exotropia 50.0%, exophoria 76.9%, orthophoria 72.7%). Univariate and multivariate linear regression analyses revealed that magnitude of deviation was not an independent risk factor for lens decentration [β = −0.00, 95% confidence interval (CI) −0.01–0.00, P = 0.180], while surface asymmetry index (SAI) (β = 0.21, 95% CI 0.02–0.40, P = 0.028) and surface regularity index (SRI) (β = −0.39, 95% CI −0.66 to −0.13, P = 0.004) had significant correlation with polar decentration. Conclusion Patients with intermittent exotropia and exophoria exhibit non-aggravated lens decentration after orthokeratology application. Thus, lens decentration is not the concern for orthokeratology prescription.

Abstract Sensitive detection of Mycobacterium tuberculosis (TB) in small percentages in metagenomic samples is essential for microbial classification and drug resistance prediction. However, traditional methods, such as bacterial culture and microscopy, are time-consuming and sometimes have limited TB detection sensitivity. Oxford nanopore technologies (ONT) MinION sequencing allows rapid and simple sample preparation for sequencing. Its recently developed adaptive sequencing selects reads from targets while allowing real-time base-calling to achieve sequence enrichment or depletion during sequencing. Another common enrichment method is PCR amplification of the target TB genes. In this study, we compared both methods using ONT MinION sequencing for TB detection and variant calling in metagenomic samples using both simulation runs and those with synthetic and patient samples. We found that both methods effectively enrich TB reads from a high percentage of human (95%) and other microbial DNA. Adaptive sequencing with readfish and UNCALLDE achieved a 3.9-fold and 2.2-fold enrichment compared to the control run. We provide a simple automatic analysis framework to support the detection of TB for clinical use, openly available at https://github.com/HKU-BAL/ONT-TB-NF . Depending on the patient's medical condition and sample type, we recommend users evaluate and optimize their workflow for different clinical specimens to improve the detection limit.

Abstract Background Wastewater treatment plants (WWTPs) are one of the largest biotechnology applications in the world and are of critical importance to modern urban societies. An accurate evaluation of the microbial dark matter (MDM, microorganisms whose genomes remain uncharacterized) proportions in WWTPs is of great value, while there is no such research yet. This study conducted a global meta-analysis of MDM in WWTPs with 317,542 prokaryotic genomes from the Genome Taxonomy Database and proposed a “wanted list” for priority targets in further investigations of activated sludge. Results Compared with the Earth Microbiome Project data, WWTPs had relatively lower genome-sequenced proportions of prokaryotes than other ecosystems, such as the animal related environments. Analysis showed that the median proportions of the genome-sequenced cells and taxa (100% identity and 100% coverage in 16S rRNA gene region) in WWTPs reached 56.3% and 34.5% for activated sludge, 48.6% and 28.5% for aerobic biofilm, and 48.3% and 28.5% for anaerobic digestion sludge, respectively. This result meant MDM had high proportions in WWTPs. Besides, all of the samples were occupied by a few predominant taxa, and the majority of the sequenced genomes were from pure cultures. The global-scale “wanted list” for activated sludge contained four phyla that have few representatives and 71 operational taxonomic units with the majority of them having no genome or isolate yet. Finally, several genome mining methods were verified to successfully recover genomes from activated sludge such as hybrid assembly of the second- and third-generation sequencing. Conclusions This work elucidated the proportion of MDM in WWTPs, defined the “wanted list” of activated sludge for future investigations, and certified potential genome recovery methods. The proposed methodology of this study can be applied to other ecosystems and improve understanding of ecosystem structure across diverse habitats. Video Abstract

Abstract In this work, on-chip three-dimensional (3D) photonic integrated optical sources based on active fluorescent polymer waveguide microdisks are proposed for light display application. Fluorescent green and red oligomers with high-efficiency photoluminescence are doped into epoxy crosslinking SU-8 polymer as the waveguide gain medium. The microdisk-based on-chip optically pumping light sources are designed and fabricated using the organic functionalized materials by direct UV written process. The promising stacking dual-microdisk structures with double gain layers could provide white signal light source generated perpendicular to the chip, and green signal light source stimulated in the chip. The approach could realize the monolithically on-chip assembled vertical and horizontal bright emitters. The optical pumping threshold power is obtained as 50 mW with continuous-wave (CW) pumping. The average gain coefficient of a white light source is measured by vertical fiber coupling as 112 dB/W, and that of green light source by horizontal fiber coupling as 137 dB/W, respectively. The rising and falling response time of the on-chip optical sources are 60 and 80 µs under modulating pulsed pumping. This technique is very promising for achieving 3D integrated light display application, including photonic circuits and optical information encryption.

Treatment options in patients with recurrent endometrial carcinoma (EC) are limited and response rates to chemotherapy are poor. Here the authors report the results of a phase II trial of niraparib (PARP inhibitor) monotherapy or in combination with dostarlimab (anti-PD1) in recurrent EC.